Biotechnological production of glycolic acid and ethylene glycol: current state and perspectives

Abstract

Glycolic acid (GA) and ethylene glycol (EG) are versatile two-carbon organic chemicals used in multiple daily applications. GA and EG are currently produced by chemical synthesis, but their biotechnological production from renewable resources has received a substantial interest. Several different metabolic pathways by using genetically modified microorganisms, such as Escherichia coli, Corynebacterium glutamicum and yeast have been established for their production. As a result, the yield of GA and EG produced from sugars has been significantly improved. Here, we describe the recent advancement in metabolic engineering efforts focusing on metabolic pathways and engineering strategies used for GA and EG production.

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Integrated Analysis of Transcriptome and Prognosis Data Identifies FGF22 as a Prognostic Marker of Lung Adenocarcinoma

Technology in Cancer Research &Treatment, Volume 18, Issue , January 2019.


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Chronic stress: a crucial promoter of cell apoptosis in atherosclerosis

Journal of International Medical Research, Ahead of Print.


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Assessment of fragile histidine triad expression in ameloblastoma, odontogenic keratocyst and dentigerous cyst

Vanishri Chandrashekhar Haragannavar, Anand S Tegginamani, Shashidara Raju, Shailesh Kudva, Celestina Dawn Peter, DK Shruthi

Indian Journal of Pathology and Microbiology 2019 62(1):3-6

Background: FHIT (Fragile histidine triad) a member of tumor suppressor family, has been extensively studied in many solid tumors including head and neck squamous cell carcinoma. Among all head and neck cyst and tumors odontogenic lesions account approximately 3%-9%. The molecular pathogenesis of these lesions is less explored. Defects in cell cycle regulators and tumor suppressor genes could result in the development of odontogenic cyst and tumors. Hence, we aimed to determine the significant role of a tumor suppressor gene FHIT in most commonly occurring odontogenic lesions mainly ameloblastoma, odontogenic keratocyst and dentigerous cyst. Subjects and Methods: Immunohistochemical analysis of FHIT was done in ameloblastoma, odontogenic keratocyst, dentigerous cyst and dental follicle. Interpretation of the stained slides were done using standard scoring criteria by two pathologist. The results were subjected for statistical analysis. Results: Expression of FHIT varied among the groups, with highest negative expression in ameloblastoma 44.4% followed by odontogenic keratocyst 14% and 100%positive expression was seen in dentigerous cyst. The expression levels between the groups were statistically insignificant. Conclusion: The varied expression or negative expression of FHIT could be considered as an indicator for aggressive behavior and transformation of preneoplastic/cystic epithelium.

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Intraosseous ganglion of the distal tibia: Clinical, radiological, and histopathological highlights

Ridhi Sood, Rajnish Garg, Harpreet Kaur, Neena Sood

Indian Journal of Pathology and Microbiology 2019 62(1):183-184



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Tumor budding in laryngeal carcinoma

Sumeyye Ekmekci, Ulku Kucuk, Seda Kokkoz, Ebru Cakir, Murat Gumussoy

Indian Journal of Pathology and Microbiology 2019 62(1):7-10

Background: Tumor budding was defined as a single cancer cell or a cluster of fewer than five cancer cells in the stroma of the invasive tumor margin. It has been suggested as a prognostic factor in various cancers, such as esophageal, lung, colorectal, and endometrial. There are only a few studies about the prognostic signifi cance of tumor budding in laryngeal carcinomas. Materials and Methods: A total of 81 patients with laryngeal carcinoma diagnosed between 2011 and 2016 and treated by partial or total laryngectomy were evaluated. Clinicopathologic parameters were correlated with the presence and grade of tumor budding. Results: The study was consisted of 77 (95.1%) male and 4 (4.9%) female patients. The mean age of the patients was 60.2 years (min: 42 and max: 78). Median follow-up time was 25 months (min: 7 and max: 54) (SD ±11.5). Histopathologic diagnosis was squamous cell carcinoma (SCC) in all patients. Of the 62 cases showing budding, 2 (3.2%) were stage 1, 12 (19.4%) stage 2, 16 (25.8%) stage 3, and 32 (51.6%) were stage 4. Fifteen cases with budding (24.2%) showed lymphovascular invasion (LVI). None of the nonbudding cases had LVI and perineural invasion (PNI). Statistical analysis revealed that LVI and PNI were signifi cantly associated with budding (P = 0.017 and P = 0.012). Among the tumors showing budding, 37% had lymph node metastasis (LNM). In nonbudding cases 15% had LNM. There was a statistically significant correlation between LNM and budding (P = 0.017). None of the parameters correlated with grade of tumor budding statistically. Conclusion: The results of this study suggest that tumor budding might be used as a prognostic factor in laryngeal SCCs.

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Extramedullary plasmacytoma of tonsil: an unusual site

Ritesh Sachdev, Manoj Tayal, Shalini Goel, Rashi Sharma, Dheeraj Gautam

Indian Journal of Pathology and Microbiology 2019 62(1):167-168



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Effectuation to Cognize malignancy risk and accuracy of fine needle aspiration cytology in salivary gland using “Milan System for Reporting Salivary Gland Cytopathology”: A 2 years retrospective study in academic institution

Veer Karuna, Priya Gupta, Monika Rathi, Kriti Grover, Jitendra Singh Nigam, Nidhi Verma

Indian Journal of Pathology and Microbiology 2019 62(1):11-16

Background: To accost things in a particular disciple, egress related to Fine Needle Aspiration Cytology (FNAC) and to standardize reporting pattern, a framework "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) has been sponsored. Aim: Aim of this study was to evaluate the potency of salivary gland FNAC reported under Milan guidelines, to calculate malignancy risk, and to compare the preoperative cytological diagnoses with the postoperative histopathological diagnoses. Settings and Design: This was a retrospective study over a period of 2 years (May 2016 to April 2018), which was classified according to Milan system and correlation with histopathology. Furthermore, the risk of malignancy was calculated for all the diagnostic categories. Materials and Methods: FNAC were analyzed on 105 patients with palpable salivary gland. Results were distributed into six categories. About 76 cases were surgically treated and resected tissues were submitted for histopathological examination. Statistical Analysis: The various diagnostic values of the procedure were calculated using the standard formula. Results: We reviewed 105 salivary gland FNA samples and recorded interpretations according to the proposed standardized six categories. Among them, category IV (neoplastic) had more cases (57.14%). The rates of malignancy in histology were as follows: (1) nondiagnostic, 0.0%; (2) nonneoplastic, 0.0%; (3) atypia of undermined significance, 50.00%; (4a) benign, 02.44%; (4b) uncertain malignant potential, 33.33%; (5) suspicious for malignancy, 100%; and (6) malignancy, 93.33%. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of Milan system came out to be 85.00%, 98.14%, 94.44%, 94.64%, and 94.59%, respectively. Conclusion: The six-tier diagnostic categories of the Milan system helps in triaging patients with salivary gland swelling and thus facilitate individualized management.

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Undifferentiated embryonal sarcoma of the liver in elderly: Case report and review of the literature

Gunter Gerson, José Telmo Valença, Juliana M Cavalcante, River De Alencar Bandeira Coêlho

Indian Journal of Pathology and Microbiology 2019 62(1):129-131

Sarcomas are rare lesions of the liver and represent <1% of primary liver tumors. Embryonic sarcoma (undifferentiated) of the liver is a rare and aggressive malignant tumor that usually occurs in children with a peak incidence between 6 and 10 years. In adults, it is extremely rare with only 13 cases described in patients older than 40 years and 68 cases reported in patients older than 15 years. There is a slight predominance of females in adults. With an emphasis on morphological and immunohistochemical features, as well as on clinical data and imaging studies, we present this case report, in addition to extensive literature review on the topic.

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A rare case of disseminated penicilliosis - first of its kind from North India

Surekha Yadav, Richa Gupta, S Anuradha, Ayush Mohan Makkar

Indian Journal of Pathology and Microbiology 2019 62(1):156-158

Penicilliosis is a rare opportunistic fungal infection caused by Talaromyces marneffei, especially in the HIV-infected patients. The untreated disease is highly fatal. The infection is endemic in Southeast Asia and Northeast India. The present case is the first case of disseminated penicilliosis from North India and Delhi in a 31-year-old male, recently diagnosed with HIV. This case highlights the importance of considering an unusual organism as the cause of disseminated disease in the nonendemic area.

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Epidermal growth factor receptor and anaplastic lymphoma kinase mutation in adenocarcinoma lung: Their incidence and correlation with histologic patterns

Pankaj Gupta, Swarnalata Gowrishankar, Meenakshi Swain

Indian Journal of Pathology and Microbiology 2019 62(1):24-30

Introduction: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational analysis in adenocarcinoma lung are growing in importance as these tests are essential in guiding the use of targeted therapy. However, the prevalence of these mutations in various populations in India has not been studied. Furthermore, the correlation of histologic pattern with the mutation is not clear. Materials and Methods: A total of 64 biopsy-proven lung adenocarcinomas were selected. In 51 of these, EGFR mutational analysis was performed using Qiagen EGFR pyrosequencing kit and in 56 cases of these ALK1 immunohistochemistry (IHC) was done using ALK (D5F3) antibody and the Ventana Benchmark® XT automated IHC slide staining system for the detection of overexpression. The adenocarcinomas were classified into well, moderate, and poorly differentiated, and the histological pattern was recorded according to the WHO 2014 classification. Results: EGFR mutation was positive in 23 cases (45.10%) and positive ALK1 expression by IHC in 12 cases (21.43%). Both mutations were positive in two cases. Both mutations were seen in well-differentiated and moderately differentiated adenocarcinoma, and the expression was highest in tumors with a predominant acinar pattern. Conclusions: The incidence of both EGFR and ALK1 mutations is higher in the population studied and seem to correlate with a well differentiated, acinar pattern on morphology.

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SETTLE tumor of thyroid: Oldest case in literature

Hamsa Nandini, Vivek Shetty, Akhila Lakshmikantha, HV Sunil, Subramanian Kannan

Indian Journal of Pathology and Microbiology 2019 62(1):175-177



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Second evaluation of the mesenteric tissue after ethanol fixation improved the total and metastatic number of lymph nodes in colorectal resections

Asli Cakir, İlknur Cetinaslan Turkmen, Asli Unlu Akhan, Merve Akkoc, Pinar Korkmaz

Indian Journal of Pathology and Microbiology 2019 62(1):31-35

Context: There is a correlation between prognosis of the colorectal carcinomas and the number of retrieved and metastatic lymph nodes (LNs) from mesentery/mesorectal region. At least 12 LNs must be sampled for accurate evaluation of patients. A number of factors related to surgeon, pathologist, patient and disease could affect the total LN number. For maximizing LN yield, pathologist can use ancillary methods, as fat clearance and special solutions. Aims: This study investigates the effect of second evaluation after ethanol fixation on total and metastatic LN number and assesses factors that influence the dissected LN number. Materials and Methods: 177 colorectal resections were refixed with ethanol for a night, after standard LN sampling. Mesentery/mesorectal tissue was reevaluated for missed LNs. Results were statistically analyzed, P values <0.05 were considered significant. Results: Mean LN number increased from 26 to 30 (median: 20 to 25, P < 0.001) after ethanol fixation. Fourteen cases had additional metastatic LNs after reevaluation of the fat tissue and 5 of them upstaged. 22.5% (44/177) of the patients had <12 LNs before ethanol fixation and this decreased to 14.3% (26/177) after ethanol fixation. Resection type and length, tumor localization, size and histologic degree, pT and neoadjuvant therapy (P < 0.001) had an impact on the LN number (P = 0.034 for histologic degree, P = 0.02 for pT, P < 0.001 for others). Conclusions: Carrying out a second evaluation with ethanol fixation increased total and metastatic LN number and could lead upstage of pN. Ethanol fixation is cost-effective, easy accessible and applicable method; it may improve accuracy of LN assessment and staging, which are important for patients' outcome.

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From Editor's desk

Ranjan Agrawal

Indian Journal of Pathology and Microbiology 2019 62(1):1-2



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A study of morphological prognostic factors in colorectal cancer and survival analysis

S Poornakala, NS Prema

Indian Journal of Pathology and Microbiology 2019 62(1):36-42

Context: Globally, colorectal cancer (CRC) is one of the leading causes of cancer death. Many Asian countries experience an increasing incidence of CRC due to changes in diet and lifestyle. Many pathological prognostic factors other than the tumor-node-metastasis (TNM) staging reflect the biological behavior of tumor tissue and influence the treatment and survival. Aims: The aim is to evaluate: (1) Various morphological prognostic factors of colorectal cancer, (2) the correlation of the prognostic factors with survival, and (3) the prognostic factors with independent prognostic significance. Settings and Design: Descriptive study conducted in a tertiary care center in Kerala. Materials and Methods: Five hundred and eighty-seven resected specimens of CRC received from January 1, 2007 to October 31, 2012 were studied for various morphological prognostic factors. Overall survival and disease-free survival were obtained by Kaplan Meier survival analysis. Cox regression analysis was performed to identify the predictors of survival. Results: CRC incidence was higher in the age group 40–60 years and males were dominant. Rectum was the common site with bleeding per rectum as a common symptom. Predominant tumors had ulcerative gross configuration, size ≤5 cm and were free of transverse, radial margin involvement. Majority of tumors were well-differentiated adenocarcinoma with invasion beyond muscularis propria, without vascular, perineural invasion, and lymph node involvement and were in Stage II. The overall and disease-free 3-year survival rates were 89.1% and 88%, respectively. Among the eight significant factors in univariate analysis, tumor histology, depth of invasion, and perineural invasion were found to have independent prognostic significance in multivariate analysis. Conclusions: In addition to the TNM staging, other morphological prognostic factors should be given importance, while considering the patients for adjuvant therapy to improve the survival rates in CRC.

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Sclerosing polycystic adenosis: A case report with review of the literature

Sreelekha Appasani, Preethi Thattaruparambil Ramadas, Jayapriya Gangadharan, Anitha Mathews

Indian Journal of Pathology and Microbiology 2019 62(1):136-138

Sclerosing polycystic adenosis (SPA) is primarily a disease of major salivary glands. It was recognized as a distinct morphologic entity by Smith et al. in 1996. To best of our knowledge, 67 cases of SPA are reported in English literature. Here, we describe a case of SPA showing classic histomorphological features, involving the parotid gland of a 17-year-old girl. It was diagnosed as mucoepidermoid carcinoma at a peripheral hospital and was referred to our center. Histologically, it was well circumscribed and composed of lobules, separated by hyalinized stroma. Lobules showed adenosis, foci of acinic cell hyperplasia, and intraductal epithelial proliferation. Immunohistochemistry with p63 highlighted myoepithelial layer around every duct, acinus, and also in foci showing epithelial hyperplasia. There was no evidence of malignancy. Awareness of SPA, a benign rare entity, is essential to avoid misdiagnosing it as other common salivary gland tumors which it may mimic.

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Neu Laxova syndrome

Tanima Dwivedi, Manasi Gosavi

Indian Journal of Pathology and Microbiology 2019 62(1):149-152

NeuLaxova syndrome (NLS) is a rare congenital abnormality involving multiple systems. Until date, only 60 cases of this syndrome have been reported in the literature. A stillborn fetus from a 23-year-old female with bad obstetrics history and consanguinity marriage, presented at 41 weeks gestation and not appreciating fetal movements for the past 3 days. Ultrasound examination revealed the absence of fetal cardiac activity and features of growth retardation. The fetus was sent for pathological examination. At autopsy, fetus had ichthyosis over the scalp and face, depressed nasal bridge, low set ears, microcephaly, slopping forehead, wide interdigital spaces, edema of hands and feet, hypoplastic penis, right leg showed congenital talipes equinovarus and left leg showed rocker bottom foot. On dissection, all organs were in situ. Both lungs were hypoplastic, brain was atrophied, and heart showed right ventricle hypertrophied. A diagnosis of NLS was made. Genetic counseling and early serial ultrasound examination should be performed at high-risk families because of its autosomal recessive mode of inheritance. Early diagnosis of the disease may offer termination of the pregnancy as an option. The prognosis is poor, and the affected newborns are either stillborn or die immediately after birth.

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Immunohistochemistry and morphometric analysis of pelviureteric junction complexes in children with hydronephrosis

Pradyumna Pan, Neeraj Sachdeva

Indian Journal of Pathology and Microbiology 2019 62(1):49-53

Aim: The study aimed to analyze the musculature and innervations of pelviureteric junction (PUJ) complex and upper ureter by morphometry and immunohistochemistry in surgically resected specimens of PUJ obstruction and compares the findings with normal controls. Materials and Methods: Specimens of the PUJ were obtained from twenty patients with hydronephrosis due to PUJ obstruction undergoing surgical treatment in this unit from 2013 to 2015. In the control group, seven PUJ complexes were taken from patients who had nephrectomy due to trauma and Wilms tumor. The sections were stained with H and E stain and elastic von Gieson stain. For immunohistochemistry, the tissue sections were immunostained by an indirect immunoperoxidase method for S-100 and neuron-specific enolase. Results: Histopathologically, the predominant arrangement of muscle fibers was layered, i.e., a thick circular layer surrounded by two longitudinal layers on either side in PUJ of obstruction patients. S-100 immunoreactivity in the muscle layer showed dense neural innervation in PUJ complex of obstructed patients. Conclusions: Circular enhanced musculature may cause a sphincter-like activity with holding up of urine. The higher density of neuronal expression in PUJ might be responsible for causing constant contraction and intrinsic obstruction.

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Sialadenoma papilliferum of the hard palate: A rare case report

Saede Atarbashi-Moghadam, Ali Lotfi, Mohammad Moshref, Sepideh Mokhtari

Indian Journal of Pathology and Microbiology 2019 62(1):163-164

Sialadenoma papilliferum (SP) is a rare benign salivary gland tumor with unclear cell origin. This report presents a new case of SP of the hard palate occurring in a 50-year-old female. The lesion was completely excised, and the microscopic features were consistent with SP. The knowledge of this rare entity contributes to proper diagnosis and prevents unnecessary radical surgery and treatment.

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Differential expression of cyclin E, p63, and Ki-67 in gestational trophoblastic disease and its role in diagnosis and management: A prospective case–control study

Asaranti Kar, Chandraprava Mishra, Priyadarshini Biswal, Tushar Kar, Sasmita Panda, Subhasini Naik

Indian Journal of Pathology and Microbiology 2019 62(1):54-60

Background: Gestational trophoblastic disease (GTD) constitutes a spectrum of tumors and tumor-like conditions, characterized by proliferation of pregnancy-associated trophoblastic tissue of progressive malignant potential. It is very difficult to differentiate these complex groups of lesions basing on histomorphology alone. Immunohistochemistry (IHC) with cyclin E, P63, and Ki-67 has a definite role in the identification of different trophoblasts and entities of GTD and also in the determination of biological behavior. Aims: The aim of this study is to find the differential expression of cyclin E, p63, and Ki-67 in normal placenta, hydropic abortus (HA), and various entities of GTD. Design and Settings: A prospective case–control study conducted in a government medical college. Methods: Total 96 cases, divided into Group A (48 histologically confirmed cases of GTD) and Group B (controls comprising 8 HA and 40 normal placentas of different trimesters), were studied. The histological samples were subjected to IHC using cyclin E, Ki-67, and p63. Statistical Analysis: Results were analyzed using SPSS statistical method. Results: Among the three immunomarkers used, Cyclin E and Ki-67 show statistically significant difference (P < 0.05) when compared between GTD and control groups, but it was insignificant for p63 (P = 0.369). Strong staining intensity of cyclin E and Ki-67 is seen in complete moles, choriocarcinoma, and placental site trophoblastic tumor. Conclusion: This study was done to evaluate the role of cell cycle regulatory proteins such as cyclin E and p63 and proliferation marker Ki-67 in the detection of various trophoblasts and differential diagnosis of the lesions associated with them.

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Clinical Characteristics of Tracheobronchopathia Osteochondroplastica

BACKGROUND:Tracheobronchopathia osteochondroplastica (TO) consists of benign lesions of tracheal and bronchial mucosa with multiple nodular hyperplasia of bone or cartilage protruding into the lumen.METHODS:We diagnosed 73 subjects with TO with the use of bronchoscopy in the Department of Respiratory and Critical Care Medicine of Xiangya Hospital between January 2000 and April 2017. Clinical manifestations, radiographic characteristics, bronchoscopic manifestations, histopathological findings, and treatments were analyzed retrospectively.RESULTS:Subjects included 30 women and 43 men (mean age, 52.8 ± 11.7 y). Twenty-seven subjects were diagnosed with other diseases, including tuberculosis in 11 subjects, carcinoma in 13, bronchiectasis in 2, and pulmonary hamartomas in 1 subject. The most common symptom was cough (n = 34). Other initial manifestations included hemoptysis (n = 17), expectoration (n = 15), and chest pain (n = 8). Of those who underwent a computed tomography scan in our hospital, 28 of 32 subjects had noted calcification of the tracheal wall, with 4 of 32 subjects appearing normal. Bronchoscopy revealed typical accumulation of diffuse cartilaginous and osseous nodules of TO, and 9 had observable tracheal stenosis. Histopathologic results included the presence of chronic inflammation (n = 47), ossification (n = 38), and cartilage formation (n = 10). Most subjects received symptomatic treatment, although 3 subjects with severe airway obstruction received bronchoscopic treatment.CONCLUSION:The results indicated that TO lacks clinical specificity, which means that special therapy and bronchoscopy with histopathological and radiographic assistance is important for its diagnosis. The treating physicians' awareness about this condition is also important to its diagnosis and management.

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Accuracy of Transcutaneous Carbon Dioxide Levels in Comparison to Arterial Carbon Dioxide Levels in Critically Ill Children

BACKGROUND:Widespread use of transcutaneous PCO2 (PtcCO2) monitoring is currently limited by concerns many practitioners have regarding accuracy. We compared the accuracy of PtcCO2 with that of PaCO2 measurements in critically ill children, and we investigated whether clinical conditions associated with low cardiac output or increased subcutaneous tissue affect this accuracy.METHODS:We performed a single-center prospective study of critically ill children placed on transcutaneous monitoring.RESULTS:There were 184 children enrolled with paired PaCO2 and PtcCO2 values. Subjects had a median age of 31.8 mo (interquartile range 3.5–123.3 mo). Most children were mechanically ventilated (n = 161, 87.5%), and many had cardiac disease (n = 76, 41.3%). The median PaCO2 was 44 mm Hg (interquartile range 39–51 mm Hg). The mean bias between PaCO2 and PtcCO2 was 0.6 mm Hg with 95% limits of agreement from −13.6 to 14.7 mm Hg. The PtcCO2 and PaCO2 were within ±5 mm Hg in 126 (68.5%) measurements. In multivariable modeling, cyanotic heart disease (odds ratio 3.5, 95% CI 1.2–10, P = .02) and monitor number 2 (odds ratio 3.8 95% CI 1.3–10.5, P = .01) remained associated with PtcCO2 ≥ 5 mm Hg higher than PaCO2. Serum lactate, fluid balance, renal failure, obesity, vasoactive-inotrope score, and acyanotic heart disease were not associated with high or low PtcCO2 values. In 130 children with a second paired PtcCO2 and PaCO2 measurement, predicting the second measured PaCO2 by subtracting the initial observed difference between the PtcCO2 and PaCO2 from the subsequent measured PtcCO2 decreased the mean bias between observed and predicted PaCO2 to 0.2 mm Hg and the 95% limits of agreement to −9.4 to 9.7 mm Hg.CONCLUSIONS:PtcCO2 provides an acceptable estimate of PaCO2 in many critically ill children, including those with clinical conditions that may be associated with low cardiac output or increased subcutaneous tissue, although it does not perform as well in children with cyanotic heart disease. PtcCO2 may be a useful adjunct monitoring method, but it cannot reliably replace PaCO2 measurement.

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Home Oxygen Therapy Devices: Providing the Prescription

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In Vitro-In Silico Comparison of Pulsed Oxygen Delivery From Portable Oxygen Concentrators Versus Continuous Flow Oxygen Delivery

BACKGROUND:Portable oxygen concentrators (POCs) deliver oxygen in intermittent pulses. The challenge of establishing equivalence between continuous flow oxygen and nominal pulse flow settings on different POCs is well known. In vitro bench measurements and in silico mathematical modeling were used to compare the performance of 4 POCs versus continuous flow oxygen by predicting the FIO2 at the trachea and entering the acini.METHODS:Each of the 4 POCs was connected to a 3-dimensional printed replica of a human adult nasal airway via nasal cannula. A test lung simulated 3 breathing patterns representative of a patient with COPD at rest, during exercise, and while asleep. POCs were tested for each breathing pattern at all integer pulse flow settings. Volume-averaged FIO2 was calculated by analyzing oxygen concentrations and inhalation flow over time. In vitro oxygen waveforms were then combined with a single-path mathematical model of the lungs to assess oxygen transport through the conducting airways. In vitro experiments and mathematical modeling were repeated for continuous flow oxygen.RESULTS:Continuous flow oxygen consistently delivered more (>2% absolute) oxygen in terms of volume-averaged FIO2 for all nominally equivalent pulse flow settings of >2. Differences were also observed when comparing performances between different POCs, particularly at high device settings (5 and 6). Simulations showed that efficiency of delivery to the acinar region of the lungs was higher in pulse flow than in continuous flow oxygen but that continuous flow oxygen generally delivered a higher absolute volume of oxygen. Differences in absolute oxygen delivery per breath between continuous flow oxygen and pulse flow were smaller for acinar delivery than for tracheal delivery.CONCLUSIONS:Significant differences in POC performance based on volume-averaged FIO2 were found between pulse flow and continuous flow oxygen, and among pulse flow modes in different POCs. Although pulse flow was a more efficient mode of delivery than continuous flow oxygen, continuous flow oxygen delivered a greater absolute volume of oxygen per breath.

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Humidification Performance of Passive and Active Humidification Devices Within a Spontaneously Breathing Tracheostomized Cohort

BACKGROUND:Most heat-and-moisture exchangers (HMEs) for patients with tracheostomy and spontaneously breathing are small and have suction ports that allow some expiratory gas to escape, which loses water vapor held in the expired gas. Recently, a heated-and-humidified high-flow system for spontaneously breathing patients with tracheostomy was developed. Little is known, however, about the humidifying performance of HMEs or heated-and-humidified high-flow systems for spontaneous breathing patients with a tracheostomy.OBJECTIVE:To investigate the humidifying performance of the HMEs and heated-and-humidified high-flow systems for spontaneously breathing patients with tracheostomy.METHODS:Adult spontaneously breathing subjects with tracheostomy and were enrolled when their respiratory parameters and SpO2 were stable. We measured absolute humidity, relative humidity, and temperature by using a capacitance-type moisture sensor at the outlet of the tracheostomy tube. Heated-and-humidified high flow was delivered via the a humidifier and tracheostomy interface, and a selected HME. The subjects received heated-and-humidified high flow, after which an HME was used for humidification before switching back to a heated-and-humidified high-flow system.RESULTS:Ten subjects (5 men, 5 women; mean ± SD age, 72 ± 12 y) were enrolled. The admission diagnoses were neurologic (5 subjects), respiratory failure (3), and cardiac arrest (2). The APACHE (Acute Physiology and Chronic Health Evaluation) II score was 24 (interquartile range, 20–27). Tracheostomy was performed on day 7 (interquartile range, 5–11 d) after endotracheal intubation, and the duration of mechanical ventilation was 10 d (interquartile range, 6–11 d). The temperature with the HME was 29.9 ± 1.0°C and, during heated-and-humidified high-flow use was 35.3 ± 0.8°C (P < .001). With both the HME and the heated-and-humidified high-flow system, the relative humidity reached 100%; the absolute humidity with HME was 30.2 ± 1.8 mg/L, and, with the heated-and-humidified high-flow system, was 40.3 ± 1.8 mg/L (P < .001).CONCLUSIONS:In spontaneously breathing subjects with tracheostomy, an heated-and-humidified high-flow system achieved higher absolute humidity than did an HME.

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Assessment of Peripheral Muscle Function in Cystic Fibrosis: Why and How?

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Effects of Diaphragmatic Breathing With and Without Pursed-Lips Breathing in Subjects With COPD

BACKGROUND:Breathing exercises, such as diaphragmatic breathing and pursed-lips breathing, play a role in some individuals with COPD and might be considered for those patients who are unable to exercise. However, in the literature are reports of some adverse effects of diaphragmatic breathing in patients with COPD. Thus, the purpose of this study was to assess the effects of diaphragmatic breathing and diaphragmatic breathing combined with pursed-lips on chest wall kinematics, breathlessness, and chest wall asynchrony in subjects with COPD, and also to assess whether the combination of both exercises reduces the adverse effects of diaphragmatic breathing while maintaining its benefits.METHODS:Seventeen subjects with COPD, mean ± SD, 65 ± 7 y of age, with a history of smoking and clinical stability without hospitalization or symptoms of exacerbation in the past 4 wk, were evaluated. On day 1, participants' characteristics were collected, and they learned diaphragmatic breathing and its combination with pursed-lips breathing. On day 2, the participants were evaluated by optoelectronic plethysmography with the participants in the seated position while performing breathing exercises.RESULTS:Diaphragmatic breathing and diaphragmatic breathing plus pursed-lips breathing promoted a significant increase in chest wall tidal volume and its compartments as well as a reduction in breathing frequency compared with quiet breathing. No significant changes were observed in dyspnea or end-expiratory volume of the chest wall. A significant increase in asynchrony (inspiratory-expiratory phase ratio) was observed during diaphragmatic breathing and diaphragmatic breathing plus pursed-lips breathing compared with quiet breathing, with no differences observed between the exercises.CONCLUSIONS:Despite the increase in asynchrony, both breathing exercises were able to improve chest wall volumes without affecting dyspnea. The combination of exercises maintained the benefits but did not reduce the adverse effects of diaphragmatic breathing.

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Pulmonary Thromboses in Pediatric Acute Respiratory Distress Syndrome

Pediatric ARDS continues to be a management challenge in the ICU with prolonged hospitalizations and high mortality. Thromboembolic pulmonary embolism and in situ pulmonary artery thrombosis might represent underappreciated thrombotic processes for a subset of these patients. Although well described in the adult literature, descriptions of pulmonary thromboses with pediatric ARDS are limited to case reports. However, many risk factors for pulmonary thromboses are present in children with ARDS (eg, coagulopathy, endothelial injury, central venous catheters, concomitant inflammatory diseases), suggesting a much higher incidence is plausible. Based on an interpretation of animal, pediatric, and adult data, we propose a diagnostic algorithm to facilitate a timely and accurate diagnosis. Observing an alveolar dead space fraction ≥ 0.25, or either a 50% increase in physiologic dead space/tidal volume or a central venous saturation ≤ 60% over 24 h, triggers the algorithm. Together with targeted heparin treatment and right ventricular afterload reduction, clinical outcomes might improve if this particular patient subgroup can be identified early. While anticoagulation is recommended in adults with confirmed pulmonary embolism and low early mortality risk, data for children are limited.

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Effects of Mechanical Insufflation-Exsufflation on the Breathing Pattern in Stable Subjects With Duchenne Muscular Dystrophy: A Step in a Wrong Direction

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Inspiratory Capacity and Vital Capacity of Healthy Subȷects 9-81 Years of Age at Moderate-High Altitude

BACKGROUND:Measurements of inspiratory capacity (IC) and vital capacity (VC) are used to recognize dynamic hyperinflation, but appropriate reference values are required to achieve accurate clinical interpretations. Altitude above sea level is a potential determining factor for lung volumes, including IC and VC.OBJECTIVE:To describe IC and VC for healthy people who live in Mexico City at an altitude of 2,240 m above sea level.METHODS:Healthy subjects ages 9–81 y completed slow spirometry by following 2005 American Thoracic Society/European Respiratory Society standards. Once associations were explored, linear regression models were constructed and values were compared with those from previously published equations.RESULTS:A total of 441 healthy subjects (55.1% women) participated. The mean age was 32 y (minimum age, 9 y; maximum age, 81 y). IC and VC measurements were associated with sex, age, height, and weight. An accelerated increase in IC and VC was evident from 9 to 20 y of age, followed by a gradual decrease in both sexes. In general, IC was higher in our population than predicted by previously published reference equations.CONCLUSIONS:IC in healthy people at 2,240 m above sea level was higher than that of previous reports about European and Latin-American subjects of the same height, sex, and age who were at sea level. The present study provided robust reference values for persons who lived at a moderate altitude.

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Editor's Commentary

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Evaluation of the Clinical Learning Environment in Respiratory Therapy Education: Student Perceptions

BACKGROUND:Clinical facilities are essential components not only of health care delivery systems, but also of health care education programs. The clinical learning environment (CLE) is important in training the future health care workforce. Because respiratory therapy (RT) is a practice-based profession, it is essential to integrate clinical education into RT education. RT education programs face several issues with respect to the need for preparing a proper CLE in various clinical settings. The purpose of this study was to determine the perceptions of RT students on the CLE of clinical facilities affiliated with an RT program at an urban state university and to determine the impact of education level on student perception of the CLE of clinical facilities.METHODS:We used an exploratory research design to evaluate the essential aspects of a CLE in RT education. An adapted Clinical Learning Environment Supervision and Nurse Teacher (CLES+T) evaluation scale was utilized to evaluate 34 RT students' perceptions of clinical facilities in RT education; 32 students participated in the survey, with a response rate of 94.1%.RESULTS:Responses included 2 groups of students: second-year undergraduates (68.8%), in which women accounted for 81% and men 19%, and graduate students (31.2%), in which women accounted for 60% and men 40%. Results obtained from the study indicated that both graduate and undergraduate RT students gave high median scores to the CLE, the supervisory relationship, and the role of clinical instructors. A statistically significant difference was obtained between the graduate and undergraduate students regarding multidimensional learning (P = .043). We found that the majority of students positively rated the CLE in RT education.CONCLUSIONS:Education level influenced students' perceptions of the CLE of clinical facilities. Overall, respiratory therapy students rated their CLE experiences as positive and they were satisfied with the clinical instructor and team model.

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A COPD Case-Finding Program in a Large Cohort of HIV-Infected Persons

BACKGROUND:COPD screening guidelines in patients with HIV are lacking, and data about its under-diagnosis are still limited. This study aimed to determinate the feasibility of a case-finding program and the prevalence of COPD under-diagnosis in a large cohort of HIV-infected subjects.METHODS:All out-patients attending their routine visit for HIV monitoring at Spedali Civili General Hospital in Brescia, Italy, from February 2015 to January 2016, were enrolled. The case-finding program was structured in three steps: questionnaire administration, pre-bronchodilator spirometry testing measured with a portable spirometer, and post-bronchodilator diagnostic spirometry during a pulmonology appointment.RESULTS:A total of 1,463 subjects were included; the average age was 46.2 ± 10.3 y. Two hundred eighty-two subjects had a positive questionnaire; 190 completed portable spirometry, and approximately 34% (65 of 190 subjects) reported respiratory impairment; of these 65 subjects, 33 completed diagnostic spirometry, and 66.7% (22 of 33) showed evidence of COPD, including 2 subjects with severe airway obstruction (GOLD stage 3, according to the Global Initiative for Chronic Obstructive Lung Disease). High dropout rates were observed in our program. Individuals with COPD exacerbations showed lower CD4+ cell counts at screening compared to those without acute worsening of symptoms (534 cells/mm3 for subjects with GOLD 1 exacerbations and 495 cells/mm3 for subjects with GOLD 2 exacerbations vs 781 cells/mm3 for those without acute worsening of symptoms). The positive predictive value of the COPD screening questionnaire and portable spirometry was 33.8%.CONCLUSIONS:COPD may be under-diagnosed in HIV-infected people, and case-finding programs are an urgent issue to address as part of routine practice in these individuals.

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Lung Ultrasound: The Emerging Role of Respiratory Therapists

Lung ultrasound is a point-of-care imaging tool that is routinely used in acute care medicine. Traditionally, radiology physicians were the primary practitioners of diagnostic ultrasound, but with the recognition of its importance in intensive care medicine, critical care physicians have also adopted this practice. Within the intensive care unit inter-professional team is the respiratory therapist, who participates actively in the care of ventilated patients. Their scope of responsibility is expanding with newer technologies being brought into clinical use on a regular basis. This review focuses on the scope and benefits of ultrasound training within respiratory care–related areas.

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Objective Versus Self-Reported Adherence to Airway Clearance Therapy in Cystic Fibrosis

BACKGROUND:Historically, studies of adherence to airway clearance therapy in cystic fibrosis (CF) have relied on self-reporting. We compared self-reported airway clearance therapy adherence to actual usage data from home high-frequency chest wall compressions (HFCWC) vests and identified factors associated with overestimation of adherence in self-reports.METHODS:Pediatric patients who perform airway clearance therapy with a HFCWC vest were eligible to participate. Objective adherence data were obtained from the HFCWC device, which records cumulative utilization time. Two readings at least 5 weeks apart were collected. Objective adherence was recorded as a ratio of mean-to-prescribed daily use (%). Self-reported adherence data were collected with a caregiver survey at enrollment. Adherence rates were categorized as low (< 35% of prescribed), moderate (36–79% of prescribed), and high (≥ 80% of prescribed). An overestimation was present when self-reported adherence was at least one category higher than objective adherence.RESULTS:In the final sample (N = 110), mean adherence by usage data was 61%. Only 35% of subjects (n = 38) were highly adherent, and 28% (n = 31) were low adherent. In contrast, 65% of subjects (n = 72) reported high adherence and only 8% (n = 9) reported low adherence (P < .001). Nearly half of self-reports (46%) overestimated adherence. In a multiple regression analysis, overestimation was associated with multiple airway clearance therapy locations (odds ratio 7.13, 95% CI 1.16–43.72, P = .034) and prescribed daily use ≥ 60 min (odds ratio 3.85, 95% CI 1.08–13.76, P < .038). Among subjects with prescribed daily airway clearance therapy ≥ 60 min, the odds of overestimating adherence increased 3-fold (odds ratio 3.04, 95% CI 1.17–7.87, P = .02) in a lower-income (< $50,000/y) environment.CONCLUSIONS:Self-reports overestimated actual adherence to airway clearance therapy, and the overestimation increased with treatment occurring in multiple households and prescribed therapy duration. Among participants with prescribed airway clearance therapy ≥ 60 min, overestimation increased with lower income. Objective measures of adherence are needed, particularly for lower-income children and those receiving treatments in multiple locations.

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Conditioning Inspired Gases for Tracheostomy

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Measurement of Dynamic Hyperinflation During the 6-Minute Walk Test Using a Mobile Device

BACKGROUND:Dynamic hyperinflation is a major cause of dyspnea in patients with COPD. Dynamic hyperinflation is usually measured with cardiopulmonary exercise testing, but this test requires maximal effort from the patient, and inspiratory capacity (IC) measurements may influence test results. This study investigated another approach by measuring dynamic hyperinflation during the more natural and better-tolerated 6-min walk test (6MWT), using a mobile system for IC measurements.METHODS:Twenty subjects were studied, including 10 healthy subjects and 10 subjects with COPD. Each subject performed a pair of 6MWTs.RESULTS:The study showed that test-retest reliability in healthy subjects was excellent (intraclass correlation coefficient 0.995). In addition, mean resting IC in healthy subjects (3.27 ± 0.77 L) was not affected at the end of the 6MWT, whereas mean resting IC in subjects with COPD (2.45 ± 0.90 L) decreased to 1.93 L ± 0.68 L at the end of the 6MWT (P = .004). The tolerability of the device for subjects with COPD appeared to be only slightly hampered by an increased sense of dyspnea attributed to wearing a mask.CONCLUSIONS:This study provides a proof of principle for mobile IC measurements during the 6MWT, demonstrating good test performance, reasonable tolerability, and a power to differentiate normal from pathologic conditions.

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Effects of Mechanical Insufflation-Exsufflation on the Breathing Pattern in Stable Subȷects With Duchenne Muscular Dystrophy: “A Step Into New Knowledge”

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Factors Influencing Activities of Daily Living in Subjects With COPD

BACKGROUND:Activities of daily living (ADL) are important for an independent life. As COPD progresses, the ability to complete ADL is usually reduced. Knowing the possible factors that influence the ability to perform ADL may allow better targeting of appropriate rehabilitation programs to increase the independence levels and/or to prevent further decreases in patients with COPD. Therefore, the aim of this study was to investigate ADL performance as measured by the London Chest Activity of Daily Living scale, which is a commonly used measure in patients with COPD.METHODS:This cross-sectional study included 44 clinically stable subjects who were not taking antibiotics and had not made any changes in their medications for at least three weeks with a COPD diagnosis based on Global Initiative for Chronic Obstructive Lung Disease. Demographic characteristics, pulmonary function, ADL measured by the London Chest Activity of Daily Living scale, functional exercise capacity via the 6-min walk distance, disease-related symptoms measured by the COPD Assessment Test, and peripheral and respiratory muscle strength were evaluated. A multiple linear regression (stepwise) analysis was used to determine the variables that have the greatest influence on ADL (ie, the London Chest Activity of Daily Living scale score).RESULTS:The London Chest Activity of Daily Living scale score had moderate correlations with the COPD Assessment Test score (r = 0.31, P = .041), maximum expiratory pressure value (r = −0.37, P = .01), 6-min walk distance (r = −0.48, P = .001), knee extensor muscle strength (r = −0.47, P = .001), handgrip strength (r = −0.44, P = .003). The 6-min walk distance, COPD Assessment Test score and maximal expiratory pressure values were significant and independent determinants of the London Chest Activity of Daily Living scale, with 40.1% of the variance in subjects with COPD.CONCLUSIONS:Functional exercise capacity, disease-related symptoms, and expiratory muscle strength have the greatest influence on ADL in the subjects with COPD. The level of independence to perform ADL can be increased by improving functional exercise capacity, reducing symptoms, and increasing expiratory muscle strength in subjects with COPD.

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Structural and functional differentiation of the microbial community in the surface and subsurface peat of two minerotrophic fens in China

Abstract

Background and aims

Microbial communities are the primary drivers of organic matter decomposition in peatlands. However, limited knowledge is available regarding depth-dependent microbial community structure and function in East Asian peatlands, using cultivation independent approaches.

Methods

We investigated the vertical stratification of prokaryote and fungal communities in a moderately rich fen in northeast China (Hani) and a rich fen in southwest China (Riganqiao).

Results

Fungal and prokaryotic operational taxonomic unit (OTU) composition exhibited strong site and/or depth responses. Prokaryotic OTUs exhibited the greatest alpha diversity at the mesotelm 'hot spot', whereas the predicted metagenomic metabolic functions did not align with the pattern of prokaryote alpha diversity. The large cover of shrubs contributed to a greater relative abundance of ericoid- and ecto-mycorrhizal fungi at Hani, whereas Riganqiao showed more arbuscular mycorrhizal fungi. Soil pH and water table depth were among the predominant abiotic factors associated with microbial community composition.

Conclusions

Projected shifts in hydrology and/or vegetation with global change may cause substantial impacts on peatland microorganisms and thus the associated biogeochemistry. It is critical to better understand the mechanism of the discrepancy between microbial community structure and the functions at the mesotelm 'hot spot' when evaluating the ecosystem functions in peatlands.

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Differential response to warming of the uptake of nitrogen by plant species in non-degraded and degraded alpine grasslands

Abstract

Purpose

Chemical niche differentiation and changes in the dominance of plant species have been proposed as mechanisms for the coexistence of different types of plants. We explored how dominant plant species take up ammonium (NH₄⁺), nitrate (NO₃⁻), and glycine under conditions of warming and soil degradation in alpine grasslands.

Materials and methods

Open-top chambers were used to simulate warming in degraded and non-degraded plots in an alpine grassland ecosystem on the Tibetan Plateau. Plant species were selected in both non-degraded (Kobresia pygmaea and Aster tataricus) and degraded (Aster tataricus and Chenopodium glaucum) plots. Short-term ¹⁵N-labeling experiments with NH₄⁺-N, NO₃⁻-N, and glycine (¹³C¹⁵N-glycine) were conducted in each of four subplots with water alone as the control.

Results and discussion

All of the selected plant species took up both organic and inorganic forms of N in the K. pygmaea grassland. Warming increased the uptake of glycine-N by the dominant species, whereas the uptake of NH₄⁺-N by the non-dominant species increased in both non-degraded and degraded grasslands. Warming changed the N uptake preference of A. tataricus from NO₃⁻-N to NH₄⁺-N in non-degraded grasslands, but did not change the preference of A. tataricus under degraded conditions. This suggests that degradation can affect the preference of different plant species for particular forms of N as a response to warming.

Conclusions

Plants in K. pygmaea grasslands take up organic N, although inorganic N is the dominant form of N used. The effects of warming on the uptake of N by plants varied with species, the form of N, and the degradation of the grassland. Degradation modified the effect of warming on the preference of plants for different forms of N. Different plant species developed different patterns for the uptake of N in both non-degraded and degraded plots, which may facilitate their coexistence in alpine grasslands.

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Preclinical PET tracers for the evaluation of sarcomas: understanding tumor biology.

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Preclinical PET tracers for the evaluation of sarcomas: understanding tumor biology.

Am J Nucl Med Mol Imaging. 2018;8(6):428-440

Authors: Sigal IR, Sebro R

Abstract
Sarcomas are rare tumors of mesenchymal origin. Sarcomas display significant histological heterogeneity, resulting in significant imaging heterogeneity. 18F-FDG PET has is increasingly used for the evaluation, staging and surveillance of patients with sarcomas. 18F-FDG PET maximum SUV has been shown to be correlated with sarcoma grade and overall survival. This has led to interest in alternative PET tracers to assess the biological characteristics of tumors and guide treatment decisions. Here we investigate novel PET/CT tracers used for the evaluation of sarcomas over the past 20 years and summarize what we have learned about sarcoma tumor biology from these studies.

PMID: 30697463 [PubMed]

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FDG PET imaging in multiple myeloma: implications for response assessments in clinical trials.

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FDG PET imaging in multiple myeloma: implications for response assessments in clinical trials.

Am J Nucl Med Mol Imaging. 2018;8(6):421-427

Authors: Sundaram S, Driscoll J, Fernandez-Ulloa M, de Lima M, Malek E

Abstract
18F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (18F-FDG PET/CT) is an effective modality to assess disease burden, detect extra-medullary disease and monitor minimal residual disease (MRD) for multiple myeloma (MM) patients. This modality of imaging is incorporated in the International Myeloma Working Group (IMWG) response criteria that are widely used in MM clinical trials. Interpretative pitfalls are commonly encountered in 18F-FDG PET/CT studies and proper interpretation requires knowledge of the normal physiologic distribution of the tracer affecting available 18F-FDG for tumor tissue uptake. We describe a series of MM patients who exhibited a deep response to treatment, based on clinical features, serum markers and bone marrow (BM) biopsy. However, these patients seemed to have new lesions on post-therapy 18F-FDG PET/CT images which could be interpreted as progressive disease according to the IMWG criteria. Sequestration phenomenon, which is the disappearance of 18F-FDG sequestration by myeloma-infiltrated marrow after successful anti-myeloma therapy, could lead to unmasking of new 18F-FDG-avid lesions on post-therapy PET/CT due to higher 18F-FDG bioavailability to residual tumor tissue. Clinical correlation, awareness of the 18F-FDG sequestration in myeloma infiltrated BM and its impact on other 18F-FDG avid areas in the body are necessary to avoid potential pitfalls in end-of-treatment imaging interpretation. While considering patients for clinical trials, clinicians should be mindful of this sequestration phenomenon in the interpretation of post-therapy PET/CT imaging in MM patients with initially heavily infiltrated marrow.

PMID: 30697462 [PubMed]

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Utility of metabolic heterogeneity factor in differentiating malignant versus benign parotid uptake on 18F FDG PET-CT.

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Utility of metabolic heterogeneity factor in differentiating malignant versus benign parotid uptake on 18F FDG PET-CT.

Am J Nucl Med Mol Imaging. 2018;8(6):415-420

Authors: Alipour R, Smith S, Gupta SK

Abstract
Differentiation of benign and malignant parotid uptake on Fluorine 18 Fluro-Deoxy-Glucose Positron Emission Tomography-Computed Tomography (18F FDG PET-CT) is of paramount importance due to the poor prognosis of the later but usual quantitative measures such as standardized uptake value (SUV) are not reliable for this purpose. Metabolic heterogeneity, being a characteristic of malignant tumors, would potentially be able to make this distinction. In this study, seventy-one FDG-avid parotid lesions were retrospectively separated histologically into benign and malignant groups. The heterogeneity factor (HF) of all the lesions was then calculated and compared between the two groups. There was significant difference in HF between malignant (median -0.17) and benign group (median -0.03); P=0.0006. On receiver operating characteristic (ROC) analysis, a cut-off value of ≤ -0.06 for HF was associated with the highest sensitivity and specificity (sensitivity and specificity of 94.6% and 60.0%, respectively-AUC=0.789; P=0.0001). Hence, it was concluded that HF is a reliable value in distinguishing benign from malignant parotid uptake on 18F FDG PET-CT.

PMID: 30697461 [PubMed]

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Pre-treatment partial-volume-corrected TLG is the best predictor of overall survival in patients with relapsing/refractory non-hodgkin lymphoma following radioimmunotherapy.

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Pre-treatment partial-volume-corrected TLG is the best predictor of overall survival in patients with relapsing/refractory non-hodgkin lymphoma following radioimmunotherapy.

Am J Nucl Med Mol Imaging. 2018;8(6):407-414

Authors: Taghvaei R, Zadeh MZ, Sirous R, Shamchi SP, Raynor WY, Seraj SM, Moghbel M, Wang S, Werner TJ, Zhuang H, Alavi A

Abstract
The role of fluorodeoxyglucose-positron emission tomography (FDG-PET) has been well established in assessment of lymphoma, including non-Hodgkin lymphoma (NHL). The aim of this study was to compare changes and survival predictive values of various quantification parameters of FDG-PET/CT in patients with relapsing/refractory lymphoma before and after radioimmunotherapy (RIT). Data from 17 patients with relapsing/refractory NHL, treated with targeted RIT after chemotherapy/radiotherapy, were retrospectively collected. FDG-PET/CT scans were performed approximately three months before and six months after RIT. An adaptive contrast-oriented thresholding algorithm was used to segment lesions on the FDG-PET images. Wilcoxon signed-rank tests were used to assess changes in SUVmax, SUVmean, partial volume-corrected SUVmean (pvcSUVmean), total lesion glycolysis (TLG), and pvcTLG before and after treatment. The patients were followed up after completing RIT for up to 10 years. Kaplan-Meier and Cox regression analyses evaluated the association between the quantification parameters and survival data. In the survived group, the decrease in mean percentage of change for TLG and pvcTLG was greater than SUVmax, SUVmean and pvcSUVmean [TLG: 253.9 to 106.9, -81.4%; P = 0.052 and pvcTLG: 368.9 to 153.3, -58.4%; P = 0.04]. In addition, overall survival (OS) was shorter in patients with pre-RIT pvcTLG more than 644 compared to those below this value (log-rank P < 0.01). In univariate Cox regression for OS, a higher baseline pvcTLG was a significant prognostic factor (HR: 6.8, P = 0.02). Our results showed that pre-treatment pvcTLG was the best predictor of OS in patients with relapsing/refractory NHL following RIT.

PMID: 30697460 [PubMed]

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Evaluation of planar bioluminescence imaging and microPET/CT for therapy monitoring in a mouse model of pigmented metastatic melanoma.

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Evaluation of planar bioluminescence imaging and microPET/CT for therapy monitoring in a mouse model of pigmented metastatic melanoma.

Am J Nucl Med Mol Imaging. 2018;8(6):397-406

Authors: Pasquereau-Kotula E, Hosten B, Hontonnou F, Vignal N, Antoni F, Poyet JL, Rizzo-Padoin N, Sarda-Mantel L

Abstract
Bioluminescence imaging (BLI) is widely used for in-vivo monitoring of anti-cancer therapy in mice. [18F]MEL050 is a Positron Emission Tomography (PET) radiotracer which specifically targets melanin. We evaluated planar BLI and [18F]MEL050-PET/CT for therapy (pro-apoptotic peptide LZDP) monitoring in a mouse model of metastatic pigmented melanoma. Twelve B6-albino mice were intravenously injected with B16-F10-luc2 cells on day 0 (D0). The mice received daily from D2 to D17 either an inactive peptide (G1, n=6), or LZDP (G2, n=6). They underwent both BLI and [18F]MEL050-PET/CT imaging on D2, D8 and D17. The number of visible tumors was determined on BLI and PET/CT. [18F]MEL050 uptake in tumor sites was quantified on PET/CT. After sacrifice (D17), the number of black tumors was counted ex-vivo. On D2, BLI and PET/CT images were visually negative. On D8, BLI detected 8 tumor sites in 4/6 mice of G1 vs 5 in 3/6 mice of G2 (NS); PET/CT was visually negative. On D17, BLI detected 17 tumor sites in 5/6 mice of G1 vs 10 in 4/6 mice of G2 (NS). PET/CT detected 18 tumor sites in 4/4 mice of G1 vs 14 in 3/4 mice of G2 (NS). Mean %ID/g of [18F]MEL050 in tumor sites was lower in G2 than in G1 on D17 (P<0.001), whereas bioluminescence intensity was not different between the 2 groups. Ex-vivo examination confirmed lower number of tumors in G2 (P<0.03). In the small number of animals tested in this study, [18F]MEL050-PET/CT and ex-vivo examination could affirm anti-tumoral effect of LZDP, but not BLI.

PMID: 30697459 [PubMed]

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Metabolic and densitometric correlation between atherosclerotic plaque and trabecular bone: an 18F-Natrium-Fluoride PET/CT study.

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Metabolic and densitometric correlation between atherosclerotic plaque and trabecular bone: an 18F-Natrium-Fluoride PET/CT study.

Am J Nucl Med Mol Imaging. 2018;8(6):387-396

Authors: Fiz F, Bauckneht M, Piccardo A, Campi C, Nieri A, Piva R, Ferrarazzo G, Artom N, Morbelli S, Marini C, Piana M, Bagnasco M, Canepa M, Sambuceti G

Abstract
Increasing evidence links atherosclerosis to a decreased bone thickness. This correlation could reflect a bone/plaque interaction. Hereby we analyzed Hounsfield density (HU) and mineral turnover in bone and in the arterial calcifications (AC), using a computational method applied to PET/CT data. 79 18F-NaF PET/CT from patients with AC were retrospectively analyzed. Mean AC density and background-corrected uptake (TBR) were estimated after semi-automatic isocontour segmentation. The same values were assessed in the trabecular bone, using an automatic adaptive thresholding method. Patients were then stratified into terciles, according to their mean HU plaque density ("light", "medium" or "heavy" calcifications"). 35 18F-NaF PET/CT from patients without AC served as controls. Vertebral density and TBR were lower in patients than in controls (137±25 vs. 160±14 HU, P<0.001); (6.2±3.9 vs. 8.4±3.4, P<0.05). Mean trabecular TBR values were 8.3±4, 4.5±2.1 and 3.5±1.8 in light, medium and heavy AC groups, respectively (P<0.05 for light vs. medium and P<0.01 for light vs. heavy). Similarly, mean trabecular HU was 143±19, 127±26 and 119±18 in the three groups, respectively (P<0.01 for light vs. heavy). Mean AC density was inversely associated with the trabecular HU (R=-0.56, P<0.01). Conversely, plaques' TBR directly correlated with the one in trabecular bone (R=0.63, P<0.001). At multivariate analysis, the sole predictor of vertebral density was plaque HU (P<0.05). Our data highlight a correlation between plaque and bone morpho-functional parameters and suggest that observing skeletal bone characteristics could represent a novel window on atherosclerosis pathophysiology.

PMID: 30697458 [PubMed]

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Multi-level otsu method to define metabolic tumor volume in positron emission tomography.

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Multi-level otsu method to define metabolic tumor volume in positron emission tomography.

Am J Nucl Med Mol Imaging. 2018;8(6):373-386

Authors: Im HJ, Solaiyappan M, Lee I, Bradshaw T, Daw NC, Navid F, Shulkin BL, Cho SY

Abstract
This study was to validate reliability and clinical utility of a PET tumor segmentation method using multi-level Otsu (MO-PET) in standard National Electrical Manufacturers Association (NEMA) image quality (IQ) phantom and patients with osteosarcoma. The NEMA IQ phantom was prepared with a lesion-to-background ratio (LBR) of either 8:1, 4:1, or 1.5:1. The artificial lesions in the phantom were segmented using MO-PET, gradient-based method (PETedge), relative threshold methods, and background threshold methods. Metabolic tumor volumes (MTVs) using MO-PET and PETedge were named as MTV (MO-PET) and MTV (PETedge), respectively. Among the MTVs using multiple methods, only MTV (MO-PET) and MTV (PETedge) showed excellent agreements with the actual volume of NEMA IQ phantom across the different LBRs (intraclass correlation coefficient, ICC = 0.987, 0.985 in LBR 8:1, 0.981, 0.993 in LBR 4:1 and 0.947, 0.994 in LBR 1.5:1). Repeated measurements of MTV (MO-PET) of the primary tumors showed excellent reproducibility with ICC of 0.994 (0.989-0.997) in patients with osteosarcoma. Also, MTV (MO-PET) was found to be predictive of Event Free Survival (EFS) [Hazard ratio (95% CI) = 6.1 (2.1-17.2), log rank P = 0.0003] in patients with osteosarcoma. We have validated in NEMA IQ phantom that the MTV (MO-PET) is accurate, and importantly, stable and consistent across a range of lesion sizes and LBRs representative of clinical tumor lesions. Furthermore, MTV (MO-PET) showed excellent reproducibility and was predictive for EFS in patients with osteosarcoma.

PMID: 30697457 [PubMed]

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Early perfusion and dopamine transporter imaging using 18F-FP-CIT PET/CT in patients with parkinsonism.

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Early perfusion and dopamine transporter imaging using 18F-FP-CIT PET/CT in patients with parkinsonism.

Am J Nucl Med Mol Imaging. 2018;8(6):360-372

Authors: Hong CM, Ryu HS, Ahn BC

Abstract
Combined use of 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) for dopamine transporter imaging and 18F-fludeoxyglucose (FDG) for glucose metabolism shows good diagnostic performance for differential diagnosis of Parkinson disease (PD) and Parkinson plus syndrome (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies). A recent study showed that 18F-FP-CIT positron emission tomography (PET) with early perfusion imaging is useful for the differential diagnosis of PD and Parkinson plus syndrome with lower radiation exposure, time, and cost. In this review, we summarize the advantages of using 18F-FP-CIT PET for perfusion and dopamine transporter imaging, as well as clinical features useful for the differential diagnosis of PD and Parkinson plus syndrome.

PMID: 30697456 [PubMed]

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Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial

Summary

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Twelve patients with advanced lung adenocarcinoma were enrolled, the primary endpoint was safety. Two doses of apatinib, 250 mg/day (level 1) and 500 mg/day (level 2), were evaluated in combination with 60 mg/m² doxetacel every 3 weeks. Six patients have been treated at levels 1 and 2, respectively. Optimal dose of apatinib was determined by dose-limiting toxicity (DLT). Results Six patients have been treated at levels 1 and 2. At level 1, one of six patients experienced grade 3 acneiform rash as DLTs. At level 2, two patients experienced grade 3 hypertension and one experienced grade 3 nasal bleeding. MTD and recommended dose for phase II study was 250 mg/day. Most frequent adverse events of any grade were bilirubin elevation, hypertension, alanine aminotransferase elevation, transglutaminase elevation, hand foot syndrome and fatigue. The median progression-free survival was 2.76 month. Moreover, three patients had developed progressive disease and the mean duration of response was 2.79 months. Conclusion Apatinib plus docetaxel was well tolerated and showed promising efficacy in advanced lung adenocarcinoma. This combination therapy may represent a potent therapeutic option for advanced lung adenocarcinoma patients with wild-type EGFR.

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Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo

Summary

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3⁺ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

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Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines

Summary

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and sensitizes glioblastoma cells to temozolomide cytotoxicity. Herein, we report in vitro activity of three semi-synthetic ingenol compounds derived from E. tirucalli, IngA (ingenol-3-trans-cinnamate), IngB (ingenol-3-hexanoate) and IngC (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Antineoplastic effects of the three semi-synthetic compounds were assessed using MTS assays on 70 cancer cell lines from a wide array of solid tumors. Additionally, their antitumor potential was compared with known compounds of the same class, namely ingenol-3-angelate (Picato®) and ingenol 3,20-dibenzoate and in combination with standard chemotherapeutic agents. We observed that IngA, B, and C exhibited dose-dependent cytotoxic effects. Amongst the semi-synthetic compounds, IngC displayed the best activity across the tumor cell lines. In comparison with ingenol-3-angelate and ingenol 3,20-dibenzoate, IngC showed a mean of 6.6 and 3.6-fold higher efficacy, respectively, against esophageal cancer cell lines. Besides, IngC sensitized esophageal cancer cells to paclitaxel treatment. In conclusion, the semi-synthetic ingenol compounds, in particular, IngC, demonstrated a potent antitumor activity on all cancer cell lines evaluated. Although the underlying mechanisms of action of IngC are not elucidated, our results provide insights for further studies suggesting IngC as a putative therapy for cancer treatment.

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Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo

Summary

We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.

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Antibacterial effects of iron oxide (Fe 3 O 4 ) nanoparticles: distinguishing concentration-dependent effects with different bacterial cells growth and membrane-associated mechanisms

Abstract

Nowadays, the influence of nanoparticles (NPs) on microorganisms attracts a great deal of attention as an alternative to antibiotics. Iron oxide (Fe₃O₄) NPs' effects on Gram-negative Escherichia coli BW 25113 and Gram-positive Enterococcus hirae ATCC 9790 growth and membrane-associated mechanisms have been investigated in this study. Growth specific rate of E. coli was decreased, indicating the bactericidal effect of Fe₃O₄ NPs. This inhibitory effect of NPs had a concentration-dependent manner. The reactive oxygen species together with superoxide radicals and singlet oxygen formed by Fe₃O₄ NPs could be the inhibition cause. Fe₃O₄ NPs showed opposite effects on E. hirae: the growth stimulation or inhibition was observed depending on NPs concentration used. Addition of NPs altered redox potential kinetics and inhibited H₂ yield in E. coli; no change in intracellular pH was determined. Fe₃O₄ NPs decreased H⁺-fluxes through bacterial membrane more in E. coli than in E. hirae even in the presence of DCCD and increased ATPase activity more in E. hirae than in E. coli. Our results showed that the Fe₃O₄ NPs demonstrate differentiating effects on Gram-negative and Gram-positive bacteria likely due to the differences in bacterial cell wall structure and metabolic peculiarities. Fe₃O₄ NPs of different concentrations have no hemolytic (cytotoxic) activity against erythrocytes. Therefore, they can be proposed as antibacterial agents in biomedicine, biotechnology, and pharmaceutics.

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Enhanced production and identification of antioxidants in in vitro cultures of the cacti Mammillaria candida and Turbinicarpus laui

Abstract

Cacti are an important source of metabolites but present limitations for their commercial exploitation, like slow growth and a decrease of wild populations. An alternative to obtain their biocompounds without affecting the natural environment are the in vitro culture techniques. We established in vitro cultures from Mammillaria candida Scheidweiler and Turbinicarpus laui Glass and Foster and used different stresses to increase metabolites and antioxidant activity. The cultures were exposed to 1.25% polyethylene glycol to induce a moderate drought stress, 50 g L⁻¹ sucrose to generate an osmotic stress, chitosan (1.25 to 5 mg mL⁻¹) to simulate a biotic attack, or to UV light. Chitosan was the best elicitor improving 1.5 times the concentration of phenolics, 9 to 10 times the content of flavonoids and betalains, and 16% the antioxidant activity in M. candida suspensions. In T. laui suspensions, this elicitor duplicates the flavonoids content and antioxidant activity. The antioxidant levels in elicited suspensions increased 5 to 10 times in relation to plant tubercles. Eleven compounds were identified in M. candida suspensions being digalloyl rhamnoside and epicatequin gallate the most abundant; in the T. laui suspensions, 16 compounds were detected and the most abundant were 17-decarboxi neobetanin and derivatives of luteolin. Thus, cacti in vitro culture is an efficient system to obtain high level of metabolites of biological interest.

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What is the importance of saving lean mass in the treatment of obesity and related diseases?

L'articolo What is the importance of saving lean mass in the treatment of obesity and related diseases? sembra essere il primo su European Review.

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Activated YAP causes renal damage of type 2 diabetic nephropathy

OBJECTIVE: Yes-associated protein (YAP) is a critical factor of Hippo pathway. It can control organ size, regulate proliferation, differentiation, and apoptosis of cells, and mediate epithelial-mesenchymal transition and cell contact inhibition. It has gradually become a hot spot in the field of diabetic nephropathy (DN). Tea domain (TEAD) is a factor with a deoxyribose nucleic acid (DNA) binding domain, which combines with activated YAP to control the expression of their important target factor – connective tissue growth factor (CTGF).

PATIENTS AND METHODS: We have investigated the role of YAP in type 2 diabetic nephropathy and evaluated the correlation between YAP and the progress of type 2 diabetic nephropathy. We have detected the expression of YAP, TEAD and CTGF in normal people (n=10) and patients with DN (n=51) by immunohistochemical and immunofluorescence staining and evaluated the relationship among clinical, pathologic data and YAP expression in type 2 diabetic nephropathy.

RESULTS: In kidneys of type 2 diabetic nephropathy, YAP, TEAD and CTGF were highly expressed in the nucleus of glomerular podocytes. In those healthy kidneys, however, all three of the above factors were mainly expressed in cytoplasm. Furthermore, the high expression of YAP in DN had relevance to increasing systolic blood pressure (SBP) (r=0.484, p=0.019), blood urea nitrogen (BUN) (r=0.522, p=0.032), creatinine (Cr) (r=0.496, p=0.031), progression of DN stage (r=0.647, p=0.001) and progression of DN pathologic classification (r=0.298, p=0.033). In addition, decreasing serum albumin (SAlb) (r=-0.656, p=0.001) and estimated glomerular filtration rate (eGFR) (r=-0.607, p=0.006) were also correlated with the high expression of YAP in DN.

CONCLUSIONS: High expression of YAP, TEAD and CTGF in kidney tissues suggested that YAP played a significant role in the renal damage of type 2 diabetic nephropathy. YAP that is correlated with SBP, BUN, Cr, DN stage, DN pathologic classification, SAlb and eGFR, suggested that inhibition of the activity of YAP might have the effect in delaying DN progression.

L'articolo Activated YAP causes renal damage of type 2 diabetic nephropathy sembra essere il primo su European Review.

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Long non-coding RNA Tubulin Alpha 4B (TUBA4B) inhibited breast cancer proliferation and invasion by directly targeting miR-19

OBJECTIVE: Long non-coding RNA (lncRNA) is a significant member of the non-coding RNA family. New evidence has shown that it plays a pivotal role in the processes of tumor genesis and development. According to previous verification, the lncRNA Tubulin Alpha 4B (TUBA4B) is a tumor-associated molecule, but how TUBA4B expresses and functions in breast cancer is still not clear.

PATIENTS AND METHODS: We conducted this study to examine what expression and biological role TUBA4B plays in breast cancer. The expression of TUBA4B was measured in breast cancer samples and cell lines. CCK8 assays and transwell assays were used for evaluating the effects of TUBA4B on breast cancer cell proliferation and invasion. Luciferase reporter assays were used for identifying the direct target of TUBA4B.

RESULTS: According to the results, TUBA4B was largely downregulated in breast cancer samples and cell lines. The functional analysis demonstrated that breast cancer cells proliferation and invasion could be inhibited by overexpression of TUBA4B. The results of Luciferase reporter assays indicated that TUBA4B directly targeted miR-19, which could rescue the effects of TUBA4B on breast cancer cells.

CONCLUSIONS: It is suggested that TUBA4B was downregulated in breast cancer and suppressed proliferation and invasion of breast cancer by targeting miR-19.

L'articolo Long non-coding RNA Tubulin Alpha 4B (TUBA4B) inhibited breast cancer proliferation and invasion by directly targeting miR-19 sembra essere il primo su European Review.

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RNA-seq analysis of diet-driven obesity and anti-obesity effects of quercetin glucoside or epigallocatechin gallate in Drosophila adults

OBJECTIVE: High-fat diet (HFD) feeding stimulates fat accumulation in mammals and Drosophila. In the present study, we examined whether simultaneous feeding of familiar anti-obesity drugs, quercetin glycosides (QG) and epigallocatechin gallate (EGCG), to Drosophila has the same suppressive effect on fat accumulation as previously reported in rats and mice. To understand the underlying molecular mechanisms of HFD diet-induced obesity and the suppression effect of the drugs, we performed transcriptome analyses.

MATERIALS AND METHODS: We induced extra fat accumulation by feeding Drosophila fly food containing 20% coconut oil and quantified the triglyceride accumulated in flies. The effects of anti-obesity drugs were also evaluated. We isolated total RNA from each sample and performed RNA-seq analyses and quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) to investigate altered gene expression.

RESULTS: The mRNA levels of several genes involved in lipid metabolism, glycolysis/gluconeogenesis, and anti-oxidative stress changed in HFD-fed adults. Moreover, the levels altered in those fed an HFD with QG or EGCG. The qRT-PCR further confirmed the RNA-seq data, suggesting that the expression of five essential genes for lipid metabolism changed in HFD-fed flies and altered in the flies treated with anti-obesity drugs. The most remarkable alteration was observed in the dHSL gene encoding a lipase involved in lipid-storage after HFD feeding and HFD with QG or EGCG. These alterations are consistent with HFD-induced fat accumulation as well as the anti-obesity effects of the drugs in mammals, suggesting that the genes play an important role in anti-obesity effects.

CONCLUSIONS: These are the first reports to date of entire profiles of altered gene expression under the conditions of diet-induced obesity and its suppression by anti-obesity drugs in Drosophila.

L'articolo RNA-seq analysis of diet-driven obesity and anti-obesity effects of quercetin glucoside or epigallocatechin gallate in Drosophila adults sembra essere il primo su European Review.

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Advancements in uterus transplant: new scenarios and future implications

Women suffering from Uterine Factor Infertility (UFI) arising from congenital conditions (e.g., Rokitansky-Kuster-Hauser syndrome) or hysterectomy can fulfill their wish to achieve motherhood only by resorting to surrogacy, which is, however, banned in most countries. Medical research has long been looking into uterus transplant (UTx), which may constitute a valuable alternative for such patients. Following decades of animal testing and clinical trials, several successful pregnancies have been carried to term. Yet UTx is still to be considered as an experimental procedure. The report's authors believe UTx has the potential to become a mainstream surgical practice, but for the time being, several ethical issues need to be weighed in before it does.

L'articolo Advancements in uterus transplant: new scenarios and future implications sembra essere il primo su European Review.

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Occurrence, speciation, and risks of trace metals in soils of greenhouse vegetable production from the vicinity of industrial areas in the Yangtze River Delta, China

Abstract

The effect of industrial activities on trace metals in farmland of rapidly industrializing regions in developing countries has increasingly been a concern to the public. Here, soils were collected from 13 greenhouse vegetable production (GVP) farms or bases near industrial areas in the Yangtze River Delta of China to investigate the occurrence, speciation, and risks of Cr, Cu, Zn, Cd, Ni, and Pb in GVP soil. The results revealed that the main metal elements causing GVP soil pollution were Cd, Zn, Ni, and Cu, of which contamination levels were generally unpolluted to moderately polluted. Zinc pollution was mainly attributed to heavy fertilization, while Cd, Ni, and Cu pollution may be greatly ascribed to industrial effluents and coal combustion. Metal speciation studies showed that most of Cr, Ni, Cu, and Zn was present in residual fraction while more than half of Cd and Pb was present in non-residual fractions. Additionally, pollution of Cd, Cu, Ni, and Zn in GVP soil increased their corresponding mobile fractions. Risk assessment using potential ecological risk index and risk assessment code showed that Cd was the major risk contributor. Specifically, Cd generally posed moderate or considerable ecological risk as well as displayed medium or high mobility risk in GVP soil. Thus, great attention should be paid to the contribution of both industrial discharges and intensive farming to soil pollution by trace metals, especially Cd, because of its high mobility risk.

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Techno-economic assessment of coconut biodiesel as a potential alternative fuel for compression ignition engines

Abstract

Over the past years, there were dramatic improvements in identifying and assessing various feedstocks for the production of biodiesel fuels. To promote a particular feedstock as a renewable source of energy, it is important to analyze their energy, economic, and engine performance characteristics. The current work attempts to evaluate the net energy and economic indices for both fossil diesel and coconut-blended diesel (B20) considering the diesel consumption by the Indian railways. Further, we present the experimental results of a multi-cylinder diesel engine operated with neat coconut biodiesel (B100) and fossil diesel at various load and speed conditions. The engine experiments reveal that the coconut biodiesel exhibits leaner combustion and shorter ignition delay than fossil diesel. Lower amount of carbon monoxide, hydrocarbon, and smoke emission is observed in the case of coconut biodiesel, with higher levels of nitric oxide (14%) and fuel consumption than diesel. The coefficient of variation in indicated mean effective pressure is within the range of better driveability zone for both the fuels at all test conditions. Overall the engine performance, emission and combustion results with neat coconut biodiesel are favorable with a penalty in NO emission at high load conditions. The techno-economical study highlights higher production cost per liter of B20 than the cost of fossil diesel. However, the net energy ratio (NER) for B20 is 1.021, favoring higher output than diesel and thus lowers the dependency on crude oil.

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Biodegradation of anthracene and different PAHs by a yellow laccase from Leucoagaricus gongylophorus

Abstract

Laccases produced by Leucoagaricus gongylophorus act in lignocellulose degradation and detoxification processes. Therefore, the use of L. gongylophorus laccase (Lac1Lg) was proposed in this work for degradation of anthracene and others polycyclic aromatic hydrocarbons without the use of mediators. Degradation reactions were performed in buffer aqueous solution with 10 ppm of anthracene and other PAHs, Tween-20 in 0.25% v/v and a laccase preparation of 50 U. The optimum condition (pH 6.0 and 30 °C) was determined by response surface methodology with an excellent coefficient of determination (R²) of 0.97 and an adjusted coefficient of determination (R²_adj) of 0.93. In addition, the employment of the mediator ABTS decreased the anthracene biodegradation from 44 ± 1% to 30 ± 1%. This optimum pH of 6.0 suggests that the reaction occurs by a hydrogen atom transfer mechanism. Additionally, in 24 h Lac1Lg biodegraded 72 ± 1% anthracene, 40 ± 3% fluorene and 25 ± 3% phenanthrene. The yellow laccase from L. gongylophorus biodegraded anthracene and produced anthrone and anthraquinone, which are interesting compounds for industrial applications. Moreover, this enzyme also biodegraded the PAHs phenanthrene and fluorene justifying the study of Lac1Lg for bioremediation of these compounds in the environment.

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Serum levels of histamine and diamine oxidase in multiple sclerosis.

Related Articles

Serum levels of histamine and diamine oxidase in multiple sclerosis.

Am J Clin Exp Immunol. 2018;7(6):100-105

Authors: Rafiee Zadeh A, Falahatian M, Alsahebfosoul F

Abstract
BACKGROUND: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system, mostly affecting young adults. Diamine oxidase is an enzyme essential for histamine production. Histamine which is produced mostly by mast cells can have effects on different aspects of immune system via its different histamine receptors (H1R, H2R, H3R and H4R). The crucial role of diamine oxidase and histamine in immune balance has been documented in different studies and experiments both on MS patients and on experimental allergic encephalomyelitis (EAE). In this regard, we aimed to measure the level of histamine and diamine oxidase in the serum of MS patients.
METHODS: A total number of 50 relapsing-remitting MS (RRMS) patients and 41 age and sex matched controls were enrolled in this study. Assessments of serum levels of histamine and diamine oxidase enzyme were performed using enzyme-linked immune sorbent assay (ELISA).
RESULTS: The serum levels of histamine and diamine oxidase in RRMS patients were lower than healthy controls (P-value = 0.00, for both).
CONCLUSION: Our research team found significant low levels of histamine and diamine oxidase in RRMS patients; however the pathogenesis of this issue was unclear.

PMID: 30697467 [PubMed]

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Pressure pain assessment may predict the outcome of spinal cord stimulation for refractory epilepsy.

Related Articles

Pressure pain assessment may predict the outcome of spinal cord stimulation for refractory epilepsy.

Am J Clin Exp Immunol. 2018;7(6):95-99

Authors: Feng L, Fan LH, Wu DZ

Abstract
It was well-documented that epilepsy and pain arise from an excitation-inhibition imbalance within neuronal networks. A previous meta-analysis of data from clinical trials showed an association between anticonvulsants and specific pain types, e.g. multiple sclerosis pain. Multiple multicentre randomized controlled trials have shown that antiepileptic drugs have a prominent role in the treatment of several types of pain, e.g. neuropathic pain. Many anticonvulsants have been introduced to better manage acute postoperative pain, with improvements in analgesic efficacy and safety. These data suggested that there existed the similar mechanisms of certain forms of epilepsy and pain, and the therapeutic mechanism of spinal cord stimulation for certain forms of epilepsy and pain may be involved in the melanocortinergic signaling, and the change in cerebral glucose metabolism. We hypothesized that pressure pain assessment may predict the outcome of spinal cord stimulation in refractory epilepsy.

PMID: 30697466 [PubMed]

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Heterologous expression of nifA or nodD genes improves chickpea- Mesorhizobium symbiotic performance

Abstract

Aims

The aim of this study was to investigate whether the overexpression of NifA and NodD regulators contribute to the symbiotic improvement of chickpea mesorhizobia.

Methods

The native strains V-15b, ST-2, and PMI-6 were transformed with extra copies of nifA or nodD genes and several plants trial were performed.

Results

Plant growth assays showed that nifA overexpression was able to improve the symbiotic effectiveness of V-15b, while nodD overexpression lead to the improvement of ST-2 and PMI-6. Hydroponic assays showed that plants inoculated with V15bnifA⁺ and PMI6nodD⁺ started developing nodules earlier than those inoculated with the corresponding control strains. In addition, the number of nodules was always higher in plants inoculated with the strains overexpressing the symbiotic genes. Analysis of histological sections of nodules formed by V15bnifA⁺ showed a more developed fixation zone when compared with control. On the other hand, nodules induced by PMI6nodD⁺ did not show a senescent zone, which was observed in nodules from plants inoculated with the control strain. Plants inoculated with PMI6nodD⁺ and ST2nodD⁺ showed a higher number of infection threads than the corresponding control inoculations.

Conclusion

These results indicate that overexpressing nifA and nodD may be an important tool to achieve the improvement of the symbiotic performance of mesorhizobia.

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Tracing root-felt sodium concentrations under different transpiration rates and salinity levels

Abstract

Aims

(1) Monitoring 'root-felt' salinity by using rhizoslides as a non-invasive method, (2) Studying how transpiration rate, salinity in irrigation water, and root water uptake affect sodium distribution around single roots, (3) Interpreting experimental results by using simulations with a 3-D root system architecture model coupled with water flow and solute transport models.

Methods

Tomato plants were grown on rhizoslides under various salinity levels and two transpiration rates: high and low. Daily root images were processed with GIMP and incorporated into a 3-D numerical model. The experiments were simulated with R-SWMS, a 3-dimensional numerical model that simulates water flow and solute transport in soil, into the root and inside root systems.

Results

Both experimental and simulation results displayed higher root-felt sodium concentrations compared with the bulk concentrations, and larger accumulation at higher transpiration rate. The simulations illustrated that the root-felt to bulk concentration ratio changed during the experiment depending both on the irrigation water salinity and transpiration rate.

Conclusions

Changes in sodium concentrations with transpiration rates are most likely caused by root water uptake and ion exclusion. Simulation results indicate that root-scale process models are required to link root system architecture, environmental, and soil conditions with root-felt salinities.

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Antimony tolerance and accumulation in a metallicolous and a non-metallicolous population of Salvia spinosa L.

Abstract

Aims

Antimony (Sb) is locally found at potentially toxic concentrations in mineralized soils, usually together with arsenic (As). However, local adaptation of plant populations to Sb toxicity has never been shown thus far. Here we compared Sb tolerance and accumulation between a non-metallicolous (NM) population of Salvia spinosa, and a con-specific metallicolous (M) population from a strongly Sb/As-enriched soil in Dashkasan, Iran.

Methods

Plants were exposed in hydroponics to a series of Sb[III] and Sb[V] concentrations. After 3 weeks the dry weights and Sb concentrations of roots and shoots were determined.

Results

Estimated from the effects on shoot dry weight, the M population was more tolerant than the NM one, particularly to Sb[V], but to a lower degree also to Sb[III]. In both populations Sb[III] was taken up and translocated at higher rates than Sb[V]. The Sb concentrations in roots and shoots were slightly, but significantly higher in the M than in the NM population.

Conclusions

Since Sb[V] and As[V] seem to follow very different detoxification pathways, it can be argued that the superior tolerance to Sb[V] in M represents a local adaptation to Sb[V] toxicity itself, rather than being a mere by-product of hypertolerance to its chemical analogue, As[V]. Since Sb[III] and As[III] or As[V] share common detoxification pathways, the apparent Sb[III] hypertolerance in the M population might represent a by-product of As hypertolerance.

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