Azacitidine-induced Sweet syndrome: Two unusual clinical presentations

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Treatment of Hailey–Hailey disease with botulinum toxin

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Female gonadal shielding with automatic exposure control increases radiation risks

Abstract

Background

Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area.

Objective

We assess changes in dose–area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography.

Materials and methods

We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry.

Results

Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21–51% in the 5-year-old phantom and 17–100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom.

Conclusion

Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation.

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Study finds lamotrigine to be safe during pregnancy

Use of the epilepsy drug lamotrigine during pregnancy does not increase the risk of birth malformations or neurodevelopmental disorder, according to research published in the British Journal of...

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Treating Hepatitis C Infection in Patients With Chronic Kidney Disease: Our Options Have Improved Greatly

Opinion statement

Chronic hepatitis C infection (HCV) is a common problem in patients with kidney disease (Corouge M. et al. Liver Int (2016); 36:28–33, Fabrizi F. et al. Int. J. Artif. Organs (2017); 0). In the past, treatment of hepatitis C infection was very difficult due to poor efficacy, significant side effects, and the multiple comorbidities that affect patients with advanced kidney disease (Pockros PJ et al. Gastroenterology (2016); 150:1590–1598). Significant recent advances in oral interferon-free treatment regimens allow patients with hepatitis C to be treated effectively with minimal side effects. For patients with genotype 1a, 1b, or 4, there are several recommended oral regimens that achieve virologic cure in greater than 95% of patients, even in patients with severe or end-stage renal disease. For other genotypes, specifically 2, 3, 5, and 6, treatment with direct acting antiviral (DAA) agents that are used in patients with normal renal clearance has significant potential for side effects and is not recommended. Patients who are waiting for a kidney transplant or who have received a kidney transplant and have estimated eGFR greater than 30 ml/min can be treated with multiple regimens in an attempt to cure their hepatitis C (Fabrizi F. et al. Int. J. Artif. Organs (2017); 0). Patients with kidney-related complications due to their chronic hepatitis C infection can also be treated with a significant chance of resolution of the complication (Corouge M. et al. Liver Int (2016); 36:28–33, Kamar N. et al. Clin. Nephrol (2008); 69:149–160).

The timing of HCV treatment and kidney transplant depends on the individual transplant centers protocol and the patient's position on the waiting list for a kidney (Fabrizi F Clin. Liver Dis 2005; 9: 503, viii). USA transplant centers in order to reduce the time on the waiting list have decided to offer HCV-infected patients a kidney from an HCV-positive donor. Treatment of the HCV is then done early after recovery from the transplant surgery. Due to significant advances in developing oral direct acting antiviral agents, we now have safe and effective oral regimens to treat HCV-infected patients with renal disease, including those on hemodialysis, waiting for a kidney transplant, or after a renal transplant.

The purpose of this review is to summarize the currently recommended treatment regimens and provide clinicians with guidance in terms of the efficacy and safety of the new direct acting antiviral agents (DAAs) in treating HCV-infected patients who have advanced kidney disease.

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Consumer health information seeking in social media: a literature review

Abstract

Objective

The objective of this literature review was to summarise current research regarding how consumers seek health-related information from social media. Primarily, we hope to reveal characteristics of existing studies investigating the health topics that consumers have discussed in social media, ascertaining the roles social media have played in consumers' information-seeking processes and discussing the potential benefits and concerns of accessing consumer health information in social media.

Methods

The Web of Science Core Collection database was searched for existing literature on consumer health information seeking in social media. The search returned 214 articles, of which 21 met the eligibility criteria following review of full-text documents.

Conclusion

Between 2011 and 2016, twenty-one studies published explored various topics related to consumer information seeking in social media. These ranged from online discussions on specific diseases (e.g. diabetes) to public health concerns (e.g. pesticide residues). Consumers' information needs vary depending on the health issues of interest. Benefits of health seeking on social media, in addition to filling a need for health information, include the social and emotional support health consumers gain from peer-to-peer interactions. These benefits, however, are tempered by concerns of information quality and authority and lead to decreased consumer engagement.

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Predictors of Clinicopathologic Stage Discrepancy in Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Risk of Development of Second Primary Head and Neck Cancer following an Index Breast Cancer

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Desmoplastic Small Round Cell Tumor Presenting as an Ocular Mass: Unusual Localization and Remarkable Surgical Approach

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare tumor that was first described by Gerald and Rosai in 1989 as a mesenchymal entity. This tumor has a unique translocation t (11:22) (p:13, q:12) resulting in EWS/WT1 gene fusion that is diagnostic for DSCRT. The overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death as high as 90%. Although the majority of patients undergo chemotherapy following surgery, the prognosis has been shown to be independent of whether the surgical process preceded or followed chemotherapy. In this review, we provide insights for the management of DSCRT that requires aggressive multimodality therapy.

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Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

Abstract

In the past 15 years, the proteasome has been validated as an anti-cancer drug target and 20S proteasome inhibitors (such as bortezomib and carfilzomib) have been approved by the FDA for the treatment of multiple myeloma and some other liquid tumors. However, there are shortcomings of clinical proteasome inhibitors, including severe toxicity, drug resistance, and no effect in solid tumors. At the same time, extensive research has been conducted in the areas of natural compounds and old drug repositioning towards the goal of discovering effective, economical, low toxicity proteasome-inhibitory anti-cancer drugs. A variety of dietary polyphenols, medicinal molecules, metallic complexes, and metal-binding compounds have been found to be able to selectively inhibit tumor cellular proteasomes and induce apoptotic cell death in vitro and in vivo, supporting the clinical success of specific 20S proteasome inhibitors bortezomib and carfilzomib. Therefore, the discovery of natural proteasome inhibitors and researching old drugs with proteasome-inhibitory properties may provide an alternative strategy for improving the current status of cancer treatment and even prevention.

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Viruses, Vol. 9, Pages 302: Marine Viruses: Key Players in Marine Ecosystems

Viruses, Vol. 9, Pages 302: Marine Viruses: Key Players in Marine Ecosystems

Viruses doi: 10.3390/v9100302

Authors: Mathias Middelboe Corina Brussaard

Viruses were recognized as the causative agents of fish diseases, such as infectious pancreatic necrosis and Oregon sockeye disease, in the early 1960s [1], and have since been shown to be responsible for diseases in all marine life from bacteria to protists, mollusks, crustaceans, fish and mammals [2].[...]

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Medication-related osteonecrosis of the jaw (MRONJ): treatment and prevention

This Cochrane review of interventions for the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ) identified 5 trials. Three were related to prevention and two to treatment providing limited evidence to support interventions. More high quality studies are needed.

The post Medication-related osteonecrosis of the jaw (MRONJ): treatment and prevention appeared first on National Elf Service.

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Identification of Aptamers That Bind to Sickle Hemoglobin and Inhibit Its Polymerization

Nucleic Acid Therapeutics , Vol. 0, No. 0.


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Perioperative management of paraganglioma and catecholamine-induced cardiomyopathy in child– a case report and review of the literature

Paragangliomas are catecholamine-secreting tumors of the paraganglia. Perioperative mortality of children with paraganglioma is high, but preoperative therapy and anesthetic management of paraganglioma resecti...

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Preparing for the unexpected: special considerations and complications after sugammadex administration

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular...

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Intraoperative continuous cerebral microcirculation measurement in patients with aneurysmal subarachnoid hemorrhage: preliminary data on the early administration of magnesium sulfate

In patients with subarachnoid hemorrhage (SAH), vasospasm remains one of the major complications. The application of intravenous magnesium sulfate (MgSO4) has been under discussion to prevent cerebral ischemia. O...

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Role of tube size and intranasal compression of the nasotracheal tube in respiratory pressure loss during nasotracheal intubation: a laboratory study

Small nasotracheal tubes (NTTs) and intranasal compression of the NTT in the nasal cavity may contribute to increasing airway resistance. Since the effects of size, shape, and partial compression of the NTT on...

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Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age

Thyroid , Vol. 0, No. 0.


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Rebuttal to Smith and Janssen

Thyroid , Vol. 0, No. 0.


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Diffuse large B cell lymphoma

Diffuse large B cell lymphoma: a type of non-Hodgkin lymphoma, a cancer of the cells that make up the immune system. Diffuse large B-cell lymphoma is one of the most common types of non-Hodgkin lymphoma. The term "B-cell" refers to a specific type of white blood cell, the B-lymphocyte. The terms "diffuse" and "large cell" are used to describe the appearance of the cancer cells under the microscope. The incidence of diffuse large B-cell lymphoma increases with age. Symptoms can include swollen, painless lymph nodes anywhere in the body, fever, weight loss, night sweats, weakness, and tiredness. DLBCL is usually an aggressive tumor, and the cause is poorly understood. Having a weakened immune system is a risk factor for the development of DLBCL.

Also referred to as DLBCL or DLBL.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Anti-human immunodeficiency virus-1 activities of pratensein and pratensein glycoside from Alhaji maurorum and its parasite Cuscuta kotchiana

Abstract

Objective

To test the anti-human immunodeficiency virus (HIV) activity of pure compounds isolated from aerial part extracts of Alhaji maurorum and its parasite Cuscuta kotchiana.

Methods

The anti-HIV-1 and anti-HIV-2 activities of these extracts were performed by use of quantitative polymerase chain reaction assay and high pure viral nucleic acid kit. The most active fractions against HIV-1 were detected by nuclear magnetic resonance as pratensein and pratensein glycoside respectively in A. maurorum and C. campestris.

Results

These two extracts have low toxicity on HIV-2 replication. The 50% effective concentration for HIV-1 replication of pratensein and pratensein glycoside were 100 and 22 μg/mL, respectively. The time of addition assay showed that pratensein and pratensein glycoside were most effective when added at the early stage (0–4 h) of virus replication.

Conclusion

The pratensein glycoside inhibits HIV-1 replication in host cells more than pratensein and both extracts are potent inhibitors of HIV-1 entry.

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Shenyi Capsule (参一胶囊) plus chemotherapy versus chemotherapy for non-small cell lung cancer: A systematic review of overlapping meta-analyses

Abstract

Objective

To assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence by performing a systematic review of overlapping meta-analyses regarding Shenyi Capsule (参一胶囊, SC) plus chemotherapy versus chemotherapy of non-small cell lung cancer (NSCLC).

Methods

A literature search was conducted to select systematic reviews comparing SC plus chemotherapy with chemotherapy for NSCLC. Meta-analyses only composed of randomized controlled trials (RCTs) met the inclusion criteria. Two authors individually estimated the quality of meta-analysis and extracted data. The Jadad decision algorithm was applied to guarantee which meta-analysis provided the best original evidence.

Results

A total of 5 meta-analyses were included. All the studies composed of RCTs or quasi-RCTs and were regarded as level-II evidence. The scores of the Assessment of Multiple Systematic Reviews ranged from 3 to 6 (median 4). A high-quality meta-analysis with more RCTs was chosen, which suggested that SC plus chemotherapy could increase incidence of short-term efficacy, improve the quality of life and survival rate in comparison to chemotherapy. However, there was no statistically significant difference between SC plus chemotherapy and chemotherapy regarding chemotherapy-induced side effect, such as liver and kidney function obstacle, leukopenia, hemoglobin decrement and gastrointestinal adverse reaction.

Conclusions

Based on the best available evidence, treatment effect of SC plus chemotherapy was better than chemotherapy and did not increase side effects. Therefore, SC plus chemotherapy may be superior to chemotherapy for treating NSCLC. However, due to some limitations, SC plus chemotherapy should be cautiously considered, and further high-quality meta-analyses are needed.

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Prediction of protein complexes in Trypanosoma brucei by protein correlation profiling mass spectrometry and machine learning. [Technology]

A disproportionate number of predicted proteins from the genome sequence of the protozoan parasite Trypanosoma brucei, an important human and animal pathogen, are hypothetical proteins of unknown function. This paper describes a protein correlation profiling mass spectrometry approach, using two size exclusion and one ion exchange chromatography systems, to derive sets of predicted protein complexes in this organism by hierarchical clustering and machine learning methods. These hypothesis-generating proteomic data are provided in an open access online data visualisation environment (http://ift.tt/2yo7KFg). The data can be searched conveniently via a user friendly, custom graphical interface. We provide examples of both potential new subunits of known protein complexes and of novel trypanosome complexes of suggested function, contributing to improving the functional annotation of the trypanosome proteome. Data are available via ProteomeXchange with identifier PXD005968.

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Anti-human immunodeficiency virus-1 activities of pratensein and pratensein glycoside from Alhaji maurorum and its parasite Cuscuta kotchiana

Abstract

Objective

To test the anti-human immunodeficiency virus (HIV) activity of pure compounds isolated from aerial part extracts of Alhaji maurorum and its parasite Cuscuta kotchiana.

Methods

The anti-HIV-1 and anti-HIV-2 activities of these extracts were performed by use of quantitative polymerase chain reaction assay and high pure viral nucleic acid kit. The most active fractions against HIV-1 were detected by nuclear magnetic resonance as pratensein and pratensein glycoside respectively in A. maurorum and C. campestris.

Results

These two extracts have low toxicity on HIV-2 replication. The 50% effective concentration for HIV-1 replication of pratensein and pratensein glycoside were 100 and 22 μg/mL, respectively. The time of addition assay showed that pratensein and pratensein glycoside were most effective when added at the early stage (0–4 h) of virus replication.

Conclusion

The pratensein glycoside inhibits HIV-1 replication in host cells more than pratensein and both extracts are potent inhibitors of HIV-1 entry.

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Shenyi Capsule (参一胶囊) plus chemotherapy versus chemotherapy for non-small cell lung cancer: A systematic review of overlapping meta-analyses

Abstract

Objective

To assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence by performing a systematic review of overlapping meta-analyses regarding Shenyi Capsule (参一胶囊, SC) plus chemotherapy versus chemotherapy of non-small cell lung cancer (NSCLC).

Methods

A literature search was conducted to select systematic reviews comparing SC plus chemotherapy with chemotherapy for NSCLC. Meta-analyses only composed of randomized controlled trials (RCTs) met the inclusion criteria. Two authors individually estimated the quality of meta-analysis and extracted data. The Jadad decision algorithm was applied to guarantee which meta-analysis provided the best original evidence.

Results

A total of 5 meta-analyses were included. All the studies composed of RCTs or quasi-RCTs and were regarded as level-II evidence. The scores of the Assessment of Multiple Systematic Reviews ranged from 3 to 6 (median 4). A high-quality meta-analysis with more RCTs was chosen, which suggested that SC plus chemotherapy could increase incidence of short-term efficacy, improve the quality of life and survival rate in comparison to chemotherapy. However, there was no statistically significant difference between SC plus chemotherapy and chemotherapy regarding chemotherapy-induced side effect, such as liver and kidney function obstacle, leukopenia, hemoglobin decrement and gastrointestinal adverse reaction.

Conclusions

Based on the best available evidence, treatment effect of SC plus chemotherapy was better than chemotherapy and did not increase side effects. Therefore, SC plus chemotherapy may be superior to chemotherapy for treating NSCLC. However, due to some limitations, SC plus chemotherapy should be cautiously considered, and further high-quality meta-analyses are needed.

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Study finds lamotrigine to be safe during pregnancy

Use of the epilepsy drug lamotrigine during pregnancy does not increase the risk of birth malformations or neurodevelopmental disorder, according to research published in the British Journal of...

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Human pupillary light reflex during successive irradiation with 1-ms blue- and green-pulsed light

In the human retina, the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) to the regulation of the pupillary response remains poorly understood. The objective of the current study w...

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Designing equitable workplace dietary interventions: perceptions of intervention deliverers

Workplaces are a good setting for interventions that aim to support workers in achieving a healthier diet and body weight. However, little is known about the factors that impact on the feasibility and implemen...

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New dentist is part of the drill in Eyota

It has already used just over $70,000 to bring a dental clinic to the city and improve the facades of some downtown businesses, but most of the money remains, said Cathy Enerson, the city's economic development director. "They are very strategic and thoughtful about how they are using that money, and it's community driven," she said.

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Relationship between dietary factors and bisphenol a exposure: the second Korean National Environmental Health Survey (KoNEHS 2012–2014)

This study was aimed at finding out the exposure level of bisphenol A (BPA), a well-known endocrine disruptor, in relation to dietary factors using a data representing the Korean general population.

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Bisphenol A promotes hyperuricemia via activating xanthine oxidase [Research]

The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor. XO led to the accumulation of uric acid after xanthine was added, with the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary structures of XO were found by circular dichroism analysis in the conditions of different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO to be the preferred binding sites for BPA. Mutation of both sites significantly blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia exhibited higher levels of serum BPA than subjects without hyperuricemia. These findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid synthesis via the activation of XO, probably through direct binding.—Ma, L., Hu, J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T., Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S. Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

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Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1 [Research]

Microtubule-based motors contribute to the efficiency and selectivity of Golgi exit and post-Golgi transport of membrane proteins that are targeted to distinct compartments. Cytoplasmic dynein moves post-Golgi vesicles that carry rhodopsin toward the base of the connecting cilium in photoreceptor cells; however, the identity of the motors that are involved in the vesicular trafficking of ciliary membrane proteins in nonphotoreceptor cells remains unclear. Here, we demonstrate that the minus end–directed kinesin KIFC1 (kinesin family member C1) is required for both ciliary membrane protein transport and serum starvation–induced ciliogenesis in retinal pigmented epithelial 1 cells. Although KIFC1 is known as a mitotic motor that is sequestered in the nucleus during interphase, KIFC1 immunoreactivity appeared in the Golgi region after serum starvation. Knockdown of KIFC1 inhibited the export of ciliary receptors from the Golgi complex. KIFC1 overexpression affected the Golgi localization of GMAP210 (Golgi microtubule-associated protein 210) and IFT20 (intraflagellar transport 20), which are involved in membrane protein transport to cilia. Moreover, KIFC1 physically interacted with ASAP1 (ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain 1), which regulates the budding of rhodopsin transport carriers from the Golgi complex, and KIFC1 depletion caused Golgi accumulation of ASAP1. A decrease in the centrosomal levels of IFT20 and TTBK2 (-tubulin kinase 2) was associated with ciliogenesis defects in KIFC1-depleted cells. Our results suggest that KIFC1 plays roles in the Golgi exit of ciliary receptors and in the recruitment of ciliogenesis regulators.—Lee, S.-H., Joo, K., Jung, E. J., Hong, H., Seo, J., Kim, J. Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1.

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Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines [Research]

GPCRs have diverse signaling capabilities, based on their ability to assume various conformations. Moreover, it is now appreciated that certain ligands can promote distinct receptor conformations and thereby bias signaling toward a specific pathway to differentially affect cell function. The recently deorphanized G protein-coupled receptor OGR1 [ovarian cancer G protein-coupled receptor 1 (GPR68)] exhibits diverse signaling events when stimulated by reductions in extracellular pH. We recently demonstrated airway smooth muscle cells transduce multiple signaling events, reflecting a diverse capacity to couple to multiple G proteins. Moreover, we recently discovered that the benzodiazepine lorazepam, more commonly recognized as an agonist of the -aminobutyric acid A (GABA_A) receptor, can function as an allosteric modulator of OGR1 and, similarly, can promote multiple signaling events. In this study, we demonstrated that different benzodiazepines exhibit a range of biases for OGR1, with sulazepam selectively activating the canonical Gs of the G-protein signaling pathway, in heterologous expression systems, as well as in several primary cell types. These findings highlight the potential power of biased ligand pharmacology for manipulating receptor signaling qualitatively, to preferentially activate pathways that are therapeutically beneficial.—Pera, T., Deshpande, D. A., Ippolito, M., Wang, B., Gavrila, A., Michael, J. V., Nayak, A. P., Tompkins, E., Farrell, E., Kroeze, W. K., Roth, B. L., Panettieri, R. A. Jr., Benovic, J. L., An, S. S., Dulin, N. O., Penn, R. B. Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.

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Zinc finger protein 365 is a new maternal LPS-binding protein that defends zebrafish embryos against gram-negative bacterial infections [Research]

Zinc finger protein 365 (ZNF365) is widespread in animals, but its function and mechanism remains poorly defined. Here we clearly demonstrate that zebrafish ZNF365 is a newly identified LPS-binding protein capable of interacting with the gram-negative bacteria Escherichia coli, Vibrio anguillarum, and Aeromonas hydrophila, and functions as an antibacterial effector molecule capable of directly killing the bacteria. We also reveal that N-terminal residues 30–55 consisting of the ZnF_C2H2 domain are indispensable for ZNF365 antimicrobial activity. Importantly, microinjection of recombinant ZNF365 into early embryos significantly enhanced the resistance of the embryos against pathogenic A. hydrophila challenge, whereas down-regulation of ZNF365 by injection of znf365 morpholino into embryos considerably lowered their resistance against A. hydrophila challenge. Furthermore, the N-terminal peptide Z_30–55 with in vitro antibacterial activity also promoted the resistance of embryos against A. hydrophila, but the peptide Z_56–345 without in vitro antibacterial activity did not. Collectively, these results indicate that ZNF365 is a maternal LPS-binding protein that can protect the early embryos of zebrafish against pathogenic attacks, a novel role to be assigned to ZNF365 proteins. This work also provides new insights into the immunologic function of the zinc finger proteins that are widely distributed in various animals.—Du, X., Zhou, Y., Song, L., Wang, X., Zhang, S. Zinc finger protein 365 is a new maternal LPS-binding protein that defends zebrafish embryos against gram-negative bacterial infections.

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Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats [Research]

Dairy proteins—whey protein, in particular—are satiating and often recommended for weight control; however, little is known about the mechanisms by which whey protein and its components promote satiety and weight loss. We used diet-induced obese rats to determine whether the hypophagic effects of diets that are enriched with whey and its fractions, lactalbumin and lactoferrin, are mediated by the gut hormone, peptide YY (PYY). We demonstrate that high protein diets that contain whey, lactalbumin, and lactoferrin decreased food intake and body weight with a concurrent increase in PYY mRNA abundance in the colon and/or plasma PYY concentrations. Of importance, blockade of PYY neuropeptide Y receptor subtype 2 (Y2) receptors with a peripherally restricted antagonist attenuated the hypophagic effects of diets that are enriched with whey protein fractions. Diets that are enriched with whey fractions were less preferred; however, in a modified conditioned taste preference test, PYY Y2 receptor blockade induced hyperphagia of a lactoferrin diet, but caused a reduction in preference for Y2 antagonist-paired flavor, which suggested that PYY signaling is important for lactoferrin-induced satiety, but not essential for preference for lactoferrin-enriched diets. Taken together, these data provide evidence that the satiety of diets that are enriched with whey protein components is mediated, in part, via enhanced PYY secretion and action in obese male rats.—Zapata, R. C., Singh, A., Chelikani, P. K. Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats.

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Alternaria alternata (Fr.) Keissl with mutation G143A in the Cyt b gene is the source of a difficult-to-control allergen

Abstract

The saprotrophic fungus Alternaria alternata is widespread in the agro-environment and produces more than ten allergenic proteins, mostly protein Alt a 1. The frequency of the Alt a 1 gene was analyzed in a group of A. alternata isolates from winter wheat kernels obtained in Poland, and the effectiveness of various fungicides targeting the pathogen was evaluated. The Alt a 1 gene was identified in four of the seven tested isolates. A. alternata colonized 35.67% kernels on average, but its frequency increased in stored grain where the presence of epiphytes was noted on 23.09 to 51.38% kernels, and endophytes—in 26.21 to 42.01% of kernels. The efficacy of field-applied fungicides did not exceed 50%, despite the fact that A. alternata is highly sensitive to propiconazole, fenpropimorph, and tebuconazole under in vitro conditions. The analyzed isolates were characterized by limited sensitivity to azoxystrobin (EC₅₀ ranged from 0.505 to 1.350 μg cm⁻³) due to a mutation at codon 143 of the CYT b gene, responsible for resistance to quinone outside inhibitor fungicides, which was noted in all isolates. The spread of A. alternata can be effectively controlled with suitable fungicides and by monitoring the prevalence of pathogenic isolates in the environment.

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MBSAQIP Database Should Be Used as a Tool to Continually Improve Our Clinical Practices for Optimal Patient Outcomes

A Message from Dr. Raul J. Rosenthal Raul J. Rosenthal, MD, FACS, FASMBS, Clinical Editor, Bariatric Times; Professor of Surgery and Chairman, Department of General Surgery; Director of Minimally Invasive Surgery and The Bariatric and Metabolic Institute; General Surgery Residency Program Director; and Director, Fellowship in MIS and Bariatric Surgery, Cleveland Clinic Florida, Weston, Florida […]

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The Gut Microbiome in Obesity: A New Frontier in Therapeutic Targets

A Message from Dr. Christopher Still Christopher Still, DO, FACN, FACP, Co-Clinical Editor, Bariatric Times; Medical Director for the Center for Nutrition and Weight Management, and Director for Geisinger Obesity Research Institute, Geisinger Medical Center, Danville, Pennsylvania.   Dear Readers, In this issue of Bariatric Times, we feature a fantastic article and CEU-accredited activity in […]

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Medical tourism: A Financial and Ethical Problem in Bariatric Surgery

Funding/financial disclosures: The author has no conflicts of interest relevant to the content of this letter. No funding was received for the preparation of this letter. Bariatric Times. 2017;14(10):10–11. Dear Bariatric Times Editor: I saw a patient in the office for a weight loss consultation the other day. She met all of the criteria for […]

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The Role of the Human Microbiome in Obesity-related Health

Bariatric Times. 2017;14(10):12–20 A Message from the Department Editor Dear Colleagues: It is with great pleasure that we present another wonderful contribution to our Integrated Health Continuing Education department on a stimulating topic that is one of the most exciting frontiers in medicine today—the role of the human microbiome in obesity-related health. The human gut […]

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Update on ASMBS/ACS Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program

This column is dedicated to sharing the vast knowledge and opinions of the American Society for Metabolic and Bariatric Surgery leadership—past and present—on relevant topics in the field of bariatric surgery. This month's interview with: John M. Morton, MD, MPH, FACS, FASMBS John M. Morton, MD, MPH, FACS, FASMBS, is Chief of the Section of Bariatric […]

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Walter Pories’s Cartoon Corner

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SOCS1 gene therapy improves radiosensitivity and enhances irradiation-induced DNA damage in esophageal squamous cell carcinoma

STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared to 9/24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the anti-apoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3 expression increased radioresistance, whereas expression of the STAT3 negative regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the STAT3-Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a murine xenograft model compared to the individual therapies. Tumor repopulation occurred transiently after treatment by irradiation but not the combination SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of γ-H2AX and low levels of Ki-67, which was maintained after cessation of treatment. Overall, we demonstrated that inhibiting the STAT3-Mcl-1 signaling axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a new ESCC treatment.

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Restoration of natural killer cell anti-metastatic activity by IL-12 and checkpoint blockade

Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases. Notably, checkpoint blockade therapy synergized with IL-12 to fully enable tumor control by NK cells, demonstrating that checkpoint blockers are not only applicable to enhance T cell-mediated immunotherapy, but also to restore the tumor-suppressive capacity of NK cells.

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Autophagy induction under carbon starvation conditions is negatively regulated by carbon catabolite repression. [Metabolism]

Autophagy is a conserved process in which cytoplasmic components are sequestered for degradation in the vacuole/lysosomes in eukaryotic cells. Autophagy is induced under a variety of starvation conditions, such as the depletion of nitrogen, carbon, phosphorus, zinc and others. However, apart from nitrogen starvation, it remains unclear how these stimuli induce autophagy. In yeast, for example, it remains contentious whether autophagy is induced under carbon starvation conditions, with reports variously suggesting both induction and lack of induction upon depletion of carbon. We therefore undertook an analysis to account for these inconsistencies, concluding that autophagy is induced in response to abrupt carbon starvation when cells are grown with glycerol but not glucose as the carbon source. We found that autophagy under these conditions is mediated by nonselective degradation that is highly dependent on the autophagosome associated scaffold proteins Atg11 and Atg17. We also found that the extent of carbon starvation induced autophagy is positively correlated with cells oxygen consumption rate, drawing a link between autophagy induction and respiratory metabolism. Further biochemical analyses indicated that maintenance of intracellular ATP levels is also required for carbon starvation-induced autophagy, and that autophagy plays an important role in cell viability during prolonged carbon starvation. Our findings suggest that carbon starvation induced autophagy is negatively regulated by carbon catabolite repression.

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Plant pathogenesis-related proteins of the cacao fungal pathogen Moniliophthora perniciosa differ in their lipid-binding specificities [Lipids]

Moniliophthora perniciosa is the causative agent of witches' broom disease, which devastates cacao cultures in South America. This pathogenic fungus infects meristematic tissues and derives nutrients from the plant apoplast during an unusually long-lasting biotrophic stage. In order to survive, the fungus produces proteins to suppress the plant immune response. Proteins of the Pathogenesis Related 1 (PR-1)/CAP superfamily have been implicated in fungal virulence and immune suppression. The genome of M. perniciosa encodes eleven homologues of plant PR-1 proteins, designated MpPR-1 proteins, but their precise mode of action is poorly understood. In this study, we expressed MpPR-1 proteins in a yeast model lacking endogenous CAP proteins. We show that some members of the MpPR-1 family bind and promote secretion of sterols whereas others bind and promote secretion of fatty acids. Lipid-binding by purified MpPR-1 occurs with micromolar affinity and is saturable in vitro. Sterol binding by MpPR-1 requires the presence of a flexible loop region containing aromatic amino acids, the caveolin-binding motif. Remarkably, MpPR-1 family members that do not bind sterols can be converted to sterol binders by a single point mutation in the caveolin-binding motif. We discuss the possible implications of the lipid-binding activity of MpPR-1 family members with regard to the mode of action of these proteins during M. perniciosa infections.

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A genome-wide screen in Escherichia coli reveals that ubiquinone is a key antioxidant for metabolism of long chain fatty acids [Microbiology]

Long chain fatty acids (LCFAs) are used as a rich source of metabolic energy by several bacteria including important pathogens. Since LCFAs also induce oxidative stress, which may be detrimental to bacterial growth, it is imperative to understand the strategies employed by bacteria to counteract such stresses. Here, we performed a genetic screen in Escherichia coli on the LCFA, oleate, and compared our results with published genome-wide screens of multiple non-fermentable carbon sources. This large-scale analysis revealed that amongst components of the aerobic electron transport chain (ETC), only genes involved in the biosynthesis of ubiquinone, an electron carrier in the ETC, are highly required for growth in LCFAs when compared to other carbon sources. Using genetic and biochemical approaches, we show that this increased requirement of ubiquinone is to mitigate elevated levels of reactive oxygen species (ROS) generated by LCFA degradation. Intriguingly, we find that unlike other ETC components whose requirement for growth is inversely correlated with the energy yield of non-fermentable carbon sources, the requirement of ubiquinone correlates with oxidative stress. Our results therefore suggest that a mechanism in addition to the known electron carrier function of ubiquinone is required to explain its antioxidant role in LCFA metabolism. Importantly, among the various oxidative stress combat players in E. coli, ubiquinone acts as the cell's first line of defense against LCFA-induced oxidative stress. Taken together, our results emphasize that ubiquinone is a key antioxidant during LCFA metabolism and therefore provides a rationale for investigating its role in LCFA-utilizing pathogenic bacteria.

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Wilms tumor protein-dependent transcription of VEGF receptor 2 and hypoxia regulate expression of the testis-promoting gene Sox9 in murine embryonic gonads [Developmental Biology]

The Wilms tumor protein 1 (WT1) has been implicated in the control of several genes in sexual development, but its function in gonad formation is still unclear. Here, we report that WT1 stimulates expression of Kdr, the gene encoding VEGF receptor 2, in murine embryonic gonads. We found that WT1 and KDR are co-expressed in Sertoli cells of the testes and somatic cells of embryonic ovaries. Vivo-morpholino-mediated WT1 knockdown decreased Kdr transcripts in cultured embryonic gonads at multiple developmental stages. Furthermore, WT1 bound to the Kdr promoter in the chromatin of embryonic testes and ovaries. Forced expression of the WT1(-KTS) isoform, which functions as a transcription factor, increased KDR mRNA levels, whereas the WT1(+KTS) isoform, which acts presumably on the post-transcriptional level, did not. ChIP indicated that WT1(-KTS), but not WT1(+KTS), binds to the KDR promoter. Treatment with the KDR tyrosine kinase inhibitor SU1498 or the KDR ligand VEGFA revealed that KDR signaling represses the testis-promoting gene Sox9 in embryonic XX gonads. WT1 knockdown abrogated the stimulatory effect of SU1498-mediated KDR inhibition on Sox9 expression. Exposure to 1% O2 to mimic the low-oxygen conditions in the embryo increased Vegfa expression, but did not affect Sox9 mRNA levels in gonadal explants. However, incubation in 1% O2 in the presence of SU1498 significantly reduced Sox9 transcripts in cultured testes and increased Sox9 levels in ovaries. These findings demonstrate that both the local oxygen environment and WT1, which enhances KDR expression, contribute to sex-specific Sox9 expression in developing murine gonads.

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The Serum Protein Renalase Reduces Injury in Experimental Pancreatitis [Cell Biology]

Acute pancreatitis is a disease associated with inflammation and tissue damage. One protein that protects against acute injury, including ischemic injury to both the kidney and heart, renalase, which is secreted into the blood by the kidney and other tissues. However, whether renalase reduces acute injury associated with pancreatitis is unknown. Here, we used both in vitro and in vivo murine models of acute pancreatitis to study renalase effects on this condition. In isolated pancreatic lobules, pretreatment with recombinant human renalase (rRNLS) blocked zymogen activation caused by cerulein, carbachol, and a bile acid. Renalase also blocked cerulein-induced cell injury and histological changes. In the in vivo cerulein model of pancreatitis, genetic deletion of renalase resulted in more severe disease, and administering rRNLS to cerulein-exposed WT mice after pancreatitis onset was protective. Because pathological increases in acinar cell cytosolic calcium levels are central to the initiation of acute pancreatitis, we also investigated whether rRNLS could function through its binding protein, calcium ATPase 4b (PMCA4b), which excretes calcium from cells. We found that PMCA4b is expressed in both murine and human acinar cells and that a PMCA4b selective inhibitor worsens pancreatitis-induced injury and blocked the protective effects of rRNLS. These findings suggest that renalase is a protective plasma protein that reduces acinar cell injury through a plasma membrane calcium ATPase. Since exogenous rRNLS reduces the severity of acute pancreatitis, it has the potential as a therapeutic agent.

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Posttranslational processing and membrane translocation of the yeast regulatory Mid1 subunit of the Cch1/VGCC/NALCN cation channel family [Cell Biology]

Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit. We herein investigated the processing and membrane translocation of Mid1. Mid1 was found to have a 20-amino-acid-long N-terminal signal peptide and appeared to be entirely localized extracellularly. A signal peptide-deleted Mid1 protein, Mid1ΔN23, was N-glycosylated and retained Ca2+ influx activity through Cch1. Moreover, an N-terminal truncation analysis revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was N-glycosylated and maintained Ca2+ influx activity. A 219-amino-acid-truncated Mid1 protein lost this activity, but was still N-glycosylated. In the sec71Δ and sec72Δ single mutants defective in the post-translational protein transport into the endoplasmic reticulum (ER), Mid1ΔN23 could not mediate Ca2+ influx and did not undergo N-glycosylation, while wild-type Mid1 exhibited normal Ca2+ influx activity and N-glycosylation in these mutants. Therefore, the signal peptide-lacking Mid1ΔN23 protein may be translocated to the ER exclusively through the posttranslational protein translocation, which typically requires an N-terminal signal peptide. Mid1 may provide a tool for studying mechanisms of protein translocation into the ER.

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Analysis of substrate specificity of Trypanosoma brucei OSTs by functional expression of domain-swapped chimeras in yeast [Microbiology]

N-linked protein glycosylation is an essential and highly conserved post-translational modification in eukaryotes. The transfer of a glycan from a lipid-linked oligosaccharide (LLO) donor to the asparagine residue of a nascent polypeptide chain is catalyzed by an oligosaccharyltransferase (OST) in the lumen of the endoplasmic reticulum (ER). Trypanosoma brucei encodes three paralogue single protein OSTs called TbSTT3A, TbSTT3B and TbSTT3C that can functionally complement the Saccharomyces cerevisiae OST, making it an ideal experimental system to study the fundamental properties of OST activity. We characterized the LLO and polypeptide specificity of all three TbOST isoforms and their chimeric forms in the heterologous expression host S. cerevisiae where we were able to apply yeast genetic tools and newly developed glycoproteomics methods. We demonstrated that TbSTT3A accepted LLO substrates ranging from Man5GlcNAc2 to Man7GlcNAc2. In contrast, TbSTT3B required more complex precursors ranging from Man6GlcNAc2 to Glc3Man9GlcNAc2 structures and TbSTT3C did not display any LLO preference. Sequence differences between the isoforms cluster in three distinct regions. We have swapped the individual regions between different OST proteins and identified region 2 to influence the specificity towards the LLO and region 1 to influence polypeptide substrate specificity. These results provide a basis to further investigate the molecular mechanisms and contribution of single amino acids in OST interaction with its substrates.

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Development of novel biosensors to study receptor-mediated activation of Gs and Golf [Signal Transduction]

Gαs (Gs) and Gαolf (Golf) are highly homologous G protein α; subunits that activate adenylate cyclase, thereby serving as crucial mediators of intracellular signaling. Owing to their dramatically different brain expression patterns, we studied similarities and differences between their activation processes with the aim of comparing their receptor coupling mechanisms. We engineered novel luciferase- and Venus-fused Gα constructs that can be used in bioluminescence resonance energy transfer (BRET) assays. In conjunction with molecular simulations, these novel biosensors were used to determine receptor activation-induced changes in conformation. Relative movements in Gs were consistent with the crystal structure of β2 adrenergic receptor in complex with Gs. Conformational changes in Golf activation are shown to be similar to those in Gs. Overall the current study reveals general similarities between Gs and Golf activation at the molecular level and provides a novel set of tools to search for Gs- and Golf-specific receptor pharmacology. In view of the wide functional and pharmacological roles of Gs- and Golf- coupled dopamine D1 receptor (D1R) and adenosine A2A receptor (A2AR) in the brain and other organs, elucidating their differential structure-function relationships with Gs and Golf might provide new approaches for the treatment of a variety of neuropsychiatric disorders. In particular, these novel biosensors can be used to reveal potentially therapeutic D1R and A2AR ligands with functionally selective properties between Gs and Golf signaling.

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1{alpha},25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear exclusion of the FoxO1 transcription factor in diabetic mice [Gene Regulation]

1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the active form of vitamin D, which is responsible for reducing the risk for diabetes mellitus (DM), decreasing insulin resistance, and improving insulin secretion. Previous studies have shown that 1,25(OH)2D3 inhibited the activity of FoxO1, which has been implicated in the regulation of glucose metabolism. However, its function and mechanism of action in DM-induced energy disorders and also in bone development remains unclear. Here, using in vitro and in vivo approaches including osteoblast-specific, conditional FoxO1-knockout mice, we demonstrate that 1,25(OH)2D3 ameliorates abnormal osteoblast proliferation in DM-induced oxidative stress conditions, and rescues the impaired glucose and bone metabolism through FoxO1 nuclear exclusion resulted from the activation of PI3K/Akt signaling. Using Alizarin red staining, Alkaline phosphatase assay, Western blot and Real-time qPCR techniques, we found that 1,25(OH)2D3 promotes osteoblast differentiation and expression of osteogenic phenotypic markers (i.e. alkaline phosphatase (1), collagen 1 [COL-1], osteocalcin [OCN], and osteopontin [OPN]) in a high-glucose environment. Moreover, 1,25(OH)2D3 increased both total OCN secretion and levels of uncarboxylated OCN (GluOC) by phosphorylating FoxO1 and promoting its nuclear exclusion, indicated by Western blot and cell immunofluorescence analyses. Taken together, our findings confirm that FoxO1 is a key mediator involved in glucose homeostasis and indicate that 1,25(OH)2D3 improves glucose metabolism and bone development via regulation of PI3K/Akt/FoxO1/OCN pathway.

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Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4 [Cell Biology]

The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division. Mechanistic studies show that Numb inactivates Notch via endocytosis and proteasomal degradation that directly reduce Notch protein levels at the cell surface. However, some aspects of how Numb antagonizes Notch remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch antagonist by controlling the intracellular destination and stability of the Notch ligand Delta-like 4 (Dll4) through a postendocytic-sorting process. We observed that Numb/Numblike knockdown increases the stability and cell-surface accumulation of Dll4. Further study indicated that Numb acts as a sorting switch to control the postendocytic trafficking of Dll4. Of note, the Numb/Numblike knockdown decreased Dll4 delivery to the lysosome, while increasing the recycling of Dll4 to the plasma membrane. Moreover, we demonstrate that this enrichment of Dll4 at the cell surface within Numb/Numblike knockdown cells could activate Notch signaling in neighboring cells. We also provide evidence that Numb negatively controls the Dll4 plasma membrane recycling through a well-documented recycling regulator protein AP1. In conclusion, our study has uncovered a molecular mechanism whereby Numb regulates the endocytic trafficking of the Notch ligand Dll4. Our findings provide a new perspective on how Numb counteracts Notch signaling and shed additional critical insights into the antagonistic relationship between Numb and Notch signaling.

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Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex [Metabolism]

Transcription Factor 19 (TCF19) has been reported as type 1 diabetes associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbours both a plant homeodomain (PHD) and a forkhead-associated domain (FHA) implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation (H3K4Me3) through its PHD finger. Knocking down TCF19 under high glucose condition affected many metabolic processes, including gluconeogenesis. We found that TCF19 overexpression represses de novo glucose production in HepG2 cells. The transcriptional repression of key genes, induced by TCF19 coincided with NuRD (nucleosome-remodeling-deacetylase) complex recruitment to the promoters of these genes. TCF19 interacted with chromodomain helicase DNA-binding protein 4 (CHD4), which is a part of the NuRD complex, in a glucose concentration independent manner. In summary, our results show that TCF19 interacts with an active transcription mark and recruits a co-repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our study offers critical insights into the molecular mechanisms of transcriptional regulation of gluconeogenesis and into the roles of chromatin readers in metabolic homeostasis

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Estimation of meteorological drought indices based on AgMERRA precipitation data and station-observed precipitation data

Abstract

Meteorological drought is a natural hazard that can occur under all climatic regimes. Monitoring the drought is a vital and important part of predicting and analyzing drought impacts. Because no single index can represent all facets of meteorological drought, we took a multi-index approach for drought monitoring in this study. We assessed the ability of eight precipitation-based drought indices (SPI (Standardized Precipitation Index), PNI (Percent of Normal Index), DI (Deciles index), EDI (Effective drought index), CZI (China-Z index), MCZI (Modified CZI), RAI (Rainfall Anomaly Index), and ZSI (Z-score Index)) calculated from the station-observed precipitation data and the AgMERRA gridded precipitation data to assess historical drought events during the period 1987–2010 for the Kashafrood Basin of Iran. We also presented the Degree of Dryness Index (DDI) for comparing the intensities of different drought categories in each year of the study period (1987–2010). In general, the correlations among drought indices calculated from the AgMERRA precipitation data were higher than those derived from the station-observed precipitation data. All indices indicated the most severe droughts for the study period occurred in 2001 and 2008. Regardless of data input source, SPI, PNI, and DI were highly inter-correlated (R ²=0.99). Furthermore, the higher correlations (R ²=0.99) were also found between CZI and MCZI, and between ZSI and RAI. All indices were able to track drought intensity, but EDI and RAI showed higher DDI values compared with the other indices. Based on the strong correlation among drought indices derived from the AgMERRA precipitation data and from the station-observed precipitation data, we suggest that the AgMERRA precipitation data can be accepted to fill the gaps existed in the station-observed precipitation data in future studies in Iran. In addition, if tested by station-observed precipitation data, the AgMERRA precipitation data may be used for the data-lacking areas.

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Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer

Bone metastases are common in patients with advanced solid tumors [1]. Cancers particularly associated with bone metastases include those of the prostate and breast (65–75% of patients) [1], and those affecting the lung (30–40%) [1] and kidney (20–32%) [1,2]. A substantial proportion of patients with advanced cancer and bone metastases will develop skeletal complications known collectively as skeletal-related events (SREs); these include pathologic fracture, spinal cord compression and hypercalcemia, as well as radiation or surgery to bone, which are surrogate markers for skeletal pain and fractures [3].

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Astronaut wee could show us how the plumes on Enceladus work

The way spaceships vent urine and water may be a good stand-in for studying how jets of vapour escape the hidden ocean on one of Saturn's icy moons

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Butchery of a black rhino wins Wildlife Photographer award

The winner of 2017's Wildlife Photographer of the Year awards captures the plight of rhinos, more than 1000 of which are slaughtered yearly for their horn.

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Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer

Bone metastases are common in patients with advanced solid tumors [1]. Cancers particularly associated with bone metastases include those of the prostate and breast (65–75% of patients) [1], and those affecting the lung (30–40%) [1] and kidney (20–32%) [1,2]. A substantial proportion of patients with advanced cancer and bone metastases will develop skeletal complications known collectively as skeletal-related events (SREs); these include pathologic fracture, spinal cord compression and hypercalcemia, as well as radiation or surgery to bone, which are surrogate markers for skeletal pain and fractures [3].

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Multiscale Thermal Hydraulic Study under the Inadvertent Safety Injection System Operation Scenario of Typical Pressurized Water Reactor

The Reactor Pressure Vessel (RPV) inlet nozzles and downcomer wall in Pressurized Water Reactors (PWR) may suffer serious thermal shock caused by cold water from reactor Safety Injection System (SIS) in some unexpected accident scenarios. It implies the formation of great temperature gradient on the inlet nozzles and RPV wall, leading to the localized stresses and propagation of possible flaws that appeared in the material. In this paper, the multiscale thermal hydraulic analysis was performed for Chashma Nuclear Power Plant (NPP) under the inadvertent SIS operation scenario. The primary loop and SIS were modeled using one-dimensional method, while the three-dimensional models of reactor cold leg, RPV inlet nozzles, and downcomer were established. Then, the inadvertent Safety Injection System operation scenario was simulated using RELAP5 code, providing the boundary conditions for three-dimensional Computational Fluid Dynamics (CFD) analysis. The fluid and solid coupling heat transfer simulation method was employed. Results show that the maximum temperature difference was about 80 K in the most conservative condition and the RPV inlet nozzle region was the most critical region during the accident. This work could provide in-depth understanding on the effect of cold coolant injection along the main pipes and RPV wall during the accident scenario.

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The Global Optimal Algorithm of Reliable Path Finding Problem Based on Backtracking Method

There is a growing interest in finding a global optimal path in transportation networks particularly when the network suffers from unexpected disturbance. This paper studies the problem of finding a global optimal path to guarantee a given probability of arriving on time in a network with uncertainty, in which the travel time is stochastic instead of deterministic. Traditional path finding methods based on least expected travel time cannot capture the network user's risk-taking behaviors in path finding. To overcome such limitation, the reliable path finding algorithms have been proposed but the convergence of global optimum is seldom addressed in the literature. This paper integrates the -shortest path algorithm into Backtracking method to propose a new path finding algorithm under uncertainty. The global optimum of the proposed method can be guaranteed. Numerical examples are conducted to demonstrate the correctness and efficiency of the proposed algorithm.

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A Case of Invasive Pneumococcal Infection with Septic Shock and Rare Complications

Invasive pneumococcus is a serious illness with potentially devastating outcomes. A 64-year-old female with a medical history of psoriatic arthritis and diabetes was transferred from an outside hospital for ventilator dependent respiratory failure and altered mental status. She initially presented with worsening back pain and was found to have leukocytosis with bandemia and acute renal failure but she was in septic shock upon arrival to our tertiary care center. Her blood cultures grew Streptococcus pneumoniae and MRI of the brain revealed pus within the posterior lateral ventricles and multiple infarcts. MRI of the spine revealed a psoas abscess. Transesophageal echocardiogram revealed mitral valve vegetation and her right eye developed endogenous endophthalmitis. She was treated with intravenous and intravitreal antibiotics and underwent drainage of the abscess with no improvement in mental status. Repeat imaging revealed multiple new thalamic, basal ganglia, and parietal lobe infarcts likely from septic emboli. After a protracted ICU stay, the patient's family opted for comfort care. The incidence of invasive pneumococcal infections has declined rapidly since the advent of antibiotics and vaccines. With the growing incidence of antibiotic resistance as well as the emergence of new immunomodulating drugs for various pathologies, there is a concern that invasive infections will reemerge. Ventriculitis and endogenous endophthalmitis are very rare complications of pneumococcal bacteremia.

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Surface Corrosion and Microstructure Degradation of Calcium Sulfoaluminate Cement Subjected to Wet-Dry Cycles in Sulfate Solution

The hydration products of calcium sulfoaluminate (CSA) cement are different from those of Portland cement. The degradation of CSA cement subjected to wet-dry cycles in sulfate solution was studied in this paper. The surface corrosion was recorded and the microstructures were examined by scanning electron microscopy (SEM). The results show that , Na+, Mg2+, and Cl− have an effect on the stability of ettringite. In the initial period of sulfate attack, salt crystallization is the main factor leading to the degradation of CSA cement specimens. The decomposition and the carbonation of ettringite will cause long-term degradation of CSA cement specimens under wet-dry cycles in sulfate solution. The surface spalling and microstructure degradation increase significantly with the increase of wet-dry cycles, sulfate concentration, and water to cement ratio. Magnesium sulfate and sodium chloride reduce the degradation when the concentration of sulfate ions is a constant value.

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The Cascadic Multigrid Method of the Weak Galerkin Method for Second-Order Elliptic Equation

This paper is devoted to the analysis of the cascadic multigrid algorithm for solving the linear system arising from the weak Galerkin finite element method. The proposed cascadic multigrid method is optimal for conjugate gradient iteration and quasi-optimal for Jacobi, Gauss-Seidel, and Richardson iterations. Numerical results are also provided to validate our theoretical analysis.

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First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin

Aim. To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients with penicillin allergy. Methods. Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results. Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1–100%; ). The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3–94.4%) in the ITT and 82.7% (95% CI: 64.2–94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion. Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

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Irreversible Thermodynamic Description of Dark Matter and Radiation Creation during Inflationary Reheating

We investigate matter creation processes during the reheating period of the early Universe, by using the thermodynamic of open systems. The Universe is assumed to consist of the inflationary scalar field, which, through its decay, generates relativistic matter and pressureless dark matter. The inflationary scalar field transfers its energy to the newly created matter particles, with the field energy decreasing to near zero. The equations governing the irreversible matter creation are obtained by combining the thermodynamics description of the matter creation and the gravitational field equations. The role of the different inflationary scalar field potentials is analyzed by using analytical and numerical methods. The values of the energy densities of relativistic matter and dark matter reach their maximum when the Universe is reheated up to the reheating temperature, which is obtained as a function of the scalar field decay width, the scalar field particle mass, and the cosmological parameters. Particle production leads to the acceleration of the Universe during the reheating phase, with the deceleration parameter showing complex dynamics. Once the energy density of the scalar field becomes negligible with respect to the matter densities, the expansion of the Universe decelerates, and inflation has a graceful exit.

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Shorter Decentralized Attribute-Based Encryption via Extended Dual System Groups

Decentralized attribute-based encryption (ABE) is a special form of multiauthority ABE systems, in which no central authority and global coordination are required other than creating the common reference parameters. In this paper, we propose a new decentralized ABE in prime-order groups by using extended dual system groups. We formulate some assumptions used to prove the security of our scheme. Our proposed scheme is fully secure under the standard -Lin assumption in random oracle model and can support any monotone access structures. Compared with existing fully secure decentralized ABE systems, our construction has shorter ciphertexts and secret keys. Moreover, fast decryption is achieved in our system, in which ciphertexts can be decrypted with a constant number of pairings.

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Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential.

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Recent Progress on the Description of Relativistic Spin: Vector Model of Spinning Particle and Rotating Body with Gravimagnetic Moment in General Relativity

We review the recent results on development of vector models of spin and apply them to study the influence of spin-field interaction on the trajectory and precession of a spinning particle in external gravitational and electromagnetic fields. The formalism is developed starting from the Lagrangian variational problem, which implies both equations of motion and constraints which should be presented in a model of spinning particle. We present a detailed analysis of the resulting theory and show that it has reasonable properties on both classical and quantum level. We describe a number of applications and show how the vector model clarifies some issues presented in theoretical description of a relativistic spin: (A) one-particle relativistic quantum mechanics with positive energies and its relation with the Dirac equation and with relativistic Zitterbewegung; (B) spin-induced noncommutativity and the problem of covariant formalism; (C) three-dimensional acceleration consistent with coordinate-independence of the speed of light in general relativity and rainbow geometry seen by spinning particle; (D) paradoxical behavior of the Mathisson-Papapetrou-Tulczyjew-Dixon equations of a rotating body in ultrarelativistic limit, and equations with improved behavior.

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High Fasting Plasma Glucose during Early Pregnancy: A Review about Early Gestational Diabetes Mellitus

Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

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(2 + 1)-Dimensional Coupled Model for Envelope Rossby Solitary Waves and Its Solutions as well as Chirp Effect

Using the method of multiple scales and perturbation method, a set of coupled models describing the envelope Rossby solitary waves in ()-dimensional condition are obtained, also can be called coupled NLS (CNLS) equations. Following this, based on trial function method, the solutions of the NLS equation are deduced. Moreover, the modulation instability of coupled envelope Rossby waves is studied. We can find that the stable feature of coupled envelope Rossby waves is decided by the value of . Finally, learning from the concept of chirp in the optical soliton communication field, we study the chirp effect caused by nonlinearity and dispersion in the propagation of Rossby waves.

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Polymicrobial blood stream infection: Consensus definition is required

Sunil Kumar Garg, Pragya Garg

Indian Journal of Critical Care Medicine 2017 21(10):712-713



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Capillary leak syndrome following snakebite envenomation

V Udayabhaskaran, ET Arun Thomas, Bhagya Shaji

Indian Journal of Critical Care Medicine 2017 21(10):698-702

Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and hemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion. There are no other proven effective treatment modalities, except a few reports of successful treatment with plasmapheresis. Methylprednisolone pulse therapy, terbutaline, aminophylline, and intravenous immunoglobulin are other treatment modalities tried.

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A pilot study of nebulized heparin for prevention of ventilator induced lung injury: Comparative effects with an inhaled corticosteroid

Farzin Ghiasi, Mohsen Sadeghian, Mohammad Emami, Babak Ali Kiaie, Sarah Mousavi

Indian Journal of Critical Care Medicine 2017 21(10):634-639

Background: Ventilator-induced lung injury (VILI) is a side effect of mechanical ventilation. Lung inflammation and pulmonary activation of coagulation are induced by mechanical stress. Clinical and preclinical studies show that heparin possesses anti-inflammatory properties. Therefore, we assessed the effects of nebulized heparin in VILI. Methods: Sixty critically ill adult patients who require mechanical ventilation for more than 48 h were included in this prospective, nonrandomized controlled study. Patients received nebulized heparin (10,000 U every 6 h) for 5 days. The matched control group received nebulized budesonide as routine practice in our center. This study assessed changes in partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2) and rapid shallow breathing index (RSBI) during the study as primary endpoints. Results: The average daily PaO2/FiO2ratio was not statistically significant between both groups (187 ± 11.6 vs. 171 ± 11.6, P = 0.35). The RSBI also did not differ between groups (P = 0.58). Heparin administration was associated with a higher number of ventilator-free days among survivors but not significantly (7.7 ± 10.6 vs. 5.1 ± 8, 95* confidence interval − 2.2–7.5, P = 0.28). Successful weaning from mechanical ventilation was higher in the heparin group (P = 0.42). We did not observe any serious or increased adverse effects from nebulized heparin. Conclusion: The results of this study show that the overall effectiveness of nebulized heparin is at least as comparable with a potent corticosteroid (budesonide). Heparin could be a safe and effective modality for patients who at risk of VILI.

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Epidemiological study of patients of road traffic injuries attending emergency department of a trauma center in New Delhi

Puneet Misra, Anindo Majumdar, Mahesh Chandra Misra, Shashi Kant, Sanjeev Kumar Gupta, Amit Gupta, Subodh Kumar

Indian Journal of Critical Care Medicine 2017 21(10):678-683

Background and Aims: There is paucity of data regarding some of the lesser known contextual and epidemiological factors with respect to road traffic injuries (RTIs). The objective was to study the epidemiological profile of RTI victims attending an emergency department of a tertiary care trauma center. Methods: The present study was a hospital-based cross-sectional study conducted in the emergency department of a tertiary care trauma center in New Delhi. All patients of RTI attending the emergency department during the designated data collection days were included in the study. Patients brought dead were excluded from the study. A semi-structured interview schedule was developed for collecting data on various domains such as sociodemographic characteristics, vehicle-related factors, accident site-related factors, personal protection measures, contextual factors, and prehospital care-related factors. Results: A total of 984 patients and informants were approached and finally data of 900 participants were analyzed after excluding those who refused participation and those for whom incomplete data were available. Out of 900 RTI victims, 756 were male (84.0*) and 144 (16.0*) were female. Mean age of the victims was 32.7 years. Most of the victims, i.e., 377 out of 900 (41.9*) were occupants rather than drivers. Majority of victim's vehicle meeting accidents were motorized two-wheelers (53.4*), and majority of the colliding vehicle was a four-wheeler (39.3*). Helmet use was found to be low (63.3*), but seat belt use was particularly low (32.4*). Most accidents (28*) happened between midnight and 6 A.M. More than half of the victims were in a hurry on the day of the accident. An ambulance was used to transport the victims in only 14.6* cases. Conclusion: In road traffic accidents some lesser known epidemiological data were generated that may be useful in defining preventive measures.

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Enhancing hospital well-being and minimizing intensive care unit trauma: Cushioning effects of psychosocial care

Usha Chivukula, Meena Hariharan, Suvashisa Rana, Marlyn Thomas, Asher Andrew

Indian Journal of Critical Care Medicine 2017 21(10):640-645

Context: Hospitalization has the potential to induce hospital anxiety, while admission in the Intensive Care Unit (ICU) is found to surpass the anxiety and result in what is termed as "ICU Trauma." Aims: This study aimed to determine the impact of psychosocial care and quality of ICU on ICU trauma and hospital well-being in patients who underwent coronary artery bypass grafting (CABG). Settings and Design: This correlational study involved 250 CABG patients, who were recruited from five major corporate hospitals. Participants and Methods: The ICU Psychosocial Care Scale, Hospital Wellbeing Scale, and ICU Trauma Scale were used. Each of the participants was assessed individually. The ICU Practices Checklist was used to assess the environment of the ICU in the hospital. Statistical Analysis Used: Descriptive statistics, correlation, and simple and multiple linear regression analyses were done. Results: The results revealed the significant contribution of psychosocial care in ICU in enhancing hospital well-being as well as minimizing ICU trauma of patients who underwent CABG. The results of multiple regressions clearly indicated that psychosocial care was a powerful predictor of hospital well-being and ICU trauma. Conclusions: Although psychosocial care was not a component of hospital well-being and had a negative correlation with ICU trauma, it contributed significantly with a cushioning effect to minimize trauma and helped enhance the feelings and experiences of well-being among patients in ICU.

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Hypercapnic respiratory failure in case of chiari 1.5 malformation: Case Report and review of the literature

Viralkumar M Vasani, Subhas Kanti Konar, S Satish

Indian Journal of Critical Care Medicine 2017 21(10):707-709

Type 2 respiratory failure is defined as hypercapnia associated with hypoxia. Chiari 1.5 is known as herniation of the cerebellar tonsils along with brain stem and fourth ventricle. We report a 35-year-old male who presented with acute hypercapnic respiratory failure (Type 2), without any preexisting neurological or respiratory abnormality. Analysis of blood gases in emergency revealed a pH of 7.12, pCO2of 132 mmHg, and arterial oxygen tension of 118 mm Hg. He was intubated and ventilated. Magnetic resonance imaging brain revealed herniation of the cerebellar tonsils along with brain stem and fourth ventricle. The patient underwent surgery and gradually weaned off. He was mobilized and discharged on day 6. Acute respiratory failure has not been reported with Chiari 1.5 malformation. The lesson to be learned from this case is that craniospinal pathology must be looked for in a patient with hypercapnic respiratory failure.

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The effects of atorvastatin on inflammatory responses and mortality in septic shock: A single-center, randomized controlled trial

Ratender Kumar Singh, Vikas Agarwal, Arvind Kumar Baronia, Sudeep Kumar, Banani Poddar, Afzal Azim

Indian Journal of Critical Care Medicine 2017 21(10):646-654

Aim of the Study: Pleiotropic effect of statins can modulate inflammation in septic shock. We tested the hypothesis whether statins can reduce mortality in septic shock. Patients and Methods: We conducted a randomized double-blinded trial with treatment (40 mg dose of atorvastatin for 7 days) and control (placebo) arm in adult septic shock patients admitted to the Intensive Care Unit. Primary (28-day mortality) and secondary (vasopressor-, ventilation-, and renal replacement therapy-free days) outcomes, with lipid profile and adverse effects, were documented. Inflammatory biomarkers (interleukin [IL]-1, IL-6, tumor-necrosis-factor [TNF]-α, interferon [IFN], and C-reactive protein [CRP]), were also measured before (day 1 [D1]) and after start of trial drug (D4 and D7). Results: Seventy-three septic shock patients with 36 and 37 included in the atorvastatin and placebo group, respectively. Both groups were equally matched. Twenty-eight-day mortality, event-free days, lipid profile, and adverse effects were also not significantly different between groups. Reduced levels of IL-1, IL-6, TNF-α, IFN, and CRP were observed in the atorvastatin group. Also observed were significant day-wise changes in inflammatory biomarkers. Conclusions: Atorvastatin-induced changes in inflammatory biomarkers did not confer mortality benefit in septic shock (ClinicalTrials.govNCT02681653).

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Mapping the characteristics of critical care facilities: Assessment, distribution, and level of critical care facilities from central India

Saurabh Saigal, Jai Prakash Sharma, Abhijit Pakhare, Santosh Bhaskar, Sanjay Dhanuka, Sanjay Kumar, Yogesh Sabde, Pradip Bhattacharya, Rajnish Joshi

Indian Journal of Critical Care Medicine 2017 21(10):625-633

Background: In low- and middle-income countries such as India, where health systems are weak, the number of available Critical Care Unit (Intensive Care Unit [ICU]) beds is expected to be low. There is no study from the Indian subcontinent that has reported the characteristics and distribution of existing ICUs. We performed this study to understand the characteristics and distribution of ICUs in Madhya Pradesh (MP) state of Central India. We also aimed to develop a consensus scoring system and internally validate it to define levels of care and to improve health system planning and to strengthen referral networks in the state. Methods: We obtained a list of potential ICU facilities from various sources and then performed a cross-sectional survey by visiting each facility and determining characteristics for each facility. We collected variables with respect to infrastructure, human resources, equipment, support services, procedures performed, training courses conducted, and in-place policies or standard operating procedure documents. Results: We identified a total of 123 ICUs in MP. Of 123 ICUs, 35 were level 1 facilities, 74 were level 2 facilities, and only 14 were level 3 facilities. Overall, there were 0.17 facilities per 100,000 population (95* confidence interval [CI] 0.14–0.20 per 100,000 populations). There were a total of 1816 ICU beds in the state, with an average of 2.5 beds per 100,000 population (95* CI 2.4–2.6 per 100,000 population). Of the total number of ICU beds, 250 are in level 1, 1141 are in level 2, and 425 are in level 3 facilities. This amounts to 0.34, 1.57, and 0.59 ICU beds per 100,000 population for levels 1, 2, and 3, respectively. Conclusion: This study could just be an eye opener for our healthcare authorities at both state and national levels to estimate the proportion of ICU beds per lac population. Similar mapping of intensive care services from other States will generate national data that is hitherto unknown.

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Astronaut wee could show us how the plumes on Enceladus work

The way spaceships vent urine and water may be a good stand-in for studying how jets of vapour escape the hidden ocean on one of Saturn's icy moons

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Butchery of a black rhino wins Wildlife Photographer award

The winner of 2017's Wildlife Photographer of the Year awards captures the plight of rhinos, more than 1000 of which are slaughtered yearly for their horn.

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Plasmacytoid dendritic cells drive acute exacerbations of asthma

Although acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthma, there is still very little known about the pathophysiological mechanisms involved. Plasmacytoid DCs (pDCs), prominent cells of antiviral immunity, exhibit pro-inflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored.

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Mysterious particles spotted in Saturn’s atmosphere

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Ancient bird gland gives up its chemical secrets

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Multi-site lymphatic venous anastomosis using echography to detect suitable subcutaneous vein in severe lymphedema patients

The method of lymphatic venous anastomosis (LVA), including its indications or pre-operative examinations, has not been established. The purpose of this study is to reveal the possible application of pre-operative echography in surgical LVA outcome.

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Three-stage folded forehead flap for nasal reconstruction: objective and subjective measurements of aesthetic and functional outcomes.

This three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF the nose shape and function.

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