The TORC1/2 inhibitor TAK228 sensitizes atypical teratoid rhabdoid tumors to cisplatin-induced cytotoxicity

Abstract

Background

Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity.

Methods

Activation of mTOR in AT/RT was determined by measuring pS6 and pAKT (Ser473) by immunohistochemistry on tissue microarray of 18 primary AT/RT tumors. In vitro growth assays (BrdU and MTS), death assays (CC3, c-PARP by western blot), and survival curves of AT/RT orthotopic xenograft models were used to measure the efficacy of TAK228 alone and in combination with cisplatin.

Results

Lentiviral short hairpin RNA–mediated knockdown of LIN28A led to decreased mTOR activation. Primary human AT/RT had high levels of pS6 and pAKT (Ser473) in 21% and 87% of tumors by immunohistochemistry. TAK228 slowed cell growth, induced apoptosis in vitro, and nearly doubled median survival of orthotopic xenograft models of AT/RT. TAK228 combined with cisplatin synergistically slowed cell growth and enhanced cisplatin-induced apoptosis. Suppression of AKT sensitized cells to cisplatin-induced apoptosis and forced activation of AKT protected cells. Combined treatment with TAK228 and cisplatin significantly extended survival of orthotopic xenograft models of AT/RT compared with each drug alone.

Conclusions

TAK228 has efficacy in AT/RT as a single agent and synergizes with conventional chemotherapies by sensitizing tumors to cisplatin-induced apoptosis. These results suggest TAK228 may be an effective new treatment for AT/RT.

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The interplay between metabolic remodeling and immune regulation in glioblastoma

Abstract

The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute to a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). However, this pathway represents one of numerous metabolic pathways that may modulate the immune system. For example, metabolites associated with aerobic glycolysis, adenosine, arginine, and prostaglandin metabolism have all been implicated in cancer-mediated immune tolerance and represent attractive therapeutic targets. In this review, we will provide an overview of the emerging interface between these 2 timely areas of cancer research and provide an overview of strategies currently being tested to target these next-generation metabolic immune checkpoints.

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Adult IDH wild-type lower-grade gliomas should be further stratified

Abstract

Background

Astrocytoma of the isocitrate dehydrogenase (IDH) wild-type gene is described as a provisional entity within the new World Health Organization (WHO) classification. Some groups believe that IDH wild-type lower-grade gliomas, when interrogated for other biomarkers, will mostly turn out to be glioblastoma. We hypothesize that not all IDH wild-type lower-grade gliomas have very poor outcomes and the group could be substratified prognostically.

Methods

Seven hundred and eighteen adult WHO grades II and III patients with gliomas from our hospitals were re-reviewed and tested for IDH1/2 mutations. One hundred and sixty-six patients with IDH wild-type cases were identified for further studies, and EGFR and MYB amplifications, mutations of histone H3F3A, TERT promoter (TERTp), and BRAF were examined.

Results

EGFR amplification, BRAF, and H3F3A mutations were observed in 13.8%, 6.9%, and 9.5% of patients, respectively, in a mutually exclusive pattern in IDH wild-type lower-grade gliomas. TERTp mutations were detected in 26.8% of cases. Favorable outcome was observed in patients with young age, oligodendroglial phenotype, and grade II histology. Independent adverse prognostic values of older age, nontotal resection, grade III histology, EGFR amplification, and H3F3A mutation were confirmed by multivariable analysis. Tumors were further classified into "molecularly" high grade (harboring EGFR, H3F3A, or TERTp) (median overall survival = 1.23 y) and lower grade (lacking all of the 3) (median overall survival = 7.63 y) with independent prognostic relevance. The most favorable survival was noted in molecularly lower-grade gliomas with MYB amplification.

Conclusion

Adult IDH wild-type lower-grade gliomas are prognostically heterogeneous and do not have uniformly poor prognosis. Clinical information and additional markers, including MYB, EGFR, TERTp, and H3F3A, should be examined to delineate discrete favorable and unfavorable prognostic groups.

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Disrupted development and integrity of frontal white matter in patients treated for pediatric medulloblastoma

Abstract

Background

Treatment of pediatric medulloblastoma is associated with known neurocognitive deficits that we hypothesize are caused by microstructural damage to frontal white matter (WM).

Methods

Longitudinal MRI examinations were collected from baseline (after surgery but before therapy) to 36 months in 146 patients and at 3 time points in 72 controls. Regional analyses of frontal WM volume and diffusion tensor imaging metrics were performed and verified with tract-based spatial statistics. Age-adjusted, linear mixed-effects models were used to compare patient and control images and to associate imaging changes with Woodcock–Johnson Tests of Cognitive Abilities.

Results

At baseline, WM volumes in patients were similar to those in controls; fractional anisotropy (FA) was lower bilaterally (P < 0.001) and was associated with decreased Processing Speed (P = 0.014) and Broad Attention (P = 0.025) performance at 36 months. During follow-up, WM volumes increased in controls but decreased in patients (P < 0.001) bilaterally. Smaller WM volumes in patients at 36 months were associated with concurrent decreased Working Memory (P = 0.026) performance.

Conclusions

Lower FA in patients with pediatric medulloblastoma compared with age-similar controls indicated that patients suffer substantial acute microstructural damage to supratentorial frontal WM following surgery but before radiation therapy or chemotherapy. Additionally, this damage to the frontal WM was associated with decreased cognitive performance in executive function 36 months later. This early damage also likely contributed to posttherapeutic failure of age-appropriate WM development and to the known association between decreased WM volumes and decreased cognitive performance.

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Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN

Abstract

Background

Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha.

Methods

European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth).

Results

Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3–17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0–8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8–9.7) years.

Conclusions

Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities—important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.

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Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma

Abstract

Background

Interferons (IFNs) are cytokines typically induced upon viral infection but are constitutively expressed also in the absence of acute infection. The physiological role of autocrine and paracrine IFN signaling, however, remains poorly understood, and its function in glioblastoma has not been explored in depth.

Methods

Using RNA interference-mediated gene silencing, we characterized constitutive type I IFN signaling and its role in human glioma cells.

Results

We observed constitutive expression of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) and myxovirus resistance protein A (MxA), a classical IFN-response marker, in the absence of exogenous IFN-β. In vivo, we found higher MxA expression in gliomas than in normal tissue, suggesting that IFN signaling is constitutively active in these tumors. To demonstrate the presence of an autocrine type I IFN signaling loop in glioma cells in vitro, we first confirmed the expression of the type I alpha/beta receptor (IFNAR)1/2, and its ligands, IFN-α and IFN-β. Small interfering RNA–mediated receptor gene silencing resulted in reduced expression of MxA at mRNA and protein levels, as did gene silencing of the ligands, corroborating the hypothesis of an autocrine signaling loop in which type I IFNs induce intracellular signaling through IFNAR1/2. On a functional level, following IFNAR1 or IFNAR2 gene silencing, we observed reduced programmed death ligand 1 (PD-L1) and major histocompatibility complex (MHC) class I and II expression as well as an enhanced susceptibility to natural killer immune cell lysis, suggesting that autocrine IFN signaling contributes to the immune evasion of glioma cells.

Conclusions

Our findings point to an important role of constitutive IFN signaling in glioma cells by modulating their interaction with the microenvironment.

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DNA methylation of a novel PAK4 locus influences ototoxicity susceptibility following cisplatin and radiation therapy for pediatric embryonal tumors

Abstract

Background

Ototoxicity is a common adverse side effect of platinum chemotherapy and cranial radiation therapy; however, individual susceptibility is highly variable. Therefore, our objective was to conduct an epigenome-wide association study to identify differentially methylated cytosine-phosphate-guanine (CpG) sites associated with ototoxicity susceptibility among cisplatin-treated pediatric patients with embryonal tumors.

Methods

Samples were collected for a discovery cohort (n = 62) and a replication cohort (n = 18) of medulloblastoma and primitive neuroectodermal tumor patients. Posttreatment audiograms were evaluated using the International Society of Paediatric Oncology (SIOP) Boston Ototoxicity Scale. Genome-wide associations between CpG methylation and ototoxicity were examined using multiple linear regression, controlling for demographic and treatment factors.

Results

The mean cumulative dose of cisplatin was 330 mg/m² and the mean time from end of therapy to the last available audiogram was 6.9 years. In the discovery analysis of 435233 CpG sites, 6 sites were associated with ototoxicity grade (P < 5 × 10⁻⁵) after adjusting for confounders. Differential methylation at the top CpG site identified in the discovery cohort (cg14010619, PAK4 gene) was replicated (P = 0.029) and reached genome-wide significance (P = 2.73 × 10⁻⁸) in a combined analysis. These findings were robust to a sensitivity analysis evaluating other potential confounders.

Conclusions

We identified and replicated a novel CpG methylation loci (cg14010619) associated with ototoxicity severity. Methylation at cg14010619 may modify PAK4 activity, which has been implicated in cisplatin resistance in malignant cell lines.

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Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas

Abstract

Background

Primary and adaptive resistance against chemo- and radiotherapy and local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that glioma cells can extend ultra-long membrane protrusions, "tumor microtubes" (TMs), for brain invasion, proliferation, and interconnection of single cells to a syncytium that is resistant to radiotherapy. We wondered whether TMs also convey resistance to the other 2 standard treatment modalities.

Methods

Patient-derived glioblastoma stemlike cell (GBMSC) lines were implanted under a cranial window in mice. Longitudinal in vivo two-photon laser scanning microscopy was used to follow tumor growth, including the fate of single glioma cells over months.

Results

After a cylindrical surgical lesion, GBMSCs increasingly extended TMs toward the lesion area, which contributed to the repopulation of this area over many weeks. In fact, an excessive "healing response" was observed in which tumor cell densities significantly exceeded those of unlesioned brain regions over time. Inhibition of TM formation and function by genetic targeting of growth associated protein-43 robustly suppressed this surgery-induced tumor growth reaction, in contrast to standard postsurgical anti-inflammatory treatment with dexamethasone. After one cycle of temozolomide chemotherapy, intra- and intertumoral heterogeneity of TM formation and interconnection was strongly associated with therapy response: when tumor cells were integrated in TM networks, they were more likely to resist chemotherapy.

Conclusion

TMs can contribute to the resistance against standard treatment modalities in gliomas. Specific inhibition of TMs is a promising approach to reduce local recurrence after surgery and lower resistance to chemotherapy.

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Brain invasion in meningiomas—clinical considerations and impact of neuropathological evaluation: a systematic review

Abstract

With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added as a stand-alone criterion for atypia and can therefore impact grading and indirectly adjuvant therapy. Regarding this rising clinical importance, we have reviewed the current knowledge about brain invasion with emphasis on its implications on current and future clinical practice. We found various definitions of brain invasion and approaches for evaluation in surgically obtained specimens described over the past decades. This heterogeneity is reflected by weak correlation with prognosis and remains controversial. Similarly, associated clinical factors are largely unknown. Preoperative, imaging-guided detection of brain invasion is unspecific, and intraoperative assessment using standard and new high-magnification microscopic techniques remains imprecise. Despite the increasing knowledge about molecular alterations of the tumor/ brain surface, pharmacotherapeutic options targeting brain invasive meningiomas are lacking. Finally, we summarize the impact of brain invasion on histopathological grading in the WHO classifications of brain tumors since 1979.In conclusion, standardized neurosurgical sampling and neuropathological analyses could improve diagnostic reliability and reproducibility of future studies. Further research is needed to improve pre- and intraoperative visualization of brain invasion and to develop adjuvant, targeted therapies.

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MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles

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Asymmetric dumbbell-shaped silver nanoparticles and spherical gold nanoparticles green-synthesized by mangosteen (Garcinia mangostana) pericarp waste extracts

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Registry data show increase in joint replacement surgery

The number of joint replacement procedures is rising, with a low rate of revisions to replace first time joint implants but a higher risk in younger patients, show the latest figures from the...

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RT @RachelAHollis : September is Childhood Cancer Awareness Month an we think of children across the world who have limited access to trea…

RT @RachelAHollis : September is Childhood Cancer Awareness Month an we think of children across the world who have limited access to trea…

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The @CRUKresearch #LungCancer Conference brings together world experts from across disciplines. Don’t miss out:… https://t.co/SvPdt60Ql8

The @CRUKresearch #LungCancer Conference brings together world experts from across disciplines. Don't miss out:… https://t.co/SvPdt60Ql8

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Diagnose #osteonecrosisofthejaw with Prof Cesar Migliorati in our new module: https://t.co/1XnCKFbcR1 https://t.co/Z8XwwRudBW

Diagnose #osteonecrosisofthejaw with Prof Cesar Migliorati in our new module: https://t.co/1XnCKFbcR1 https://t.co/Z8XwwRudBW

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E-waste management and sustainability: a case study in Brazil

Abstract

The advancement of technology and development of new electronic and electrical equipment with a reduced life cycle has increased the need for the disposal of them (called Waste of Electric and Electronic Equipment or simply e-waste) due to defects presented during use, replacement of obsolete equipment, and ease of acquisition of new equipment. There is a lack of consumer awareness regarding the use, handling storage, and disposal of this equipment. In Brazil, the disposal of post-consumer waste is regulated by the National Solid Waste Policy, established by Law No. 12305 and regulated on the 23rd December 2010. Under this legislation, manufacturers and importers are required to perform a project for the Reverse Logistics of e-waste, though its implementation is not well defined. This work focuses on the verification of the sustainability of reverse logistics suggested by the legislation and the mandatory points, evaluating its costs and the possible financial gain with recycling of the waste. The management of reverse logistics and recycling of waste electrical and electronic equipment, or simply recycling of e-waste, as suggested by the government, will be the responsibility of the managing organization to be formed by the manufacturers/importers in Brazil.

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Current pesticide dietary risk assessment in light of comparable animal study NOAELs after chronic and short-termed exposure durations

Abstract

Dietary risk assessment (DRA) of pesticides includes the estimation of chronic and acute exposures from crop residues, but assesses acute exposures only for pesticides with an acute reference dose (ARfD). Acute estimation uses high percentiles of food consumption surveys which are considerably higher than per capita lifetime averaged food consumption values which are used for chronic estimations. Assessing acute risks only for pesticides with an ARfD tacitly assumes that chronic risk assessment covers also intermittent occurring exposures which could significantly exceed chronic estimates. The present investigation conducted on 2200 rat studies from 436 pesticides provides evidence demonstrating that pesticides with and without ARfD have no-observed-adverse-effect levels (NOAELs) which remain statistically unchanged in developmental, subacute, subchronic, reproductive and chronic toxicity studies covering exposure durations between 2 and 104 weeks. DRA of pesticides without ARfD needs reconsideration in light of equally high toxic dose levels after short- and long-term exposures, suggesting that intermittent exposures could be toxic, if they repeatedly exceed the acceptable chronic daily intake (ADI; conceptually the human counterpart of chronic animal NOAEL). As such risks are currently not assessed for pesticides without ARfD, the current DRA concept, which automatically presumes the use of low chronic exposure estimates entirely covers the risks of not acutely toxic pesticides, needs reconsideration. Furthermore, risks to intermittent occurring high exposures are probably also insufficiently assessed for pesticides where the ARfD is significantly higher than the ADI. As an example, the maximum residue limit for bifenazate in peaches is discussed.

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Frakturen der unteren Extremität im Kindesalter

Zusammenfassung

Kindliche Frakturen sind im klinischen Alltag eine große Herausforderung. Die Entscheidung über die richtige Frakturversorgung fällt unter Berücksichtigung individueller Faktoren. Essenziell sind das Alter des Kindes und das resultierende Restwachstum. Dieser Beitrag soll die strukturierte Untersuchung, Diagnostik und Therapie erleichtern. Der erste Teil dieser Serie befasst sich mit Besonderheiten der Oberschenkel- und der kniegelenksnahen Frakturen. Das Besondere am kindlichen Knochen ist sein Wachstum. Hieraus resultieren eine wesentlich höhere Heilungstendenz und ein größeres Korrekturpotenzial als beim Erwachsenen. Für die Frakturausheilung ist wesentlich, die Toleranzgrenzen bezüglich Achsfehlstellungen sowie das spontane Korrekturpotenzial und das daraus resultierende Remodeling in die Therapieentscheidung einfließen zu lassen. Die verschiedenen operativen Maßnahmen müssen gezielt eingesetzt werden. Inkongruenzen von Gelenken und deutliche Längendifferenzen sind zu vermeiden.

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Chemical composition, antioxidant and antibacterial activities of essential oil and methanol extract of Artemisia vulgaris and Gaultheria fragrantissima collected from Nepal

Publication date: Available online 18 September 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Bishnu Prasad Pandey, Rupak Thapa, Anil Upreti
ObjectiveTo identify the chemical constituents and biological activities of essential oil and crude methanol extract of Artemisia vulgaris (A. vulgaris) and Gaultheria frarantissima (G. fragrantissima).MethodsPhytochemical screening, total phenolic and flavonoid content, antibacterial activities, anti-oxidant assay of the crude extract were carried out to identify the biological activities and phytonutrients present in the extract. Furthermore, the chemical constituents present in the essential oil and crude methanol extract were analyzed using gas chromatography mass spectroscopy and high performance liquid chromatography (HPLC) analysis.ResultsGas chromatography mass spectroscopy analysis of essential oil from the aerial part of A. vulgaris revealed 24 different compoundsin it. Sabinene (11.29%), β-thujone (19.19%), chrysanthenone (4.48%), camphor (11.89%), borneol (4.44%) and germacrene D (8.42%) were the major compounds. Similarly, leaves of G. fragrantissimacontained methyl salicylate (95%) and asarone (4.64%). Furthermore, methanol extract of leaves of A. vulgaris and G. fragrantissima were found rich in the total flavonoids and phenolic content. HPLC analysis of the methanol extract of leaves A. vulgaris revealed the presence of morin and luteolin, whereas rutin was found as a major flavonoids compound in the leaves of G. fragrantissima. Further, methanol extract of the A. vulgaris and G. fragrantissima showed the highest antioxidant and antibacterial properties compared to the essential oil.ConclusionsThe HPLC analysis of the methanol extract of A. vulgaris shows the presence of luteolin and morin, whereas G. fragrantissima reveals the presence of rutin and a glycosylated flavonoids. Results reveal that A. vulgaris oil is the rich source of monoterpene and sesqueterpene compounds. Furthermore, A. vulgaris and G. fragrantissima are the rich source of the phenolic and flavonoids compounds and show good antioxidant and antibacterial activity.



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Commentary: The inescapability of the ethical

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Commentary: Inequalities and health: an opportunity missed?

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Commentary: Tackling the health gap: the role of psychosocial processes

In The Health Gap, Michael Marmot describes how, starting even before birth, social conditions set individuals on trajectories that eventuate in inequities in health and longevity. In addition to race and ethnicity, socioeconomic status linked to income and education plays a major role in determining health trajectories. The effects emerge not only at the very bottom of the socioeconomic spectrum, but across the whole range.¹

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The Health Gap: The Challenge of an Unequal World: the argument

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Commentary: A multi-factorial and dynamic approach to health inequalities–lessons from Marmot’s The Health Gap

Michael Marmot's book, The Health Gap: The Challenge of an Unequal World,¹ combines autobiographical notes with epidemiological and other scientific evidence, topped with moral concern. It examines the scientific arguments on the generation of health inequalities and how they might be addressed. It also shows Marmot's 'trademark' energy and profound determination to contribute scientifically to policy making.

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Making epidemiology matter

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Population Health Science

Population Health Science.KeyesKatherine M. and GaleaSandro. Oxford, UK: Oxford University Press2016, pp. 224, £29.99, ISBN-13: 9780190459376

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Cohort Profile: The Korean Genome and Epidemiology Study (KoGES) Consortium

First published online: 15 April 2016, Int J Epidemiol, 2016, doi: http://ift.tt/2ymgSaD

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Reply to Naimi

Naimi's letter,¹ which criticizes an article we have written about causal inference in epidemiology,² repeats many of the arguments and errors in the response to our article by Daniel et al.,³ involving mischaracterization of our critique of uncritical use of directed acyclic graphs (DAGs) and misunderstandings of what a critical analysis of racial/ethnic health inequities entails. Rather than repeat ourselves to correct these errors, we refer readers to our response⁴ to the Daniel et al. article and the other commentaries, as well as to our original article.² The problematic treatment of race/ethnicity in epidemiologic research–including but not limited to research premised on a potential outcomes approach–has long been a mutual concern of ours^2,5 and this concern is reinforced, not rebutted, by the problematic approaches and assertions of both the Daniel et al. article³ and Naimi's letter.¹

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On wagging tales about causal inference

Krieger and Davey Smith (KDS) have written a lengthy polemic on the increasingly popular use of methods for causal modelling ('causal inference') in epidemiology.¹ This paper has instigated a lively discussion on the use of counterfactual modelling in epidemiology.^2–8 Yet much confusion remains. For example, in their last editorial for the Journal, Ebrahim et al.⁹ state that 'the potential outcomes approach can be seen as … too far removed from many of the complex 'dirty' problems … of social epidemiology' (page 1704), but also note that '(c)ounterfactual methods … might help drive a new wave of social epidemiology focused on reducing social inequalities in health' (page 1708).

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Traumatic spinal cord injury in Uganda: a prevention strategy and mechanism to improve home care

Abstract

In low- and middle-income countries (LMICs), the burden of traumatic spinal cord injury (TSCI) is largely unknown. The estimated incidence of TSCI in LMICs is 25.5/million/year, and the impact on affected patients and their families is presumed to be immense due to the social structure, limited health system resources and reliance on family to care for those that survive injury to return home. In sub-Saharan Africa, extrapolated regional figures for incidence range from 21 – 29/million/year, and the occurrence of a spinal injury is likely to be fatal within a year.

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Epidemiology of sudden cardiac death in Cameroon: the first population-based cohort survey in sub-Saharan Africa

Abstract

Background

Incidence estimates of sudden cardiac death (SCD) in sub-Saharan Africa (SSA) are unknown.

Method

Over 12 months, the household administrative office and health community committee within neighbourhoods in two health areas of Douala, Cameroon, registered all deaths among 86 188 inhabitants aged >18 years. As part of an extended multi-source surveillance system, the Emergency Medical Service (EMS), local medical examiners and district hospital mortuaries were also surveyed. Whereas two physicians investigated every natural death, two cardiologists reviewed all unexpected natural deaths.

Results

There were 288 all-cause deaths and 27 (9.4%) were SCD. The crude incidence rate was 31.3 [95% confidence interval (CI): 20.3–40.6]/100 000 person-years. The age-standardized rate by the African standard population was 33.6 (95% CI: 22.4–44.9)/100 000 person-years. Death occurred at night in 37% of cases, including 11% of patients who died while asleep. Out-of-hospital sudden cardiac arrest occurred in 63% of cases, 55.5% of which occurred at home. Of the 88.9% cases of witnessed cardiac arrest, 63% occurred in the presence of a family member and cardiopulmonary resuscitation was attempted only in 3.7%.

Conclusion

The burden of SCD in this African population is heavy with distinct characteristics, whereas awareness of SCD and prompt resuscitation efforts appear suboptimal. Larger epidemiological studies are required in SSA in order to implement preventive measures, especially in women and young people.

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Three-Year Follow-Up of Participants from a Self-Weighing Randomized Controlled Trial

Frequent self-weighing is associated with weight loss maintenance. Several years ago, we investigated frequent self-weighing's effect on weight loss and found the participants lost a significant amount of weight. Three years after this trial's end, participants were contacted for an update on their weight and self-weighing frequency. Weight change and self-weighing frequency since the end of the study were assessed. We hypothesized that participants who maintained frequent self-weighing behavior would have maintained their weight loss. Out of 98 participants enrolled in the RCT, 37% (n = 36) participated in this follow-up study. Total weight loss during the trial for the follow-up participants was 12.7 ± 19.4 lbs (). Three years after intervention, participants regained 0.9 ± 4.34 lbs, a value that was not statistically different from zero (). This did not differ by gender (). Over 75% of these participants continued to weigh themselves at least once a week. Frequent self-weighing may be an effective, low-cost strategy for weight loss maintenance. Future research should further investigate the role of self-weighing in long-term weight gain prevention.

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Avoidance of Total Knee Arthroplasty in Early Osteoarthritis of the Knee with Intra-Articular Implantation of Autologous Activated Peripheral Blood Stem Cells versus Hyaluronic Acid: A Randomized Controlled Trial with Differential Effects of Growth Factor Addition

In this randomized controlled trial, in early osteoarthritis (OA) that failed conservative intervention, the need for total knee arthroplasty (TKA) and WOMAC scores were evaluated, following a combination of arthroscopic microdrilling mesenchymal cell stimulation (MCS) and repeated intra-articular (IA) autologous activated peripheral blood stem cells (AAPBSCs) with growth factor addition (GFA) and hyaluronic acid (HA) versus IA-HA alone. Leukapheresis-harvested AAPBSCs were administered as three weekly IA injections combined with HA and GFA (platelet-rich plasma [PRP] and granulocyte colony-stimulating factor [hG-CSF]) and MCS in group 1 and in group 2 but without hG-CSF while group 3 received IA-HA alone. Each group of 20 patients was evaluated at baseline and at 1, 6, and, 12 months. At 12 months, all patients in the AAPBSC groups were surgical intervention free compared to three patients needing TKA in group 3 (). Total WOMAC scores showed statistically significant improvements at 6 and 12 months for the AAPBSC groups versus controls. There were no notable adverse events. We have shown avoidance of TKA in the AAPBSC groups at 12 months and potent, early, and sustained symptom alleviation through GFA versus HA alone. Differential effects of hG-CSF were noted with an earlier onset of symptom alleviation throughout.

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Aloperine Protects Mice against DSS-Induced Colitis by PP2A-Mediated PI3K/Akt/mTOR Signaling Suppression

Colitis is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases. The present study aimed to examine the molecular mechanisms underlying aloperine-mediated colitis protection. We found that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS) based on body weight, disease activity index, colonic length, and spleen index. Aloperine also effectively attenuated DSS-induced intestinal inflammation based on the pathological score and myeloperoxidase expression and activity in colon tissues. In addition, aloperine regulated T-cell proportions and promoted Foxp3 expression in the spleens and mesenteric lymph nodes of DSS-induced colitis mice and in the spleens of the Foxp3GFP mice. Aloperine inhibited Jurkat and mouse naïve T-cell apoptosis. Furthermore, aloperine inhibited PI3K/Akt/mTOR signaling and upregulated PP2A expression in the DSS-induced colitis mice and in Jurkat cells, but LB-100 (PP2A inhibitor) resulted in an elevated Akt activity in Jurkat cells, activated T-cells, and human splenic mononuclear cells. Aloperine inhibited T-cell and lymphocyte proliferation, but LB-100 reverse these effects. In conclusion, aloperine regulates inflammatory responses in colitis by inhibiting the PI3K/Akt/mTOR signaling in a PP2A-dependent manner.

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A Feeding Strategy in Inner L-Shape Ring Hot Rolling Process

In order to make the inner L-shape ring polling process with a closed die structure (ILRRCDS) on the top and bottom of the driven roll stable, at first, this paper established the mathematical model for ILRRCDS. Then, the plastic penetration and biting-in conditions for ILRRCDS were deduced based on plain ring rolling theory. Moreover, a feeding strategy that can realize a constant growth of the ring's outer radius was proposed and the reasonable value ranges of the feed rate of the mandrel were determined. The numerical simulation model for ILRRCDS is established based on ABAQUS software. Finally, the equivalent plastic strain (PEEQ) and temperature distributions of rolled ring were obtained. The results indicated that the proposed feeding strategy can realize a stable ILRRCDS. At the end of ILRRCDS, the PEEQ at the inner radius surface of the ring is maximum, the PEEQ at the outer radius surface of the ring takes the second place, and the PEEQ at the middle part of ring is minimum. With the increase of rolling time, the higher temperature zone of the rolled ring gradually moves from the center part of the ring to the "inner corner zone" of the ring.

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The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis

Objective. To determine the effect of aerobic exercise on brain-derived neurotrophic factor (BDNF) levels in people with neurological disorders. Data Sources. Six electronic databases (CINAHL, PubMed, Cochrane, PsycINFO, SportDiscus, and Web of Science) were searched until the end of December 2016. Study Selection. Experimental or observational studies of people with neurological disorders who undertook an exercise intervention with BDNF as an outcome measure. The search strategy yielded 984 articles. Data Extraction. Study data were independently extracted from each article. Methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. A meta-analysis was planned based on the assessment of predetermined criteria. Data Synthesis. Eleven articles were included. Studies employed either a program of aerobic exercise, a single bout of aerobic exercise, or both. A meta-analysis of studies comparing a program of aerobic exercise against usual care/nil therapy showed a large effect (SMD: 0.84, 95% CI 0.47–1.20, ) in favour of aerobic exercise to increase levels of BDNF. Findings for a single bout of aerobic exercise were mixed. Quality of studies was low (PEDro average score 4.3/10). Conclusions. A program of aerobic exercise may contribute to increased levels of BDNF in neurological populations.

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Correlates of Calcaneal Quantitative Ultrasound Parameters in Patients with Diabetes: The Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes

Objective. Quantitative ultrasound (QUS) provides an estimate of bone mineral density (BMD) and also evaluates bone quality, which has been related to increased fracture risk in people with diabetes. This study aimed at assessing the correlates of calcaneal QUS parameters in diabetic subjects encompassing various degrees of micro and macrovascular complications and a wide-range of peripheral nerve function. Methods. Four hundred consecutive diabetic patients were examined by QUS to obtain values of broadband ultrasound attenuation (BUA), the speed of sound (SOS), quantitative ultrasound index (QUI), and BMD. Results. Among surrogate measures of complications, sensory and motor nerve amplitude and heart rate response to cough test and standing correlated with QUS parameters at univariate analysis, together with age, body mass index (BMI), waist circumference, lipid profile, and renal function. Multivariate analysis revealed that BUA, SOS, QUI, and BMD were independently associated with age, male gender, hemoglobin A1c, BMI (or fat, but not fat-free mass), and somatic and autonomic nerve function parameters. Conclusions. These data indicate that peripheral nerve dysfunction is associated with worse QUS parameters, possibly contributing to increased fracture risk in diabetes. The positive relation of QUS measures with adiposity needs further investigation. This trial is registered with ClinicalTrials.gov (NCT01600924).

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An Insight into Phage Diversity at Environmental Habitats using Comparative Metagenomics Approach

Abstract

Bacteriophages play significant role in driving microbial diversity; however, little is known about the diversity of phages in different ecosystems. A dynamic predator–prey mechanism called "kill the winner" suggests the elimination of most active bacterial populations through phages. Thus, interaction between phage and host has an effect on the composition of microbial communities in ecosystems. In this study, secondary phage metagenome data from aquatic habitats: wastewater treatment plant (WWTP), fresh, marine, and hot water spring habitat were analyzed using MG-RAST and STAMP tools to explore the diversity of the viruses. Differential relative abundance of phage families—Siphoviridae (34%) and Myoviridae (26%) in WWTP, Myoviridae (30%) and Podoviridae (23%) in fresh water, and Myoviridae (41%) and Podoviridae (8%) in marine—was found to be a discriminating factor among four habitats while Rudiviridae (9%), Globuloviridae (8%), and Lipothrixviridae (1%) were exclusively observed in hot water spring. Subsequently, at genera level, Bpp-1-like virus, Chlorovirus, and T4-like virus were found abundant in WWTP, fresh, and marine habitat, respectively. PCA analysis revealed completely disparate composition of phage in hot water spring from other three ecosystems. Similar analysis of relative abundance of functional features corroborated observations from taxa analysis. Functional features corresponding to phage packaging machinery, replication, integration and excision, and gene transfer discriminated among four habitats. The comparative metagenomics approach exhibited genetically distinct phage communities among four habitats. Results revealed that selective distribution of phage communities would help in understanding the role of phages in food chains, nutrient cycling, and microbial ecology. Study of specific phages would also help in controlling environmental pathogens including MDR bacterial populations using phage therapy approach by selective mining and isolation of phages against specific pathogens persisting in a given environment.

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An Efficient Method for Hair Containment During Head and Neck Surgery.

The authors present a simple technique for operations around hair-bearing areas such as during a rhytidectomy. Hair surrounding the surgical field is twisted into bundles and clipped with duckbill clips. The authors repeat the procedure for each strand of hair. Between 5 and 7 duckbill clips may be required per surgery. The clippers are faster, easily applicable, and well performing. They can be used with different hair lengths, and they do not require any additional trimming or shaving; clips also keep the hair firmly in place, and they do not loosen up in the process. This technical note explains a very simple, economical, and less time-consuming method to control hair located around the surgical site. It may be applied to all procedures within the field of the hair-bearing scalp, including craniofacial and maxillofacial surgery. (C) 2017 by Mutaz B. Habal, MD.

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A Shift in the Orbit: Immediate Endoscopic Reconstruction After Transnasal Orbital Tumors Resection.

Endoscopic endonasal resection of orbital lesions is a safe and common approach. Nevertheless, medial orbital wall defects following the procedure are not routinely addressed, potentially leading to diplopia and enophthalmos. In this article, the authors propose a new technique for purely endoscopic endonasal reconstruction of orbital wall defects following endoscopic endonasal resection of orbital lesions. The patient, a 43-year-old male, suffering from right exophthalmos and diplopia due to a venous malformation of the right orbit underwent endoscopic endonasal resection of the mass. Excision was followed by immediate transnasal endoscopic reconstruction with a commercially available porous polyethylene mesh (Medpor). The postoperative course was uneventful. The patient did not report any residual orbital asymmetry or diplopia. No recurrence of the venous malformation, mesh infection, or reconstruction instability was reported during the follow-up. The authors believe that this new technique could spur head and neck surgeons in strategically rethinking their approach to orbital tumors, proposing reconstruction to patients on a routine basis, and developing even more reliable and manageable solutions. (C) 2017 by Mutaz B. Habal, MD.

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Long-Term Follow-Up of Osseointegrated Orbital Prosthetic Reconstruction.

Background: Osseointegrated implants have been used for craniofacial prosthetic reconstruction since 1979. The authors sought to review long-term outcomes of osseointegrated orbital reconstruction at the Institute for Reconstructive Sciences in Medicine (iRSM). Methods: Twenty-six patients have undergone osseointegrated orbital prosthetic (OOP) reconstruction at iRSM since 1991. A retrospective chart review was performed and patient satisfaction assessed through a questionnaire used in previous osseointegration studies. Multivariate binary logistic regression analysis was performed to assess the relationship between smoking, age, sex, and previous radiation treatment with the occurrence of skin reactions and implant failures. A [chi]2 test was used to assess the relationship between implant position within the orbit and development of a skin reaction or implant failure. Results: Patients received an average of 5.8 implants during the course of treatment. Follow-up ranged from 6 months to 24 years (mean = 10.6 years). A statistically significant correlation was found between skin reaction and age (P = 0.022), with younger patients more likely to develop a reaction. No variables in our model were significant for predicting implant failure. Overall, there were 39 failures of 155 osseointegrated implants, for a success rate of 74.8%. There was no relationship between skin reaction and implant failure compared to implant position within the orbit. Survey responses were received from 11 of 19 patients (58% response rate). Ninety-one percent of patients were overall satisfied with their prosthesis. Conclusions: There are minimal contraindications for consideration of OOP reconstruction. Patients find their prosthesis comfortable, report increased self-confidence, and are happy to have undergone reconstruction. (C) 2017 by Mutaz B. Habal, MD.

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Evaluation of the Changes in the Quality of Life in Patients Undergoing Orthognathic Surgery: A Multicenter Study.

Orthognathic surgery can affect patients' quality of life. The aim of the present study was to assess changes in quality of life during combined orthodontics-surgery treatment and effect of orthodontist-surgeon teamwork on final patient's satisfaction. Twenty-six orthognathic patients who were referred to oral and maxillofacial department of 3 hospitals in Tehran were included in the study. Orthognathic quality of life questionnaire (OQLQ) was given to patients 1 week before, 4 weeks and 4 months after surgery. Two self-designed forms were used for evaluating mood and comfort of patients 1 week before surgery and 4 days after surgery. Self-designed forms were given to the orthodontists and the maxillofacial surgeons to assess quality of teamwork and difficulty of the procedure. Twenty-four patients (15 females and 9 males) with the mean age of 22.62 +/- 3.57 completed the study. Quality of life increased from 1 week before surgery to 4 months after surgery (P

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Cleft Lip and Palate: An Experience of a Developing Center in Egypt.

Background: Cleft lip and palate is the most common congenital anomaly in the head and neck region. These clefts are not just a distortion of the normal appearance, but they may impose a major influence on the whole patient's life, both functionally and psychologically. Clefts affect feeding, teething, hearing, speech, and social communication. The incidence of cleft lip and palate is variable in different countries and different communities. The surgical correction of cleft lip and palate went through many evolutions, but still there is no single universal protocol of repair; however, many European countries have adopted national protocols and have established cleft centers for the management and follow up of affected population. Patient and Methods: In this study, the problem of cleft lip and palate in the area of upper Egypt was presented through the records of patients admitted to the Department of Plastic Surgery at the Sohag University Hospital in a 15-year period (2001-2015). Results: A total number of 1318 patients, who were admitted and had been operated upon in our department, were included in this study. The majority of patients presented to the department with a primary disease, yet 14.7% (194 patients) of them were first presented for a secondary interference after being operated upon elsewhere. A total number of 1923 surgical procedures were performed. (C) 2017 by Mutaz B. Habal, MD.

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Fibular Graft-Effective Panorama for Prosthetic Rehabilitation of Resected Mandible.

Surgical management of extensive tumors in the mandibular region leads to massive disfigurement of the face. Also the prosthetic outcome of such patients rehabilitated with free soft tissue flaps is very poor. Reconstruction of extensive defects to overcome the disfigurement is a challenging procedure and can be achieved with free fibula flap. Free fibula graft provides sufficient length of bone for the reconstruction of the postsurgical defects. Excellent vascularity of fibula flap allows for easy uptake of the graft and osseointegration of the dental implants. The addition of a skin island allows for absolute tension-free intraoral closure that enhances tongue mobility. Fibula graft allows proper tissue support after mandibular reconstruction. After rehabilitation with free fibula graft we can plan for prosthodontic rehabilitation with implant retained prosthesis leading to improved masticatory function. It also helps to improve speech outcome as a stable prosthesis can be delivered with the help of implants retained in the fibula graft. It is essential to assess the outcome of surgical reconstruction with fibula graft followed by prosthetic rehabilitation with implant retained prosthesis for their recognition as a treatment of preference. This article details the clinical report along with various clinical parameters for implant retained prosthetic rehabilitation of the patient who had undergone mandibular resection and reconstruction with free fibula graft. (C) 2017 by Mutaz B. Habal, MD.

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A Craniometric Analysis of Cranial Base and Cranial Vault Differences in Patients With Metopic Craniosynostosis.

Purpose: The effect of synostosis is not confined to the immediate vicinity of the suture. The authors hypothesized metopic craniosynostosis results in migration of lateral structures from midline, and differences in segmental volume of the cranial fossa. Methods: A retrospective case-controlled cohort analysis of patients with nonsyndromic metopic craniosynostosis was performed. Craniometric angles, distances to landmarks from midline, cephalic index, and segmented volume ratios were calculated. A comparison group consisted of patients without cranial pathology or with mild positional plagiocephaly. Results: Twenty patients with metopic craniosynostosis and 19 controls were identified. The bifrontal angle was significantly more acute in metopic patients. Distance from midline to the medial carotid, the foramen ovale, and the hypoglossal canal were all significantly longer in metopic patients. Ratio of anterior third to total cranial vault volume was significantly smaller in metopic patients; however, ratio of middle third to total cranial vault volume was significantly larger. As the bifrontal angle decreased by 1[degrees], the volume of the anterior third of the cranial vault was observed to decrease by 0.17% (P

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Immediate Dental Implant Placement After Removal of Complex Odontoma.

The aim of the authors was to report a clinical case about immediate implant placement after the removal of complex odontoma. A 35-year-old female patient presented to private service complaining about absence of lower right first premolar. The computed tomographic showed radiopaque attenuation, surrounded by a narrow radiolucency in the area of dental absence, suggesting a mineralized lesion. The surgical removal of lesion was performed by intraoral access with general anesthesia and the implant of 3.75 x 10 mm (Neodent) was placed with the aid of a surgical guide, following the drill sequence established by the manufacturer. No complications were observed after 1 year with the prosthetic rehabilitation. (C) 2017 by Mutaz B. Habal, MD.

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Review of "Safety of Overlapping Surgery at a High-Volume Referral Center" by Hyder JA, Hanson KT, Storlie CB, Glasgow A, Madde NR, Brown MJ, Kor DJ, Cima RR, Habermann EB in Ann Surg 265: 639-644, 2017.

No abstract available

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Maxillary Corticotomies With Bone-to-Bone Retraction and Mandibular Segmental Osteotomy for Correcting an Anterior Double Protrusion.

Backgrounds: This article presents maxillary corticotomies with bone-to-bone retraction and anterior segmental osteotomy (ASO) as an alternative to 2-jaw orthognathics in the bimaxilary protrusion patient with partially anchylosed maxillary anterior tooth. Methods: The 18-year-old male, complaining of anterior protrusion, with a trauma history to the maxillary central incisor, and requesting rapid treatment, was treated with maxillary corticotomies in 2 stages and ASO in the mandible. The mandibular ASO and palatal corticotomy were done under local anesthesia and 2 weeks later, labial corticotomy followed. The anterior segment was retracted bodily using buccal C-tubes and a combination of the C-lingual retractor and palatal C-plate. Results: Due to a concern about ankylosis of the maxillary right central incisor, retraction of the anterior bone/tooth segment was chosen over any attempt to move teeth through the bone. After bone-to-bone retraction, the remaining extraction space was closed by protraction of posteriors. The total treatment period was 18 months. There was good retraction of the anterior segment and retrusion of the lips. Conclusions: A combination of maxillary corticotomies with skeletal anchorage for bone-to-bone retraction and a mandibular ASO under local anesthesia might be an alternative treatment option for excellent profile change in a short treatment period. (C) 2017 by Mutaz B. Habal, MD.

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Impact of Septoplasty on Eustachian Tube Functions.

Objective: To evaluate the impact of nasal septum deviation (NSD) and septoplasty on eustachian tube (ET) functions. Material and Methods: The study was designed as a prospective controlled study and conducted in a tertiary referral center. A study group of 25 patients who were scheduled for septoplasty for NSD; and a control group of 25 healthy individuals having no ear or nose symptoms were formed. Tympanometric analysis of ET function, subjective and objective analysis of nasal functions with acoustic rhinometry and rhinomanometry were performed. Patients in study group underwent nasal surgery and tests were repeated at postoperative 1st and 3rd months. Results: Eustachian tube functions of study group were significantly worse than the control group (P = 0.032). ET functions were found to be poorer as the nasal airway resistances increase which was found to be close to significance (P = 0.056). One and 3 months after corrective surgery, both nasal airway functions and ET functions improved significantly reaching to the level of control group. Conclusions: Nasal septum deviation was associated with higher rates of ET dysfunction, which could be improved by the nasal surgery. However, in some patients, nasal surgery itself caused ET dysfunction in the early postoperative period. (C) 2017 by Mutaz B. Habal, MD.

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Use of Pedicled Buccal Fat Pad for Midface Augmentation.

The pedicled buccal fat pad has occasionally been used for the closure of oroantral and oronasal fistulae. However, this versatile and convenient technique has not been used widely in the field of esthetic surgery. The main cosmetic interest in the buccal fat pads was to surgically extract them to reduce cheek prominence. Here, the authors introduce a novel operative technique using the pedicled buccal fat pad for midface augmentation in patients with deficient soft-tissue volume, particularly in the anterior malar or paranasal region. This rather simple surgical method can be performed either individually or concomitantly with reduction malarplasty. The surgical outcomes include a natural appearance with reliable long-term stability. (C) 2017 by Mutaz B. Habal, MD.

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Effects of toothpastes on white spot lesions around orthodontic brackets using quantitative light-induced fluorescence (QLF)

Abstract

Aim

The aim of this study was to investigate the effects of toothpastes with different contents on the remineralization of white spot lesions around orthodontic brackets by quantitative light-induced fluorescence (QLF).

Materials and methods

A total of 45 freshly extracted human mandibular first molars were selected. Artificial caries lesions were created on enamel surfaces using an acidified gel system for 7 days. Initial relative fluorescence loss was calculated as the pretreatment (baseline) fluorescence value by QLF device. Molar tubes were bonded using light-cured resin composite cement. The specimens were randomly divided into three experimental groups (n = 15). Different toothpastes were applied to demineralized enamel: (1) fluoride-containing toothpaste (Colgate Total^®), (2) Novamin-containing toothpaste (Sensodyne^® Repair and Protect), (3) probiotic-containing toothpaste (GD Probiotic Toothpaste^®). After 2 weeks of treatment, fluorescence loss and lesion area were measured with QLF. To determine fluorescence changes, intergroup comparisons were performed with a multivariate analysis of variance, followed by Tukey's test at a probability value of p < 0.05.

Results

Significant differences were observed between initial and posttreatment QLF measurements of the demineralized enamel specimens treated with the various agents (p < 0.05). In all experimental groups, significant fluorescence radiance increase and decrease of the lesion area (p = 0.000) was found.

Conclusion

Novamin-containing toothpaste provided more increase of fluorescence compared to fluoride- and probiotic-containing toothpastes.

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Development of a Rapid Analysis Method for Bone Resection Margins for Oral Squamous Cell Carcinoma by Immunoblotting

Abstract

The purpose of this proof-of-principle study was to develop a rapid and approachable method to analyse bone resection margins in patients with oral squamous cell carcinoma (OSCC) in an intraoperative setting, similar to assessing frozen sections of soft tissue. Bone excision and risk of remaining tumour cells could be minimised, thus improving reconstruction measures and facilitating convalescence. Frozen, sawed wafers of porcine bone artificially combined with porcine skin (simulating OSCC properties) were used to develop and evaluate a new molecular method: protein transfer from non-decalcified, sawed wafers onto a membrane stained by immunofluorescence (Tissue-ProtTrans). Tissue-ProtTrans was based on the detection of keratin 5/6 as a marker of tumour cells. The results were compared to standard immunohistochemistry (IHC) and H&E results of the same wafers after decalcification. Tissue-ProtTrans resulted in a total assay time of 3.5 h using the Trans-Blot^® Turbo™ Transfer System (Bio-Rad) for protein transfer. Amersham Protran^® Premium Nitrocellulose Membranes 0.2 µm (GE Healthcare) were stained with a primary antibody to keratin 5/6 (Dako Agilent) and a secondary antibody labelled with IRDye^® 800CW (LI-COR). Visualisation was performed with an infrared laser scanner (Odyssey). Upon comparison, five independent experiments on porcine specimens processed with the Tissue-ProtTrans showed similar results to standard IHC and H&E analysis. In comparison to standard IHC results (requiring several days due to decalcification) Tissue-ProtTrans provided similar results, but was much faster (3.5 h). This highly promising method has good potential for further time reduction and will be suitable for intraoperative assessment.

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Vaccines, Vol. 5, Pages 26: An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine

Vaccines, Vol. 5, Pages 26: An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine

Vaccines doi: 10.3390/vaccines5030026

Authors: Robert Wauters Camellia Hernandez Maureen Petersen

Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

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Stunning shots capture how we interact with our natural world

These evocative pictures by photographer Lucas Foglia catalogue his quest to capture our turbulent relationship with nature

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Hyperspectral satellite data analysis for pure pixels extraction and evaluation of advanced classifier algorithms for LULC classification

Abstract

The study was carried out for Indian capital city Delhi using Hyperion sensor onboard EO-1 satellite of NASA. After MODTRAN-4 based atmospheric correction, MNF, PPI and n-D visualizer were applied and endmembers of 11 LCLU classes were derived which were employed in classification of LULC. To incur better classification accuracy, a comparative study was also carried out to evaluate the potential of three classifier algorithms namely Random Forest (RF), Support Vector Machines (SVM) and Spectral Angle Mapper (SAM). The results of this study reemphasize the utility of satellite borne hyperspectral data to extract endmembers and also to delineate the potential of random forest as expert classifier to assess land cover with higher classification accuracy that outperformed the SVM by 19% and SAM by 27% in overall accuracy. This research work contributes positively to the issue of land cover classification through exploration of hyperspectral endmembers. The comparison of classification algorithms' performance is valuable for decision makers to choose better classifier for more accurate information extraction.

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Selective knockout of astrocytic Na+/H+ exchanger isoform 1 reduces astrogliosis, BBB damage, infarction, and improves neurological function after ischemic stroke

Abstract

Stimulation of Na⁺/H⁺ exchanger isoform 1 (NHE1) in astrocytes causes ionic dysregulation under ischemic conditions. In this study, we created a Nhe1^flox/flox (Nhe1^f/f) mouse line with exon 5 of Nhe1 flanked with two loxP sites and selective ablation of Nhe1 in astrocytes was achieved by crossing Nhe1^f/f mice with Gfap-Cre^ERT2 Cre-recombinase mice. Gfap-Cre^ERT2+/−;Nhe1^f/f mice at postnatal day 60–90 were treated with either corn oil or tamoxifen (Tam, 75 mg/kg/day, i.p.) for 5 days. After 30 days post-injection, mice underwent transient middle cerebral artery occlusion (tMCAO) to induce ischemic stroke. Compared with the oil-vehicle group (control), Tam-treated Gfap-Cre^ERT2+/−;Nhe1^f/f (Nhe1 KO) mice developed significantly smaller ischemic infarction, less edema, and less neurological function deficits at 1–5 days after tMCAO. Immunocytochemical analysis revealed less astrocytic proliferation, less cellular hypertrophy, and less peri-lesion gliosis in Nhe1 KO mouse brains. Selective deletion of Nhe1 in astrocytes also reduced cerebral microvessel damage and blood–brain barrier (BBB) injury in ischemic brains. The BBB microvessels of the control brains show swollen endothelial cells, opened tight junctions, increased expression of proinflammatory protease MMP-9, and significant loss of tight junction protein occludin. In contrast, the Nhe1 KO mice exhibited reduced BBB breakdown and normal tight junction structure, with increased expression of occludin and reduced MMP-9. Most importantly, deletion of astrocytic Nhe1 gene significantly increased regional cerebral blood flow in the ischemic hemisphere at 24 hr post-MCAO. Taken together, our study provides the first line of evidence for a causative role of astrocytic NHE1 protein in reactive astrogliosis and ischemic neurovascular damage.

• Stimulation of astrocytic NHE1 protein at the BBB is detrimental in ischemic brains.
• Deletion of astrocytic Nhe1 gene inhibits astrogliosis, reduces stroke volume, prevents BBB damage, and improves rCBF and neurological function after stroke.

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April Fritz

The International Agency for Research on Cancer (IARC) is saddened by the passing of Mrs April Fritz, a long-time IARC collaborator, who died on Tuesday 12 September 2017 to cancer.

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Peak nasal inspiratory flow as outcome for provocation studies in allergen exposure chambers: a GA2LEN study

The GA2LEN chamber has been developed as a novel mobile allergen exposure chamber (AEC) allowing standardized multicenter trials in allergy. Hitherto, subjective nasal symptom scores have been the most often used...

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Effects of toothpastes on white spot lesions around orthodontic brackets using quantitative light-induced fluorescence (QLF)

Abstract

Aim

The aim of this study was to investigate the effects of toothpastes with different contents on the remineralization of white spot lesions around orthodontic brackets by quantitative light-induced fluorescence (QLF).

Materials and methods

A total of 45 freshly extracted human mandibular first molars were selected. Artificial caries lesions were created on enamel surfaces using an acidified gel system for 7 days. Initial relative fluorescence loss was calculated as the pretreatment (baseline) fluorescence value by QLF device. Molar tubes were bonded using light-cured resin composite cement. The specimens were randomly divided into three experimental groups (n = 15). Different toothpastes were applied to demineralized enamel: (1) fluoride-containing toothpaste (Colgate Total^®), (2) Novamin-containing toothpaste (Sensodyne^® Repair and Protect), (3) probiotic-containing toothpaste (GD Probiotic Toothpaste^®). After 2 weeks of treatment, fluorescence loss and lesion area were measured with QLF. To determine fluorescence changes, intergroup comparisons were performed with a multivariate analysis of variance, followed by Tukey's test at a probability value of p < 0.05.

Results

Significant differences were observed between initial and posttreatment QLF measurements of the demineralized enamel specimens treated with the various agents (p < 0.05). In all experimental groups, significant fluorescence radiance increase and decrease of the lesion area (p = 0.000) was found.

Conclusion

Novamin-containing toothpaste provided more increase of fluorescence compared to fluoride- and probiotic-containing toothpastes.

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A Method to Assign Age at Thelarche in Girls with Inconsistent or Missing Maturation Staging

Longitudinal cohort studies of pubertal maturation are the preferred design but present challenges in data analysis of pubertal events when missed observations or apparent pubertal regression occur. Many past studies have used the mid-point of the interval encompassing the missed observations, which assumes equal probability of the event across the interval. Some have dropped subjects who experienced maturation prior to or after the period of observation, but these subjects may be very informative for assessing the relationship between the risk factor and age at the pubertal event.

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The Fernald Community Cohort: Lessons Learned from Developing a Large Epidemiology Cohort with a 25 Year Heritage

Members of the Fernald Community Cohort (FCC, N=9782) received medical screenings from 1990-2008 (18 years). Although eligibility for the medical monitoring program was based on living within 5 miles of a uranium refinery, exposure studies conducted by CDC demonstrated that much of the cohort never experienced uranium exposure beyond usual background levels, and thus there are both uranium-exposed and non-exposed persons in the cohort. Cohort follow-up continues to the present. Members of this multi-generational cohort completed yearly questionnaires (total 96,091) on a wide array of health risk factors and received a comprehensive medical examination every 2 or 3 years (total 43,283) including clinical laboratory tests, mammograms, PFTs, EKGs, and chest x-rays.

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Hepatitis C testing for West African Immigrants in the US: Screening for the Millenium

Hepatitis C (HCV) testing is not recommended for immigrants from the continent of Africa except those from Egypt. Yet preliminary data from small-scale studies in Africa suggest that HCV is present in other countries. We present data from a pilot study conducting HCV testing for all West Africans receiving health care services in a Federally Qualified Health Center look-alike setting in urban US.

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Aggregation of Connecticut Towns for Precise Population Health Indicator Assessment

Estimates of population health indicators for small geographic areas are important for public health programs targeting local populations; however, such small area estimates often have poor precision. One approach to address such imprecision is to aggregate small areas into larger regions to achieve minimal population sizes needed to achieve target levels of precision while maintaining optimal homogeneity of smaller areas, as well as geographic contiguity. We sought to develop a general framework for such aggregation using sociodemographic data for the 169 towns in Connecticut.

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Assessing Risk of Influenza Infection on a College Campus: An Emphasis on Housing Arrangement

Each year, millions of cases of influenza are reported in the United States. The virus can spread rapidly on college campuses, partially due to housing arrangements and social activities. The purpose of this study was to determine if housing arrangements were associated with increased influenza or influenza-like-illnesses (ILIs) infection rates at Liberty University.

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Association of Perfluoroalkyl substances with Hyperuricemia and Gout

Previous population cross-sectional studies have reported a positive association of perfluoroalkyl and polyfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with hyperuricemia and chronic kidney diseases (CKD) defined as estimate glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2.

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Influence of Socioeconomic Status on the Whole Blood Transcriptome in African Americans

The correlation between low socioeconomic status (SES) and poor health outcome or higher risk of disease has been consistently reported by many epidemiological studies across various race/ancestry groups. It is postulated that social factors play an important etiologic role in the racial disparities in health observed in African-Americans. However, the biological mechanisms linking low SES to disease and/or disease risk factors are not well understood and remain relatively under-studied. The analysis of the blood transcriptome is a promising window for elucidating how social and environmental factors influence the molecular networks governing health and disease.

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Worldwide Sex Ratio Variations in Cancer Incidence

Cancer is a major public health problem and a common indicator of the cancer burden is the incidence rate. This measure, which is useful in investigating etiology, is often obtained from population-based cancer registries in different regions. However, the incidence rate of cancer in any registry is only valid if the ascertainment of cancer cases approaches 100%. Incomplete ascertainment can lead to biased comparisons of incidence rates across worldwide regions. Sex ratio (SR) analysis of cancer incidence (age-standardized incidence rates in males relative to females) mitigates some of the methodological challenges created by imperfect case ascertainment in international cancer registries such as inter-regional variability in diagnostic techniques, prevention strategies, tumor definitions, coding practices and socio-cultural factors (provided that the ascertainment is similar among males and females in those registries).

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Acute Poisoning in Moroccan Children: A 14-year Retrospective Study

Acute poisoning is a major preventable public health problem among children in the world. According to the World Health Organization (WHO), acute poisoning accounts for an estimated 45 000 deaths annually among children and youth people under the age of 20 years. The aim of this study is to determine the epidemiological characteristics of acute poisoning in children in Morocco.

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Associations between Shiftwork and 25-hydroxy Vitamin D3 Levels among Police Officers

Policing is an occupation that requires shift work. Individuals working at night may develop vitamin D deficiency, which may lead to various health problems.

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Racial Differences in Survival of Pediatric Patients with Brain and Central Nervous System Cancer, United States, 2001–2012

Brain and central nervous system (CNS) cancer is the second most common childhood cancer and is the leading cause of cancer death among children and adolescents. Despite improvements in survival during the past 40 years, some data suggest a racial disparity for survival. Our study aims to describe survival by race by using national data to better understand the effects of demographic and clinical factors.

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Predictors of Weight Loss among Participants in the National Diabetes Prevention Program: A Quantile Regression Approach

To determine whether the association between percent weight loss and its predictors varies across weight loss quantiles and race/ethnicity groups among participants in the National Diabetes Prevention Program (National DPP).

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Distribution of C-reactive Protein among US Adults from National Health and Nutrition Examination Survey (NHANES), 2009-2010

The cardiovascular disease (CVD) is the leading cause of morbidity and mortality among US adult population. In addition, disparities in CVD morbidity and mortality exist as CVD risk factors differ by gender and ethnicity. According to the American Heart Association in 2014, among blacks, 46.0% males and 47.7 % females had CVD and number of deaths 49,210 in males and 48,573 in females. Recently, C-reactive protein (CRP), a biomarker of chronic inflammation emerges as an independent predictor of CVD.

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Author Index

Abramson D.M., P84

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Andrea Fleisch Marcus, PhD, MPH winner of the American College of Epidemiology Annals of Epidemiology Junior Investigator Award, 2017

The American College of Epidemiology is pleased to announce the selection of Andrea Fleisch Marcus, PhD, MPH as the winner of this year's Annals of Epidemiology Best Junior Investigator Award. This prize of $1,000 is the inaugural, annual award to the first author of the manuscript chosen by the Publication Committee of the American College of Epidemiology as the best article by a student or early stage investigator within five years of receipt of their terminal degree in epidemiology. This award underscores the close affiliation of the College with the Annals of Epidemiology.

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Sepsis-Induced Cardiomyopathy: Oxidative Implications in the Initiation and Resolution of the Damage

Cardiac dysfunction may complicate the course of severe sepsis and septic shock with significant implications for patient's survival. The basic pathophysiologic mechanisms leading to septic cardiomyopathy have not been fully clarified until now. Disease-specific treatment is lacking, and care is still based on supportive modalities. Septic state causes destruction of redox balance in many cell types, cardiomyocytes included. The production of reactive oxygen and nitrogen species is increased, and natural antioxidant systems fail to counterbalance the overwhelming generation of free radicals. Reactive species interfere with many basic cell functions, mainly through destruction of protein, lipid, and nucleic acid integrity, compromising enzyme function, mitochondrial structure and performance, and intracellular signaling, all leading to cardiac contractile failure. Takotsubo cardiomyopathy may result from oxidative imbalance. This review will address the multiple aspects of cardiomyocyte bioenergetic failure in sepsis and discuss potential therapeutic interventions.

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Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration and Neuroinflammation

Acid-sensing ion channels (ASICs) are a family of proton-sensing channels that are voltage insensitive, cation selective (mostly permeable to Na+), and nonspecifically blocked by amiloride. Derived from 5 genes (ACCN1–5), 7 subunits have been identified, 1a, 1b, 2a, 2b, 3, 4, and 5, that are widely expressed in the peripheral and central nervous system as well as other tissues. Over the years, different studies have shown that activation of these channels is linked to various physiological and pathological processes, such as memory, learning, fear, anxiety, ischemia, and multiple sclerosis to name a few, so their potential as therapeutic targets is increasing. This review focuses on recent advances that have helped us to better understand the role played by ASICs in different pathologies related to neurodegenerative diseases, inflammatory processes, and pain.

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Effect of the Mg/Al Ratio on Activated Sol-Gel Hydrotalcites for Photocatalytic Degradation of 2,4,6-Trichlorophenol

Currently, interest has grown in finding effective solutions for the treatment of water pollution by toxic compounds. Some of the latter that have acquired importance are phenols and chlorophenols, due to their employment in the manufacture of pesticides, insecticides, cords of wood, paper industry, among others. The problem is rooted in that these compounds are very persistent in the environment because they are partially biodegradable and cannot be photodegraded directly by sunlight. Chlorophenols are extremely toxic, especially 2,4,6-trichlorophenol, which is potentially carcinogenic. In this work, Mg/Al-mixed oxide catalysts were obtained from the thermal treatment of hydrotalcite-type materials, synthesized by sol-gel method with different Mg/Al ratios. Hydrotalcites and Mg/Al-mixed oxides were physicochemically characterized by X-ray diffraction, thermal analysis (DTA and TGA), and N2 physisorption. The results were obtained on having proven the photocatalytic degradation of 2,4,6-trichlorophenol as a pollutant model by water. The catalysts obtained present the hydrotalcite phase with thermal evolution until achieving Mg/Al-mixed oxides at 500°C. The catalysts are of mesoporous materials and exhibiting large surface areas. The catalysts demonstrated good photocatalytic activity with good efficiency, reaching degradation percentages with Mg/Al = 1, 2, 4, 5, and 7 ratios of 94.2, 92.5, 86.2, 84.2, and 63.9%, respectively, until achieving mineralization.

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Asymptotic Behaviour of the QED Perturbation Series

I will summarize the present state of a long-term effort to obtain information on the large-order asymptotic behaviour of the QED perturbation series through the effective action. Starting with the constant-field case, I will discuss the Euler-Heisenberg Lagrangian in various dimensions and up to the three-loop level. This Lagrangian holds the information on the N-photon amplitudes in the low-energy limit, and combining it with Spinor helicity methods explicit all-N results can be obtained at the one-loop and, for the "all +" amplitudes, also at the two-loop level. For the imaginary part of the Euler-Heisenberg Lagrangian, an all-loop formula has been conjectured independently by Affleck, Alvarez, and Manton for Scalar QED and by Lebedev and Ritus for Spinor QED. This formula can be related through a Borel dispersion relation to the leading large-N behaviour of the N-photon amplitudes. It is analytic in the fine structure constant, which is puzzling and suggests a diagrammatic investigation of the large-N limit in perturbation theory. Preliminary results of such a study for the dimensional case throw doubt on the validity of the conjecture.

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Genes, Vol. 8, Pages 234: Circulating microRNAs and Bioinformatics Tools to Discover Novel Diagnostic Biomarkers of Pediatric Diseases

Genes, Vol. 8, Pages 234: Circulating microRNAs and Bioinformatics Tools to Discover Novel Diagnostic Biomarkers of Pediatric Diseases

Genes doi: 10.3390/genes8090234

Authors: Antonella Baldassarre Cristina Felli Giorgio Prantera Andrea Masotti

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Current studies have shown that miRNAs are also present in extracellular spaces, packaged into various membrane-bound vesicles, or associated with RNA-binding proteins. Circulating miRNAs are highly stable and can act as intercellular messengers to affect many physiological processes. MicroRNAs circulating in body fluids have generated strong interest in their potential use as clinical biomarkers. In fact, their remarkable stability and the relative ease of detection make circulating miRNAs ideal tools for rapid and non-invasive diagnosis. This review summarizes recent insights about the origin, functions and diagnostic potential of extracellular miRNAs by especially focusing on pediatric diseases in order to explore the feasibility of alternative sampling sources for the development of non-invasive pediatric diagnostics. We will also discuss specific bioinformatics tools and databases for circulating miRNAs focused on the identification and discovery of novel diagnostic biomarkers of pediatric diseases.

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Leaflet repair techniques in mitral valve reconstruction

Abstract

Recently, there has been tremendous development in mitral valve repair, especially in imaging modalities, minimally invasive approaches and surgical techniques. Among various surgical techniques, leaflet techniques have also advanced for treatment of different types of mitral valve diseases. The optimal leaflet technique depends on the involvement of anterior or posterior leaflet, aetiology of the disease and the usage of surgical approach. In degenerative disease for posterior leaflet prolapse, the current trends are from classical quadrangular resection to limited triangular resection. Development of techniques like peeling and pericardial leaflet augmentation has made mitral valve repair feasible in rheumatic heart disease. Similarly, with better understanding of pathophysiology of ischemic mitral regurgitation, the new techniques involving leaflets and subvalvular apparatus have also progressed for more stable and durable repair. In this review, various leaflet repair techniques, which are applicable to various types of functional classification for different aetiology, have been described in detail.

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Mediterranean Diet Cookbook For Dummies, 2nd Edition

Benefit from the Mediterranean diet For decades, doctors and nutritional experts have observed—and confirmed—that people in Mediterranean countries have much lower occurrences in vascular disease, obesity, cancer, and diabetes than their counterparts in northern European countries and the United States. Now, Mediterranean Diet Cookbook For Dummies shows you how to cook meals inspired by the cuisines of Italy, Greece, Spain, and southern France so you Read More...

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Personalizing Precision Medicine: A Global Voyage from Vision to Reality

The author uses decades of experience and interviews with experts in precision medicine to explain past, present, and future of precision medicine. She reviews the full continuum of personalizing precision medicine, including diagnostics, therapeutics, big data, supportive care, regulation, and reimbursement and innovation in precision medicine worldwide. •    Combines a unique cross section of history, current technologies, and future directions for Read More...

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The relationship between CO 2 emission, energy consumption and economic growth in Malaysia: a three-way linkage approach

Abstract

This study examines the three-way linkage relationships between CO₂ emission, energy consumption and economic growth in Malaysia, covering the 1975–2015 period. An autoregressive distributed lag approach was employed to achieve the objective of the study and gauged by dynamic ordinary least squares. Additionally, vector error correction model, variance decompositions and impulse response functions were employed to further examine the relationship between the interest variables. The findings show that economic growth is neither influenced by energy consumption nor by CO₂ emission. Energy consumption is revealed to be an increasing function of CO₂ emission. Whereas, CO₂ emission positively and significantly depends on energy consumption and economic growth. This implies that CO₂ emission increases with an increase in both energy consumption and economic growth. Conclusively, the main drivers of CO₂ emission in Malaysia are proven to be energy consumption and economic growth. Therefore, renewable energy sources ought to be considered by policy makers to curb emission from the current non-renewable sources. Wind and biomass can be explored as they are viable sources. Energy efficiency and savings should equally be emphasised and encouraged by policy makers. Lastly, growth-related policies that target emission reduction are also recommended.

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Analysis of influence mechanism of energy-related carbon emissions in Guangdong: evidence from regional China based on the input-output and structural decomposition analysis

Abstract

It is important to analyze the influence mechanism of energy-related carbon emissions from a regional perspective to effectively achieve reductions in energy consumption and carbon emissions in China. Based on the "energy-economy-carbon emissions" hybrid input-output analysis framework, this study conducted structural decomposition analysis (SDA) on carbon emissions influencing factors in Guangdong Province. Systems-based examination of direct and indirect drivers for regional emission is presented. (1) Direct effects analysis of influencing factors indicated that the main driving factors of increasing carbon emissions were economic and population growth. Carbon emission intensity was the main contributing factor restraining carbon emissions growth. (2) Indirect effects analysis of influencing factors showed that international and interprovincial trades significantly affected the total carbon emissions. (3) Analysis of the effects of different final demands on the carbon emissions of industrial sector indicated that the increase in carbon emission arising from international and interprovincial trades is mainly concentrated in energy- and carbon-intensive industries. (4) Guangdong had to compromise a certain amount of carbon emissions during the development of its export-oriented economy because of industry transfer arising from the economic globalization, thereby pointing to the existence of the "carbon leakage" problem. At the same time, interprovincial export and import resulted in Guangdong transferring a part of its carbon emissions to other provinces, thereby leading to the occurrence of "carbon transfer."

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JCM, Vol. 6, Pages 87: Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia

JCM, Vol. 6, Pages 87: Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia

Journal of Clinical Medicine doi: 10.3390/jcm6090087

Authors: Gregory Roloff Catherine Lai Christopher Hourigan Laura Dillon

Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice.

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JCM, Vol. 6, Pages 88: Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

JCM, Vol. 6, Pages 88: Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

Journal of Clinical Medicine doi: 10.3390/jcm6090088

Authors: Hamid Merchant

Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of these subjects are non-alcoholic and have a normal body mass index (BMI), an intensive lifestyle change program is not usually recommended. This report presents an otherwise healthy non-alcoholic subject with incidental NAFLD having a normal BMI and a waist circumference below 90 cm who successfully reversed his condition by undertaking a lifestyle intervention. The case report is expected to encourage large cohort studies to substantiate the benefits of dietary interventions in alleviating hepatic steatosis among non-obese individuals.

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