Malignant peripheral nerve sheath tumor of the femoral nerve: imaging findings and correlation with histopathology.

Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive soft tissue sarcomas. MPNST diagnosis is made based on biopsy, but distinct features are present on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). We present a case of a 24-year-old man presenting with abdominal pain and lower-extremity weakness found to have a large MPNST originating from the left femoral nerve and describe findings on imaging and their histopathologic correlation.

Correction: Evaluating adherence to government recommendations for post-exposure rabies vaccine among animal-bite victims: A hospital-based study in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgph.0002506.].

Nonalcoholic Fatty Liver Disease (NAFLD) and Cardiovascular Risk: Is Imaging Helpful?

Nonalcoholic Fatty Liver Disease (NAFLD) is proving to be a globally prevalent condition. Moreover, NAFLD may be an independent risk factor associated with higher cardiovascular (CVD) morbidity and mortality. Further studies are needed to assess whether NAFLD needs to be included in the atherosclerotic risk score algorithms or whether patients with NAFLD need to be screened early on to assess their CVD risk especially since imaging such as positron emission tomography can be used to assess both NAFLD and CV disease at the same time. Therefore employing cardiovascular imaging modalities to investigate the incidence, extent, and nature of atherosclerotic lesions in NAFLD may be beneficial. Additionally, whether treating NAFLD halts the progression of CVD on imaging remains to be seen. Further research to delineate NAFLD and CVD associations, deciphering screening imaging modalities, and investigating targeted interventions could improve CVD morbidity and mortality in NAFLD.

Giant mandibular osteoma, CT findings for the primary care provider.

We report a very rare case of 35-year-old female with a giant mandibular osteoma in the angle of the mandible. We highlight the importance of CT in diagnosing as well as defining the extent of this rare case so that proper management can be undertaken. We also showcase the importance of angiography to show relationship of this mass with the surrounding vessels.

Evaluating adherence to government recommendations for post-exposure rabies vaccine among animal-bite victims: A hospital-based study in Bangladesh.

Rabies is a fatal but preventable zoonotic disease with an approximately 100% case fatality rate. The most common way to contract rabies is through the bite of a rabid animal. Post-exposure prophylaxis (PEP) by vaccination and/or immunoglobulin therapy is the most effective measure for rabies prevention. The effectiveness of vaccination depends on the level of completion of vaccination. In Bangladesh, no previous studies were conducted to evaluate adherence to government recommendations for post-exposure rabies vaccine among animal-bite cases. We conducted a cross-sectional study to collect information about adherence to government recommendations for post-exposure rabies vaccine. A total of 457 animal bite victims were selected to collect data and follow up after one month of enrollment. The majority of participants (58%, n = 265, 95% CI: 53-63%) had a history of animal bites. Most of the participants (77%) were advised to receive three doses of vaccine and 100% of them completed 3-dose of vaccine. Among the 4-dose recommended group of participants (n = 105), 78% completed full vaccination. Of the 457 participants, 20% received post-exposure vaccine on the day of bite/scratch and the majority of the participants (66%, n = 303, 95% CI: 62-71%) received post-exposure vaccine on the day between the first and third day of bite or scratch. Increasing awareness of the importance of timely vaccination is the key to reducing the time gap between animal bites and intake of the first dose post-exposure vaccine.

Identification of genes critical for inducing ulcerative colitis and exploring their tumorigenic potential in human colorectal carcinoma.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease leading to continuous mucosal inflammation in the rectum extending proximally towards the colon. Chronic and/or recurrent UC is one of the critical predisposing mediators of the oncogenesis of human colorectal carcinoma (CRC). Perturbations of the differential expression of the UC-critical genes exert an intense impact on the neoplastic transformation of the affected tissue(s). Herein, a comprehensive exploration of the UC-critical genes from the transcriptomic profiles of UC patients was conducted to study the differential expression, functional enrichment, genomic alterations, signal transduction pathways, and immune infiltration level encountered by these genes concerning the oncogenesis of CRC. The study reveals that WFDC2, TTLL12, THRA, and EPHB3 play crucial roles as UC-CRC critical genes and are positively correlated with the molecular transformation of UC to CRC. Taken together, these genes can be used as potential biomarkers and therapeutic targets for combating UC-induced human CRC.

Prevalence of hepatitis B and C, and syphilis among aspirant migrant workers of Bangladesh.

Background: In Bangladesh, labour migration is a source of employment and workers' remittances are critical to poverty mitigation. The aim of this study was to assess the prevalence of hepatitis B, C, HIV, tuberculosis, syphilis, kidney and liver diseases along with presence of infections among aspirant migrant workers of Bangladesh. Method: This study was carried out from September-December 2019. We analysed data collected on screening tests of specific diseases of aspirant workers. For each test, the prevalence was computed with 95% confidence interval. Association between categorical data was determined by the Chi-square test. Results: A total of 2385 aspirants, 1988 (83.35%) males, aged between 18 and 65 years (29.76±6.578) were studied. Positive results for screening tests of HBsAg were 38 (1.6%,), anti-HCV were 2 (0.08%), TPHA were 25 (1.05%) and VDRL were 5 (0.21%) though no individual was positive for HIV and TB. Elevated level of SGOT (n=99, 4.2%), SGPT (n=322, 13.5%), RBS (n=57, 2.4%), bilirubin (n=46, 1.92%), creatinine (n=7, 0.3%) and ESR (n=19, 0.8%) were found in the workers. Conclusion: Diagnosis of diseases of workers is obligatory before going abroad to safeguard the health of the workers and residents of destination country. Consequently, it will contribute to reducing the global burden of infectious diseases.

Rib osteochondroma presenting as acute paraparesis.

Osteochondromas are usually osseous outgrowths arising from the metaphyseal region of cortical bone. Moreover, osteochondroma can also arise from flat bones and the spine. However, their origin in the ribs is extremely rare and always near the costochondral junction. We present a 26-year-old male who presented with chief complaints of difficulty in walking for 2 weeks subsequently diagnosed with osteochondroma based on the presence of a cartilage cap on Magnetic resonance imaging.

Oncogenic gain of function due to p53 amyloids occurs through aberrant alteration of cell cycle and proliferation.

Transcription factor p53 (also known as TP53) has been shown to aggregate into cytoplasmic and nuclear inclusions, compromising its native tumor suppressive functions. Recently, p53 has been shown to form amyloids, which play a role in conferring cancerous properties to cells, leading to tumorigenesis. However, the exact pathways involved in p53 amyloid-mediated cellular transformations are unknown. Here, using an in cellulo model of full-length p53 amyloid formation, we demonstrate the mechanism of loss of p53 tumor-suppressive function with concomitant oncogenic gain of functions. Global gene expression profiling of cells suggests that p53 amyloid formation dysregulates genes associated with the cell cycle, proliferation, apoptosis and senescence along with major signaling pathways. This is further supported by a proteome analysis, showing a significant alteration in levels of p53 target proteins and enhanced metabolism, which enables the survival of cells. Our data indicate that specifically targeting the key molecules in pathways affected by p53 amyloid formation, such as cyclin-dependent kinase-1, leads to loss of the oncogenic phenotype and induces apoptosis of cells. Overall, our work establishes the mechanism of the transformation of cells due to p53 amyloids leading to cancer pathogenesis. This article has an associated First Person interview with the first author of the paper.

Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death.

Nutrient surplus and consequent free fatty acid accumulation in the liver cause hepatosteatosis. The exposure of free fatty acids to cultured hepatocyte and hepatocellular carcinoma cell lines induces cellular stress, organelle adaptation, and subsequent cell death. Despite many studies, the mechanism associated with lipotoxicity and subsequent cell death still remains poorly understood. Here, we have used the proteomics approach to circumvent the mechanism for lipotoxicity using hepatocellular carcinoma cells as a model. Our quantitative proteomics data revealed that ectopic lipids accumulation in cells severely affects the ubiquitin-proteasomal system. The palmitic acid (PA) partially lowered the expression of deubiquitinating enzyme USP7 which subsequently destabilizes p53 and promotes mitotic entry of cells. Our global phosphoproteomics analysis also provides strong evidence of an altered cell cycle checkpoint proteins' expression that abrogates early G2/M checkpoints recovery with damaged DNA and induced mitotic catastrophe leading to hepatocyte death. We observe that palmitic acid prefers apoptosis-inducing factor (AIF) mediated cell death by depolarizing mitochondria and translocating AIF to the nucleus. In summary, the present study provides evidence of PA-induced hepatocellular death mediated by deubiquitinase USP7 downregulation and subsequent mitotic catastrophe.

Choline Chloride Induces Growth Performance of Indian Major Carps and Air-Breathing Fish Species with an Outcome of Quality Food-Fish under a Semi-Intensive Culture System: A Biochemical Investigation.

The present study was intended to determine the possible influences of direct field application of choline chloride into pond water in addition to farm-made-aqua-feed under a semi-intensive culture system on the growth and biochemical parameters of two Indian major carps (IMCs), Catla catla (Catla) and Labeo rohita (Rahu), and two air-breathing species, Clarias batrachus (Magur) and Anabas testudineus (Koi), cultured in a ratio of 2:5:1:1 (Catla/Rahu/Magur/Koi) in three experimental ponds for a period of 90 days during the breeding season (June to August). Results were compared with control (C: fed only with farm-made-aqua-feed) and treatment (T: P1 and P2: farm-made-aqua-feed plus choline chloride into pond water directly at the rate of 350 g bigha-1 fortnightly or 350 g per 1600 square meter fortnightly). A significant increasing trend was observed in the growth parameters including total length-final (TLF), standard length-final (SLF), mean weight-final (MWF), % gain of mean total length (MTL), % gain of mean standard length (MSL), % weight gain (WG), specific growth rate (SGR) % per day, and survivability %. However, a reverse pattern was noticed in the food conversion ratio (FCR) both in IMCs and air-breathing fish species under choline supplementation. Serum biochemical responses, e.g., total protein (PRO), lactate dehydrogenase (LDH), glucose (GLU), and calcium (Ca) showed significant enhancement, and alkaline phosphatase (ALP), alanine amino transaminase (ALT), aspartate amino transaminase (AST), cholesterol (CHOLES), and triglycerides (Trig) showed gradual significant reduction during the breeding season under choline exposure. Treated fishes showed prevention from liver dysfunction and fatty liver formation, and increased body crude protein content. Results indicated favorable growth and yield, which may benefit fish farmers during their culture practices, and the output fish species under choline supplementation resulted in quality food-fish for human consumption.

S-Nitrosylation of OTUB1 Alters Its Stability and Ubc13 Binding.

S-Nitrosylation is a reversible post-translational modification that regulates protein function involving the covalent attachment of the nitric oxide (NO) moiety to sulfhydryl residues of the protein. It is an important regulator in the cell signaling process under physiological conditions. However, the release of an excess amount of NO due to dysregulated NOS machinery causes aberrant S-nitrosylation of proteins, which affects protein folding, localization, and activity. Here, we have shown that OTUB1, a deubiquitinating enzyme, undergoes S-nitrosylation under redox stress conditions in vivo and in vitro. Previously, we have shown that OTUB1 forms an amyloid-like structure that promotes phosphorylation of α-synuclein and neuronal toxicity. However, the mechanistic insight into OTUB1 aggregation remains elusive. Here, we identified that OTUB1 undergoes S-nitrosylation in SH-SY5Y neuroblastoma cells under rotenone-induced stress, as well as excitotoxic conditions, and in rotenone-treated mouse brains. The in vitro S-nitrosylation of OTUB1 followed by mass-spectrometry analysis has identified cysteine-23 and cysteine-91 as S-nitrosylation sites. S-Nitrosylated OTUB1 (SNO-OTUB1) diminished its catalytic activity, impaired its native structure, promoted amyloid-like aggregation, and compromised its binding with Ubc13. Thus, our results demonstrated that nitrosylation of OTUB1 might play a crucial role in regulating the ubiquitin signaling and Parkinson's disease pathology.

Impact of Pulmonary Hypertension on In-Hospital Outcomes and 30-Day Readmissions Following Percutaneous Coronary Interventions.

OBJECTIVE: To evaluate the impact of pulmonary hypertension (PH) on percutaneous coronary intervention (PCI) outcomes and 30-day all-cause readmissions by analyzing a national database. METHODS: We queried the 2014 National Readmissions Database to identify patients undergoing PCI using International Classification of Diseases, Ninth Revision, Clinical Modification codes. These patients were then subcategorized based on the coded presence or absence of PH and further analyzed to determine the impact of PH on clinical outcomes, health care use, and 30-day readmissions. RESULTS: Among 599,490 patients hospitalized for a PCI in 2014, 19,348 (3.2%) had concomitant PH. At baseline, these patients were older with a higher burden of comorbidities. Patients with PH had longer initial hospitalizations and higher 30-day readmission rates and mortality than their non-PH counterparts. This was largely driven by cardiac causes, most commonly heart failure (20.3% vs 9.0%, P<.001) and non-ST-segment elevation myocardial infarction. Recurrent coronary events (17.5% vs 9.5%, P<.05) including ST-segment elevation myocardial infarction predominated in the non-PH group. CONCLUSION: Patients with PH undergoing PCI are a high-risk group in terms of mortality and 30-day readmission rates. Percutaneous coronary intervention in patients with PH is associated with higher rates of recurrent heart failure and non-ST-segment elevation myocardial infarction, rather than recurrent coronary events or ST-segment elevation myocardial infarction. This perhaps indicates a predominance of demand ischemia and heart failure syndromes rather than overt atherothrombosis in the etiology of chest pain in these patients.

Cardiac computed tomography in cardio-oncology: an update on recent clinical applications.

Chemotherapy and radiotherapy have drastically improved cancer survival, but they can result in significant short- and long-term cardiovascular complications, most commonly heart failure from chemotherapy, whilst radiotherapy increases the risk of premature coronary artery disease (CAD), valve, and pericardial diseases. Cardiac computed tomography (CT) with calcium scoring has a role in screening asymptomatic patients for premature CAD, cardiac CT angiography (CTCA) allows the identification of significant CAD, also in the acute settings where concerns exist towards invasive angiography. CTCA integrates the diagnostic work-up and guides surgical/percutaneous management of valvular heart diseases and allows the assessment of pericardial conditions, including detection of effusion and pericardial calcification. It is a widely available and fast imaging modality that allows a one-step evaluation of CAD, myocardial, valvular, and pericardial disease. This review aims to provide an update on its current use and accompanying evidence-base for cardiac CT in the management of cardio-oncology patients.

Dynamic Alteration in the Vaginal Secretory Proteome across the Early and Mid-Trimesters of Pregnancy.

Pregnancy is characterized by intense physiological and structural alterations in the vagina, cervix, and overlying fetal membranes. High vaginal fluid (HVF) is a proximal fluid that covers the lower part of the female reproductive system and the severity of vaginal pathology often adversely affects pregnancy outcomes. To identify the correlation of vaginal fluid proteome dynamics and physiological changes during the progression of pregnancy, a longitudinal study was performed on 20 pregnant women who delivered a baby in >37 weeks without any complications. SWATH-MS-based label-free quantitative proteomics was performed to profile the HVF proteome at three time points defined as V1 (7-12 weeks), V2 (18-20 weeks), and V3 (26-28 weeks). Linear mixed-effect models were used to estimate protein abundance as a function of the period of gestational age. In this study, we identified 1015 HVF proteins and 61 of them were significantly altered until late second trimester. Our result demonstrates that the HVF proteins reveal gestational age-specific expression patterns and the function of these proteins is associated with tissue remodeling, organ development, and microbial defense. Our study provides an opportunity to monitor the underlying physiology of pregnancy that may be further probed for the biomarker identification in pregnancy-related adverse outcomes. Data are available via ProteomeXchange with identifiers PXD014846 and PXD021811.

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells.

Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT-interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In-depth analysis of AMOT-interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT-eIF4A binding suggested a strong AMOT-eIF4A interaction using a distinct groove encompassing amino acid residue positions 238 to 255 of AMOT. Co-immunoprecipitation of AMOT with eIF4A reaffirmed AMOT-eIF4A association in trophoblast cells. Deletion of 238 to 255 amino acids of AMOT resulted in abrogation of AMOT-eIF4A interaction. In addition, 238 to 255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT-dependent sequestration of eIF4A dampened its loading to the m7 -GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intrauterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.

Socio-Economic Burden of Myocardial Infarction Among Cancer Patients.

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in noncancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013 to 2018 derived from publicly available United States datasets, the National Health Interview Survey , and economic data from the National Inpatient Sample , we compared the socio-economic outcomes in those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 National Health Interview Survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI in cancer survivors compared with noncancer patients (8.8% vs 3.2%, p <0.001). MI was associated with increased financial worry, food insecurity, and financial burden of medical bills (p <0.001, respectively); however, concurrent cancer did not seem to be an effect modifier (p >0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. MI continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly.

Sex Differences in In-Hospital Outcomes of Transcatheter Aortic Valve Replacement.

Since the introduction of transcatheter aortic valve replacement (TAVR), there has been a paradigm shift in the management of severe aortic stenosis. While women represent almost half of the patients undergoing TAVR, there are limited data on sex-based comparisons in hospital outcomes and predictors of mortality in women and men. The National Inpatient Sample database from 2012 to 2015 was used to identify TAVR using international classification of diseases-9 clinical modification procedure codes 35.05 and 35.06. We identified 61,239 patients who underwent TAVR between 2012 and 2015. After adjusting for potential confounders, women had higher odds of all-cause mortality as compared to men [odds ratio (OR) 1.25, 95% confidence interval (CI): 1.01-1.54; P = 0.036]. Moreover, women had significantly increased odds of cardiac complications [OR 2.41, 95% CI: 1.67-3.49; P ≤ 0.01], respiratory complications [OR 1.20 95% CI: 1.07-1.34; P = 0.001], major hemorrhage requiring transfusion [OR 1.51, 95% CI: 1.37-1.67; P ≤ 0.001], neurological complications [OR 1.38, 95% CI: 0.95-1.99; P = 0.08], need for vasopressor treatment [OR 1.33, 95% CI: 1.01-1.75; P = 0.04], and vascular complications [OR 1.73, 95% CI: 1.19-2.52; P = 0.004]. On the contrary, the odds of pacemaker requirement [OR 0.85, 95% CI: 0.75-0.97; P = 0.02], and acute kidney injury [OR 0.80, 95% CI: 0.71-0.91; P = 0.001] were significantly lower in women. Among patients undergoing TAVR, women were more likely to have in-hospital complications and mortality as compared with men. Further studies are needed to identify the discrepancy in in-hospital outcomes with sex-specific factors being considered.

Juvenile dermatomyositis presenting as complete heart block in a 10-year-old girl.

Juvenile dermatomyositis (JDM) is an auto-immune inflammatory condition associated with cardiac disorders including conduction abnormalities and myocardial dysfunction. The time of presentation of cardiac abnormalities can range from disease onset to after long-term follow-up, emphasising the importance of screening for cardiac involvement in JDM. A previously healthy 10-year-old girl presented with syncope, fatigue and weakness associated with a heliotrope rash. JDM was diagnosed based on the clinical, laboratory and imaging findings. An ECG demonstrated complete heart block (CHB). All symptoms resolved following treatment with parenteral corticosteroids. In JDM, it is important to investigate for cardiac manifestations and in CHB to consider administering corticosteroids.

Salivary proteome signatures in the early and middle stages of human pregnancy with term birth outcome.

The establishment and maintenance of pregnancy in humans proceed through a continuous change of biochemical and biophysical processes. It requires a constant interaction between the fetus and the maternal system. The present prospective study aims to elucidate changes in salivary proteome from the early to middle stages of term pregnancy, and establishing an expressional trajectory for modulated proteins. To date, a comprehensive characterization of the longitudinal salivary proteome in pregnancy has not been performed and it is our immediate interest. In the discovery phase, maternal saliva (N = 20) at 6-13, 18-21, and 26-29 weeks of gestation was analyzed using level-free proteomics (SWATH-MS) approach. The expression levels of 65 proteins were found to change significantly with gestational age and distributed into two distinct clusters with a unique expression trajectory. The results revealed that altered proteins are involved in maternal immune modulation, metabolism, and host defense mechanism. Further, verification of 12 proteins was employed using targeted mass spectrometry (MRM-MS) in a separate subset of saliva (N = 14). The MRM results of 12 selected proteins confirmed a similar expression pattern as in SWATH-MS analysis. Overall, the results not only demonstrate the longitudinal maternal saliva proteome for the first time but also set the groundwork for comparative analysis between term birth and adverse pregnancy outcomes.