Spectrum of vitriolage in India: A retrospective data record-based study.

Introduction: Vitriolage or acid attack or acid throwing is a gender-based terrible violent crime. There are many everlasting sequels of vitriolage which consist of permanent scarring of the face or body, blindness as well as socioeconomic and psychological intricacy. The sufferer of acid attack is competitor, hatred, enmity or jealousy. Vitriolage are most common in the Asian countries especially in south east Asian region followed by Europe and South America. Bangladesh, India, Pakistan, Colombia and Cambodia are the countries having the highest incidence of acid attacks. There is a sharp rise in vitriolage cases in India in the last few years as indicated by data from the National Crime Record Bureau (NCRB). Seventy per cent victims of vitriolage are women in India as indicated by the annual reports of the Acid Survivor Foundation. Aims and Objective: The aim of the study was to report incidence of acid attacks in India, Indian states and metropolitan cities. To analyse various police and court procedure and to discuss various steps to give justice to the victim of vitriolage. Materials and Methods: Present study is a retrospective data record-based study. Available data for the last 5 years (from 2017 to 2021) were taken from National Crime Report Bureau (NCRB). Available as per NCRB, data were analysed as per aims and objectives. Results: The trend of incidence of acid attacks in India was decreasing in the last 5 years, that is, the incidence was 244 in the year 2017 which become 176 in the year 2021. West Bengal and Uttar Pradesh were the states having the highest number of acid attack incidence during the last 5 years. Delhi city was the top most metropolitan city having the highest acid attack incidence in the last 5 years. Police investigation of cases of acid attacks against women and cases disposed of by the police decreased in the last 5 years. The chargesheeting rate was better in metropolitan cities than overall chargesheeting in India. There was an increased trial of cases of acid attacks against women and a decrease in cases disposed of by the court during the last 5 years. Conviction rate by the court was better in India than the metropolitan cities of India during the last 5 years. Case acquitted by the court in India was 24, 9, 10, 4 and 10, and in metropolitan cities it was 2, 1, 3, 0 and 2 during year 2017, 2018, 2019, 2020 and 2021, respectively. Conclusion: Vitriolage not only destroys physical health but also destroys mental health. Despite of strict action taken by the Indian government, vitriolage is still prevalent in India. Male dominancy and inadequate legal systems are responsible for this. Though there is a standard set by the Supreme Court for the sale of acid, it remains easily available as the guidelines are frequently violated by the preparator. Case investigation and chargesheeting should increase by the police. Trial of the case and conviction should increase by the court. Vitriolage victims must be sure of their scope to obtain education and job opportunity and societal fiction should be reviewed to support people to acknowledge why vitriolage is committed mainly against females.

Postinfarction Ventricular Septal Ruptures During the COVID-19 Pandemic: Two Case Series.

This case series highlights the occurrence of hemodynamically significant ventricular septal defects (VSDs) in two patients presenting with ST-elevation myocardial infarction (STEMI) during the COVID-19 pandemic. This paper aims to emphasize the delayed presentation of cardiac emergencies, such as STEMI, due to concerns about contracting COVID-19. This delay has led to an increased risk of rare complications, including VSD, associated with STEMI. The first case involves a 92-year-old male with a history of hypertension, hyperlipidemia, chronic kidney disease, and coronary artery disease. He presented with acute chest pain, and diagnostic tests revealed ST elevations and a VSD. Despite intervention efforts, including hemodynamic support, the patient's condition deteriorated, and he passed away due to advanced age and high surgical risk. The second case involves a 62-year-old female with a medical history of diabetes, hypertension, and hyperlipidemia. She presented with left-sided chest pain, and an angiogram revealed a mid-right coronary artery stenosis and a thrombus. During the procedure, the patient experienced hypotension, requiring hemodynamic support. Subsequent evaluations identified a large VSD with right ventricular dysfunction. The patient underwent a series of interventions, including a ventricular assist device and VSD closure, but experienced multi-organ failure and ultimately passed away. VSDs following acute myocardial infarction (MI) are rare but life-threatening complications. Early revascularization is crucial in preventing the development of VSDs. These cases demonstrate the importance of prompt diagnosis and intervention, as delayed presentation increases the risk of mechanical complications. Surgical closure remains the definitive treatment for postinfarction VSDs.

Clinico-Pathological Outcomes of Patients With Crescentic Glomerulonephritis: A Single-Center Study.

Background Crescentic glomerulonephritis (CrGN) is a pathological description of rapidly progressive glomerulonephritis (RPGN). It is characterized by renal failure and is associated with a grave prognosis. This study aimed to investigate the clinical outcomes of patients diagnosed with crescentic glomerulonephritis at the King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Method This retrospective study included patients with CrGN who underwent treatment at the nephrology department at KAUH from June 2021 to August 2022. We collected and analyzed data from 56 patients diagnosed with CrGN on the basis of renal biopsies between 2002 and 2015. Result The study included 17 cases of CrGN. The mean age of patients at the time of diagnosis was 18.06 ± 13.49 years. The distribution of histological findings showed that cellular crescents (94.1%) and interstitial fibrosis and tubular atrophy (IFTA) (76.5%) were the most commonly observed histological findings. The most common underlying etiology was lupus nephritis (41.2%). Regarding the lab results, the mean serum creatinine level at admission was 378.88 ± 273.27 µmol/L, proteinuria was 1.53 ± 1.23 and glomerular filtration rate (GFR) level was 36.94 ± 45.08 mL/min. The factors associated with poor renal outcome were IFTA (P=0.01), phosphate level before discharge, serum creatinine level before and after discharge (P=0.032), and GFR level after discharge (P=0.001). Conclusion Crescentic glomerulonephritis is an important cause of acute kidney injury due to its potential to result in severe glomerular injury. In our study, 12 out of 17 patients experienced poor renal outcomes, which were associated with a high risk of morbidity and mortality. Therefore, early detection and treatment of CrGN is crucial in order to manage the disease.

Sickle Cell Anemia Associated With Increased In-Hospital Mortality in Post-Cardiac Arrest Patients.

Introduction Sickle cell anemia (SCA) is a hemoglobinopathy that arises from a point mutation in the beta-globin gene, which causes the polymerization of deoxygenated hemoglobin that leads to a wide variety of clinical complications. Deaths in patients with SCA most commonly arise from renal, cardiovascular disease, infections, and stroke. In-hospital cardiac arrest has been found to be more common in older patients and those on ventilatory life support, among others. This study aims to provide more insight into how SCA affects the risk of in-hospital mortality in post-cardiac arrest patients. Methods The National Inpatient Survey database years 2016 to 2019 was utilized. The International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10 PCS) codes for cardiopulmonary resuscitation were used to identify in-hospital cardiac arrest (IHCA) patients. ICD-10 Clinical Modification (CM) codes were used to identify SCA and other medical comorbidities. Categorical data was compared using Person's chi-square test, and continuous variables were compared using the independent samples t-test. Multinomial logistic regression was used to study the effects of SCA on post-arrest in-hospital mortality controlling for age, Charlson comorbidity score, and demographic variables. Binomial logistic regression models for dichotomous variables were utilized in the subgroup and secondary outcomes analysis. Results In patients with IHCA, patients who had SCA were found to have a significantly increased risk of in-hospital mortality adjusted for baseline characteristics and Charlson comorbidity score (OR: 1.16, 95% CI: 1.02-1.32, p=0.0025). Patient characteristics most strongly associated with an increased risk of in-hospital mortality in this cohort were found to be Black race (OR: 1.92, 95% CI: 1.87-1.97, p<0.001) and self-payer status (OR: 2.14, 95% CI: 2.06-2.22, p<0.001). Subgroup analysis revealed only patients with sickle cell disease had a statistically significant increased risk of in-hospital mortality in this cohort (OR: 4.41, 95% CI: 3.5-5.55, p<0.001), and patients with sickle cell trait did not. Conclusion In patients with IHCA, SCA is associated with an increased risk of in-hospital mortality. This risk was confined to patients with sickle cell disease and not patients with sickle cell trait.

Myocarditis as a Complication of Campylobacter jejuni-Associated Enterocolitis: A Report of Two Cases.

Myocarditis refers to inflammation of the heart muscle and may occur individually or together with pericarditis, which refers to inflammation of the saclike tissue layer that surrounds the heart. They may have infectious or non-infectious etiologies. Campylobacter jejuni, a major cause of gastroenteritis worldwide, may also cause myocarditis in rare situations. We present two cases highlighting this rare complication of diarrheal disease caused by Campylobacter jejuni infection and subsequent development of myocarditis. Both patients presented with chest pain and multiple episodes of watery diarrhea, with initial EKGs showing ST segment changes, as well as elevated inflammatory markers and elevated troponins. GI panels for both patients were positive for Campylobacter jejuni. Based on their presentations and investigative findings, they were diagnosed with myocarditis secondary to Campylobacter infection, and their symptoms subsided with appropriate management. It is unclear if the myocardial damage, in this case, is a direct effect of the toxin on cardiac myocytes or secondary to an immunologic phenomenon. Regardless, Campylobacter jejuni-associated myocarditis remains a rare phenomenon and needs to be considered in the differential of patients presenting with concurrent chest pain and diarrheal symptoms.

A Gut-Wrenching Feeling: Overcoming Cognitive Biases in an Atypical Presentation of Chronic Mesenteric Ischemia.

Chronic mesenteric ischemia is a rare but serious condition that can present with a variety of symptoms, including abdominal pain, diarrhea, and weight loss. Our case report presents a 63-year-old male with a past medical history of generalized anxiety disorder, Barrett's esophagus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD) with active smoking who initially presented with severe diffuse abdominal pain, nausea, vomiting, and chronic diarrhea resulting in malnutrition and 40-pound weight loss over a six-month span. The patient underwent extensive diagnostic evaluation and was diagnosed with Yersinia gastroenteritis via gastroenteritis panel (GI Panel), explaining all of the patient's symptoms. The patient underwent treatment for said gastroenteritis but did not experience remission of symptoms, leading to further diagnostic evaluations; a definitive diagnosis was not found, yet the patient's symptoms persisted. The patient then underwent extensive serologic and endoscopic evaluation, after extensive imaging and diagnostic work-up, the patient was finally diagnosed with chronic mesenteric ischemia (CMI) of the superior mesenteric artery (SMA) with severe celiac and inferior mesenteric artery (IMA) stenosis. The patient initially underwent stenting (7 mm by 26 mm Balloon Mounted LifestreamTM Covered Stent; Becton Dickson (BD); Franklin Lakes, NJ, USA), which provided temporary relief to his symptoms, however, the relief did not last long. Upon reimaging, the patient was found to have stenosis of the stent, leading to the eventual placement of a bare-metal stent (ExpressTM LD 7 x 27 mm balloon mounted bare-metal stent; Boston Scientific; Boston, MA, USA) across the celiac artery as well as the placement of an IMA stent (InnovaTM Self-expanding 5 x 20 mm bare-metal stent; Boston Scientific). This eventually resulted in the resolution of the patient's symptoms, eventual weight gain, and improvement in quality of life.

The consequences of sleep deprivation on cognitive performance.

Although not fully understood, sleep is accepted as a vital and organized sequence of events that follows a regular cyclic program each night to ensure the human body can perform at its optimum. A lack of sleep, or sleep deprivation (SD), is a widespread phenomenon that can induce adverse changes in cognitive performance. This review focused on the biological explanation as well as the research investigating the numerous effects that SD can have on cognition. A reduction in sleep does not occur independently of the effects on memory, attention, alertness, judgment, decision-making, and overall cognitive abilities in the brain, resulting in decreased function and impaired cognitive performance.

Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification.

BACKGROUND: Left ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis. OBJECTIVES: In this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations. METHODS: A total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV). RESULTS: Normal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03). CONCLUSIONS: Higher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.

Synchronous Liver Abscess With Cholecystitis: A Rare Case of Initial Presentation of Gallbladder Cancer Posing a Diagnosis Challenge.

Gallbladder carcinoma (GBC) is the most common of all biliary tract cancers. GBC is a multifactorial disease. Gallbladder dysplasia from any gallbladder inflammatory condition is one of the main risk factors for GBC. The late diagnosis of GBC is a major problem in its treatment. It is treated by radical resection and the prognosis is improved by adjuvant chemoradiation. We present a rare case of gall bladder cancer presenting as hepatic abscesses with severe sepsis. An 83-year-old male presented with progressive symptoms of shakiness, general weakness, vomiting, and profuse diarrhea. Lab work revealed deranged liver enzymes. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) abdomen revealed intrahepatic abscesses contiguous with the gallbladder lumen through a gallbladder wall defect and cholecystitis of unknown chronicity. Subsequently, he underwent central hepatectomy and the pathology report of the sample as well as endoscopic retrograde cholangiopancreatography (ERCP) brushings revealed gallbladder adenocarcinoma. The case was complicated by biloma, acute renal failure, and the development of malignant ascites, and the patient died almost four months after the diagnosis of gallbladder cancer.

Evaluating Dental Fear and Anxiety in Pediatric Patients Visiting a Private and a Public Dental Hospital in Lahore, Pakistan.

Background One of the biggest hurdles in treating pediatric patients is managing dental fear and anxiety. Some factors that contribute to an increase in dental anxiety are fear of pain, the presence of unknown individuals, a change in the setting of an environment, and separation from parents. Aim The aim of this study was to evaluate dental fear and anxiety in pediatric patients, between the ages of 6 and 12 years, visiting private and public dental hospitals using the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). Methods A total of 280 children, 140 in a private dental hospital setting and 140 in a public dental hospital setting, were enrolled in this study. The purpose of the study was explained to the accompanying guardian of the patient and written consent was taken. The CFSS-DS was explained verbally in Urdu and the questionnaire was given to guardians alongside the patients which they were asked to fill out following their dental treatment. Result The data obtained from the questionnaires were analyzed using the unpaired t-test. The highest dental fear mean scores and standard deviation in a private dental hospital were for "choking" (3.25 ± 1.21), "the noise of the dentist drilling" (3.24 ± 1.04), and "having somebody put instruments in your mouth" (3.19 ± 1.06), whereas, for a public dental hospital, the highest fear score was recorded in "choking" (3.17 ± 1.69), "injections" (3.07 ± 1.72), and "people in white uniforms" (1.90 ± 1.21). Conclusion The study showed a higher prevalence of dental fear and anxiety in a private dental setting when compared to a public dental setting. Factors responsible for an increase in dental fear need to be assessed for each patient and then treatment given accordingly.

Remdesivir-Associated Acute Liver Failure in a COVID-19 Patient: A Case Report and Literature Review.

There is a broad classification of the causes of acute liver failure (ALF) that include drug-induced liver injury (DILI). In this report, we aim to discuss the association between remdesivir, a novel therapeutic drug for hypoxic coronavirus disease 2019 (COVID-19) pneumonia, and DILI with subsequent ALF in a patient who was recently treated with the drug in question. Remdesivir, which is a direct-acting nucleoside RNA polymerase inhibitor, is one of the only FDA-approved drugs on the market for COVID-19 pneumonia associated with hypoxia. Our case describes a patient with an extensive past medical history who was treated for COVID-19 pneumonia with remdesivir and subsequently developed ALF in the absence of all other possible etiologies. This association has only been highlighted in anecdotal case reports in the past and to a lesser degree in the safety documentation of remdesivir.

Antiandrogen enzalutamide induced genetic, cellular, and hepatic damages: amelioration by triterpene Lupeol.

Androgen deprivation therapy is commonly used for the treatment of prostate cancer. Enzalutamide is a next-generation androgen receptor inhibitor, initially approved to treat castration-resistance prostate cancer. Lupeol, a triterpene present in various fruits, vegetables, has anti-oxidant and anti-proliferative activity. The present study aimed to evaluate the Enzalutamide-induced toxicity and its possible amelioration by Lupeol. We performed multiple in vitro and in vivo experiments to conclude our hypothesis. The results revealed that both Enzalutamide and Lupeol interact with DNA through electrostatic interactions. Enzalutamide (5-20 µM) caused cytotoxicity in both normal (PNT2) and cancer cells (LNCaP and 22Rv1). However, Lupeol (10-50 µM) specifically killed the cancer cells while sparing normal cells. The study further revealed that Lupeol could attenuate Enzalutamide-induced cytotoxicity and genotoxicity (chromosomal aberrations and micronucleus formation) to normal cells and potentially induce cytotoxicity to transformed cells. We further observed that Lupeol (40 mg/kg) mediated attenuation of the Enzalutamide (10 mg/kg) induced oxidative and DNA damages. Our study also revealed that Lupeol reverses the Enzalutamide-induced hepatic and renal damages. In conclusion, our study indicates that Lupeol can be used as an adjuvant for reducing the toxic effects and enhancing the effectiveness of Enzalutamide.

Thrombotic Thrombocytopenic Purpura and Metastatic Malignancy-Like Presentation Secondary to Hypervirulent Strain of Klebsiella pneumoniae: A Case Series.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. The majority of cases are caused by a significant enzyme deficiency in the blood called the von Willebrand factor (VWF) cleaving protease (also called ADAMTS13). TTP is classified as a hematologic emergency because of the high mortality rate. The diagnosis is difficult due to the extensive overlap in the clinical manifestations of TTP and other illnesses. Klebsiella pneumoniae infection can in very rare instances present with TTP and/or a metastatic-like presentation where the patient might have prostate, liver, brain, and lung abscesses mimicking late-stage solid organ malignancy. In this paper, we report a case of TTP secondary to Klebsiella pneumoniae infection in a 38-year-old male patient, who presented with fever, cough, and shortness of breath for five days. On examination, he was vitally unstable, confused, and not oriented, with a Glasgow Coma Scale (GCS) of 9/15. Complete blood count (CBC) showed a high white blood cell (WBC) count, very low platelet count, increased reticulocyte count, and significant elevation of schistocytes on peripheral blood film. Sputum and blood cultures were positive for Klebsiella pneumoniae. Computerized tomography (CT) scan chest showed bilateral lung parenchymal nodules. An abdominal ultrasound (US) scan detected a right hepatic lobe lesion that was both cystic and solid. The patient was initially started on meropenem, vancomycin, and levofloxacin due to shock presentation which was de-escalated to ceftriaxone later. The patient had five therapeutic plasma exchange sessions and was started on methylprednisolone for three days. The patient's situation gradually improved, and he was discharged later on. The second case is a 63-year-old-male patient who presented with fever, dry cough, night sweats, and dysuria for seven days. He was vitally stable, conscious, alert, and oriented. His hemoglobin was 9.6 g/dl. He was scheduled for an urgent colonoscopy to rule out colon cancer along with computed tomography (CT) scan of the chest, abdomen, and pelvis. The CT scan showed complex cystic lesions involving the right hepatic lobe, lungs, adrenal glands, and prostate. The clinical picture was suggestive of hyper-mucoid Klebsiella pneumoniae infection showering to the liver, adrenal glands, and prostate. A drained prostate collection and urine cultures confirmed the diagnosis. The patient was managed with surgical drainage of the collection in addition to ceftriaxone and metronidazole. The patient was discharged in good health on ciprofloxacin with follow-up as an outpatient.

A Rare Initial Presentation of Aortic Intramural Hematoma: A Case Report and Literature Review.

Aortic intramural hematoma (AIH) is a life-threatening emergency that involves aortic wall integrity and is characterized by either a direct rupture of the vasa vasorum or spontaneous bleeding of an arterial plaque located in the tunica media of the aortic wall. A notable difference between AIH and acute aortic dissection is the absence of an intimal flap, a finding discernable on computed tomography angiography (CTA). Follow-up imaging allows for the monitoring of disease progression or early findings of impending complications. While some patients may require surgical intervention, medical management with blood pressure control remains the mainstay in treatment. Our case describes a patient who was found to be in cardiac arrest secondary to ventricular fibrillation and was then found to have presumed Stanford Type A aortic dissection on CTA. After reviewing the scans, the diagnosis was reclassified to AIH due to the absence of an intimal flap, the patient was then managed medically for AIH with antihypertensive medications.

A Rare Case of Pseudomembrane-Associated Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic, life-long inflammatory bowel disease that normally presents with bloody diarrhea, fever, abdominal pain, and leukocytosis. Diagnosis is usually based on clinical presentation, endoscopy with biopsy, and exclusion of alternative diagnoses. In very rare cases, pseudomembranes may be found on colonoscopy in patients with an early UC flare. Historically, the objective finding of pseudomembranes has been exclusively used to diagnose a Clostridioides difficile infection (CDI); however, diagnostic testing must be correctly utilized to confirm whether a CDI is truly the cause of the presence of pseudomembranes, and not an alternative etiology, such as UC. In this case, we discuss a 43-year-old female who presented to the hospital with worsening chronic bloody diarrhea after being seen in the outpatient clinic for a questionable CDI. She underwent endoscopic evaluation revealing pseudomembranous colitis; however, C. difficile testing showed one positive gastrointestinal (GI) pathogen panel and multiple negative antigens and toxin enzyme immunoassays (EIA). With a clinical suspicion of early UC, the patient was treated with mesalamine enemas and improved clinically before discharge. Several months later, she underwent endoscopic evaluation with biopsy, which showed findings consistent with a diagnosis of UC.

DAVS-NET: Dense Aggregation Vessel Segmentation Network for retinal vasculature detection in fundus images.

In this era, deep learning-based medical image analysis has become a reliable source in assisting medical practitioners for various retinal disease diagnosis like hypertension, diabetic retinopathy (DR), arteriosclerosis glaucoma, and macular edema etc. Among these retinal diseases, DR can lead to vision detachment in diabetic patients which cause swelling of these retinal blood vessels or even can create new vessels. This creation or the new vessels and swelling can be analyzed as biomarker for screening and analysis of DR. Deep learning-based semantic segmentation of these vessels can be an effective tool to detect changes in retinal vasculature for diagnostic purposes. This segmentation task becomes challenging because of the low-quality retinal images with different image acquisition conditions, and intensity variations. Existing retinal blood vessels segmentation methods require a large number of trainable parameters for training of their networks. This paper introduces a novel Dense Aggregation Vessel Segmentation Network (DAVS-Net), which can achieve high segmentation performance with only a few trainable parameters. For faster convergence, this network uses an encoder-decoder framework in which edge information is transferred from the first layers of the encoder to the last layer of the decoder. Performance of the proposed network is evaluated on publicly available retinal blood vessels datasets of DRIVE, CHASE_DB1, and STARE. Proposed method achieved state-of-the-art segmentation accuracy using a few number of trainable parameters.

Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells.

We explored whether the anti-prostate cancer (PC) activity of the androgen receptor-axis-targeted agents (ARATs) abiraterone and enzalutamide is enhanced by metformin. Using complementary biological and molecular approaches, we determined the associated underlying mechanisms in pre-clinical androgen-sensitive PC models. ARATs increased androgren receptors (ARs) in LNCaP and AR/ARv7 (AR variant) in VCaP cells, inhibited cell proliferation in both, and induced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and death in VCaP but not LNCaP cells. Metformin decreased AR and ARv7 expression and induced cleaved PARP-1-associated death in both cell lines. Metformin with abiraterone or enzalutamide decreased AR and ARv7 expression showed greater inhibition of cell proliferation and greater induction of cell death than single agent treatments. Combination treatments led to increased cleaved PARP-1 and enhanced PARP-1 activity manifested by increases in poly(ADP-ribose) (PAR) and nuclear accumulation of apoptosis inducing factor (AIF). Enhanced annexin V staining occurred in LNCaP cells only with metformin/ARAT combinations, but no caspase 3 recruitment occurred in either cell line. Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death. In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.

Towards Automated Eye Diagnosis: An Improved Retinal Vessel Segmentation Framework Using Ensemble Block Matching 3D Filter.

Automated detection of vision threatening eye disease based on high resolution retinal fundus images requires accurate segmentation of the blood vessels. In this regard, detection and segmentation of finer vessels, which are obscured by a considerable degree of noise and poor illumination, is particularly challenging. These noises include (systematic) additive noise and multiplicative (speckle) noise, which arise due to various practical limitations of the fundus imaging systems. To address this inherent issue, we present an efficient unsupervised vessel segmentation strategy as a step towards accurate classification of eye diseases from the noisy fundus images. To that end, an ensemble block matching 3D (BM3D) speckle filter is proposed for removal of unwanted noise leading to improved detection. The BM3D-speckle filter, despite its ability to recover finer details (i.e., vessels in fundus images), yields a pattern of checkerboard artifacts in the aftermath of multiplicative (speckle) noise removal. These artifacts are generally ignored in the case of satellite images; however, in the case of fundus images, these artifacts have a degenerating effect on the segmentation or detection of fine vessels. To counter that, an ensemble of BM3D-speckle filter is proposed to suppress these artifacts while further sharpening the recovered vessels. This is subsequently used to devise an improved unsupervised segmentation strategy that can detect fine vessels even in the presence of dominant noise and yields an overall much improved accuracy. Testing was carried out on three publicly available databases namely Structured Analysis of the Retina (STARE), Digital Retinal Images for Vessel Extraction (DRIVE) and CHASE_DB1. We have achieved a sensitivity of 82.88, 81.41 and 82.03 on DRIVE, SATARE, and CHASE_DB1, respectively. The accuracy is also boosted to 95.41, 95.70 and 95.61 on DRIVE, SATARE, and CHASE_DB1, respectively. The performance of the proposed methods on images with pathologies was observed to be more convincing than the performance of similar state-of-the-art methods.

Extracellular Volume in Primary Mitral Regurgitation.

OBJECTIVES: This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology. BACKGROUND: Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited. METHODS: Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained. RESULTS: A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events. CONCLUSIONS: Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

Guidelines and Recommendations for Tonometry Use during the COVID-19 Era.

The novel coronavirus disease COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a substantial change in eye care and clinical practice. There has been conflicting information and weak evidence on the virus's transmission through tears. Yet, virus detection on cornea and conjunctiva surface as a gateway for infection is not well-studied. Moreover, there have been no reported cases of SARS-CoV-2 transmission through tonometry to date. Thus, this uncertainty has urged this review on evidence-based guidelines and recommendations on tonometer use in the COVID-19 era. The aim of this article is to provide ophthalmologists with recommendations for tonometry practice based on current evidence and best practice guidelines.