Evaluation of Epididymo-Orchtis-A Study of 100 Cases

Background: Acute epididymo-orchitis is a common clinical problem in urological practice. It is not an uncommon disease in our country to cause work loss particularly in active group of people. Aim of the study: The aim of this study was to see the predisposing factors involved, aetiopathology and progression of disease process.Methods:This prospective study was conducted in department of surgery, Kumudini Women’s Medical College Hospital, Tangail from April 2008 to March 2009. Hundred patients of inflammation of epididymis and testis were included in this study.Results:Out of 100 patients, majority (48%) were in monogamous relationship. All patients (100%) had scrotal pain, 22% had scrotal swelling, 59% had fever, 32% had dysuria and 11% had urethral discharge. All patients presented with tenderness of the testis and epididymis and 82% cases had both epididymal and testicular swelling. Thirty two percent cases had urinary tract infection, trauma and promiscuous sexual contact were associated with the disease in 2% and 18% cases, respectively. History of masturbation was noted in 18% cases. By urine routine microscopy 28% had pus cell and 03% had RBC in urine, 16 cases were positive in urine culture, among 15% were E.coll and 01% were found Klebsiela. Forty patients were tested Chlamydial CFT and 16(40%) were found positive, out of 12 Filarial CFT tested 01(8.33 %) was found positive, Gram staining of urethral discharge revealed Neisseria gonorhhoae in 02(18.18%) cases. In maximum cases no actiological factor was found. Majority cases under 35 years were infected with Chlamydia and patients older than 35 years were mostly infected with E.coli.Conclusion:This study reflects that maximum of our study patients report to hospital nearly at right time with relatively better health status and outcome of available treatment facilities are satisfactory.

Clinical profiles of patients with optic neuritis and papillitis: A prospective study

To analyse the demographics and presenting features of patients presenting with optic neuritis and papillitis. Clinical profiles of 40 patients presenting with optic neuritis and papillitis at a tertiary care center were collected retrospectively and prospectively. Detailed medical and ophthalmic history was taken especially about mode, duration and course of the disease, drug intake, alcoholism, smoking, pregnancy, lactation, convulsions, pyrexia, history suggestive of TB, syphilis, neurological deficit. A comprehensive ophthalmological and neurological evaluation was done for each patient along with radiological work up. Patients were prospectively followed up for an average of three months. Females in the reproductive age group constituted largest number of the patients (61.8%) in the present series. Maximum patients (70%) were between 20-50 years of age. Vision was found to be affected in all the patients at presentation and most of them presented with vision CF or HM (35.4% and 29.25% respectively) while 4 patients had complete loss of vision. Two third (66.7%) of patients reported eye pain at presentation. Abnormal pupillary reaction was found in most patients with the most common being RAPD on swinging flash light which was seen in 85.4%. Equal percentage (39.5%) of patients presented with Blurred Hyperemic (BH) disc and ophthalmoscopically normal appearing disc. Onset and progression of disease was found to be rapid in most cases ranging from few hours to days. Visual recovery post treatment was found to be good with most eyes achieving vision 6/24 or better. Optic neuritis has varied clinical presentations. Most of our patients were young to middle aged females. The most common presenting features were decrease in vision ranging from slight to profound, eye pain and abnormal pupillary reaction. Morphological abnormalities in appearance of optic disc were also found in two third of cases.Rapid progression was noted in almost all cases. Most of the cases achieved a good outcome at the end of follow up period.

Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant

Microbes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation explain the frequent presence of lasR loss-of-function mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR– derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR– lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR– lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR– cells in a CbrB-controlled manner. We propose that in vivo metabolomes are a major driver of pathogen evolution, which may influence the progression of disease and its treatment.

Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study

Cortisol exerts a broad anti-inflammatory effect on the immune system. Inflammatory cytokines contribute to the molecular signalling pathways implicated in various autoimmune and inflammatory conditions. However, the mechanisms by which cortisol modulates such signalling pathways remain uncertain. Leveraging summary-level data from the CORtisol NETwork (CORNET, n = 25,314) and FINRISK (n = 8293) genome-wide association studies, we used two-sample Mendelian randomisation to investigate the causal effect of genetically proxied increased morning cortisol levels on 42 circulating cytokines. We found that increased genetically proxied morning cortisol levels were associated with reduced levels of IL-8 and increased levels of MIF. These results provide mechanistic insight into the immunomodulatory effects of endogenous cortisol and the therapeutic effects of exogenous corticosteroids. Clinically, our findings underline the therapeutic importance of steroids in inflammatory conditions where IL-8 and MIF play a central pathophysiological role in the onset and progression of disease.

Delta-Radiomics Predicts Response to First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients with Liver Metastases

The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R−) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R− lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies.

What Should the Earliest Age be for Clinical Trials of Corneal Crosslinking for Keratoconus?

Keratoconus is often diagnosed in the second or third decade of life, with a younger mean age at diagnosis more likely among those of Middle Eastern and Asian descent (1). Studies have shown that patients with severe forms of keratoconus present at a younger age (usually in the second decade of life), and these patients have more rapid progression of disease (2-6). Pediatric keratoconus is generally attributed to disease manifesting in those less than 18 years of age, however studies that looked at progression in different age groups used varying age criteria. Léoni-Mesplié et al. found that at diagnosis, keratoconus is often more advanced in children (defined as ?15 years) than in adults (?27 years), while Tuft et al. found that patients ?18 years at time of diagnosis progressed to transplantation faster than patients >18 years of age (5-6). McMahon et al. found that the rate of change in corneal curvature was substantially greater in patients <20 years old and slowed down dramatically in those ?20 years old (7). Until the late 1990s when corneal crosslinking (CXL) was initially developed (8) there were no effective means to halt or slow progression, and keratoplasty was the definitive treatment. There was some assertion in the literature that certain contact lenses and intracorneal rings may help slow progression, but no definitive evidence was ever presented (9-11). Ring segments have been shown to improve best corrected visual acuity as well as contact lens tolerance, but do not alter progression of disease (9, 11).

The Interaction among Microbiota, Epigenetic Regulation, and Air Pollutants in Disease Prevention

Environmental pollutants can influence microbiota variety, with important implications for the general wellbeing of organisms. In subjects at high-risk of cancer, gut, and lung microbiota are distinct from those of low-risk subjects, and disease progression is associated with microbiota alterations. As with many inflammatory diseases, it is the combination of specific host and environmental factors in certain individuals that provokes disease outcomes. The microbiota metabolites influence activity of epigenetic enzymes. The knowledge of the mechanisms of action of environmental pollution now includes not only the alteration of the gut microbiota but also the interaction between different human microbiota niches such as the lung–gut axis. The epigenetic regulations can reprogram differentiated cells in response to environmental changes. The microbiota can play a major role in the progression and suppression of several epigenetic diseases. Accordingly, the maintenance of a balanced microbiota by monitoring the environmental stimuli provides a novel preventive approach for disease prevention. Metagenomics technologies can be utilized to establish new mitigation approaches for diseases induced by polluted environments. The purpose of this review is to examine the effects of particulate matter exposure on the progression of disease outcomes as related to the alterations of gut and lung microbial communities and consequent epigenetic modifications.

Evaluation of Virtual Screening Strategies for the Identification of γ-Secretase Inhibitors and Modulators

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized by γ-secretase, providing a platform for rational drug design targeting this protease. In this study, docking- and pharmacophore-based screening approaches were evaluated for their ability to identify, from libraries of known inhibitors and modulators with decoys with similar physicochemical properties, γ-secretase inhibitors and modulators. Using these libraries, we defined strategies for identifying both γ-secretase inhibitors and modulators incorporating an initial pharmacophore-based screen followed by a docking-based screen, with each strategy employing distinct γ-secretase structures. Furthermore, known γ-secretase inhibitors and modulators were able to be identified from an external set of bioactive molecules following application of the derived screening strategies. The approaches described herein will inform the discovery of novel small molecules targeting γ-secretase.

Association of Underlying Comorbidities and progression of COVID-19 Infection Among 2586 Patients Hospitalized in the National Capital Region of India: A Retrospective Cohort Study

Objectives This study is conducted to observe the association of diabetes (DM), hypertension (HTN), and chronic kidney disease on the prognosis and mortality of COVID-19 infection in hospital admitted patients.Methods This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. the burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis.Results A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in comorbidity, the risk of ICU admission and mortality increases.Conclusion Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher’s exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.