The uncommon preoperative diagnosis of a De Garengeot hernia and its more novel laparoscopic treatment.

This case report involves an elderly woman who presented with a 3-day history of a tender groin swelling on her right side. Her admission bloods were fairly unremarkable, but a preoperative ultrasound impressively confirmed a femoral hernia containing the appendix (De Garengeot hernia) and she underwent emergency laparoscopic hernioplasty with a prosthetic mesh and appendicectomy. The procedure found an incarcerated hernia with a strangulated tip of the appendix that unexpectedly separated upon gentle manipulation and histopathology revealed appendiceal inflammation. There were no complications with the patient's recovery and she was discharged 2 days after surgery.

Neuroprotective responses of quercetin in regulation of biochemical, structural, and neurobehavioral effects in 28-day oral exposure of iron in rats.

BACKGROUND: Iron is one of the essential metals that functions as a cofactor in various biological cascades in the brain. However, excessive iron accumulation in the brain may lead to neurodegeneration and may show toxic effects. Quercetin, a pigment flavonoid compound, has been proven to be a potent antioxidant and anti-inflammatory that can inhibit lipid peroxidation during metal-induced neurotoxicity. Although iron-induced neuroinflammation and neurodegeneration have been reported in many studies, but the proof for its exact mechanisms needs to be explored. PURPOSE: The key target of the study was to explore the neuroprotective effect of quercetin after oral exposure of iron in rats and explore its underlying molecular mechanisms. RESULTS: The outcomes of the study have shown that oral exposure to ferrous sulfate may modulate behavioral paradigms such as locomotor activity, neuromuscular coordination, and increased anxiety level. The pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), apoptotic protein (caspase 3), beta-amyloid and phosphorylated tau were found to be increased on iron exposure. Also, the expressions of ferritin heavy and light chain, BACE-1 and GFAP expressions were altered. These behavioral, structural, and biochemical alterations in the brain were significantly and dose-dependently reversed by treatment with quercetin. CONCLUSION: The current study provides a fundamental understanding of molecular signaling pathways, and structural proteins implicated in iron-induced neurotoxicity along with the ameliorative effects of quercetin.

Molecular and functional characteristics of receptor-interacting protein kinase 1 (RIPK1) and its therapeutic potential in Alzheimer's disease.

Inflammation and cell death processes positively control the organ homeostasis of an organism. Receptor-interacting protein kinase 1 (RIPK1), a member of the RIPK family, is a crucial regulator of cell death and inflammation, and control homeostasis at the cellular and tissue level. Necroptosis, a programmed form of necrosis-mediated cell death and tumor necrosis factor (TNF)-induced necrotic cell death, is mostly regulated by RIPK1 kinase activity. Thus, RIPK1 has recently emerged as an upstream kinase that controls multiple cellular pathways and participates in regulating inflammation and cell death. All the major cell types in the central nervous system (CNS) have been found to express RIPK1. Selective inhibition of RIPK1 has been shown to prevent neuronal cell death, which could ultimately lead to a significant reduction of neurodegeneration and neuroinflammation. In addition, the kinase structure of RIPK1 is highly conducive to the development of specific pharmacological small-molecule inhibitors. These factors have led to the emergence of RIPK1 as an important therapeutic target for Alzheimer's disease (AD).

Effect of Preoperative Volume Overload on Left Ventricular Function Recovery After Ventricular Septal Defect Repair.

Significant left-to-right shunt across a ventricular septal defect (VSD) may lead to left ventricle (LV) volume overload and dilation. The acute loss of LV preload after repair of VSD may contribute to postoperative LV systolic dysfunction. The primary aim of the study is to assess the effect of presence of preoperative LV dilation on LV systolic function recovery after VSD repair. We evaluated the LV systolic function by measuring LV longitudinal strain and ejection fraction (EF) before surgery (time point 1) and at 5 time points after VSD repair (time point 2: 0 to 2 weeks, time point 3: 2 to 6 weeks, time point 4: 6 weeks to 4 months, time point 5: 4 to 12 months, and time point 6: >12 months). A total of 120 patients were included in the study cohort. A total of 84 patients (70%) had LV dilation (group 1) and 36 patients (30%) had normal LV size on preoperative echocardiogram (group 2). Median age (interquartile range 25% to 75%) at surgery was 5.5 months (4 to 10) and 7 months (5 to 44.5) in groups 1 and 2 respectively (p = 0.03). Mean LV EF and strain were not significantly different among the 2 groups at time point 1. At time point 2, both mean EF and strain were significantly lower in group 1 compared with group 2 (p <0.05). At time point 3, mean EF was not significantly different among the two groups, while mean LV strain was significantly lower in group 1 (p = 0.044). At time points 4, 5 and 6, mean EF and strain were not significantly different between the two groups. In conclusion, presence of preoperative LV dilation is associated with a more pronounced LV systolic dysfunction in the early postoperative period only. The LV systolic function recovers back to the baseline after the first year following the repair. These are very reassuring prognostic findings.

Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies.

INTRODUCTION: Recombinant monoclonal antibodies (mAbs) are highly selective and effective biologicals with proven utility as therapeutics. mAbs have demonstrated substantial promise in the treatment of several central nervous system diseases. AREAS COVERED: Databases including PubMed and Clinicaltrials.gov were used to identify clinical studies of mAbs involving patients with neurological disorders. This manuscript reviews the current status and recent advances in the development and engineering of therapeutic blood-brain barrier (BBB)-crossing mAbs and their potential in treatment of central nervous system diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), brain tumors, and neuromyelitis optica spectrum disorder (NMSOD). In addition, the clinical implications of recently developed monoclonal antibodies are also discussed, along with the strategies to enhance their BBB permeability. The adverse events associated with the administration of monoclonal antibodies are also presented in the manuscript. EXPERT OPINION: There is growing evidence that supports the therapeutic utility of monoclonal antibodies in central nervous system and neurodegenerative diseases. Several studies have offered evidence of clinical efficacy in AD through use of anti-amyloid beta antibodies and anti-tau passive immunotherapy-based strategies. Additionally, ongoing research trials have produced promising findings for the treatment of brain tumors and NMSOD.

Perception of dental students regarding possible career challenges and associated factors towards working in rural areas: A questionnaire based survey.

OBJECTIVE: The shortage of health care professionals in rural areas contributes toward discriminatory health care delivery. The present study was planned with a similar intent and aimed to evaluate the perception of dental students regarding their future in rural areas. MATERIALS AND METHODS: The present study was designed as a cross-sectional study comprising of a 30-item questionnaire survey instrument distributed among a total of 550 dental students while the results obtained were subjected to statistical analysis. Statistical analysis was done using SPSS version 12.0 (SPSS Inc., Chicago, IL, USA). Independent student's t-test and one-way analysis of variance (ANOVA) were used for comparison among the variables while the Chi-square test was used to determine the association between the variables. P < 0.05 was considered statistically significant. RESULTS: No significant difference was observed in the attitude based on gender (P = 0.43), although, a statistically significant difference was observed in the attitude of students based on the year of their education with a positive attitude toward rural dental practice generally noted in the first year Bachelor of Dental Surgery (BDS) students which significantly declined with the increasing level of education (P = 0.01). CONCLUSIONS: Dental students were more influenced by the negative aspects of rural dental practice though they had, in their mind, a positive approach for the same at the beginning of their education, but this significantly declined with the increasing level of their education.

A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome.

Background Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high-output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. Methods and Results We sought to systematically characterize high-output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain-of-function variants in ABCC9, which encodes cardiovascular KATP (ATP-sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed ABCC9 variants (median [interquartile range] age 8 years [3-32 years], body mass index 19.9 [16.5-22.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7-103.0] g/m2 in CS, n=30; 26.6 [24.1-32.8] g/m2 in controls, n=17; P<0.0001) and low blood pressure (systolic 94.5 [90-103] mm Hg in CS, n=17; 109 [98-115] mm Hg in controls, n=17; P=0.0301; diastolic 60 [56-66] mm Hg in CS, n=17; 69 [65-72] mm Hg in control, n=17; P=0.0063). Most (21/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged >40 years on long-term follow-up. Conclusions The data define the natural history of high-output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long-term consequences of high-output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high-output heart failure.

Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Induced Severe Atypical Rash in a Patient of Non-Hodgkin's Lymphoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) infusion has been reported with the development of transient maculopapular rash with spontaneous resolution. A 54-year-old Indian female developed intense erythematous generalised rash involving the face, trunk, extremities, palms and soles following GM-CSF infusion. Focal exudation and purpura were seen. Infusion was stopped and she was managed with a short course of systemic steroids. As yet, the development of such an atypical, severe rash following this cytokine infusion has not been reported in the literature.

Peroxynitrite nitration of Tyr 56 in Hsp90 induces PC12 cell death through P2X7R-dependent PTEN activation.

The diffusion-limited reaction of nitric oxide (NO) and superoxide (O2-) produces peroxynitrite (ONOO-), a biological oxidant that has been implicated in a number of pathological conditions, including neurodegenerative disorders. We previously reported that incubation of PC12 cells with peroxynitrite triggers apoptosis by simultaneously inhibiting the PI3K/Akt survival pathway, and activating the p38 and JNK MAP kinase pathways. We also reported that peroxynitrite-treated Heat Shock Protein 90 (Hsp90) stimulates PC12 cell death. Here, we show that nitrated Hsp90 mediates peroxynitrite-induced apoptosis by regulating specific signaling pathways triggered by activation of the purine receptor P2X7 (P2X7R) and downstream activation of PTEN. Intracellular delivery of peroxynitrite-treated Hsp90 was sufficient to stimulate PC12 cell death. In contrast, intracellular delivery of peroxynitrite-treated Hsp90 in which the five tyrosine (Tyr) residues susceptible to nitration were replaced by nitration-resistant phenylalanine had no effect on PC12 cell survival. Further, only nitration of Hsp90 at Tyr 56 was necessary and sufficient to stimulate PC12 cell apoptosis, and incubation of PC12 cells with peroxynitrite resulted in Hsp90 nitration at Tyr 56. Inhibition of P2X7R or downstream inhibition of PTEN prevented PC12 cell death stimulated by both incubation with peroxynitrite and nitrated Hsp90 (Hsp90NY). Peroxynitrite, Hsp90NY, and P2X7R activation all increased p38 and JNK MAP kinases activity, while inhibiting the Akt survival pathway. These results suggest that, in undifferentiated PC12 cells, peroxynitrite triggers apoptosis via nitration of Hsp90 at Tyr 56, which in turn activates P2X7R and PTEN. These results contrast with observations in motor neurons where the nitration of either Tyr 33 or Tyr 56 in Hsp90 stimulates apoptosis, suggesting that the targets of peroxynitrite may be different in different cell types. However, uncovering the pathways through which peroxynitrite triggers cell death in neurodegenerative conditions will provide new potential targets for therapeutic treatment.

Use of 27-gauge Tuberculin Syringe for Trichloroacetic Acid Chemical Reconstruction of Skin Scars (TCA-CROSS).

Chemical Reconstruction of Skin Scars (CROSS) is a minimally invasive, safe, and cost effective technique for the management of ice pick acne scars that are otherwise generally resistant to treatment. 100% trichloro acetic acid (TCA) is usually applied using toothpicks and the end point is white discoloration of skin. The concentrated caustic agent quite often spills onto surrounding normal skin leading to superficial burns and post-inflammatory pigmentation. Use of 27-gauge tuberculin syringe gives a much more controlled access to apply TCA leading to better cosmetic outcome and fewer adverse effects.

A case of primary and secondary syphilis presenting together as immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) is a condition during the clinical course of HIV infection in which there is paradoxical worsening and/or new onset of opportunistic infections in a HIV-positive patient who has recently been started on anti-retroviral therapy (ART). We present a case of AIDS with CD4 count of 20 cells/µl who presented within 6 weeks of starting ART with a CD4 count of 160 cells/µl and a painless solitary genital ulcer along with annular dark-colored plaques over soles. His screening test for syphilis was negative both during baseline evaluation, prior to initiation of ART, and during his clinical presentation. His disease was confirmed based on a positive treponema pallidum hemagglutination test report and a suggestive skin biopsy. He responded well to three doses of Benzathine Penicillin and continuation of ART. There are very few case reports of syphilis presenting as IRIS and this case is all the more unique as he had features of both primary and secondary syphilis occurring together within 6 weeks of starting ART. This report would reiterate the fact that syphilis and HIV co-infection can alter the natural course of both the diseases and a high index of suspicion is required for treating them.

Unusual Spurts of Rosacea Like Dermatoses, Posing a Diagnostic Dilemma During Covid-19 Pandemic: A Cross-Sectional, Observational Study From a Tertiary Care Centre.

BACKGROUND: The gradual opening of healthcare system since second week of May 2020 following lockdown imposed due to corona virus pandemic saw spurts of cases of unexplained central facial dermatoses in subset of previously healthy people. The aim of the study was to find out the cause and establish the definitive diagnosis of unusual occurrence of facial dermatoses on previously healthy people so that an appropriate management can be offered to the patients. MATERIALS AND METHODS: It was a cross-sectional, observational study carried during May 15 to July 15, 2020 at a tertiary dermatology center. All cases presented with erythema on face and papular or pustular lesions on central facial area of not more than 2 months of duration were included in the study. RESULTS: Total 81 patients visited skin OPD with facial dermatoses of various types during this period, out of which 21 patients fulfilled the inclusion criteria. This was 0.72% (21/2900) of total skin OPD of the 2 months. All the patients had been using face masks during this period of symptoms due to the ongoing coronavirus situation. Dermatological examination revealed only erythema on the central area of face (n = 10), erythema and few papules (n = 3), erythmatous papules and pustules (n = 5), and erythematous papules, pustules, and telengiectasia (n = 3). All the skin biopsies showed predominantly epithelioid cells, noncaseating granuloma with a variable degree of infiltrate. CONCLUSION: There has been a definite change in the lifestyle due to the current Covid-19 pandemic. People are compulsorily using face masks to avoid the spread of Covid-19 infection. This change in behavior has brought out a surge of rosacea like lesions on the covered area of face. Partly, it can be explained by change in innate immunity due to excessive sweating and change in microenvironment of skin.

The Role of Biofilms in Chronic Otitis Media-Active Squamosal Disease: An Evaluative Study.

OBJECTIVES: To study the presence of biofilms in patients of chronic otitis media (COM)-active squamosal disease and to evaluate the microflora and clinical impact of biofilms. METHODS: A total of 35 patients suffering from COM - active squamosal disease was studied. Cholesteatoma sample was collected at the time of mastoid surgery and the same was used to image for biofilms by scanning electron microscope. The said sample was also analyzed microbiologically. RESULTS: Biofilms were present in 25 (72%) patients including 6 cases of fungal biofilms (24%). Biofilms were detected irrespective of the micro-organism growth. No statistically significant relationship was observed between biofilms and discharging ear and complications of COM. Though univariate analysis of our data found some correlation between duration of disease, the extent of cholesteatoma and ossicular necrosis but multivariate analysis revealed no such associations, thereby implying a doubtful association between these factors and biofilm. CONCLUSIONS: Biofilms are an integral part of cholesteatoma ear disease and sometimes harbors fungal isolates.