Patient’s adherence to antihypertensive drugs in a tertiary care hospital: A cross-sectional study

Background: Hypertension (HTN) is a serious public health problem. Good control of the disease has always been considered to be essential for reducing its morbidity and mortality. Poor adherence to treatment is the single most important reason for uncontrolled blood pressure, serious complications, and wastage of health-care resources. Aims and Objectives: This study aims to assess the antihypertensive medication adherence level among hypertensive study participants, and identify and evaluate the barriers to antihypertensive medication adherence. Materials and Methods: A hospital-based descriptive cross-sectional study was conducted in tertiary care medical college hospital in Madurai, Tamil Nadu, involving 332 patients and the collected data were presented as means (standard deviations) and percentages. Comparison of data was performed using Pearson’s Chi-square test. For all statistical analyses, commercially available computer program was used. Results: Among 332 study participants having age range of 31–78 years with a mean age of 57.49 ± 9.20 years, female (approx. 60%) were more than male (40%) participants. About 96.7% of respondents were aware that HTN could cause severe consequences with regard to their health and daily activity but more than half were taking medium salt (56.0%) and more than one-third (32.8%) were taking fatty rich diet. Only one-fourth (25.6%) had good medication adherence. Male participants (34.8%) were more adherent to medication than female (20.2%) and this was statistically significant with P = 0.003. Conclusion: Around 3/4th of study participants (72.9%) were poorly adherent to antihypertensive medication. Hence, there should be improvement in awareness for both the patients and the care providers.

Role of visual evoked potential as a window to detect functional changes that occur without signs of diabetic retinopathy in fundoscopy: Case series involving symptomatic overt diabetic pregnant women

Diabetic retinopathy (DR) is a microvascular complication associated with diabetes mellitus. Pregnancy is a major risk factor for DR in diabetic women. Recent evidenced suggests that in course of DR functional changes including damage of pre-ganglionic and ganglionic cells in retina precede structural microvascular changes. A number of studies in the past have highlighted the role of pattern visual evoked potential (VEP) in detecting such functional changes. However, the study of VEP changes in diabetic pregnancies remains unexplored. This case series has the objective of exploring VEP changes in symptomatic OVD cases, who had no signs of DR on fundoscopy. We present two cases of overt diabetic women who complaint of straining of eyes, headache, and difficulty in reading during pregnancy. Complete ophthalmic examination was done in both the cases followed by a VEP test. VEP test was done as a part of a research project. The ethical clearance for the project was obtained from the Institute’s Ethics Committee before the commencement of the study. Fundoscopic examination in both cases revealed that the retina was within normal limits with no signs of retinopathy. In Case 1, P100 latency was increased for the left eye and was normal for the right eye during the first visit. While P100 latency was increased for both left and right eye during the second visit. There was a substantial increase in P100 latency for both eyes in second visit as compared to first visit. In Case 2, P100 latency was increased for both left and right eye and amplitude decreased for the left eye. This is a case series consisting of symptomatic overt diabetic pregnant women who had increased P100 latency despite no signs of retinopathy in fundoscopy. The previous studies have reported that multiple follow-ups with ophthalmoscopy may not be cost-effective in diabetic pregnant women. VEP provides a window for detection of early functional changes that may help identify at risk patients for follow-up and early intervention.

M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study

The Dengue virus M protein is a 75 amino acid polypeptide with two helical transmembranes (TM). The TM domain oligomerizes to form an ion channel, facilitating viral release from the host cells. The M protein has a critical role in the virus entry and life cycle, making it a potent drug target. The oligomerization of the monomeric protein was studied using ab initio modeling and molecular dynamics (MD) simulation in an implicit membrane environment. The representative structures obtained showed pentamer as the most stable oligomeric state, resembling an ion channel. Glutamic acid, threonine, serine, tryptophan, alanine, isoleucine form the pore-lining residues of the pentameric channel, conferring an overall negative charge to the channel with approximate length of 51.9 Å. Residue interaction analysis (RIN) for M protein shows that Ala94, Leu95, Ser112, Glu124, and Phe155 are the central hub residues representing the physicochemical interactions between domains. The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.

Myocardial infarction due to septic thromboembolism in chronic rheumatic heart disease

ABSTRACT Chronic rheumatic heart disease (RHD) is the most troublesome complication of rheumatic fever. Extensive valvular scarring and ventricular remodeling due to pressure and volume overload occur in chronic RHD. Deformed valves are at potential risk for developing infective endocarditis (IE) with further systemic embolism. We hereby describe a case of a patient diagnosed with chronic rheumatic heart disease and severe ventricular dysfunction, planned for aortic valve replacement. The patient developed septic shock during a hospital stay. The autopsy revealed infective endocarditis in the aortic valve with septic thromboembolism in the peripheral branches of the coronary artery and early multifocal myocardial infarction changes.

Disseminated Nasal subtype Extranodal NK/T-cell lymphoma and its diagnostic difficulties in antemortem biopsies

ABSTRACT Extranodal NK/T- cell lymphoma (ENKTCL) is an aggressive lymphoma driven by Epstein-Barr virus (EBV) infection in genetically susceptible individuals. It was historically called a lethal midline granuloma. Due to the angio-destructive nature of ENKTCL, lymphoma cells are often accompanied and masked by necrosis and dense inflammation in the biopsy. Further, the biopsy may show vasculitis, which can mimic granulomatosis with polyangiitis. Due to these masquerades, ENKTCL is often misdiagnosed in the biopsy. Several biopsies may be required to establish the diagnosis. We describe the clinical course and autopsy findings of a young female who presented with a hard-palate ulcer. Antemortem biopsies failed to establish the diagnosis. The autopsy revealed an advanced nasal subtype of Extranodal NK/T-cell lymphoma with dissemination to the kidneys, adrenals, liver, spleen, and small intestine.

Cardiovascular Disease Risk Profile and Risk Prediction Among Unskilled Workers of a Tertiary Care Teaching Hospital

Background: The prevalence of CVD risk factors in India is steadily increasing moreover CVD in Indians has been shown to occur prematurely. The study was designed to estimate the 10-year cardiovascular risk using region specific WHO/ISH risk prediction chart among unskilled workers of a tertiary care teaching hospital and to determine factors associated with risk. Material and methods: This was a hospital based cross sectional study conducted among 250 workers selected by simple random sampling. Using structured questionnaire, life style related risk factors name-ly, average daily consumption of fruits and vegetables, physical activity, perceived stress, tobacco and al-cohol use was collected. BMI and BP were measured using standard protocol and classified following standard guidelines. Bio-chemical parameters were also measured. Results: Among 250 workers, 37.2% and 10% consumed daily minimal recommended level of vegeta-bles and fruits respectively, 21.1% was current tobacco user, 17.2% was alcohol drinkers, 50.4% were obese, 18.8% had high blood pressure and 6% had elevated cholesterol. Among the workers 46.7 % had <10% risk, 5.3% had 10% to <20% risk and, 3.3% had 20% to <30% risk to develop CVD within future 10 years of lifetime. Drivers and current alcoholics were associated with being in the high-risk group. Conclusion: Employer initiated regular work place health screening and services need to be aimed at the unskilled workers, especially for CVD targeting drivers and alcoholics.

Clinical and pathological profile of gastric neuroendocrine tumors

Background: Gastric neuroendocrine tumors (G-NETs) are classified into well-differentiated NETs with three grades and poorly differentiated neuroendocrine carcinomas based on morphology and the Ki-67 index. Besides, G-NETs are broadly classified into four types based on clinical and pathophysiological features. Aim: To study clinical and pathological features of different types and grades of G-NET. Materials and Method: All G-NETs, diagnosed from January 2011 to December 2020, were included. Clinical presentation, peritumoral findings, lymph node status, and liver involvement were obtained and correlated with different grades and types of G-NETs. Results: NET was diagnosed in 88 cases. Tumors were graded as I, II, III, and carcinoma in 58, 14, 12, and 4 cases, respectively. Type I NET (49.2%) in the background of chronic atrophic gastritis was the most common type followed by type III (33.3%). Type I tumors were predominantly graded I (91.1%) and limited to the mucosa and submucosa. MEN-1-associated G-NET (type II) was seen in eight cases. All except one type II tumor was associated with ZES syndrome. Remarkably, peritumoral mucosa showed atrophy and intestinal metaplasia in 52.1% and 24.6% cases, respectively. Two cases were associated with adenocarcinoma. Lymph node metastasis was seen in all carcinoma and grade III cases. All carcinoma cases and 58.3% of grade III tumors showed liver metastasis. Conclusion: Biological behavior of G-NET varies with different types and grades of tumor. Typing and grading of G-NET should be done whenever possible to predict the aggressiveness of the tumor.

A novel approach for drug discovery-drug repurposing

Drug repurposing refers to finding a new indication for a pre-existing drug. It is a novel way of drug discovery that greatly reduces the time and money spent in the drug discovery process. This approach is associated with a better chance of successful drug approval. Both previously approved drugs as well as drugs that have failed in the trials conducted for their original indication can be repurposed. Even drugs withdrawn from market for their original indication can be repurposed for a new indication. Starting with Sildenafil which is the oldest example of repurposed drug to the recently repurposed drug tocilizumab for COVID-19, the list of repurposed drugs is a big one. The regulatory pathway to be followed for a repurposed drug is different from that for a new chemical entity. Furthermore, the period of marketing exclusivity for repurposed drug is only 3 years as against the 20 years of patent protection period for new drug. The strategy for drug repurposing may be a serendipitous one or hypothesis driven one. The hypothesis driven strategy includes the experimental and computational approaches. Computational approaches for drug discovery, especially the Connectivity map approach, offer a lot of scope to understand the drug-disease-gene link, thereby acting as a kick-starter for drug repurposing. Drug repurposing has real potential to offer a cure for rare genetic conditions and cancers. This review covers the various drug repurposing approaches in detail, the regulatory pathway for repurposed drugs, salient examples of repurposed drugs and also the challenges associated with drug repurposing.

Rickettsia conorii infection with fatal complication

ABSTRACT Rickettsial diseases (RD) are a group of endotheliotropic infectious diseases caused by different species of genera Rickettsia. RD are not an uncommon disease and may be misdiagnosed during the evaluation of acute febrile illness due to a lack of reliable serological marker and diagnostic culture methods. Clinical manifestation of RD varies from febrile illness with rashes and myalgia to fatal complications such as shock and respiratory failure. We describe a case of a young male who presented initially with acute febrile illness, followed by shock and respiratory failure, and unfortunately succumbed to death. A post-mortem examination showed histological features of endotheliotropic infection, such as interstitial / perivascular edema in various organs and noncardiogenic pulmonary edema (suggesting increased vascular permeability) and evidence of vasculitis in the lung, liver, and intestines. Molecular studies performed from lung, liver, and kidney tissue confirm the diagnosis of spotted fever group rickettsial disease due to Rickettsia conorii.

COVID-19-associated mucormycosis and treatments

In the current pandemic, COVID-19 patients with predisposing factors are at an increased risk of mucormycosis, an uncommon angioinvasive infection that is caused by fungi with Mucor genus which is mainly found in plants and soil. Mucormycosis development in COVID-19 patient is related to various factors, such as diabetes, immunocompromise and neutropenia. Excessive use of glucocorticoids for the treatment of critically ill COVID-19 patients also leads to opportunistic infections, such as pulmonary aspergillosis. COVID-19 patients with mucormycosis have a very high mortality rate. This review describes the pathogenesis and various treatment approaches for mucormycosis in COVID-19 patients, including medicinal plants, conventional therapies, adjunct and combination therapies.

Correlation of NUF2 Overexpression with Poorer Patient Survival in Multiple Cancers / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). @*Materials and Methods@#RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2’s role in HCC in vitro and in vivo. @*Results@#NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. @*Conclusion@#NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

Non-infectious thrombotic endocarditis associated with chronic rheumatic heart disease and disseminated tuberculosis

Rheumatic heart disease is still common in developing countries and requires prompt intervention to prevent chronic complications. Vegetations in rheumatic heart disease might be due to acute episodes of rheumatic fever itself or due to either infective endocarditis (IE) or Non-infectious thrombotic endocarditis (NITE). Each form of vegetations has specific pathological characteristics on gross and microscopic examination. However, clinically IE and NITE may have overlapping signs and symptoms. A chance of misdiagnosis of NITE as culture-negative infective endocarditis is higher if the former present with infective symptoms like fever. NITE of valves can be due to underlying associated malignant neoplasm, particularly mucinous adenocarcinoma, pneumonia, cirrhosis, autoimmune disorders, and hypercoagulable state. The coexistence of tuberculosis, non-infectious thrombotic endocarditis and rheumatic valvular heart disease was rarely documented in medical literature. We describe a case of chronic rheumatic heart disease with vegetations in the posterior mitral valve leaflet, treated as culture-negative infective endocarditis, which, at autopsy, reveals the presence of Nonbacterial thrombotic endocarditis vegetation over calcified, fibrosed mitral valve leaflets and associated disseminated tuberculosis along with classic pathological sequela findings of chronic rheumatic mitral valvular heart disease in lungs and liver.

SMILE-like lesion in the anal canal

Stratified mucin-producing intraepithelial lesion (SMILE) is an intraepithelial lesion with overlapping features of the high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Currently, it is well described in the cervix. We present a case showing similar SMILE-like lesions in the polypectomy specimen from the anal canal along with invasive adenocarcinoma components. This lesion showed an immuno-profile characteristic of a SMILE lesion described in the cervix, such as p63 negativity, high ki67 index, and nuclear positivity for p16. It might be arising from the Human papillomavirus prone transitional region of the anal canal as described in the cervix. However, we could not assure this association and etiological link due to insufficient material in the formalin-fixed paraffin-embedded block. Notwithstanding, we strongly suggest that the HPV is the main driver for this SMILE-like lesion similar to what is described in the cervix. To our knowledge, this is the first case report of a SMILE lesion in the anal canal. Further studies will be required to elucidate the underlying pathogenetic mechanism of SMILE-like lesions described in the anal canal.

Phytochemical Profiling, Free-Radical Scavenging And Anti-Inflammatory Activities Of Meliosma Simplicifolia (L.)

Objective: In the current research, to determine the stem extract of Meliosma simplicifolia (L.) for total phenol, tannin, total flavonoid, antioxidant activity, anti-inflammatory and identify the phytoconstituents utilizing GC-MS and FT-IR. Methods: The ability of the plant extract to act as hydrogen/electrons donor or scavenger of radicals was determined by in vitro antioxidant assays using 2,2-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, reducing power assay, superoxide radical (O2•) scavenging activity. The anti-inflammatory activity was evaluated using carrageenan and formalin-induced paw edema models using Wistar albino rats. The GC-MS and FT-IR analysis of the methanolic stem extract of M. simplicifolia was revealed the presence of phytochemicals. Results: Quantitative studies of estimated phenol, flavonoid and tannin, as for the methanol extract of stem showed the highest content of phenolic compounds (39.83±3.62GAE mg/100). Antioxidant activities were concluded the estimation M. simplicifolia stem for as followed the studies. In stem the methanol extract showed the highest DPPH scavenging activity (124.3µg/ml). The anti-inflammatory activity has shown in high doses of methanolic extract 250 mg/kg of significant value (p<0.05) inhibition of paw edema, on 6th hour, respectively. The FT-IR analysis has confirmed their characteristic peak values and functional groups. Conclusion: M. simplicifolia has an effective of anti-inflammatory activity and constitutes a potential source for the development of new treatments.

Current Status of Nanoparticles Loaded Medication in the Management of Diabetic Retinopathy.

Diabetes Mellitus (DM) is a chronic metabolic disorder affecting a vast majority of the human population causing marked morbidity and mortality. Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in people. In this review, various nano-delivery systems to effectively deliver antidiabetic compounds in treating angiopathy and retinopathy in diabetes mellitus are discussed. This has been used to overcome many complications in traditional treatment of bioactive compounds with a lower potential antidiabetic effect due to the lower stability of those compounds in gastrointestinal systems and during absorption. Several bioactive compounds loaded into nanodelivery systems are currently in clinical trials, and once these compounds are commercially marketed, nano bioactive compounds will be available as novel medicines to treat many chronic diseases, including diabetes mellitus. DR is driven by prolonged hyperglycaemic episodes arising from suboptimal glycaemic control in patients with either Type I or II diabetes mellitus. Elevated blood glucose levels alter the regulation of a number of biochemical pathways leading to superoxide production and oxidative stress in retina. Mitochondrial dysfunction, inflammation, and hypoxia-driven Vascular Endothelial Growth Factor (VEGF) secretion giving rise to vascular and neuronal apoptosis, neovascularization and elevated vasopermeability, respectively. Several medicines loaded with nanoparticles have been developed to enhance the target effectiveness and bioavailability of medicinal compounds with antidiabetic effects in various animal and human models. Bioactive compounds have been loaded into nanoparticles for oral delivery in various antidiabetic animal models, and the results have shown improved stability, bioavailability, and sustained antidiabetic effects. Nanocarriers used in the delivery of drugs are very precise and ensure targeted drug delivery at the disease site. The antidiabetic activity of triamcinolone acetonide-loaded lipid nanocapsules, humanin peptide with elastin like polypeptide nanoassembly, loaded poly lactic-co-glycolic acid nanoparticles, anti-VEGF-aptamer modified C-Dots as hybrid nano-composite, axitinib, apatinib loaded poly lactic-co-glycolic acid nanoparticles, mulberry leaf extract mediated silver nanoparticles, resveratrol coated gold nanoparticles, fenofibrate-loaded biodegradable nanoparticles, nano-delivery of doxorubicin, insulin-loaded chitosan nanoparticles, silk fibroin nanoparticles, fluorescent silicon nanoparticles-based theranostic probes, topical curcumin nanocarriers, nanoparticles loaded-palmitoyl ethanolamide, hyaluronic acid coated albumin nanoparticles, nilvadipine loaded nanoparticles, cilostazol ophthalmic nanodispersions, naringenin-loaded sulphobutylether-β-cyclodextrin/chitosan nanoparticles, emodin-loaded magnesium silicate hollow nanocarriers, yttrium oxide nanoparticles are discussed in this review.

Comparative Study of Conventional Ziehl Neelsen and Modified Bleach Method of Ziehl Neelsen with CBNAAT in the Diagnosis of Tuberculous Lymphadenitis

Tuberculosis is one of the major health problems in developing countries like India. Even though lungs are the commonly involved organs in Tuberculosis, extrapulmonary presentations are on the rise nowadays. Among the various types of presentations of extrapulmonary tuberculosis, lymphadenitis is the most common presentation. A spectrum of investigations is available for diagnosis, and molecular methods like CBNAAT and PCR analysis are highly reliable. But their disadvantage is their cost and requirement of trained personnel. FNA is the first line of investigation but is lacking in sensitivity and culture method is time consuming. So, Modified Ziehl Neelsen method with low cost and less time may be considered as an alternative. We wanted to evaluate the sensitivity of the Modified Bleach Ziehl Neelsen method and compare the Modified and Conventional Ziehl Neelsen Method in association with the CBNAAT in the diagnosis of TB lymphadenitis.METHODSDiagnostic validation study was conducted with 30 clinically suspected cases of tuberculosis. FNA was done and aspirated material was spread on 2 slides. Slides were stained with H & E stain and convention Ziehl Neelsen stain. Part of the aspirate material was centrifuged with 5 % sodium hypochlorite. Sediment was smeared on a slide and stained with Ziehl Neelsen stain. Remaining material was subjected to CBNAAT assay.RESULTSCorrelation shows that 9, 6, and 11 out of 30 cases were positive for tuberculosis in Conventional, Modified and CBNAAT methods respectively. Sensitivity was 81.81 %; specificity was 94.74%, positive predictive value was 90% and negative predictive value was 90% for Conventional Ziehl Neelsen Method and 54.55%, 94.73%, 85.71% and 78.26%, respectively for modified bleach method.CONCLUSIONSConventional method is found to be more sensitive than modified method. CBNAAT negative results do not rule out TB. So, they should be correlated with cytology and microbiological studies.