Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Posterior Leaflet of Mitral Valve-Is it Really Tri-scalloped? -A Morphological and Morphometric Study in North Indian Cadaveric Hearts.

Background: Maintaining normal left ventricular geometry and function depends on the mitral valve's normal integrity. Irreparable damage to the mitral valve calls for its replacement using either a valve made up of biological tissue or metal, pyrolytic carbon, and similar materials. Materials and Methods: The material consists of 50 formalin-fixed adults, seemingly normal cadaveric hearts of either sex which were received from the Department of Anatomy of various institutes in the north region. These hearts were cut open to access the mitral valve in the left ventricle. Results: In this study, the posterior leaflet was semi-oval in shape being 3.72 cm wide at the base. Usually said to be tri-scalloped, interestingly, it was found so only in 56% of the hearts; being bi-scalloped in 20% and single-cusped in 16% of the hearts. Even four scallops and six scallops were observed in three (6%) and one (2%) hearts, respectively. Conclusions: To conclude, notable variation has been seen in the scallops of posterolateral cusps in the present study. The number of scallops varies greatly as single, double, three, four, or tetra-scalloped and most significant six or hexa-scalloped which has never been reported in the previous studies. To understand the rationale behind each unique architectural layout, such noticeable variations are crucial for scientists around the world. Cardiothoracic surgeons could find this information valuable for mitral valve surgery repair.

Perceived leadership quality and empathy among Indian undergraduate medical students.

BACKGROUND: Efficient leaders from the medical fraternity may understand healthcare in depth. Empathy is important for patient care, job satisfaction, and the psychological well-being of doctors. Empathic leadership is concerned with an interest in the people around them. This study aimed to observe the perceived leadership quality and empathy among Indian medical undergraduate students, find any correlation between them, and assess age, sex, and semester of study as predictor variables for leadership and empathy. MATERIALS AND METHODS: An online cross-sectional survey was conducted on Google Forms with undergraduate medical students in India with a convenient snowball sample. The Abbreviated Self Leadership Quality (ASQL) was used to find the leadership quality and the eight-item Empathy Quotient (EQ-8) to find the empathy. Spearman's correlation coefficient was calculated between ASQL and EQ-8 score. Age, sex, and semester were used as predictor variables in regression analysis with leadership and empathy as dependent variables. RESULT: A total of 439 (50.8% male, 49.2% female) Indian undergraduate students participated in the study. Males showed higher leadership qualities. There was no gender difference in empathy. Leadership was positively correlated (rs =0.13, P = .006) with empathy in the overall sample. The age (P = .001), sex (P < .0001), and semester of study (P < .0001) successfully predicts leadership (F = 57.167, P < .0001). Although age, sex, and semester combined successfully predict empathy (F = 5.31, P = .001), individually, only a semester of study (P = .009) significantly contributes to the prediction. CONCLUSION: Male and female medical students show a similar level of empathy but male shows higher leadership quality. Leadership and empathy are positively correlated; hence, students with higher leadership quality would show higher empathy and vice versa. The age, sex, and semester of study are determinants of leadership whereas semester of study is the determinant of empathy.

Hypoglycemic Effect of Nelumbo Nucifera Seed Extract on GLUT-4 mRNA and GLUT-4 Protein in Streptozotocin-Induced Diabetic Rats.

Background: To investigate the effect of N. nucifera hydroalcoholic seed extract on fasting blood glucose (FBG) levels, glucose transporter (GLUT)-4 mRNA, and GLUT-4 protein in the adipose tissue of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male Sprague Dawley (SD) rats were first fed with a high-fat diet (HFD) for three weeks, and then, diabetes was induced by intraperitoneal injection of STZ at a dose of 35 mg/kg bw. Rats were divided into four groups: group 1: normal rats (NC), group 2: STZ-induced diabetic rats (DC), group 3: diabetic rats with N. nucifera hydroalcoholic seed extract at a dose of 400 mg/kg bw (NN), and group 4: diabetic rats with metformin at a dose of 100 mg/kg bw (MET) for 28 days. Results: FBG level was significantly lower in the NN group than in the DC group (P < 0.05). Also, the NN group increased GLUT-4 mRNA expression and GLUT-4 protein in the adipose tissue when compared to the diabetic group. Conclusion: We conclude that the observed hypoglycemic effect of N. nucifera seed extraction in STZ-induced diabetic rats could be due to insulinomimetic activity.

Analytical Study of Mandible: Prerequisite for Sex Determination.

Background: Human skull consists of various bones. One of them is mandible which is quite resistant, tough and shows systemic differences in form between individuals of different sex. It resists putrefaction also. There are characteristic features in the mandible that help us to differentiate sex in case of unknown victims like in mass disasters or in case fragmentary remains of the skeleton are found. Analysis of mandible with regard to its features is of great assistance in the determination of sex. Materials and Methods: A total of 80 dry mandible bones were collected. Morphological and morphometric parameters were studied to determine their sex. A total of nine parameters, i.e., three non-metric and six metric parameters were observed for each mandible. Data was collected for each parameter. Results: Among 80 dry mandible bones, 55 were males and 25 were females. 81.2% males bones had a square chin whereas, 80% females had a rounded chin. Gonial flare was everted in 89% males and inverted in 68% females. Conclusion: Mandible exhibits significant sexual differences. Various morphological and morphometric parameters are essential for sex determination in case of mandible bone.

Current distribution of medical colleges in India and its potential predictors: A public domain data audit.

Background: A teaching hospital or medical college may help provide better health care delivery to the people of the vicinity. Hence, building new medical colleges and upgrading existing hospitals to teaching hospitals are being implemented in India. Objective: This study aimed to observe the current distribution of medical colleges in Indian states and find correlation with area, population, and net state domestic product (NSDP). Methods: We collected data from public domain websites provided by government agencies. The State-wise number of government and private medical colleges and their annual intake were obtained from the National Medical Commission website. The state-wise number of medical colleges, geographical area, and population were calculated as the percentage of total Indian colleges, area, and population, respectively. Spearman's correlation was calculated to find any correlation of colleges and annual intake versus parameters such as area, population, and NSDP. Results: India has a total of 612 [321 (52.45%) government-run and 291 (47.55%) private] medical colleges. Tamil Nadu (70), Uttar Pradesh (67), Karnataka (63), Maharashtra (62), and Telangana (34) are the top five states with 296 (48.37%) medical colleges. States and union territories such as Karnataka, Kerala, Maharashtra, Puducherry, Tamil Nadu, and Telangana have higher medical colleges, and states such as Assam, Bihar, Odisha, Madhya Pradesh, Rajasthan, and Uttar Pradesh have lower medical colleges when compared with their population percentages. There was significant positive correlation of number of medical colleges with area (rs = 0.769, P < 0.0001), population (rs = 0.91, P < 0.0001), and NSDP (rs = 0.91, P < 0.0001). Conclusion: The current distribution of medical colleges in India is clustered over some states. Although geographical area and population are major predictors of medical colleges in Indian states, a more population-based balanced distribution of medical colleges would help distribute quality health care to the majority of the population.

A cross-sectional audit of informed consent of online survey: Characteristics and adherence to prevalent guidelines.

Background: Research on human participants requires formal approval from a competent ethics committee. During the recruitment of the research participants, obtaining informed consent is a prerequisite. The online survey method is used by many researchers as it can collect the data from a diverse population in a short time. Aim: This study aimed to observe the characteristics and adherence to prevalent guidelines (set by the Indian Council of Medical Research [ICMR]) of informed consent coupled with online surveys. Methods: We collected the informed consent text from online survey links obtained from a network of colleagues who got a request to participate in a survey. Data were collected from July 2020 to June 2022. The text was anonymized for further analysis. The word count, sentences, and Flesch reading ease score were calculated. The adherence to ICMR guidelines where checked by two authors individually and a consensus was reached to prepare the final result. Results: A total of 44 online surveys in English were audited and among them, 10 did not have informed consent. The informed consent in 34 surveys had a median of 6 sentences and 84 words. The median reading ease score was 45.7 (college level). The majority of the consent states the purpose of the research (91.18%), the voluntary nature of the participation (85.29%), and mentioned that it is research (64.71%). However, the rest of the components are ignored by the majority of the survey consent form. Conclusion: Informed consent form with online surveys lacks adherence to the components suggested by ICMR. Hence, the forms should be made carefully by the researchers so that the vigor of informed consent is maintained in the online surveys.

Health Related Quality of Life in Patients with Transfusion-dependent Thalassemia.

Patients with transfusion-dependent thalassemia are expected to have an unfavorable quality of life due to multiple factors. We studied the quality of life in 72 patients (age 5-39 y) with transfusion-dependent thalassemia in the era of improved care, and assessed different parameters affecting it.

Liver X receptor: a cardinal target for atherosclerosis and beyond.

The nuclear receptor liver X receptor [LXR] is activated by endogenous oxidized derivatives of cholesterol. It constitutes a critical receptor in the regulation of various physiological functions related to the development of metabolic and cardiovascular diseases, such as atherosclerosis and diabetes, as well as various other disorders. Both isoforms of LXR, LXRα [NR1H3] and LXRß [NR1H2], form heterodimers with the isoforms of the retinoid X receptor [RXR], which then regulate the gene expression by binding to DNA sequences associated with target genes. LXR acts as a cholesterol sensor in response to an increased concentration of cholesterol in cells and induces the transcription of genes that protect cells from cholesterol overload. LXRs play numerous roles in controlling cholesterol homeostasis via their actions on bile acid synthesis and metabolism/excretion, reverse cholesterol transport and cholesterol absorption/excretion in the intestines. Therefore, these receptors show great potential as pharmacological targets for anti-atherosclerotic activities. Recent discoveries have also emphasized the important involvement of LXRs in the pathogenesis of diabetes, Alzheimer's disease, inflammation, adrenal steroid synthesis, skin aging and male fertility. However, LXR activation has also been shown to stimulate lipogenesis via sterol regulatory element binding protein-1c, leading to liver steatosis and hypertriglyceridemia. This review summarizes recent scientific discoveries and the biological actions of LXR with a special focus on the involvement of this type of receptor in important diseases and conditions.

A biceps plantaris in the popliteal region - case report

A double plantaris muscle was observed in the right popliteal fossa during undergraduate medical dissection which was performed on a male cadaver of about 40 years. Its proximal belly originated from the lower part of the lateral supracondylar ridge, and the distal belly from the posterior aspect of the lateral femoral condyle. Both bellies had a single long tendon inserted into the calcaneum. After careful dissection, the muscle was observed to be innervated by the tibial nerve

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Use of peritoneal dialysis in AKI: a systematic review.

BACKGROUND AND OBJECTIVES: The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. RESULTS: Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I(2)=73%, P=0.03). CONCLUSIONS: There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area.

Gender differences in the quality of life of patients with liver cirrhosis related to hepatitis C after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, which adversely affects the quality of life (QoL) of the patient. The gender of the patient may be an important variable in the way severity of the disease is perceived. The aim of our study is to evaluate the effect of the gender variable on QoL in HCV-positive patients. METHODS: This study included a total of 52 patients (26 men and 26 women) who completed a 1-year follow-up after liver transplantation. QoL was assessed using the SF-36 questionnaire. RESULTS: Male subjects have significantly higher scores on physical role functioning, bodily pain and physical activity compared with females. Females have a better QoL compared to males with regard to the emotional state and mental health. CONCLUSIONS: These results show a significant effect of the gender variable on QoL in HCV patients.

Synthesis of [DTPA-bis(D-ser)] chelate (DBDSC): an approach for the design of SPECT radiopharmaceuticals based on technetium.

D-Serine is a physiological coagonist of the N-methyl D-aspartate (NMDA) type of glutamate receptor-a key excitatory neurotransmitter receptor in the brain. D-Serine appears to be a part of the synapse through a variety of transporters located on both neurons and astrocytes. The development of 99mTc radiolabeled amino acid based radiopharmaceuticals for imaging a variety of tumors has found to be useful in diagnostic imaging. Diethylene triamine penta acetic acid (DTPA) is one of the most well-known chelating reagent for the production of stable complexes with various heavy metal ions. We have synthesized [DTPA-bis(D-ser)] in 90% yield and analyzed the chelate by spectroscopic techniques. The DBDSC chelate binds to 99mTc with high efficiency at ambient temperature. The resulting chelate is stable under physiological conditions (37oC, pH=7.4) for at least 24 h after radiocomplexation. The receptor binding studies of 99mTc-[DTPA-bis(D-ser)] in established lung adeno carcinoma A549 exhibited Kd value to be 26nM. A549 Tumor in athymic mice was accumulated in the γ-images. The major accumulation of the radiotracer was observed in tumor, followed by kidneys. 99mTc-[DTPA-bis(D-ser)] has promising utility as SPECT-radiopharmaceutical.

Medical management of renal stone.

Kidney stone is a common clinical problem faced by clinicians. The prevalence of the disease is increasing worldwide. As the affected population is getting younger and recurrence rates are high, dietary modifications, lifestyle changes, and medical management are essential. Patients with recurrent stone disease need careful evaluation for underlying metabolic disorder. Medical management should be used judiciously in all patients with kidney stones, with appropriate individualization. This chapter focuses on medical management of kidney stones.

Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis.

BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients. METHODS: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed. RESULTS: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01). CONCLUSIONS: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.

Cardio-renal syndrome type 5: epidemiology, pathophysiology, and treatment.

The cardio-renal syndromes (CRS) recently were defined systematically as disorders of the heart or kidney whereby dysfunction of one organ leads to dysfunction of another. Five types of CRS are defined. The first four types describe acute or chronic cardio-renal or renocardiac syndromes. Type 5 CRS refers to secondary cardio-renal syndrome or cardio-renal involvement in systemic conditions. It is a clinical and pathophysiological entity to describe the concomitant presence of renal and cardiovascular dysfunction. Type 5 CRS can be acute or chronic and it does not strictly satisfy the definition of CRS. However, it encompasses many conditions in which combined heart and kidney dysfunction is observed. Because this entity has been described only recently there is limited information about the epidemiology, clinical course, and treatment of this condition.

New biomarkers for acute renal injury.

Incidence of acute kidney injury (AKI) is increasing rapidly to epidemic proportions. Development of AKI, especially in intensive care settings, is associated with increased morbidity, mortality and hospitalization costs. Currently available diagnostic tools are mostly insensitive for early diagnosis, however prompt diagnosis and risk stratification are necessary for guiding therapy and preventing progression of disease. Finding an early, reliable, suitable, easily reproducible, economical and accurate biomarker for AKI is a top research priority. In recent years, many urinary and serum proteins have been investigated as possible early markers of AKI and some of them have shown great promise. This topic reviews some of the emerging biomarkers of AKI.

Hepatitis C virus adversely affects quality of life.

BACKGROUND: Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. METHODS: Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. RESULTS: Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. CONCLUSIONS: These results show a significant impact of HCV infection on health status and subjective satisfaction.

Collagenofibrotic glomerulopathy in association with Hodgkin's lymphoma.

Deposit glomerulopathies are characterized by fibrillary deposits of various sizes, mainly in the mesangial area. Collagenofibrotic glomerulopathy is a rare type of such fibrillary glomerulopathies characterized by deposits of 60-80 nm fibrils in the sub-endothelial and mesangial areas. It is also associated with increased levels of serum pro-collagen type III peptide (PIIINP). Although most of the initial reports have emanated from Japan, many other scientists around the globe have later reported this disease. Possibility of systemic disease affecting metabolism of type III collagen is postulated but so far no such association has been identified. We report a 26-year-old male patient who presented with insidious onset of febrile illness associated with lymphadenopathy and proteinuria. Lymph node biopsy revealed features of Hodgkin's lymphoma while percutaneous renal biopsy showed features of collagenofibrotic glomerulopathy.

Biomarkers in kidney and heart disease.

There is much symptomatic similarity between acute kidney disease and acute heart disease. Both may present with shortness of breath and chest discomfort, and thus it is not surprising that biomarkers of acute myocardial and renal disease often coexist in many physicians' diagnostic work-up schedules. In this review we explore the similarities and differences between current and future tests of myocardial and renal injury and function, with particular emphasis on the diagnostic utility of currently available biomarkers to assist with the diagnosis of cardiorenal syndromes. Imaging studies have not traditionally been viewed as clinical biomarkers, but as tests of structure and function; they contribute to the diagnostic process, and we believe that they should be considered alongside more traditional biomarkers such as blood and urine measurements of circulating proteins and metabolites. We discuss the place of natriuretic peptides, novel tests of kidney damage as well as kidney function and conclude with a discussion of their place in guiding future research studies whose goals must include better characterization of the degree of dysfunction imposed on one organ system by failure of the other.