Thamnostylum piriforme, a novel etiological agent of superficial mycosis.

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.

Dobutamine Stress Cardiovascular Magnetic Resonance Derived 2-Dimension Feature Tracking Strain Analysis in Pediatric Population with Anomalous Aortic Origin of Right Coronary Artery.

Anomalous aortic origin of right coronary artery (AAORCA) is associated with myocardial ischemia and sudden cardiac arrest/death. Risk stratification remains challenging and relies upon provocative test results. This study describes the utility of dobutamine stress cardiovascular magnetic resonance (DSCMR) and potential benefit of strain analysis in children with AAORCA. All patients less than 21 years of age with AAORCA who underwent DSCMR between July 2018 and December 2022 were included. Visual wall motion abnormalities (VWMA) at rest and during protocolized increments of dobutamine infusion were assessed. Regional and global left ventricular circumferential (GCS) and radial (GRS) strain using 2-dimension Feature tracking (2D-FT) analysis (cvi42, Circle Cardiovascular Imaging Inc.) were calculated at rest and peak response. Of the total 54 DSCMR studies performed in 51 children with median age (IQR) of 13.5 (11-15) years, FT analysis was reliably performed in 52 (96%) studies. None had VWMA. The absolute change in GCS and GRS from rest to peak dobutamine stress was 4% (1-6%) and 11% (4-18%), respectively. There was no significant difference in GCS and GRS in patients with exertional symptoms vs no/non-exertional symptoms as well as between those considered to be high-risk vs low-risk anatomical features. DSCMR-derived 2D-FT strain analysis is feasible to assess myocardial deformation in children with AAORCA and may enhance this method of provocative testing. Although there were no statically significant differences in GCS and GRS values between high and low-risk subgroups, the absolute change in GCS between rest and peak stress is diminished when compared to normal adult reports.

Mucormycosis and Its Upsurge During COVID-19 Epidemic: An Updated Review.

Although mucormycosis may have reached an epidemic situation during the COVID-19 pandemic, the term was much more familiar even before the COVID-19 period. The year 2020 showed an outbreak of novel coronavirus (SARS-CoV-2) which affected millions of people all over the world. One of the noticeable complications observed to be associated with this disease is mucormycosis. It is an opportunistic infection caused by members of the Order Mucorales existing worldwide and has been commonly reported as a laboratory contaminant for a long time. However, nowadays due to the changes in the host environment, they have been emerging as potent opportunistic pathogens responsible for causing primary infections or coinfections with other diseases eventually resulting in morbidity and even mortality in severe cases. Although immunocompromised patients are more susceptible to this infection, few cases have been reported in immunocompetent individuals. Various risk factors which are responsible for the acquisition of mucormycosis include diabetes mellitus type 2, ketoacidosis, hematological malignancies, organ transplants, and chemotherapy recipients. Among the various etiological agents, Rhizopus is found to be the most common, and rhino-cerebral to be the most frequent clinical presentation. As far as pathogenesis is concerned, host cell invasion, thrombosis, and necrosis are the main events in the progression of this disease. The aim of the present review is to address a complete spectrum of mucormycosis and COVID-19-associated mucormycosis (CAM) in a single article. Both global and Indian scenarios of mucormycosis are taken into account while framing this review.

Tolerability and efficacy of a reduced dose adenosine stress cardiac magnetic resonance protocol under general anesthesia in infants and children.

BACKGROUND: Intravenous adenosine induces pharmacological stress by causing vasodilatation and thus carries the risk of severe hypotension when combined with vasodilatory effects of anesthetic agents. OBJECTIVE: This study describes our experience with a reduced dose adenosine cardiac magnetic resonance imaging (MRI) protocol in young children under general anesthesia (GA). MATERIALS AND METHODS: This is a retrospective report of all patients from birth to 18 years who underwent adenosine stress cardiac MRI under GA between August 2018 and November 2022. Based on our anecdotal experience of severe adverse effects in patients receiving adenosine infusion under GA and in discussion with the pediatric anesthesia team, we developed a modified protocol starting at a dose of 110 mcg/kg/min with incremental escalation to a full dose of 140 mcg/kg/min to achieve desired hemodynamic effect. RESULTS: Twenty-two children (mean age 6.5 years, mean weight 28 kg) satisfied the inclusion criteria. The diagnoses included Kawasaki disease (7), anomalous aortic origin of left coronary artery (3), anomalous aortic origin of right coronary artery (2), coronary fistula (3), repaired d-transposition of great arteries (2), repaired anomalous left coronary artery from pulmonary artery (2), repaired truncus arteriosus with left coronary artery occlusion (1), extracardiac-Fontan with left coronary artery myocardial bridge (1), and post heart transplantation (1). Nine patients needed dose escalation beyond 110 mcg/kg/min. Two patients had transient hypotension during testing (systemic blood pressure drop > 25 mmHg). No patient developed significant heart block or bronchospasm. Six patients (repeat study in one) demonstrated inducible perfusion defects (27%) on stress perfusion sequences-5 of whom had confirmed significant coronary abnormalities on angiography or direct surgical inspection. CONCLUSION: A reduced/incremental dose adenosine stress cardiac MRI protocol under GA in children is safe and feasible. This avoids severe hypotension which is both unsafe and may result in inaccurate data.

Pregnancy in Eisenmenger syndrome: a case series from a tertiary care hospital of Northern India.

BACKGROUND: Despite advances in medical care, we still come across pregnancy in Eisenmenger syndrome. Eisenmenger syndrome represents the severe end of the spectrum for disease in pulmonary artery hypertension associated with CHD. Due to very high maternal and perinatal morbidity and mortality, pregnancy is contraindicated among these women. Current guidelines also recommend that the women who become pregnant should opt for early termination of pregnancy. Here, we present a case series of 11 women of Eisenmenger syndrome and their pregnancy outcome. METHODS: It was a retrospective analysis of 12 pregnancies among 11 women with Eisenmenger syndrome who were managed in a tertiary care referral centre of Northern India. RESULTS: The mean age of these women was 28 ± 4 years (range 22 to 36 years). Almost 80% of them (9/11) were diagnosed with Eisenmenger syndrome during pregnancy. The commonest cardiac lesion was Ventricular Septal defect (54.5%) followed by Atrial Septal defect (27.3%) and Patent Ductus arteriosus (9.1%). Only three women opted for medical termination of pregnancy, rest eight continued the pregnancy or presented late. Pregnancy complications found include pre-eclampsia (50%), abruption (22%), and fetal growth retardation (62.5%). There were three maternal deaths (mortality rate 27%) in postpartum period. CONCLUSION: This case series highlights the delay in diagnosis and treatment of CHD despite improvement in medical care. Women with Eisenmenger syndrome require effective contraception, preconceptional counselling, early termination of pregnancy, and multidisciplinary care.

Astigmatic reduction after dermoid excision in a child with Goldenhar syndrome.

Goldenhar syndrome is a rare congenital disorder. Limbal dermoid associated with this syndrome can cause high astigmatism and amblyopia in children. We report significant reduction in astigmatism, after limbal dermoid excision with lamellar keratoplasty, in a rare case of Goldenhar syndrome. A three-year-old female patient, with left-sided limbal dermoid with high astigmatism and amblyopia, was referred to us for visual rehabilitation. The patient had left-sided limbal dermoid and preauricular appendages. Oral examination revealed bifid labial frenum, a deep antegonial notch on the left side of the mandible and missing left upper central incisor teeth. She was diagnosed as a case of Goldenhar syndrome. Her best-corrected visual acuity was 20 of 20 in the right eye and 20 of 200 in the left eye. Refraction showed astigmatism of 10 diopters in her left eye. She underwent limbal dermoid excision with lamellar keratoplasty in her left eye, after which her astigmatism reduced considerably. Early surgical intervention is recommended in cases of limbal dermoid with high astigmatism as it provides not only good cosmetic but also good visual benefits by early institution of treatment for amblyopia.

Facility-based stillbirth surveillance review and response: an initiative towards reducing stillbirths in a tertiary care hospital of India.

OBJECTIVES: India has the highest number of stillbirths in the world in 2019, with an estimated stillbirth rate of 13.9 per 1,000 births. Towards better identification and documentation, a stillbirth surveillance pilot was initiated with the World Health Organization Southeast Asia collaboration in Northern India in 2014. This study aimed to assess whether stillbirth surveillance is feasible and whether this approach provides sufficient information to develop strategies for prevention. METHODS: This study followed the framework provided in "WHO Making Every Baby Count" in which mortality audit is conducted in six steps; (1) identifying cases; (2) collecting information; (3) analysis; (4) recommending solutions; (5) implementing solutions; and (6) evaluation. RESULTS: A total of 5,284 births were examined between December 2018 and November 2019; 266 stillbirths were identified, giving a stillbirth rate of 50.6 per 1,000 births in a tertiary care referral hospital of northern India. Out of 266 stillbirths, 223 cases were reviewed and recommendations were formulated to strengthen obstetric triage, implementing fetal growth charts, strengthen the existing referral system and improve the communication skills of health care providers for better compliance with clinical practice guidelines. CONCLUSIONS: Conducting stillbirth surveillance review and the response of cases in low-middle income countries setting is feasible. As countries progress towards ending preventable mortality, this has the potential to serve as a key process in improving evidence-based and context-specific planning and preventive strategies towards improving the quality of care.

Epidermal growth factor receptor inhibitors as potential anticancer agents: An update of recent progress.

Epidermal growth factor receptor (EGFR) is a vital intermediate in cell signaling pathway including cell proliferation, angiogenesis, apoptosis, and metastatic spread and also having four divergent members with similar structural features, such as EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). Despite this, clinically exploited inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific thus provoking unenviable adverse effects. Some of the paramount obstacles to generate and develop new lead molecules of EGFR inhibitors are drug resistance, mutation, and also selectivity which inspire medicinal chemists to generate novel chemotypes. The discovery of therapeutic agents that inhibit the precise stage in tumorous cells such as EGFR is one of the chief successful targets in many cancer therapies, including lung and breast cancers. This review aims to compile the various recent progressions (2016-2021) in the discovery and development of diverse epidermal growth factor receptor (EGFR) inhibitors belonging to distinct structural classes like pyrazoline, pyrazole, imidazole, pyrimidine, coumarin, benzothiazole, etc. We have summarized preclinical and clinical data, structure-activity relationships (SAR) containing mechanistic and in silico studies to provide proposals for the design and invention of new EGFR inhibitors with therapeutic significance. The detailed progress of the work in the field will provide inexorable scope for the development of novel drug candidates with greater selectivity and efficacy.

Recent developments in mitogen activated protein kinase inhibitors as potential anticancer agents.

The mitogen activated protein kinase (MAPK) belongs to group of kinase that links the extracellular stimuli to intracellular response. The MAPK signalling pathway (RAS-RAF-MEK-ERK) involved in different pathological conditions like cancer, caused due to genetic or any other factor such as physical or environmental. Many studies have been conducted on the pathological view of MAPK cascade and its associated element like RAS, RAF, MEK, ERK or its isoforms, and still the research is going on particularly with respect to its activation, regulation and inhibition. The MAPK signalling pathway has become the area of research to identify new target for the management of cancer. A number of heterocyclics are key to fight with the cancer associated with these enzymes thus give some hope in the management of cancer by inhibiting MAPK cascade. In the present article, we have focussed on MAPK signalling pathway and role of different heterocyclic scaffolds bearing nitrogen, sulphur and oxygen and about their potential to block MAPK signalling pathway. The heterocyclics are gaining importance due to high potency and selectivity with less off-target effects against different targets involved in the MAPK signalling pathway. We have tried to cover recent advancements in the MAPK signalling pathway inhibitors with an aim to get better understanding of the mechanism of action of the compounds. Several compounds in the preclinical and clinical studies have been thoroughly dealt with. In addition to the synthetic compounds, a significant number of natural products containing heterocyclic moieties as MAPK signalling pathway inhibitors have been put together. The structure activity relationship along with docking studies have been discussed to apprehend the mechanistic studies of various compounds that will ultimately help to design and develop more MAPK signalling pathway inhibitors.

Novel cases of cutaneous phaeohyphomycosis by Alternaria alstromeriae, Epicoccum tritici and Phialemonium obovatum from North India.

BACKGROUND: A growing number of non-dermatophytic moulds and yeasts with the ability to act as human pathogens are reported every year. Dematiaceous fungi cause phaeohyphomycosis which encompasses a broad spectrum of diseases ranging from superficial (cutaneous and subcutaneous) to disseminated infections. Such fungal infections are responsible for causing significant morbidity and mortality, frequently in immunocompromised patients and rarely in immunocompetent patients. OBJECTIVES: To investigate the prevalence of cutaneous mycosis in Jammu district (India) and to isolate and identify the recovered causal agents from the affected skin of the patients. METHODS: For direct microscopy, 10% KOH was used. Skin samples were collected carefully from the affected areas of suspected patients, followed by the isolation and identification of the causal agents by cultural examination, morphological examination and ITS sequencing. RESULTS: Herein, we report and describe three new cases of cutaneous phaeohyphomycosis from District Jammu of Union Territory Jammu and Kashmir, India. The age of the patients under study ranged from 17 to 42 years and the duration of infection from 1 to 2 years. The etiological agents that were recovered from the patients under study were Alternaria alstromeriae, Epicoccum tritici and Phialemonium obovatum. These dematiaceous fungal species were isolated from the skin specimen of immunocompetent hosts. CONCLUSION: Among the three isolated etiological agents, two (Alternaria alstromeriae, Epicoccum tritici) represent new global records and one (Phialemonium obovatum) new record to India as causal agents of cutaneous phaeohyphomycosis. Careful microscopic and mycological examination form the basis of correct diagnosis of such fungal infections in the absence of simple and reliable laboratory tests (serologic or antigen tests).

Superficial mycoses, a matter of concern: Global and Indian scenario-an updated analysis.

Superficial mycoses of skin, nails and hair are among the common fungal infections. They are caused by dermatophytes, non-dermatophyte moulds, yeasts and yeast-like fungi. Such fungal infections are widespread all over the world and are predominant in tropical as well as subtropical regions. Environmental factors, such as warm, humid and pitiable hygienic conditions, are conducive for their growth and proliferation. Although it does not cause mortality, it is known to be associated with excessive morbidity which may be psychological or physical. This affects the quality of life of the infected individuals which leads to a negative impact on their occupational, emotional and social status. Such infections are increasing on a global scale and, therefore, are of serious concern worldwide. This review article covers the global and Indian scenario of superficial mycoses taking into account the historical background, aetiological agents, prevalence, cultural and environmental factors, risk factors, pathogenesis and hygienic practices for the prevention of superficial mycoses.

Pharmacological properties, therapeutic potential, and legal status of Cannabis sativa L.: An overview.

Marijuana, or Cannabis sativa L., is a common psychoactive plant used for both recreational and medicinal purposes. In many countries, cannabis-based medicines have been legalized under certain conditions because of their immense prospects in medicinal applications. With a comprehensive insight into the prospects and challenges associated with the pharmacological use and global trade of C. sativa, this mini-review focuses on the medicinal importance of the plant and its legal status worldwide; the pharmacological compounds and its therapeutic potential along with the underlying public health concerns and future perspective are herein discussed. The existence of major compounds including Δ9 -tetrahydrocannabinol (Δ9 -THC), cannabidiol, cannabinol, and cannabichromene contributes to the medicinal effects of the cannabis plant. These compounds are also involved in the treatment of various types of cancer, epilepsy, and Parkinson's disease displaying several mechanisms of action. Cannabis sativa is a plant with significant pharmacological potential. However, several aspects of the plant need an in-depth understanding of the drug mechanism and its interaction with other drugs. Only after addressing these health concerns, legalization of cannabis could be utilized to its full potential as a future medicine.

Second trimester medical abortion in a primigravida with lupus nephritis and rapidly progressive renal failure: challenges and outcome.

In the second trimester, medical abortion is preferred as it is less invasive, and the surgical method carries more risk. There is a paucity of published literature on medical abortion in women with renal failure requiring haemodialysis. We came across a woman who presented with rapidly progressive renal failure at 18 weeks of gestation and required therapeutic abortion. We are reporting the challenges, outcomes, and precautions to be taken while performing a medical abortion in such a case.

Classifying stillbirths in a tertiary care hospital of India: International Classification of Disease-perinatal Mortality (ICD-PM) versus cause of death-associated condition (CODAC) system.

A number of classification system are available to classify stillbirths, but there remains a lack of a uniform global system of classification. This study evaluated the feasibility of the ICD-PM classification system and COD-AC to classify the stillbirths and to discuss the interpretation of "the newer" classification system (ICD-PM) over the COD-AC system. Over a period of one year, out of 5776 total births 314 were stillborns with a stillbirth rate of 54 per 1000 total births. As per ICD PM Classification System, 69.1% of stillbirths were ante partum and rest intrapartum. The associated maternal conditions at the time of foetal death were also classified into five groups and maximum mothers (44.3%) were grouped under M4-medical/surgical disorders. According to COD-AC system of classification 90% of cases were assigned the cause of death, rest 10% remained unexplained. The ICD-PM and CODAC classification both seem to be feasible but ICD-PM clearly defines the time of foetal death and correlates feto-maternal dyad together.IMPACT STATEMENTWhat is already known on this subject? Classifying stillbirths is crucial to recognise the actual cause of foetal death and to gather the relevant information for planning the preventive strategies especially in low middle-income countries (LMICs) which contribute to 98% of total global burden of 2.6 million stillbirths annually. In literature CODAC system was found most suitable for low middle-income countries. In 2016, WHO proposed a newer system, i.e., ICD-PM: WHO application of ICD-10 to deaths during the perinatal period.What do the results of this study add? With ICD-PM classification stillbirths were categorised more clearly in different groups and feto-maternal condition were linked together along with both intrapartum and ante partum stillbirth which can help to set the priorities and future planning for prevention. The proportion of unexplained stillbirth has also reduced significantly compared to CODAC system.What are the implications of these findings for clinical practice and/or further research? CD-PM system of classification seems feasible and would facilitate the uniform and consistent stillbirth data even from LMICs for global comparison although more number of studies are needed for conclusion. The system has been changed to ICD-PM in our institute.

Sn-MOF@CNT nanocomposite: An efficient electrochemical sensor for detection of hydrogen peroxide.

A novel approach for the assembly of Sn-based metal organic framework (Sn-MOF) via solvothermal method and its composite (Sn-MOF@CNT) with electroactive material, carbon nanotubes (CNT) by sonochemical means, is described that is useful for hydrogen peroxide sensing; large surface area and pore volume of Sn-MOF were exploited where in the crystallinity of the Sn-MOF was preserved upon inclusion of CNT over its surface. The surface morphology and structural analysis of Sn-MOF and its composite form, Sn-MOF@CNT, were determined analytically through Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), Scanning electron microscopy (SEM), Brunauer-Emmett-Teller and Energy-dispersive X-ray spectroscopy (EDX). The developed Sn-MOF@CNT sensor was expansively used to determine and optimize the effect of scan rate, concentration and detection limits including the EDX and SEM analysis of used Sn-MOF@CNT nanocomposite's post hydrogen peroxide sensing. The electrochemical sensing with Sn-MOF@CNT revealed a lower limit of detection ~4.7 × 10-3 µM with wide linear range between 0.2 µM and 2.5 mM. This study has explored a new strategy for the deposition of CNT over Sn-MOF via a simple sonochemical methodology for successful electrochemical detection of H2O2, an approach that can be imitated for other applications.

Effect of different fat and protein levels in calf ration on performance of Sahiwal calves.

OBJECTIVE: The current study was carried out to examine the response of different levels of fat and protein in calf starter on nutrient utilisation, nitrogen metabolism, weight gain, blood parameters and immunity level in pre-ruminant calves. METHODS: Twenty four calves (5 days old) were divided into six groups in a 2x3 factorial design, with two levels of fat (10% and 14 %) and three levels of protein (18%, 21% and 24%). The calves were kept in individual pens for 120 days and fed with whole milk (1/10th of body weight) and calf starter ad-libitum. Daily dry matter intake (DMI) was recorded; whereas body weight was taken on fortnightly basis to calculate average daily gain (ADG). During the growth trial blood samples were collected at 30 days interval to estimate blood glucose, albumin, total protein, total leucocyte count, total immunoglobulin and IgG levels. A metabolic trial of seven days was carried out to find out the digestibility of different nutrients. RESULTS: The DMI was reduced (p<0.05) with higher fat and protein levels whereas feed conversion efficiency (FCE) was improved (p<0.05) with higher protein level. Different levels of fat and protein in calf ration did not affect average daily gain in calves.The dry matter (DM), organic matter (OM) and crude protein (CP) digestibility were significantly (p<0.01) higher with increased level of protein. The nitrogen retention was also significantly higher (p<0.05) at 24 % protein level, similarly the total immunoglobulin was significantly (p< 0.05) high in higher protein fed groups, showed better immunity. CONCLUSION: The present finding suggested that 10 % fat and 18 % protein level of calf starter could be used in Sahiwal calves for optimum performance in terms of weight gain and immunity.

Role of Autopsy in Elective Termination of Pregnancy for Fetal Anomaly (ETOPFA): A Study from a Tertiary Care Hospital in India.

OBJECTIVE: To evaluate the fetal anomalies in all the patients who underwent elective termination of pregnancy for fetal anomalies (ETOPFA) before 20 weeks of gestation and to compare prenatal diagnosis with final diagnosis made after autopsy. METHODOLOGY: Prospective study done in a tertiary care hospital in India over a period of two years which include 252 women who underwent ETOPFA. The prenatal diagnosis was compared with final diagnosis made after autopsy. RESULTS: In 75.4% of cases autopsy findings were concordant with prenatal diagnosis where as in 21.6% of cases, additional findings were added. In 2.9 % of cases prenatal diagnosis was not confirmed by autopsy and found to be discordant. CONCLUSIONS: Autopsy plays an important role in completing the final diagnosis along with verification of prenatal diagnosis. To avoid discrepancy especially in cases of severe oligohydramnios, MRI or amnioinfusion could be offered for conformation of the diagnosis before offering ETOPFA.