Severe Form Research Articles

Epigenetics of nonobstructive azoospermia.

Nonobstructive azoospermia (NOA) is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis. Although various factors are well defined in the disruption of spermatogenesis, not all aspects due to the heterogeneity of the disorder have been determined yet. In this review, we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.

Is Chronic Pelvic Inflammatory Disease an Exclusively Medical Gynecological Disease, or It May Be a Surgical Challenge?

Pelvic inflammatory disease is an infectious condition affecting women’s upper genital tract, including the uterus, fallopian tubes, and ovaries. It primarily arises from an infection that spreads upward from the lower genital area. The relationship between chronic pelvic pain and coexisting conditions is a key focus in its diagnosis and treatment. This type of pain is also considered a form of reflex dystrophy, involving both neurological and psychological components, the first line treatment consists in antibiotherapy. For patients with complex or severe pelvic abscesses, surgical intervention may be considered in selected cases. The primary surgical techniques employed are open and laparoscopic surgery, both aimed for abscess removal. MRI or Doppler ultrasonography may be employed when there is a suspicion of adnexal torsion, adenomyosis or deep pelvic endometriosis, especially if the ultrasound results are unclear or inconclusive Laparoscopic surgery has increasingly become favored by both healthcare professionals and patients. Moreover, laparoscopy has emerged as the most valuable tool for diagnosing chronic pelvic pain. The approach to treating pelvic abscesses in women of reproductive age depends greatly on clinical assessments, individual patient factors, and the desire to preserve fertility. However, laparoscopy may present technical difficulties in patients with severe pelvic abscesses, particularly those with extensive adhesions or a closed-off pelvic area, requiring advanced surgical expertise. Women with associated conditions such as endometriosis often experience a more severe form of pelvic inflammatory disease, which is less responsive to antibiotics and more frequently requires surgical resolution. The surgical treatment should be performed individualized to the clinical condition of the patient and the time of intervention must be carefully chosen.

Rare diseases: a challenge in paediatric dentistry.

Rare diseases are an often an overlooked public health problem. Although they are infrequent, occurring on average in 100-500 people per million, these diseases represent a significant challenge in paediatric dentistry due to their complex manifestations and the need for specialised care. Conditions such as X-linked hypophosphatemic rickets (XLH), hypophosphatasia (HPP), and osteogenesis imperfecta (OI) exemplify the intersection of systemic health issues and oral health, requiring a multidisciplinary approach for their effective management. Dentists frequently play a crucial role in identifying genetic alterations through their dental manifestations and then referring patients to the geneticist for a definitive diagnosis. X-linked hypophosphatemia is the most common genetic form of rickets, with a prevalence of 1/20,000 - 1/60,000. XLH is characterised by stunted growth with disproportionate short stature, bowing of the lower limbs associated with reduced motor skills, osteoarticular pain, hypotonia, and dental and periodontal anomalies. XLH is due to inactivating mutations in the PHEX gene which cause excessive production of fibroblast growth factor 23 (FGF23). Increased concentration of FGF23 represents the main pathogenetic mechanism of XLH, stimulating urinary phosphate loss and renal 24-hydroxylase activity, and reducing renal 1α-hydroxylase activity with insufficient production of 1,25 -dihydroxy-vitamin D (1,25(OH)2D). PHEX protein is also expressed in osteoblasts, osteocytes, and odontoblasts. Regardless of FGF23's systemic effects on phosphate homeostasis, odontoblast differentiation, and dentin formation, its overexpression directly reduces osteoblast differentiation and matrix mineralisation. In patients with XLH, the deficit of 1,25(OH)2D induced by FGF23 causes poor enamel mineralisation with presence of cracks on teeth surface. XLH patients have recurrent dental abscesses with fistulas. Radiographic investigations highlight a generalised enlargement of the pulp chambers, molars with short roots, and a taurodontic appearance. Hypophosphatasia (HPP) is another condition in which dental manifestations precede systemic symptoms; it is a rare genetic disease (1/300,000 for severe forms, 1/100,000 for moderate forms. The incidence is perhaps underestimated due to missed diagnosis of moderate forms of the disease). It mainly affects bone and dental mineralisation. It is caused by pathogenic variant mutations in the ALPL gene which is located on the short arm of chromosome 1 and encodes the non-tissue-specific alkaline phosphatase (TNSALP) enzyme. TNSALP deficiency results in vitamin B6 (pyridoxine) deficiency and pathological accumulation of alkaline phosphatase substrates which may be responsible for extra-osseous manifestations, such as neurologic ones (pyridoxine sensitive seizures) as well as involvement of muscles and joints (arthropathies, muscle fatigue/hypotonia). Early non-traumatic loss of primary teeth between the ages of 2 and 4 years (and sometimes earlier) with an intact, non-resorbed root is a sign of disease. Tooth mobility precedes exfoliation of the tooth/teeth, most often without associated gum inflammation or pain. The primary incisors are the most affected teeth, and the number and type of primary teeth lost are proportional to the severity of the disease. From a radiologic perspective, characteristic signs include localised or generalised horizontal alveolar bone loss, large pulp chambers, intrapulpal calcifications, and reduced enamel thickness. Osteogenesis imperfecta, or brittle bone disease, is a rare condition characterised by bone fragility and osteopenia. It combines skeletal signs of varying severity (mainly fractures, hyperlaxity, and ligament deformities) and extra skeletal signs (bluish sclera, deafness, vascular fragility). It may also involve dentinogenesis imperfecta. The severity of clinical manifestations is highly variable, ranging from moderate forms that can go unnoticed to major forms that are lethal in the perinatal period. The birth prevalence of osteogenesis imperfecta is approximately 1 in 10,000 people. In approximately 90% of cases, it is an autosomal dominant disease due to monoallelic mutations in the COL1A1, COL1A2 or IFITM5 genes. Ten percent of cases are recessive forms characterised by dentinogenesis imperfecta, where the dental manifestations include teeth discoloration and weakness. The timely recognition of dental manifestations of these rare genetic diseases can allow providers to make an early diagnosis even prior to the development of systemic complications, and for this reason paediatric dentists have a key role in the recognition and management of these patients. Once the diagnosis is suspected, the dentist should refer patients for a genetic evaluation so as to ensure multidisciplinary management and initiation of medical therapies with the collaboration of paediatricians, endocrinologists and other health specialists. The role of dental professionals is not limited to the diagnosis of these rare diseases, but it also encompasses delivering specific, patient-tailored treatments, encouraging preventive care with regular dental visits and educating patients with the ultimate goal to promote not only oral health but the patient's overall wellbeing.

Anatomy of the Right and Left Ventricular Subvalvular Apparatus of the Horse (Equus caballus).

Due to the growing interest among veterinarians and the increasing market demands, the development of equine cardiology is necessary. Currently, veterinary medicine for companion animals needs to catch up to human medicine-equine medicine included. A common condition in older horses is aortic valve regurgitation resulting from fibrosis, while its more severe form occurs in younger horses or develops due to a bacterial infection. Mitral valve regurgitation, especially dangerous due to the possibility of sudden death, has a better prognosis if the horse has valve prolapse. Tricuspid valve regurgitation usually does not pose a clinical problem, although its severe cases may lead to heart failure. Some pathologies can be treated surgically, which requires excellent knowledge of anatomy. The object of this study consisted of twenty domestic horse hearts. The focus was on the normal and comparative anatomy of the left and right subvalvular apparatus. The number of muscular bellies of the papillary muscles and the type of connection of the muscles were analysed. Moreover, the height of muscle originating from the ventricle wall was determined, the morphological regularity of the papillary muscle was assessed, and the chordae tendineae originating from the papillary muscles were examined. The conducted research allowed for comparing domestic horses with different species through other studies, the authors of which described this particular aspect. Interspecies similarities which may be correlated with the evolutionary relatedness, as well as differences that could reflect adaptation to different lifestyles, environmental conditions, or metabolic requirements of the animals, have been found. This study expands the knowledge of animals' normal and comparative anatomy, and contributes to the development of veterinary surgery, internal medicine, and biology.

Immunoproteomic discovery of Mycobacterium bovis antigens, including the surface lipoprotein Mpt83 as a T cell antigen useful for vaccine development

Tuberculosis (TB) is one of the leading causes of death from infectious diseases, killing approximately 1.3 million people worldwide in 2022 alone. The current vaccine for TB contains a live attenuated bacterium, Mycobacterium bovis BCG (Bacille Calmette-Guérin). The BCG vaccine is highly effective in preventing severe forms of childhood TB but does not protect against latent infection or disease in older age groups. A new or improved BCG vaccine for prevention of pulmonary TB is urgently needed.In this study, we infected murine bone marrow derived dendritic cells from C57BL/6 mice with M. bovis BCG followed by elution and identification of BCG-derived MHC class I and class II-bound peptides using tandem mass spectrometry. We identified 1436 MHC-bound peptides of which 94 were derived from BCG. Fifty-five peptides were derived from MHC class I molecules and 39 from class II molecules. We tested the 94 peptides for their immunogenicity using IFN- γ ELISPOT assay with splenocytes purified from BCG immunized mice and 10 showed positive responses. Seven peptides were derived from MHC II and three from MHC class I. In particular, MHC class II binding peptides derived from the mycobacterial surface lipoprotein Mpt83 were highly antigenic. Further evaluations of these immunogenic BCG peptides may identify proteins useful as new TB vaccine candidates.

A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy.

LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive disorder and one of the most common congenital muscular dystrophies. Due to promising therapies in preclinical development, there is an increasing effort to better define the epidemiology and natural history of this disease. The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland. The study used data collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD). Diagnostic findings were derived from genetics, muscle biopsy, creatine kinase-level and electrophysiological testing, as well as from brain MRIs. Further clinical information included motor assessments (CHOP INTEND, MFM20/32), joint contractures, scoliosis, ophthalmoplegia, weight gain, feeding difficulties, respiratory function, cardiac investigations, EEG findings, IQ and schooling. Eighteen patients with LAMA-RD were included in the Swiss-Reg-NMD as of May 2023 (age at inclusion into the registry: median age 8.7 years, range 1 month - 31 years F = 8, M = 10). Fourteen patients presented with the severe form of LAMA2-RD (were never able to walk; CMD), whereas four patients presented with the milder form (present or lost walking capability; LGMD). All patients classified as CMD had symptoms before 12 months of age and 11/14 before the age of six months. 15 carried homozygous or compound heterozygous pathogenic or likely pathogenic variants in LAMA2 and two were homozygous for a variant of unknown significance (one patient unknown). Brain MRI was available for 14 patients, 13 had white matter changes and 11 had additional structural abnormalities, including cobblestone malformations, pontine hypoplasia and an enlarged tegmento-vermial angle not reported before. This study describes the Swiss cohort of patients with LAMA2-RD and gives insights into measuring disease severity and disease progression, which is important for future clinical trials, as well as for a better clinical understanding and management of patients with LAMA2-RD.

Effects of Isotretinoin treatment on human body - review

Introduction: Isotretinoin (13-cis-Retinoic Acid) is a part of the retinoid group, and is used in dermatology for the treatment of acne, due to its demonstrated inhibitory effect on sebaceous gland activity and proliferation. Isotretinoin is a highly lipophilic drug, for this reason taking it with food, doubles the bioavailability of the substance, during systemic treatment. Isotretinoin as a drug has been used effectively for more than 40 years in the treatment of acne, although its exact mechanism of action is not known. Objective: The objective of this study is to gather and analyze literature regarding the adverse effects of isotretinoin therapy on mental health and the digestive, cardiovascular, immune, urinary, and reproductive systems. Materials and Methods: A literature review was conducted using the PubMed database with the following search terms : retinoids, isotretinoin, acne, 13-cis-retinoic acid. Current Knowledge: Isotretinoin therapy has a vast spectrum of side effects affecting various systems of the human body. During the use of isotretinoin, special caution should be taken in patients with depression, lipid disorders, and abnormal liver function. In addition, in patients of childbearing age, make sure to use contraception one month before, during and one month after the end of isotretinoin therapy due to its teratogenicity. Conclusion: Isotretinoin is still the most effective drug in the systemic treatment of severe forms of acne, nevertheless its potential side effects should be kept in mind. Regular monitoring of patients should be a mainstay during isotretinoin therapy, especially with regard to lipid profile and liver parameters.

Spinal Dural Ectasia Spectrum: Management of Two Cases and Systematic Review of the Therapeutic Options.

To describe 2 cases with pathologic expansion of lumbosacral dura mater exerting compression on lumbosacral nerves treated with placement of lumboperitoneal shunt (LPS). Although dural ectasia (DE) is asymptomatic in most cases, a systematic review of the literature was performed focusing on the management when it causes symptoms. Pubmed/Medline and Embase databases were searched for the surgical management of DE. Both pediatric and adult patients were included. The presence of a cerebrospinal fluid leak was considered an exclusion criterion. An additional search was performed to provide a more complete picture of the DE spectrum considering meningoceles as a severe form of dural expansion. Differentiating DE from meningocele, only 20 patients were treated for symptomatic DE. Surgical management varied according to presentation and etiopathogenesis: blood patch or fibrin glue were attempted in case of intracranial hypotension, followed eventually by LPS or marsupialization or dura reduction in cases of failure, whereas LPS or spinal decompression were proposed in cases of radiculopathy or cauda equina syndrome. DE is a rare condition mostly associated with connective tissue disorders. The different etiopathogenesis may explain how it causes symptoms in specific conditions. Treatments should be chosen according to this and may be proposed at the appearance of symptoms since dural expansion is a self-sustained mechanism.

Vaccinium spp. Berries in the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease: A Comprehensive Update of Preclinical and Clinical Research.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder marked by the buildup of triacylglycerols (TGs) in the liver. It includes a range of conditions, from simple steatosis to more severe forms like non-alcoholic steatohepatitis (NASH), which can advance to fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD's prevalence is rising globally, estimated between 10% and 50%. The disease is linked to comorbidities such as obesity, type 2 diabetes, insulin resistance, and cardiovascular diseases and currently lacks effective treatment options. Therefore, researchers are focusing on evaluating the impact of adjunctive herbal therapies in individuals with NAFLD. One herbal therapy showing positive results in animal models and clinical studies is fruits from the Vaccinium spp. genus. This review presents an overview of the association between consuming fruits, juices, and extracts from Vaccinium spp. and NAFLD. The search used the following keywords: ((Vaccinium OR blueberry OR bilberry OR cranberry) AND ("non-alcoholic fatty liver disease" OR "non-alcoholic steatohepatitis")). Exclusion criteria included reviews, research notes, book chapters, case studies, and grants. The review included 20 studies: 2 clinical trials and 18 studies on animals and cell lines. The findings indicate that juices and extracts from Vaccinium fruits and leaves have significant potential in addressing NAFLD by improving lipid and glucose metabolism and boosting antioxidant and anti-inflammatory responses. In conclusion, blueberries appear to have the potential to alleviate NAFLD, but more clinical trials are needed to confirm these benefits.

Base editing of the GLB1 gene is therapeutic in GM1 gangliosidosis patient-derived cells

GM1 gangliosidosis is an autosomal recessive neurodegenerative lysosomal storage disease caused by pathogenic variants in the GLB1 gene, limiting the production of active lysosomal β-galactosidase. Phenotypic heterogeneity is due in part to variant type, location within GLB1, and the amount of residual enzyme activity; in the most severe form, death occurs in infancy. With no FDA approved therapeutics, development of efficacious strategies for the disease is pivotal. CRISPR/Cas based approaches have revolutionized precision medicine and have been indispensable to the development of treatments for several monogenic disorders with bespoke strategies central to current research pipelines. We used CRISPR/Cas-adenine base editing to correct the GLB1 c.380G>A (p.Cys127Tyr) variant in patient-derived dermal fibroblasts compound heterozygous with the GLB1 c.481T>G (p.Trp161Gly) pathogenic variant. Nucleofection of plasmids encoding the target sgRNA and ABEmax restored the canonical guanine (32.2 ± 2.2 % of the target allele) and synthesis of active β-galactosidase. Analysis of cellular markers of pathology revealed normalization of both primary glycoconjugate storage and lysosomal pathology. Furthermore, analysis of off-target sites nominated by the in silico tools Cas-OFFinder and/or CRISTA revealed no significant editing or indels. This study supports the use of CRISPR/Cas-based approaches for the treatment of GM1 gangliosidosis, and provides foundational data for future translational studies.

Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression.

Lung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To examine cellular and molecular dynamics driving evolving BPD in humans, we performed single-cell RNA sequencing of preterm infant lungs in early stages of BPD and BPD+PH compared to term infants. Analysis of the endothelium revealed a unique aberrant capillary cell-state primarily in BPD+PH marked by ANKRD1 expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factor FOXF1 within the alveolar parenchyma in neonatal lung samples with BPD/BPD+PH. Loss of semaphorin signaling was replicated in a murine BPD model and in humans with alveolar capillary dysplasia (ACDMPV), suggesting a mechanistic link between the developmental programs underlying BPD and ACDMPV and a critical role for semaphorin signaling in normal lung development.

A New-fangled COVID-19 Variant, Eris, Might be the One to Lookout in 2023 or far from Over.

Coronavirus Disease-19 (COVID-19) is an infectious disease brought on by the extremely pathogenic and contagious severe acute respiratory syndrome-virus-2 (SARS-CoV-2). The agenda for the COVID-19 pandemic is dynamic and includes recent developments. Seven variants under monitoring (VUMs), one variant of interest (VOI), XBB.1.5, and their offspring lineages are currently being actively monitored by WHO. The VUMs are BA.2.75, CH.1.1, BQ.1, XBB (with the exception of XBB.1.5, XBB.1.16, and XBB.1.9.1), XBF, and XBB.1.16. With 95 countries having reported finding XBB.1.5 (VOI), it is still the most common strain worldwide, responsible for 47.9% of cases from epidemiological January to March 2023. Seventy nations discovered XBB.1.5 in February and March 2023 and posted sequencing data to GISAID. Of the 43 nations that uploaded more than 50 sequences, XBB.1.5 prevalence has increased to more than 50% in 11 nations. Over 23000 deaths and 3 million new cases were recorded globally in March and April 2023. Worldwide detection of a new COVID-19 strain has prompted specialists to issue a warning that the virus is "circulating unchecked". The Greek goddess of conflict and discord Eris has inspired the nicknaming of EG 5.1, a subvariant of Omicron. The strain is becoming more prevalent in the USA and cases are increasing in the UK. The severity of each SARS-CoV- 2 variant has been comparable, although a more severe form might develop. Eris is an ancestor of Omicron and exhibits some of its characteristics. Reinfection risk can be influenced by a variety of variables, including age, location, and health equity and the COVID-19 vaccine is more or less effective depending on the strain.

A Review of Arsenic Trioxide in the Treatment of Acute Promyelocytic Leukemia: Clinical Efficacy, Toxicity, and Future Directions

Acute promyelocytic leukemia (APL) is a severe and life-threatening form of leukemia characterized by unique genetic and chromosomal abnormalities, often leading to fatal complications such as hemorrhage and embolism. Arsenic trioxide (ATO) has become a key therapeutic agent for APL, achieving high remission rates, including in patients with relapsed disease, and offering advantages over other treatments such as bone marrow transplantation and all-trans retinoic acid (ATRA). This review examines the chemical and pharmacological properties of ATO, its mechanisms of action in APL treatment, and its clinical efficacy and toxicity based on studies conducted worldwide. Additionally, this review explores potential applications of ATO beyond APL and discuss future research directions to expand its therapeutic scope in clinical settings.

Vitamin D treatment distinctly modulates cytokine production by peripheral blood mononuclear cells among patients with chronic cardiac and indeterminate clinical forms of Chagas disease.

Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease. To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cellsof patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines. Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10-7 M) for 24 h and cytokines were dosed in the culture supernatant. Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ(IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid),interleukin(IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells. In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.

Dengue In Brazil: Challenges And Strategies For Public Health Management

This academic essay explores the complex landscape of dengue in Brazil, a viral arbovirus transmitted by the Aedesaegypti mosquito, with significant impacts due to its high incidence and frequent epidemic outbreaks, especially during warm and rainy periods conducive to vector reproduction. The symptoms range from high fever and muscle pain to severe forms such as dengue hemorrhagic fever, requiring urgent medical intervention. The country's dengue control strategies include eliminating breeding sites, using insecticides, and conducting public awareness campaigns. The disease not only strains healthcare services but also adversely affects the economy and social well-being, underscoring the importance of robust epidemiological surveillance systems and coordinated responses. Initiatives such as the Health in Schools Program (PSE) and the roles played by Community Health Agents (ACS) and Endemic Disease Control Agents (ACE) are crucial in prevention and control efforts. Collaborative efforts across health, education, and community sectors are essential to address the challenges of dengue comprehensively. Therefore, Brazil must continue investing in research, vaccines, and innovative strategies to sustainably and effectively reduce the burden of dengue and safeguard public health.

RECK in placenta small extracellular vesicles: potential origin and diagnostic of the severe form of preeclampsia.

RECK in placenta small extracellular vesicles: potential origin and diagnostic of the severe form of preeclampsia.

Maternal prepregnancy weight as an independent risk factor for congenital heart defect: systematic review and meta-analysis stratified by subtype and severity of defect.

To assess the association between increased maternal prepregnancy body mass index (BMI) and the risk of congenital heart defect (CHD) in offspring. This systematic review and meta-analysis searched PubMed/MEDLINE, Web of Science and Scopus from inception to 20 April 2023. Risk estimates were abstracted or calculated for increased BMI categories (overweight, obesity, moderate obesity and severe obesity) compared with normal weight (reference). Fixed-effects or random-effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes before and during pregnancy. Subgroup analyses for specific CHD subtypes were conducted if there were at least two studies with available data. Findings were presented for groups of defects, categorized using severity and topographic-functional criteria, and for individual defects. The certainty of the evidence for each effect estimate was evaluated according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Overall, 31 studies comprising 4 861 693 patients and 86 136 CHD cases were included. The risk of CHD increased progressively from moderate to severe obesity (pooled odds ratio (OR), 1.15 (95% CI, 1.11-1.20) and 1.39 (95% CI, 1.27-1.53), respectively). Sensitivity analysis indicated that this effect persisted independently of maternal diabetes status before or during pregnancy. In the subgroup analysis, obesity was associated with up to a 1.5-fold increase in the risk of severe CHD (pooled OR, 1.48 (95% CI, 1.03-2.13)). Severe obesity was associated with an even higher risk, with 1.8-times higher odds compared with the reference group for specific CHD subtypes, including tetralogy of Fallot (pooled OR, 1.72 (95% CI, 1.38-2.16)), pulmonary valve stenosis (pooled OR, 1.79 (95% CI, 1.39-2.30)) and atrial septal defect (pooled OR, 1.71 (95% CI, 1.48-1.97)). Maternal weight is a crucial modifiable risk factor for CHD, particularly for severe forms of defect. Further research is needed to investigate whether weight management before pregnancy might serve as a preventive measure against CHD. In pregnant women with obesity, fetal echocardiography should be a routine diagnostic procedure. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Demographics, Clinical Characteristics and In-Hospital Outcome of Coronavirus Disease 2019 (COVID-19) Patients With or Without Diabetes Mellitus

Introduction Diabetes Mellitus (DM) is one of the important co-morbidity that may negatively influence the clinical outcome of the coronavirus disease 2019 (COVID-19) if it co-exists. There is a paucity of data regarding the characteristics and outcomes of COVID-19 diabetic patients in comparison to non-diabetic patients. Thus, we aimed to compare demographics and clinical characteristics, and in-hospital outcome in COVID-19 positive patients with or without DM. Method This prospective observational study included all consecutive confirmed symptomatic and asymptomatic COVID-19 positive patients from March 8th 2020 to July 7th 2023at the National Heart Foundation Hospital &amp; Research Institute of Bangladesh. Patients were divided into two groups based on whether they had diabetes: Group I- patients with DM and group II- patients without DM. Baseline and clinical characteristics &amp; in-hospital outcome of patients in both groups were assessed for comparison. Result This study included a total of 2506 confirmed COVID-19 positive patients. Of them 1003 (40%) patients had DM (Group-I) &amp; 1503 (60%) were without DM (Group-II). Diabetic COVID-19 positive patients were older (56.87 ±11.84 years vs 45.92 ± 16.91 years; p=0.001) and had more co-morbidities (p= 0.001) than patients without DM. Only 4.2% healthcare personnel had DM. Diabetic patients (G-I) had more risk factors and comorbidities than non-diabetic patients (G-II): cardiovascular disease (90.4% vs 65.7%; p=0.001); hypertension (84.3% vs 41.4%; p=0.001); chronic kidney disease (47.7% vs 29.8%;p=0.001); smoking (37.8% vs 25.9%; p=0.001); dyslipidemia (37.2% vs 17.4%;p=0.001); and chronic obstructive pulmonary disease/bronchial asthma (7.5% vs 4.3%; p=0.001). Most of the patients with DM (G-I) were symptomatic (77.5% vs 66.7%; p=0.001). Shortness of breath was significantly higher in diabetic patients (44.8% vs 30.6%; p=0.001). Sore throat (12.0% vs 2.9%; p=0.001), diarrhea (5.4% vs 1.2%; 0.001), anosmia (10.6% vs 3.8%; p=0.001), and headache (16.5% vs 8.8%; p=0.001) were significantly higher in Group-II patients. Diabetic patients had more severe form of COVID-19 disease {(moderate: 3.5% vs 1.4%; p=0.001), (severe: 9.5% vs 4.1%; p=0.001), and (critical ill: 1.3% vs 0.4%; p=0.01)}.Most of the diabetic patients were hospitalized (52.0% vs 29.6%; p=0.001) and most of the non-diabetic patients were treated either in home isolation or in institutional isolation (70.4% vs 48.0%; p=0.001). COVID-19 patients with DM had worse outcome than patients without DM (mortality rate- 6.1% vs 2.6%; p=0.001). Conclusion COVID-19 diabetic patients were usually older, have more comorbidities, a higher probability of hospitalization, increased risk of severe/critical COVID-19 and associated with higher mortality rate as compared with patients without DM. Bangladesh Heart Journal 2024; 39(2): 108-116

Time in Therapeutic Range of Unfractionated Heparin-Based Therapy in Critically Ill Patients with COVID-19 Pneumonia.

Anticoagulation therapy aims to improve the outcome of critically ill patients with severe COVID-19-associated pneumonia. Activated partial thromboplastin time (aPTT) is commonly used to maintain the target therapeutic range of continuous infusion of unfractionated heparin (UFH). The UFH infusion efficacy can be evaluated by determining the time in therapeutic range (TTR) using a modified Rosendaal method. The present study's primary aim was to evaluate TTR based on the aPTT in critically ill patients with severe forms of COVID-19 pneumonia and its influence on survival. The secondary aim was to evaluate the time spent above (TATR) and below the therapeutic range (TBTR). We performed a retrospective analysis of critically ill patients with COVID-19-associated pneumonia. All patients received a continuous infusion of UFH from the 2nd to 8th day since admission to the ICU. TTR, TATR, and TBTR were calculated using the modified Rosendaal method, and survival days were analyzed by regression (censored after 60 days). Of 103 patients, the median TTR was 49% (IQR 38-63%), TATR 11% (IQR 5-20%), and TBTR 33% (IQR 22-51%). The regression analysis indicated a positive impact of higher TTR and TATR on the number of survival days [β=0.598 (p=0.0367) and β=1.032 (p=0.0208), respectively] and a negative impact of higher TBTR [β=-0.681 (p=0.0033)] on the number of survival days. Higher TTR and TATR were associated with better survival of critically ill patients with a severe course of COVID-19-associated pneumonia. Higher TBTR was associated with worse survival in these patients.

Averrhoa carambola Leaf Extract Induces Apoptosis-Like Death with Increased ROS Generation in Leishmania donovani.

The parasitic disease leishmaniasis is responsible for high mortality and morbidity rates worldwide. The visceral form is the most severe form of leishmaniasis (or leishmaniosis), which is caused predominantly by Leishmania donovani. Currently, clinically recommended antileishmanial drugs are not convenient because of several medical complications and resistance issues. Phytocompounds are the best candidates in this regard. The present study aimed to evaluate the antileishmanial activity of Averrhoa carambola leaf extract. The antipromastigote activity and cytotoxicity were assessed using the MTT assay. Morphological distortions were determined using phase contrast microscopy and scanning electron microscopy (SEM). Reactive oxygen species (ROS) production, nonprotein thiol depletion and apoptotic death in promastigotes were determined via flow cytometry. UV-visible spectroscopy and energy dispersive X-ray (EDX) spectroscopy was performed for elemental analysis. Fourier-transform infrared spectroscopy (FTIR) and liquid chromatography‒mass spectrometry (LCMS) were used to characterize the phytocomponent(s) present in the extract. The chloroform extract of Averrhoa carambola leaf (ACCEX) (IC50 = 50.76 ± 1.7µg/mL) exhibited the highest activity, followed by the ethyl acetate, hexane, and methanol extracts. ACCEX has also exhibited lower toxicity towards host macrophages. ACCEX also induced morphological distortions in promastigotes, with significant generation of ROS and the concomitant apoptosis initiation followed by a decrease in the nonprotein thiol level. The major phytometabolites present in ACCEX were identified from the National Institute of Standards and Technology (NIST) database and from a literature review. This study suggested that Averrhoa carambola leaf extracts are rich in some classes of biologically active phytocompounds and exhibit good antileishmanial activity.