A comprehensive review of Wolbachia-mediated mechanisms to control dengue virus transmission in Aedes aegypti through innate immune pathways.

The Dengue virus (DENV), primarily spread by Aedes aegypti and also by Aedes albopictus in some regions, poses significant global health risks. Alternative techniques are urgently needed because the current control mechanisms are insufficient to reduce the transmission of DENV. Introducing Wolbachia pipientis into Ae. aegypti inhibits DENV transmission, however, the underlying mechanisms are still poorly understood. Innate immune effector upregulation, the regulation of autophagy, and intracellular competition between Wolbachia and DENV for lipids are among the theories for the mechanism of inhibition. Furthermore, mainly three immune pathways Toll, IMD, and JAK/STAT are involved in the host for the suppression of the virus. These pathways are activated by Wolbachia and DENV in the host and are responsible for the upregulation and downregulation of many genes in mosquitoes, which ultimately reduces the titer of the DENV in the host. The functioning of these immune pathways depends upon the Wolbachia, host, and virus interaction. Here, we summarize the current understanding of DENV recognition by the Ae. aegypti's immune system, aiming to create a comprehensive picture of our knowledge. Additionally, we investigated how Wolbachia regulates the activation of multiple genes associated with immune priming for the reduction of DENV.

Corneal Deposits Following Combined Gatifloxacin and Prednisolone Therapy Post-Keratoplasty: A Report of a Rare Case.

Corneal deposits associated with topical medications, particularly fluoroquinolones, are a recognized complication in ophthalmic practice. We present a case of a 66-year-old female with pseudophakic bullous keratopathy who developed corneal crystalline deposits following prolonged use of gatifloxacin and prednisolone eye drops post-penetrating keratoplasty. The patient presented with diminished vision and significant corneal opacity in the affected eye. Anterior segment examination and OCT imaging confirmed deposits extending from the epithelium to the anterior stroma. Management included corneal scrapping and transition to topical tobramycin and propylene glycol eye drops, resulting in the resolution of deposits and improvement in vision. This case underscores the importance of vigilant monitoring and judicious use of topical medications to mitigate adverse effects in high-risk ophthalmic patients undergoing corneal procedures.

Rare Instances of Culture-Positive Dengue-Related Panophthalmitis: A Case Series.

Panophthalmitis is an exceptionally rare but severe ocular complication of dengue fever, which is currently a significant health concern in parts of India. It is a purulent inflammation encompassing all structures of the globe (choroid, retina, vitreous fluid, aqueous fluid, cornea, sclera, and conjunctiva) along with surrounding orbital and periorbital structures. This case series highlights the occurrence of panophthalmitis in three patients diagnosed with dengue, who were aged 35, 50, and 75 years. Despite aggressive medical management, including intravenous antibiotics, the patients were ultimately scheduled for evisceration surgery due to the extreme severity of the condition. Healthcare providers must be aware of the potential ocular complications in dengue cases and diagnose them promptly. While ocular involvement in dengue is rare, this case series emphasizes the importance of recognizing ocular manifestations in dengue patients, as early diagnosis and prompt intervention can prevent severe complications.

Unlocking the Therapeutic Symphony: A Systematic Review Exploring the Role of Levosimendan in the Management of Heart Failure.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emerged as a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) in non-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

Alcohol Endotheliitis: A Report of a Rare Case.

Sudden transient loss of vision after an acute bout of alcohol consumption in patients with chronic alcoholism is rare. The underlying mechanism is a transient depression of the endothelial pump due to ethanol toxicity following a large amount of alcohol consumption in chronic alcoholic patients. Here, we report a rare case of a 60-year-old male patient who came to the outpatient department with complaints of sudden loss of vision associated with redness following a large amount of alcohol consumption. The case was managed by prompt diagnosis and topical and oral corticosteroid therapy. This is a rare case of acute toxic endotheliitis due to ethanol toxicity with only a few cases reported in the past.

MicroRNA-452-5p regulates fibrogenesis via targeting TGF-ß/SMAD4 axis in SCN5A-knockdown human cardiac fibroblasts.

The mutated SCN5A gene encoding defective Nav1.5 protein causes arrhythmic ailments and is associated with enhanced cardiac fibrosis. This study investigated whether SCN5A mutation directly affects cardiac fibroblasts and explored how defective SCN5A relates to cardiac fibrosis. SCN5A knockdown (SCN5AKD) human cardiac fibroblasts (HCF) had higher collagen, α-SMA, and fibronectin expressions. Micro-RNA deep sequencing and qPCR analysis revealed the downregulation of miR-452-5p and bioinformatic analysis divulged maladaptive upregulation of transforming growth factor ß (TGF-ß) signaling in SCN5AKD HCF. Luciferase reporter assays validated miR-452-5p targets SMAD4 in SCN5AKD HCF. Moreover, miR-452-5p mimic transfection in SCN5AKD HCF or AAV9-mediated miR-452-5p delivery in isoproterenol-induced heart failure (HF) rats, resulted in the attenuation of TGF-ß signaling and fibrogenesis. The exogenous miR-452-5p significantly improved the poor cardiac function in HF rats. In conclusion, miR-452-5p regulates cardiac fibrosis progression by targeting the TGF-ß/SMAD4 axis under the loss of the SCN5A gene.

A Case of Horner's Syndrome Aiding the Diagnosis of Internal Carotid Artery Dissection (ICAD): A Life-Saving Twist of Fate.

A 59-year-old male patient came to the outpatient department with complaints of left-sided hemicranial headache with drooping of the left upper eyelid (UL) for three days associated with difficulty in swallowing and deviation of the tongue. The patient had a history of vigorous coughing for the past 15 days for which he did not take any medications. He was thoroughly evaluated in the outpatient department and diagnosed with Horner's syndrome. Acute Horner's syndrome with pain is nearly a hallmark of carotid dissection, and MRI of the brain and orbit was thus advised. On MRI, a hyperdense area was noted around the left internal carotid artery for which he was advised magnetic resonance angiography, which revealed internal carotid artery dissection (ICAD) of the left side. The patient was diagnosed with left-sided Horner's syndrome following left ICAD with involvement of the left hypoglossal nerve. He was started on antiplatelets and anticoagulants and closely followed up. Early diagnosis and prompt treatment were lifesaving for this patient.

A Study of the Demographic Profile, Screening, and Management of Patients Visiting a Retinopathy of Prematurity Clinic.

Background and objective Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease affecting premature infants. Despite improvements in neonatal care and management, ROP still remains a major cause of childhood blindness worldwide. Studying the demographic profile and screening is essential to develop predictive models, to gain insights into the cause of retinal vascular diseases and diseases of prematurity, and to determine the future management and research in ROP. The objective of the present study was to estimate the incidence of ROP, to identify the risk factors that predispose to ROP, and to assess the outcome of these cases. Hence, this study was conducted in a tertiary care hospital in Maharashtra. Method A prospective, observational study was conducted from 10 August 2022 to 10 October 2022. Infants with gestational ages < 34 weeks, birth weights < 2000 g, infants who received supplemental oxygen therapy, or patients who required NICU stay were screened for ROP. Demographic details were recorded to assess the risk factors and treatment was given according to the severity of ROP grade. Result A total of 160 eyes of 80 infants were screened and analysed. The overall incidence of "any ROP" was 19 patients (38 eyes), i.e., 24%. Out of 80 patients, six were of 28 weeks gestational age, of whom four (67%) were positive for ROP. The mean birth weight of infants with ROP was 1331.58 ± 238.532 g (p < 0.0001). ROP stage 1 was seen in five patients (26.32%), stage 2 in 10 patients (52.63%), and stage 3 in four patients (21.0%), with no subjects in stages 4 & 5. Out of 19 patients, six (32%) had type 1 ROP, and 13 (68%) had type 2 ROP. Out of 19 cases, 13 (68%) received follow-up care based on the severity of their disease, and six (32%) were treated with panretinal photocoagulation (PRP) laser. Conclusion Incidence of any ROP was 24%. Prematurity, low birth weight, and oxygen therapy remain the most significant risk factors associated with the development of ROP. Early referral, diagnosis, and timely intervention will play a monumental role in improving the prognosis of this potentially blinding disease.

A Rare Case of Pseudoxanthoma Elasticum Identified by Ocular Angioid Streaks.

A 42-year-old female with a known case of hypertension for three years, symptoms of metamorphopsia, and decreased vision in both eyes reported to the ophthalmology outpatient department. There was no recorded history of ocular injury or surgery. Several observational techniques, such as fundus inspection, fundus camera photography, and optical coherence tomography (OCT), were utilized to assess the patient. We referred her to the Department of Dermatology for additional assessment because of her symptoms as well as the appearance of her neck's skin, which matched "plucked chicken skin." There, the diagnosis of pseudoxanthoma elasticum (PE) was confirmed. She was subsequently scheduled for an intravitreal bevacizumab injection called Avastin, which improved her visual acuity.

Updates on traditional methods for combating malaria and emerging Wolbachia-based interventions.

The escalating challenge of malaria control necessitates innovative approaches that extend beyond traditional control strategies. This review explores the incorporation of traditional vector control techniques with emerging Wolbachia-based interventions. Wolbachia, a naturally occurring bacteria, offers a novel approach for combatting vector-borne diseases, including malaria, by reducing the mosquitoes' ability to transmit these diseases. The study explores the rationale for this integration, presenting various case studies and pilot projects that have exhibited significant success. Employing a multi-dimensional approach that includes community mobilization, environmental modifications, and new biological methods, the paper posits that integrated efforts could mark a turning point in the struggle against malaria. Our findings indicate that incorporating Wolbachia-based strategies into existing vector management programs not only is feasible but also heightens the efficacy of malaria control initiatives in different countries especially in Pakistan. The paper concludes that continued research and international collaboration are imperative for translating these promising methods from the laboratory to the field, thereby offering a more sustainable and effective malaria control strategy.

Maternal hygiene and knowledge on complementary feeding during infancy and early childhood in Lahore, Pakistan.

Objectives: To assess practice and knowledge levels regarding complementary feeding among mothers of infants. METHODS: The analytical cross-sectional study was conducted in CMH Lahore Medical College & Institute of Dentistry, Cantonment, Lahore, Pakistan, from December 2021 to April 2022, and comprised mothers of children aged 6-24 months. Data was collected using a self-administered questionnaire exploring hygiene practices and knowledge related to complementary feeding. Data was analysed using SPSS 23. RESULTS: Of the 117 mothers with mean age 38.5±27.3 years, 115(98.3%) were married and 97(82.9%) resided in urban settings. Among the infants, 70(59.8%) were aged 12-24 months, 55(47%) were first-born, 72(61.5%) were exclusively breastfed for the first 6 months and 45(38.5%) continued breastfeeding along with complementary feeding after 6 months. Hygiene practices correlated to both marital status and the type of family (pa;lt;0.05). A significant association was found between mother's occupation to breastfeeding and hygiene practices (pa;lt;0.05). There was no significant association of breastfeeding practices with maternal age and maternal education (p>0.05). CONCLUSIONS: Maternal information related to complementary feeding was found to be good, and breastfeeding practices were significantly associated with the mother's occupation. Maternal hygiene practices were also good, and were significantly associated with the mother's occupation and type of family.

2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent Pathway in Zebrafish Larvae.

Previous studies have reported the feminizing effects of 2,4-dichlorophenol (2,4-DCP) on zebrafish (Danio rerio). However, the effect of 2,4-DCP on the number of primordial germ cells (PGCs), an indicator for early sex differentiation, remains elusive. In the present study, Tg (piwil1:egfp-UTR nanos3) zebrafish (GFP-labeled PGCs) were treated with 2,4-DCP (10, 20, and 40 µg/L) from 5 to 15 days postfertilization to explore the effect on PGC numbers and to elucidate associated molecular mechanisms. The results showed that 2,4-DCP exposure increased PGC numbers, as evidenced by larger GFP fluorescent areas, upregulated expressions of PGC marker genes (vasa and dnd), and raised the female ratio. Notably, the mRNA level of estrogen receptor 2a (esr2a) was also increased subsequently. Moreover, docking studies revealed stable 2,4-DCP interactions with ESR2a, speculating a role of ESR2a signaling pathway in 2,4-DCP toxicity. Furthermore, in esr2a knockout (esr2a-/-) zebrafish, the effects of 2,4-DCP were considerably minimized, proving the involvement of the ESR2a signaling pathway in the 2,4-DCP-mediated increase in PGC numbers. Dual-luciferase reporter gene assay and point mutation studies demonstrated that 2,4-DCP-stimulated promoter activity was mediated by estrogen response element (ERE) located in -686/-674 of the vasa promoter and -731/-719 of the dnd promoter. Overall, 2,4-DCP can potentially enhance the expression of vasa and dnd by binding to zebrafish ESR2a, thus leading to increased PGC numbers and subsequent female-biased sex differentiation.

Indicators Of Hepatopulmonary Syndrome In Patients With Portal Hypertension. Its Various Aetiologies, Clinical Presentations And Outcome.

BACKGROUND: Hepatopulmonary syndrome is severe pulmonary vascular complication of chronic liver disease requiring liver transplant. This study was conducted to evaluate different indicators of HPS in patients with portal hypertension, its varied aetiologies, clinical features & outcome. METHODS: Hospital based descriptive study, 203 patients were enrolled, divided in to 2 groups positive and negative on the basis of presence or absence of HPS as per diagnostic criteria. RESULTS: It included 203 patients with portal Hypertension of varied aetiologies. Age range was 8.76±3.69 years. 54.7% were male & 45.3% female. Commonest diagnosis for portal hypertension was portal vein thrombosis in 48 (23.6%) while Least common was biliary atresia seen in 6 (3%) of cases. Fifteen patients were included in Positive group and 188 in negative group. Clinical & laboratory parameters in order of frequency in positive group were hypoxia & cyanosis in 100% & 93.3% followed by dyspnoea & grade 4 clubbing in 86.6% patients (p<0.001). Child scoring was also done in all patients. In negative group 7 (3.7%) had dyspnoea, I (0.53%) had grade 4 clubbing while none showed evidence of hypoxia or cyanosis (p<0.001). Three patients underwent successful liver transplant. One patient of biliary atresia & another of CHF expired. CONCLUSIONS: In All children with CLD and/or PHT with unexplained dyspnoea, cyanosis and grade 4 clubbing, HPS should be suspected. It is an indication for early LT even in absence of liver failure.

Targeting EHMT2/ G9a for cancer therapy: Progress and perspective.

Euchromatic histone lysine methyltransferase-2, also known as G9a, is a ubiquitously expressed SET domain-containing histone lysine methyltransferase linked with both facultative and constitutive heterochromatin formation and transcriptional repression. It is an essential developmental gene and reported to play role in embryonic development, establishment of proviral silencing in ES cells, tumor cell growth, metastasis, T-cell immune response, cocaine induced neural plasticity and cognition and adaptive behavior. It is mainly responsible for carrying out mono, di and tri methylation of histone H3K9 in euchromatin. G9a levels are elevated in many cancers and its selective inhibition is known to reduce the cell growth and induce autophagy, apoptosis and senescence. We carried out a thorough search of online literature databases including Pubmed, Scopus, Journal websites, Clinical trials etc to gather the maximum possible information related to the G9a. The main messages from the cited papers are presented in a systematic manner. Chemical structures were drawn by Chemdraw software. In this review, we shed light on current understanding of structure and biological activity of G9a, the molecular events directing its targeting to genomic regions and its post-translational modification. Finally, we discuss the current strategies to target G9a in different cancers and evaluate the available compounds and agents used to inhibit G9a functions. The review provides the present status and future directions of research in targeting G9a and provides the basis to persuade the development of novel strategies to target G9a -related effects in cancer cells.

Haemobilia: secondary to micro aneurysms of hepatic artery.

Hepatic artery is the fourth most common site of the intraabdominal aneurysm, after infra renal aorta, iliac artery and splenic artery aneurysms. Rupture of the aneurysm may lead to the upper gastrointestinal haemorrhage. Here we report a 5 years old boy, who presented with fever, abdominal distension and unexplained upper GI bleed. Upper GI endoscopy revealed a normal esophagus and stomach with clear evidence of haemobilia with blood oozing from the ampulla. Fluoro- guided angiography followed by embolization of hepatic artery branches with 5 metallic coils was performed in this case by an interventional radiologist.

Is Hepatovenocaval Syndrome a Different Entity from Budd-Chiari Syndrome in Children?

OBJECTIVE: To differentiate between clinical and demographic spectrum, and outcome in hepatovenocaval syndrome (HVCS) and Budd-Chiari syndrome (BCS). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Children Hospital, Lahore, from January 2014 to January 2017. METHODOLOGY: All children less than 18 years of age, presenting with ascites and visible veins over abdomen, flanks and back were enrolled in the study. Real time Doppler Ultrasonogram was performed in all children for documentation of intra- hepatic part of IVC obstruction along with or without hepatic venous obstruction. Children meeting inclusion criteria underwent liver profile, coagulation profile, diagnostic paracentesis for SAAG gradient, and Gadolinium enhanced multiphasic MR scan. Liver biopsy and venography was performed in selected patients. RESULTS: A total of 92 children presented with ascites, among them 58 children met our inclusion criteria. Intrahepatic IVC obliteration, i.e. HVCS, found in 67% (n=39) and hepatic venous outflow obstruction, i.e. BCS was found in 33% (n=19) children. Children with BCS were older than HVCS with mean age of 9.5 ±2.58 versus 4.12 ±0.977 years. HVCS group had 14 boys and 24 girls with a ratio of 1:1.8, while BCS had a ratio of 1:0.9 with 10 boys and 9 girls. No etiological factor was found for HVCS, while most of patients with BCS had a procoagulant disorder. Caudate lobe hypertrophy was a consistent feature in BCS, while IVC obstruction was found in HVCS persistently. Orthotopic liver transplant was needed in three cases (7.6%) of HVCS and four (20.96%) of BCS cases. Antibiotic therapy has a good role in HVCS, while anticoagulation and diuretics had good result in BCS. CONCLUSION: Hepatovenocaval syndrome (HVCS) mostly affected younger children, especially girls. BCS usually affected older age groups with pro-coagulant disorders who responded to anticoagulation and diuretic. Further studies are needed to compare both conditions.

Berardinelli-Seip Congenital Generalised Lipodystrophy.

Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is a rare genetic disorder caused by dysregulation of glycemic and lipid metabolism. We report five BSCL cases with typical clinical pictures and complications. These, to the best of our knowledge, represent the first case series from Pakistan. BSCL is characterized by marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. We could not perform genetics studies in any patient owing to non-availability of genetic laboratory in Pakistan. All the cases presented hypertriglyceridemia. One case developed hyperinsulinism controlled with metformin. There is no curative treatment and the current approach is low-fat diet and management of insulin resistance and diabetes. Recently published studies showed that leptin-replacement therapy is promising in the metabolic correction of complications of BSCL. This highlights the importance of further research in BSCL treatment.

Causes Of Chronic Non-Infectious Diarrhoea In Infants Less Than 6 Months Of Age: Rarely Recognized Entities.

BACKGROUND: Non-infectious causes of chronic diarrhoea are important and easily missed. The study was done with the objectives to identify different causes of chronic non-infectious diarrhoea in infants less than 6 months of age. METHODS: All patients less than 6 months of age presenting for the first time to a Paediatric Gastroenterology tertiary care centre with a history of chronic diarrhoea and negative stool cultures were enrolled over a period of 8 months. Demographical profile and various factors under observation were recorded in this observational study. Collected data was analysed using SPSS version 20. Chi square test was applied as a test of significance for any qualitative variable, p value (p<0.05) was taken as significant. RESULTS: Among 72 enrolled patients, female to male ratio was1.05:1. Age at onset of symptoms was between 15 days to 6 months. Aetiology found was Cow's milk protein allergy (CMPA) in 58 (80.6%), Primary intestinal lymphangiectasia (PIL) 6 (8.3%), Cystic fibrosis (CF) 3 (4.2%), Immunodeficiency (SCID) 2 (2.8%), 1 (1.4%) for each Abetalipoproteinemia (ABL), Glucose galactose malabsorption (GGM) and Congenital chloride diarrhoea (CCD). CONCLUSIONS: Among noninfectious causes of chronic diarrhoea in early infancy, cow's milk protein allergy is most common followed by Primary intestinal lymphangiectasia and Cystic fibrosis.

Mucopolysaccharidoses - Clinical Spectrum and Frequency of Different Types.

OBJECTIVE: To determine the relative frequency and clinical features of different varieties of mucopolysaccharidosis. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital and The Institute of Child Health, Lahore, from January 2013 to December 2015. METHODOLOGY: All patients who had any feature suggestive of mucopolysaccharidosis were screened with detailed history, clinical examination and skeletal survey. Urine samples for glycosaminoglycan (GAGs) levels and dried blood samples for enzyme analysis were sent. Patients who were confirmed to be suffering from mucopolysaccharidosis were included in the study. The data was analysed using SSPS version 20. RESULTS: A total of 90 confirmed MPS cases, 52 males and 38 females, median age 42 months, were included. Hurler/Hurler-Scheie syndrome was the most frequent (75, 83.33%) followed by Morquio (6, 6.67%), Sanfilippo (5, 5.56%), Maroteaux-Lamy (3, 3.33%) and Hunter (1, 1.11%) syndromes. Consanguinity was present in 79 (87.78%) cases. Common features were hepatomegaly (80, 88.89%), coarse facies (70, 77.78%), splenomegaly (67, 74.44%), and bone disease (48, 53.33%). CONCLUSION: Most common variety of mucopolysaccharidosis was Hurler/Hurler Scheie followed by Morquio syndrome. Most of the patients were born to consanguineous parents. Common clinical features were coarse facies, hepatosplenomegaly and dysostosis multiplex.