Common Cause Research Articles

A chemical screen identifies structurally diverse metal chelators with activity against the fungal pathogen Candida albicans.

Candida albicans, one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against C. albicans is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug's target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a C. albicans clinical isolate and identified 17 molecules that inhibited C. albicans growth by >80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans Candida, including Candida auris and Candida glabrata, with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould Aspergillus fumigatus. Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued C. albicans growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen C. albicansIMPORTANCEThe worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen Candida albicans is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against C. albicans. Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including Candida auris and Aspergillus fumigatus. Finally, we determined that these compounds inhibit the growth of C. albicans in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.

International survey of equine orthopaedic specialists reveals diverse treatment strategies for horses with overriding spinous processes.

Overriding spinous processes, also known as 'kissing spines', are one of the most common causes of back pain in horses. The aim of this study was to investigate which options for diagnosis and treatment are preferred by equine orthopaedic specialists and assess which techniques are used for local injection. An online survey was distributed among members of the European/American College of Veterinary Surgeons, the European/American College of Veterinary Sports Medicine and Rehabilitation, the International Society of Equine Locomotor Pathology and nationally recognised advanced equine orthopaedic practitioners. The survey was completed by 353 respondents. The injection techniques most commonly used involve placing two needles abaxial to the interspinous space (42%) under ultrasonographic guidance (32%) or one needle in the midline (35%) between two spinous processes. The most popular combination for overriding dorsal spinous process therapy was local injection (26.7%) combined with controlled exercise (25.5%). Manual therapy was considered by 42% of European and 25% of American specialists (p = 0.01). Surgical intervention as a first-line treatment was recommended mainly by specialists working in the United States, the UK or Ireland (p = 0.001). Overall, most equine orthopaedic veterinarians (71%; n = 201) preferred conservative management and recommended surgery only for horses that did not respond to conservative therapy. Respondents' personal bias may have skewed the findings. Despite a growing body of evidence, the therapeutic approach to 'kissing spines' in horses is influenced by professional specialisation and regional preferences. Variations in injection techniques and differing criteria for surgical intervention warrant further investigation.

The Frequency of Death Associated with Burn Injury in General Population of Peshawar City

Background: Burn injuries represent a significant public health issue worldwide, with a notably higher incidence and mortality rate in low and middle-income countries. These injuries are characterized by their devastating physical, psychological, and economic impacts on victims and their families. In Peshawar city, the lack of comprehensive data on burn-related deaths has hindered effective prevention and management strategies. Objective: This study aims to provide a demographic profile of burn-related deaths in Peshawar city, focusing on the factors influencing these fatalities and the manner of death, to inform better clinical practices and preventive measures. Methods: A retrospective study was conducted in the burn and trauma unit of Hayatabad Medical Complex, Peshawar, from May 1, 2021, to May 1, 2022. Data on 80 cases of death due to burns were collected and analyzed, categorizing by age, sex, cause of injury, nature and extent of burns, total body surface area (TBSA) affected, toxicological findings, location of the incident, duration of survival post-injury, and mechanism of death. The study adhered to the Declaration of Helsinki principles, with ethical approval obtained from the institutional review board. Results: The study found that out of 80 burn-related deaths, 70% (56 cases) were females and 30% (24 cases) were males. The highest number of fatalities was observed in individuals under 12 years, comprising 28.75% of the cases. Accidental burns were the leading cause of death, with more than 60% of incidents falling into this category. The average TBSA affected in fatal cases was significant, emphasizing the severity of injuries leading to mortality. Conclusion: Burn-related fatalities in Peshawar city predominantly affect females and young children, with accidental burns being the most common cause. This underscores the necessity for targeted preventive strategies, public awareness campaigns, and improvements in burn care facilities to address the high incidence and mortality rates of burn injuries in the region.

The pomegranate-derived peptide Pug-4 alleviates nontypeable Haemophilus influenzae-induced inflammation by suppressing NF-kB signaling and NLRP3 inflammasome activation.

The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is the most common cause of exacerbation of chronic obstructive pulmonary disease (COPD), of which an excessive inflammatory response is a hallmark. With the limited success of current medicines there is an urgent need for the development of novel therapeutics that are both safe and effective. In this study, we explored the regulatory potential of pomegranate-derived peptides Pug-1, Pug-2, Pug-3, and Pug-4 on NTHi-induced inflammation. Our results clearly showed that to varying degrees the Pug peptides inhibited NTHi-induced production of IL-1β, a pivotal cytokine in COPD, and showed that these effects were not related to cytotoxicity. Pug-4 peptide exhibited the most potent inhibitory activity. This was demonstrated in all studied cell types including murine (RAW264.7) and human (differentiated THP-1) macrophages as well as human lung epithelial cells (A549). Substantial reduction by Pug-4 of TNF-α, NO and PGE2 in NTHi-infected A549 cells was also observed. In addition, Pug-4 strongly inhibited the expression of nuclear-NF-κB p65 protein and the NF-κB target genes (determined by IL-1β, TNF-α, iNOS and COX-2 mRNA expression) in NTHi-infected A549 cells. Pug-4 suppressed the expression of NLRP3 and pro-IL-1β proteins and inhibited NTHi-mediated cleavage of caspase-1 and mature IL-1β. These results demonstrated that Pug-4 inhibited NTHi-induced inflammation through the NF-κB signaling and NLRP3 inflammasome activation. Our findings herein highlight the significant anti-inflammatory activity of Pug-4, a newly identified peptide from pomegranate, against NTHi-induced inflammation. We therefore strongly suggest the potential of the Pug-4 peptide as an anti-inflammatory medicine candidate for treatment of NTHi-mediated inflammation.

Defecatory disorders are a common cause of chronic constipation in Parkinson disease.

Up to 50% of patients with Parkinson disease have constipation (PD-C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD-C is unknown. We aimed to compare anorectal function of patients with PD-C versus idiopathic chronic constipation (CC). Anorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry (HR-ARM) in patients with PD-C and control patients with CC, matched for age and sex. We identified 97 patients with PD-C and 173 control patients. Eighty-six patients with PD-C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD-C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET. In the multivariate model comparing CC and PD-C (AUROC = 0.76), PD-C was associated with a lower anal squeeze increment (odds ratio [OR] for PD-C, 0.93 [95% CI, 0.91-0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03-1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66-0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08-1.26]). Compared with CC, PD-C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

The role of the C. albicans transcriptional repressor NRG1 during filamentation and disseminated candidiasis is strain dependent.

Candida albicans is one of the most common causes of superficial and invasive fungal diseases in humans. Its ability to cause disease is closely linked to its ability to undergo a morphological transition from budding yeast to filamentous forms (hyphae and pseudohyphae). The extent to which C. albicans strains isolated from patients undergo filamentation varies significantly. In addition, the filamentation phenotypes of mutants involving transcription factors that positively regulate hyphal morphogenesis can also vary from strain to strain. Here, we characterized the virulence, in vitro and in vivo filamentation, and in vitro and in vivo hypha-associated gene expression profiles for four poorly filamenting C. albicans isolates and their corresponding deletion mutants of the repressor of filamentation NRG1. The two most virulent strains, 57055 and 78048, show robust in vivo filamentation but are predominately yeast phase under in vitro hypha induction; the two low-virulence strains (94015 and 78042) do not undergo filamentation well under either condition. In vitro, deletion of NRG1 increases hyphae formation in the SC5314 derivative SN250, but only pseudohyphae are formed in the clinical isolates. Deletion of NRG1 modestly increased the virulence of 78042, which was accompanied by increased expression of hypha-associated genes without an increase in filamentation. Strikingly, deletion of NRG1 in 78048 reduced filamentation in vivo, expression of candidalysin (ECE1), and virulence without dramatically altering establishment of infection. Thus, the function of the conserved repressor NRG1 in C. albicans shows strain-based heterogeneity during infection.IMPORTANCEClinical isolates of the human fungal pathogen Candida albicans show significant variation in their ability to undergo in vitro filamentation and in the function of well-characterized transcriptional regulators of filamentation. Here, we show that Nrg1, a key repressor of filamentation and filament specific gene expression in standard reference strains, has strain-dependent functions, particularly during infection. Most strikingly, loss of NRG1 function can reduce filamentation, hypha-specific gene expression such as the toxin candidalysin, and virulence in some strains. Our data emphasize that the functions of seemingly fundamental and well-conserved transcriptional regulators such as Nrg1 are contextual with respect to both environment and genetic backgrounds.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

Use, failure, and non-compliance of respiratory personal protective equipment and risk of upper respiratory tract infections-A longitudinal repeated measurement study during the COVID-19 pandemic among healthcare workers in Denmark.

Upper respiratory tract infections (URTI) are common and a common cause of sick-leave for healthcare workers, and furthermore pose a threat especially for patients susceptible to other diseases. Sufficient use of respiratory protective equipment (RPE) may protect both the workers and the patients. The COVID-19 pandemic provided a unique opportunity to study the association between use of RPE and URTI in a real-life setting. The aim of this study was to examine if failure of RPE or non-compliance with RPE guidelines increases the risk of non-COVID-19 URTI symptoms among healthcare workers. In a longitudinal cohort study, we collected self-reported data daily on work tasks, use of RPE, and URTI symptoms among healthcare workers with patient contact in 2 Danish Regions in 2 time periods during the COVID-19 pandemic. The association between failure of RPE or non-compliance with RPE guidelines and URTI symptoms was analyzed separately by generalized linear models. Persons tested positive for severe acute respiratory syndrome coronavirus 2 were censored from the analyses. The 2 waves of data collection were analyzed separately, as there were differences in recommendations of RPE during the 2 waves. We found that for healthcare workers performing work tasks with a risk of transmission of viruses or bacteria, failure of RPE was associated with an increased risk of URTI symptoms, RR: 1.65[0.53-5.14] in wave 1 and RR: 1.30[0.56-3.03] in wave 2. Also non-compliance with RPE guidelines was associated with an increased risk of URTI symptoms compared to the use of RPE in wave 1, RR: 1.28[0.87-1.87] and wave 2, RR: 1.39[1.01-1.91]. Stratifying on high- versus low-risk tasks showed that the risk related to failure and non-compliance was primarily associated with high-risk tasks, although not statistically significant. The study was conducted during the COVID-19 pandemic and thus may be affected by other preventive measures in society. However, this gave the opportunity to study the use of RPE in a real-life setting, also in departments that did not previously use RPE. The circumstances in the 2 time periods of data collection differed and were analyzed separately and thus the sample size was limited and affected the precision of the estimates. Failures of RPE and non-compliance with RPE guidelines may increase the risk of URTI, compared to those who reported use of RPE as recommended. The implications of these findings are that the use of RPE to prevent URTI could be considered, especially while performing high-risk tasks where other prevention strategies are not achievable.

Adrenarche-accompanied rise of adrenal sex steroid precursors prevents NAFLD in Young Female rats by converting into active androgens and inactivating hepatic Srebf1 signaling

BackgroundNon-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease in children and adolescents, but its etiology remains largely unknown. Adrenarche is a critical phase for hormonal changes, and any disturbance during this period has been linked to metabolic disorders, including obesity and dyslipidemia. However, whether there is a causal linkage between adrenarche disturbance and the increasing prevalence of NAFLD in children remains unclear.ResultsUsing the young female rat as a model, we found that the liver undergoes a transient slowdown period of growth along with the rise of adrenal-derived sex steroid precursors during adrenarche. Specifically blocking androgen actions across adrenarche phase using androgen receptor antagonist flutamide largely increased liver weight by 47.97% and caused marked fat deposition in liver, thus leading to severe NAFLD in young female rats. Conversely, further administrating nonaromatic dihydrotestosterone (DHT) into young female rats across adrenarche phase could effectively reduce liver fat deposition. But, administration of the aromatase inhibitor, formestane across adrenarche had minimal effects on hepatic de novo fatty acid synthesis and liver fat deposition, suggesting adrenal-derived sex steroid precursors exert their anti-NAFLD effects in young females by converting into active androgens rather than into active estrogens. Mechanistically, transcriptomic profiling and integrated data analysis revealed that active androgens converted from the adrenal sex steroid precursors prevent NAFLD in young females primarily by inactivating hepatic sterol regulatory element-binding transcription factor 1 (Srebf1) signaling.ConclusionsWe firstly evidenced that adrenarche-accompanied rise of sex steroid precursors plays a predominant role in preventing the incidence of NAFLD in young females by converting into active androgens and inactivating hepatic Srebf1 signaling. Our novel finding provides new insights into the etiology of NAFLD and is crucial in developing effective prevention and management strategies for NAFLD in children.

Vitamin A deficiency impairs neutrophil-mediated control of Salmonella via SLC11A1 in mice

In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation. Immature neutrophils had reduced expression of Slc11a1, a gene that encodes a metal ion transporter generally thought to restrict pathogen growth in macrophages. Adoptive transfer of SLC11A1-proficient neutrophils, but not SLC11A1-deficient neutrophils, reduced systemic Salmonella burden in Slc11a1−/− mice or mice with vitamin A deficiency. Loss of terminal granulopoiesis regulator CCAAT/enhancer-binding protein ϵ (C/EBPϵ) also decreased neutrophil-mediated control of Salmonella, but not that mediated by peritoneal macrophages. Susceptibility to infection increased in Cebpe−/−Slc11a1+/+ mice compared with wild-type controls, in an Slc11a1-expression-dependent manner. These data suggest that SLC11A1 deficiency impairs Salmonella control in part by blunting neutrophil-mediated defence.

Prevalence and predictors of hypercoagulability detected by rotational thromboelastometry in peritoneal malignancy patients undergoing cytoreductive surgery

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for peritoneal malignancy. A hypercoagulable state in these patients and the associated risk of venous thromboembolism (VTE), remains the most common cause of 30-day mortality. This study aimed to evaluate the prevalence and perioperative factors associated with baseline hypercoagulability detected by rotational thromboelastometry (ROTEM), a point-of-care haemostatic assay, in peritoneal malignancy patients. Methods: A retrospective cohort study was performed in a peritoneal malignancy unit on patients undergoing CRS between 2019 and 2023, who underwent preoperative ROTEM testing. Patients were divided into group A (hypercoagulable) and Group B (normal coagulation). Baseline characteristics, pathology results, operative details and post operative outcomes were reviewed. Univariate and multivariate analysis were used to identify factors associated with baseline hypercoagulability. Results: The 70 patients were included, 23 patients in group A (32.9%) and 47 patients in group B (67.1%). Group A had a lower preoperative haemoglobin (p&lt;0.001), higher platelet count (p&lt;0.001) and median peritoneal carcinomatosis index (33 vs 10, p=0.003). Appendiceal primary was associated with hypercoagulability (47.8% vs 23.4%, p=0.039). Group A required more intraoperative transfusion with red blood cells (p=0.014) but not platelets (p=0.6) or cryoprecipitate (p=0.8). Although group A had a higher incidence of VTE events (30.4% vs 23.4%) this was not statistically significant. Conclusions: Baseline hypercoagulability exists in one-third of patients with peritoneal malignancy and was associated with increased tumour burden and appendiceal primary. The increasing use of ROTEM is a valuable tool for perioperative management of complex peritoneal malignancy patients.

Bronchogenic carcinoma: the added value of FDG PET/CT advanced volumetric and metabolic parameters in initial evaluation and their impact on prognosis and clinical outcome

Abstract Background Bronchogenic carcinoma is considered to be one of the most common causes of cancer-related mortalities. It is divided into two main subtypes; small cell and non-small cell carcinoma. CT is considered the most commonly used radiological modality for early detection and staging. PET/CT can efficiently give both structural and functional information about the tumoral mass and malignant activity overall the body and hence can accurately assess the tumor staging and tumor response to therapy. Our study aim was to evaluate the different 18F-FDG PET/CT advanced volumetric and metabolic parameters in initial staging of bronchogenic carcinoma and their capability to predict the impact on prognostic pathway and hence the clinical outcomes. Results Forty patients with pathologically proven bronchogenic carcinoma were included in this study, and all of them did PET/CT in which different volumetric and metabolic parameters were measured and showed significant differences in different tumor grades. Conclusion PET/CT can give both structural and functional data about the tumor mass adding to its proper assessment of the initial evaluation and predicting its prognostic pathway.

Management of stage III non-small-cell lung cancer: rays of hope.

Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.

Revisiting the Blocksom Vesicostomy Technique in a very sick child with Bilateral high-grade VUR: A Case Report

Vesicoureteric reflux (VUR) is a common cause of repeated urinary tract infections (UTIs) in children. Vesicostomy is considered in selective cases of high grade as an initial temporary procedure to effectively empty the bladder, prevent urinary stasis and chances of reflux, and reduce the incidence of UTI, thereby protecting the upper tracts. The most commonly followed temporary urinary diversion procedure is the one described by Blocksom in 1957. The method is simple, effective, and easy to perform, reversible, protects the upper tracts, and minimizes the incidence of UTIs. Keywords: Vesicoureteric Reflux, Temporary Urinary Diversion, Vesicostomy, Blocksom Vesicostomy, Reversible.

Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms

Introduction/ObjectivesMutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. Methods, Results and ConclusionsWe present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

Association between MTHFR C677T polymorphism and cognitive impairment in patients with cerebral small vessel disease: a cross-sectional study.

Cerebral small vessel disease (CSVD) is the most common vascular cause of cognitive impairment. This study aimed to explore the association between MTHFR C677T polymorphism and cognitive impairment in CSVD patients. Demographic, medical, laboratory, cognitive evaluation, and MTHFR C677T polymorphism data were collected from CSVD patients admitted to our hospital between January 2019 and July 2023. Inclusion criteria for CSVD were based on the Standards for Reporting Vascular changes on Neuroimaging (STRIVE) criteria, with age ≥ 45 years. Binary logistic regression models were used to analyze risk factors associated with WMH and cognitive impairment. A total of 330 CSVD participants were recruited in this study, including 179 male and 151 female, with a median age of 64 years (interquartile range: 58-73 years). There were 185 patients (56.1%) with cognitive impairment, 236 patients (71.5%) with WMH, 89 patients (27.0%) with CMB, 87 patients (26.4%) with lacunes. All participants completed MTHFR polymorphism analysis, 149 cases (45.2%) of the CC genotype, 112 cases (33.9%) of the CT genotype and 69 cases (20.9%) of the TT genotype. Patients with TT genotype exhibited higher plasma homocysteine levels and more severe WMH and cognitive impairment (p < 0.001). Multivariable binary logistic regression model showed that WMH was significantly associated with age (p = 0.019), history of hypertension (p = 0.011), HHcy (p = 0.019) and MTHFR genotype (p = 0.041); while cognitive impairment was significantly associated with age (p = 0.033), history of hypertension (p = 0.019), HHcy (p = 0.040), MTHFR genotype (p = 0.039), WMH (p = 0.041), and lacunes (p = 0.001). In this cross-sectional study, we investigated the association between MTHFR C677T polymorphism and cognitive function in CSVD patients. We found that MTHFR 677 TT genotype was an independent risk factor for the progression of WMH and cognitive impairment in CSVD patients.

Role of nasal endoscopy in evaluation and management of epistaxis

Background: Epistaxis is the most common ENT emergency. The localization of bleeding site and its control in profuse epistaxis is of major concern for the ENT surgeon. Nasal endoscope has proved to be a boon for the otolaryngologist and is an important tool in diagnosing these bleeding points and their immediate management which reduces the incidence of nasal packing either anterior or posterior. Aim was to study the importance of nasal endoscopy in diagnosing the cause and site of epistaxis and managing them appropriately. Methods: It was a prospective study conducted in 187 patients of epistaxis visiting ENT emergency at SMGSH, Jammu after getting IEC clearance. Results: 139 (73.8%) had anterior and 48 (26.2%) posterior epistaxis. Dry nasal septum and mass lesions were the common local causes followed by deviated nasal septum. Anterior part of septum (little’s area) was the common site of bleeding followed by woodruff’s area. The overall success rate of diagnosing the local cause and site of epistaxis was 99% with nasal endoscopy and only 47% with combined anterior and posterior rhinoscopy. Thus, eliciting the importance of nasal endoscopy over conventional anterior and posterior rhinoscopy. Conclusions: Nasal endoscopy helps in detecting the site and cause of epistaxis and also aids in its appropriate management. It helps in endoscopic guided direct pressure packing, bipolar electrocautery, endoscopy assisted mass excision and endoscopic guided foreign body removal. However, nasal endoscopy is not a substitute for nasal packing.

Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models.

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.

AYURVEDIC MANAGEMENT OF PARIPLUTAA YONIVYAPAD W.S.R. TO BILATERAL TUBAL BLOCKAGE: A CASE STUDY

Tubal blockage is the second most common cause of female infertility. Acharya Charaka and Vagbhata have considered that complications of Yonivyapad lead to infertility. A common complication of PIDs (Pelvic In-flammatory Diseases) is tubal blockage; hence, tubal blockage can be co-related with Paripluta Yonivyapad, which is caused by Vata and Pitta Dosha is similar to the preliminary stage of the tubal block as all its symptoms are suggestive of PID. The methodology used was a single-armed, open-labelled case study of a subject of 34 years old female. Her history revealed early pregnancy loss, posterior wall intramural fibroid followed by infer-tility due to bilateral tubal blockage and also had dyspareunia. She was advised to undergo surgical manage-ment, but she refused and then approached our hospital. After thorough examinations, she was treated with Ayurvedic medications followed by Uttarabasti, having Shophaghna, Shulahara, Rasayana, Tridoshahara and Pramaathi actions. As a result, she successfully got conceived. It concludes that Ayurvedic management is suc-cessful and safe, so an effort has been made to share the protocol for the advancement of Ayurvedic science for the welfare of mankind.

THE EFFICACY OF LEKHANIYA GANA SIDDHA ANUVASANA BASTI ON PCOS

Infertility is the failure of a person /couple to conceive after one year of regular sexual attempts without contra-ception. Ayurveda says fertility factors are Ritu, kshetra, ambu and beeja. Any ailments in any of these four fac-tors are causes of infertility. Polycystic ovarian syndrome (PCOS) is the most common cause of chronic anovula-tion associated with hyperandrogenism. PCOS is responsible for more than half of infertility in women. An obese woman suffers mental stress due to obesity, and if she suffers from PCOS, it leads to infertility. At pre-sent, PCOS is treated by hormonal therapy, anti–diabetic, symptomatic treatment and surgical drilling. They may lead to obesity. Herbal medicines, according to Ayurveda, followed by Shodhana karma like ANUVASANA-BASTI, can be a great benefit in PCOS. In Charak Samhita, lekhaniyadashemani, which is a group of 10 drugs, acts by scraping, scratching, or by removal of the excess Doshas. In this regard, the Lekhana drug could be ef-fective in reducing obesity. Considering this view, Lekhaniyagana savasana basti has been selected for treating PCOS. This study focuses on the effect of LEKHANIYAGANA SIDDHA TAILAANUVASANABASTI on PCOS. We have compared the effects of Kuberakshavati and Lekhaniyagana siddha Anuvasana basti on 30 patients for three months. By comparing both the drugs given for PCOS, we have concluded that Shodhanachikitsa, followed by Shamana chikitsa, helps in treating PCOS.