Vidarabine as a novel antifungal agent against Candida albicans: insights on mechanism of action.

Around 1.5 million mortality cases due to fungal infection are reported annually, posing a massive threat to global health. However, the effectiveness of current antifungal therapies in the treatment of invasive fungal infections is limited. Repurposing existing antifungal drugs is an advisable alternative approach for enhancing their effectiveness. This study evaluated the antifungal efficacy of the antiviral drug vidarabine against Candida albicans ATCC 90028. Antifungal susceptibility testing was performed by microbroth dilution assay and further processed to find the minimum fungicidal concentration. Investigation on probable mode of vidarabine action against C. albicans was assessed by using the ergosterol reduction assay, reactive oxygen species (ROS) accumulation, nuclear condensation, and apoptosis assay. Results revealed that C. albicans was susceptible to vidarabine action and exhibited minimum inhibitory concentration at 150 µg/ml. At a concentration of 300 µg/ml, vidarabine had fungicidal activity against C. albicans. 300 µg/ml vidarabine-treated C. albicans cells demonstrated 91% reduced ergosterol content. Annexin/FITC/PI assay showed that vidarabine (150 µg/ml) had increased late apoptotic cells up to 31%. As per the fractional inhibitory concentration index, vidarabine had synergistic activity with fluconazole and caspofungin against this fungus. The mechanism underlying fungicidal action of vidarabine was evaluated at the intracellular level, and probably because of increased nuclear condensation, enhanced ROS generation, and cell cycle arrest. In conclusion, this data is the first to report that vidarabine has potential to be used as a repurposed antifungal agent alone or in combination with standard antifungal drugs, and could be a quick and safe addition to existing therapies for treating fungal infections.

Antifungal Activity of Mefloquine Against Candida albicans Growth and Virulence Factors: Insights Into Mode of Action.

The antimalarial drug Mefloquine has demonstrated antifungal activity against growth and virulence factors of Candida albicans. The current study focused on the identification of Mefloquine's mode of action in C. albicans by performing cell susceptibility assay, biofilm assay, live and dead assay, propidium iodide uptake assay, ergosterol quantification assay, cell cycle study, and gene expression studies by RT-PCR. Mefloquine inhibited the virulence factors in C. albicans, such as germ tube formation and biofilm formation at 0.125 and 1 mg/ml, respectively. Mefloquine-treated cells showed a decrease in the quantity of ergosterol content of cell membrane in a concentration-dependent manner. Mefloquine (0.25 mg/ml) arrested C. albicans cells at the G2/M phase and S phase of the cell cycle thereby preventing the progression of the normal yeast cell cycle. ROS level was measured to find out oxidative stress in C. albicans in the presence of mefloquine. The study revealed that, mefloquine was found to enhance the ROS level and subsequently oxidative stress. Gene expression studies revealed that mefloquine treatment upregulates the expressions of SOD1, SOD2, and CAT1 genes in C. albicans. In vivo, the antifungal efficacy of mefloquine was confirmed in mice for systemic candidiasis and it was found that there was a decrease in the pathogenesis of C. albicans after the treatment of mefloquine in mice. In conclusion, mefloquine can be used as a repurposed drug as an alternative drug against Candidiasis.

Clinical Efficacy of Concentrated Growth Factors for the Management of Marginal Tissue Recession: A Systematic Review and Meta-Analysis.

INTRODUCTION: To systematically review existing scientific literature to determine, compare, and evaluate whether concentrated growth factors (CGF) or connective tissue grafts (CTG) is a better treatment alternative for patients with marginal tissue recession (MTR). METHODS: Electronic databases like PubMed, Embase, Scopus, and Google Scholar were screened from the last 20 years reporting treatment of MTR using CGF or CTG and other techniques. Periodontal parameters like probing depth, clinical attachment level, recession depth, recession width, keratinized tissue width, root coverage, increase in gingival thickness and plaque index, and gingival index were compared. Standardized mean difference was used as a summary statistic measure with a random effect model and P value <0.05 as statistically significant. RESULTS: Six studies fulfilled eligibility criteria and were included in qualitative synthesis, of which only 4 studies were suitable for meta-analysis. The pooled estimate through standardized mean difference signifies that CGF was superior to CTG in the reduction of probing depth, gingival index, and plaque index and gain in clinical attachment level while CTG was superior in reducing the recession depth and recession width. Both the procedures had an overall equal effect on keratinized tissue width and root coverage, but these differences were statistically insignificant (P>0.05). Publication bias through the funnel plot showed symmetric distribution without systematic heterogeneity. CONCLUSION: The present study suggests that treatment of MTR with CTG or CGF resulted in clinically favorable outcomes, but no statistically significant differences was observed between these 2 procedures regarding the outcome.

Outcomes of an enhanced recovery after surgery (ERAS) program to limit perioperative opioid use in outpatient minimally invasive GI and hernia surgeries.

BACKGROUND: Perioperative pain management is important for patient satisfaction while returning to homeostasis in the safest way possible. Studies show that patients don't require as much opioids as once thought. The benefits of ERAS pathways extend beyond enhancement of patients' perioperative experience, and include reducing opioid prescriptions in the face of the ongoing nationwide opioid crisis and evidence of prescription opioids as a contributor. METHODS: We performed a retrospective cohort study of patients undergoing same day minimally invasive surgery (MIS) procedures for GI and hernia disease using a minimal-opioid ERAS protocol at two community hospitals between January 2020 and May 2022. We included elective laparoscopic cholecystectomy (LC), laparoscopic appendectomy (LA) for acute appendicitis without perforation, and minimally invasive (laparoscopic and robotic) inguinal and ventral hernia repair or abdominal wall reconstruction (AWR). Primary outcome was postoperative opioid use. RESULTS: A total of 509 patients were included, undergoing procedures of MIS hernia repair (52.5%), LC (43.6%), and LA (7.9%). Only 9.4% of patients received opioid prescriptions at discharge, with no difference between groups. Among the patients receiving a prescription at discharge, there was a significant difference in morphine milligram equivalents (MME) prescribed (25.0 ± 0.0 in the LA group, 65.0 ± 41.4 in the LC group, 100.6 ± 46.2 in the MIS hernia/AWR group; P = 0.015). Nine percent of patients called with pain management concerns postoperatively. ASA score ≥ 3 was associated with increased odds for postoperative opioid prescription (OR 2.084; P = 0.014). CONCLUSIONS: We demonstrate that an opioid-sparing ERAS program effectively manages pain for patients undergoing multiple outpatient MIS GI/hernia procedures, and suggests generalizability across a diverse range of operations. Therefore, the use of ERAS may safely and effectively expand beyond inpatient MIS and open surgeries that target reduced length of stay to also minimize opioids for outpatient procedures.

Genetic analysis for semen quality traits in buffalo bulls.

This study was attempted to estimate the genetic parameters of semen quality traits in buffalo bulls. The study data consisted of 10975 ejaculates from 45 Murrah buffalo bulls (aged 24-72 months) used for breeding program during year 2010 to 2020. Semen quality traits (ejaculate volume, concentration of sperm, mass activity, initial and post-thaw motility, number of sperms per ejaculate, motile sperm number and discard rates) were studied. It was observed that average ejaculate volume was 2.82 ± 1.45 mL with mean concentration of 1040.12 ± 523.26 million/mL. Higher heritability was observed for number of sperms per ejaculate, number of motile sperm and sperm concentration. Significant phenotypic correlation was obtained between volume and number of sperms per ejaculate as well as volume and number of motile sperms. Likewise, significant phenotypic correlation was evident between sperm concentration with sperm number per ejaculate. Highest phenotypic correlation was obtained between sperm count per ejaculate and motile sperm count. Estimated genetic trends showed significant change in volume and motile sperm number. In conclusion, this study ascertains that genetic parameters of semen traits can be considered during the selection of buffalo bulls in breeding program.

Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents.

Psoriasis is a systemic inflammatory disease associated with increased risk of comorbidities, such as psoriatic arthritis, Crohn's disease, malignancy, obesity, and cardiovascular diseases. These factors have a significant impact on the decision to use one therapy over another. The past decade has seen a paradigm shift in our understanding of the pathogenesis of psoriasis that has led to identification of new therapeutic targets. Several new drugs have gained approval by the US Food and Drug Administration, expanding the psoriasis armamentarium, but still a large number of patients continue to be untreated or undertreated. Treatment regimens for psoriasis patients should be tailored to meet the specific needs based on disease severity, the impact on quality of life, the response to previous therapies, and the presence of comorbidities. The first article in this continuing medical education series focuses on specific comorbidities and provides insights to choose appropriate systemic treatment in patients with moderate to severe psoriasis.

Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections.

Despite the availability of several new systemic agents for psoriasis treatment, choosing the right therapy in certain patient populations can be challenging. There are few up-to-date reviews on systemic drugs for moderate to severe psoriasis in pregnant and pediatric patients and in patients with concomitant chronic infections, such as hepatitis, HIV, and latent tuberculosis. These groups are usually excluded from clinical trials, and much of the available evidence is based on anecdotal case reports and case series. As a chronic disease, psoriasis requires long-term treatment, and there are concerns of adverse maternal-fetal outcomes, long-term side effects in children, and the reactivation of latent infections with the use of systemic agents in these patients. The second article in this continuing medical education series provides insights for choosing appropriate systemic agents for treating moderate to severe psoriasis in pregnant and pediatric patients and in the setting of chronic infections, such as hepatitis, HIV, and latent tuberculosis.

The ß-isoform of BCCIP promotes ADP release from the RAD51 presynaptic filament and enhances homologous DNA pairing.

Homologous recombination (HR) is a template-driven repair pathway that mends DNA double-stranded breaks (DSBs), and thus helps to maintain genome stability. The RAD51 recombinase facilitates DNA joint formation during HR, but to accomplish this task, RAD51 must be loaded onto the single-stranded DNA. DSS1, a candidate gene for split hand/split foot syndrome, provides the ability to recognize RPA-coated ssDNA to the tumor suppressor BRCA2, which is complexed with RAD51. Together BRCA2-DSS1 displace RPA and load RAD51 onto the ssDNA. In addition, the BRCA2 interacting protein BCCIP normally colocalizes with chromatin bound BRCA2, and upon DSB induction, RAD51 colocalizes with BRCA2-BCCIP foci. Down-regulation of BCCIP reduces DSB repair and disrupts BRCA2 and RAD51 foci formation. While BCCIP is known to interact with BRCA2, the relationship between BCCIP and RAD51 is not known. In this study, we investigated the biochemical role of the ß-isoform of BCCIP in relation to the RAD51 recombinase. We demonstrate that BCCIPß binds DNA and physically and functionally interacts with RAD51 to stimulate its homologous DNA pairing activity. Notably, this stimulatory effect is not the result of RAD51 nucleoprotein filament stabilization; rather, we demonstrate that BCCIPß induces a conformational change within the RAD51 filament that promotes release of ADP to help maintain an active presynaptic filament. Our findings reveal a functional role for BCCIPß as a RAD51 accessory factor in HR.

Conversion of post consumer waste polystyrene into a high value adsorbent and its sorptive properties for Congo Red removal from aqueous solution.

Using post-consumer waste polystyrene (WPS), a conjugated microporous polymer (CMP) was synthesised and activated into a sulphonic-group carrying resin (SCMP). The surface chemistry of the materials showed a decline in both the aromatic CH and aliphatic CH2 stretching vibrations confirming successful crosslinking. The synthesised polymers were thermally stable with decomposition temperatures above 300 °C, had surface heterogeneity, and BET surface areas of 752 and 510 m2/g, respectively. A distribution of pores ranging from meso- to micro-pores was comparable to other CMPs. The materials had maximum adsorption capacities of 500 and 357 mg/g for Congo Red (CR) on CMP and SCMP, respectively. Converting waste polystyrene to an adsorbent is a cost effective way of handling waste and simultaneously providing material for wastewater remediation.

Genetic Counselors' Perspectives and Practices Regarding Expanded Carrier Screening after Initial Clinical Availability.

Expanded carrier screening (ECS), introduced in 2009, identifies carriers for dozens or hundreds of recessive diseases. At the time of its introduction into clinical use, perspectives of the genetic counseling community regarding ECS were unknown. We conducted a survey in early 2012 of GCs and report the results here. They represent a snapshot of opinions and usage at that time, providing a baseline for comparison as the technology continues to evolve and as usage increases. The survey assessed personal perspectives, opinions on clinical implementation and clinical utilization of ECS. The sample included 337 GCs of varying clinical fields, of whom 150 reported practicing in reproductive settings. Our findings demonstrate that, at the time, GCs indicated general agreement with ECS as a concept - for example, most GCs agreed that carrier screening should address diseases outside of current guidelines and also indicated personal interest in electing ECS. There were also disagreements or concerns expressed regarding appropriate pre- and post-test counseling (e.g., the content and delivery mode of adequate informed consent) and practical implementation (e.g., the amount of time available for follow-up care). This was the first quantitative study of a large number of GCs and it revealed initial overall support for ECS among the GC profession. The authors plan to re-administer a similar survey, which may reveal changes in opinions and/or utilization over time. A follow up survey would also allow further exploration of questions uncovered by these data.

Changing trends in carrier screening for genetic disease in the United States.

Genetic disease is the leading cause of infant death in the United States, accounting for approximately 20% of annual infant mortality. Advances in genomic medicine and technological platforms have made possible low cost, pan-ethnic expanded genetic screening that enables obstetric care providers to offer screening for over 100 recessive genetic diseases. However, the rapid integration of genomic medicine into routine obstetric practice has raised some concerns about the practical implementation of such testing. These changing trends in carrier screening, along with concerns and potential solutions, will be addressed.

Chronic pruritus in HIV-positive patients in the southeastern United States: its prevalence and effect on quality of life.

BACKGROUND: Prevalence of chronic pruritus in HIV-positive patients is an underevaluated topic in the United States. The characteristics, severity, and quality of life (QOL) in patients with HIV and chronic pruritus have not been well documented using validated tools. OBJECTIVES: We sought to assess the prevalence and intensity of chronic pruritus and its effect on QOL in HIV-positive patients in a US population. METHODS: HIV-positive patients (n = 201) were asked to complete a sociodemographic data form and 2 itch questionnaires. Patients with itching rated their itch intensity on a numeric visual analog scale. Laboratory parameters were obtained from patients' medical records. RESULTS: The prevalence of chronic itch in the study group was 45% with an average visual analog scale score of 5.93 during an itch episode. Patients with high visual analog scale score had significantly decreased QOL. Patients with HIV reported greater negative impact of pruritus on daily lives. LIMITATIONS: Because of the cross-sectional design, this study demonstrates an association between HIV and pruritus but cannot prove causation. CONCLUSION: Patients with HIV surveyed in a large clinic in the southeastern United States have a high prevalence of pruritus; HIV pruritus has a significant effect on QOL and itch is the most common skin manifestation found in this population.

Compound Volvulus: A Rare Case of Intestinal Obstruction.

Compound volvulus or ileosigmoid knotting is an uncommon surgical emergency that causes intestinal obstruction. The sigmoid and ileum are mostly involved in this closed-loop intestinal obstruction. It is regarded as a rather uncommon cause of intestinal obstruction. It's important to distinguish between an ileosigmoid knot and a simple sigmoid volvulus since the management of the two is different. CT and MRI are more helpful in the diagnosis than abdominal X-ray findings, which are not pathognomonic. After resuscitation, a patient with ileosigmoid knotting typically needs an emergency laparotomy. Different resectional and non-resectional surgical procedures may be employed depending on the viability of the ileum and sigmoid colon.

Unusual Triggers of Acute Intestinal Obstruction in Surgical Emergencies: A Series of Five Cases.

Intestinal obstruction is a common surgical emergency that can be caused by mechanical causes or by different pathological processes. The most common cause of small bowel intestinal obstruction is post-operative adhesion, and the most common cause of large bowel obstruction is malignancy. These are classified into dynamic and adynamic types. The patient was selected based on the presentation management plan. Some cases require immediate operative intervention; however, some cases, as mentioned in this case series, require further investigation and a different approach. In this study, we report the rare causes of intestinal obstruction presented to Safdarjung Hospital, Department of General Surgery, New Delhi: one case of foreign body impaction, one case of spontaneous migration of feeding jejunostomy, one case of extrauterine IUCD causing intestinal obstruction, one case of mesentery band causing obstruction, and one case of abdominopelvic mass causing small bowel obstruction. These cases presented to the surgical emergency department with challenges in their diagnosis, intraoperative findings, and their outcomes.

Male Breast Cancer With Dual BRCA2 and BRIP1 Deleterious Gene Mutations.

Background: Male breast cancer remains relatively underexplored in the medical literature. At present, male patients with breast cancer follow the same treatment guidelines as female patients with breast cancer, principally because of similar outcomes with treatment. However, this practice should not preclude generating evidence for male breast cancer surveillance, diagnosis, and management. BRCA2 gene mutations are associated with an increased risk of male breast cancer, along with lesser-known gene mutations that could also increase this risk, such as mutations of the BRIP1 gene. This case report presents a male patient with dual BRCA2 and BRIP1 deleterious gene mutations. To our knowledge, this combination has not been reported in the medical literature to date. Case Report: A 53-year-old male presented with a palpable symptomatic mass underneath the right nipple-areolar complex. Biopsies confirmed a poorly differentiated, infiltrating ductal carcinoma that was estrogen and progesterone receptor positive and human epidermal growth factor receptor-2 negative. The patient underwent a left modified radical mastectomy, with a right prophylactic simple mastectomy. Postoperatively, he underwent adjuvant chemotherapy and endocrine therapy. Conclusion: This novel case of genetically based male breast cancer with dual deleterious gene mutations provides insight into current treatment recommendations and the subtle differences between male breast cancer and female breast cancer. Engaging in discussions surrounding such rare cases not only raises awareness of male breast cancer but also indicates the need for further research aimed at establishing evidence-based management strategies for male patients with breast cancer.

A Comprehensive Study on Ruptured Liver Abscess in a Tertiary Care Center.

Background Bacteria and parasites cause liver abscesses (LAs), with the unusual but fatal consequence of ruptured LA. Along with the clinical signs of icterus, right upper quadrant pain, and a history of loose stools, patients present with non-specific symptoms such as fever, nausea, and generalized weakness. Consistent findings include male sex prevalence and frequent alcohol consumption. Leukocytosis, abnormal liver function, and an increased international normalized ratio have been identified by biochemical analysis; however, these findings are not specific to a ruptured LA diagnosis, and imaging is necessary to reach a definitive diagnosis. Ultrasonography usually confirms the diagnosis, and computed tomography is required in certain situations. In confined ruptures, percutaneous drainage combined with antibiotic therapy is typically the initial treatment course. Generally reserved for non-responders or moribund patients with delayed presentation, an open surgical approach may involve simple draining of a ruptured abscess or ileocecal resection, or right hemicolectomy in cases of large bowel perforations, both of which increase patient morbidity. A definite guide to management is still missing in the literature. In this article, we have discussed and correlated with data the predictors of surgery and preoperative predictors of perforation. Materials and methods This retrospective study was performed at Safdarjung Hospital, New Delhi, between January 2022 and December 2023. The study included 115 patients diagnosed with ruptured LA by ultrasound. Medical records were analyzed, and various parameters of the illness, clinical features, hematological and biochemical profiles, ultrasound features, and therapeutic measures were noted and assessed. Results Of the 115 patients, 88% (n = 101) were male. The most common symptoms were abdominal pain (114 patients) and right upper abdominal tenderness (107 patients). Fifty-two patients were treated with percutaneous drainage, and 42 underwent laparotomy. Intercostal drainage (ICD) tubes were placed in 19 patients. Sixteen patients had large bowel perforations. Twenty-three patients died (20%), including 17 patients who underwent laparotomy and nine patients who had large bowel perforation (39.1% associated with overall mortality, 52.9% associated with mortality in laparotomy). One patient with percutaneous drainage and a right ICD tube died in the intensive care unit. Four patients died before intervention. Significant associations were noted between perforation and mortality in patients who underwent surgical drainage. Loose motions, alcohol and smoking consumption, and deranged creatinine and albumin levels were found to have a significant association with surgical drainage. Conclusion The study found that a ruptured liver abscess (LA) may require surgery to drain the collection or repair the pathological bowel, which increases the morbidity, but it is a lifesaving procedure over percutaneous catheter drainage. The study also identified factors associated with a higher risk of death, such as a history of loose stools and low blood albumin levels.

Prolactin regulates TRPV1, TRPA1, and TRPM8 in sensory neurons in a sex-dependent manner: Contribution of prolactin receptor to inflammatory pain.

Prolactin (PRL) is a hormone produced in the anterior pituitary but also synthesized extrapituitary where it can influence diverse cellular processes, including inflammatory responses. Females experience greater pain in certain inflammatory conditions, but the contribution of the PRL system to sex-dependent inflammatory pain is unknown. We found that PRL regulates transient receptor potential (TRP) channels in a sex-dependent manner in sensory neurons. At >20 ng/ml, PRL sensitizes TRPV1 in female, but not male, neurons. This effect is mediated by PRL receptor (PRL-R). Likewise, TRPA1 and TRPM8 were sensitized by 100 ng/ml PRL only in female neurons. We showed that complete Freund adjuvant (CFA) upregulated PRL levels in the inflamed paw of both male and female rats, but levels were higher in females. In contrast, CFA did not change mRNA levels of long and short PRL-R in the dorsal root ganglion or spinal cord. Analysis of PRL and PRL-R knockout (KO) mice demonstrated that basal responses to cold stimuli were only altered in females, and with no significant effects on heat and mechanical responses in both sexes. CFA-induced heat and cold hyperalgesia were not changed in PRL and PRL-R KO compared with wild-type (WT) males, whereas significant reduction of heat and cold post-CFA hyperalgesia was detected in PRL and PRL-R KO females. Attenuation of CFA-induced mechanical allodynia was observed in both PRL and PRL-R KO females and males. Thermal hyperalgesia in PRL KO females was restored by administration of PRL into hindpaws. Overall, we demonstrate a sex-dependent regulation of peripheral inflammatory hyperalgesia by the PRL system.

Metal doped nanosized titania used for the photocatalytic degradation of rhodamine B dye under visible-light.

Metal-doped anatase nanosized titania photocatalysts were successfully synthesized using a sol-gel process. Different amounts of the dopants (0.2, 0.4, 0.6, 0.8 and 1.0%) of the metals (Ag, Ni, Co and Pd) were utilized. The UV-Vis spectra (solid state diffuse reflectance spectra) of the doped nanoparticles exhibited a red shift in the absorption edge as a result of metal doping. The metal-doped nanoparticles were investigated for their photocatalytic activity under visible-light irradiation using Rhodamine B (Rh B) as a control pollutant. The results obtained indicate that the metal-doped titania had the highest activity at 0.4% metal loading. The kinetic models revealed that the photodegradation of Rh B followed a pseudo first order reaction. From ion chromatography (IC) analysis the degradation by-products Rhodamine B fragments were found to be acetate, chloride, nitrite, carbonate and nitrate ions.

Segmental ulcerated perineal hemangioma of infancy: a complex case of PELVIS syndrome successfully treated using a multidisciplinary approach.

We report a case of PELVIS (perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus and skin tag) syndrome in which hemangioma in the perineal area was misdiagnosed at birth as diaper rash. Investigations revealed associated vesicorenal and spinal abnormalities. We emphasize careful diagnosis of suspicious lesions at birth and confirm the successful use of propranolol in treating ulcerated segmental hemangiomas.

Rare Hernias as Surgical Emergencies: A Case Series of Five Cases.

Hernia is one of the most common clinically diagnosed cases seen in day-to-day practice. But some of them might pose a challenge in diagnosing the condition and, thus, their further management. Some types of hernias are rare and mimic the common presentation of the acute abdomen, thus requiring extra caution to keep hernias as a differential diagnosis in the acute abdomen. In this series, we report five cases of rare hernias presented to a tertiary care center in northern India over the course of one year. Two cases of paraduodenal hernias (PHs), a right and left, respectively, a male femoral hernia, an Amayand hernia, and an obturator hernia presented as acute abdomen in the emergency department, with challenges in their diagnosis, intraoperative findings, and their outcomes. Computed tomography is a useful diagnostic tool for arriving at the diagnosis pre-operatively in these situations.