Auranofin-loaded PLGA nanoparticles alleviate cognitive deficit induced by streptozotocin in rats model: modulation of oxidative stress, neuroinflammatory markers, and neurotransmitters.

Alzheimer's disease remains an unsolved neurological puzzle with no cure. Current therapies offer only symptomatic relief, hindered by limited uptake through the blood-brain barrier. Auranofin, an FDA-approved compound, exhibits potent antioxidative and anti-inflammatory properties targeting brain disorders. Yet, its oral bioavailability challenge prompts the exploration of nanoformulation-based solutions enhancing blood-brain barrier penetrability. The study aimed to investigate the neuroprotective potential of auranofin nanoparticles in streptozotocin-induced AD rats. Auranofin-containing polylactic-co-glycolic acid nanoparticles were formulated by the multiple emulsion solvent evaporation method. Characterization was done by determining entrapment efficiency, particle size distribution, surface charge, and morphology. An in vivo study was performed by administering streptozotocin (3 mg/kg/i.c.v., days 1 and 3), auranofin (5 and 10 mg/kg), auranofin nanoparticles (2.5 and 5 mg/kg), and donepezil (2 mg/kg) for 14 days orally. Behavioral deficits were evaluated using the open field test, Morris water maze, objective recognition test, change in oxidative stress levels, and AD markers in the brain. Following the decapitation of the rats, the brains were excised to isolate the hippocampus. Subsequent analyses included the quantification of biochemical and neuroinflammatory markers, as well as the assessment of neurotransmitter levels. The characterization of auranofin nanoparticles showed an entrapment efficiency of 98%, an average particle size of 101.5 ± 10.3 nm, a surface charge of 27.5 ± 5.10 mV, and a polydispersity index of 0.438 ± 0.12. In vivo, administration of auranofin and auranofin nanoparticles significantly reversed streptozotocin-induced cognitive deficits, biochemical alteration, neuroinflammatory markers, and neurotransmitter levels. The present finding suggests that auranofin nanoparticles have more significant neuroprotective potential than auranofin alone. The therapeutic efficacy may be attributed to its antioxidant and anti-inflammatory properties, as well as its positive neuromodulatory effects. Therefore, our findings suggest that it could be a promising candidate for Alzheimer's disease therapy.

Monoclonal Antibodies: Current Advancements and Future Potential for Atopic Dermatitis Therapy.

BACKGROUND: Atopic Dermatitis (AD) is an inflammatory skin condition with a severe itch. The topical therapy using corticosteroids is not sufficient for the effective therapy of moderate to severe cases of AD. The investigation and development of immunological targetspecific human monoclonal antibodies have changed the paradigm for the therapy of moderate to severe cases of AD. OBJECTIVE: The establishment of target-specific, tolerable, and efficacious human monoclonal antibodies might lead to the better management of moderate to severe cases of AD. METHODOLOGY: The scientific literature available in databases, such as Pubmed and Clinicaltrial.gov, was searched and discussed for available clinical therapeutic information. DISCUSSION: The present review has discussed the potential immunological targets of specific monoclonal antibodies developed and approved or which are under investigation in clinical trials. CONCLUSION: The development of targeted monoclonal antibodies can improve the understanding of the role of different immunological pathways and biomarkers in AD and become the future of AD treatment.

Reproductive functions and pregnancy outcome in female patients with celiac disease.

BACKGROUND AND AIM: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD. METHODS: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited. RESULTS: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001]). CONCLUSIONS: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD.

Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer's disease.

Alzherimer's disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood-brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Round Window Visibility in Cochlear Implantation : Pre-operative Prediction Using Various Radiological Parameters.

Purpose: The round window approach has become the most preferred route for electrode insertion in cochlear implant surgery; however, it is not possible at times due to difficult round window membrane (RWM) visibility. Our study aims to investigate the relationship between preoperative radiological parameters and the surgical visibility of the RWM in Cochlear implant patients. Methodology: A prospective cross-sectional study of 31 patients, age < 6 years, with bilateral severe to profound sensorineural hearing loss was conducted at a tertiary care hospital. The preoperative HRCT temporal bone scan was studied, and the parameters evaluated were facial nerve location, facial recess width, and RWM visibility prediction. All patients were operated on via the posterior tympanotomy. The surgical RWM visibility was done after optimal drilling of the posterior tympanotomy recess. The relationship between the radiological parameters and surgical visibility of RWM was evaluated. Results: The difference in the facial nerve location as per the type of RWM was found to be significant (p value < 0.05). However, the facial recess width was not significantly associated with RWM visibility. The radiological prediction of RWM visibility by tracing the prediction line over RWM was significantly associated with intraoperative RWM visibility. Conclusion: The goal to look for preoperative scans is to predict the ease or difficulty of RWM visibility during surgery. The difficult visualization of the RWM, can result in dire intraoperative consequences. A comprehensive understanding of preoperative radiological parameters, coupled with meticulous surgical planning, is crucial to address these challenges effectively by focusing on enhancing RWM visualization.

Genitourinary Fistula: epidemiology, changing trends in etiology and management: A tertiary care institute's perspective.

INTRODUCTION: Urogenital fistula is a physically, socially and psychologically devastating condition for the patient. In developed countries, these fistulae are typically related to gynecological surgery, pelvic pathology like malignancy or post radiation therapy. In contrast, classical teaching is that urogenital fistulae in the developing countries like India are usually associated with prolonged labor and obstetric complications. This retrospective study conducted at a tertiary care health Institute shows a paradigm shift in epidemiology, etiology and management of genitourinary fistulae in India in recent times. METHODS: This retrospective study included patients undergoing surgical repair for various genitourinary fistulae at our institute from 2016 to 2022. Epidemiology, etiology, site, size and number of fistulae, clinical presentation, and management records of these patients were recorded and reviewed retrospectively. RESULTS: In our study, the mean age of the patients was 38.4 ± 10.2 years. Vesicovaginal Fistula (VVF) was found to be most common fistula in the study population (87.5%) followed by vesicouterine (7.1%) and urethrovaginal fistula (5.4%). The causes of genitourinary fistula were iatrogenic (73.2%), carcinoma of cervix (16.1%), obstructed prolonged labor (7.1%), and genitourinary tuberculosis (3.57%). Among the 48 vesicovaginal fistulas that underwent surgery, 45.8% were treated using a transvaginal approach, 29.2% were managed through a laparoscopic transabdominal repair, and 25% were addressed using a robotic approach. Recurrence occurred in 7.1% of the operated patients. CONCLUSION: Enhanced healthcare services in the country have contributed to a decrease in the incidence of obstructed labor, subsequently reducing related injuries. Iatrogenic injuries resulting from gynecological surgeries and carcinoma cervix have given rise to more complex fistulas, necessitating the implementation of advanced treatment strategies.

Knowledge, attitude, and practices of ward attendant and housekeeping staffs towards dead body care of COVID-19 patients at tertiary care hospital : A cross sectional study

BackgroundHealthcare workers worked untiringly during entire pandemic period and taken efforts to protect individuals, families and communities in adverse situations with stretched resources. Among health care workers role of ward attendant and housekeeping staffs have been very significant particularly in infection control practices and dead body management. Present studys aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of ward attendant and housekeeping staffs towards dead body management. MethodsHospital-based cross-sectional study design was conducted among ward attendant and housekeeping staffs working in COVID units. A total of 62 participants were selected using simple random sampling technique. Self-administered questionnaire was used to collect data. Binary logistic regression model was used to see association between outcome and independent variables. ResultPresent study found mean knowledge, attitude and practice score of participants were 6.1, 49.9 and 12.28 indicates good knowledge, positive attitude and inappropriate practice towards dead body care. Study result also shows that odds of good knowledge were not significantly associated with demographic variables. However, the participants who didnt receive any training on dead body care were found to have positive attitude towards dead body care(AOR=3.90,95%CI=1.092-13.92), whereas gender (AOR=1.85,95%CI=.430-7.96), working experience in COVID units (AOR=99.5,95%CI=.913-98.8) and educational qualification (AOR=30.33,95%CI=1.5-577) were significantly associated with practice of dead body care of COVID-19 patients. ConclusionThe study found that majority of participants were having good knowledge, positive attitude and inappropriate practice towards dead body care of COVID-19 patients. Hospital administration should conduct regular training of dead body care of COVID-19 patients for all the housekeeping staffs and ward attendant to minimise the risk of exposure to infections and better management of dead bodies.

Knowledge practice gap of nurses towards COVID-19 patients dead body care in a tertiary care hospital.

AimTo know the dead body care of COVID-19 patients. ObjectiveO_LITo determine health care professionals, knowledge, attitude, and practice towards Covid-19 dead body care. C_LIO_LITo find the association of knowledge, attitude, practice with selected demographic variables. C_LI BackgroundCOVID-19 was a global pandemic and it was a serious note for health care professionals from many aspects. The virus was infective and causes serious infectionsto patients which were easily transmitted, hence specific dead body care is required for such kinds of patients. To keep this background in mind the study was conducted to identify the knowledge, practice and attitude towards COVID-19 dead body care among nurses. MethodologyA cross sectional survey based study was done on 282 samples.Quantitative research design with purposive sampling technique data was collected for knowledge,attitude, and practice. ResultKnowledge, attitude and practice were assessed and association was done with demographic profile. Hence the good knowledge, attitude and practicewere observed in experienced and trained nurses (p value<0.005. Whereas no significant changes were observed with age, gender and education qualification. ConclusionOverall knowledge, attitude and practice regarding COVID-19 dead body care were moderate to good. But it was important to identify the gap as it was a global pandemic and higher chances of spreading of infection.

Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver

Background/Aims@#Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. @*Methods@#Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. @*Results@#In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. @*Conclusions@#Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.

Minimally Invasive Microscope-Assisted Stand-Alone Transarticular Screw Fixation without Gallie Supplementation in the Management of Mobile Atlantoaxial Instability

STUDY DESIGN: Retrospective study. PURPOSE: To evaluate the clinico-radiological efficacy of stand-alone minimally invasive transarticular screw (MIS-TAS) fixation without supplemental Gallie fixation in the management of mobile C1–C2 instability. OVERVIEW OF LITERATURE: Data evaluating the efficacy and feasibility of MIS-TAS in the literature is scanty. METHODS: Patients with mobile atlantoaxial instability and >2 years follow-up were included and managed by stand-alone TAS fixation using the Magerl technique and morselized allograft without additional fixation. Patient demographics and intra-operative parameters were noted. Clinical parameters (Visual Analog Scale [VAS] and Oswestry Disability Index [ODI]), neurology (modified Japanese Orthopaedic Association [mJOA]), and radiological factors (anterior atlanto-dens interval and space available for cord) were evaluated pre and postoperatively. Computed tomography (CT) was performed in patients who did not show interspinous fusion on X-ray at 1 year, to verify intra-articular fusion. Statistical analysis was performed using IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA); the Student t-test and analysis of variance were used to assess statistical significance (p <0.05). RESULTS: A total of 82 consecutive cases (three males, one female; mean age, 36.26±5.78 years) were evaluated. In total, 163 TASs were placed. Significant improvement was noticed in clinical (mean preoperative VAS=7.2±2.19, postoperative VAS=3.3±1.12; mean preoperative ODI=78.3±4.83, postoperative ODI=34.05±3.26) and neurological features (mean preoperative mJOA=14.73±2.68, postoperative mJOA=17.5±2.21). Radiological evidence of fusion was noted in 97.5% cases at final follow-up. Seventeen patients were found to have no interspinous fusions upon X-rays, but CT revealed facet fusion in all patients except in two. Inadvertent vertebral artery injury was noted in three cases. CONCLUSIONS: Stand-alone TAS fixation with morselized allograft provides excellent radiological and clinical outcomes. The addition of a supplementary tension band and structural graft are not essential. This provides the opportunity to avoid the complications associated with graft harvesting and wiring.

Comparing the Efficacy of Latanoprost (0.005%), Bimatoprost (0.03%), Travoprost (0.004%), and Timolol (0.5%) in the Treatment of Primary Open Angle Glaucoma

PURPOSE: To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma. METHODS: This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events. RESULTS: The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student's t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements. CONCLUSIONS: Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.