Prevalence and Risk Factors of Pressure Ulcers in Bedbound Diabetic vs. Non-diabetic Patients in a Lower-Middle-Income Country.

Introduction Pressure ulcers, also known as bedsores, are a significant concern for bedridden individuals, presenting both physical and socioeconomic challenges. Factors such as prolonged immobility, chronic medical conditions, and poor nutrition contribute to their development. Despite extensive research in some regions, studies comparing diabetic and non-diabetic populations remain limited, particularly in low-income settings. This study aimed to investigate the risk factors and frequency of pressure ulcers among bedridden patients, addressing this gap in understanding and guiding targeted interventions. Materials and methods A cross-sectional study was conducted across four government hospitals in Peshawar, Pakistan. A total of 388 bedridden patients with pressure ulcers were included, and data were collected through a questionnaire. The questionnaire covered demographics, comorbidities, duration of bedbound status, BMI, and caregivers' awareness of pressure ulcer care. Data analysis was performed using SPSS version 22.0 (Armonk, NY: IBM Corp.), with qualitative data presented as frequencies and percentages and quantitative data as mean and standard deviation. Chi-square tests were utilized for significance, with p<0.05 considered significant. Results Of the 388 patients analyzed, 230 (59.3%) were diabetic, highlighting the prevalence of diabetes among pressure ulcer cases. The majority of diabetic patients with ulcers were over 41 years old, and 293 (75.5%) had comorbidities. Surgical intervention was the primary cause of ulcers in 213 (54.8%) cases, followed by stroke in 77 (19.8%) cases. Notably, 252 (65%) of caregivers exhibited inadequate knowledge regarding ulcer care. Stage II ulcers were prevalent in both diabetic and non-diabetic cohorts. Conclusions Pressure ulcers are poorly controlled complications observed in bedridden individuals, highlighting a critical need for comprehensive preventive measures and caregiver education to alleviate the burden of pressure ulcers, especially in diabetic patients. Factors such as prolonged immobility, surgical interventions, and insufficient caregiver knowledge contribute to the development of pressure ulcers. Understanding these complexities is essential for implementing effective care approaches and mitigating the impact of pressure ulcers.

Total Endoscopic or Endoscope-Assisted Excision of Non-embolized Advanced Juvenile Nasopharyngeal Angiofibroma: A Clinical Case Series.

Background Surgical excision is the primary treatment for juvenile nasopharyngeal angiofibroma (JNA), but this procedure is challenging due to its high vascularity and local aggressiveness. Moreover, preoperative embolization is a subject of debate. Objective The objective of this study is to assess the efficacy, safety, and feasibility of endoscope-assisted excision as a surgical intervention for non-embolized advanced JNA. Materials and methods This case series involved six male patients (mean age: 16 years) with JNA, classified as stages Ⅱc to Ⅲb according to the Radkowski classification. None underwent preoperative embolization. Results Two stage Ⅱc cases underwent total endoscopic endonasal excision. One patient with stage Ⅲa and another with stage Ⅲb underwent surgery via an endoscope-assisted sublabial approach. Two patients, one with stage Ⅱc JNA and another with Ⅲb, underwent a two-stage procedure. Postoperative CT scans showed no residual disease at the six-month mark. On average, each procedure required 1.5 units of blood transfusion. One patient experienced intraoperative bleeding, whereas the remaining patients were free of any major complications. The mean operation duration was 175 minutes per procedure. The mean length of stay at the hospital was 3.75 days per procedure. Conclusion Endoscope-assisted or purely endoscopic approaches can be safely and effectively employed for the complete excision of non-embolized advanced JNAs.

First report of Anaplasma spp., Ehrlichia spp., and Rickettsia spp. in Amblyomma gervaisi ticks infesting monitor lizards (Varanus begalensis) of Pakistan.

Ticks pose significant health risks to both wildlife and humans due to their role as vectors for various pathogens. In this study, we investigated tick infestation patterns, tick-associated pathogens, and genetic relationships within the tick species Amblyomma gervaisi, focusing on its prevalence in monitor lizards (Varanus bengalensis) across different districts in Pakistan. We examined 85 monitor lizards and identified an overall mean intensity of 19.59 ticks per infested lizard and an overall mean abundance of 11.98 ticks per examined lizard. All collected ticks (n = 1019) were morphologically identified as A. gervaisi, including 387 males, 258 females, 353 nymphs, and 21 larvae. The highest tick prevalence was observed in the Buner district, followed by Torghar and Shangla, with the lowest prevalence in Chitral. Lizard captures primarily occurred from May to October, correlating with the period of higher tick infestations. Molecular analysis was conducted on tick DNA, revealing genetic similarities among A. gervaisi ticks based on 16S rDNA and ITS2 sequences. Notably, we found the absence of A. gervaisi ITS2 sequences in the NCBI GenBank, highlighting a gap in existing genetic data. Moreover, our study identified the presence of pathogenic microorganisms, including Ehrlichia sp., Candidatus Ehrlichia dumleri, Anaplasma sp., Francisella sp., Rickettsia sp., and Coxiella sp., in these ticks. BLAST analysis revealed significant similarities between these pathogenic sequences and known strains, emphasizing the potential role of these ticks as vectors for zoonotic diseases. Phylogenetic analyses based on nuclear ITS2 and mitochondrial 16S rDNA genes illustrated the genetic relationships of A. gervaisi ticks from Pakistan with other Amblyomma species, providing insights into their evolutionary history. These findings contribute to our understanding of tick infestation patterns, and tick-borne pathogens in monitor lizards, which has implications for wildlife health, zoonotic disease transmission, and future conservation efforts. Further research in this area is crucial for a comprehensive assessment of the risks associated with tick-borne diseases in both wildlife and humans.

A Rare Case of P63-Negative Sinonasal Nut Midline Carcinoma in the Elderly.

A nuclear protein in testis (NUT) midline carcinoma arises from squamous cells and is often located in the head, neck, and lungs. This report focuses on the negative p63 mutation and older age at the diagnosis of a NUT carcinoma, which has significant prognostic implications. A 62-year-old patient presented initially with a three-year history of recurring frontal headaches, intermittent nasal bleeding, and a sensation of a nasal cavity mass. An incisional biopsy revealed a poorly differentiated NUT carcinoma in the left maxillary sinus. A functional endoscopic sinus surgery was performed, but the cancer recurred. As a result, a total maxillectomy was performed, and the patient was declared cancer-free with no evidence of residual disease. This is a rare instance of a p63-negative midline NUT cell carcinoma (NCC) in an elderly patient, which could potentially contribute to a more favourable prognosis and longer survival compared to other reported cases. LEARNING POINTS: Molecular analysis of a NUT carcinoma and age at diagnosis may serve as a potential means for predicting patient prognosis in cases of midline NCC.Each patient should receive careful monitoring and a personalised treatment strategy based on their molecular studies. Surgical resection, along with a combination of radiotherapy and chemotherapy, has the potential to improve overall survival rates.In line with the commonly observed relationship between increased p63 mutation and poorer survival rates, a negative p63 expression in squamous cell carcinomas may indicate a more favorable prognosis. This hypothesis highlights the importance of further research to validate these findings.

The association of ABCB1 gene polymorphism with clinical response to carbamazepine monotherapy in patients with epilepsy.

BACKGROUND: Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation. RESULTS: Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05). CONCLUSIONS: Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient's response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.

Audiological Outcomes of Type 1 Tympanoplasty Using Conchal Cartilage and Temporalis Fascia.

OBJECTIVE: To compare the efficacy of conchal cartilage graft and temporalis fascia graft in Type 1 tympanoplasty in terms of graft uptake and hearing improvement. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Otolaryngology, Khyber Teaching Hospital, Peshawar, Pakistan, from January 2020 till December 2022. METHODOLOGY: Using quota sampling, 2 groups were made i.e. conchal cartilage group (Group A) and temporalis fascia group (Group B). Total of 124 records were selected with 62 records from each group. Graft uptake rate and audiological outcomes were compared between the groups. Moreover, postoperative complication rate was also noted for each group. RESULTS: The graft uptake rates between Group A and B at 3rd month were compared postoperatively (98.39%, 93.55%, p=0.36). The difference between preoperative mean air-bone gap (ABG, 28.05 ± 2.19dB, 28.68 ± 2.38 dB, p=0.12) and postoperative mean ABG (13.35 ± 3.45, 14.47 ± 3.29, p=0.69) was also statistically not significant. However, the differences regarding audiological success rate between cartilage and fascia groups (96.77%, 82.25%, p=0.01) and average operating time (51.8 ± 2.1 vs. 43.5 ± 3.2 minutes, p=0.009) were significantly different. CONCLUSION: In chronic otitis media (COM) patients with subtotal perforations, endoscopic tympanoplasty using conchal cartilage or temporalis fascia as graft yielded comparable outcomes in terms of graft uptake, hearing improvement, and postoperative complications. However, using conchal cartilage, the procedure showed better audiological success rate. With temporalis fascia as graft, the procedure was performed in a shorter time. KEY WORDS: Chronic otitis media, Tympanoplasty, Temporalis fascia, Conchal cartilage, Subtotal perforation.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Overview, Treatment, and a Case Study.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon immune-mediated neuropathy with an often unknown etiology. Patients typically present with gradual muscle weakness, sensory loss, and reduced deep tendon reflexes. Diagnostic challenges persist due to the absence of specific lab findings and definitive criteria. Treatment commonly involves glucocorticoids, IVIG, or plasma exchange, with varied long-term outcomes. We aim to elucidate the diagnostic complexities and treatment modalities associated with chronic CIDP through a comprehensive review of a patient's clinical presentation, diagnostic work-up, and therapeutic interventions. A 70-year-old female with a complex medical history, including dermatomyositis and IgG subclass deficiency, presented with progressive lower extremity weakness and numbness. Initial workup including MRI and CT scans were inconclusive. She was diagnosed with CIDP based on electromyography (EMG)/nerve conduction studies and cerebrospinal fluid (CSF) analysis. Plasma exchange (PLEX) treatment was initiated but led to multifocal cerebral infarcts, complicating her course. Subsequent rounds of PLEX alongside dual antiplatelet therapy showed no adverse neurological events and yielded minimal to moderate improvement in her mobility. The patient was discharged to an inpatient rehabilitation center for continued care. Elevated WBCs and other abnormal lab results were monitored throughout, underscoring the need for a multidisciplinary approach in complex cases like this one. Our comprehensive overview of CIDP and its diagnostic and treatment complexities underscores the challenges clinicians face in both accurate diagnosis and effective management. The multifaceted approach - spanning history-taking, electrodiagnostic studies, and advanced imaging - highlights the necessity for a nuanced, evidence-based practice. The variability in treatment outcomes emphasizes the need for personalized medicine and continuous research to optimize therapeutic strategies. Given the inconclusive nature of some diagnostic tools and the variable treatment responses, there remains a clear need for ongoing study and long-term follow-up to further refine our understanding and management of CIDP.

Trends and racial disparity in primary pressure ulcer hospitalizations outcomes in the US from 2005 to 2014.

In the United States (US), pressure ulcers affect ≤3 million people and costs exceed 26.8 billion US dollars in spending. To examine trends in primary pressure ulcer (PPU) hospitalization mortality, length of hospital stay (LOS), and inflation-adjusted charges (IAC) in the US from 2005 to 2014 by race/ethnicity. We secondarily examined the relationship between race/ethnicity with PPU mortality, LOS, and IAC with race/ethnicity. This cross-sectional study used Nationwide Inpatient Sample (NIS) data from 2005 to 2014. The study sample included all hospitalizations with the designated ICD-9-CM code of 707.20-25 (pressure ulcer). There was a notable decline in PPU hospitalization from 11.5% to 7.77 % between 2005 and 2014. The mean mortality decreased from 2.32% to 1.12% (P < .001), the mean LOS declined from 9.39 days (P < .001), and the mean IAC per hospitalization decreased from $30,935 to $29,432 (P < .001). Positive changes observed in mortality, LOS, and IAC trends were consistent across different racial and ethnic groups. The results of multivariable logistic and linear regression analyses revealed that Black patients (ß = 0.68, 95% CI 0.36-1.01, P < .001) and patients belonging to the Other race/ethnic category (ß = 0.93, 95% CI 0.18-1.69) had longer hospital stays compared to their White counterparts. Regarding IAC, Black patients (ß = 2846, 95% CI 1254-4439, P < .005), Hispanic patients (ß = 6527, 95% CI 4925-8130), and patients from the Other race/ethnic category (ß = 3473, 95% CI 1771-5174) had higher IAC for PPU treatment compared to their White counterparts. PPU hospitalization discharges, as well as hospitalization mortality, LOS, and IAC, decreased during the study period, however, our findings revealed disparities in PPU outcomes among different racial/ethnic groups. Implications of the findings are discussed.

Revealing the metabolomics and biometrics underlying phytotoxicity mechanisms for polystyrene nanoplastics and dibutyl phthalate in dandelion (Taraxacum officinale).

Micro/nanoplastics (M/NPs) and phthalates (PAEs) are emerging pollutants. Polystyrene (PS) MPs and dibutyl phthalate (DBP) are typical MPs and PAEs in the environment. However, how dandelion plants respond to the combined contamination of MPs and PAEs remains unclear. In this study, we evaluated the individual and combined effects of PS NPs (10 mg L-1) and DBP (50 mg L-1) on dandelion (Taraxacum officinale) seedlings. The results showed that compared to control and individual-treated plants, coexposure to PS NPs and DBP significantly affected plant growth, induced oxidative stress, and altered enzymatic and nonenzymatic antioxidant levels of dandelion. Similarly, photosynthetic attributes and chlorophyll fluorescence kinetic parameters were significantly affected by coexposure. Scanning electron microscopy (SEM) results showed that PS particles had accumulated in the root cortex of the dandelion. Metabolic analysis of dandelion showed that single and combined exposures caused the plant's metabolic pathways to be profoundly reprogrammed. As a consequence, the synthesis and energy metabolism of carbohydrates, amino acids, and organic acids were affected because galactose metabolism, the citric acid cycle, and alanine, aspartic acid and glutamic acid metabolism pathways were significantly altered. These results provide a new perspective on the phytotoxicity and environmental risk assessment of MPs and PAEs in individual or coexposures.

Use and outcomes of antihypertensive medication treatment in the US hypertensive population: A gender comparison.

Background: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications' use and the effect of using antihypertensive medication treatment on blood pressure control among the U.S. adult with hypertension. Methods: Analysis of National Health and Nutrition Examination Survey (NHANES) data from (1999-2012) including individuals≥18 years old with hypertension. Study variables included gender, age, race/ethnicity, obesity, smoking, comorbidities, treatment medication type, and continuity of care. We used multivariate logistic regression in STATA V14. The data is presented as adjusted odds ratios (ORs) and 95% confidence interval (CI). Results: Of the 15719 participants, 52% were female. 49% of the antihypertensive medication users had their blood pressure under control (95% CI). In the adjusted logistic regression analysis, use of antihypertensive medications was found to be 12% greater in females as compared to males (OR=1.12; CI=1.02-1.22; P<0.05). No association between gender and blood pressure control was found. Blood pressure control was less likely achieved among 50 years or younger individuals, Blacks and Hispanics, obese, and those taking calcium channel blocker (CCB). Conclusion: Hypertensive females are more likely than males to use antihypertensive medications. The effectiveness of treatment to control blood pressure is equal across males and females. Our findings have implications for practitioners to account gender-specific approaches when discussing adherence to hypertension medication treatment with their patients.

Phytotoxicity assessment of dandelion exposed to microplastics using membership function value and integrated biological response index.

Microplastic (MP) pollution is a critical environmental issue. Dandelions could be used as a biomonitor of environmental pollution. However, the ecotoxicology of MPs in dandelions remains unclear. Therefore, the toxic effects of polyethylene (PE), polystyrene (PS), and polypropylene (PP) at concentrations of 0, 10, 100, and 1000 mg L-1 on the germination and early seedling growth of dandelion were investigated. PS and PP inhibited seed germination and decreased root length and biomass while promoting membrane lipid peroxidation, increasing O2•-, H2O2, SP, and proline contents, and enhancing the activities of SOD, POD, and CAT. Principal component analysis (PCA) and membership function value (MFV) analysis indicated that PS and PP could be more harmful than PE in dandelion, especially at 1000 mg L-1. In addition, according to the integrated biological response (IBRv2) index analysis, O2•-, CAT, and proline were sensitive biomarkers of dandelion contamination by MPs. Here we provide evidence that dandelion has the potential to be a biomonitor to assess the phytotoxicity of MPs pollution, especially PS with high toxicity. Meanwhile, we believe that if dandelion is to be used as a biomonitor for MPs, attention should also be paid to the practical safety of dandelion.

Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus.

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-ß-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.

Plant Metabolomics: An Overview of the Role of Primary and Secondary Metabolites against Different Environmental Stress Factors.

Several environmental stresses, including biotic and abiotic factors, adversely affect the growth and development of crops, thereby lowering their yield. However, abiotic factors, e.g., drought, salinity, cold, heat, ultraviolet radiations (UVr), reactive oxygen species (ROS), trace metals (TM), and soil pH, are extremely destructive and decrease crop yield worldwide. It is expected that more than 50% of crop production losses are due to abiotic stresses. Moreover, these factors are responsible for physiological and biochemical changes in plants. The response of different plant species to such stresses is a complex phenomenon with individual features for several species. In addition, it has been shown that abiotic factors stimulate multi-gene responses by making modifications in the accumulation of the primary and secondary metabolites. Metabolomics is a promising way to interpret biotic and abiotic stress tolerance in plants. The study of metabolic profiling revealed different types of metabolites, e.g., amino acids, carbohydrates, phenols, polyamines, terpenes, etc, which are accumulated in plants. Among all, primary metabolites, such as amino acids, carbohydrates, lipids polyamines, and glycine betaine, are considered the major contributing factors that work as osmolytes and osmoprotectants for plants from various environmental stress factors. In contrast, plant-derived secondary metabolites, e.g., phenolics, terpenoids, and nitrogen-containing compounds (alkaloids), have no direct role in the growth and development of plants. Nevertheless, such metabolites could play a significant role as a defense by protecting plants from biotic factors such as herbivores, insects, and pathogens. In addition, they can enhance the resistance against abiotic factors. Therefore, metabolomics practices are becoming essential and influential in plants by identifying different phytochemicals that are part of the acclimation responses to various stimuli. Hence, an accurate metabolome analysis is important to understand the basics of stress physiology and biochemistry. This review provides insight into the current information related to the impact of biotic and abiotic factors on variations of various sets of metabolite levels and explores how primary and secondary metabolites help plants in response to these stresses.

Bacteremia Associated With a Toothpick Lodged in the Duodenal Wall.

Toothpick ingestion and perforation of the gastrointestinal tract, although a very rare phenomenon, carries a very high mortality risk. Most cases of toothpick ingestion remain unnoticed until very late. The symptoms are often vague, with the most common being abdominal pain. Any obscure case of abdominal pain with bacteremia must be investigated for foreign body ingestion and perforation. A CT scan is the best initial diagnostic modality for toothpick perforation but has low sensitivity with laparoscopy, and endoscopy is the preferred diagnostic tool. No single bacterium is involved in bacteremia due to toothpick ingestion. Surgical or endoscopic removal of the impacted toothpick along with prompt antibiotic therapy leads to excellent outcomes. If left untreated or in case of a late diagnosis, it may lead to life-threatening consequences. Here, we present a case of a 44-year-old man who had ingested a toothpick that pierced through and was lodged in the duodenal wall, leading to bacteremia. The patient was successfully treated and discharged.

Assessing the impact of green consumption behavior and green purchase intention among millennials toward sustainable environment.

Social media is playing a vital role in the promotion of green products by reshaping the millennial green purchasing intention and green consumption behaviors, resulting in progressive growth toward sustainable environment and lower carbon emission. Non-organic consumption among humans has increased the carbon emission in contrary risked environment; therefore, consumption behavior and purchasing intention are required to change for better sustainable environment. This study's goal is to determine the effects of social media in molding the consumption behaviors while considering eco-labeling, eco-branding, social norms, and purchase intensions among millennials to promote green consumption and lower carbon emission. It was decided to use a cross-sectional questionnaire survey to get information from the students of different faculties including social sciences, engineering, and bio-sciences. SPSS.V.22 and Smart-PLS were used to analyzed the data. Results indicated that social media has a profoundly good impact on molding and impacting youth behaviors regarding the green consumption, resulting in increasing intention toward sustainable environment which results in lower carbon emission. The results are in line with the predictions and contextual analysis, as the whole world is coming back toward natural life and is working for environmental protection and sustainability specially to lower the carbon emission. Therefore, students are molding themselves toward green consumption. The study recommends that future research may be conducted to study more contextual variables, who has influence on the green consumption among the general public regarding green consumptions and lowering carbon emission and stepping toward the sustainable environment.

The likelihood approach for potential role of "GABRG2 (C588T, C315T) gene polymorphisms" on the poor response to carbamazepine therapy in Pakhtun population of Pakistan.

BACKGROUND: Gamma-aminobutyric acid A receptor, gamma 2 gene (GABRG2) encode the GABAA receptor which is responsible for fast neuronal inhibition. Polymorphisms in GABGR2 gene affect the clinical response of anti-epileptic drugs (AEDs). Therefore, we carried out an updated study to find the association GABRG2 gene polymorphisms with carbamazepine (CBZ) non-responsive therapy in the Pakhtun population. METHODS: A clinical prospective cohort study was conducted in 79 CBZ treated patients upon consent after the approval of Khyber Medical University Advanced Study and Research Board. Blood sample were taken at optimal dose of CBZ at base line, third and sixth months of the treatment. Blood level of CBZ was measure through reverse phase high performance liquid chromatography (HPLC). Restriction fragment length polymorphisms techniques were used to genotype GABRG2 gene in these patients. CBZ responses were evaluated on three and six months of study by measuring the decrease in frequency of seizure per week. RESULTS: The average maximum dose of CBZ was 455 ±â€…133 mg/day at baseline, 479 ±â€…142 mg/day at third month and 495 ±â€…133 mg/day at sixth month of the treatment. CBZ level was found within therapeutic range (4-12 mg/L) without any significant (P > .5) variations among the CC, CT and TT genotypes of GABRG2 (C588T and C315T) gene. But the poor clinical response during CBZ treatment was linked (P < .05) with CT and TT genotypes of GABRG2 (C588T and C315T) gene in Pakhtun Population. CONCLUSION: A poor response to CBZ was found in variant genotypes (CT and TT) of GABRG2 (C588T and C315T) gene in Pakhtun Population.

Probiotics (Bacillus clausii and Lactobacillus fermentum NMCC-14) Ameliorate Stress Behavior in Mice by Increasing Monoamine Levels and mRNA Expression of Dopamine Receptors (D1 and D2) and Synaptophysin.

Stress is a physiological consequence of the body to adversity. The gut-brain axis and probiotics are gaining interest to provide better treatment for stress and other neurological disorders. Probiotic (Lactobacillus fermentum NMCC-14 and Bacillus clausii, 1010 colony-forming unit/day/animal, per oral) effects were investigated in acute (up to day 7) and subacute (days 8-14) restraint-stressed and normal mice through behavioral paradigms (elevated plus maze: EPM, light dark box/dark light box: LDB, and open field test: OFT). Time spent in the open arms of the EPM, time spent in the light compartment of the LDB, and movable time and time spent in the center of the OFT were significantly (p ≤ 0.05, n = 5) increased in probiotic-treated restraint-stressed mice. Enzyme-linked immunoassay determined blood cortisol and adrenocorticotropic hormone (ACTH) levels, which were reduced significantly (p < 0.05, n = 5) in probiotic-treated restraint-stressed mice. Hematoxylin and eosin-stained hippocampal slides also showed less or no neurodegeneration in the probiotic-treated animals. High-performance liquid chromatography and quantitative polymerase chain reaction were performed to determine the monoamine levels and mRNA expression of dopamine receptor subtypes (D1 and D2) and synaptophysin in the mice hippocampus (HC) and prefrontal cortex (PFC). The dopamine, serotonin, and norepinephrine levels were also significantly (p < 0.05, n = 5) increased in the HC and PFC of probiotic-treated animal brains. Fold expression of mRNA of D1 and D2 (except HC, LF-S, day 14) receptors and synaptophysin was also significantly (p < 0.05, n = 5) increased in the same brain parts of probiotic-treated restraint-stressed mice. Comparing mice in the Lactobacillus fermentum NMCC-14 and Bacillus clausii groups to mice in the normal group, only a significant (p < 0.05, n = 5) decrease was observed in the serum ACTH and cortisol levels on day 14 in Bacillus clausii-treated mice, where all other parameters also showed improvement. In comparison, Bacillus clausii showed greater stress suppressant activity than Lactobacillus fermentum NMCC-14. However, both probiotic bacteria can be a better and safer therapeutic alternative for ailments than currently available drugs.

Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer.

Thyroid cancer in humans has a fast-growing prevalence, with the most common lethal endocrine malignancy for unknown reasons. The current study was aimed to perform qualitative and quantitative investigation and characterization of the gut bacterial composition of euthyroid thyroid cancer patients. The fecal samples were collected from sixteen euthyroid thyroid cancer patients and ten from healthy subjects. The PCR-DGGE was conducted by targetting the V3 region of 16S rRNA gene, as well as real-time PCR for Bacteroides vulgatus, E.coli Bifidobacterium, Clostridium leptum and Lactobacillus were carried. High-throughput sequencing of V3+V4 region of 16S rRNA gene was performed on Hiseq 2500 platform on 20 (10 healthy & 10 diseased subjects) randomly selected fecal samples. The richness indices and comparative diversity analysis showed significant gut microbial modification in euthyroid thyroid cancer than control. At phylum level, there was significant enrichment of Firmicutes, Verrucomicrobia, while a significant decrease in Bacteroidetes was detected in the experimental group. At family statistics, significant high levels of Ruminococcaceae and Verrucomicrobiaceae, while the significant lower abundance of Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Alcaligenaceae was after observed. It also found that the significantly raised level of Escherichia-Shigella, Akkermansia [Eubacterium]_coprostanoligenes, Dorea, Subdoligranulum, and Ruminococcus_2 genera, while significantly lowered genera of the patient group were Prevotella_9, Bacteroides and Klebsiella. The species-level gut microbial composition showed a significantly raised level of Escherichia coli in euthyroid thyroid cancer. Thus, this study reveals that euthyroid thyroid cancer patients have significant gut microbial dysbiosis. Moreover, Statistics (P<0.05) of each gut microbial taxa were significantly changed in euthyroid thyroid cancer patients. Therefore, the current study may propose new approaches to understanding thyroid cancer patients' disease pathways, mechanisms, and treatment.