Reduction of APOE accounts for neurobehavioral deficits in fetal alcohol spectrum disorders.

A hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in the APOE enhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

Zamzam Water Mitigates Cardiac Toxicity Risk through Modulation of GUT Microbiota and the Renin-angiotensin System.

BACKGROUND: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam). OBJECTIVE: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions. METHODS: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p). RESULTS: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte. CONCLUSION: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.

Design of a pyrolysis system and the characterisation data of biochar produced from coconut shells, carambola pruning, and mango pruning using a low-temperature slow pyrolysis process.

Biochar production is an effective approach to managing abundant agricultural wastes. Pruning wastes from trimming the branches of trees such as carambola and mango, as well as coconut shells, are among the agricultural wastes that have reutilisation potential, which would simultaneously reduce the space required for disposal. In this study, the potential use of these wastes by converting them into biochar was investigated. The data presented in this study highlight the design of a pyrolysis system for a low-temperature slow pyrolysis process, as well as the characterisation data of the biochar produced using this system. The data collected included the elemental composition, porosity, as well as surface and adsorption characteristics of the biochar. These data indicate that the biochar produced had certain qualities that would enable its use for specific agricultural and industrial purposes. Meanwhile, the design indicated that it could facilitate small farms with specific outputs. In brief, these data can be used as references for developing a small-scale system for agricultural waste management using different types of crops.

Analysis of Correlation Between LncRNA TDRG1 Expression and its Prognosis in Cervical Carcinoma Tissues.

To explore and analyze the correlation between LncRNA TDRG1 expression degree and the prognosis of cervical carcinoma tissues. The cervical cancer tissues and para-carcinoma tissues of 106 patients with cervical carcinoma surgically removed in our hospital were chosen as specimens. LncRNA TDRG1 expression in cervical carcinoma tissues and para-carcinoma tissues was inspected by real-time fluorescence quantitative PCR, and the correlation between LncRNA TDRG1 and the clinicopathological parameters and disease prognosis was analyzed. The relative expression of LncRNA TDRG1 in cervical carcinoma tissues was critically gone up (P < 0.05) compared to para-carcinoma tissues. The relative expression of LncRNA TDRG1 in cervical carcinoma was correlated with FIGO staging, lymph node metastasis, infiltrating depth of cervical basal, and the differentiation of cancer cells (P < 0.05). According to the results of the Kaplan-Meier curve and Log-rank test, the overall survival conditions of subjects with low-lncRNA TDRG1 were superior to that of those with high-lncRNA TDRG1 expression (P < 0.05). The expression of LncRNA TDRG1 in cervical carcinoma tissues and the clinicopathological features in predicting the overall survival (OS) in sufferers with cervical carcinoma were investigated by the Cox regression model. LncRNA TDRG1 expression in cervical carcinoma tissues is tightly associated with the progression and prognosis of cervical carcinoma, which may be a latent biological indicator for clinical diagnosis and prognosis of cervical carcinoma.

New paracetamol hybrids as anticancer and COX-2 inhibitors: Synthesis, biological evaluation and docking studies.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.

Mature teratoma of liver in an adult male patient.

Teratomas are germ cell tumors occurring usually in gonadal organs. They are neoplasms composed of one or more of the three germ layers. Extragonadal teratomas are uncommonly reported in the literature. The liver is an extremely rare site for teratoma, constituting < 1% of all teratomas. The majority of the liver teratomas are found in the pediatric population with only a dozen cases reported in adults to the best of our knowledge. We present a case of a 27-year-old male with a history of abdominal pain of 5 months duration. CT scan revealed liver mass suggesting teratoma. The patient underwent cholecystectomy and segmental liver resection. Histopathology revealed mature cystic teratoma. Complete resection remains the best treatment option. Teratomas of the liver are extremely rare, constituting < 1% of all teratomas. An extensive review of the literature yielded < 50 cases of primary hepatic teratomas with only a dozen cases in adults and only two cases in males.

Fatty acid metabolism changes in association with neurobehavioral deficits in animal models of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) show behavioral problems due to prenatal alcohol exposure (PAE). A previous study reports changes in gene expressions linked to fatty acid (FA) metabolism in the cerebral cortex of the PAE mouse model. We find an increase of palmitic acid and arachidonic acid in phospholipid in the cerebral cortex of PAE at postnatal day 30. The increase of palmitic acid is consistent with increase of the producing enzyme, Fasn (fatty acid synthase). Decrease of 26:6 FA is also consistent with the increase of the enzyme which uses 26:6 as a substrate for making very long chain FAs, Elovl4 (elongation of very long chain fatty acids protein 4). However, there is no increase in the elongated products. Rather, lipid droplets (LDs) accumulated in the brain. Although FA-associated metabolic measurements are not affected by PAE, the abundance of FA-related gut microbiota is altered. This suggests that the gut microbiome could serve as a tool to facilitate uncovering the brain pathophysiology of FASD and a potential target to mitigate neurobehavioral problems.

Susceptibility of Diabetic Patients to COVID-19 Infections: Clinico-Hematological and Complications Analysis.

BACKGROUND: Coronavirus disease 2019 has become a global health threat resulting in a catastrophic spread and more than 3.8 million deaths worldwide. It has been suggested that there is a negative influence of diabetes mellites (DM), which is a complex chronic disease, on COVID-19 severe outcomes. Other factors in diabetic patients may also contribute to COVID-19 disease outcomes, such as older age, obesity, hyperglycaemia, hypertension, and other chronic conditions. METHODS: A cohort study was conducted on the demographics, clinical information, and laboratory findings of the hospitalised COVID-19 with DM and non-DM patients were obtained from the medical records in King Faisal Specialist Hospital and Research Centre, Saudi Arabia. RESULTS: Among the study population, 108 patients had DM, and 433 were non-DM patients. Patients with DM were more likely to present symptoms such as fever (50.48%), anorexia (19.51%), dry cough (47.96%), shortness of breath (35.29%), chest pain (16.49%), and other symptoms. There was a significant decrease in the mean of haematological and biochemical parameters, such as haemoglobin, calcium, and alkaline phosphate in people with diabetes compared to non-diabetics and a considerable increase in other parameters, such as glucose, potassium, and cardiac troponin. CONCLUSIONS: According to the findings of this study, patients who have diabetes have a greater risk of developing more severe symptoms associated with COVID-19 disease. This could result in more patients being admitted to the intensive care unit as well as higher mortality rates.

Preanalytical Errors in a Hematology Laboratory: An Experience from a Tertiary Care Center.

BACKGROUND: Laboratory errors arise at any stage of testing. Detecting these inaccuracies before results are revealed might delay diagnosis and treatment, causing patient distress. Here, we studied the preanalytical errors in a hematology laboratory. METHODS: This one-year retrospective analysis was conducted at the laboratory of a tertiary care hospital and included information on blood samples that were taken for hematology tests from both outpatients and inpatients. Laboratory records included sample collection and rejection information. The type and frequency of preanalytical errors were expressed as a proportion of total errors and sample number. Microsoft Excel was utilized to enter data. The results were presented in the form of frequency tables. RESULTS: This research included 67,892 hematology samples. For preanalytical errors, 886 samples (1.3%) were discarded. The most common preanalytical error was insufficient sample (54.17%), and the least common was an empty/damaged tube (0.4%). Erroneous samples in the emergency department were mostly insufficient and clotted, whereas pediatric sample errors were caused by insufficient and diluted samples. CONCLUSION: Inadequate samples and clotted samples account for the vast majority of preanalytical factors. Insufficiency and dilutional errors were most frequent from pediatric patients. Adherence to best laboratory practices can drastically cut down on preanalytical errors.

Prevalence of Undiagnosed Iron Deficiency Anemia and Associated Factors Among Female Undergraduate Medical Students in Makkah, Saudi Arabia.

INTRODUCTION: Iron deficiency anemia is the most common type of anemia according to the World Health Organization. Females are more likely to be affected than males. There are several factors causing iron deficiency anemia, such as increased loss of iron, decreased intake of iron, and increased utilization of iron. There are limited research studies evaluating the risk factors that cause anemia among female medical students in Saudi Arabia. For this, the study aimed to identify the prevalence of undiagnosed iron deficiency anemia (IDA) among young female university students and to identify if there is any correlation between IDA and several factors including dietary habits, psychological stress, anxiety status, and body mass index. MATERIALS AND METHODS: A cross-sectional observational study was performed between October 2022 and December 2022 with a sample of 100 healthy female students aged between 19 and 23 years, who were studying at the medical colleges of Umm Al-Qura University, Saudi Arabia. Blood samples were collected to perform complete blood count and iron profile tests. Also, a survey was done to find correlation between iron deficiency anemia and dietary intake, drinks, stress, anxiety, and body mass index (BMI). Independent t-test or Mann-Whitney U test were used to compare values for non-anemic with anemic participants, and linear regression tests were used to analyze differences between non-anemic and anemic participants' dietary intake factors and stress and anxiety scores. The level of significance was set at p<0.05. RESULTS: The findings represent an overall prevalence of iron deficiency anemia in female medical students based on the lab finding results. Thus, students were divided into two following groups: anemic (13%) with hemoglobin (Hb) concentration <12 g/dL and non-anemic (84%) with Hb concentration ≥12 g/dL. When comparing the two groups, results showed significant differences in the majority of RBC indices (hematocrit {HCT}, mean corpuscular volume {MCV}, mean corpuscular hemoglobin {MCH}, red cell distribution width {RDW}) and iron profiles, p-value was <0.05. On evaluation of the different types of food consumption, the mean iron intake was around 7 mg/day, and in 65% of the participants, it was below the estimated average requirement (EAR) of iron (8.1 mg/dL). The perceived stress scale (PSS) shows that 63% of the participants experienced moderate stress and 58% reported severe anxiety by the generalized anxiety disorder (GAD) scale. In multiple linear regression, iron was positively associated with hemoglobin concentrations, whereas stress scores were negatively associated with hemoglobin concentrations. CONCLUSION: There is a relatively low prevalence of anemia and most of it was found of the microcytic type, indicating that this condition is a common health issue among local female college students. There was no independent association between stress or anxiety and hemoglobin levels.

Prevalence of depression, anxiety, stress and its relationship with knowledge about COVID-19 in medical and laboratory medicine students of Umm-Al-Qura University: a cross-sectional survey.

Introduction: Coronavirus disease 2019 (COVID-19) pandemic has continued relentlessly for over one and half years now, causing a threat to life, fear of falling sick, helplessness, anxiety, depression and, pessimism about the future. There has been an increasing concern over student mental health in higher education. Our study was designed to measure current mental health status and its relationship with sociodemographic variables and level of knowledge about COVID-19 in Saudi Arabia. Method: A cross-sectional survey was conducted among laboratory medicine students of Makkah city, Saudi Arabia from October, 2020 to January, 21. A semi-structured questionnaire was circulated through mail and What's App. Data collected included sociodemographic details and level of knowledge towards the COVID-19 among the students. Depression anxiety and stress-21 item (DASS 21) was used to assess psychological status. Result: Our study reported 51.4% depressive symptoms, 57.9% anxiety symptoms, and 48.5% stress in the study participants. History of being hospitalized with COVID-19 and ICU reported high anxiety (p = 0.0003) and depression scores (p = 0.04). Respiratory droplet as a mode of transmission revealed higher scores on anxiety subscale (p = 0.007), whereas surface contamination reported high score of stress (p = 0.004) and anxiety (p = 0.002). Knowing that COVID-19 can also clinically present with gastrointestinal symptoms was found to show high stress (p = 0.005) and anxiety (p = 0.01) scores than any other way of clinical presentation. Conclusion: COVID-19 is likely to cause negative effect on the psychological health of students.

Knowledge and Attitude toward Hemoglobinopathies in Premarital Screening Program among the General Population in the Western Region of Saudi Arabia.

The National Premarital Screening Program, which includes sickle cell disease and thalassemia, was made mandatory in 2004 by the Kingdom of Saudi Arabia (KSA), and the earlier studies have shown a poor knowledge and negative attitude toward this program in the different study groups. This study was conducted to assess the knowledge and attitudes toward premarital screening (PMS) in a randomly selected national sample of the Saudi population, 18 years and above. This was a cross-sectional study conducted in the Saudi population in the western region between July and December 2021. Valid and reliable questionnaire and data were collected from 893 participants aged ≥18 years. The χ2 test was used to ascertain if there is an association between categorical variables. Multivariate logistic regression was used to determine factors predicting satisfactory knowledge. All 893 study participants had heard about PMS with 625 (70.0%), 244 (27.3%) and 24 (2.7%) having satisfactory, fair and poor knowledge, respectively. Participants aged 26-35 years (p =0 .038), females (p < 0.001), those with higher education (p = 0.003) and employed (p = 0.004), had a better knowledge compared to other groups. Most of the participants had a positive attitude toward PMS. There is a changing trend in the knowledge and attitude toward PMS with a greater number of people wanting to go for PMS. There is also an improvement in the number of participants opting out of marriage in case of incompatibility with their future partner. However, the health education programs need to be improved regarding the hemoglobinopathies.

Multi-omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress.

Entamoeba histolytica is responsible for dysentery and extraintestinal disease in humans. To establish successful infection, it must generate adaptive response against stress due to host defense mechanisms. We have developed a robust proteomics workflow by combining miniaturized sample preparation, low flow-rate chromatography, and ultra-high sensitivity mass spectrometry, achieving increased proteome coverage, and further integrated proteomics and RNA-seq data to decipher regulation at translational and transcriptional levels. Label-free quantitative proteomics led to identification of 2344 proteins, an improvement over the maximum number identified in E. histolytica proteomic studies. In serum-starved cells, 127 proteins were differentially abundant and were associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport. The virulence factor, Gal/GalNAc-inhibitable lectin subunits, was significantly altered. Integration of transcriptomic and proteomic data revealed that only 30% genes were coordinately regulated at both transcriptional and translational levels. Some highly expressed transcripts did not change in protein abundance. Conversely, genes with no transcriptional change showed enhanced protein abundance, indicating post-transcriptional regulation. This multi-omics approach enables more refined gene expression analysis to understand the adaptive response of E. histolytica during growth stress.

Trends in methicillin-resistant Staphylococcus aureus in the Gulf Cooperation Council countries: antibiotic resistance, virulence factors and emerging strains

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous pathogen that is increasing in Gulf Cooperation Council (GCC) countries. It is implicated in a wide range of infections, from superficial skin infections to life-threatening syndromes. MRSA has moved beyond healthcare facilities, affecting individuals in the community without substantial risk factors. Aims: To review the prevalence and molecular characterization of MRSA in GCC countries during 2011–2021. Methods: We comprehensively searched PubMed using the following keywords: MRSA, Staphylococcus aureus, GCC, Kuwait, Saudi Arabia, Bahrain, Oman, Qatar, UAE, prevalence, and molecular characterization for articles published after 2011. Results: Thirty-nine of 111 articles examined, fulfilled the purpose of this review. Most studies were in Kuwait (44%), Saudi Arabia (28%) and United Arab Emirates (10%). Studies from other GCC countries were sporadic. Several studies demonstrated a clear emergence in antibiotic resistance especially against fusidic acid, ciprofloxacin and clindamycin. Regional prevalence of MRSA is reported as 25–35%, with clear dominance of community-acquired (CA)-MRSA. Panton–Valentine leucocidin (PVL)-producing strains accounted for 35–45%, with clear association with CA-MRSA emergence, but there were some sporadic reports of incorporation of PVL in healthcare-associated (HA)-MRSA. The reported dominant strains included EUST80, USA1100 and WA-MRSA-51. Novel strains are more likely to produce PVL and show fusidic acid resistance. Conclusion: There is a need for national and regional MRSA surveillance programmes, especially with the emergence of strains that require no underlying risk factors to cause illness, as well as the propagation of chimeric resistance elements in both HA-MRSA and CA-MRSA.

Anemia Burden among Hospital Attendees in Makkah, Saudi Arabia.

Background: Anemia is a major health problem in Saudi Arabia and has multiple etiologies. Many studies have been conducted in Saudi Arabia in specific population groups like school children, adolescents, university students, and females in the reproductive age group, and most have reported high prevalence of anemia. This study was conducted in a specialist hospital in Makkah city and includes all outpatients aged 15 years and above. Objective: To study the burden of anemia among hospital attendees, its stratification based on gender and age, and its severity along with the morphological types of anemia. Methods: This is a study conducted at a specialist hospital in Makkah city and one-month data were collected retrospectively from the laboratory database and include demographic and routine hematological results of complete blood count (CBC). Results: A total of 21,524 patients were included, out of which 9444 (43.9%) were males and 12020 (56.1%) were females. The overall prevalence of anemia was 38.7% (8339). Prevalence was very high in females, accounting for 68.2% (5689), whereas it was 31.8% (2650) in males. There were 39.6% (3301), 43.9% (3657), and 16.6% (1381) cases of mild, moderate, and severe anemia, respectively. In females, anemia was more prevalent in the age group of 15 to 49, which is considered as the reproductive age group. Microcytic anemia was the most prevalent type observed in this age group, accounting for 40.7% of all anemia cases. Normocytic anemia was more prevalent in the males, accounting for 52%. Conclusion: Our study showed high prevalence of anemia among the patients attending outpatient departments in a specialist hospital. Females have high prevalence of anemia when compared to male population. Microcytic anemia was the most common anemia type among females and was seen in the 15-49 age group. There is an increase in prevalence of anemia with age for males, whereas, in females, increased prevalence is observed in the reproductive age groups and the anemia prevalence maintained a steady decrease towards the 5th to the 9th decades. Normocytic anemia was more prevalent in the 5th to the 9th decades, indicating that there are more etiologies other than iron deficiency in the causation of anemia. Macrocytic anemia was the least reported anemia type. Anemia of mild and moderate severity was predominant in both genders, although severe anemia showed higher prevalence in females as compared to males. Conclusion: Our study showed high prevalence of anemia among the patients attending outpatient departments in a specialist hospital. Females have high prevalence of anemia when compared to male population. Microcytic anemia was the most common anemia type among females and was seen in the 15-49 age group. There is an increase in prevalence of anemia with age for males, whereas, in females, increased prevalence is observed in the reproductive age groups and the anemia prevalence maintained a steady decrease towards the 5th to the 9th decades. Normocytic anemia was more prevalent in the 5th to the 9th decades, indicating that there are more etiologies other than iron deficiency in the causation of anemia. Macrocytic anemia was the least reported anemia type. Anemia of mild and moderate severity was predominant in both genders, although severe anemia showed higher prevalence in females as compared to males. Conclusion. Anemia is highly prevalent in adolescents, adults, and the elderly in Makkah region. The most common cause is thought to be iron deficiency, although other causes are not uncommon. The authorities need to address the problem of prevention and reduction in anemia prevalence by taking effective measures and interventions.

Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19.

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.

Why myringoplasties fail? Impact of relevant clinical factors on the surgical outcome; a study from pakistan.

BACKGROUND: Myringoplasty is the reconstruction of the tympanic membrane by grafting. Success varies from 50-100%. A study was conducted to unveil the vital causes for failed myringoplasty with an aim to attenuate graft rejections and augment better outcomes. METHODS: It was descriptive case series in which data was retrospectively collected at a tertiary care hospital (Rawalpindi, Pakistan) from January 2009 to December 2018. First 600 consecutive patients who qualified for inclusion/ exclusion criteria, underwent myringoplasties were followed-up for 6 months. Graft Take/Failure, the main outcome variable, was correlated with relevant independent variables. Data was collected on a structured pro forma, approved by hospital ethical committee. Data was analysed using IBM-SPSS- 21.0. RESULTS: Out of 600, 164 (27.3%) had graft rejection; failure being significantly enhanced by increasing age (p<0.001), larger perforation (p-0.025), co-morbidities (p<0.001), especially diabetics (p=0.040) and Eustachian tube (p-0.016) dysfunction amongst among systemic and ENT diseases respectively, and discharge-free ear (Dry Ear) for <4 weeks (p<0.001); while best graft take was achieved with end-aural surgical technique (p=0.048). Gender (p-0.897) did not caste a significant impact on graft outcome. CONCLUSIONS: The results of various surgical approaches of myringoplasty are equitable. Proper socio-demographic and clinical evaluation can improve graft outcome, and this surgery shall be discouraged in patients with diabetes mellitus and defective Eustachian Tube functions.

Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure.

Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging, and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. In C3H/HeJ mice, similar numbers of proteins were differentially regulated between sexes at baseline compared with within each sex after sub-chronic nicotine administration. In C57BL/6J mice, there were significantly greater numbers of proteins differentially regulated between sexes at baseline compared with within each sex after chronic nicotine administration and withdrawal. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.

Primary cilia safeguard cortical neurons in neonatal mouse forebrain from environmental stress-induced dendritic degeneration.

The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown. Here we show, using neonatal mouse as a model system, that primary cilia, hair-like protrusions from the neuronal cell body, play an essential role in protecting immature neurons from the negative impacts of exposure to environmental stress. More specifically, we found that primary cilia prevent the degeneration of dendritic arbors upon exposure to alcohol and ketamine, two major cell stressors, by activating cilia-localized insulin-like growth factor 1 receptor and downstream Akt signaling. We also found that activation of this pathway inhibits Caspase-3 activation and caspase-mediated cleavage/fragmentation of cytoskeletal proteins in stress-exposed neurons. These results indicate that primary cilia play an integral role in mitigating adverse impacts of environmental stressors such as drugs on perinatal brain development.

Long-term spatial tracking of cells affected by environmental insults.

BACKGROUND: Harsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny. METHODS: The reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP+ and RFP- cortical neurons in animals prenatally exposed to arsenite. RESULTS: We detected RFP+ neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP+ cortical neurons. CONCLUSION: The reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism.