Consanguineous Marriages and Dental Anomalies: A Cross-Sectional Analytical Study.

Objective: To determine the correlation between consanguineous marriages and dental anomalies. Study Design. A cross-sectional analytical study. Materials and Methods: This cross-sectional analytical multicentered study was carried out at Foundation University College of Dentistry after approval of the Ethical Research Committee (ERC) from September 2021 to November 2021 in Pakistan. All pediatric patients (4-10 years old) with dental malformations undergoing dental procedures or examinations and born with spontaneous vaginal delivery and uncomplicated cesarean section participated in the study. First, second, and third-degree relatives' marriages of parents were used to define consanguinity. The Basic Pay Scale was the reference of estimation of socioeconomic status. Participants with a history of orofacial trauma, pertinent parental history (infertility, hormonal treatment, or infectious diseases during pregnancy, conception with assisted reproductive techniques, prolonged complicated labor, premature deliveries, and twin births), and prolonged hospital admission immediately after birth were excluded from the study. Results: The mean maternal and paternal age was recorded to be 23.86 ± 5.4 and 27.07 ± 9.6, respectively, whereas the mean age of participants was 6.60 ± 1.67. There were 297 children with congenital abnormalities, with 203 (68.4%) males and 94 (31.6%) females. The prevalence of consanguineous marriage was found to be in 210 (70.7%) participants. Congenital dental anomalies correlation was found to be significant with consanguineous marriages (p value <0.001). Consanguineous marriages were more frequent in the lower socioeconomic group when compared with the middle and upper socioeconomic groups, respectively (74.7% vs. 8.1% vs. 17.2%, p value 0.007). Conclusion: Congenital dental anomalies were significantly prevalent in consanguineous marriages with greater incidence in lower socioeconomic groups. Consanguineous marriages have the propensity to transmute population conformation, but due to religious and social beliefs, literature is hesitant to ascribe congenital dental anomalies persuasive relevance with consanguinity.

Evaluation of adverse effects with COVID-19 vaccination in Pakistan.

OBJECTIVES: Vaccinations work with different mechanisms to offer protection against disease; however, process of immunity building can cause symptoms. Therefore, this study aimed to determine the immediate side effects of COVID-19 vaccination in the Pakistani Population. METHODS: This cross-sectional analytical study was conducted at Foundation University College of Dentistry, Islamabad from February to April 2021. 0.5 mL per dose of the Covid-19 vaccine was administered to the candidates. These 205 candidates receiving vaccination were then interviewed investigating the adverse effects of the vaccine. Post-vaccination side effects were compared among categorical groups using the Chi-Square test, whereas post-vaccination side effects were compared with age using independent samples T-test. A p-value of ≤0.05 was statistically significant. RESULTS: Among post-vaccination side effects, fever was reported by 69 participants, while 56 of 205 reported soreness, redness, and swelling at the injection site. It was reported by 42/205 participants to have felt chills and rigor, whereas gastrointestinal disturbance and flu-like symptoms were reported in 55/205 and 28/205 participants, respectively. Younger participants were more likely to develop gastrointestinal disturbance and flu-like symptoms following vaccination as compared to older participants. CONCLUSION: Malaise, headache, and fever were observed to be the most common side effects of the vaccine, moreover there was a linear relationship between manifestations of adverse effects and history of comorbidities.

Extracellular microRNAs: key players to explore the outcomes of in vitro fertilization.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. METHODS: This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. RESULTS: The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865). CONCLUSION: Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve.

Real-Time Polymerase chain reaction trends in COVID-19 patients.

OBJECTIVE: To assess trends of real-time Polymerase Chain Reaction test in Coronavirus infected Patients. METHODOLOGY: This cross-sectional analytical study was conducted at Tertiary Care Institute, Rawalpindi from March 2020 to June 2020. All patients confirmed COVID positive by real-time Polymerase Chain Reaction (PCR) with recent travel history, close contact with known diagnosed patients and had symptoms of fever or upper respiratory tract with body aches. Nasopharyngeal swabs were taken and results generated within 48 hours. Positive PCR was admission criteria follow up was carried out at 7th and 8th day, with negative PCR were discharged. However, those who had persistent positive PCR on the 8th day were tested again on 11th and 12th day. Those with persistent positive results beyond 12th day were shifted to specialized quarantine centres. RESULTS: A total of three hundred and ninety-two patients with mild to moderate illness, PCR positive for COVID 19 were included study with age range 9 - 45 and mean 33.22±7.98 years. A total of 8 (2%) patients were females and 384(98%) males. The duration of the negative test result was Mean ± Std. Deviation 9.05±2.00 with 7 - 8 days 152(38.8%)in and 11 - 12 days in 160(40.8%). PCR results on Day 7 and 8 were negative in 144(36.7%) patients whereas positive in 248(63.3%). PCR results on Day 11 and 12 were negative in 312(79.6%) patients whereas positive in 80 (20.4%). CONCLUSION: To conclude Real-Time Polymerase Chain Reaction (rT-PCR) inclines to give false negative results additionally can stay positive in asymptomatic patients for moderately longer-term. Hence decision to discharge ought to be intricately adjusted between RT-PCR, clinical judgement, radiological examinations, and biochemical assays.

Melatonin levels and microRNA (miRNA) relative expression profile in the follicular ambient microenvironment in patients undergoing in vitro fertilization process.

PURPOSE: Intrafollicular fluid (IFF) melatonin plays a decisive role in maintaining granulosa cells' DNA integrity and protects them against apoptosis. It reduces oxidative stress and improves the oocyte quality with a higher fertilization rate. METHOD: This prospective study investigated the antioxidant property of IFF melatonin and its impact on IVF outcome parameters. We also explored the relative expression of five microRNAs (miR-663b, miR-320a, miR-766-3p, miR-132-3p, miR-16-5p) and levels of cell-free DNA (cfDNA) by real-time PCR in unexplained infertile patients. We collected 425 follicular fluid (FF) samples containing mature oocytes from 295 patients undergoing IVF. RESULTS: Patients were subgrouped based on IFF melatonin concentration (group A ≤ 30 pg/mL, group B > 70 to ≤ 110 pg/mL, group C > 111 to ≤ 385 pg/mL). Our results showed that patients with ≤ 30 pg/mL IFF melatonin levels have significantly higher oxidative stress markers, cfDNA levels, and lower relative expression of miR-663b, miR-320a, miR-766-3p, miR-132-3p, and miR-16-5p compared to other subgroups (p < 0.001). Similarly, they have a low fertilization rate and a reduced number of high-quality day 3 embryos. CONCLUSION: Findings suggest that the therapeutic use of melatonin produces a considerable rise in the number of mature oocytes retrieved, fertilization rate, and good-quality embryo selection. Furthermore, miRNA signature enhances the quality of embryo selection, thus, may allow us to classify them as non-invasive biomarkers to identify good-quality embryos.

Establishment of Diagnostic Protocols for COVID-19 Patients.

OBJECTIVE: To evaluate the oscillation of laboratory parameters among indoor patients infected with COVID-19. METHODS: This cross-sectional analytical study was conducted at Tertiary Care Institute, Rawalpindi from 01 March 2020 to 20 May 2020. Three hundred and ninety-two patients with mild to moderate illness, PCR positive for COVID 19 were included. Prevalence of typical symptoms of coronavirus disease cough, fever, sore throat and shortness of breath was recorded.PCR was repeated after seven days of admission, if declared negative, another executed on consecutive day. Discharge Criteria was two consecutive negative PCR. RESULTS: A total of 392 patients enrolled in the study with age range 9-45 and mean 33.22±7.98 years. A total of 8 (2%) patients were females and 384(98%) males. 296(75.5%) did not have a cough whereas 96(24.5%) presented with the trait. 296 (75.5%) patients did not have associated fever whereas 96(24.5%) manifested with fever. Chest x-ray had a bilateral patch in 96 (24.5%) patients only. Ferritin was raised in 96 (24.5%) patients however were recorded within normal limits in 296(75.5%) patients. Coagulation Profile was deranged in 64(16.3%) patients whereas was within range in 328(83.7%) patients. Serum Bilirubin, Serum Alkaline phosphatases, Serum Albumin, Serum Urea, Serum Potassium were essentially in typical tolls in 392(100%) patients. However Serum Alanine Aminotransferase was raised in 32(8.2%), Serum C reactive Protein was elevated in 48(12.2%). An exaggerated values of serum creatinine and serum sodium were noticed in 24(6.1%) and 16(4.1%) respectively. CONCLUSION: Routine haematological tests, biochemical tests, serological tests, and radiographic tests are crucial to conclusion, foundation and progression of ailment in COVID-19 contaminated patients.

Synhesis of Silver and Copper Nanoparticles from Plants and Application as Adsorbents for Naphthalene decontamination.

Synthesis of nanoparticles by using plants is biological method of synthesis that is ecofriendly as well as low cost. Naturally available precursor in the form of plants extract is used. In our research we used three different plants such as Aloe barbedensis, Azadirachta indica and Coriandrum sativum that are easy to cultivate and also available everywhere. By using above mentioned plants we synthesize two types of nanoparticles one is (Ag-NPs) and other one is (Cu-NPs). Chemical method of nanoparticles synthesis have hazardous to health as well as have environmental threats but as comparison with biological method of nanoparticles synthesis is very environment friendly also safe in use. FTIR (Fourier Transform Infrared) spectroscopy analysis and UV-Visible Spectrophotometer are used for characterization. Our research work is actually based on wastewater remediation by using silver and copper nanoparticles. Water that is contaminated with naphthalene used, further decontaminated and purify by using nanoparticles. Different batch experiments are conducted to check the efficiency of these synthesized nanoparticles by using naphthalene (PAHs) as removal area. 98.81% removal is higher by using plant Azadirachta indica and least adsorption power is in case of Coriandrum sativum that is 95.29%. At the end, kinetic and equilibrium study applied.

Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment.

Despite many advances in assisted reproductive technology (ART), the most viable embryo selection remains a challenge for infertility treatment. This study was designed to investigate whether intra-follicular circulating cell-free DNA (cfDNA) fragments and Melatonin levels predict embryo quality in patients undergoing IVF treatment. A total of eight hundred and ninety-five follicular fluid (ff) samples were collected from 325 infertile patients undergoing IVF treatment. Patients were enrolled from August 2017 to December 2018 in the infertility center of a tertiary care hospital. A clear non-hematic follicular fluid was aspirated after the removal of eggs from the dominant follicles (>18mm) of each patient. Melatonin and E2 levels in each follicular sample were estimated by immune-chemiluminescence using commercially available kits. ALU-qPCR evaluated cfDNA levels in individual follicular fluid samples. Our study presented a significant and negative relationship between intra-follicular cfDNA and melatonin concentration (-0.541: P<0.001). Each individual follicle contains measurable copy number of cfDNA [mean: 1.85±2.98ng/µl (median; 1.86ng/µl (95% Cl: 0.96-2.87)]. In pregnant women cfDNA copy number was significantly decreased in follicular fluid samples(ff) aspirated from matured oocytes than in immature ones [p<0.01; ß = -0.42±0.49; median; 1.45ng/ml (95% Cl: 0.36-2.97) vs. 3.57ng/µl (95% Cl: 0.37-4.01) respectively. While melatonin concentration in ff samples corresponding to mature oocytes was significantly higher than in ff samples related to immature oocytes (p<0.001). Moreover, in pregnant women cfDNA level was significantly lower in ff samples related to oocytes which produces top-quality embryos versus low quality embryos [p<0.001; ß=1.81±0.91; median; 1.25ng/µl (95% Cl: 0.35-1.97)] vs. [(median; 3.65ng/ml (95% Cl: 1.23-6.36)] respectively. Likewise, in non-pregnant women melatonin levels were significantly decreased in ff samples related to embryos with high fragmentation rate (≥25%) than embryos with low fragmentation rate (<25%; p<0.001). Conclusively, this study indicates that Intra-follicular cfDNA and melatonin concentration possibly a new supplemental tool that supports to establish an advanced non-invasive early prognostic test for the patients undergoing IVF/ICSI procedure.

Chondrosarcoma of right big toe with metastases to left orbital and left infra temporal region.

To report a case of chondrosarcoma of right big toe with left orbital and left infra temporal metastases. Chondrosarcoma is the second most frequent primary malignant tumour of the bone. A 56 year old man had history of trauma on his right big toe, which was amputated and the biopsy in 2011 at Sindh Institute of Urology and Transplantation (SIUT) revealed chondrosarcoma with clear margins. Eventually the patient was presented with swelling of the left eye, pain and gradual loss of vision of that eye. Later a CT scan of his chest, brain and orbit showed pulmonary and pleural based nodule, with mediastinal and hilar lymphadenopathy representing metastatic deposit in left orbit, extending to left infra temporal region. A treatment of palliative chemotherapy was started with doxorubicin and ifosfamide, after which he was referred for radiotherapy. At that time he had loss of vision, pain and exopthalamus, and palliative radiotherapy was delivered to the left orbit with the prescribed dose of30 Gy/300cGy×10 fraction. Thereafter his case will be followed up at the oncology OPD after a 03 month interval.

Antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) are the predictors of natural fecundability have similar trends irrespective of fertility status and menstrual characteristics among fertile and infertile women below the age of 40 years.

BACKGROUND: Despite being born with a significant number of primordial cells which representing the ancestor cells of the germ-line, women experience a depletion of ovarian reserve and sub-fertility mid-way into their healthy lives. The poor ovarian response is a substantial limiting factor amplified with higher maternal age and associated with a considerably lower likelihood of pregnancy. METHODS: A present analytical prospective cross-sectional study was conducted to explore whether infertile women below the age of 40 years have low ovarian reserve than fertile women of same age, assessed by Antral follicle count (AFC) and anti-Müllerian hormone (AMH), at tertiary care infertility center: Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital. The study population including 423 infertile and 388 fertile female patients from June 2013 to November 2016. Patients and controls were aged between 25 and 39 years. Serum levels of FSH, LH, AMH were assessed, and AFC was measured by transvaginal sonography on cycle days 2 or 3. RESULTS: A total of 35.6% of infertile women stated a menstrual cycle length shorter than 21 days, while 21% had a regular cycle length between 24 and 38 days, and 43.2%, longer than 38 days. Overall, the two cohorts did not significantly differ on cycle length. The age-specific reduction of the ovarian reserve was similar in both cohorts; serum AMH concentration decreased by 6% (95% Cl: 5-8%) and AFC decline by 4.5% (95% Cl: 5-7%) per year with increased age. Aged patients (36-39 years) had a 5.3% (95% Cl, 1.5; 7.2) higher risk ratio of having an AMH level < 0.7 ng/ml than women of younger age groups (Kruskal-Wallis test, p < 0.01). CONCLUSION: This study indicates that the possible common observation of low respondent in ART might not be a result of over-representation of patients with an early age-specific decline in the ovarian reserve, but rather primarily as a consequence of age-specific depletion in the stock of developing follicles at the time of recruitment and selection.

Longer trinucleotide repeats of androgen receptor are associated with higher testosterone and low oxytocin levels in diabetic premature ejaculatory dysfunction patients.

BACKGROUND: Despite its worldwide high occurrence, the obscurity regarding the description, epidemiology and management of premature ejaculation remains provocative. It is well established that male premature ejaculatory dysfunction is an increasing problem due to spontaneous ejaculation across a variety of general and clinical subjects. The main goal of this study was to determine the relationships between trinucleotide repeats of the androgen receptor (AR), sex steroids, and pituitary hormones with sexual function in men with type 2 diabetes mellitus (DM) and reported with acquired premature ejaculation (PE). METHODS: A total of 150 normal and 250 PE + DM subjects were enrolled in this study. Each subject was invited to fill out an elaborative questionnaire to acquire precise selective information regarding BMI, duration of PE + DM, self-reported Intra-Vaginal Ejaculatory Latency Time (IELT), sexual and mental health status by using the premature ejaculation diagnostic tool (PEDT) and Beck Depression Inventory-II (BDI-II). Pearson's correlation analysis was used to analyze the relationship between clinical, hormonal, and genetic variables. Ward's minimum variance cluster analysis and principal component analysis were used for evaluation of dependence between genetic, clinical, and demographic parameters. RESULTS: The patients who have the lowest number of (≤21) (CAG)n repeats have higher serum oxytocin levels (114.2 pg/ml; n = 54, 43.2%) than the controls (69.18 pg/ml; n = 22, 17.6%) and the patients with the highest (≥26) number of (CAG)n repeats (62.9 pg/ml; n = 108, 43.2%).On the other hand, patients who have the highest numbers of (CAG)n repeats (≥26) have higher serum testosterone (6.1 ng/ml; n = 108, 43.2% of cohort) lower prolactin (3.01 ng/ml; n = 108, 43.2% of cohort) levels than the controls and patients with the lowest numbers (≤21) of (CAG)n repeats and their TSH (1.53 mIU/L, P < 0.05) levels are lower than those of controls. In the Pearson correlation model, self-estimated IELT demonstrated significantly negative correlation with both (CAG)n and (GCC)n repeats (r = - 0.16, p = 0.0001; r = - 0.19, p = 0.0001) respectively. These repeats have positive correlation with PEDT (r = 0.28, p = 0.0001: r = 0.24, p = 0.0001, whole model) and inversely correlated with BDI-II (r = - 0.25, p = 0.0001). CONCLUSION: This study indicates that androgen receptor polymorphism modulates the endocrine effect on ejaculatory reflex and depends strongly on its "cofactors". Moreover, our results also confirmed an association between long tri-nucleotide repeats of androgen receptor, sex steroids, pituitary, and thyroid hormones in relation to  acquired premature ejaculatory dysfunction in diabetic patients. However, endocrine regulation of PE reflex is a complex phenomenon that requires further investigation.

CONTEXTE: Malgré une fréquence élevée partout dans le monde de l'éjaculation prématurée (EP), le caractère obscur de sa description, de son épidémiologie et de sa prise en charge reste provocateur. Il est avéré que la dysfonction masculine représentée par l'EP est un problème croissant en raison de l'occurrence de l'éjaculation spontanée dans de nombreux sujets généraux et cliniques. L'objectif principal de la présente étude était de déterminer les relations entre le nombre de répétions de trinucléotides du récepteur aux androgènes (RA), les stéroïdes sexuels et les hormones hypophysaires d'une part, et la fonction sexuelle d'hommes qui présentent un Diabète de type 2 (DT2) et qui rapportent une EP acquise. SUJETS ET MÉTHODES: Un total de 150 sujets normaux et de 250 sujets qui présentaient une EP et un DT2 ont été enrôlés dans cette étude. Il a été demandé à chaque sujet de remplir un questionnaire approprié au recueil sélectif d'informations précises concernant l'indice de masse corporelle, la durée de l'EP+ DT2, le temps de latence éjaculatoire intra vaginal (IELT) auto-rapporté, ainsi que les statuts sexuel et mental sur la base de l'outil diagnostic de l'éjaculation prématurée (PEDT) et de l'inventaire de dépression de Beck-II (BDI-II). Les coefficients de corrélation de Pearson ont été utilisés pour évaluer les relations entre les paramètres génétiques, cliniques et démographiques. L'analyse de variance minimale des groupements de Ward et l'analyse en composante principale ont été utilisées pour évaluer la dépendance entre les paramètres génétiques, clinique et démographiques. RÉSULTATS: Les sujets qui avaient le plus faible nombre (≤21) de répétitions de (CAG)n présentaient des taux sériques plus élevés d'ocytocine (114.2 pg/ml; n = 54, 43.2%) que les témoins (69.18 pg/ml; n = 22, 17.6%) et que les sujets avec le nombre le plus élevé (≥26) de répétitions de (CAG)n (62.9 pg/ml; n = 108, 43.2%).D'un autre côté, les sujets qui présentaient le nombre le plus élevé (≥26) de répétitions de (CAG)n avaient des taux sériques de testostérone plus élevés (6.1ng/ml; n = 108, 43.2% de la cohorte) et de prolactine plus bas (3.01ng/ml; n = 108, 43.2% de la cohorte) que les témoins et que les sujets qui présentaient le nombre le plus bas (≥21) de répétitions de (CAG)n; et leurs taux sériques de TSH était plus bas (1.53 mIU/L; p < 0.05) que ceux des témoins. Dans le modèle de corrélation de Pearson, l'IELT auto-rapporté présentait une corrélation négative avec les répétitions à la fois des triplets (CAG)n (r = -0.16, p = 0.0001) et des triplets (GGC)n (r = -0.19, p = 0.0001). Ces répétitions étaient respectivement corrélées positivement avec PEDT (r = 0.28, p = 0.0001; r = 0.24, p = 0.0001, modèle global) et inversement corrélées avec BDI-II (r = -0.25, p = 0.0001). CONCLUSION: Cette étude montre que le polymorphisme du récepteur aux androgènes module l'effet endocrinien sur le reflexe éjaculatoire et qu'il est étroitement dépendant de ses « cofacteurs ¼. De plus, les présents résultats confirment aussi l'association entre les longues répétions de trinucléotides du récepteur aux androgènes, les stéroïdes sexuels, les hormones pituitaires et thyroïdiennes en relation avec une dysfonction éjaculatoire prématurée acquise chez les patients diabétiques. La régulation endocrine du réflexe de l'EP est toutefois un phénomène complexe qui nécessite de futures investigations.

Tri-nucleotide consortium of androgen receptor is associated with low serum FSH and testosterone in asthenospermic men.

Androgen mediating signaling is implicated in regulating the expression of reproductive related genes. Any deviation in the gene expression might be the ignitable precursor for genomic instability that inflames the genomic rearrangements and a leading cause of cancer. The main goal of this study was to determine the relationships between trinucleotide repeats of androgen receptor (AR), sex steroids, and sexual function in men presenting with reduced sperm motility. We investigated the singleton or combinatorial effects of the length of trinucleotide repeats of AR on reproductive hormones, clinical parameters, semen analyses, as well as sexual assessment function of 210 asthenospermic outpatients along with 125 normal subjects. Sexual assessment was executed using the International Index of Erectile Function (IIEF-15 score) which measures erectile function (EF), orgasmic function (OR), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction. Our findings suggest that long (>26 CAG)n repeats have an inverse correlation with circulatory FSH and T, whereas long (>25 GGC)n repeats have moderated affiliation with reduced sperm concentration. The study revealed a novel finding by exploring the negative correlation between elongated (CAG)n repeats and the cumulative IIEF-15 score, orgasm function (OR), and erectile function (EF) in asthenospermic men. This study examines the tri-nucleotide correlation with sexual function in Punjabi men enhancing our understanding of the regulatory mechanisms of sexual performance. ABBREVIATIONS: AR: androgen receptor; IIEF-15 score: International Index of Erectile Function; EF: erectile function; OR: orgasmic function; SD: sexual desire; IS: intercourse satisfaction; FSH: follicular stimulating hormone; T: testosterone; NTD: N-terminal transactivation domain; DBD: DNA-binding domain; LBD: ligand binding domain; TNR: tri-nucleotide repeat.

Problems in Mitochondrial DNA forensics: while interpreting length heteroplasmy conundrum of various Sindhi and Baluchi ethnic groups of Pakistan.

The insight heterodox genetics of mtDNA infer new perspectives at the level of human mitochondrial control region heteroplasmy, which is substantial in evolutionary as well as forensic interpretation. The main goal of this study is to interrogate the recurrence and resolve the ambiguity of blurry spectrum of heteroplasmy in the human mtDNA control region of 50 Baluchi and 116 Sindhi unrelated individuals. Sanger sequencing was employed classically, that was further investigated by minisequencing. Only 20% Baluchi and 25.8% Sindhi were homoplasmic, whereas rest of 80% Baluchi and 74.1% Sindhi exhibited at least one heteroplasmy within the specimen. In total, 166 individuals have length heteroplasmy (LH) found at positions 16189, 303-315, 568-573, and 514-524, whilst point mutation heteroplasmy (PMH) was detected at positions 73, 16093, 16189, and 16234, respectively. Overall LH was observed albeit high frequency in Sindhi ethnic group (82%) rather than Baluchi's (37%), whereas PMH accumulation was relatively extensive (24%) in Baluchi's than Sindhi's (11.2%). The obtained results ascertained that growing knowledge of heteroplasmy assisted to develop consciences in the forensic community that heteroplasmy plays a pivotal role in the legal interpretation on a regular basis and knowledge of its biological underpinnings has a vital niche in the forensic science. Limited studies have focused on heteroplasmy, yet scientific attention should be given, in order to determine its magnitude in different ethnic boundaries.

Genetic perspective of uniparental mitochondrial DNA landscape on the Punjabi population, Pakistan.

To investigate the uniparental genetic structure of the Punjabi population from mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain and Gujar) belonging to territory of Punjab. The complete control region was elucidated by Sanger sequencing and the subsequent 58 different haplotypes were designated into appropriate haplogroups according to the most recently updated mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup uniformity among the Punjab Province and exhibited a strong connotation with the European populations. Punjabi castes are primarily a composite of substantial South Asian, East Asian and West Eurasian lineages. Moreover, for the first time we have defined the newly sub-haplogroup M52b1 characterized by 16223 T, 16275 G and 16438 A in Gujar caste. The vast array of mtDNA variants displayed in this study suggested that the haplogroup composition radiates signals of extensive genetic conglomeration, population admixture and demographic expansion that was equipped with diverse origin, whereas matrilineal gene pool was phylogeographically homogenous across the Punjab. This context was further fully acquainted with the facts supported by PCA scatterplot that Punjabi population clustered with South Asian populations. Finally, the high power of discrimination (0.8819) and low random match probability (0.0085%) proposed a worthy contribution of mtDNA control region dataset as a forensic database that considered a gold standard of today to get deeper insight into the genetic ancestry of contemporary matrilineal phylogeny.

Genetic analysis of mitochondrial DNA control region variations in four tribes of Khyber Pakhtunkhwa, Pakistan.

Due to its geo strategic position at the crossroad of Asia, Pakistan has gained crucial importance of playing its pivotal role in subsequent human migratory events, both prehistoric and historic. This human movement became possible through an ancient overland network of trails called "The Silk Route" linking Asia Minor, Middle East China, Central Asia and Southeast Asia. This study was conducted to analyze complete mitochondrial control region samples of 100 individuals of four major Pashtun tribes namely, Bangash, Khattak, Mahsuds and Orakzai in the province of Khyber Pakhtunkhwa, Pakistan. All Pashtun tribes revealed high genetic diversity which is comparable to the other Central Asian, Southeast Asian and European populations. The configuration of genetic variation and heterogeneity further unveiled through Multidimensional Scaling, Principal Component Analysis and phylogenetic analysis. The results revealed that Pashtun are the composite mosaic of West Eurasian ancestry of numerous geographic origin. They received substantial gene flow during different invasive movements and have a high element of the Western provenance. The most common haplogroups reported in this study are: South Asian haplogroups M (28%) and R (8%); whereas, West Asians haplogroups are present, albeit in high frequencies (67%) and widespread over all; HV (15%), U (17%), H (9%), J (8%), K (8%), W (4%), N (3%) and T (3%). Moreover, we linked the unexplored genetic connection between Ashkenazi Jews and Pashtun. The presence of specific haplotypes J1b (4%) and K1a1b1a (5%) pointed to a genetic connection of Jewish conglomeration in Khattak tribe. This was a result of an ancient genetic influx in the early Neolithic period that led to the formation of a diverse genetic substratum in present day Pashtun.

TRPM channels: same ballpark, different players, and different rules in immunogenetics.

Transient receptor potential (TRP) channels belong to a large family of cation channels and are the "border guards" predominantly localized to the plasma membrane. Research over the years has considerably and highly developed the knowledge of expression and functional aspects of the TRPM channels. A closer look at the channel dynamics has dismantled undeniable substantiation for multifaceted roles for TRPM channel-mediated extracellular Ca(2+) influx in several physiological and pathophysiological functions. Given the wealth of literature unfolding the multiple roles of TRP channels in physiology in a very extensive range of different mammalian tissues, this review confines itself to the literature describing the multiple roles of TRPM channels in diabetes, smooth muscle cell regulation, immunological responses, and emerging aspects of cancer. We also focus on differential activities of TRPM channels after post-transcriptional and post-translational processing and their exquisite roles at various cellular and molecular levels.