Association between the single nucleotide variants of the mitochondrial cytochrome B gene (MT-CYB) and the male infertility.

BACKGROUND: Idiopathic male infertility can be attributed to genetic predispositions that affect sperm performance and function. Genetic alterations in the mitochondrial DNA (mtDNA) have been linked to certain types of male infertility and abnormal sperm function. Mutations in the mitochondrial cytochrome B (MT-CYB) gene might lead to some deficiencies in mitochondrial function. Thus, in the current study, we aimed to investigate the effect of mutations in the MT-CYB gene on sperm motility and male infertility. METHODS AND RESULTS: Semen specimens were collected from 111 men where 67 men were subfertile and 44 were fertile. QIAamp DNA Mini Kit and REPLI-g Mitochondrial DNA Kit from QIAGEN were used to isolate and amplify the mitochondrial DNA. Followed by PCR and Sanger sequencing for the target sequence in the MT-CYP gene. Sequencing of the MT-CYB gene revealed a total of thirteen single nucleotide polymorphisms (SNPs). Eight SNPs were non-synonymous variant (missense variant) including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155. While five SNPs were Synonymous variant: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124. Among these SNPs, three variants showed a significant difference in the frequency of the genotypes between subfertile and fertile groups: rs527236194 (T15784C) (P = 0.0005), rs28357373 (T15629C) (P = 0.0439), and rs41504845 (C15833T) (P = 0.0038). Moreover, two SNPs showed a significant association between allelic frequencies of rs527236194 (T15784C) (P = 0.0014) and rs41504845 (C15833T) (P = 0.0147) and male subfertility. CONCLUSION: The current study showed a significant association between the MT-CYB gene polymorphisms and the development of male infertility. In particular, rs527236194, rs28357373 and rs41504845 variants were found to be the most related to the subfertility group. Further studies on larger and other populations are required to reveal the exact role of this gene in the development of male infertility. In addition, functional studies will be helpful to elucidate the molecular impact of the MT-CYP polymorphisms on mitochondrial function.

A lack of a definite correlation between male sub-fertility and single nucleotide polymorphisms in sperm mitochondrial genes MT-CO3, MT-ATP6 and MT-ATP8.

BACKGROUND: An inability of a man to conceive a potentially fertile woman after a year of unprotected intercourse is defined as male infertility. It is reported that 30-40% of males in their reproductive years have abnormalities in sperm production, either qualitatively or quantitatively, or both. However, genetic factors result in up to 15% of male infertility cases. The present study aimed to analyze the possible correlations between sub-fertility and polymorphisms in sperm mitochondrial CO3, ATP6 and ATP8 genes in sub-fertile men. METHODS AND RESULTS: For 67 sub-fertile and 44 fertile male samples, Sanger sequencing of selected mitochondrial DNA genes was done. A total of twelve SNPs in the MT-CO3 gene: rs2248727, rs7520428, rs3134801, rs9743, rs28358272, rs2853824, rs2856985, rs2854139, rs41347846, rs28380140, rs3902407, and 28,411,821, fourteen SNPs in the MT-ATP6: rs2001031, rs2000975, rs2298011, rs7520428, rs9645429, rs112660509, rs6650105, rs6594033, rs6594034, rs6594035, rs3020563, rs28358887, rs2096044, and rs9283154, and ten SNPs in the MT-ATP8: rs9285835, rs9285836, rs9283154, rs8179289, rs121434446, rs1116906, rs2153588, rs1116905, rs1116907, and rs3020563 were detected in the case and control groups at different nucleotide positions. Only the rs7520428 in the MT-CO3 and MT-ATP6 showed a statistically significant difference between sub-fertile and fertile groups in the genotype's and allele's frequency test (P < 0.0001 for both). CONCLUSION: The results of our study suggest that male sub-fertility is linked with rs7520428 SNP in MT-CO3 and MT-ATP6. The studied polymorphic variations in the MT-ATP8 gene, on the contrary, did not reveal any significant association with male sub-fertility.

Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility.

Tobacco's genotoxic components can cause a wide range of gene defects in spermatozoa such as single- or double-strand DNA breaks, cross-links, DNA-adducts, higher frequencies of aneuploidy and chromosomal abnormalities. The aim in this study was to determine the correlation between sperm quality determined by standard parameters, sperm DNA maturity tested by Chromomycin A3 (CMA3) staining, sperm DNA fragmentation tested by TUNEL assay and tobacco smoking in association with the single nucleotides polymorphisms (SNP) of three nuclear protein genes in spermatozoa (H2BFWT, PRM1 and PRM2). In this study, semen samples of 167 male patients were collected and divided into 54 non-smokers and 113 smokers. The target sequences in the extracted sperm DNA were amplified by PCR followed by Sanger sequencing. The results showed the presence of three variants: rs7885967, rs553509 and rs578953 in H2BFWT gene in the study population. Only one variant rs737008 was detected in PRM1 gene, and three variants were detected in the PRM2 gene: rs2070923, rs1646022 and rs424908. No significant association was observed between the concentration, progressive motility, morphology and the occurrence of H2BFWT, PRM1 and PRM2 SNPs. However, sperm parameters were significantly lower in heavy smokers compared to controls (p < 0.01) (sperm count: 46.00 vs. 78.50 mill/ml, progressive motility: 15.00% vs. 22.00%, and morphology 4.00% vs. 5.00%, respectively). Moreover, the heavy smoker individuals exhibited a considerable increase in CMA3 positivity and sDF compared to non-smokers (p < 0.01) (29.50% vs. 20.50% and 24.50% vs. 12.00%, respectively). In conclusion, smoking altered sperm parameters and sperm DNA integrity, but did not show a linkage with genetic variants in H2BFWT, and protamine genes (PRM1 and PRM2).

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility.

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%-30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.

Mitochondrial nicotinamide adenine dinucleotide hydride dehydrogenase (NADH) subunit 4 (MTND4) polymorphisms and their association with male infertility.

PURPOSE: The purpose of the present study was to determine the relationship between infertility and the polymorphisms of mitochondrial NADH dehydrogenase subunit 4 (MTND4) by spermatozoa analysis in fertile and subfertile men. METHODS: Samples were divided into 68 subfertile men (case group) and 44 fertile men (control group). After semen analysis, samples were purified. The whole genome was extracted using a QIAamp DNA Mini Kit and the mitochondrial DNA was amplified by using the REPLI-g Mitochondrial DNA Kit. Polymerase chain reaction (PCR) was used to amplify the MT-ND4 gene. Then, samples were purified and sequenced using the Sanger method. RESULTS: Twenty-five single-nucleotide polymorphisms (SNPs) were identified in the MTND4 gene. The genotype frequencies of the study population showed a statistically significant association between rs2853495 G>A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G>A (Gly320Gly) and rs869096886 A>G (Leu164Leu) were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374-4.983, P = 0.002; adjusted OR = 2.237, 95% CI = 1.245-4.017, P = 0.007, respectively). CONCLUSION: In conclusion, our findings suggested that male infertility was correlated with rs2853495 and rs869096886 SNPs in MTND4.

CAG Repeats in the androgen receptor gene is associated with oligozoospermia and teratozoospermia in infertile men in Jordan.

CAG trinucleotide repeats are coded for the polyglutamine tract in the N-terminal of the androgen receptor (AR) gene which varies in normal individuals from 6 to 36 residues. In this study, we inspected the impact of the CAG repeats on the spermatogenic defects by measuring the size of AR-CAG repeats length in a cohort of 260infertile and 169 fertile Jordanian men. The infertile group included three subgroups of a zoospermic, oligozoospermic and teratozoospermia men. The CAG allele size was determined by direct sequencing. The results showed a significant association between the length of the AR-CAG repeats and men's infertility (p = .001). In particular, the current cohort demonstrated a significant association between the AR-CAG length polymorphism and oligozoospermia (p < .001) and teratozoospermia (p < .001) but not azoospermia. According to distributions of allele frequency, the risk of oligozoospermia was 5.5-fold greater than normal when alleles frequency > 20 repeats, while the risk of teratozoospermia was > 10.6 folds greater than normal when allele frequency > 22 repeats. In conclusion, our results underscored that the long repeats of the AR-CAG polymorphism within the normal range might be associated with abnormal spermatogenesis such as teratozoospermia and oligozoospermia and contributing to infertility in Jordanian men.

Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility.

Breast cancer (BC) is the most common cancer and the second leading cause of death among women worldwide. Only 10% of BC cases have been related to genetic predisposition. Rad51, a homologous recombination (HR) protein plays an important role in HR in meiosis and repairing DNA double-strand breaks. Expression of RAD51 may be a predictive biomarker in certain types of cancers. The exact mechanisms involved in the regulation of RAD51 expression are not fully understood, but certain transcription factors have been suggested to be the tuning mechanism of its expression. In this study, we propose that polymorphisms in the 5'-UTR promoter region of the RAD51 gene are prognostic factors for BC development. Direct sequencing of 106 samples from sporadic BC patients and 54 samples from a control group was performed. FFPE samples were the choice of sample collection, which might be a limitation of our study. Homologous variant T172T alone was found to be significantly associated with BC risk (OR 3.717, 95% CI 2.283-6.052, p < 0.0001). On the other hand, heterozygous G135C did not show any significant relationship with risk of sporadic BC (OR 1.598, 95% CI 0.5638-4.528, p > 0.05). Moreover, both variants; homozygous T172T and heterozygous G135C together; showed a significant relationship with sporadic BC susceptibility.

Vitamin B12 deficiency in diabetic patients treated with metformin: A narrative review.

Metformin is the most prescribed oral hypoglycemic drug and is considered by many health practitioners as the first-line treatment for non-insulin-dependent diabetes mellitus (T2DM). It is used either as a monotherapy or adjuvant to other anti-hyperglycemic agents. Most of its side effects are usually mild and self-limiting. However, several studies have shown an association between the use of metformin and low vitamin B12 levels in diabetic patients. The current review aimed to provide a literature review of the current published reports on the association, the possible mechanisms, and the related individualized risk factors that might lead to this incidence. The most accepted mechanism of the effect of metformin on vitamin B12 level is related to the absorption process where metformin antagonism of the calcium cation and interference with the calcium-dependent IF-vitamin B12 complex binding to the ileal cubilin receptor. In addition, many risk factors have been associated with the impact of metformin on vitamin B12 levels in diabetic patients such as dose and duration where longer durations showed a greater prevalence of developing vitamin B12 deficiency. Male patients showed lower levels of vitamin B12 compared to females. Black race showed a lower prevalence of vitamin B12 deficiency in metformin-treated patients. Moreover, chronic diseases including T2DM, hyperlipidemia, coronary artery disease, polycystic ovary disease (PCOD), obesity, and metformin therapy were significantly associated with increased risk of vitamin B12 deficiency.

Exploring the Impact of Cigarette Smoke Extracts on Vitamin B12: Insights into the Transformation of Methylcobalamin and Hydroxycobalamin to Cyanocobalamin through In Vitro Evaluation.

Vitamin B12 (cobalamin) is a water-soluble molecule required for the proper functioning of metabolism, blood and DNA synthesis, and neurological development. Vitamin B12 exists in several forms: methylcobalamin (MeCbl), adenosylcobalamin (AdoCbl), hydroxycobalamin (OHCbl), and cyanocobalamin (CNCbl). This study aimed to evaluate the effect of cigarette smoke on the chemical structure of methylcobalamin and hydroxycobalamin forms of vitamin B12. MeCbl and OHCbl were markedly affected by exposure to cigarette smoke. The resemblance of the Rt between MeCbl and OHCbl and CNCbl indicates that exposure to cigarette smoke extracts chemically alters MeCbl and OHCbl to CNCbl, warranting in vivo research investigations.

The impact of COVID-19 pandemic lockdown on smoking habits and lifestyle: A cross-sectional study.

Background and Aims: Throughout the COVID-19 lockdown, the resultant psychological disturbances led to more tobacco consumption and deteriorated smoking behaviors among smokers. In this study, we aimed to investigate the impact of the COVID-19 pandemic on the smoking behaviors of the Jordanian population. Methods: A cross-sectional online survey was designed using the Google Forms service and distributed by social media platforms. Responses were collected starting from November 12, 2020, until November 24, 2020. Results: A total of 2511 respondents completed the survey, 77.3% were females. Males were significantly smoking more than females (p < 0.0001). Smoking was significantly more common among respondents who were older than 18 years old, married, held master's and PhD degrees, and working in non-health-related fields (p < 0.0001). Participants who smoke were more likely to adopt an unhealthy lifestyle during the pandemic. Females who started smoking last year were 2.6-fold more than males (p < 0.0001). We also noticed that there is a significant relationship between those who started smoking and are <18 years, living in a family consisting of seven members or more, being unemployed, having a diploma or bachelor's degree in a health-related major, having no chronic illnesses, increasing of daily meals or night meals, almost daily sugar intake, starting to follow social media account concerning physical activity, exercising once or twice a week, and sleeping more hours per day since the beginning of the pandemic (p < 0.01). Conclusion: The results of our study showed that the lockdown had a significant impact on people's lifestyles including smoking habits. Most of our sample's smoker participants experienced a change in their smoking level mostly, an increase. While those who had a decrease in their smoking level experienced a somehow healthier lifestyle regarding nutrition and other aspects.

Estrogens and the risk of breast cancer: A narrative review of literature.

In female mammals, the development and regulation of the reproductive system and non-reproductive system are significantly influenced by estrogens (oestrogens). In addition, lipid metabolism is another physiological role of estrogens. Estrogens act through different types of receptors to introduce signals to the target cell by affecting many estrogen response elements. Breast cancer is considered mostly a hormone-dependent disease. Approximately 70% of breast cancers express progesterone receptors and/or estrogen receptors, and they are a good marker for cancer prognosis. This review will discuss estrogen metabolism and the interaction of estrogen metabolites with breast cancer. The carcinogenic role of estrogen is discussed in light of both conventional and atypical cancers susceptible to hormones, such as prostate, endometrial, and lung cancer, as we examine how estrogen contributes to the formation and activation of breast cancer. In addition, this review will discuss other factors that can be associated with estrogen-driven breast cancer.

Nanomedicine tactics in cancer treatment: Challenge and hope.

Defeating cancer is the ultimate challenge and goal of oncologists, facing various obstacles along with finding effective anti-cancer therapies and understanding drug delivery mechanisms. Additionally, the translation of the experimental findings to the clinical outcomes such as specificity, delivery, toxicity, clearance, and bioavailability is another health concern. Nanomedicine is a branch of nanotechnology that has been drastically developed in the last decades. Due to the fact of various nanomaterial formulas, different nanomedicine drug delivery tactics have been developed as anti-cancer therapies. The most effective and less toxic approaches involved the active targeting drug delivery tactic, which relies on the recognition of the drug nanoparticle carriers and the cell surface marker. Accordingly, FDA approved such a group of nanomedicine drug delivery systems while other formulas are still under the clinical trial phases. Nanomedicine is showing a bright future in the treatment of cancer. Oncologists learned from cancer research the possible drug resistance that could be developed. Consequently, researchers need to be prepared for the possible adverse effect of the nanomedicine approach.

Impact of genetic polymorphisms at the promoter area of IL-10 gene on tacrolimus level in Jordanian renal transplantation recipients.

Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients. Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients. Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 . Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.

Robot-Assisted Tubal Reanastomosis after Sterilization: A Choice for Family Planning.

A variety of procedures have been used for family planning. One of these is sterilization surgery, which can be reversed by a tubal reanastomosis. In the present report, we compare Robot-assisted tubal reanastomosis sterilization with other methods of family planning and discuss factors related to the choice of the approach. The keywords used for the electronic search in PubMed were family planning, sterilization, Robot-assisted, tubal reanastomosis, depression, and regret. The decision in favor of or against sterilization surgery has been a sensitive issue for several years. Robot-assisted technology is a modern and precise approach. It has contributed to the flexibility of the decision between sterilization and its reversal through tubal reanastomosis, as well as enhanced the success rate of the surgery. Based on our analysis of the published literature, we believe that Robot-assisted tubal anastomosis is the optimum approach. However, to ensure the quality of health care, the surgeon must be well trained, well versed with the anatomy of the fallopian tubes, and thoroughly informed on the psychological impact of family planning.

Impact of COVID-19 pandemic on the Jordanian eating and nutritional habits.

Since the emergence of the COVID-19 pandemic, variable measures have been implemented to control the invasion of SARS-CoV-19 worldwide. Some of these measures included lockdowns for several months in some countries. In Jordan, various protocols have been implemented to deal with the epidemic, such as border closures, closures and local protocols for open days until we reach the partial opening in mid-2021. These measures and protocols have affected all sectors in the country, including the education system and the economy. In addition, lifestyle is one of the measurement issues that have been affected by government regulations during the COVID-19 pandemic. In this study, we aimed to investigate the impact of the COVID-19 pandemic on the eating and nutrition habits of the Jordanian population. An online sectional survey was built using Google Forms from Google. Responses were collected from November 12, 2020, through November 24, 2020. Researchers submitted a total of 2,511 responses. The results showed that there was a significant decrease in sugar intake (P = <0.005) with no critical fat and oil intake (P = 0.12). There was a significant change in daily consumption of fruits, vegetables, garlic, onions, and ginger, and downloads of health-related applications and supplements (P < 0.005). In addition, there was an increase in appetite, weight and number of daily meals. These changes are attributed to the extra free time due to lockdown and studying or working from home has significant impacts. However, 31.4% of respondents reported that the limited economic availability of food products and the closure of restaurants and cafes lead to a healthier lifestyle. Only 26.2% have been influenced by family members, friends, doctors, or social media to change their eating habits during the pandemic.

Continuous Saline Bladder Irrigation in Reducing Recurrence and Progression When Compared to Immediate Mitomycin- C Instillation Post- Resection of Bladder Tumor: A Short Communication.

INTRODUCTION: Intravesical chemotherapy instillation by mitomycin - C (MMC) immediately after transurethral resection of bladder tumor (TURBT), although effective in reducing the incidence of non- muscle invasive bladder cancer (NMIBC) recurrence, can result in non desirable effects like bladder irritation and hematuria . Continuous bladder irrigation with saline post resection has been studied as an alternative. In our study we  compare the rates of  NMIBC recurrence and progression in patients who were treated with either MMC or CSBI immediately after tumor resection. METHODS: We retrospectively reviewed the medical records of patients with NMIBC at our institution in Jordan university hospital in the period between 2015-2019. Postoperative instillation of MMC or CSBI for four hours was recorded. Follow up of the patients for recurrence or progression in the first 2 years after diagnosis was recorded and compared for  both groups. RESULTS: One hundred nineteen patients met inclusion criteria. Fifty four patients received MMC and 65 patients received CSBI immediately post TURBT. Kaplan-Meieranalysis for recurrence- free survival and progression- free survival didn't show a significant difference between both groups with P- value 0.88 and 0.14 respectively. CONCLUSION: Postoperative CSBI for four hours following tumor resection is equivalent to immediate postoperative MMC instillation for NMIBC in terms  of recurrence or progression rates with fewer side effects . However further  research is needed in this field .

Anti-proliferative, Anti-angiogenic and Anti-inflammatory Effects of Moringa peregrina Leaf Extracts on Testosterone- Induced Benign Prostatic Hyperplasia in Rats.

AIM: To investigate the potential anti-inflammatory and biochemical effects of Moringa peregrina leaf extracts on testosterone-induced benign prostatic hyperplasia (BPH) in rats. METHODS: Six groups of rats (each group included 5 rats) were included in this study. The groups included: 1) the control group, 2) the testosterone-induced BPH group, 3) with 50 mg/kg bwt (bodyweight) oil-treated BPH, 4) with 100 mg/kg bwt. oil-treated BPH, 5) with 500mg/kg bwt. ethanol treated BPH and 6) with 1,000 mg/kg bwt. aqueous treated BPH group. Biochemical markers were measured to evaluate the effect of M. peregrina leaf extracts. RESULTS: Our results showed a significant improvement in the thickness of epithelial cells of the BPH glandular tissues when treated with different M. peregrina extracts (p < 0.05). In addition, M. peregrina extracts showed anti-inflammatory, anti-proliferative and anti-angiogenesis effects on the BPH tissues by reduction of IL-6, PCNA and VEGF-A, respectively. CONCLUSION: Our preclinical study concluded that M. peregrina leaf extracts showed a significant effect on BPH by reducing inflammation, proliferation, and angiogenic processes with no signs of toxicity.

Elevated BMI is considerably associated with IDD rather than polymorphic variations in interleukin-1 and vitamin D receptor genes: A case-control study.

BACKGROUND: Intervertebral disc degeneration (IDD) is a musculoskeletal disorder and one of the major causes of low back pain leading to the disability with high economic repercussions worldwide. This study applied the candidategene approach to investigate the potential association of selected polymorphisms with IDD development in a Jordanian population. METHODS: MRI-diagnosed IDD patients (N=155) and asymptomatic individuals as a control group (N=55). Whole blood samples for four variants in three genes (rs1800587 of IL-1α, rs1143634 of IL-1ß and rs2228570 and rs731236 of VDR) were genotyped by PCR-RFLP. RESULTS: There was no significant association between the studied polymorphisms or their allelic frequency and the occurrence of IDD. However, the cohort presented a significant reverse association between rs1143634 C > T of the IL-1ß gene and the occurrence of IDD (p<0.0001). In addition, BMI showed a significant association with the IDD in the study population (p<0.005). The current study was conceptualized based on the candidate-gene approach to investigate the role of inflammatory and metabolic genes, IL and VDR, respectively, in the occurrence of IDD. CONCLUSIONS: While the data presented in this study showed that polymorphisms in these genes were not associated with IDD of the cohort investigated, elevated BMI, as a measure of obesity, is strongly associated with IDD. Investigating potential roles of other structural genes, such as col-IX and aggrecan (ACAN), in IDD and considering a GWAS to elucidate a genomically global look at the basis of IDD development would be of considerable impact on our understanding of IDD.

Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia.

A relatively recent addition to the arsenal of antidiabetic drugs used for the treatment of type 2 diabetes mellitus (T2DM) has been the "incretin mimetics," a group of drugs that work on the glucagon-like peptide-1 (GLP-1) receptor and enhance insulin secretion from the pancreatic ß-cells in a glucose-dependent manner, more potently in hyperglycemic conditions, while suppressing glucagon secretion at the same time. Therefore, it was assumed that this class of drugs would have a lower risk of hypoglycemia than insulin secretagogues like sulphonylureas. However, GLP-1 receptor agonists have been proposed to cause hypoglycemia in healthy normoglycemic subjects implying that their action is not as glucose-dependent as once thought. Other studies concluded that they might not induce hypoglycemia and the risk is dependent on other individual factors. However, the FDA announced that the 12 GLP-1 receptor agonists currently available on the market had potential safety signs and evaluated the need for regulatory action. This review provides an overview of the studies that investigated the possible hypoglycemic effect of GLP-1 receptor agonists. In addition, the current review describes other adverse effects of GLP-1 receptor agonist treatment.

6th year medical students' future specialty preferences: A cross-sectional study.

BACKGROUND: Studying career preferences can help in designing and improving health service systems. Determining the preferred specialty and understanding the compulsion affecting specialty choice will provide clues to influence such choice in the future to shift the balance of specialties among practitioners. The current study aimed to determine medical students' preferable specialty choices and the factors influencing their choices and their attitude towards postgraduate medical education in Jordan and abroad. MATERIALS AND METHODS: The descriptive cross-sectional study design included 6th-year medical students in medical faculties in Jordan. An online questionnaire was created on Google Forms and posted on platforms accessible by medical students at level six. Numbers and percentages were presented for all variables. Frequency distributions were also presented. Chi-square distribution was used to measure the association between categorical data. Alpha level of 0.05 was used. RESULTS: Most students 188 (74.3%) preferred to continue their post-graduate training abroad, while only 65 (25.7%) favored Jordan. 150 (59.3%) of the respondents are interested in the medical - non-surgical - specialties. The most important factor that encouraged the students to choose a specialty was Job opportunity (32.5%) followed by the number of years required to complete the training and the expected income (27.7%) each. CONCLUSION: Supportive steps should be undertaken to motivate medical graduates toward the needed specialties. Moreover, local Specialty training programs need to be -reevaluated to ensure proper post graduate medical learning.