Novel Mutations in AKT1 Gene in Prostate Cancer Patients in Jordan.

The AKT1 oncogene is related to various cancers due to its critical role in the PIC3CA/AKT1 pathway; however, most of the studies screened the hotspot mutation AKT1 (E17K) with various incidences. Low frequency or lack of AKT1 (E17K) mutation was reported in prostate cancer (PC) patients. This study aims to explore genetic alterations in the AKT1 PH domain by extending the sequencing to include AKT1 gene exons 3 and 4. Genomic DNA was extracted from 84 Formalin-Fixed Paraffin-Embedded samples of PC patients in Jordan, and then subjected to PCR and sequencing for the targeted exons. This study revealed the presence of two novel mutations (N53Y and Q59K) and a high frequency of mutations in exon 4, with a lack of mutations in the E17K hotspot. Nine missense and two synonymous mutations were detected in exon 4 (Phe27Tyr, Phe27Leu, Ala58Thr, Ser56Phe, Arg41Trp, Phe35Leu, Asp32Glu, Phe35Tyr, and Gln43Lys) and (Ser56 and Glu40), respectively. Two synonymous mutations were detected in exon 3 (Leu12 and Ser2). It is concluded that there is a high frequency of AKT1 mutation in PC patients in Jordan with two novel missense mutations in the Pleckstrin homology (PH) domain. E17K hotspot mutation was not detected in any tested samples, which underlined the significant role of mutations in other AKT1 exons in PC development.

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).

Stem cell-related knowledge and attitudes among physicians in Jordan.

BACKGROUND: Rapid advancement of stem cell (SC) therapies provides both opportunities and risks for patients and physicians alike. Physicians have a role in counselling patients about unproven SC therapies, requiring a basic level of knowledge and access to information about SCs. OBJECTIVE: This study sought to assess SC-related knowledge of and attitudes among physicians in Jordan to elucidate areas of deficiency that can be addressed. METHODS: A cross-sectional survey, comprising questions on demographics and SC knowledge and attitudes, was designed as a scoring system to evaluate physicians' knowledge and attitudes. Participants were recruited from 10 major hospitals in Jordan over 3 months between February and April 2019. The internal consistency of the scoring scales was calculated using Cronbach's alpha reliability coefficient. Gender differences were evaluated with an independent t-test. RESULTS: In total, 382 physicians in Jordan completed the survey (59.9% response rate). They demonstrated a low/moderate level of overall SC knowledge (51.3%), but most lacked confidence in their ability to answer patients' questions about SC therapies (64.7%). However, the total attitude score was moderate/high positive (66.8%) and most were interested in learning more about SCs (80.8%). Male physicians reported significantly more knowledge than females (P < .0001). CONCLUSIONS: This study reveals Jordanian physicians' hesitancy to counsel patients about SC therapies, largely because of gaps in knowledge. However, overall attitudes toward SC research and therapies are positive. The results of this study demonstrate a need to cover SC-related information in medical curricula in Jordan, as well as to support initiatives to regulate SC tourism in Jordan.

Coronaviruses in children: A review of potential mechanisms of childhood protection.

AIM: The 2019 coronavirus disease (COVID-19) has spread worldwide and the number of cases continues to rise exponentially. Epidemiologic reports indicate that severity of illness increases with age. However, the reasons behind the relative protection of children and infants are unclear. Whether the rationale is host-related or virus dependent is important to determine since the latter could change with viral mutations. We review factors that could affect the susceptibility of children to the novel coronavirus. METHODS: We search publications indexed on PUBMED. RESULTS: Descriptions of the pathophysiology of current and previous coronavirus infections suggest several viral targets and immunomodulatory pathways affecting the severity of illness. There is limited evidence to suggest age-variability of viral cell receptors and transmembrane co-factors required for coronavirus entry and replication. However, the ensuing cytokine storm and the effect of higher melatonin in children are age-dependent and could explain decreased disease variability in children. CONCLUSION: We believe that current evidence suggests host factors can play a role in disease severity in children and thus may remain protective despite potential virus mutation in the future. However, we recognise and discuss avenues of future research that can further illuminate the reasons children are protected from severe COVID-19 illness.

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.

4,977-bp human mitochondrial DNA deletion is associated with asthenozoospermic infertility in Jordan.

Male infertility is commonly associated with sperm abnormalities including asthenozoospermia. The molecular basis of asthenozoospermia was linked to mitochondrial DNA (mtDNA) mutations. The 4,977-bp human mtDNA deletion is one of the most common mutations of spermatozoa and results in loss of about 33% of the mitochondrial genome. In this preliminary study, we aimed to investigate the presence of 4,977-bp mtDNA deletion in asthenozoospermic infertile men in Jordan. Semen specimens of 120 asthenozoospermic infertile men and 80 normozoospermic individuals were collected at the in vitro fertilization unit. MtDNA was extracted after the enrichment of spermatozoa; then, polymerase chain reaction was performed using 4,977-bp mtDNA deletion-specific primers. The deletion of 4,977-bp mtDNA was detected in 79.2% of asthenozoospermic patients compared to 10% in normozoospermic controls. The results showed a significant association between the presence of 4,977-bp mtDNA deletion and the asthenozoospermia and infertility (OR = 34.2000, 95% CI = 14.57-80.26, p-value < .001). In conclusion, our findings underscored a strong association between 4,977-bp mtDNA deletion and asthenozoospermia in the Jordanian population.

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.

Homologous G776G Variant of Transcobalamin-II Gene is Linked to Vitamin B12 Deficiency.

Vitamin B12 (Cobalamin) deficiency, due to improper internalization of cobalamin, is a metabolic disorder prevalent in impoverished and elderly populations and is associated with megaloblastic anemia and dementia. It has been suggested that mutations in transcobalamin II (TCN2) or gastric intrinsic factor (GIF) proteins can alter their binding efficiency to cobalamin or reduce the ability of their receptors to internalize them. In this case-control study, the correlation between vitamin B12 deficiency and alternative alleles of TCN2 and GIF was investigated in a Jordanian population. One hundred individuals with vitamin B12 deficiency (B12 < 200 mg/mL) were enrolled in our study to evaluate the TCN2 and GIF polymorphisms. The control group (B12 > 200 mg/mL) included 100 individuals. Our results indicated a significant association between the homologous variant of the TCN2 gene (G776G) and vitamin B12 deficiency, and an intermediate phenotype in heterozygous individuals (p < 0.001, OR = 5.6, 95% CI = 2.95 to 10.63). The GIF gene, however, showed no correlation between the A68G variant and vitamin B12 deficiency (p = 0.2). This study expounds the association of TCN2 polymorphism with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2 and GIF genes polymorphisms on vitamin B12 deficiency and associated disorders.

Heat shock proteins gene expression and physiological responses in durum wheat (Triticum durum) under salt stress.

Salt stress is a major abiotic stress causing adverse effects on plant growth and development. The aim of this study was to investigate the effect of NaCl stress on growth, stress indicator parameters (lipid peroxidation, chlorophyll content and proline content), yield, and the expression of heat shock proteins genes (Hsp17.8, Hsp26.3, Hsp70 and Hsp101) of five Jordanian durum wheat (Triticum durum) landraces. Plants were irrigated with tap water as control or 200 mM NaCl. Significant differences among the 5 Triticum durum landraces in terms of growth parameters, stress indicator parameters, and expression of heat shock proteins genes were observed. Salt stressed landraces demonstrated decreased growth, increased levels of stress indicator parameters, and upregulation in Hsp17.8, Hsp26.3, Hsp70 and Hsp101 expression. Landraces T11 and M23 showed the highest growth, lowest levels of stress indicator parameters, and high expression of heat shock protein genes under NaCl stress. Whereas, J2 and A8 landraces showed the lowest growth, highest levels of stress indicator parameters and low expression of heat shock protein genes under NaCl stress. In conclusion, NaCl stress caused significant reduction in growth parameters, increased level of lipid peroxidation and proline content and upregulation in heat shock proteins gene expression levels. Growth, stress indicator parameters and gene expression results suggest that T11 and M23 landraces are the most NaCl stress tolerant landraces and could be used to enhance the gene pool in wheat breeding programs.

C4 photosynthesis and transition of Kranz anatomy in cotyledons and leaves of Tetraena simplex.

PREMISE OF THE STUDY: Tetraena simplex is an independently evolved C4 species in the Zygophylloideae (Zygophyllaceae) and a characteristic forb of saline flats in hot and sandy desert habitats. During early ontogeny, the species had a morphological shift from planar cotyledons (dorsiventral symmetry) to terete, succulent leaves (radial symmetry). We tested whether this shift had a corresponding change in internal Kranz anatomy and tissue patterning. METHODS: For a comprehensive characterization of C4 photosynthesis across early ontogeny in T. simplex, structural and ultrastructural anatomical properties and localization patterns, activities, and immunoblotting of key C4 photosynthetic enzymes were compared in mesophyll and bundle sheath tissues in cotyledons and leaves. KEY RESULTS: Cotyledons and leaves possessed different types of Kranz anatomy (atriplicoid type and a "Tetraena" variant of the kochioid type, respectively), reflecting the change in leaf morphology. In bundle sheath cells, key differences in ultrastructural features included increased organelle numbers and chloroplast thylakoid stacking. C4 enzymes had strict tissue-specific localization patterns within bundle sheath and mesophyll cells in both cotyledons and leaves. The decarboxylase NAD-ME maintained the highest activity, increasing from cotyledons to leaves. This classified T. simplex as fully C4 across ontogeny and a strictly NAD-ME biochemical subtype. CONCLUSIONS: Tetraena simplex cotyledons and leaves showed differences in Kranz type, with associated progression in ultrastructural features, and differing activities/expression levels of C4 enzymes. Furthermore, leaves characterized a new "Tetraena" variation of the kochioid Kranz anatomy.

Inhibitory Effect of Thymoquinone on Testosterone-Induced Benign Prostatic Hyperplasia in Wistar Rats.

This study addresses the possible protective effects of thymoquinone (TQ) against the development of experimentally-induced benign prostatic hyperplasia (BPH) in Wistar rats. Eighteen adult male rats were divided into three groups; the negative control group (n = 6) received vehicle, and two groups received subcutaneous testosterone injection (3 mg/kg). Animals receiving testosterone were randomized to untreated BPH group (n = 6) and BPH + TQ treated group (n = 6, 50 mg/kg orally for 14 days). Histological changes and the mRNA levels of transforming growth factor-ß1 (TGF-ß1 ) and vascular endothelial growth factor-A (VEGF-A) were analyzed. Additionally, dihydrotestosterone and interleukin-6 (IL-6) serum levels were determined. The presented research shows significant increases in prostate weight/body weight ratio, prostate epithelial thickness, serum IL-6 and dihydrotestosterone levels, and the prostatic expressions of TGF-ß1 and VEGF-A in the untreated BPH rats. Histological examination of the prostate tissues in the BPH rats showed an elevated level of proliferation in the stromal area and glandular epithelia with abundant intraluminal papillary folds. However, a reduction in prostate weight/body weight ratio, epithelial hyperplasia, serum IL-6 levels, and the expressions of TGF-ß1 and VEGF-A were observed in the BPH + TQ treated rats compared with the untreated BPH rats. The findings support TQ as a useful natural treatment for animal BPH model. Copyright © 2017 John Wiley & Sons, Ltd.

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.

The risk of solid organ tumors in patients with chronic kidney disease: A narrative review of literature.

Chronic kidney disease (CKD) has been correlated with certain pathological conditions such as cardiovascular diseases and other renal-related dysfunctions. Some other reports suggested an association between CKD and the development of certain solid cancers. Therefore, we aimed to generate this narrative review to present the available literature on the risk of solid cancer development in CKD patient populations. We explored the associations between CKD, organ transplantation, and the development of specific solid organ tumors such as kidney, thyroid, lung, breast, bladder, gastric, and prostate cancers. In conclusion, the previous reports showed an increase in the risk of certain solid cancers such as kidney, lung, bladder, and possibly breast cancer in CKD patients and transplant recipients. On the other hand, thyroid, gastric, and prostate cancers showed unclear association with CKD. Despite the suggested impact of smoking and immunosuppression on the development of cancers in CKD patients, more studies are needed to elucidate the mechanism and the risk factors that might be related to the development of cancer in CKD patients.

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.

Depressed "ping pong" skull fractures in the newborns: A cohort study.

Background and Aims: A ping pong fracture is a rare depressed skull fracture (DSF) observed in infants. It occurs due to the inward buckling of the calvarium, creating a cup-like shape. Trauma during childbirth, particularly from instrumental delivery or the application of pressure by physicians or midwives during challenging deliveries, is the primary cause. This study aimed to investigate the epidemiologic characteristics associated with DSF in newborns and to identify the main factors related to its incidence and the type of hematoma involved. Methods: This is a retrospective case-control analysis of all newborns delivered with DSF at King Abdulla University Hospital in Jordan between January 2008 and December 2020. The medical records were reviewed, and clinical data were collected and analyzed. Results: Out of 42,955 live births delivered at King Abdulla University Hospital, 13 cases of DSF were observed, giving an incidence of 3.0 in 10,000 live births. All cases were delivered at full term. Of the 13 cases, nine cases were associated with the use of instrumental delivery. Seven of those nine cases were delivered vaginally, while the other two cases required cesarean section following unsuccessful instrumental delivery. Four cases were spontaneous, with no history of trauma or instrument use, and delivered by cesarean section. Only 3 of the 13 cases required neurosurgical elevation of DSF. The outcome was excellent in all cases, both cosmetically and neurologically. Conclusion: Ping-pong skull fractures are seen in newborns infrequently in the Jordanian population, with an incidence of 0.03%. Most of the cases have resulted from difficult deliveries though spontaneous fractures can be encountered rarely. The treatment is usually conservative with spontaneous resolution. The overall prognosis is excellent both neurologically and cosmically.

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.

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.