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There is significant uncertainty in describing prognosis and a lack of reliable entry criteria for palliative care studies in children with advanced heart disease (AHD). This study evaluates the utility of the surprise question-"Would you be surprised if this child died within the next year?"-to predict one-year mortality in children with AHD and assess its utility as entry criteria for future trials. This is a prospective cohort study of physicians and nurses caring for children (1 month-19 years) with AHD hospitalized ≥ 7 days. AHD was defined as single ventricle physiology, pulmonary vein stenosis or pulmonary hypertension, or any cardiac diagnosis with signs of advanced disease. Primary physicians were asked the surprise question and medical record review was performed. Forty-nine physicians responded to the surprise question for 152 patients. Physicians responded "No, I would not be surprised if this patient died" for 54 (36%) patients, 20 (37%) of whom died within 1 year, predicting one-year mortality with 77% sensitivity, 73% specificity, 37% positive predictive value, and 94% negative predictive value. Patients who received a "No" response had an increased 1-year risk of death (hazard ratio 7.25, p < 0.001). Physician years of experience, subspecialty, and self-rated competency were not associated with the accuracy of the surprise question. The surprise question offers promise as a bedside screening tool to identify children with AHD at high risk for mortality and help physicians identify patients who may benefit from palliative care and advance care planning discussions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and rs10519694, in a population of Iranian descent., Design: Case-control., Participants: One hundred seventy-eight subjects with KC and 180 clinically healthy subjects participated in the study., Methods: Genomic DNA was extracted from peripheral blood samples, and their genotypes were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction., Main Outcome Measures: Allele frequency for rs2956540 and rs10519694., Results: Genotype frequency was significantly different between cases and controls for rs2956540 ( P value = 0.019). The rs2956540 C allele carriers were significantly more frequent among KC cases than healthy controls ( P value chi-square  = 0.015, P value Fisher exact  = 0.017). There was a significant difference in genotype frequency between groups for rs10519694 ( P value = 0.001). T allele carriers were significantly more frequent among KC patients ( P value chi-square  = 0.002, P value Fisher exact  = 0.001). Sex stratification revealed no significant differences in genotype frequency between males and females in cases and controls. Fitting the general linear model showed that rs10519694 could be considered a predictor for the development of KC ( P value = 0.001); however, this was not observed for rs2956540 ( P value = 0.323)., Conclusions: rs2956540 and rs10519694 are associated with KC in a population of Iranian descent. rs10519694 could potentially be used for KC risk prediction., (© 2022 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Objective: To define the prevalence of hypothyroidism in women with chronic lower urinary tract symptoms (LUTS) and to compare the severity of each symptom between patients with hypothyroidism and controls., Subjects and Methods: In this prospective observational study, we screened all adult women who came to the urology clinic between March 2017 and September 2020, and enrolled patients with chronic LUTS in the study. We assessed thyroid function. We evaluated the severity of voiding and storage urinary symptoms by the International Prostate Symptom Score. We also assessed the severity of urge urinary incontinence (UUI) and stress urinary incontinence (SUI). For between-group analysis, we selected age-matched cases and controls and compared them regarding the distribution and severity of urinary symptoms., Results: Seven hundred and twenty-five women with a mean age of 51.7 ± 14.0 years were included in the final analysis. Two hundred fifty-eight patients (35.6%) had hypothyroidism. Age-matched case and control groups consisting of 210 patients each were selected. There was no significant difference in the severity and distribution of voiding LUTS and UUI between the study groups (P values >0.05). The severity of storage symptoms was lower in patients with hypothyroidism (P = 0.04). Sixty-seven patients with hypothyroidism (31.9%) had SUI, which was significantly higher than controls (23.3%) (P = 0.03)., Conclusion: More than one-third of women with chronic LUTS have hypothyroidism which is much more frequent than in the general population. We also suggest a possible relationship between hypothyroidism and the severity of SUI and an inverse relationship between hypothyroidism and storage symptoms., (© 2022 John Wiley & Sons Australia, Ltd.)

Background: The current study aims to assess the effects of the large simple renal cyst (SRC) surgery on renal function for the first time., Materials and Methods: This case-series study included 22 patients with larger than 50 mm single SRC who underwent laparoscopic cyst unroofing surgery. Twenty-four-hour urinary protein, creatinine, and volume along with plasma creatinine and estimated glomerular filtration rate (GFR) were measured in patients before and 1 month after surgery. Patients underwent abdominopelvic computed tomography-scan without contrast and parenchymal thickness diameter adjacent to the cyst was measured before and after surgery., Results: Mean age and weight of patients were 52.2 ± 8.9 years and 77 ± 10.9 akg, respectively. There was no significant difference between plasma creatinine and GFR before and after surgery ( P = 0.25 and 0.37, respectively). Twenty-four-hour urinary volume, creatinine, and protein before and after surgery revealed no significant changes ( P = 0.37, 0.08, and 0.31, respectively). The mean improvement of parenchymal thickness diameter after surgery was 10.4 ± 0.7 mm which was statistically significant ( P = 0.001). However, it was not correlated with the mean estimated GFR change ( r = 0.349, P = 0.13)., Conclusions: Although laparoscopic unroofing of renal cyst recovered renal parenchymal thickness noticeably, it did not improve renal function significantly; therefore, the latter factor lonely should not be considered a reason for surgery decision. Observation can be chosen as a safe treatment strategy in large SRCs without concern about renal function., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

Importance: Lack of pediatric end-of-life care quality indicators and challenges ascertaining family perspectives make staff perceptions valuable. Cardiac intensive care unit (CICU) interdisciplinary staff play an integral role supporting children and families at end of life., Objectives: To evaluate the Pediatric Intensive Care Unit Quality of Dying and Death (PICU-QODD) instrument and examine differences between disciplines and end-of-life circumstances., Design, Setting, and Participants: This cross-sectional survey included staff at a single center involved in pediatric CICU deaths from July 1, 2019, to June 30, 2021., Exposures: Staff demographic characteristics, intensity of end-of-life care (mechanical support, open chest, or cardiopulmonary resuscitation [CPR]), mode of death (discontinuation of life-sustaining therapy, treatment limitation, comfort care, CPR, and brain death), and palliative care involvement., Main Outcomes and Measures: PICU-QODD instrument standardized score (maximum, 100, with higher scores indicating higher quality); global rating of quality of the moment of death and 7 days prior (Likert 11-point scale, with 0 indicating terrible and 10, ideal) and mode-of-death alignment with family wishes., Results: Of 60 patient deaths (31 [52%] female; median [IQR] age, 4.9 months [10 days to 7.5 years]), 33 (55%) received intense care. Of 713 surveys (72% response rate), 246 (35%) were from nurses, 208 (29%) from medical practitioners, and 259 (36%) from allied health professionals. Clinical experience varied (298 [42%] ≤5 years). Median (IQR) PICU-QODD score was 93 (84-97); and quality of the moment of death and 7 days prior scores were 9 (7-10) and 5 (2-7), respectively. Cronbach α ranged from 0.87 (medical staff) to 0.92 (allied health), and PICU-QODD scores significantly correlated with global rating and alignment questions. Mean (SD) PICU-QODD scores were more than 3 points lower for nursing and allied health compared with medical practitioners (nursing staff: 88.3 [10.6]; allied health: 88.9 [9.6]; medical practitioner: 91.9 [7.8]; P < .001) and for less experienced staff (eg, <2 y: 87.7 [8.9]; >15 y: 91, P = .002). Mean PICU-QODD scores were lower for patients with comorbidities, surgical admissions, death following treatment limitation, or death misaligned with family wishes. No difference was observed with palliative care involvement. High-intensity care, compared with low-intensity care, was associated with lower median (IQR) rating of the quality of the 7 days prior to death (4 [2-6] vs 6 [4-8]; P = .001) and of the moment of death (8 [4-10] vs 9 [8-10]; P =.001)., Conclusions and Relevance: In this cross-sectional survey study of CICU staff, the PICU-QODD showed promise as a reliable and valid clinician measure of quality of dying and death in the CICU. Overall QODD was positively perceived, with lower rated quality of 7 days prior to death and variation by staff and patient characteristics. Our data could guide strategies to meaningfully improve CICU staff well-being and end-of-life experiences for patients and families.

Background: Access to pediatric sub-specialty training is a critical unmet need in many resource-limited settings. In Rwanda, only two pediatric cardiologists are responsible for the country's clinical care of a population of 12 million, along with the medical education of all pediatric trainees. To strengthen physician training opportunities, we developed an e-learning curriculum in pediatric cardiology. This curriculum aimed to "flip the classroom", allowing residents to learn key pediatric cardiology concepts digitally before an in-person session with the specialist, thus efficiently utilizing the specialist for additional case based and bedside teaching., Methods: We surveyed Rwandan and US faculty and residents using a modified Delphi approach to identify key topics in pediatric cardiology. Lead authors from Rwanda and the USA collaborated with OPENPediatrics™, a free digital knowledge-sharing platform, to produce ten core topics presented in structured videos spanning 4.5 h. A mixed methods evaluation was completed with Rwandan pediatric residents, including surveys assessing knowledge, utilization, and satisfaction. Qualitative analysis of structured interviews was conducted using NVivo., Results: Among the 43 residents who participated in the OPENPediatrics™ cardiology curriculum, 33 (77%) completed the curriculum assessment. Residents reported using the curriculum for a median of 8 h. Thirty-eight (88%) reported viewing the curriculum on their personal or hospital computer via pre-downloaded materials on a USB flash drive, with another seven (16%) reporting viewing it online. Twenty-seven residents viewed the course during core lecture time (63%). Commonly reported barriers to utilization included lack of time (70%), access to internet (40%) and language (24%). Scores on knowledge assessment improved from 66.2% to 76.7% upon completion of the curriculum (p < 0.001) across all levels of training, with most significant improvement in scores for PGY-1 and PGY-2 residents. Residents reported high satisfaction with the visuals, engaging presentation, and organization of the curriculum. Residents opined the need for expanded training material in cardiac electrocardiogram and echocardiogram and requested for slower narration by foreign presenters., Conclusion: Video-based e-learning via OPENPediatrics™ in a resource-limited setting was effective in improving resident's knowledge in pediatric cardiology with high levels of utilization and satisfaction. Expanding access to digital curriculums for other pediatric sub-specialties may be both an effective and efficient strategy for improving training in settings with limited access to subspecialist faculty., (© 2022. The Author(s).)

Background: Preterm birth (PTB) remains a significant problem in obstetric care. Progesterone supplements are believed to reduce the rate of preterm labor, but formulation, type of administration, and dosage varies in different studies. This study was performed to compare oral Dydrogesterone with intramuscular 17α-hydroxyprogesterone caproate (17α-OHPC) administration in prevention of PTB., Methods: In this randomized clinical trial, we studied 150 women with singleton pregnancy in 28 Th -34 Th  Gestational week, who had received tocolytic treatment for preterm labor. Participants were divided to receive 30 mg oral Dydrogesterone daily, 250 mg intramuscular 17α-OHPC weekly, or no intervention (control group). All treatments were continued until 37 Th  Week or delivery, whichever occurred earlier. Obstetric outcomes, including latency period, gestational age at delivery, birth weight, neonatal intensive care unit (NICU) admission, and neonatal mortality were recorded. All patients were monitored biweekly until delivery., Results: Baseline gestational age was not significantly different between groups. Latency period was significantly longer in the progesterone group compared with Dydrogesterone and control groups (41.06 ± 17.29 vs. 29.44 ± 15.6 and 22.20 ± 4.51 days, respectively; P < 0.001). The progesterone group showed significantly better results compared with the other two groups, in terms of gestational age at delivery, birth weight, and Apgar score (P < 0.001). None of the participants showed severe complications, stillbirth, or gestational diabetes., Conclusion: Progesterone caproate can strongly prolong the latency period and improve neonatal outcomes and therefore, is superior to oral Dydrogesterone in the prevention of PTB., (© 2022. The Author(s).)

Background: Caudal epidural block (CEB) in hypospadias surgery has the benefit of reducing post-operative pain and possibly intra-operative bleeding. Some studies, however, have suggested that this technique may increase the rate of post-operative complications. Considering the uncertainty about the effect of CEB on surgical complications of hypospadias repair, the current study was performed., Objective: The aim of this randomized clinical trial was to compare the complication rates between patients who receive CEB after hypospadias surgery and those who did not., Study Design: This double-blind randomized controlled trial was conducted on boys aged 6-35 months, who underwent hypospadias repair surgery in a university hospital from March 2018 to March 2019. Sixty patients were randomly divided into two groups (group A: 31 and group B: 29). In group B, CEB was performed, using 0.5 mg/kg of 0.125% bupivacaine (Marcaine). Postoperative complications including fistula, meatal stenosis, dehiscence, and occurrence of bleeding were assessed during six months after surgery., Results: The patients were assessed for possible complications at 24 h, one week, one, three and six months after surgery. No remarkable differences were observed between the patients in the two groups in terms of the frequency of dehiscence, fistula, and meatal stenosis (P > 0.05). Moreover, the difference in complication rates between the patients with proximal and distal hypospadias did not reach statistical significance (P = 0.549)., Discussion: Assessment of complications showed no significant difference between the two study groups in terms of dehiscence, fistula, and meatal stenosis (Clavien type III). In addition, complication rate was not significantly different according to severity of hypospadias between the two groups. Our study had limitations such as short follow up and small sample size, which resulted in insignificant difference in complication rate between proximal and distal hypospadias. These limitations request large studies with long term follow up., Conclusion: The current study showed that the use of caudal block anesthesia in comparison with general anesthesia did not increase surgical complications, which approved CEB protocol as a safe method in hypospadias repair., Competing Interests: Conflicts of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Schizophrenia is a severe, disabling psychiatric disorder with unclear etiology. Family-based, twins, and adoption studies have shown that genetic factors have major contributions in schizophrenia occurrence. Until now, many studies have discovered the association of schizophrenia and its comorbid symptoms with functional polymorphisms that lie within serotonin reuptake pathway genes. Here, we aimed to investigate the association of three variable number tandem repeats (VNTR) functional polymorphisms in MAOA and SLC6A4 with schizophrenia in the Iranian population. Two hundred and forty-one subjects with schizophrenia and three hundred and seventy age and sex-matched healthy controls were genotyped for MAOA promoter uVNTR, 5-HTTLPR, and STin2 polymorphisms. Genotyping was performed by polymerase chain reaction (PCR) with locus-specific primers and running the PCR product on agarose 2.5% gel electrophoresis. Finally, the statistical inference was performed using R programming language and Haploview software. MAOA promoter uVNTR analysis of allele frequency showed no differences between schizophrenia subjects and healthy controls in both males and females and no significant differences were observed between female cases and female controls in MAOA promoter uVNTR 4 repeat frequency. Also, there were no differences between Schizophrenia and healthy control groups in 5-HTTLPR allele and genotype frequency but, 5-HTTLPR S allele carriers are significantly more frequent among cases. In addition, STin2.12 repeats were significantly more frequent among schizophrenia patients. Genotype comparison suggested that 5-HTTLPR S allele and STin2.12 repeat carriers were significantly more frequent among schizophrenia cases and being STin2.12 repeat carrier significantly increase the risk of schizophrenia occurrence. Besides, analysis of haplotype showed stronger linkage disequilibrium between 5-HTTLPR and STin2 haplotype block in cases than controls. These results suggest that SLC6A4 functional polymorphisms potentially could play a possible role as risk factors for the incidence of schizophrenia., (© 2022. The Author(s).)

Aims: Breast cancer (BC) is one of the most common cancers among women. The influence of genetic variations on BC risk has been thus far assessed via genome-wide association studies. NF-κB has been recognized as a major player in BC progression. In this study, the association between rs28362491 and BC was evaluated in a population from northeastern Iran. Materials & methods: This study was conducted on 476 patients with BC and 524 healthy controls. The genotyping method used was an amplification-refractory mutation system. Results: The INS/DEL genotype conferred a statistically significant increased risk in patients in comparison with controls. Additionally, in the recessive model, INS/INS + INS/DEL versus DEL/DEL was statistically significant (OR = 0.34; 95% CI: 0.12-0.96; p = 0.042). Conclusion: This study found that rs28362491 , as a susceptibility genetic factor, may affect BC risk in the Iranian population.

Background: The combination of MRI-guided targeted biopsy (MRGB) with systematic biopsy (SB) provides the highest accuracy in detecting prostate cancer. There is a controversy over the superiority of fusion targeted biopsy (fus-MRGB) over cognitive targeted biopsy (cog-MRGB). The present head-to-head randomized controlled trial was performed to compare diagnostic yield of fus-MRGB in combination with SB with cog-MRGB in combination with SB., Methods: Biopsy-naive patients with a prostate-specific antigen level between 2 and 10 ng/dL who were candidates for prostate biopsy were included in the study. Multiparametric MRI was performed on all patients and patients with suspicious lesions with Prostate Imaging Reporting and Data System score of 3 or more were randomized into two groups. In the cog-MRGB group, a targeted cognitive biopsy was performed followed by a 12-core SB. Similarly, in the fus-MRGB group, first targeted fusion biopsy and then SBs were performed. The overall and clinically significant prostate cancer detection rates between the two study groups were compared by the Pearson χ 2 test. McNemar test was used to compare detection rates yielded by SB and targeted biopsy in each study group., Results: One-hundred men in the cog-MRGB group and 99 men in the fus-MRGB group were compared. The baseline characteristics of patients including age, PSA level, prostate volume, PSA density, and clinical stage were similar in the two groups (p > 0.05). Both the overall and clinically significant prostate cancer detection rates in the fus-MRGB group (44.4% and 33.3%, respectively) were significantly higher than cog-MRGB group (31.0% and 19.0%, respectively) (p = 0.035 and p = 0.016, respectively)., Conclusion: The accuracy of identifying overall and clinically significant prostate cancer by fus-MRGB in biopsy-naive patients with PSA levels between 2 and 10 ng/dL is significantly higher than cog-MRGB and if available, we recommend using fus-MRGB over cog-MRGB in these patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Maternal immune activation (MIA) model has been profoundly described as a suitable approach to study the pathophysiological mechanisms of neuropsychiatric disorders, including schizophrenia. Our previous study revealed that prenatal exposure to lipopolysaccharide (LPS) induced working memory impairments in only male offspring. Based on the putative role of prefrontal cortex (PFC) in working memory process, the current study was conducted to examine the long-lasting effect of LPS-induced MIA on several neuroinflammatory mediators in the PFC of adult male pups. We also investigated whether maternal zinc supplementation can alleviate LPS-induced alterations in this region. Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline on gestation days 15/16 and supplemented with ZnSO4 (30 mg/kg) throughout pregnancy. At postnatal day 60, the density of both microglia and astrocyte cells and the expression levels of IL-6, IL-1β, iNOS, TNF-α, NF-κB, and GFAP were evaluated in the PFC of male pups. Although maternal LPS treatment increased microglia and astrocyte density, number of neurons in the PFC of adult offspring remained unchanged. These findings were accompanied by the exacerbated mRNA levels of IL-6, IL-1β, iNOS, TNF-α, NF-κB, and GFAP as well. Conversely, prenatal zinc supplementation alleviated the mentioned alterations induced by LPS. These findings support the idea that the deleterious effects of prenatal LPS exposure could be attenuated by zinc supplementation during pregnancy. It is of interest to suggest early therapeutic intervention as a valuable approach to prevent neurodevelopmental deficits, following maternal infection. Schematic diagram describing the experimental timeline. On gestation days (GD) 15 and 16, pregnant dams were administered with intraperitoneal injections of either LPS (0.5 mg/kg) or vehicle and supplemented with ZnSO4 (30 mg/kg) throughout pregnancy by gavage. The resulting offspring were submitted to qPCR, immunostaining, and morphological analysis at PND 60. Maternal zinc supplementation alleviated increased expression levels of inflammatory mediators and microglia and astrocyte density induced by LPS in the PFC of treated offspring. PND postnatal day, PFC prefrontal cortex., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Introduction: Community Health Worker (CHW) programs have long been used to provide acute care for children and women in healthcare shortage areas, but their provision of comprehensive longitudinal care for chronic problems is rare. The Village Health Worker (VHW) program, initiated in 2007, is an example of a long standing "horizontal" CHW program in rural Southwestern Uganda that has delivered village-level care for chronic disease based on a biannual village health census that identifies individual and family health risks. To facilitate continuity of care for problems identified, health census data were electronically transformed into family-specific Family Health Sheets (FHS) in 2016 which summarize the pertinent demographic and health data for each family, as well as health topics the family would like to learn more about. The FHS, evaluated and discussed here, serves as an epidemiologically-informed "bedside" tool to help VHWs provide longitudinal care in their villages., Methods: 48 VHWs in the program completed a survey on the utility of the FHS and 24 VHWs participated in small discussion groups. Responses were analyzed using both quantitative and standard conceptual content analysis models RESULTS: 46 out of 48 VHWs reported that the FHS made them a "much better VHW." In addition to helping target interventions in child health, women's health, and sanitation, the FHS assisted follow-up of non-communicable diseases in the community. In discussion groups, VHWs reported that the FHS helped them understand risks for future disease, facilitated earning stipends, and increased credibility and trust in the community. Limitations cited were the infrequent updates of the FHS, only biannually with the census, and the lack of cross-reference capability by health problem., Discussion: The FHS supports VHWs in providing longitudinal and comprehensive healthcare of chronic diseases in their villages. Limitations, potential solutions, and future directions are discussed., (© 2021. The Author(s).)

Acetyl-L-carnitine has been shown to exert neuroprotection against neurodegenerative diseases. The present study was performed to evaluate neuroprotection effects of acetyl-L-carnitine against lipopolysaccharide (LPS) -induced neuroinflammation and clarify possible mechanisms. A single dose (500 µg/kg) of LPS was intraperitoneally injected to rats to induce model. The animals were intraperitoneally treated with different doses of acetyl-L-carnitine (30, 60, and 100) for 6 days. Y-maze task, single-trial passive avoidance and novel object recognition tests were used to evaluate memory impairments. ELISA assay was used to evaluate the expression of TLR4/NFκB, autophagic and oxidative stress markers. Our result showed that intraperitoneal injection of LPS resulted in initiation of neuroinflammation by activation of TLR4/NFκB, suppression of autophagic markers such as LC3 II/ LC3 I ratio and becline-1, and excessive production of ROS and MDA. Intraperitoneal administration of acetyl-L-carnitine contributed to neuroprotection against LPS -induced neuroinflammation by suppression of TLR4/NFκB pathway, restoring activity of autophagy and inhibition of oxidative stress. Collectively, our findings show that acetyl-L-carnitine attenuated LPS-induced neuroinflammation by targeting TLR4/NFκB pathway, autophagy and oxidative stress., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Skeletal dysplasia is a common, clinically and genetically heterogeneous disorder in the human population. An increasing number of different genes are being identified causing this disorder. We used whole exome sequencing (WES) for detection of skeletal dysplasia causing mutation in a fetus affected to severe lethal skeletal dysplasia., Patient: Fetus was assessed by ultrasonography in second trimester of pregnancy. He suffers from severe rhizomelic dysplasia and also pathologic shortening of ribs. WES was applied to finding of causal mutation. Furthermore, bioinformatics analysis was performed to predict mutation impact., Results: Whole exome sequencing (WES) identified a homozygous frameshift mutation in the TMEM263 gene in a fetus with severe lethal skeletal dysplasia. Mutations of this gene have been previously identified in dwarf chickens, but this is the first report of involvement of this gene in human skeletal dysplasia. This gene plays a key role in the growth hormone signaling pathway., Conclusion: TMEM263 can be considered as a new gene responsible for skeletal dysplasia. Given the complications observed in the affected fetus, the mutation of this gene appears to produce much more intense complications than that found in chickens and is likely to play a more important role in bone development in human.

As a complex neurodevelopmental disorder, autism affects children in three major cognitive domains including social interactions, language learning and repetitive stereotyped behaviors. Abnormal regulation of cell proliferation in the brain during the embryonic period via the TGF-β signaling pathway and TRIM33 gene that encodes a protein with a corepressor and regulatory role in this pathway has been considered as an etiology for autism. Here, we investigated the association of a variation of TRIM33 with autism symptoms at levels of mRNA and protein expression. We used Autism Diagnostic Interview-Revised (ADI-R) and Childhood Autism Rating Scale (CARS) as behavioral diagnostic tools. Normal and autistic children were genotyped for a TRIM33 polymorphism (rs11102807), and then expression was assessed at transcriptional and translational levels. Results demonstrated that the frequency of the homozygous A allele (AA genotype of rs11102807) was significantly higher in children with autism (P < 0.001), whereas carriers of the G allele were mostly among healthy individuals. Children homozygous for the rs11102807 A allele were associated with an increase in CARS and ADI-R scores, indicating a significant correlation with autism symptoms. TRIM33 gene expression at both mRNA (P < 0.01) and protein (P < 0.001) levels was significantly higher in controls compared to autistic children. A remarkable association between higher TRIM33 gene expression at the transcriptional level and lower scores for both CARS and ADI-R was observed in non-autistic children. It seems that rs11102807 modulates the function and expression of the TRIM33 gene, implying that the A allele may increase the risk of autism in children by reducing gene expression and altering the TGF-β signaling pathway.

Purpose: It is unclear how dietary intake influences the ovarian cancer. The present paper sets out to systematically review and meta-analyze research on dietary intake to identify cases having high- or low-risk ovarian cancer., Methods: Scopus, PubMed, and Wiley Online Libraries were searched up to the date November 24, 2019. Two reviewers were requested to independently extract study characteristics and to assess the bias and applicability risks with reference to the study inclusion criteria. Meta-analyses were performed to specify the relationship between dietary intake and the risk of ovarian cancer identifying 97 cohort studies., Results: No significant association was found between dietary intake and risk of ovarian cancer. The results of subgroup analyses indicated that green leafy vegetables (RR = 0.91, 95%, 0.85-0.98), allium vegetables (RR = 0.79, 95% CI 0.64-0.96), fiber (RR = 0.89, 95% CI 0.81-0.98), flavonoids (RR = 0.83, 95% CI 0.78-0.89) and green tea (RR = 0.61, 95% CI 0.49-0.76) intake could significantly reduce ovarian cancer risk. Total fat (RR = 1.10, 95% CI 1.02-1.18), saturated fat (RR = 1.11, 95% CI 1.01-1.22), saturated fatty acid (RR = 1.19, 95% CI 1.04-1.36), cholesterol (RR = 1.13, 95% CI 1.04-1.22) and retinol (RR = 1.14, 95% CI 1.00-1.30) intake could significantly increase ovarian cancer risk. In addition, acrylamide, nitrate, water disinfectants and polychlorinated biphenyls were significantly associated with an increased risk of ovarian cancer., Conclusion: These results could support recommendations to green leafy vegetables, allium vegetables, fiber, flavonoids and green tea intake for ovarian cancer prevention.

Finding effective treatments for cardiac diseases is among the hottest subjects in medicine; cell-based therapies have brought great promises for managing a broad range of life-threatening heart complications such as myocardial infarction. After clarifying the critical role of angiogenesis in tissue repair and regeneration, various stem/progenitor cell were utilized to accelerate the healing of injured cardiac tissue. Embryonic, fetal, adult, and induced pluripotent stem cells have shown the appropriate proangiogenic potential for tissue repair strategies. The capability of stem cells for differentiating into endothelial lineages was initially introduced as the primary mechanism involved in improving angiogenesis and accelerated heart tissue repair. However, recent studies have demonstrated the leading role of paracrine factors secreted by stem cells in advancing neo-vessel formation. Genetically modified stem cells are also being applied for promoting angiogenesis regarding their ability to considerably overexpress and secrete angiogenic bioactive molecules. Yet, conducting further research seems necessary to precisely identify molecular mechanisms behind the proangiogenic potential of stem cells, including the signaling pathways and regulatory molecules such as microRNAs. In conclusion, stem cells' pivotal roles in promoting angiogenesis and consequent improved cardiac healing and remodeling processes should not be ignored, especially in the case of stem cell-derived extracellular vesicles., (© 2021 International Union of Biochemistry and Molecular Biology.)

This is a novel case of a 16-month-old boy with a history of prematurity with intrauterine growth restriction, severe failure to thrive, microcephaly, pachygyria, agenesis of the corpus callosum, and postnatal embolic stroke, who presented with new-onset diabetes mellitus with diabetic ketoacidosis in the setting of severe acute respiratory syndrome coronavirus 2 infection, with a course complicated by atypical hemolytic syndrome (aHUS). This patient demonstrated remarkable insulin resistance in the period before aHUS diagnosis, which resolved with the first dose of eculizumab therapy. There is increasing evidence that COVID-19 is associated with thrombotic disorders and that microangiopathic processes and complement-mediated inflammation may be implicated. In this case report, we describe a pediatric patient with COVID-19 and a new complement-mediated microangiopathic thrombotic disease. Because whole-exome sequencing and extensive workup returned without a clear etiology for aHUS, this is likely a COVID-19 triggered case of aHUS versus an idiopathic case that was unmasked by the infection., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: The aim of the present study is to validate, and assess the reliability of the Persian version of Voice Handicap Index-Throat (VHI-Tp) as a self-reported questionnaire for patients with throat problems that could make the patients' estimation of the throat discomforts possible. It is a subscale to be used independently., Study Design: This is a cross-sectional study., Materials and Method: During this study, the VHI-Tp was administered to120 patients with throat problems related to laryngeal discomfort (51 male and 69 female, age range: 30-60 years).The diagnosis of Voice disorder was performed by an ENT physician based on video-laryngoscopy evidences and medical examination. To assess the content validity, the questions were first given to 15 experts to comment on content applicability and relevance through a Likert scale. Eighty patients rated its importance to detect face validity. To evaluate the concurrent validity, the same 80 patients completed both the VHI-Tp as well as the Persian version of Voice Symptom Scale. The VHI-Tp total scores of the patients with diagnosed throat problem related to laryngeal discomfort and of the 40 healthy participants were compared to test the clinical validity (discriminant validity). Also, internal consistency reliability was assessed using Cronbach α coefficient. The relative reliability was calculated by asking 40 of all patients out of the 80 participants, to complete the VHI-Tp twice, with a week of interval between the first and the second times. To detect the absolute reliability, Standard Error of Measurement and Smallest Detected Change were calculated., Results: Discriminative validity differed significantly between patients and healthy participants. There was a significant correlation between the VHI-Tp and Voice Symptom Scale total scores (r = 0.6, P < 0.05). The internal consistency was confirmed (Cronbach α = 0.78). The test-retest reliability was excellent (intraclass correlation coefficient = 0.95).The Standard Error of Measurement and Smallest Detected Changes were acceptable (0.39 and 1.08), respectively., Conclusion: The Persian version of the VHI-T was demonstrated to be a valid and reliable self-rated questionnaire for use in Persian patients with throat problem related to laryngeal discomfort., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: Increasing the occurrence of non-albicans Candida species with intrinsic or acquired resistance to antifungals as well as the emergence of multidrug Candida species coupled with the limited antifungal agents challenges the treatment of candidiasis. Consequently, a class of secondary metabolites of plants exhibiting decent antifungal activity. Therefore, this study aimed to evaluate the antifungal potential of various monoterpenes including Carvone, Limonene, Pinene, Menthone, Menthol, Camphor, Thujone, Citronellol, and Piperitone against standard and clinical isolates of Candida., Methods and Results: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of compounds were determined, using the broth Microdilution method based on M27-A3 protocol documented by clinical laboratory standard institute (CLSI). Amongst the tested monoterpenes, oxygenated terpenoids showed strong antifungal activity. Specifically, alcoholic terpenoids such as (±)-Citronellol possess more efficacy than the corresponding ketonic ones with MICs ranging from 0·03 to 2·00 μl ml -1 (0·16-10·80 mmol l -1 ). Among the examined yeasts, Candida tropicalis was the most susceptible species to (±)-Citronellol. Moreover, the examined monoterpenes successfully inhibited the growth of fluconazole-resistant Candida species. Moreover, statistical analysis showed no statistically significant difference between the (+) and (-) isomers, except for (±)-α-Pienene and (±) Menthone (ρ-value < 0·05)., Conclusion: Among the tested monoterpenes, (±)-Citronellol was the most potent compounds followed by (+)-α-Pinene and Menthol. Considering the significant antifungal activity of the examined monoterpenes, they could be used in controlling or treating candidiasis. Those potent antifungal monoterpenes with GRAS status in addition to their pleasant taste and odour make them appropriate additive or preservative compounds in food and cosmetics products. Furthermore, these data might help researchers to predict EOs antifungal activities, after determining its constituents., Significance and Impact of the Study: This study provides new information about the antifungal activities of monoterpenes and their isomers presented widely in essential oils. Screening results against pathogenic yeasts confirm the correlation between the chemical structure of tested monoterpenes and their antifungal effects. The present findings might be helpful to anticipate the antifungal activity of essential oils., (© 2020 The Society for Applied Microbiology.)

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5' UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer's disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls [F (1, 50) = 12.283; p = 0.001]. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype.

Insulin-like growth factor-binding protein acid-labile subunit (IGFALS) encodes a protein which binds to IGF1 and IGFBP-3 to regulate the growth, differentiation, and other physiological processes. The aim of this study was the identification of allelic polymorphisms of the IGFALS gene using the PCR-RFLP technique and evaluation of their association with growth traits. For this end, 120 blood samples were randomly collected from each breed. Following amplification of an 1113-bp fragment of exon 1 and a part of intron 1 of the IGFLAS gene, genotyping was conducted by three restriction enzymes including HinfI, MscI, and PvuII. The results showed that only one allele was observed in IGFALS-PvuII site, while in IGFLAS-MscI site, three AA, AB, and BB genotypes with the frequencies of 17.5%, 32%, and 50.5% and 11%, 37.5%, and 51.5% were observed in Makouei and Ghezel sheep breeds, respectively. Additionally, in the IGFLAS-HinfI site, two AB and BB genotypes with the frequency of 34.2% and 65.8% were observed in Makouei sheep and AA, AB, and BB genotypes with the frequency of 9%, 21%, and 70% were observed in Ghezel sheep. So that, Makouei sheep with AB genotype had more chest girth (CG) compared with other genotypes. Furthermore, a significant association was observed between the genotypes of IGFLAS-HinfI with birth weight (BW) in Ghezel and BW, weaning weight (BW3), and CG in Makouei sheep. Haplotype analysis revealed an association between paternal haplotypes and BW in both Ghezel and Makouei breeds. So that, AAB and ABB haplotypes showed more BW than others in Makouei and Ghezel sheep, respectively.

Objectives: Genu recurvatum deformity shifts the mechanical axis of lower extremity posteriorly which may disturb the balance and lead to injury. The aim of this research was to compare postural sways in genu recurvatum subjects with healthy controls while manipulating visual and proprioceptive systems., Methods: 10 female subjects with genu recurvatum (20.04 ± 4.64 years) and 11 female healthy controls (20.11 ± 4.64 years) participated in the study. The back knee angle was measured using a goniometer. Dynamic BIODEX balance system was used to measure the total, anteroposterior, and mediolateral postural sways while manipulating the stability of the base of support (stable versus unstable) and visual system (open versus closed eyes)., Result: During standing on the stable level, in both visual conditions, genu recurvatum subjects demonstrated greater total and anteroposterior postural sways than controls in both standing on the right and left foot (p<0.05). Similarly, when standing on the unstable base of support, in all conditions, the postural sways of genu recurvatum subjects were significantly greater than controls in both right and left foot (p<0.05). The vision had a main effect on postural control of genu recurvatum group (p=0.0001). There was a significant interaction between vision, the stability of the base of support and group factors (p=0.003)., Conclusion: The results indicated that genu recurvatum subjects have a proprioceptive deficiency and they mainly rely on visual system inputs to control and maintain their balance. Thus, the proprioceptive system and balance control should be considered in assessment and designing an appropriate treatment regimen for genu recurvatum., Competing Interests: Declaration of competing interest No conflicts of interest were stated by authors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Human sperm cryopreservation is a common technique which is used in assisted reproductive technologies. Despite the existence of evidence supporting the production of ROS and DNA fragmentation during sperm cryopreservation, there is little and equivocal information about the cryopreservation effects on methylation of imprinted genes and imprinting control regions. In this study, we have investigated the effects of cryopreservation on DNA methylation in promoter regions of SNURF-SNRPN and UBE3A imprinted genes, PWS-ICR and AS-ICR in the chromosome 15q11-q13 region. Semen samples from 10 healthy normozoospermic men were collected and each sample was divided into four equal aliquots: fresh, cryoprotectant, cryopreservation, and H 2 O 2 . We measured the ROS levels and DNA fragmentation using DCFH-DA and TUNEL assay respectively by flow cytometry. DNA methylation in promoter regions of SNURF-SNRPN and UBE3A imprinted genes, PWS-ICR and AS-ICR in the chromosome 15q11-q13 region were evaluated by quantitative methylation-specific PCR technique. Intracellular levels of ROS and percentage of TUNEL-positive spermatozoa significantly increased in cryopreservation group compared to fresh group. Exposure to cryoprotectant had no significant effect on ROS levels and DNA fragmentation. Neither cryopreservation nor exposure to cryoprotectant significantly affected DNA methylation of the selected gene regions. However, DNA fragmentation had positive correlation with DNA methylation of AS-ICR. In conclusion, based on our study, clinical use of sperm cryopreservation for fertility treatments appear to be safe in regard to DNA methylation in the chromosome 15q11-q13 region.

Objective: Our aim was to report the long-term follow-up for minimally invasive open pyeloplasty in children., Material and Methods: A total of 213 children with a mean age 16.33 months underwent miniature open pyeloplasty for ureteropelvic junction obstruction between January 2010 and May 2016. Anderson-Hynes dismembered pyeloplasty was performed through a subcostal miniature incision. The intraoperative and postoperative parameters including surgical operative time, incision size, intraoperative blood loss volume, postoperative analgesic use, hospital stay, complications, and success rate were documented., Results: The mean surgery time was 65 min (50-85 min), and incision size was 16.99 mm (12-36 mm). None of the patients required blood transfusion or narcotic analgesics in the postoperative period. The mean hospital stay was 21.97 h (10-48 h). Minor side effects included urinary tract infection (3.8%) and urinary leakage in one case (0.004%). Major complications were not observed. The mean antero-posterior pelvic diameter before and after surgery was 28.69 ± 11.54 mm and 15.89 ± 9.29 mm, respectively with a mean difference of 12.78 mm, which shows a significant decrease (P value = 0.001). The success rate was 98.1% with a mean follow-up of 21.43 months (3-56 months). Two of the recurrences occurred in the first postoperative year, another one after 1.5 years, and the last one after 4 years., Conclusion: Our study confirms minimally invasive open pyeloplasty in children as a safe and efficient procedure with the least complication and hospital stay rate in comparison with other minimally invasive techniques. Moreover, long-term follow-up is a requirement in pyeloplasty surgery.

Fluconazole-resistant Candida albicans is a big scary reality. The authors assessed the antifungal effects of magnetic iron-oxide nanoparticles on fluconazole-resistant colonising isolate of C. albicans and determined the expression of ERG11 gene, protein sequence similarity and ergosterol content. C. albicans isolates were characterised and fluconazole resistance is recognised using World Health Organization's WHONET software. Susceptibility testing of magnetic iron-oxide nanoparticles against fluconazole-resistant colonising isolate of C. albicans was performed according to Clinical and Laboratory Standards Institute guidelines. The expression patterns of ERG11 and protein sequence similarity were investigated. Ergosterol quantification has been used to gauge the antifungal activity of magnetic iron-oxide nanoparticles. The findings indicated that 93% of C. albicans isolates were resistant to fluconazole. Magnetic iron-oxide nanoparticles were presented activity against fluconazole-resistant colonising isolate of C. albicans with minimum inhibitory concentration at 250-500 µg/ml. The expression level of ERG11 gene was downregulated in fluconazole-resistant colonising isolate of C. albicans . The results revealed no differences in fluconazole-resistant colonising isolate of C. albicans by comparison with ERG11 reference sequences. Moreover, significant reduction was noted in ergosterol content. The findings shed a novel light on the application of magnetic iron-oxide nanoparticles in fighting against resistant C. albicans .

The available antiviral agents and their potential for the management of coronavirus disease 2019 (COVID-19) outbreak are important interventions. A systematic review and meta-analysis was performed to summarize the available evidence on the efficacy of nanoscale materials against coronaviruses in vitro and in animal models. PubMed, Scopus and Wiley Online Library databases were searched up to 4 March 2020. Studies that developed the efficacy of nanoscale materials against coronaviruses were included. Two reviewers independently extracted study characteristics and assessed risk of bias and applicability in the included studies. Meta-analyses were conducted to determine the overall inhibition efficacy of nanoscale materials against coronaviruses. A total of 21 studies were identified. Positive association was found between efficacy of nanoscale materials and coronaviruses in vitro and in animal models. The inhibition efficacy of nanoscale materials against coronavirus in vitro and in animal models were 1.84 (95% CI: 1.57, 2.15) and 1.66 (95% CI: 1.36, 2.02), respectively. Results of subgroup analysis of selected studies revealed that the nanoscale materials with spherical morphology were found to be more antiviral activity than the other morphologies against Middle East respiratory syndrome-coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Using systematic review and meta-analysis, our results indicate that nanoscale materials are positive affect against coronaviruses. We might clarify the possible potential for the use of nanoscale materials for SARS-CoV-2.

The literature on the global burden of noncommunicable diseases (NCDs) contrasts a spiraling epidemic centered in low-income countries with low levels of awareness, risk factor control, infrastructure, personnel and funding. There are few data-based reports of broad and interconnected strategies to address these challenges where they hit hardest. Kisoro district in Southwest Uganda is rural, remote, over-populated and poor, the majority of its population working as subsistence farmers. This paper describes the 10-year experience of a tri-partite collaboration between Kisoro District Hospital, a New York teaching hospital, and a US-based NGO delivering hypertension services to the district. Using data from patient and pharmacy registers and a random sample of charts reviewed manually, we describe both common and often-overlooked barriers to quality care (clinic overcrowding, drug stockouts, provider shortages, visit non-adherence, and uninformative medical records) and strategies adopted to address these barriers (locally-adapted treatment guidelines, patient-clinic-pharmacy cost sharing, appointment systems, workforce development, patient-provider continuity initiatives, and ongoing data monitoring). We find that: 1) although following CVD risk-based treatment guidelines could safely allocate scarce medications to the highest-risk patients first, national guidelines emphasizing treatment at blood pressures over 140/90 mmHg ignore the reality of "stockouts" and conflict with this goal; 2) often-overlooked barriers to quality care such as poor quality medical records, clinic disorganization and local employment practices are surmountable; 3) cost-sharing initiatives partially fill the gap during stockouts of government supplied medications, but still may be insufficient for the poorest patients; 4) frequent prolonged lapses in care may be the norm for most known hypertensives in rural SSA, and 5) ongoing data monitoring can identify local barriers to quality care and provide the impetus to ameliorate them. We anticipate that our 10-year experience adapting to the complex challenges of hypertension management and a granular description of the solutions we devised will be of benefit to others managing chronic disease in similar rural African communities., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Transurethral resection of the prostate (TURP) is considered to be the gold standard surgical procedure for medium-sized prostates. However, there is a drastic difference between the weight of resected tissue reported by the pathologist and the sonographic estimate of prostate weight before the operation. The present study investigates the role of electrocoagulation in tissue loss during monopolar (M-) and bipolar (B-) TURP. Methods: In this experimental in vitro study, 33 prostate glands removed from patients by open suprapubic prostatectomy were roughly divided in half and the weight of each half was recorded precisely. One half of the specimen was resected using a monopolar resectoscope and the other half was resected by bipolar resectoscope in an out-of-body simulated condition. The weight of obtained chips was measured and the amount of lost tissue was calculated. Data from prostates with final pathologic diagnosis of benign prostatic hyperplasia were included in the analysis. The mean difference of prostate weight before and after out-of-body resection and also the proportion of tissue loss between M-TURP and B-TURP were compared using t -test. Results: Data from 62 prostate halves were included in the final analysis. The mean weight of samples after M-TURP was considerably lower than before resection (38.0 ± 6.9 and 48.7 ± 9.0, respectively, p  < 0.001). Similarly, the mean weight of prostate samples after B-TURP was lower than the weight before resection (36.2 ± 7.3 and 48.4 ± 9.1, respectively, p  < 0.001). However, the ratio of tissue loss in B-TURP (25.3% ± 2.5%) was significantly higher than in M-TURP (21.3% ± 3.7%) ( p  < 0.001). Conclusion: Prostate resection using electrocoagulation leads to a significant prostate tissue loss due to heat effect. Furthermore, tissue loss in B-TURP is slightly more than M-TURP.

Objective: Evaluate the effectiveness of home talks (HTs), a novel model of health education delivered by village health workers (VHWs) with primary-level education to rural African mothers. Talk recipients were assessed by health census to be at risk for ill-health in one of 5 ways: malnutrition, diarrhea, respiratory disease, HIV, and poverty due to family size., Methods: Each participant received a pre-test, immediate post-test and delayed post-test on their assigned HT topic and a pre-test and delayed post-test on a randomly assigned control topic. Differences in scoring were examined against controls and over time using paired t-tests and general linear regression analysis, respectively., Results: Subjects lost knowledge gained from the HTs over time, but what they retained at 3 months was far greater than what they learned about the control topics (p-values <0.0001), independent of subjects' educational level., Conclusion: Targeted HTs to people with health census-identified risk factors resulted in learning and significant retention of knowledge., Practice Implications: Positive behavioral change resulting from health education has been shown in diverse contexts. This personal model of home talk education by VHWs targeting vulnerable families is flexible and effective and may be used to improve community health in other impoverished settings worldwide., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Naturally, in human body, there is a balance between free radicals and the antioxidant system. Yet, cigarette consumption in smokers increases free radicals and decreases antioxidants. A vast body of research showed that the ROS level of seminal fluid is reduced using oral antioxidant complements through enhancing the clearing capacity of free radicals. Thus, the present research aimed to explore the effect of vitamin complement consumption on changing male infertility indices among smokers., Methods: In the present randomized clinical trial which was single-blinded, 50 infertile oligospermic and asthenospermic men participated. They were selected in a randomized convenient sampling method. Before the study began, a semen sample was taken from all participants for analysis. Subsequently, the patients received 30 mg of Q10 coenzyme, 8 mg of zinc, 100 mg of vitamin C, 12 mg of vitamin E, 400 mg of folic acid for a whole duration of 3 months on a daily basis (once a day) and 200 mg of selenium every other day after lunch. A second sample of seminal fluid was taken from patients and semen parameters were compared between the pre- and post-test. The relevant statistical analyses were conducted in SPSS.23., Results: A comparison of pre-test and post-test results revealed that all sperm parameters including the volume, morphology, motion, count and progressive motility were significantly increased after the intervention (p ≥ 005). Moreover, a statistically significant improvement was observed in the pH and concentration of seminal fluid., Conclusion: The present research showed that consuming vitamin complements (30 mg of Q10, mg of zinc, 100 mg of vitamin C, 12 mg of vitamin E, 400 mg of folic acid) once a day as well as 200 mg of selenium every other day can effectively improve the qualitative parameters (pH and concentration) and quantitative parameters (volume, motion, morphology, count and progressive motility) in infertile male smokers., (© 2020 the Author(s), licensee AIMS Press.)

Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects. To test the hypothesis, pregnant rats were treated with intraperitoneal injection of either saline or LPS (0.5 mg/kg) at gestational day 15 and 16, and zinc supplementation (30 mg/kg) was administered throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to evaluate working memory of offspring. Moreover, the expression levels of catechol O-methyltransferase (COMT) and glutamate decarboxylase 67 (GAD67) were measured in the frontal cortex of the brain samples. Only male offspring prenatally exposed to LPS showed a significant impairment in working memory. In addition, prenatal LPS exposure causes a moderate decrease in GAD67 expression level in the male pups, while COMT expression was found unchanged. Interestingly, zinc supplementation restored the alterations in working memory as well as GAD67 mRNA level in the male rats. No alteration was detected for neither working memory nor COMT/GAD67 genes expression in female offspring. This study demonstrates that zinc supplementation during pregnancy can attenuate LPS-induced impairments in male pups. These results support the idea to consume zinc supplementation during pregnancy to limit neurodevelopmental deficits induced by infections in offspring., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: The medical community recognizes the importance of confronting structural racism and implicit bias to address health inequities. Several curricula aimed at teaching trainees about these issues are described in the literature. However, few curricula exist that engage faculty members as learners rather than teachers of these topics or target interdisciplinary audiences., Methods: We developed a longitudinal case conference curriculum called Health Equity Rounds (HER) to discuss and address the impact of structural racism and implicit bias on patient care. The curriculum engaged participants across training levels and disciplines on these topics utilizing case-based discussion, evidence-based exercises, and two relevant conceptual frameworks. It was delivered quarterly as part of a departmental case conference series. We evaluated HER's feasibility and acceptability by tracking conference attendance and administering postconference surveys. We analyzed quantitative survey data using descriptive statistics and qualitatively reviewed free-text comments., Results: We delivered seven 1-hour HER conferences at our institution from June 2016 to June 2018. A mean of 66 participants attended each HER. Most survey respondents (88% or more) indicated that HER promoted personal reflection on implicit bias, and 75% or more indicated that HER would impact their clinical practice., Discussion: HER provided a unique forum for practitioners across training levels to address structural racism and implicit bias. Our aim in dissemination is to provide meaningful tools for others to adapt at their own institutions, recognizing that HER should serve as a component of larger, multifaceted efforts to decrease structural racism and implicit bias in health care., Competing Interests: None to report., (Copyright © 2019 Perdomo et al.)

Background: Concentrations of plasma lipids levels during pregnancy clearly increases. According to some studies, dyslipidemia is effective in the incidence of preeclampsia and insulin resistance. Objective: This study aimed to examine the relationship between hyperlipidemia and maternal and neonatal outcomes in pregnant women., Materials and Methods: This is a cross-sectional study which was conducted on two groups of pregnant women with hyperlipidemia and normal ones to assess maternal and neonatal outcomes. Maternal data including gestational age, mother's age, body mass index, and maternal weight gain during pregnancy, gestational diabetes mellitus, preeclampsia, cholestasis, and delivery method. Also, birth weight and Apgar score were gathered as the neonatal outcomes., Results: The results showed that the prevalence of abnormal lipid parameters increased with increasing gestational age. In pregnant women with dyslipidemia in combination with increased triglyceride, cholesterol and Low-density lipoprotein, and decreased High-density lipoprotein, the incidence rates of gestational diabetes (p < 0.001), preeclampsia (p < 0.001), cholestasis (p = 0.041), fetal growth retardation (p < 0.001), and macrosomia (p < 0.001) were statistically higher., Conclusion: Dyslipidemia was associated with some adverse effects of pregnancy and harmful fetal outcomes. Therefore, it seems that adding laboratory assessment of lipid profiles before and during pregnancy can be effective in early diagnosis of dyslipidemia., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2019 Seyedeh Hajar Sharami et al.)

Dopamine is an important regulator of male sexual function and behaviour. Decreased levels of this substance have been observed in blood and seminal plasma of infertile men. Hence, this study was carried out to determine the impact of varicocelectomy on 24-hr urine dopamine values in patients with both premature ejaculation (PE) and varicocele. In this prospective study, 55 consecutive patients with premature ejaculation and grade 2 or 3 varicocele were enrolled. The urine dopamine level was measured in a 24-hr sample by HPLC method in a single laboratory centre. Two samples were gathered from each patient, one before and the other 1 month after varicocelectomy. The mean initial and final 24-hr urine dopamine levels were 259.6 ± 86.3 and 602.9 ± 88.4 micrograms, respectively, showing statistically significant increase (p = .0001), while there was no statistically significant difference between urine volume and creatinine. However, the change in intravaginal ejaculation latency time value was not statistically significant at this short time visit. According to our findings, varicocelectomy results in a significant increase in 24-hr urine dopamine levels in patients with premature ejaculation and varicocele. However, the effect of this change on premature ejaculation in the long term has yet to be determined., (© 2019 Blackwell Verlag GmbH.)

The link between inappropriate parenting style and both bullying and victimization is well documented. However, it is not clear as to which kind of parenting style is associated with victimization. Furthermore, no studies have yet been conducted regarding the role of parental stress in bullying and victimization. This study aimed to examine the role of parenting styles and maternal stress in pupils' bullying and victimization. A total of 300 primary school pupils, enrolled in fourth and fifth grades, participated in the study. Initially, 100 noninvolved pupils were randomly selected using a multistage cluster sampling method. Then using a screening method, 100 bully pupils and 100 victimized peers were selected. Olweus Bullying Scale and teacher nomination were administered for screening these pupils. Baumrind Parenting Style Questionnaire and revised version of Abidin Parental Stress Index (short form) were also applied to all pupils in the study. Data were analyzed using discriminant function analysis. The findings showed that (a) with regard to parenting styles, significant differences were found among groups. Authoritarian parenting style could significantly predict pupils' bullying behavior, whereas victimization was predictable in families with permissive parenting style. In addition, noninvolved pupils were predicted to have authoritative parenting style. (b) Considering maternal stress, significant differences were observed across groups. Parents of bullies and victims were predicted to have higher maternal stress than noninvolved pupils. The implications of the study in relation to the role of mothers in bullying and victimization are discussed.

Competing Interests: Conflict of interests The authors declare that there is no conflict of interest.

The oxytocinergic system influences attentional bias towards emotional cues and feedback-based learning. Considering a tag single-nucleotide polymorphism (SNP) found through analysis of an intronic haplotype in the oxytocin receptor (OXTR) gene, we investigated the effect of oxytocin on risky decision-making via the Iowa Gambling Task (IGT). Young healthy males received intranasal oxytocin or placebo, and the IGT was performed where raw scores, net scores and total time were recorded, and ratio of advantageous to disadvantageous choices was calculated. Using PCR-pyrosequencing, a 761 bp target sequence in the OXTR gene was amplified and sequenced after the extraction of whole blood DNA. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all 14 SNPs in the intronic region were determined based on D' and LOD values, and rs2254295 with the highest LD was indicated as the tag SNP. GTT was shown to have the highest frequency among the found haplotypes. Oxytocin group and participants with the TT genotype demonstrated a significantly increased raw score, net score and advantageous choices, whereas the total time was not influenced remarkably. This means that oxytocin significantly reduced the risk taking in decision-making, and participants with the TT genotype had less premature or risky decisions than those with the CT and CC genotypes. rs2254295 may modulate the function or expression of the OXTR gene, implying that T allele may increase the expression of the OXTR gene compared to C allele. We suggest that oxytocin may remarkably moderate the risk attitude and its consequences during uncertain decision-making., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The X-linked ZMYM3 gene (also known as ZNF261) contains the longest STR, (GA)32, identified in a human protein-coding gene 5'UTR (ENST00000373998.5: ZMYM3-207). This STR reaches maximum length in human, and is located in a complex string of four consecutive GA-STRs with a human-specific formula across the complex. A previous study in Iranian male schizophrenia (SCZ) patients revealed co-occurrence of the extreme short and long alleles of the STR with SCZ. Here we studied the allelic distribution of this STR in bipolar disorder (BD) type I. The interval encompassing the human ZMYM3 STR complex was PCR-amplified and sequenced in 546 male subjects, consisting of 157 BD patients and 389 controls., Results: We found three alleles at the extreme short (17-repeat) and long (38- and 43-repeat) ends of the allele distribution curve in the BD cases (4.4% of the BD alleles) that were not detected in the controls (Mid p < 0.0001). These alleles overlapped with the extreme disease-only alleles detected previously in the SCZ patients. Domain reconstruction of the GA-STR complex revealed significant structural alteration as a result of various sequence repeats and nucleotide compositions at the inter and intraspecies levels., Conclusion: The ZMYM3 "exceptionally long" 5' UTR STR findings may alter our perspective of disease pathogenesis in psychiatric disorders, and set an example in which the low frequency alleles at the extreme short and long ends of the human STRs are, at least in part, a result of natural selection against these alleles and their unambiguous link to major human disorders., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: In recent years, endoscopic subureteral injection has gained popularity as a therapeutic alternative to open surgery because of its high success rates and low morbidity. We compared the success and complication rates of Polyacrylate polyalcohol copolymer (PPC) and Dextranomer/Hyaluronic acid (Dx/HA) in the endoscopic treatment of VUR., Materials & Methods: We retrospectively reviewed the patients who underwent endoscopic correction of their VUR by subureteric injection of PPC or Dx/HA from Jan 2010 to April 2016. The injection technique was STING (subureteric), distal HIT (intraureteric), and double HIT according the hydrodistention (HD) grade. The success rate, injection technique, injection volume, VUR grade, and obstruction rate were evaluated and compared between two groups., Results: 107 renal refluxing units (RRU) with a mean age 55.23±36.58 months and 64 RRU with a mean age 52.13±31.66 months were treated in Dx/HA and PPC groups, respectively. The PPC group showed a more successful outcome in comparison to the Dx/HA group (92.2% versus 75.7% of the RRU with P value<0.001) at 3 months follow up. The injection technique was not significantly different between two groups. In PPC group the success rate was decreased significantly with increasing reflux grade but this reduction was not statistically significant in Dx/HA group. The injected volume was significantly more in PPC group; in addition, there was statistically significant correlation between injected volume of the bulking agent and obstruction rate. However, the obstruction rate did not establish significant difference between the two groups (P value=0.83), however it was earlier in Vantris (4 months versus 22 months)., Conclusions: Our investigation approved PPC as a more effective material, regardless of other confounding variables such as reflux grade, learning cure, and technique of injection, in endoscopic treatment of VUR. In addition, the other remarkable point is this effectiveness is not accompanied by more post-operation obstruction.

Among the many challenges facing health systems grappling with the explosive growth of chronic disease in Africa are continuity of care, particularly in poor, rural areas. We report the strategy, field experience, and results of an ongoing 6-year follow-up program operating in a rural district hospital in Kisoro, Uganda, that attempts to locate and reengage patients lost to follow-up (LTFU) from communities that are largely without phones, addresses, or paved roads. The program works with diverse hospital clinics, including chronic diseases, HIV, tuberculosis (TB), nutrition, and women's health, to identify patients who have not returned to care, employing a modest staff who spend about 20 days monthly making outreach visits by motorcycle in search of approximately 130 patients. We describe the organization of this unique "horizontal" program and report on follow-up outcomes between November 2015 to October 2016. Between 30% and 60% of patients were found to have lapses in care. The follow-up program was able to locate 64% of patients, with a reengagement rate of 54% to 92% (average, 69%) depending on the clinic. The program costs approximately US$5 per patient LTFU but about US$40 per patient maintained in care. The hospital-based follow-up program that cuts across diverse clinics and wards was novel and feasible in this rural sub-Saharan African setting., (© Alizadeh et al.)

Background: Cystinuria as an autosomal recessive sickness is a relatively rare disease. Formation of cystine stones indicates cystinuria. Few studies are considered the cysteine crystal volume in management of cystinuria. Selenium may inhibit organization of crystal stone, growth and stone aggregation. Since the role of selenium on inhibition of cystine crystal formation is not known, the aim of this study was to evaluate the effect of selenium supplementation on cystine crystals volume in patients with cystinuria., Materials and Methods: This double-blind clinical trial study was conducted on 48 patients in Al-Zahra hospital, Isfahan, Iran from 2015 to 2017. These patients received selenium (200 mg/ daily) for 6 weeks. The urine crystal volume was evaluated before and after treatment. Data were entered SPSS and analyzed by Paired sample T test, Spearman and Pearson coefficient correlation. P- value < 0.05 was considered significant., Results: In current study, mean cystine crystal volume before and after treatment was 6787.4 ± 11902.6 and 3110.9 ± 7225.4, respectively. Significant difference was observed before and after treatment in terms of cystine crystal volume (p < 0.001). No relation was observed between the mean cystine crystal volume with sex, age and type of medical procedures (p > 0.05)., Conclusion: In this study, selenium treatment affected cystine crystal volume. It seems that selenium had the potential value to alleviate the volume of cystine crystal. Therefore, since reducing of cystine crystal volume decreases crystal formation, selenium may be effective to cure patients with cystinuria. However, age, sex and type of medical procedures did not affect cysteine crystal volume., (© Author(s) 2018. This article is published with open access by China Medical University.)

TCF4 and GRM8, two significant genes involved in the normal nervous development and glutamate pathway, are thought to be involved in the pathogenesis of schizophrenia (SCZ). We aimed to explore the association of TCF4 and GRM8 gene polymorphisms with risk of SCZ. The rs8766 in TCF4 and rs712723 in GRM8 were selected for genotyping in a set of Iranian case-control samples including 215 patients and 220 matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Although rs8766 increased the OR, we found that rs8766 allele and genotype frequencies were not significantly different between case and control groups and a significant association cannot be suggested for the selected SNP. However, allele C and genotype CC (allele C: OR 1.48, 95% CI 1.13-1.94; genotype CC: OR 1.71, 95% CI 1.09-2.68) of rs712723 polymorphism was found to have a significant association with risk of SCZ. Frequency of allele C (P = 0.003) and genotype CC (P = 0.017) was higher in the schizophrenic patients, while allele T (P = 0.003) and genotype TT (P = 0.028) frequencies were found lower in patients. Our findings indicate that rs712723 in GRM8 may play an important role in the pathogenesis of SCZ. However, our conclusion needs to be confirmed in other population.