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Indoxyl sulfate (IS) is one of the most potent uraemic toxins involved in the progression of chronic kidney disease (CKD) through the induction of inflammation and oxidative stress. This study assessed the potential benefits of reducing IS concentrations through dialysis treatment to improve renal function, inflammation, and oxidative stress. A prospective, observational cohort study of 50 patients with CKD undergoing dialysis treatment was conducted. IS levels, inflammatory markers (IL-6 and hs-CRP), and oxidative status (Cu/Zn-SOD) were measured using immunoenzymatic methods, and the albumin ratio (HNA/HMA) was assessed using high-performance liquid chromatography. Blood samples were collected at baseline and, at 8 weeks and 16 weeks after treatment. At baseline, patients with CKD had elevated levels of IS, renal function indicators, inflammatory markers (IL-6 and CRP), and oxidative markers (Cu/Zn-SOD and albumin ratio HNA/HMA). Dialysis treatment reduced IS levels, and a correlation among IS, renal function, and SOD levels ( P < 0.0001) at 8 and 16 weeks was observed. The reduction in IS levels was associated with improved inflammatory marker levels (CRP and IL-6; P < 0.0001) and a significant decrease in the HNA/HMA ratio ( P <0.0001) at 8 and 16 weeks. These associations strengthened over time. The results of this study suggest that IS levels may be a therapeutic target for improving outcomes in patients with CKD by improving renal function, inflammation, and oxidative stress. More research is needed to understand how IS contributes to CKD complications., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Tuberculosis (TB) remains a significant public health concern worldwide. Given the dense living and interactive nature of university environments, students may be at higher risk. This cross-sectional study assessed tuberculosis-related knowledge, attitudes, and practices (KAP) among students at Taif University (TU) from November 2022 to May 2023. Using a self-administered online questionnaire with 40 items, 1155 students participated. Key demographics: 68.2% females, 96.9% Saudi citizens, 94.5% unmarried, and 87.5% non-smokers. Of the respondents, 26.5% had no knowledge of TB. The TB-related KAP scores among the aware students were 64.9%, 74.8%, and 81%, respectively. Medical college students exhibited significantly higher TB-related knowledge and attitudes than their non-medical peers ( p < 0.001). The findings indicate a commendable level of TB-awareness among TU students, but there remains a substantial uninformed segment. Campaigns to enhance TB knowledge among TU students are suggested.

Background: In many developed countries, the scope of community pharmacy services has extended to include advanced applications. Unlike traditional practices that focus on pharmaceutical sales, extended community pharmacy services (ECPSs) are patient-centred and typically offered by specialised healthcare centres, which improve public health, reduce pressure imposed on healthcare professionals, and rationalise health system expenditures. However, based on the findings of several studies, community pharmacies (CPs) only provide marginalised services. Public reviews are thus crucial to effectively utilise such services. This study explored CPs use among the Saudi public in terms of knowledge, attitudes, and barriers to ECPSs., Materials and Methods: We conducted a cross-sectional web-based survey of a non-probability sample between October and December 2021. Numerical and graphical descriptive statistics were employed with an additional analytical assessment using binary logistic regression to determine the association between participant characteristics and the barriers to ECPSs use., Results: A total of 563 individuals participated in this study, approximately 33% of which revealed CPs as the first place they visit for medication concerns. Most individuals were not aware of medication therapy management and health screening services (77% and 68%, respectively). Pharmacy clinics offering private counselling and receiving patient electronic medical records were unknown to the participants (78% and 63%, respectively). A substantial proportion of the cohort considered lack of privacy (58%) and inadequate communication with community pharmacists (56%) as key barriers to the use of ECPSs. Logistic regression analysis revealed that the underdeveloped infrastructure of CPs was significantly associated with almost all factors., Conclusion: Most services and facilities were found to be underutilised. Positive public attitudes were associated with concerns regarding privacy and cost of services. Consistent with Saudi Vision 2030, supporting CPs and increasing the public awareness of ECPSs have significant implications on public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alghamdi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

On March 11 th , 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) a pandemic. To control the pandemic, billions of vaccine doses have been administered worldwide. Predictors of COVID-19 vaccine-related side effects are inconsistently described in the literature. This study aimed to identify the predictors of side effects' severity after COVID-19 vaccination among young adult students at Taif University (TU) in Saudi Arabia. An online, anonymous questionnaire was used. Descriptive statistics were calculated for numerical and categorical variables. Possible correlations with other characteristics were identified using the chi-square test. The study included 760 young adult participants from TU. Pain at the injection site (54.7%), headache (45.0%), lethargy and fatigue (43.3%), and fever (37.5%) were the most frequently reported COVID-19 vaccine-related side effects after the first dose. The most frequent side effects were reported among the 20-25-year-old age group for all doses of all vaccines. Females experienced remarkably more side effects after the second (p < 0.001) and third doses (p = 0.002). Moreover, ABO blood groups significantly correlated with vaccine-related side effects after the second dose (p = 0.020). The participants' general health status correlated with the side effects after the first and second doses (p < 0.001 and 0.022, respectively). The predictors of COVID-19 vaccine-related side effects in young, vaccinated people were blood group B, female gender, vaccine type, and poor health status., (© 2023. The Author(s).)

Background: Recent epidemiological studies have reported an association between the ABO blood group and the acquisition, symptom severity, and mortality rate of coronavirus disease 2019 (COVID-19). However, the association between the ABO blood group antigens and the type and severity of COVID-19 vaccine-related adverse reactions has not been elucidated. Patients and Methods: We conducted a cross-sectional, questionnaire-based study in Saudi Arabia from February to April 2022. The study cohort included adults who had received or were willing to receive at least two doses of a COVID-19 vaccine of any type. We used Chi-square test to assess the association between the ABO blood groups and vaccine-related adverse reactions. p values of <0.05 were considered significant. Results: Of the 1180 participants, approximately half were aged 18-30 years old, 69.2% were female, and 41.6% reported their blood group as O. The most frequent COVID-19 vaccine-related adverse reactions were fatigue (65%), pain at the injection site (56%), and headache (45.9%). These adverse reactions demonstrated significant correlations with the education level ( p = 0.003) and nationality ( p = 0.018) of the participants following the first dose, with gender ( p < 0.001) following the second dose, and with the general health status ( p < 0.001) after all the doses. Remarkably, no correlation was observed between the severity of the vaccine-related adverse reactions and ABO blood groups. Conclusion: Our findings do not support a correlation between the severity of COVID-19 vaccine-related adverse reactions and the ABO blood groups of the vaccinees. The creation of a national database is necessary to account for population differences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Almalki, Khalifa, Alhemeidi, Ewis, Shady and Abdelwahab.)

The gold-standard approach for diagnosing and confirming Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection is reverse transcription-polymerase chain reaction (RT-PCR). This method, however, is inefficient in detecting previous or dormant viral infections. The presence of antigen-specific antibodies is the fingerprint and cardinal sign for diagnosis and determination of exposure to infectious agents including Corona virus disease-2019 (COVID-19). This cross-sectional study examined the presence of SARS-CoV-2 spike-specific immunoglobulin G (IgG) among asymptomatic blood donors in Makkah region. A total of 4368 asymptomatic blood donors were enrolled. They were screened for spike-specific IgG using ELISA and COVID-19 RNA by real-time PCR. COVID-19 IgG was detected among 2248 subjects (51.5%) while COVID-19-RNA was detected among 473 (10.8%) subjects. The IgG frequency was significantly higher among males and non-Saudi residents (p < 0.001 each) with no significant variation in IgG positivity among blood donors with different blood groups. In addition, COVID-19 RNA frequency was significantly higher among donors below 40-years old (p = 0.047, χ2 = 3.95), and non-Saudi residents (p = 0.001, χ2 = 304.5). The COVID-19 IgG levels were significantly higher among the RNA-positive donors (p = 001), and non-Saudi residents (p = 0.041), with no variations with age or blood group (p > 0.05). This study reveals a very high prevalence of COVID-19 IgG and RNA among asymptomatic blood donors in Makkah, Saudi Arabia indicating a high exposure rate of the general population to COVID-19; particularly foreign residents. It sheds light on the spread on COVID-19 among apparently healthy individuals at the beginning of the pandemic and could help in designing various control measures to minimize viral spread.

Background and objective Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases worldwide. It causes an unpleasant effect on patients' lives and may lead to serious complications resulting in a significant burden on healthcare systems. Despite being a common gastrointestinal disease, very few studies have been conducted on the condition in Saudi Arabia; and there has never been a study to estimate the prevalence of GERD in the Al-Qunfudah Governorate. In light of this, we conducted this study with an aim to assess the prevalence of GERD and its associated risk factors among the Al-Qunfudah population. Methods A cross-sectional study was conducted in the Al-Qunfudah Governorate by using an online self-administrated questionnaire that was shared through social media during the first week of January 2021. The questionnaire consisted of a general section on sociodemographic data and a section on the diagnosis of GERD based on the validated gastroesophageal reflux disease questionnaire (GERD-Q). A total of 1,180 eligible participants responded to the questionnaire. Results Nearly one-third (32.9%) of the study participants had GERD based on their reported symptoms and calculated scores (GERD-Q score ≥8). About 14.8% of the participants (175/1,180) reported that they had already been diagnosed with GERD before their participation in our survey. Regarding risk factors of GERD, about 35% reported experiencing psychological stress, 28.3% had a family member diagnosed with GERD, and 18.1% were smokers; 49.4% of the participants had their symptoms aggravated by consuming fatty or fried food and 46.7% by spicy food. One of the factors that helped to relieve GERD symptoms was avoiding symptom-aggravating food, as reported by more than half (50.7%) of the participants. Conclusion The prevalence of GERD in the Al-Qunfudah population is high as the condition has affected one-third of the adult population. Our study confirms that male gender, age of 30 years or above, being overweight or obese, being married, smoking habit, use of non-steroidal anti-inflammatory drugs (NSAIDs), having psychological stress, being asthmatic, or having a family history of GERD are factors that significantly increase the likelihood of developing GERD. The reported risk factors include experiencing psychological stress, a family history of GERD, high BMI, and smoking., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Odah et al.)

University students are at elevated risk for mental health problems. The COVID-19 pandemic and subsequent public health measures taken to combat it burdened the students' life with additional dramatic psychological impacts. The aim of this study was to investigate the psychological impacts that affected the university students in Egypt during the COVID-19 pandemic. An online survey was sent to the Egyptian university students via all means of online communication during the first week of May 2020 by using a non-probability snowball sampling. A survey included a short version Depression Anxiety Stress Scale-21 (DASS-21) and socio-demographic data. Overall, 70.5, 53.6 and 47.8% of Egyptian students had depression, anxiety and stress, respectively. Being a female, having a relative or acquaintance infected with COVID-19, having a preexisting chronic disease and lacking of psychological support from families, community and universities increase the risk of depression, anxiety and stress among Egyptian students. Being a medical student is associated with depression while, spending more time to follow news of COVID-19 pandemic is associated with increased anxiety. Egyptian students experience varying levels of psychological disturbance during COVID-19 pandemic. This study suggests that mental health of the university students should be carefully, monitored during the crisis and the universities should provide psychological-oriented services, adapted to these circumstances to mitigate its emotional impact on the students., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pancreatic cancer (PC) is a serious and rapidly progressing malignancy. Identifying risk factors including dietary elements is important to develop preventive strategies. This study focused on possible links between diet and PC. Methods: We conducted a case-control study including all PC patients diagnosed at Minia Cancer Center and controls from general population from June 2014 to December 2015. Dietary data were collected directly through personal interviews. Principal component analysis (PCA) was performed to identify dietary groups. The data were analyzed using crude odds ratios (ORs) and multivariable logistic regression with adjusted ORs and 95% confidence intervals (CIs). Results: A total of 75 cases and 149 controls were included in the study. PCA identified six dietary groups, labeled as cereals and grains, vegetables, proteins, dairy products, fruits, and sugars. Bivariate analysis showed that consumption of vegetables, fruits, sugars, and total energy intake were associated with change in PC risk. In multivariable-adjusted models comparing highest versus lowest levels of intake, we observed significant lower odds of PC in association with vegetable intake (OR 0.24; 95% CI, 0.07-0.85, P=0.012) and a higher likelihood with the total energy intake (OR 9.88; 95% CI, 2.56-38.09, P<0.0001). There was also a suggested link between high fruit consumption and reduced odds of PC. Conclusions: The study supports the association between dietary factors and the odds of PC development in Egypt. It was found that higher energy intake is associated with an increase in likelihood of PC, while increased vegetable consumption is associated with a lower odds ratio., (Creative Commons Attribution License)

Objectives: Estimating the burden of child labor in a rural community of El-Minia governorate, Egypt and exploring its determinants and health impact., Methods: One hundred and ninety nine children randomly participated from a randomly selected village; 147 (73.9%) males and 52 (26.1%) females, whose ages ranged from 6 to 17 years (mean age 12.1 ± 2.9). All children were subjected to interview questionnaire, and medical examination., Results: Ninety (45.2%) of the children reported that they are engaged in a work. The working children belonged to 65.6 and 85.6% of illiterate fathers and mothers, respectively. The majority of the working children were engaged in jobs at quarries (58.9%), followed by farming (21.1%), then small proportions of children were working in other jobs. Poverty, big families and insufficient family's income were the most frequently reported reasons for starting to work (80%). There was a significant higher prevalence of the reported health complaints among working children., Conclusions: Working children are at high risk of many health problems. Poverty, parents' illiteracy, large family size and fathers' absence are the driving force for child labor in the rural community of Eastern Minia.

Cutaneous leishmaniasis (CL) is an endemic parasitic infection in the Mediterranean region, including Libya and its Al-jabal Al-gharbi province. We aimed at studying the occupational relevance as well as other epidemiological aspects of CL. We investigated 140 CL cases who attended at Gharyan outpatient polyclinic during a period of 6 months in 2009. CL infection was clinically diagnosed and confirmed by demonstration of Leishmania parasites on smears from lesions. Our findings showed that males were more affected than females (P=0.04), and people above 10-years were more affected than younger ones (P=0.0001). A significant percent of CL cases belonged to Al-Kawasem subprovince (P=0.0001). Farm-related activities were the most frequent occupations among CL cases (P=0.04). In addition to farm workers, housewives and students are at risk groups since they are engaged at farm activities. Moreover, those who have occupations that require staying outdoors for a part of night, e.g., policemen, are also at risk. Compared to children, adult CL patients had multiple lesions (P=0.001) that were more prevalent in their upper and lower extremities than the face (P=0.0001). We conclude that CL is a major health problem in Al-jabal Al-gharbi province of Libya. The presence of rodents and sandflies makes it a suitable environment for Leishmania to spread in an endemic epidemiological pattern. Being engaged in farming activities or outdoor occupations increases the risk of infection. Various clinical patterns of CL suggest the presence of more than 1 species of Leishmania at Al-jabal Al-gharbi province. We propose that the 2 species responsible for CL in this area are L. major and L. tropica. Further investigations to identify the leishmanial species responsible for CL at Al-jabal Al-gharbi together with adoption of preventive and control programs are needed.

Identification of an individual plays a vital part of any medico-legal investigation. Fingerprints are considered to be one of the most reliable methods of identification. The present study was conducted on 752 healthy adult Egyptian subjects (380 males and 372 females) with age ranged from 20 to 30 years. Consents were obtained from all participants and their 10 digits were photographed to determine the sexual dimorphism by some fingertip features (ridge count, square area, finger breadth and finally ridge density) in Egyptians. Statistical analysis was made using a multivariate logistic regression variation analyses. Results showed that females tend to have statistically significant shorter (narrower) finger breadth (right: male > 9.54 ≥ female, left: male > 9.38 ≥ female), smaller square area (right: male ≥ 16.1 > female, left: male > 15.1 ≥ female), more ridge count (right: female > 21.0 ≥ male, left: female > 21.2 ≥ male), and higher ridge density (right: female >1.35 ≥ male, left: female > 1.5 ≥ male) when compared with males. The ridge density of the left hand was the most single accurate parameter in correct sex determination. The best classification accuracy of 82% was generated upon combining ridge count, square area and ridge density. It was concluded that fingertip features of Egyptians can be used by medico-legal experts for accurate sex identification., (Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

We previously performed a survey of the sperm characteristics of the partners of pregnant women in four cities in Japan. In the present study, we analyzed the sperm characteristics of these subjects and the correlations between these sperm characteristics and climatic changes or Y chromosome haplogroups. Our results showed that more haplogroup D2a1 males than O2b1 males were born in the first half of the year (January to June), whereas more O2b1 males were born in the last half of the year (July to December) (P<0.05). This was agreed and correlated with the seasonal variations in their mean sperm concentrations. The haplogroup C, D* and D2a1 males displayed lower sperm concentrations from March to May, followed by an increase in their sperm concentrations starting in June or July, while the O2b1 males displayed higher sperm concentrations in the first half of the year followed by a sudden decrease from July to August (P<0.05). We hypothesize that the Japanese climate has different effects on the sperm characteristics and reproductive seasonality of males from different lineages; and therefore, has influenced the modern population of Japan.

Measurements of talus have been shown to be sexually dimorphic in South African blacks and whites and Prehistoric New Zealand Polynesians. Since several studies have demonstrated that discriminant function equations used to determine the sex of a skeleton are population specific, the purpose of the present study was to derive similar equation for the tali of Egyptians. The sample consisted of 110 tali (67 male & 43 female) whose age at death ranged between 20 and 60 years. The tali were obtained from Anatomy departments of Minia and Cairo Universities and also from Forensic Medicine department of Justice Office in Minia governates - Egypt. Twelve measurements were taken for every talus. Data were analyzed by SPSS version 16. All measurements showed significant sexual differences (P < 0.05) except calcaneus articular surface width and navicular articular surfaced width. Talar length was found to be the most sexual dimorphic (90.9%). Combination of talar length, talar width and neck width gave a percentage of accuracy of 85.5%. Finally, it is concluded that the talus of Egyptian population is useful for sex estimation., (Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

The SRY (sex-determining region on the Y chromosome) is essential for male development; however, the molecular mechanism by which the SRY induces testis development is still unclear. To elucidate the mechanism of testis development, we identified SRY-interacting proteins using a yeast two-hybrid system. We found two ribosomal proteins, RPS7 (ribosomal protein S7) and RPL13a (ribosomal protein L13a) that interact with the HMG (high-mobility group) box domain of SRY. Furthermore, we confirmed the intracellular distributions of RPS7, RPL13a and SRY and found that the three proteins were co-expressed in COS1 cells. SRY, RPS7 and RPL13a were co-localized in nuclear speckles. These findings suggest that SRY plays an important role in activities associated with nuclear speckles via an unknown mechanism.

Pleural plaques are asymptomatic focal thickenings of the pleura and considered the hallmark of asbestos exposure. However, it is often difficult to detect pleural plaques on chest x-rays (CXR). In a retrospective study, using chest CT scans of 140 Japanese asbestos-exposed construction workers who have probable or definite findings of pleural plaque on CXR; firstly, we proposed plaque morphology-based classification for CXR findings, and then we examined if those classified findings could be confirmed as pleural plaques on CT scans. Our morphology-based classification of pleural plaque findings included nine types. The percentages of confirmed pleural plaques on CT scans by type (number of confirmed pleural plaque on CT/number of observed on CXR) were 93% (40/43) for straight, 89% (56/63) for diamond, 88% (7/8) for double, 83% (19/23) for tapered medially, 80% (20/25) for parallel, 77% (23/30) for crescent, 79% (11/14) for tenting, 72% (18/25) for tapered-laterally (long type), and 0% (0/9) for tapered-laterally (short type). When added to the ILO classification, morphology-based classification of CXR pleural plaque findings makes its detection easier and hence chest radiograph continues to be a suitable tool for screening asbestos-related pleural plaques based on its simplicity, low radiation exposure, wide availability and cost-effectiveness.

In mammals, sex is determined by the presence or absence of the Y chromosome that bears a male-dominant sex-determining gene SRY, which switches the differentiation of gonads into male testes. The molecular signaling mechanism turning on the switch, however, has remained unclear for 18 years since the identification of the gene. Here, we describe how this gene emerged and started to work. From amino acid homology, we realized that SRY is a hybrid gene between a portion of the first exon of DiGeorge syndrome critical region gene 8 (DGCR8) and the high-mobility group (HMG) box of SRY box-3 (SOX3) gene. We identified the regulatory sequence in the SRY promotor region by searching for a common motif shared with DGCR8 mRNA. From the motif search between DGCR8 mRNA and the SRY upstream sequence, we found that the transcription factor CP2 (TFCP2) binding motif is present in both. TFCP2 overexpression did not show a significant increase of SRY mRNA expression, and TFCP2 suppression by RNA interference (RNAi) significantly reduced SRY mRNA expression. Furthermore, electrophoretic mobility shift assay (EMSA) demonstrated that TFCP2 acts as a regulator by directly binding to the SRY promoter. We conclude that SRY is a hybrid gene composed of two genes, DGCR8 and SOX3; and TFCP2 is an essential transcription factor for SRY expression regulation.

We have previously reported that 26S proteasome subunit mRNA expressions correlate with male body mass index (BMI). In this study, to investigate whether proteasome activities are correlated with BMI, we recruited 61 healthy young Japanese male subjects, measured proteasome activities in their plasma, and correlated them with their BMI and various metabolic factors. We found that among three different proteasome activities, chymotrypsin-like activity in plasma was positively correlated with BMI in healthy Japanese male subjects. Furthermore, we analyzed proteasome activity in vitro during the differentiation of human adipose-derived stem cell (hADSC) into mature adipocytes. In the early stage of differentiation, proteasome activity was at its highest level, and proteasome inhibitor could inhibit hADSC adipocyte differentiation. Our findings suggest that proteasome is an important controlling factor for the development of obesity and adipogenesis.

Childhood overweight/obesity is growing steeply, globally. It is usually regarded as a risk factor for severe obesity over life-time course. Here, we investigated temporal course of overweight/obesity development in Japanese school children. A six-year longitudinal study was performed on 16,245 Japanese primary school children (8,427 boys and 7,818 girls) comprising three cohorts of 1(st) approximately 3(rd) grade. A baseline survey was conducted at 2001, followed by annual baseline studies from 2002 approximately 2007 to determine the prevalence and track overweight/obesity. Our results showed that the prevalence of overweight was 15 approximately 23% in boys and 15 approximately 18% in girls, however, for obesity it ranged between 4 approximately 7% in boys; and 2 approximately 4% in girls. As regards for tracking status, 60 approximately 80% of overweight and 35 approximately 70% of obese Japanese primary school boys track into overweight or obese junior high school adolescents. However, these percentages are lower among primary school girls, where only 50 approximately 70% overweight and 30 approximately 60% obese primary school girls track into overweight and obese adolescents, respectively. We conclude that Japanese boys are fatter than girls; and approximately 80% of overweight/obese Japanese primary school children track into junior high school overweight/obese adolescents.

Childhood obesity is one of the most serious public health problems in Japan, especially in Tokushima compared with other prefectures. This study was designed to clarify the life habits which predispose to development of obesity and can be modified through an appropriate intervention program to combat childhood obesity and its lifestyle-related diseases. A total of 216 school children from Itano Town, a municipality of Tokushima Prefecture, Japan, who are attending the fourth grade (9-10 years) of elementary schools, participated in the study from 2004 to 2007. The study included child's life habits questionnaire, investigating physical activity by recording the daily steps using a pedometer, anthropometric measurements, hematological examination and hemodynamometry in a cross-sectional survey during a two-month period from June to July every year. We conclude that there are considerable gender-related differences for developing obesity and other lifestyle-related diseases; and all intervention strategies against obesity must consider such gender differences. For example, restriction of television watching hours must be intervened for controlling obesity in boys, however for girls, promotion of exercise practice or making more steps per day with adequate sleeping periods should be intervened as the proper approaches for preventing and controlling obesity and other lifestyle-related diseases.

Childhood overweight is an important worldwide problem of public health concern, with metabolic, physical and psychosocial complications. More and more evidence is accumulating that children who gain weight rapidly earlier in life are at higher risk of becoming overweight later in adulthood life. Therefore, in a seven-year longitudinal study, we studied mid-childhood and early adolescence weight and height growth velocities among 5,024 Japanese 2(nd) grade primary school boys and girls along with its effect on the likelihood of being overweight adolescents by the age of 14 y. Our findings showed that weight growth velocity of both sexes was associated with being overweight at the end of longitudinal study. Boys' risk of accelerated weight growth velocity and becoming overweight adolescents was almost doubled during ages 7 approximately 11 y and become reduced afterward. Otherwise, odds ratios of girls' weight growth velocity peaks were found only at ages from 9 approximately 10 and 10 approximately 11 y. Thus, we suggest a critical window of mid-childhood period associated with adolescence risk of overweight, and we recommend that studying weight growth determinants during 7 approximately 11 y of boys and 9 approximately 11 y of girls may help in developing and applying proper programs for prevention and intervention of overweight problem.

Prolonged life expectancy must be recognized as an excellent achievement of modern medicine, but not all the elderly people are satisfied with their lives. Life satisfaction is a multi-dimensional issue that depends on many objective and subjective characteristics. In this study, we aimed at investigating the factors affecting life satisfaction of 314 elderly Japanese women attending in 28 elderly-care and welfare facilities at Tokushima Prefecture, Japan. Our results indicated that elderly subjects with depression tendencies always show significantly lower degrees of life satisfaction than others who are not depressed (p<0.001) regardless of their cognitive status. Furthermore, elderly women who shared decision for their living place and whose opinions were considered for daily life decisions reported significantly more life satisfaction levels than others. We conclude that elderly life satisfaction is affected by various determinants however, with different influencing weight. Life satisfaction of elderly people, with or without dementia, is greatly affected by their mood status and share in decision making. Avoiding elderly people depressive mood, sharing them in various daily decisions, considering their opinions, and allowing them to decide their elderly-care facility placement are crucial determinants for their life satisfaction and essential for their coping, adaptation, well-being and successful aging.

The SRY gene (sex-determining region on the Y chromosome) was isolated in 1990 and is known as the testis-determining factor on the Y chromosome. The SRY has been considered as a transcription factor since it contains an HMG box, which functions as a DNA-binding domain. However, a direct target for SRY remains to be identified. We have investigated the function of SRY through proteomics and transcriptome approaches, and by using two stable SRY-overexpressing cell lines (SRY1 and SRY2) in NT2/D1 cells derived from human testicular embryonal cell carcinoma. The results of 2-dimensional gel electrophoresis show that SRY overexpression causes a considerable downregulation of many chaperone proteins. SRY also upregulates laminin, which is important for Sertoli cell differentiation. Additionally, transcriptome analysis shows that SRY overexpression upregulates many zinc finger proteins and downregulates cellular growth factors with S or G(2)/M arrest of the cell cycle and inhibition of cellular proliferation.

Obesity as well as its associated chronic diseases and adverse health consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease are afflicting middle-aged adults and an ever greater number of children globally. We planned to investigate new obesity-related factors using proteomics approaches in a randomly selected three high and three low BMI samples of Epstein-Barr-transformed B (EBV-B) lymphoblastoid cell lines prepared from two groups of young Japanese men with different BMI. To search novel obesity-related factors, comparisons of protein expressions between high and low BMI groups were carried out by two-dimensional gel electrophoresis (2-DE). Gene transcripts of proteasome subunits found out from 2-DE were further determined by quantitative real-time PCR. Results from proteomics approach showed that the expression of proteasome alpha subunit type 5 (PSMA5) was significantly lower in the high BMI male group than in those with low BMI (P < 0.05). To validate these results, we expanded the study to include 20 more men and used real-time PCR to quantify the mRNA expression level in their EBV-B cells. Both PSMA5 and PSMA2 of EBV-B cells showed negative correlation with BMI. Furthermore, the mRNA levels measured in the peripheral blood B lymphocytes for many proteasome subunits in 75 healthy men and women showed significant negative correlation with BMI in healthy men. Our findings suggest that proteasome expression may play a key role in obesity.

The proteasome is the main proteolytic enzyme that functions in the ubiquitin-proteasome system. The 26S proteasome has multi-subunit protease complexes consisting of 20S subunits composed of four seven-numbered rings with two outer rings containing alpha subunits and two central rings composed of beta subunits, and 19S caps of 6 ATPase and 11 non-ATPase subunits; however, it is unclear how these subunits are regulated and the 26S proteasomes assembled. To verify whether each subunit's mRNA expression is associated with the mRNA expression of other proteasome subunits, we carried out expression analysis of 34 proteasome subunits mRNA on peripheral blood from 75 subjects. The expression of proteasome subunits mRNA was comparable in each individual of the studied population and the mRNA expression has been investigated in each 20S or 19S proteasome. Our results suggest that each type of subunit is regulated by respectively common factors, and that the 20S and 19S proteasomes are regulated by different systems.

Background: NB-UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium-YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo., Purpose: In the present study, we are exploring the effect of the use of ER:YAG laser skin ablation and application of 5FU on the outcome of short-term NB-UVB therapy for patients with non-segmental vitiligo (NSV)., Methods: This study included 50 adult patients with a total of 65-paired symmetrical NSV lesions in different body parts. One side was treated with ER:YAG laser ablation, followed by 5FU application before simultaneous NB-UVB therapy of both sides for a maximum period of 4 months. The outcome was then evaluated both qualitatively and quantitatively., Results: The overall response to therapy was better using the combination therapy. Fifty patients (78.1%) experienced a moderate-marked repigmentation response in the combination group compared with 23.4% in the mono-therapy group. The response was significantly higher when using the combination therapy in different body parts (P value is <0.05), except for feet lesions, which were better but not statistically significant (P value=0.15). Tolerable pain during ablation or at sites of 5FU application was reported in all cases. Transient hyperpigmentation occurred in 30% of cases and 3.1% of lesions healed by a transient slate blue color. Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient., Conclusion: We concluded that prior use of ER:YAG laser skin ablation, followed by 5FU application before NB-UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short-term NB-UVB therapy and is expected to increase patient compliance.

Obesity in children has become a major global public health concern. The prevention of obesity must start from early childhood in order to establish sound lifestyle habits and promote healthy adulthood. In this study, we evaluated factors associated with the prevention of obesity and the development of healthy lifestyle habits in children. A cross-sectional, questionnaire-based survey was performed in elementary and junior high school students in Tokushima Prefecture, Japan, during the summer of 2004. The questionnaire consisted of 30 items such as physique, sleep, eating habits, diet, exercise, free time, and attending after-school lessons. Our study revealed that eating meals as a family every day is associated with a lower rate of obesity as well as getting good lifestyle habits such as eating balanced meals and getting enough sleep. Of the 3,291 students who responded to the questionnaire, 2,688 (81.7%) reported that they eat meals with their family every day. The percentage of students who eat meals with their family every day decreased with increasing school grade, with the lowest percent in the junior high school students. However, the results regarding female junior high school students revealed a marked association between eating meals with the family every day and good lifestyle habits. We recommend that parents and school teaching staff encourage the establishment of sound, healthy lifestyle habits in children from early childhood as an effective measure for the prevention of obesity.

To date, molecular evidence studies for bladder cancer, using the microarray technology, are focusing on the transitional cell carcinoma, however, similar fingerprinting studies have rarely been performed on the other molecular phenotypes of bladder cancer, squamous cell carcinoma (SCC). This study was conducted to monitor the gene expression profiles for bilharzial-related SCC of the bladder to be able to compare its data with transitional cell carcinoma microarray data. A total of 17 paired bilharzial urinary bladder SCC specimens and their corresponding normal urothelium were analyzed using the complementary deoxyribonucleic acid microarray hybridization approach to study the molecular basis of the development of SCC of the urinary bladder. Validation of the microarray results was performed using the Northern blotting technique. After supervised analysis of the microarray data, there was at least a 3-fold difference in the expression between SCC of the bladder and normal urothelium in 82 genes. A total of 38 genes were up-regulated in SCC of the bladder, including matrix degradation-related genes, growth factors, different oncogenes, and immunology related genes. Conversely, 44 genes were down-regulated in SCC of the bladder, including integrins, laminins, cadherins, nonmetastatic cell 1 (NM23) and apoptosis-related genes. Our findings can explain the aggressive behavior of SCC of the bladder. Such gene profiling studies will add to our understanding of the mechanisms of carcinogenesis, and may also improve our ability to diagnose and treat bladder cancer.

In the present study, we typed our previously reported two microsatellite markers, DXYS241 and DXYS266 together with a basic set of nine Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DXYS156Y, DYS413) on Y chromosomes from two Bolivian populations. Unrelated males from communities living at high- (N=59) and low- (N=142) altitude, were studied. Combining the alleles into 11 Y-STRs haplotypes revealed that the high-altitude population is significantly less diverse than the low-altitude population. Haplotype diversities of 0.927+/-0.029 and 0.996+/-0.002 were found within the high-altitude, and the low-altitude populations, respectively. Within the high-altitude population 40 haplotypes were detected, whereas in the low-altitude population 113 haplotypes were found. Only three haplotypes were shared between both populations. Haplotyping-based discrimination using the 11 Y-STRs including our new two microsatellite markers DXYS241 and DXYS266 was shown to be powerful than using the conventional 9 Y-STRs, especially for the low-altitude Bolivian population. This 11 Y-STRs-based haplotyping system shows a very high potential for discrimination and could provide an ideal tool for forensic analysis and population studies. Moreover, this study includes data about two Bolivian populations which were not previously reported, this will help in building a world-wide database for future use in forensic and legal studies.

Background: Despite being relatively uncommon, testicular germ cell tumors (TGCT) are the most common malignant disease in young men. Epidemiological studies concerning patients with testicular cancer indicate that the most of them have poor semen quality or testicular dysgenesis. However, many studies have shown that the Y chromosome harbors many candidate genes responsible for spermatogenesis process and development and maintenance of the germ cells. The Y chromosome is thought to have a relationship with the formation and progression of TGCT., Materials and Methods: To verify this relationship, we investigated if there is any correlation between the Y chromosome structural variations presented as different haplogroups and the occurrence of TGCT in the Japanese population. Using combined haplogroups based on typing of three Y chromosome polymorphic binary markers, we analyzed 68 TGCT derived from Japanese patients together with randomly selected 104 unrelated healthy Japanese matched male controls who were confirmed as residents of the same geographic area., Results: Our findings showed a lack of association between the incidence of TGCT and the different Y- chromosome haplogroups in Japanese population., Conclusion: We concluded that there are no significant variations in males from different Y chromosome lineages regarding their susceptibility or resistance for developing TGCT. The previously hypothesized role of the Y chromosome in the development of TGCT is still uncertain and needs further verification.

For the amplification and ultrafast separation of the genetic markers and DNA sequences that are related to human male infertility, a multiplex PCR for amplifying three DNA sequence-tagged sites (STS) located on the human Y chromosome with possible roles in the spermatogenesis process has been designed and applied followed by separation on a microchip. First, the optimum T(m) degree for the three DNA markers was optimized and determined experimentally, and the three DNA STS were amplified. These three DNA markers were then separated on a 12-lane microchip electrophoresis system, which can analyze the DNA markers on 12 channels simultaneously. The combination of these two technologies, multiplex PCR and microchip electrophoresis, allows the analysis of 36 DNA markers (12x3) within only 180 s.

Background: Hexavalent chromium has been extensively investigated regarding its mutagenicity and carcinogenicity; however, its mechanism for initiating and enhancing the development of lung cancer is still obscure. Biomarkers of exposure, effect or susceptibility are required for risk assessment and for epidemiologic research studies especially in occupational settings. Since the surfactant protein system (SP) is very important for normal lung function and for mediating local airway conditions and in the clearance of the upper respiratory tract from the occupational and environmental dusts, we hypothesize that SP genes may represent good candidates to study susceptibility for lung cancer., Methods: Using PCR genotyping methods with gel electrophoresis and confirmation of results with precise DNA fragment size measurement on microchip electrophoresis, we analyzed SP-B intron-4 polymorphism in 230 subjects who were classified into groups; chromate-related lung cancer, control chromate workers who had not developed lung cancer, control individuals with non chromate-related adenocarcinoma or squamous cell carcinoma of the lungs, or healthy Japanese control individuals., Results: Our results indicated that the SP-B variants (deletion/insertion) were significantly overrepresented (61.3%) in the chromate-related lung cancer group than other groups (X2 = 47.6; DF = 4, P = 0.0001). There was a significant difference between the chromate lung cancer group and both of the control groups, healthy individuals and chromate workers who did not develop lung cancer, showing odds ratios (OR) with 95% confidence intervals (CI) of 21.9 (7.3-65.7) and 19.0 (3.78-95.4), respectively. Compared with 46 non chromate-related SCC of the lung, the SP-B variants were significantly overrepresented in the chromate-related SCC (18/28; 64.3%) than the non-chromate SCC (11/46; 23.9%) of the lung samples (X(2) = 10.27, P = 0.01), OR with 95% CI is 5.73 (2.05-16.01)., Conclusion: These findings indicate a very strong association of the SP-B intron-4 variants with mechanisms that may enhance lung cancer susceptibility, especially in workers who are employed in chromate industry. Moreover, confirmation of such results may help to suggest adding the SP-B intron-4 typing to be one of the screening tests of the pre-placement medical examination to confirm that the worker has no variations of the SP-B gene before being engaged in a chromium-related industry, with the intention of providing proper medical counseling., (Copyright 2006 Wiley-Liss, Inc.)

This study was performed to identify differences in gene expression between superficial noninvasive and invasive transitional cell carcinoma (TCC) of the bladder in human beings. We used complementary deoxyribonucleic acid microarrays containing 14,551 different genes to analyze gene expression among 6 cases of superficial and 6 cases of invasive TCC of the bladder to identify differences in gene expression, which might explain differences in the biology and clinical outcomes of these histologic subtypes of TCC. Quantitative real-time polymerase chain reaction was performed for selected genes to validate the microarray data. Significant up-regulation of 40 genes was associated with cases of superficial noninvasive, but not in invasive, TCC of the urinary bladder. This effect included genes involved in epithelial cell dedifferentiation and keratinization, as well as genes related to cell cycle, cell adhesion, transcription, and apoptosis. Conversely, significant up-regulation of 34 genes was associated with cases of invasive TCC, but not in superficial TCC, including genes related to extracellular matrix degradation, immune responses, cell cycling, and angiogenesis. This study shows the usefulness of complementary deoxyribonucleic acid microarray technology for identifying differences in gene expression among different histotypes of bladder cancer.

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b(*), O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b(*) and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16-4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.

For the diagnosis of unexplained male infertility a multiplex PCR for 6 markers, which are well-known as candidate genes for studying male infertility and located on the human Y-chromosome, has been designed. The multiplex PCR products have been separated on a 12 channel microchip electrophoresis system, which can analyze different samples simultaneously. By combining the technologies of multiplex PCR with multichannel microchip electrophoresis, the number of the DNA markers that can be screened simultaneously is increased to be 72 marker (12 x 6) in a single run while the electrophoresis analysis time is reduced to be only 180 s.

A Y chromosomal polymorphic markers screening strategy using a multiplex polymerase chain reaction (PCR) and DNA microchip electrophoresis technology has recently been developed. It is a part of the human Y chromosome haplotyping system for studying Japanese population genetics and its relationship with male spermatogenic failure. This strategy is based on optimizing and modifying the primer set concentrations while keeping all other components of the PCR mixtures and conditions similar to those of a singleplex PCR. Well-balanced PCR products are obtained without changing even the DNA oligomer melting temperatures. Here, a panel of primer sets are used to amplify two groups of Y chromosome markers. The first consists of five markers and the second consists of seven markers. Both are possibly deleted in infertile men. The microchip electrophoresis technology is fast and sensitive, enables direct molecular typing of several Y chromosomal markers, and is separated by a difference of as many as six base pairs.

The fundamental strategy of the current postgenomic era or the era of functional genomics is to expand the scale of biologic research from studying single genes or proteins to studying all genes or proteins simultaneously using a systematic approach. As recently developed methods for obtaining genome-wide mRNA expression data, oligonucleotide and DNA microarrays are particularly powerful in the context of knowing the entire genome sequence and can provide a global view of changes in gene expression patterns in response to physiologic alterations or manipulation of transcriptional regulators. In biomedical research, such an approach will ultimately determine biologic behavior of both normal and diseased tissues, which may provide insights into disease mechanisms and identify novel markers and candidates for diagnostic, prognostic and therapeutic intervention. However, microarray technology is still in a continuous state of evolution and development, and it may take time to implement microarrays as a routine medical device. Many limitations exist and many challenges remain to be achieved to help inclusion of microarrays in clinical medicine. In this review, a brief history of microarrays in biomedical research is provided, including experimental overview, limitations, challenges and future developments.

We have developed a novel technique for mass production of microfabricated capillary array electrophoresis (mu-CAE) plastic chips for high-speed, high-throughput genetic analysis. The mu-CAE chips, containing 10 individual separation channels of 50-microm width, 50-microm depth, and a 100-microm lane-to-lane spacing at the detection region and a sacrificial channel network, were fabricated on a poly(methyl methacrylate) substrate by injection molding and then bonded manually using a pressure-sensitive sealing tape within several seconds at room temperature. The conditions for injection molding and bonding were carefully characterized to yield mu-CAE chips with well-defined channel and injection structures. A CCD camera equipped with an image intensifier was used to monitor simultaneously the separation in a 10-channel array with laser-induced fluorescence detection. High-performance electrophoretic separations of phiX174 HaeIII DNA restriction fragments and PCR products related to the human beta-globin gene and SP-B gene (the surfactant protein B) have been demonstrated on mu-CAE plastic chips using a methylcellulose sieving matrix in individual channels. The current work demonstrated greatly simplified the fabrication process as well as a detection scheme for mu-CAE chips and will bring the low-cost mass production and application of mu-CAE plastic chips for genetic analysis.

Validation of microchip electrophoresis in DNA analysis has been carried out using an Agilent 2100 Bioanalyzer. With a DNA 500 Assay Kit, the reproducibility and accuracy of fragment sizing of a 10 bp DNA ladder have been shown to be satisfactory with the relative standard deviation and the relative error mostly below 1.0 and 5.0% (n = 12), respectively. Both intraday and interday validations of fragment sizing and quantitation have also been performed with a 7500 Assay Kit (n = 48). Although the results of quantitation are not as good as that of sizing, due to the manual introduction of samples and markers into the chip wells, they are still sufficient to carry out further analyses of practical samples. Based on such reliable results, fast analysis of DNA polymorphisms on the human Y-chromosome has been realized with microchip electrophoresis. The total analysis times of three genomic polymorphisms on the Y-chromosome, Y Alu polymorphism, 47z/StuI, and 12f2, are all within 100 s, and the relative standard deviation and relative error of fragment sizes are below 3.5 and 3.7%, respectively. In addition, a mixture of nine DNA markers on the human Y-chromosome related to examine the cause of spermatogenic failure have been separated successfully with the smallest fragment size difference of 7 bp. Our results demonstrate the potential of microchip electrophoresis in polymorphism analysis with the advantages of high speed, good reproducibility, high precision, and high resolution.