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Abstract Trichuris trichiura is one of four soil-transmitted helminth species that, collectively, are responsible for a considerable public health burden. The World Health Organization recommends preventive chemotherapy as the main intervention to eliminate soil-transmitted helminthiasis as a public health problem. Clinical trials estimated the efficacy of different drugs and treatment regimen against T. trichiura and other soil-transmitted helminth species, whilst meta-analyses and modeling efforts were conducted to determine the most efficacious drugs and drug combinations. Of note, the diagnostic error was often neglected, and hence, cure rates (CRs) might be overestimated. We developed a Bayesian model, which estimates drug efficacy against T. trichiura, taking into account the transmission mechanism and the diagnostic error. The model was fitted to individual-level egg count data from an ensemble of seven trials with 29 treatments. We estimated the ‘true’ CRs, which were consistently lower than those reported in the literature. In our analysis, the treatment with the highest CR was combination therapy of albendazole plus pyrantel pamoate plus oxantel pamoate with a CR of 79% and an egg reduction rate (ERR) of 91%. Albendazole plus oxantel pamoate showed the highest ERR of 97% and a CR of 69%. Additionally, we estimated the intensity-dependent sensitivity of the Kato-Katz technique. For 24 eggs per gram of stool, the sensitivity was around 50% for a single Kato-Katz thick smear and increased to almost 70% for duplicate Kato-Katz thick smears. Combination therapies against soil-transmitted helminthiasis should be considered and the evaluation of infection intensity in low transmission settings via multiple Kato-Katz thick smears is recommended.

Abstract Recently, hydrogen-based distributed generators (DG) have gained significant attention for modern energy generation systems. These modem DGs are typically outfitted with power electronics converters, resulting in harmonic pollution. Furthermore, increasing the growth of modern nonlinear loads may result in exceeding the harmonic beyond the permitted level. This research proposes a framework for optimal incorporation of inverter-based distributed generation (a fuel cell connected to an AC distribution system) for minimizing power losses, enhancing the voltage profile, and limiting both total and individual harmonic distortion according to the IEEE-519 standard. In addition, for accounting system sustainability, the proposed framework considers load variation and the expected rise in demand. Therefore, the suggested framework comprises three stages, which include fundamental and harmonic power flow analysis. The first stage identifies the optimal size and location of the DG in relation to the base load operating condition. While, with the optimal DG of the first stage, the amount of harmonic pollution may violate the limits during a high level of nonlinear load penetration, as a result, the second stage resizes the DG, considering the connection bus of the first stage, to mitigate the harmonics and optimize the system at a higher level of nonlinear load penetration. Both the first and second stages are performed off-line, while the third stage optimizes the system operation during run time according to loading conditions, harmonic pollution, and the available DG capacity of the previous stages. DG’s harmonic spectrum is represented according to recently issued IEEE 1547-2018 for permissible DG’s current distortion limits. The suggested approach is applied and evaluated using an IEEE 33-bus distribution system for various combinations of linear and nonlinear loads. For run-time operation throughout the day, the presented framework reduces the energy losses from 5.281 to 2.452 MWh/day (about 53.57% energy savings). This saving is associated with voltage profile enhancement without violating the permissible standard levels of harmonics and other system constraints.

Abstract This work is an attempt to develop flexible radiation shielding based on a blend of polymethyl methacrylate (PMMA)/polyvinyl acetate (PVAc) and LaFeO3 nanoparticles (NPs). LaFeO3 and LaFeO3/PMMA/PVAc were made using simple chemical techniques. A high-resolution transmission electron microscope (HR-TEM) and X-ray diffraction (XRD) showed that well-crystallized LaFeO3 NPs with particles 79 nm in size and an orthorhombic shape were obtained. In addition, XRD confirmed the existence of PMMA, PVAc, and LaFeO3 in the nanocomposite films. Fourier transform infrared (FTIR) confirmed that the LaFeO3 NPs and the reactive functional groups in the blend interacted with each other. Field emission-scan electron microscope (FE-SEM) analysis showed that PMMA and PVAc form a homogenous blend and that the LaFeO3 NPs were spread out inside and on the blend surface. The samples showed transmittance in the range of 30–74% and a small extinction coefficient (≤ 0.08). The samples exhibited a dual-band gap structure, and the direct (indirect) band gap shrank from 5.1 to 4.7 eV (4.9 to 4.4 eV). The thermal analyses showed that the samples are thermally stable up to 260 °C. The Phy-X/PSD software was used to figure out the theoretical gamma-ray attenuation parameters, such as the mass attenuation coefficient, the mean free path, and the half-value layer, for different PMMA/PVAc + x% LaFeO3 composites. It is demonstrated that the PMMA/PVAc + 10 wt% LaFeO3 sample exhibits much better shielding effectiveness than PMMA/PVAc, and hence it is suitable for protecting against radiation.

Abstract This study investigates the physical and optical properties as well as the radiation shielding capacity of polyvinyl chloride (PVC) loaded with x% of bismuth vanadate (BiVO4) (x = 0, 1, 3, and 6 wt%). As a non-toxic nanofiller, the designed materials are low-cost, flexible, and lightweight plastic to replace traditional lead, which is toxic and dense. XRD patterns and FTIR spectra demonstrated a successful fabrication and complexation of nanocomposite films. In addition, the particle size, morphology, and elemental composition of the BiVO4 nanofiller were demonstrated through the utilization of TEM, SEM, and EDX spectra. The MCNP5 simulation code assessed the gamma-ray shielding effectiveness of four PVC + x% BiVO4 nanocomposites. The obtained mass attenuation coefficient data of the developed nanocomposites were comparable to the theoretical calculation performed with Phy-X/PSD software. Moreover, the initial stage in the computation of various shielding parameters, such as half-value layer, tenth value layer, and mean free path, besides the simulation of linear attenuation coefficient. The transmission factor declines while radiation protection efficiency increases with an increase in the proportion of BiVO4 nanofiller. Further, the current investigation seeks to evaluate the thickness equivalent (Xeq), effective atomic number (Zeff), and effective electron density (Neff) values as a function of the concentration of BiVO4 in a PVC matrix. The results obtained from the parameters indicate that incorporating BiVO4 into PVC can be an effective strategy for developing sustainable and lead-free polymer nanocomposites, with potential uses in radiation shielding applications.

Adolescent girls' capacity to lead healthy lives and perform well in school has been hampered by their lack of awareness about menstruation and the requirements for its hygienic management. Lack of enabling infrastructure, improper menstrual supplies, and limited socioeconomic support for good menstrual health and cleanliness are characteristics of schools in Africa South of the Sahara. We evaluated school-age girls' knowledge of menstrual hygiene and identified bottlenecks that could affect policy and programming for menstrual health and hygiene. A school-based cross-sectional study involved 8,012 adolescent school girls in the age group of 11-18 years (mean age = 14.9 years). The study evaluated students' knowledge of menstrual health and hygiene (MHH) from the viewpoints of schools and communities using a combination of qualitative and quantitative approaches. Data was collected using self-administered surveys, focus group discussions, in-depth interviews, and site observations. Girls' older age (AOR = 1.62, P 0.001), having a female guardian (AOR = 1.39: P = 001), and having a parent in a formal job (AOR = 1.03: P 0.023) were positively associated with Menstrual health and Hygiene Knowledge. MHH knowledge levels varied significantly between girls attending government (53.3) and non-government schools (50.5%, P = 0.0001), although they were comparable for girls attending rural and urban schools. Only 21% of the study's schools had at least one instructor who had received training in MHH instruction for students. We have established that the majority of adolescent girls in schools have inadequate knowledge on menstrual health and hygiene, and that school teachers lack the skills to prepare and support young adolescents as they transition into puberty. Concerted actions aimed at building supportive policy are paramount, for school-aged teenagers to learn about and reap the long-term advantages of good menstrual health practices.

Infertility is an important socio-economic problem due to the fact that planned childbearing occurs much later than three decades ago. In recent years, more attention has been paid to the role of uterine leiomyoma in the development of infertility. Uterine leiomyoma is a benign monoclonal, well-demarcated encapsulated tumor originating from the smooth muscle cells of the cervix or body of the uterus. Uterine leiomyoma is the most common uterine tumor in the reproductive age group, affecting 20-50 % of women. With conceptual changes in marriage and childbearing, the number of women over 35 with leiomyoma who want to have children has also increased significantly. The need to treat submucosal fibroids is widely recognized, but fibroids of other locations and sizes remain a clinical mystery. The purpose of the literature review was to determine the role of uterine fibroids in predicting infertility. It has been established that the incidence of uterine leiomyoma in women of reproductive age is on average about 40 %, infertility associated with this pathology occurs in 5-10 % of women. In 10 % of cases of infertility, uterine leiomyoma is the only established cause of infertility. Uterine leiomyoma is common among women of reproductive age, and as women continue to delay childbearing, an increasing number of patients will require fertility-preserving treatment options. Leiomyoma affects not only fertility but also obstetric outcomes. Women with intramural fibroids without cavity deformity have a 21 % reduction in live birth rates after in vitro fertilization compared with controls without fibroids. Despite advances in fundamental understanding of the biology of leiomyomas, the role of different fibroid variants remains a matter of discussion. The question of the negative impact of submucosal nodes on infertility today is not in doubt, and the effect of subserous and intramural nodes requires further study.

Abstract Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis.

Abstract Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3Kγ inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3Kγ, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.

Abstract Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34+ and c-kit+ was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder. Renal involvement usually develops in the first few years of illness and should be detected early by periodic urine analysis and quantitation of proteinuria. The aim of our work was to evaluate the biological marker [anti-complement 1q antibodies (anti-C1q Ab)] in lupus nephritis (LN) patients and its correlation to SLE disease activity. Sixty-five subjects were divided into four groups; Group I: SLE patients with LN (proteinuria >0.5 g/day), Group II: SLE patients without LN (all of them had a lupus flares rather than nephritis; active nonrenal), Group III: SLE patients without any activity (inactive disease), and Group IV: Control group. All subjects underwent urine analysis, complete blood picture, liver function tests, kidney function tests, albumin/ creatinine ratio, antinuclear antibody, anti-double stranded DNA (anti-dsDNA) antibody, C3, C4, and anti-C1q Ab. All patients in the first group underwent renal biopsy and pathological diagnosis showed: Class II in two patients, Class III and IV in nine patients, and Class V in four patients. Anti-C1q Ab were found in the serum of SLE patients and not in the control group and showed an association with active lupus with much higher concentration in active renal group, specifically those with severe renal histological lesions (proliferative form). There was significant statistical positive correlation between anti-C1q Ab with anti-dsDNA and SLE disease activity index in both active groups. There was statistically significant negative correlation between anti-C1q Ab with C3 and C4 in both active groups. Anti-C1q Ab could be used as useful marker for active lupus, especially with nephritis.

Background: Infections with soil-transmitted helminths (STHs) predominantly affect impoverished populations in tropical environments. The periodic administration of single dose benzimidazoles (i.e., albendazole, mebendazole) to at-risk individuals in endemic regions is at the center of STH control strategies. Given the low efficacy of these drugs against trichuriasis, investigation of drug combinations including moxidectin and ivermectin has recently been initiated, yet the identification of the best treatment option requires more research. We present the protocol for a trial investigating the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole against Trichuris trichiura. Methods: We will conduct a randomized controlled trial enrolling 540 T. trichiura-infected adolescents aged 12-19 years on Pemba Island (Tanzania). The trial will be open-label with blinded outcome assessors. The primary objective is to demonstrate non-inferiority of orally co-administered single-dose moxidectin (8 mg)/albendazole (400 mg) compared to orally co-administered single-dose ivermectin (200 µg/kg)/albendazole (400 mg) in terms of egg reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days post-treatment. Secondary objectives include the assessment of the drug combinations’ superiority compared to their respective monotherapies, of the cure rates (CRs) against T. trichiura, and the safety and tolerability of all treatments, as well as CRs and ERRs against concomitant STH infections ( Ascaris lumbricoides and hookworm). Potential effects of the treatment regimens on follow-up prevalences of STH at 5-6 weeks and 3 months post-treatment and pharmacokinetic/ pharmacodynamic parameters will also be assessed. Conclusions: Results from this trial will help to inform decision- and policymakers on which anthelminthic combination therapy might improve existing deworming programs and provide a valuable adjunct tool for interrupting STH transmission. Clinicaltrials.gov registration: NCT04700423 (07/01/2021)

Biofilm infections are hard to manage using conventional antibiotic treatment regimens because biofilm structures discourage antibiotics from reaching the entire bacterial community and allow pathogen cells to persistently colonize and develop a plethora of tolerance mechanisms towards antibiotics. Moreover, the dispersed cells from biofilms can cause further complications by colonizing different sites and establishing new cycles of biofilms. Previously, we showed that alginate lyase enzyme (AlyP1400), purified from a marine Pseudoalteromonas bacterium, reduced Pseudomonas aeruginosa biofilm biomass and boosted bactericidal activity of tobramycin by degrading alginate within the biofilm extracellular polymeric substances matrix. In this work, we used a flow cytometry-based assay to analyze collected dispersal cells and demonstrated the synergy between tobramycin with AlyP1400 in enhancing the release of both live and dead biofilm cells from a mucoid P. aeruginosa strain CF27, which is a clinical isolate from cystic fibrosis (CF) patients. Interestingly, this enhanced dispersal was only observed when AlyP1400 was combined with tobramycin and administered simultaneously but not when AlyP1400 was added in advance of tobramycin in a sequential manner. Moreover, neither the combined nor sequential treatment altered the dispersal of the biofilms from a non-mucoid P. aeruginosa laboratory strain PAK. We then carried out the gene expression and tobramycin survival analyses to further characterize the impacts of the combined treatment on the CF27 dispersal cells. Gene expression analysis indicated that CF27 dispersal cells had increased expression in virulence- and antibiotic resistance-related genes, including algR, bdlA, lasB, mexF, mexY, and ndvB. In the CF27 dispersal cell population, the combinational treatment of AlyP1400 with tobramycin further induced bdlA, mexF, mexY, and ndvB genes more than non-treated and tobramycin-treated dispersal cells, suggesting an exacerbated bacterial stress response to the combinational treatment. Simultaneous to the gene expression analysis, the survival ability of the same batch of biofilm dispersal cells to a subsequent tobramycin challenge displayed a significantly higher tobramycin tolerant fraction of cells (~60%) upon the combinational treatment of AlyP1400 and tobramycin than non-treated and tobramycin-treated dispersal cells, as well as the planktonic cells (all below 10%). These results generate new knowledge about the gene expression and antibiotic resistance profiles of dispersed cells from biofilm. This information can guide the design of safer and more efficient therapeutic strategies for the combinational use of alginate lyase and tobramycin to treat P. aeruginosa biofilm-related infections in CF lungs.

Phytophthora infestans (Mont.) de Bary, a hemibiotrophic oomycete, has caused severe epidemics of late blight in tomato and potato crops around the world since the Irish Potato Famine in the 1840s. Breeding of late blight resistant cultivars is one of the most effective strategies to overcome this disruptive disease. However, P. infestans is able to break down host resistance and acquire resistance to various fungicides, possibly because of the existence of high genetic variability among P. infestans isolates via sexual and asexual reproduction. Therefore, to manage this disease, it is important to understand the genetic divergence of P. infestans isolates. In this study, we analyzed the genomes of P. infestans isolates collected from Egypt and Japan using various molecular approaches including the mating type assay and genotyping simple sequence repeats, mitochondria DNA, and effector genes. We also analyzed genome-wide single nucleotide polymorphisms using double-digest restriction-site associated DNA sequencing and whole genome resequencing (WGRS). The isolates were classified adequately using high-resolution genome-wide approaches. Moreover, these analyses revealed new clusters of P. infestans isolates in the Egyptian population. Monitoring the genetic divergence of P. infestans isolates as well as breeding of resistant cultivars would facilitate the elimination of the late blight disease.

CPF (chlorpyrifos) is an organophosphate pesticide used in agricultural and veterinary applications. Our experiment aimed to explore the effects of thymoquinone (TQ) and/or lycopene (LP) against CPF-induced neurotoxicity. Wistar rats were categorized into seven groups: first group served as a control (corn oil only); second group, TQ (10 mg/kg); third group, LP (10 mg/kg); fourth group, CPF (10 mg/kg) and deemed as CPF toxic control; fifth group, TQ + CPF; sixth group, (LP + CPF); and seventh group, (TQ + LP + CPF). CPF intoxication inhibited acetylcholinesterase (AchE), decreased glutathione (GSH) content, and increased levels of malondialdehyde (MDA), an oxidative stress biomarker. Furthermore, CPF impaired the activity of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) along with enhancement of the level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. CPF evoked apoptosis in brain tissue. TQ or LP treatment of CPF-intoxicated rats greatly improved AchE activity, oxidative state, inflammatory responses, and cell death. Co-administration of TQ and LP showed better restoration than their sole treatment. In conclusion, TQ or LP supplementation may alleviate CPF-induced neuronal injury, most likely due to TQ or LPs’ antioxidant, anti-inflammatory, and anti-apoptotic effects.

This paper presents an evaluation of the effectiveness of two types of deceleration markings on freeways in China: fishbone-shaped (FS) markings and edge-rate (ER) markings. An actual 4-lane, 6-km long freeway in Province Hebei was created in a driving simulator and used for the experiments. Three scenarios of deceleration markings were adopted: one without markings, one with FS markings, and the third with ER markings. For each scenario, three traffic flow levels were adopted (low, medium, and heavy). The appropriate dimensions of deceleration markings were first established using relevant design guidelines and then used to develop the simulation scenarios using Multigen Creator software. Sixty drivers carried out the simulation experiments with eye tracker equipment. The adequacy of deceleration markings was analyzed with respect to speed, perceived distance, pupil diameter, and geometric parameters. The results showed that both types of deceleration markings made a certain effect on vehicle speed, drivers'visual behavior, and mental characteristics. However, the effect of the FS markings was more pronounced than that of the ER marking. Specifically, the FS markings showed a speed reduction of 12.3 km/h to 15.2 km/h and a perceived distance of 70 m to 90 m, compared with 6.7 km/h to 9.9 km/h and 40 m to 60 m, respectively, for the ER markings. Application comments of the results are provided in the conclusion.

Efforts to map the burden of infections globally have shown a high prevalence of genital infections, including Chlamydia trachomatis, in sub-Saharan Africa. This retrospective study aimed to investigate the prevalence of selected non-viral genital infections among pregnant women in Pemba Island, Tanzania. Vaginal swabs were collected during pregnancy and stored in eNAT buffer. Detection of C. trachomatis, Neisseria gonorrheae, Trichomonas vaginalis, and Mycoplasma genitalium pathogens was performed by PCR using validated detection kits. Vaginal samples of 439 pregnant women between 16 and 48 years were tested. In fifty-five (12.5%) of them, at least one genital pathogen was detected. The most prevalent pathogen was T. vaginalis (7.1%), followed by C. trachomatis (4.6%) and M. genitalium (2.1%). None of the vaginal samples tested positive for N. gonorrheae. Consequently, among positive samples, 7.3% were for C. trachomatis and at least one other genital pathogen. This study provides insights on the burden of the four studied genital infections, and on the coinfections among pregnant women in Pemba Island, Tanzania. These results offer a starting point that can be useful to design further research in the field of maternal and child health in Pemba Island.

Tomato late blight caused by Phytophthora infestans (Mont.) de Bary, also known as the Irish famine pathogen, is one of the most destructive plant diseases. Wild relatives of tomato possess useful resistance genes against this disease, and could therefore be used in breeding to improve cultivated varieties. In the genome of a wild relative of tomato, Solanum habrochaites accession LA1777, we identified a new quantitative trait locus for resistance against blight caused by an aggressive Egyptian isolate of P. infestans. Using double-digest restriction site-associated DNA sequencing (ddRAD-Seq) technology, we determined 6,514 genome-wide SNP genotypes of an F2 population derived from an interspecific cross. Subsequent association analysis of genotypes and phenotypes of the mapping population revealed that a 6.8 Mb genome region on chromosome 6 was a candidate locus for disease resistance. Whole-genome resequencing analysis revealed that 298 genes in this region potentially had functional differences between the parental lines. Among of them, two genes with missense mutations, Solyc06g071810.1 and Solyc06g083640.3, were considered to be potential candidates for disease resistance. SNP and SSR markers linking to this region can be used in marker-assisted selection in future breeding programs for late blight disease, including introgression of new genetic loci from wild species. In addition, the approach developed in this study provides a model for identification of other genes for attractive agronomical traits.

Background: Hypercholesterolemia (HC) is a major risk factor in the development of coronary heart disease (CHD). Serum cholesterol is directly related to complications and mortalities associated with heart diseases. There are a few studies that describe HC among youths in the Arab Gulf countries. We sought to evaluate HC among young healthy university students to assess their risk of developing CHD.Methods: Lipid profile of 166 students between the ages of 16-30 years (Mean: 20.49±2.96) were examined and blood glucose, total protein, albumin, thyroid stimulating hormone (TSH) and the inflammation marker high sensitivity CRP (hsCRP) were determined. Each volunteer filled a questionnaire about her/his lifestyle and personal and family medical histories and height and weight were measured to determine body mass index (BMI). The data were analyzed using SPSS version 17. Chi-Square was used to determine the relation between categorical variables. A p-value

Background: Plastibell circumcision complications can be life-threatening. Objective: The aim of this paper is to review the complications of Plastibell circumcision reported in the literature and in our own patients to determine the safety of the procedure. Method: A retrospective study of 171 neonates circumcised in Sultan Qaboos University Hospital over a 4-year period from 1997 to 2000. Results: Minor complications occurred in 4 (2.3 %) of circumcisions. Two cases were converted to formal circumcision due to bleeding and failure to introduce the bell respectively. One had delayed passage of urine for 24 hours and in one neonate, the parents were concerned about inadequate removal of foreskin. Conclusion: Plastibell circumcision is a safe technique in experienced hands. The risk of complications with this procedure is increased eight-fold when performed by nurses compared to surgeons.

Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA) cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1) cell-cycle arrest and increased p27(Kip1) nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1) expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1) expression. To determine whether p27(Kip1) induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1), in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1) silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1) mRNA expression but not its protein degradation. p27(Kip1) gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1) expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1) induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1) as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

Deltamethrin is a broad-spectrum synthetic pyrethroid insecticide and acaricide widely used for agricultural and veterinary purposes. However, its human and animal exposure leads to hepatonephrotoxicity. Therefore, the present study was undertaken to examine the hepatonephroprotective and antioxidant potential of Spirulina platensis against deltamethrin toxicity in male Wistar albino rats. Deltamethrin treated animals revealed a significant increase in serum biochemical parameters as well as hepatic and renal lipid peroxidation but caused an inhibition in antioxidant biomarkers. Spirulina normalized the elevated serum levels of AST, ALT, APL, uric acid, urea and creatinine. Furthermore, it reduced deltamethrin-induced lipid peroxidation and oxidative stress in a dose dependent manner. Therefore, it could be concluded that spirulina administration able to minimize the toxic effects of deltamethrin by its free radical-scavenging and potent antioxidant activity.

BackgroundRecent research in two cholera-endemic communities of Zanzibar has shown that a majority (∼94%) of the adult population was willing to receive free oral cholera vaccines (OCVs). Since OCV uptake in the 2009 campaign reached only ∼50% in these communities, an evaluation of social and cultural factors and of barriers was conducted to understand this difference for future cholera control planning.Methodology/principal findingsA random sample of 367 adult peri-urban and rural community residents (46.6% immunized vs. 53.4% unimmunized) was studied with a semi-structured interview that inquired about social and cultural features of cholera depicted in a vignette and barriers to OCV uptake. Symptoms (rectal pain, loose skin only in rural community) and perceived causes (uncovered food, contact with contaminated water) specific for severe diarrhea were associated with uptake. Purchasing drugs from pharmacies to stop diarrhea and vomiting was negatively associated with uptake. Increasing household size, age and previous enteric illness episode were positively related to uptake, the latter only at the rural site. The most prominent barrier to uptake was competing obligations or priorities (reported by 74.5%, identified as most important barrier by 49.5%). Next most prominent barriers were lacking information about the campaign (29.6%, 12.2%), sickness (14.3%, 13.3%) and fear of possible vaccine side effects (15.3%, 5.6%). The majority of unvaccinated respondents requested repetition of the vaccination with free OCVs.Conclusions/significanceFactors associated with uptake indicated a positive impact of the vaccination campaign and of sensitization activities on vaccine acceptance behavior. Unlike communities opposed to cholera control or settings where public confidence in vaccines is lacking, identified barriers to uptake indicated a good campaign implementation and trust in the health system. Despite prospects and demand for repeating the vaccination, local decision-makers should reconsider how careful logistical arrangements may improve community coverage and thus effectiveness of vaccination campaigns.

BackgroundThe gold standard for the diagnosis of cholera is stool culture, but this requires laboratory facilities and takes at least 24 hours. A rapid diagnostic test (RDT) that can be used by minimally trained staff at treatment centers could potentially improve the reporting and management of cholera outbreaks.MethodsWe evaluated the Crystal VC™ RDT under field conditions in Zanzibar in 2009. Patients presenting to treatment centers with watery diarrhea provided a stool sample for rapid diagnostic testing. Results were compared to stool culture performed in a reference laboratory. We assessed the overall performance of the RDT and evaluated whether previous intake of antibiotics, intravenous fluids, location of testing, and skill level of the technician affected the RDT results.ResultsWe included stool samples from 624 patients. Compared to culture, the overall sensitivity of the RDT was 93.1% (95%CI: 88.7 to 96.2%), specificity was 49.2% (95%CI: 44.3 to 54.1%), the positive predictive value was 47.0% (95%CI: 42.1 to 52.0%) and the negative predictive value was 93.6% (95%CI: 89.6 to 96.5%). The overall false positivity rate was 50.8% (213/419); fieldworkers frequently misread very faint test lines as positive.ConclusionThe observed sensitivity of the Crystal VC RDT evaluated was similar compared to earlier versions, while specificity was poorer. The current version of the RDT could potentially be used as a screening tool in the field. Because of the high proportion of false positive results when field workers test stool specimens, positive results will need to be confirmed with stool culture.

BACKGROUND: We conducted a surveillance study to determine the leading causes of bloodstream infection in febrile patients seeking treatment at three district hospitals in Pemba Island, Zanzibar, Tanzania, an area with low malaria transmission. METHODS: All patients above two months of age presenting to hospital with fever were screened, and blood was collected for microbiologic culture and malaria testing. Bacterial sepsis and malaria crude incidence rates were calculated for a one-year period and were adjusted for study participation and diagnostic sensitivity of blood culture. RESULTS: Blood culture was performed on 2,209 patients. Among them, 166 (8%) samples yielded bacterial growth; 87 (4%) were considered as likely contaminants; and 79 (4%) as pathogenic bacteria. The most frequent pathogenic bacteria isolated were Salmonella Typhi (n = 46; 58%), followed by Streptococcus pneumoniae (n = 12; 15%). The crude bacteremia rate was 6/100,000 but when adjusted for potentially missed cases the rate may be as high as 163/100,000. Crude and adjusted rates for S. Typhi infections and malaria were 4 and 110/100,000 and 4 and 47/100,000, respectively. Twenty three (51%), 22 (49%) and 22 (49%) of the S. Typhi isolates were found to be resistant toward ampicillin, chloramphenicol and cotrimoxazole, respectively. Multidrug resistance (MDR) against the three antimicrobials was detected in 42% of the isolates. CONCLUSIONS: In the presence of very low malaria incidence we found high rates of S. Typhi and S. pneumoniae infections on Pemba Island, Zanzibar. Preventive measures such as vaccination could reduce the febrile disease burden.

BACKGROUND: The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever. METHODOLOGY/PRINCIPAL FINDINGS: Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1:80. CONCLUSIONS/SIGNIFICANCE: Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

The AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. Most studies have focused on its activation by Receptor Tyrosine Kinase (RTK) mediated Phosphatidylinositol-3-OH kinase (PI3K) activation or loss of Phosphatase and Tensin homolog (PTEN). We have uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. Mice expressing activated Ack1 specifically in the prostate exhibit AKT Tyr176-phosphorylation and develop murine prostatic intraepithelial neoplasia (mPINs). Further, expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast cancer patients. Thus, RTK/Ack1/AKT pathway provides a novel target for drug discovery.

The objective of this study is to ascertain the strategies employed in mitigating fraudulent activities within the realm of health services through the utilization of a whistleblowing mechanism. Methods: The present study employed a systematic review approach to examine relevant literature by utilizing specific keywords such as "whistleblowing system" and "fraud Healthcare." These keywords were then used to search for publications in the Scopus database, focusing on journals that mostly relied on secondary data. The search was conducted using the publish or perish tool. 8. Subsequently, a curation of scholarly publications and articles was conducted, employing a criterion centered on the thematic relevance of their titles. The selected publications have the objective of mitigating fraudulent activities within the healthcare industry and other interconnected industries that contribute to research endeavors. The findings of this study suggest that the implementation of a fraud reporting system is vital inside an organization, particularly within the context of health services. To enhance the caliber of healthcare services, internal healthcare staff and participants may report well, it is imperative to establish a system that ensures the preservation of reporter confidentiality, hence facilitating an increase in the volume of reports.

Abstract The most rapidly expanding type of solar cells are the Perovskite Solar Cells (PSCs), because of its high device performance, ease of synthesis, high open-circuit voltage, and affordability. Despite these advantages, the development of perovskite-based solar cells continues to be impeded by the issues with perovskite stability and the utilization of the hazardous heavy element lead (Pb). The study emphasizes on the bifacial structure that maintains the conventional absorber layer and electron transport layer (ETL) in the optimized PSC structure. This study employs SCAPS software for device simulation to comprehensively analyze how various parameters affect the performance of solar cells. Additionally, doping concentration variation in both ETL and HTL are explored. The simulation reveals that changing device structure from monofacial to bifacial significantly influences PSC performance, demonstrating that optimizing individual layers effectively enhances overall solar cell performance. The optimized structure achieves impressive PSC performance metrics through parametric analysis, such as voltage (VOC) of 1.18 V, fill factor (FF) of 82.24%, current density (JSC) of 27.12 mA/cm2, power conversion efficiency (PCE) of 27.90% for an incident solar spectrum from the ETL side, and power conversion efficiency (PCE) of 19.86% for an incident solar spectrum from the HTL side, the calculated bifaciality factor (BF) for this structure is 71.18%.