Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Rumour spread and control during the West African Ebola epidemic in Liberia.

The severity of the 2014-15 West African Ebola epidemic in Liberia was coupled with widespread misunderstanding of the virus among citizens and the proliferation of rumours. Rumour control during outbreaks is imperative to reduce the public's fears about a disease. In Liberia, a tracker system was developed to detect rumours as quickly as possible through SMS (short message service) text messaging. This study focused on assessing rumour circulation in newspapers and on radio and rumour control over time. It relied on a content analysis of SMS messages from the 'DeySay' tracker, print and audio communications of newspapers, and radio programmes, in the time frame between January 2014 and March 2015. The findings show that more rumours appeared in newspapers but were more likely to be overtly characterised as such on the radio. DeySay accurately predicted rumours before they appeared on the radio and in newspapers, supporting its usefulness in future health epidemics.

Association of MSX1 Gene Variants with Nonsyndromic Cleft Lip and/or Palate in the Pakistani Population.

OBJECTIVES: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. DESIGN: Comparative cross-sectional study.Setting: Multicenter of CL/P malformation.Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. METHODS: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). RESULTS: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16-8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. CONCLUSION: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people.

Implementation practice models for development in low- and middle-income countries: systematic review of peer-reviewed literature.

INTRODUCTION: This study operationally defines a relatively small, but growing field of study on implementation practice models for health behavior change in the context of international development. We define 'implementation practice models' as theoretical models that take a practical and practitioner-focused approach to behavior change, and we illustrate how these models have been developed and applied. The paper examines the continuum of behavioral theories and their application in the context of development programs and research in low- and middle-income countries (LMICs). We describe implementation practice models, examine how they have been used to design and evaluate theory-based interventions in LMIC, and describe the state of evidence in this field of study. METHODS: The authors conducted a systematic search of the published, peer-reviewed literature following the widely accepted PRISMA methods for systematic reviews. We aimed to identify all relevant manuscripts published in the English language in health, social science, and business literature that apply implementation practice models, located in an LMIC, with a behavior change objective. We located 1,078 articles through database searching and 106 through other means. Ultimately, we identified 25 relevant articles for inclusion. RESULTS: We found that the peer-reviewed literature on implementation practice models for development has been growing in recent years, with 80% of reviewed papers published since 2015. There was a wide range of different models revealed by this review but none demonstrated clear-cut evidence of being most effective. However, the models found in this review share common characteristics of focusing on the three central tenets of Opportunity, Ability, and Motivation (OAM). CONCLUSIONS: This review found that implementation practice models for development are a promising and growing approach to behavior change in LMICs. Intervention practice models research should be expanded and applied in new domains, such as vaccination.

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

OBJECTIVES: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. PATIENTS AND METHODS: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. RESULTS: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. CONCLUSIONS: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

Overlooking the Obvious: Communication of Efficacy by the Mass Media During the Ebola Crisis in Liberia.

The role of mass media during a public health crisis is an ineluctable part of providing the public with critical information rapidly, particularly messages about self- and response efficacy. However, little is known about the role local news media play in disseminating efficacy information during infectious disease outbreaks. Here, we use the 2014 Ebola outbreak in Liberia as a case to explore this question. We content analyzed newspaper and radio messages disseminated between March 2014 and March 2015, during the midst of the outbreak. Results show that both radio programs and newspaper articles mentioned over 21 prevention steps at some point, with noticeable differences within which disease prevention messages were communicated most frequently to the public. At least 1 mention of self-efficacy was identified in 31.5% of radio content (n = 127), 23.6% of radio programming (n = 55), and 10.6% of newspaper content (n = 745). Response efficacy, signifying effectiveness of preventive methods, was detected in 25.2% of radio (n = 127), 16.4% of radio programming (n = 55), and 15% of newspaper content (n = 745). This is important as efficacy reporting can impact public readiness to adopt preventative measures and affect beliefs about self- and response efficacy, ultimately decreasing chances of spreading the infection and poorer health outcomes.

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study.

BACKGROUND: To study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women. METHODS: After ethical approval and getting informed consent; 250 pregnant women were enrolled and equally divided into two groups (125 preeclamptic cases and 125 normotensive pregnant women). Demographic details and medical history were recorded, and 10 ml blood sample was obtained for DNA extraction. The tetra-primer amplification refractory mutation system (ARMS) assays were developed for assessing the variants of three preeclampsia related genes; F5, MTHFR and VEGFA. An association of six SNVs; F5:c.1601G > A (rs6025), F5:c.6665A > G (rs6027), MTHFR: c.665C > T (rs1801133), MTHFR: c.1286A > C (rs1801131), VEGFA: c.-2055A > C (rs699947) and VEGFA: c.*237C > T (rs3025039) with preeclampsia was determined by using different genetic models. RESULTS: Genotyping of the SNVs revealed that patients with MTHFR:c.665C > T, have increased susceptibility to preeclampsia (CT versus CC/TT: OR = 2.79, 95% CI = 1.18-6.59; P* = 0.046 and CT/TT vs CC: OR = 2.91, 95% CI = 1.29-6.57; P* = 0.0497, in overdominant and dominant models, respectively), whereas F5:c.6665A > G, (A/G vs AA/GG: OR = 0.42, 95% CI = 0.21-0.84; P* = 0.038 in overdominant model) and MTHFR:c.1286A > C, (CC versus AA: OR = 0.36, 95% CI = 0.18-0.72; P* = 0.0392 in codominant model) have significantly decreased risk for preeclampsia. F5:c.1601G > A, VEGFA: c.-2055A > C and VEGFA: c.*237C > T variants revealed no relationship with the disease. CONCLUSION: This is the first case control study describing the protective role of F5:c.6665A > G against preeclampsia in any world population. In addition, the present study confirmed the association and role of MTHFR gene variations in the development of preeclampsia in Pakistani patients. Further genetic studies may be required to better understand the complex genetic mechanism of SNVs in preeclampsia related genes in pregnant women.

Understanding modern contraception uptake in one Ethiopian community: a case study.

BACKGROUND: In the last decade, the proportion of Ethiopian women using contraceptive methods has increased substantially (from 14% in 2005 to 35% in 2016 among married women). Numerous factors have contributed to the increased uptake. An important one is the implementation of the Health Extension Program, a government-led health service delivery strategy that has deployed more than 38,000 health extension workers (HEWs) throughout the country. Key mechanisms underlying the success of this program are not well understood. Using a case study approach, the goal of this study is to describe how key features of local contexts, community perceptions, and messaging by HEWs have contributed to the increased use of modern contraception in one community in Ethiopia. METHODS: We conducted focus groups and individual interviews with men, women, adolescents, and key informants, including (HEWs), in Oromia, Ethiopia. We used a random sampling protocol to recruit all participants except key informants, with whom purposive sampling was used to ensure participants were knowledgeable on family planning in the village. Interviews were audio recorded, translated, transcribed, and then analyzed using applied thematic analysis and NVivo v.11 qualitative research software. RESULTS: We identified four themes that may explain uptake of contraception: (1) HEWs are seen as trusted and valued community members who raised awareness about family planning; (2) the HEW messaging that contraception is useful to space pregnancies among married women was effective; (3) the message that spacing is healthy for mother and child was also effective; and (4) communicating to the entire community (including men, women, adolescents, and religious leaders), contributed to changing attitudes around contraception. CONCLUSION: The four aspects of the Health Extension Program approach increased uptake of contraception in our sample. In contexts where community health workers are valued by the health systems and local communities they serve, this type of approach to widening modern contraception use could help increase uptake and address unmet need. Understanding these granular aspects of the program in one local context may help explain how use of contraception increased in the country as a whole.

Genetic Testing of Non-familial Deaf Patients for CIB2 and GJB2 Mutations: Phenotype and Genetic Counselling.

CIB2 and GJB2 genes variants contribute significantly in familial cases of prelingual recessive hearing loss (HL). This study was aimed to determine the CIB2 and GJB2 variants and associated phenotype in 150 non-familial individuals with HL. After getting informed consent, 150 non-familial deaf patients were enrolled and blood samples were obtained for DNA extraction. Pure tone air conduction audiometry was performed. Coding exons of CIB2 and GJB2 genes were Sanger sequenced. A tetra primer ARMS assay was developed for recurrent CIB2 variant. Four bi-allelic GJB2 variants, c.71G>A p.(Trp24*), c.231G>A p.(Trp77*), c.235delC p.(Leu79Cysfs3*) and c.35delG p.(Gly11Leufs24*), were found in nine hearing impaired individuals. We also found four homozygotes and five carriers of c.380G>A p. (Arg127His) variant of controversial clinical significance. CIB2 sequencing revealed single recurrent variant c.272T>C p. (Phe91Ser) segregating with HL in ten individuals. Among our patients, c.71G>A (p.Trp24*) was the most common variant, accounted for 45% of GJB2 variants. Two known GJB2 variants, c.235delC p. (Leu79Cysfs3*) and c.310del14 p. (Lys105Argfs2*), are reported here for the first time in Pakistani population. Our data further support the benign nature of c.380G>A p. (Arg127His) variant. For CIB2, c.272T>C p. (Phe91Ser) is the second common cause of HL among our sporadic cases. Phenotypically, in our patients, individuals homozygous for GJB2 variants had profound HL, whereas CIB2 homozygotes had severe to profound prelingual HL. Our results suggest that GJB2 and CIB2 are common cause of HL in different Pakistani ethnicities.

Mutational spectrum of the CYP1B1 gene in Pakistani patients with primary congenital glaucoma: novel variants and genotype-phenotype correlations.

PURPOSE: This study aimed to investigate the role of CYP1B1 mutations in primary congenital glaucoma (PCG) in Pakistani patients. METHODS: After consent was received, 20 families with at least more than one member affected with primary congenital glaucoma were enrolled in the study. The disease was confirmed with standard ophthalmological investigations. Genomic DNA was extracted from whole blood for localization of linkage and sequencing. Bioinformatics tools were used to assess the predicted pathological role of novel variants. RESULTS: Ten out of 20 families (50%, 10/20) showed homozygosity with CYP1B1-linked short tandem repeat (STR) markers. On direct sequencing of the CYP1B1 gene in the linked families, six mutations, including two novel pathogenic variants, were identified. p. R390H was the most frequently found mutation in five families (50%, 5/10), whereas c.868_869insC, p.E229K, and p.A115P were found once in three families. Two novel mutations, a missense mutation (p.G36D) and an in-frame deletion mutation (p.G67-A70del), were segregated with disease phenotype in two families. Age of disease onset was congenital in all mutations; however, disease severity and response to clinical interventions varied among the mutations and families. Haplotype analysis using five polymorphisms revealed a distinct haplotype for a common mutation. CONCLUSIONS: This is the largest cohort of Pakistani patients with PCG to be genetically screened for CYP1B1 mutations. Identifying common mutation and genotype-phenotype correlations may help in genetic testing and better prognosis for the disease. Novel mutations identified in the study may help in better understanding the pathophysiology of CYP1B1-associated glaucoma.

Relationship between aging and control of metabolic syndrome with telomere shortening: a cross-sectional study.

Aging is considered one of the major risk factors for several human disorders. The telomere plays a crucial role in regulating cellular responsiveness to stress and growth stimuli as well as maintaining the integrity of the Deoxyribonucleic Acid (DNA), and aging leads to the progressive decline in the telomere length (TL) due to continuous cell division. The aim of this study was to determine the relationship between TL and advancing age and the impact of metabolic syndrome (MetS) on TL. Firstly, we determined the association of advancing age and TL, by measuring telomere length (T/S ratio) in healthy volunteers (n = 90). The TL was compared between normal population and patients with metabolic syndrome (n = 298). The age matched controlled and uncontrolled MetS patients (n = 149) were also compared for their TL T/S ratio. The TL showed negative correlation with advancing age, whereas the significant change was observed at the cut-offs of 40 and 70 years defining 40 with longer TL and 70 as shorter TL. The longest T/S ratio at 2.46 was measured at the age range of 1 year in healthy volunteers, while elderly population showed considerably shorter TL. The patients older than 60 years with poor or uncontrolled MetS had shorter TL, as compared to the controlled MetS. In conclusion our findings suggest that TL was negatively correlated with advancing age. Uncontrolled metabolic syndrome appeared to have worsening effects on TL. Telomere length appears to have potential to be used a parameter to determine age. However, further large scale studies are recommended to make firm guidelines.

Mutational analysis of CYP1B1 (rs56010818) variant in primary open angle glaucoma (POAG) affected patients of Pakistan.

BACKGROUND: Primary open angle glaucoma (POAG) occurs due to the discrepancies in the angle of anterior chamber characterized by the alterations in intraocular pressure, optic nerves head changes and central loss of visual field. In molecular research, CYP1B1 mutations modulates an integral role in association with glaucoma. Current study was undertaken to reveal the homozygous and heterozygous patterns of CYP1B1 c.1169 G > A variant (rs56010818) in POAG patients of Pakistan. METHODS: After consent, total n = 88 POAG patients undergone through standard ophthalmological investigations before their recruitment in this study. The blood samples were utilized for DNA isolation. The genotyping of CYP1B1 c.1169 G > A variant was carried out by Sanger sequencing. The mutational patterns and its association with clinical variables were demonstrated by statistical and bioinformatic tools. RESULTS: It was evident that the frequencies of heterozygous G/A and homozygous mutants A/A genotypes were higher in males (36.5%, 7.7%) than females (30.6%, 2.8%) of POAG population. Furthermore, the juvenile patients exhibit high manifestation of carrier genotype (66.6%) in comparison to adult patients (31.7%). The results also indicated the significant relationship of intraocular pressure with homozygous mutant A/A genotype of CYP1B1 variant in POAG patients (p < 0.05). CONCLUSIONS: Our study provided the mutational data of CYP1B1 R390H variant and the patterns of homozygosity and heterozygosity along with clinical associations. Overall, this study revealed the genetic predisposition of CYP1B1 c.1169 G > A variant in the patients of POAG in Pakistan. The findings could be helpful for genetic screening and in-depth understanding of underlying causes in the pathogenesis of POAG.

Transnational determinants of health for Central American migrants to the U.S.: Results of a qualitative study.

While some research on health determinants for immigrant/refugee populations has considered migration itself as a health determinant, much of this research employs constructs that focus on factors such as language, acculturation, norms, behaviours, beliefs, and social support, in a manner analogous to health risk factors for domestic U.S. populations. These are, however, often disassociated from the broader context of migration and its transnational continuum. As a contribution towards addressing that gap, this study reports on 75 life history interviews from recent Central American immigrants to assess potential health determinants in three linked domains - home country situation, migration experience, and adjustment to the U.S. These domains were conceptualised as one transnational continuum, with health outcomes potentially resulting from combined effects across domains. Interview data showed, among other results, extensive experience with/victimisation from violence in the home countries and during migration, resulting in multiple health outcomes (including PTSD) in the U.S. It also showed some patterns of resiliency, as well as added stressors from the current political environment. The results and protocol from this pilot study are useful for broader research efforts in multiple global settings, and as narratives, should also help counter negative public representations and support improved treatment.

Review of Web-Based Toolkits for Health Care Practitioners Working With Women and Girls Affected by or at Risk of Female Genital Mutilation/Cutting.

Increased migration has given rise to more advocacy efforts against female genital mutilation or cutting (FGM/C), legislation that criminalizes the practice, and guidance to the health sector for managing care of affected groups. More women and girls who have been cut or who are at risk of FGM/C are migrating from regions where it is common to countries where it is not and interacting with health professionals and other community practitioners in these host countries. Despite numerous studies on the negative health impacts of FGM/C, little is known about toolkits on FGM/C that providers can use in their prevention and response efforts. We sought to explore the nature of Internet-based products referenced as toolkits and materials characteristic of toolkits aimed at different service providers who may interact with women and girls affected by FGM/C. Through an online search, we identified 45 toolkits and collected data about each one. We found that the toolkits targeted different audiences and offered a diverse set of information and resources. The majority of toolkits were aimed at health professionals and provided factual and epidemiological-focused content, yet many did not include research evidence, skills development application, or approaches for implementing the toolkit in practice. This review is the first completed in the area of FGM/C to show a rich diversity of online materials. Future toolkits can be improved with the provision of evidence-based information and practical skills development for use by health professionals in implementing best practices in working with women and girls affected by FGM/C.

Commercial determinants of health: an ethical exploration.

OBJECTIVES: This paper seeks to contribute toward a better understanding of commercial determinants of health by proposing a set of ethical principles that can be used by researchers and other health actors in understanding and addressing Commercial Determinants of Health (CDoH). METHODS: The paper is mainly based on a systematic review and qualitative analysis of the existing literature on CDoH and public health ethics frameworks. We conducted searches using selected search engines (Google Scholar and Pubmed). For ethical challenges relating to CDOH, our searches in Google Scholar yielded 17 papers that discussed ethical challenges that affect CDoH. For ethical frameworks relevant for CDOH, our searches in Google Scholar and Pubmed yielded 15 papers that clearly described bioethical models including relevant ethical principles. Additionally, we consulted eight experts working on CDoH. Through these two methods, we were able to identify ethical challenges as well as norms and values related to CDoH that we offer as candidates to comprise a foundational ethics framework for CDoH. RESULTS: Discussing risk factors associated with CDH frequently brings public health into conflict with the interests of industry actors in the food, automobile, beverage, alcohol, ammunition, gaming and tobacco industries including conflict between profit-making and public health. We propose the following candidate ethical principles that can be used in addressing CDoH: moral responsibility, nonmaleficence, social justice and equity, consumer sovereignty, evidence-informed actions, responsiveness, accountability, appropriateness, transparency, beneficence and holism. CONCLUSIONS: We hope that this set of guiding principles will generate wider global debate on CDoH and help inform ethical analyses of corporate actions that contribute to ill health and policies aimed at addressing CDoH. These candidate principles can guide researchers and health actors including corporations in addressing CDoH.

Gravid uterus in neglected incisional hernia with skin defect-a clinical challenge.

UNLABELLED: Incisional hernia during pregnancy with whole of gravid uterus as the content of the hernia sac is a rare occurrence. When such hernia is associated with skin defect over the sac, the management gets complicated. Very few such cases are reported in the literature. There is no consensus on the management of these cases in the available literature. Here, we are reporting two such cases managed in different ways and reviewed the literature. LEVEL OF EVIDENCE: Level V, Clinical cases.

The novel heterozygous Thr377Arg MYOC mutation causes severe Juvenile Open Angle Glaucoma in a large Pakistani family.

Glaucoma is one of the major causes of blindness worldwide with characteristic optic disc changes and elevated intraocular pressure. It is subcategorized into Primary Open Angle Glaucoma (POAG) and Juvenile Open Angle Glaucoma (JOAG) depending upon age of the disease onset. Myocilin (MYOC) is the frequently mutated gene in familial cases of glaucoma. MYOC mutations show variable phenotype and penetrance. This study was aimed to identify disease causing mutation in 8 affected of a consanguineous family diagnosed with severe form of Juvenile Open Angle Glaucoma. Homozygosity mapping with four microsatellite markers and subsequent direct sequencing of MYOC revealed a novel heterozygous transition c.1130 C>G, substituting Threonine in to Arginine at codon 377 (p.Thr377Arg) of MYOC. This mutation was segregating with phenotype in all affected and was not found in control subjects. Ophthalmological findings revealed JOAG with severe and rapidly progressive phenotype. The age of onset was in the first decade of life and maximum Intra Ocular Pressure (IOP) recorded was 25mmHg. Bioinformatic tools predicted C to G transition at c.1130 as pathogenic and no structural changes were predicted in protein. This is the first report of novel MYOC mutation from Pakistan; segregating as autosomal dominant trait in large family diagnosed with JOAG. Identification of novel disease causing allele in MYOC indicates genetic heterogeneity of the population. This finding will help to provide genetic counseling to the affected family and carriers of this mutation may be advised for early therapeutic intervention to avoid irreversible visual loss.