The role of occupational activities and work environment in occupational injury and interplay of personal factors in various age groups among Indian and French coalminers

Objective

The role of occupational hazards in occupational injury may be mediated by individual factors across various age groups. This study assessed the role of occupational hazards as well as contribution of individual factors to injuries among Indian and French coalminers.

Material and Methods

We conducted a case-control study on 245 injured workers and on 330 controls without any injuries from Indian coal mines using face-to-face interviews, and a retrospective study on 516 French coalminers using a self-administered questionnaire including potential occupational and personal factors. Data were analyzed using logistic models.

Results

The annual rate of injuries was 5.5% for Indian coalminers and 14.9% for the French ones. Logistic model including all occupational factors showed that major injury causes were: hand-tools, material handling, machines, and environment/work-geological/strata conditions among Indian miners (adjusted odds-ratios 2.01 to 3.30) and biomechanical exposure score among French miners (adjusted odds-ratio 3.01 for score the 1–4, 3.47 for the score 5–7, and 7.26 for score ≥ 8, vs. score 0). Personal factors among Indian and French coalminers reduced/exacerbated the roles of various occupational hazards to a different extent depending on workers’ age.

Conclusion

We conclude that injury roles of occupational hazards were reduced or exacerbated by personal factors depending on workers’ age in both populations. This knowledge is useful when designing prevention which should definitely consider workers’ age.     

Married men's first time experiences of early childbearing and their role in sexual and reproductive decision making: a qualitative study from rural Vietnam

Male partners' involvement in women's sexual and reproductive health has been increasingly emphasised in international health. A qualitative approach with open-ended qualitative interviews was used to explore young, married men's first time experiences of early childbearing, their sexual and reproductive decision making and the meanings they make of their role as husbands and fathers. The results offer a nuanced picture of the men's vulnerability in becoming young fathers and having to assume their role as family decision-makers, while still being inexperienced in matters related to the health of their wives and newborn child. Constraints to gender equality and traditional norms and values continue to pose barriers to both young men and women making independent decisions in relation to marriage and childbearing. Men's involvement is necessary in healthcare programmes designed to improve women's sexual and reproductive health and the health of the newborn. Young, first-time fathers, in particular, need support and empowerment.     

Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk case finding?

CONTEXT: Maternal subclinical hypothyroidism during pregnancy is associated with various adverse outcomes. Recent consensus guidelines do not advocate universal thyroid function screening during pregnancy but recommend testing high-risk pregnant women with a personal history of thyroid or other autoimmune disorders or with a family history of thyroid disorders. OBJECTIVE: The objective of the study was to assess efficacy of the targeted high-risk case-finding approach in identifying women with thyroid dysfunction during early pregnancy. DESIGN/SETTING: This was a single-center cohort study. PATIENTS/OUTCOME MEASURES: We prospectively analyzed TSH, free T4 and free T3 in 1560 consecutive pregnant women during their first antenatal visit (median gestation 9 wk). We tested thyroperoxidase antibodies in 1327 (85%). We classified 413 women (26.5%), who had a personal history of thyroid or other autoimmune disorders or a family history of thyroid disorders, as a high-risk group. We examined whether testing only such a high-risk group would pick up most pregnant women with thyroid dysfunction. RESULTS: Forty women (2.6%) had raised TSH (>4.2 mIU/liter). The prevalence of raised TSH was higher in the high-risk group [6.8 vs. 1% in the low-risk group, relative risk (RR) 6.5, 95% confidence interval (CI) 3.3-12.6, P < 0.0001]. Presence of personal history of thyroid disease (RR 12.2, 95% CI 6.8-22, P < 0.0001) or other autoimmune disorders (RR 4.8, 95% CI 1.3-18.2, P = 0.016), thyroperoxidase antibodies (RR 8.4, 95% CI 4.6-15.3, P < 0.0001), and family history of thyroid disorders (RR 3.4, 95% CI 1.8-6.2, P < 0.0001) increased the risk of raised TSH. However, 12 of 40 women with raised TSH (30%) were in the low-risk group. CONCLUSION: Targeted thyroid function testing of only the high-risk group would miss about one third of pregnant women with overt/subclinical hypothyroidism.     

Hypoxia response in asthma: differential modulation on inflammation and epithelial injury

Oxygen-sensing prolyl-hydroxylase (PHD)-2 negatively regulates hypoxia-inducible factor (HIF)1-α and suppresses the hypoxic response. Hypoxia signaling is thought to be proinflammatory but also attenuates cellular injury and apoptosis. Although increased hypoxic response has been noted in asthma, its functional relevance is unknown. The objectives of this study were to dissect the mechanisms and role of the hypoxic response in asthma pathophysiology. Experimental studies were conducted in mice using acute and chronic allergic models of asthma. The hypoxic response in allergically inflamed lungs was modulated by using pharmacologic PHD inhibitors (ethyl-3-4-dihydroxybenzoic acid [DHB], 1-10 mg/kg) or siRNA-mediated genetic knockdowns. Increased hypoxia response led to exacerbation of the asthma phenotype, with HIF-1α knockdown being beneficial. Chronically inflamed lungs from mice treated with 10 mg/kg DHB showed diffuse up-regulation of the hypoxia response, severe airway remodeling, and inflammation. Fatal asphyxiation during methacholine challenge was noted. However, bronchial epithelium restricted up-regulation of the hypoxia response seen with low-dose DHB (1 mg/kg) reduced epithelial injury and attenuated the asthmatic phenotype. Up-regulation of the hypoxia response was associated with increased expression of CX3CR1, a lymphocyte survival factor, and increased inflammatory cell infiltrate. This study shows that an exaggerated hypoxia response may contribute to airway inflammation, remodeling, and the development of asthma. However, the hypoxia response may also be protective of epithelial apoptosis at lower levels, and the net effects of modulating the hypoxia response may vary based on the context.     

Histocompatibility locus antigens regions contribute to the ethnicity bias of Epstein‐Barr virus‐associated nasopharyngeal carcinoma in higher‐incidence populations

Nasopharyngeal carcinoma (NPC) is one the most confusing and rare malignancy in most part of the world with significantly high occurrence in some populations of Southeast Asia, North Africa and Alaska. Apart from the dietary and environmental factors, NPC is well‐associated with Epstein‐Barr virus (EBV) infection in these ethnic groups. However, the internal molecular mechanism(s) for such association in specific populations is not known till date. Polymorphisms in the genes of histocompatibility locus antigens (HLA) are reported in NPC, but association of any particular polymorphism with ethnicity is not established yet. Here, we report a set of HLA polymorphisms in EBV‐infected NPC samples from Northeast Indian population. These polymorphisms might play an important role for the lack of proper immune function against EBV infection and thus, eventually, for NPC generation in endemic populations like those of Northeast India.     

A prospective,randomized, controlled,trial comparing occult-scar incision laparoscopic cholecystectomy and classic three-port laparoscopic cholecystectomy

Background

This study was designed to evaluate the outcome of laparoscopic cholecystectomy by comparing a new technique using occult-scar incision for laparoscopic cholecystectomy (OSLC) with classic three-port laparoscopic cholecystectomy (CLC). In the occult-scar incision, we moved the subcostal and subxiphoid trocar insertion sites to the suprapubic area so that operative scars were hidden in the pubic hairs and below umbilicus.

Methods

Between July 2009 and 2012, patients undergoing laparoscopic cholecystectomy were randomized to the OSLC or CLC approach after obtaining informed consent. Outcome was measured by operative time, operative complications, hospital length of stay, cost, analgesia required after surgery, and cosmetic outcomes. The patient satisfaction score (PSS) and visual analog score (VAS) also were used to evaluated the level of cosmetic result and postoperative pain.

Results

A total of 75 patients were randomized into CLC (n = 35) and OSLC (n = 40) groups. No patient was converted to an open procedure in either the CLC or OSLC group. No operative complications were reported within 30 days in either group. The PSS of 7 and 30 days after surgery were both significantly higher in the OSLC group than in the CLC group (5.8 ± 1.5 vs. 8.0 ± 1.1, P = 0.03; 6.5 ± 1.2 vs. 9.2 ± 0.8, P = 0.02). The VAS for pain was significantly lower in the OSLC group on postoperative day 3 compared with the CLC group (2.6 ± 1.2 vs. 6.3 ± 0.9, P = 0.01). There was no significant difference in operative time, hospital stay, and cost between the two groups.

Conclusions

The OSLC is a safe and feasible alternative compared with CLC in experienced hands, and it is superior for outcomes regarding pain control and cosmesis.     

Validation of RSSDI therapeutic wheel with clinical experience of Indian physicians

International Journal of Diabetes in Developing Countries - The Research Society for Study of Diabetes in India (RSSDI) has developed country-specific guidelines focusing on patient-centric...     

Highly activated and expanded natural killer cells for multiple myeloma immunotherapy

Background Patients with gene expression profiling-defined high-risk myeloma in relapse have poor outcomes with current therapies. We tested whether natural killer cells expanded by co-culture with K562 cells transfected with 41BBL and membrane-bound interleukin-15 could kill myeloma cells with a high-risk gene expression profile in vitro and in a unique model which recapitulates human myeloma. DESIGN AND METHODS: OPM2 and high-risk primary myeloma tumors were grown in human fetal bone implanted into non-obese diabetic severe combined immunodeficiency mice with a deficient interleukin-2 receptor gamma chain. These mice are devoid of endogenous natural killer and T-cell activity and were used to determine whether adoptively transferred expanded natural killer cells could inhibit myeloma growth and myeloma-associated bone destruction. RESULTS: Natural killer cells from healthy donors and myeloma patients expanded a median of 804- and 351-fold, respectively, without significant T-cell expansion. Expanded natural killer cells killed both allogeneic and autologous primary myeloma cells avidly via a perforin-mediated mechanism in which the activating receptor NKG2D, natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central role. Adoptive transfer of expanded natural killer cells inhibited the growth of established OPM2 and high-risk primary myeloma tumors grown in the murine model. The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis. Conclusions These studies provide the rationale for testing expanded natural killer cells in humans.     

Sulfur Mobilization for Fe-S Cluster Assembly by the Essential SUF Pathway in the Plasmodium falciparum Apicoplast and Its Inhibition

The plastid of the malaria parasite, the apicoplast, is essential for parasite survival. It houses several pathways of bacterial origin that are considered attractive sites for drug intervention. Among these is the sulfur mobilization (SUF) pathway of Fe-S cluster biogenesis. Although the SUF pathway is essential for apicoplast maintenance and parasite survival, there has been limited biochemical investigation of its components and inhibitors of Plasmodium SUFs have not been identified. We report the characterization of two proteins, Plasmodium falciparum SufS (PfSufS) and PfSufE, that mobilize sulfur in the first step of Fe-S cluster assembly and confirm their exclusive localization to the apicoplast. The cysteine desulfurase activity of PfSufS is greatly enhanced by PfSufE, and the PfSufS-PfSufE complex is detected in vivo. Structural modeling of the complex reveals proximal positioning of conserved cysteine residues of the two proteins that would allow sulfide transfer from the PLP (pyridoxal phosphate) cofactor-bound active site of PfSufS. Sulfide release from the l-cysteine substrate catalyzed by PfSufS is inhibited by the PLP inhibitor d-cycloserine, which forms an adduct with PfSufS-bound PLP. d-Cycloserine is also inimical to parasite growth, with a 50% inhibitory concentration close to that reported for Mycobacterium tuberculosis, against which the drug is in clinical use. Our results establish the function of two proteins that mediate sulfur mobilization, the first step in the apicoplast SUF pathway, and provide a rationale for drug design based on inactivation of the PLP cofactor of PfSufS.     

Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan

M cells, the key players of the mucosal immunity induction, are one of the intestinal barriers for the efficient delivery of vaccines to mucosal immune tissues. To overcome the barrier, we have developed an efficient oral vaccine carrier that constitutes poly (lactic-co-glycolic acid) (PLGA) microparticle coated with M cell targeting peptide. In this study, a membrane protein B of Brachyspira hyodysenteriae (BmpB) as a model vaccine against swine dysentery was loaded into porous PLGA microparticles (MPs). The PLGA MPs were further coated with the water-soluble chitosan (WSC) conjugated with M cell homing peptide (CKS9) to prepare BmpB-CKS9-WSC-PLGA MPs. Oral immunization of BmpB vaccine with CKS9-WSC-PLGA MPs in mice showed elevated secretory IgA responses in the mucosal tissues and systemic IgG antibody responses, providing a complete immune response. Specifically, the immunization with these MPs demonstrated to induce both Th1- and Th2-type responses based on elevated IgG1 and IgG2a titers. The elevated immune responses were attributed to the enhanced M cell targeting and transcytosis ability of CKS9-WSC-PLGA MPs to Peyer's patch regions. The high binding affinity of CKS9-WSC-PLGA MPs with the M cells to enter into the Peyer's patch regions of mouse small intestine was investigated by closed ileal loop assay and it was further confirmed by confocal laser scanning microscopy. These results suggest that the M cell targeting approach used in this study is a promising tool for targeted oral vaccine delivery.