Plasticity of Axial Identity among Somites: Cranial Somites Can Generate Vertebrae without Expressing Hox Genes Appropriate to the Trunk

AbstractClassic studies have shown that the presomitic mesoderm is already committed to a specific morphological fate, for example, the ability to generate a rib. Hox gene expression in the paraxial mesoderm has also been shown to be fixed early and not susceptible to modulation by an ectopic environment. This is in contrast to the plasticity of Hox expression in neuroectodermal derivatives. We reexamine here the potential of somites for morphological plasticity by transplanting the cranial (occipital) somites 1–4, that normally produce small contributions to the skull, to the trunk of avian embryos. Surprisingly, the transposed cranial somites are able to form reasonably normal vertebral anlage. In addition, the cranial somitic mesoderm produces intervertebral disks, structures not normally found in the skull. These somites are however unable to generate some elements of the vertebrae, such as the costal process. In contrast to the morphogenetic plasticity of the occipital somites, their characteristic inability to support survival of dorsal root ganglia was not significantly modified by posterior transplantation. Dorsal root ganglia initially developed and then degenerated with the same morphological stages as normally observed. In striking contrast to the plasticity of morphology, we found that all four members of the of the fourth paralogous group of Hox genes that are expressed endogenously at the level of the graft are not upregulated in the caudad-transposed cranial mesoderm. It therefore appears that genes other than those of the Hox family normally expressed at this axial level control the position-specific morphogenesis of ectopic vertebrae formed from cranial somites. In evolutionary terms, the present results imply that occipital somites that were incorporated into the “New Head” retain the ability to develop according to their original morphogenetic fate, into vertebrae

Allelic forms of the knob associated histidine-rich protein gene of Plasmodium falciparum

AbstractThe knob associated histidine-rich protein (KAHRP) gene was cloned and sequenced from two Indian isolates of Plasmodium falciparum, Pf3-92 and Pf29-92. These isolates showed major sequence differences in the C-terminal repeat domain of KAHRP. However, the biologically important domains such as spectrin-actin binding region remained highly conserved. The PCR amplification of a variable C-terminal repeat domain from the clinical isolates of P. falciparum, from Rajasthan epidemic, showed the presence of multiple alleles of KAHRP gene. The presence of multiple alleles indicates the existence of several P. falciparum strains in India. This should be taken into account for future malaria control strategies such as molecular therapy and vaccines

Vitamin A Administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1.18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs

Association of inflammatory biomarkers with lung cancer in North Indian population

Background: Lung cancer is characterized by uncontrolled cell growth of the lung tissues. It is the leading cause of cancer-related deaths worldwide.Objectives: The study aimed to determine the circulating CRP, TNF-α, IL-6 and IL-8 levels in lung cancer and healthy control and also established association between these biomarkers with the smoking status as well as the stages of the disease.Methodology: 51 lung cancer patients and 51 healthy controls were enrolled in this case-control study. The serum levels of CRP, TNF-α, IL-6 and IL-8 were measured in lung cancer patients and healthy control groups.Results: The levels of serum CRP, TNF-α, IL-6 and IL-8 were significantly higher in lung cancer patients when compared with controls(P<0.0001). The levels of these biomarkers were also significantly higher in stage iii/iv as compared to stage i/ii(P<0.001). Significant difference in the levels of these biomarkers were also found in smoker and non-smoker lung cancer patients as compared to controls(P<0.001).Conclusion: CRP, TNF-α, IL-6 and IL-8 are the promising biomarkers in the identification of lung cancer patients. The study also supports the association of inflammatory markers to lung cancer risk. Hence these findings suggest the levels of these biomarkerscould be a useful tool for guiding the diagnosis of lung cancer.Keywords: Lung cancer, biomarker, inflammation, stage, smoking

Structure–conductivity correlation in ferric chloride-doped poly(3-hexylthiophene)

Poly(3-hexylthiophene) (P3HT) matrix has been chemically doped (redox doping) by ferric chloride (FeCl3) with different molar concentrations to get P3HT–FeCl3 charge-transfer complexes. The effect of redox doping on photo-physical, structural, and morphological properties and dc electrical conductivity of P3HT matrices has been examined. The dc conductivity has been measured on films of pristine P3HT and P3HT–FeCl3 charge-transfer complexes in the temperature range 6–300 K. Analysis of dc conductivity data reveals that in the temperature range 40–300 K, the dc conductivity is predominantly governed by Mott's 3-dimensional variable range hopping (3D-VRH); however, below 40 K tunnelling seems to dominate. A slight deviation from 3D-VRH to 1D-VRH is observed with an increase in doping level or precisely with an increase in the extent of P3HT–FeCl3 charge-transfer complexes. We attribute this deviation to the induced expansion in crystallographic lattices as revealed by x-ray diffraction data and formation of discrete conducting domains as observed by atomic force microscope imaging

Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children

Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries. In a randomized, placebo-controlled trial, we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea. Methods: Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were randomized to 4 study groups. Three groups were blinded and the children supplemented daily by field workers with placebo syrup, zinc syrup, or zinc syrup and a massive dose of vitamin A at enrollment. The fourth group was open and the caretaker gave the children zinc syrup daily. Day-wise information on morbidity was obtained by household visits every fifth day. Results: The relative hazards for termination of diarrhea were 26% (95% confidence interval [CI]: 8%, 46%), 21% (95% CI: 4%, 38%), and 19% (95% CI: 2%, 40%) higher in the zinc, zinc-vitamin A, and zinc-caretaker groups, respectively, than in the placebo group. The relative risks of prolonged diarrhea (duration >7 days) in these groups were 0.57 (95% CI: 0.38, 0.86), 0.53 (95% CI: 0.35, 0.81), and 0.55 (0.37, 0.84); zinc accordingly reduced the risk of prolonged diarrhea with 43% to 47%. Five percent and 5.1% of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group, respectively, whereas this occurred after only 1.3% of placebo administrations. Vomiting during diarrhea was also more common in children receiving zinc. Conclusions: Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea. The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration

Association of inflammatory biomarkers with lung cancer in North Indian population

Background: Lung cancer is characterized by uncontrolled cell growth of the lung tissues. It is the leading cause of cancer-related deaths worldwide. Objectives: The study aimed to determine the circulating CRP, TNF-\u3b1, IL-6 and IL-8 levels in lung cancer and healthy control and also established association between these biomarkers with the smoking status as well as the stages of the disease. Methodology: 51 lung cancer patients and 51 healthy controls were enrolled in this case-control study. The serum levels of CRP, TNF-\u3b1, IL-6 and IL-8 were measured in lung cancer patients and healthy control groups. Results: The levels of serum CRP, TNF-\u3b1, IL-6 and IL-8 were significantly higher in lung cancer patients when compared with controls(P<0.0001). The levels of these biomarkers were also significantly higher in stage iii/iv as compared to stage i/ii(P<0.001). Significant difference in the levels of these biomarkers were also found in smoker and non-smoker lung cancer patients as compared to controls(P<0.001). Conclusion: CRP, TNF-\u3b1, IL-6 and IL-8 are the promising biomarkers in the identification of lung cancer patients. The study also supports the association of inflammatory markers to lung cancer risk. Hence these findings suggest the levels of these biomarkers could be a useful tool for guiding the diagnosis of lung cancer. DOI: https://dx.doi.org/10.4314/ahs.v19i2.39 Cite as: Gaur P, Bhattacharya S, Kant S, Kushwaha RAS, Garg R, Singh G, Pandey S, Sharma S. Association of inflammatory biomarkers with lung cancer in North Indian population. Afri Health Sci.2019;19(2): 2147-2155. https://dx.doi.org/10.4314/ahs.v19i2.3

A study to estimate prevalence and risk factors of Obstructive Sleep Apnoea Syndrome in a semi-urban Indian population

Obstructive Sleep Apnea Syndrome (OSAS) has been recognised as a major cause of morbidity and mortality in developing countries like India. There is still a paucity of Indian studies regarding the prevalence of OSAS. The current single centre prospective cross-sectional study was undertaken to know prevalence estimates for key symptoms and features that can indicate the presence of OSAS in an Indian population. A survey was conducted on subjects with age groups ≥ 25 years at King George's Medical University, Lucknow, Uttar Pradesh, India from August 2009 to July 2011. Data was recorded during the interview on the basis of Berlin Questionnaire (BQ). Risk factors for OSAS were also evaluated. Risk group categorization for OSAS was done with the help of a questionnaire and overnight polysomnography was performed in each group to measure apnea and hypopnea index (AHI). Out of 1816 subjects, 1512 (response rate 83.3%) finally participated in the survey with mean age 42.6±11.2 years, males 67.9% and females 32.1%. Of them 6.2% were found to be at high-risk OSAS; 12.2% were obese (Body Mass Index ≥30 kg/m2) and 33.5% of the obese population were at high-risk OSAS. Among high-risk patients with OSAS, 62.4% had hypertension. Statistically significant and independent risk factors found for OSAS were obesity, large neck size, alcoholism and use of sedatives/tranquillizers. High-risk category predicted an AHI ≥5 with a sensitivity of 86.3% (95% CI 73.1-93.8), specificity of 93.1% (95% CI 89.1-95.7), positive and negative predictive values of 70.9% (95% CI 57.9-81.4) and 97.2% (95% CI 94.1-98.8) respectively. It can be concluded that BQ questionnaire can still be used as a pre-assessment tool for predicting persons at risk for OSAS in clinical practice. Further studies on estimation of prevalence of OSAS by applying BQ are warranted in near future from other regions of India

Detection of Anaplastic Lymphoma Kinase Gene Re-Arrangement in Non-Small Cell Lung Carcinoma in the Indian Population: Comparison of Techniques and Immunohistochemistry Clones

Objective: Predictive and prognostic markers have revolutionized personalized therapy in non-small cell lung carcinoma (NSCLC). Crizotinib is now approved for locally advanced or metastatic NSCLC that is anaplastic lymphoma kinase (ALK) positive by either Fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). The current study aimed to detect the incidence of ALK gene re-arrangement in the Indian population, to compare the various IHC antibodies with FISH as a gold standard, and to analyze the morphology of cases with ALK phenotype. Material and Method: A case series of 614 cases of NSCLC were included. IHC for detection of ALK phenotype was compared with FISH using 5A4 clone (Labvision, USA), ALK-1(Dako, Denmark) and D5F3 clone (Ventana, USA). Results: ALK gene rearrangement was evident in 4.07% of the cases. Cases with ALK phenotype had unique histomorphology with presence of mucin or signet ring cells in association with necrosis, high tumour grade and poor differentiation. Comparison of various antibody clones used in IHC revealed that the sensitivity and specificity using the D5F3 clone (100%, 100%) and 5A4 clone (87.5%, 100%) were similar while the ALK-1 clone had the lowest sensitivity and specificity (50%, 95.5%). Conclusion: The incidence of ALK gene rearrangement in NSCLC in the current Indian study is within the worldwide reported range of 3-5%. This is the first study from the Indian subcontinent to compare various IHC antibodies used for detection of ALK phenotype. IHC using D5F3 clone and 5A4 clone may be considered as a rapid reliable and inexpensive method for detection of ALK gene rearrangement