Search

Background: In India, the population of elderly is predicted that it will be increased from 8% in 2015 to 19% in 2050. Geriatric population contributes around 9% of the total Odisha population and 86.3% of them reside in rural areas. The study aimed to estimate the prevalence of diabetes mellitus and find out its risk factors among rural geriatric population in Tigiria block of Odisha, India. Methods: This was a community-based study, cross-sectional in design among 725 rural geriatric populations of Odisha. Socio-demographic information was collected following the standard census of India operational definitions. Self-reported diabetes mellitus status was collected and classified as "present" or "absent". Statistical analysis was performed using "R version 4.0.4". Results: Among the total elderly, 88 (12.13%) participants were diagnosed with diabetes. Common factors found to be significant with diabetes were illiterates (AOR=0.32, CI=0.125-0.817), not working elderly (AOR=2.51, CI=1.103-5.723), high socioeconomic status (AOR=3.79, CI=1.351-10.632) and overweight elderly (AOR=2.19, CI=1.286-3.753) respectively. Conclusion: The frequency of diabetes mellitus among rural geriatric population is less but the risk is high among those not working, literate, with higher SES and overweight elderly group. The researcher should emphasize real-time diagnosis of blood sugar levels using standardized measures among the rural elderly population.

Aim: To establish the efficacy of rural outreach programme in reducing blindness caused by cataract by comparative analysis of visual outcome. Materials and Methods: Records of patients attending outreach camps conducted during 10 years i.e., 2001-02 to 2010-11 were studied. The total number of patients attending the camp and those who were detected to have visually significant cataract were noted. Similarly, the number of patients attending the outpatient department of the department of Ophthalmology and the number detected with visually significant cataract were noted. Data was tabulated and analyzed. Result: Out of 1, 16,615 patients visiting the outpatient department during those ten years, 3,014 were detected to have cataract (2.58%). 744 camps were conducted during the period of ten years, screening 60,086 patients and 6711 (11.17%) of them were detected to have cataract and were operated. These results were statistically significant. Conclusions: High numbers of cataracts were detected in the rural parts of South India with the help of outreach camps, while compared to tertiary care centres. They were given treatment in the form of cataract extraction and implantation of intraocular lens. Hence, conducting outreach camps forms an integral part in decreasing the visual morbidity due to cataract.

Xeroderma pigmentosum (XP) is a rare genetic disorder associated with multiple oculocutaneous and neurological manifestations. It occurs due to deficiency of the enzymes responsible for repairing ultraviolet radiation-induced DNA damage. Persistence of un-repaired DNA results in somatic mutations, leading to neoplasia of the skin and ocular surface. As this condition is rare, only isolated case reports of XP with ocular surface squamous neoplasia (OSSN) are found in literature.

The sustainable development of energy has always been a concern. Upgrading biomass catalysis into hydrocarbon liquid fuels is one of the effective methods. In order to upgrade biomass derivative guaiacol by Hydrodeoxygenation (HDO) catalysis, this article report a three-dimensional honeycomb structure biochar loaded with Ni nanoparticles and phosphomolybdic acid demonstrating excellent catalytic performance in a short period of time. This is due to the porous structure of biochar, which allows Ni metal nanoparticles to be highly uniformly dispersed on the support, which enhances the catalytic hydrogenation of guaiacol in terms of both rate and efficiency. Furthermore, it was observed that the added phosphomolybdic acid dissolved within the temperature range of 78-90 °C, functioning as a homogeneous catalyst in the process. This proves advantageous, as the phosphomolybdic acid becomes accessible at any location within the porous Ni/C catalyst. The detailed characterization data revealed that the carbon support prepared in this study has a high specific surface area of up to 1375.61 m 2 /g. Additionally, the phosphomolybdic acid exhibited rich acidity, with Brønsted and Lewis acid contents of 2.55 μmol/g and 21.45 μmol/g, respectively. Reaction data demonstrated that at 240 °C for 180 min, 100 % conversion and 97.9 % cyclohexane selectivity were achieved. This study introduces a bifunctional catalyst with an unique catalyst's structure, facilitating a heterogeneous-homogeneous catalytic reaction and delivering an efficient catalytic effect., (© 2024 Wiley-VCH GmbH.)

The circular economy and the depletion of Earth's resources highlight the need to transform waste into value-added emerging materials like carbon quantum dots (CQDs), which show great promise in energy storage, catalysis, and other applications. The production of catalytically active CQDs from biomass garners significant attention due to their unique advantages, such as ease of availability, natural abundance, renewability, low cost, and environmental friendliness. This review addresses the synthesis of CQDs from biomass, the factors influencing their properties and performance, and their diverse applications in catalytic hydrogenation reactions, selective reduction of nitroaromatic compounds, and azo dyes. Recent studies demonstrate that biomass-derived CQDs exhibit significantly improved catalytic activity, selectivity, and stability, effectively addressing the long-standing challenges of low activity and poor stability in catalysts derived from conventional sources., (© 2024 Wiley-VCH GmbH.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RBB has no conflicts to declare. RRN has no conflicts to declare. JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB, BMS, and AbbVie; and has received funding for investigator-initiated studies from Janssen and Pfizer.

Drugs intended to target mammalian cells can have broad off-target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non-antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off-target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose-dependent. We selected two representative simvastatin-sensitive species for more in-depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off-target effects of host-targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Purpose: Diabetic macular edema is one of the leading causes of vision loss across the world. Hard exudates at the macula can lead to structural abnormalities in the retina leading to irreversible vision loss. Systemic dyslipidemia and other modifiable risk factors when identified and treated early may help prevent substantial vision loss. The purpose of this study was to study the association between serum lipid levels and other systemic risk factors like hemoglobin, HbA1c, and serum creatinine with hard exudates and macular edema in patients with diabetic retinopathy., Methods: It is a prospective cross-sectional study conducted in a tertiary health care center in South India. 96 patients having diabetic retinopathy with hard exudates were included. Modified Airlie house classification was used to grade the hard exudates. Blood investigations including serum lipid profile, hemoglobin, HbA1c, and serum creatinine were carried out. Central subfield macular thickness was measured using optical coherence tomography., Results: 96 patients of type II DM with diabetic retinopathy were divided into three groups of hard exudates. A statistically significant correlation was observed between the severity of hard exudates and total cholesterol (p = 0.00), triglycerides (p = 0.00), LDL (p = 0.00), and VLDL (p = 0.00). HbA1c levels showed a statistically significant correlation with the severity of hard exudates (p = 0.09), no significant correlation was noted between hard exudates and hemoglobin levels (p = 0.27) and with serum creatinine (p = 0.612). A statistically significant association between CSMT and hard exudates (p = 0.00) was noted., Conclusion: In our study, we concluded that the severity of hard exudates is significantly associated with increasing levels of serum total cholesterol, triglycerides, LDL, VLDL, and HbA1c levels in type II DM patients presenting with diabetic retinopathy. The increasing duration of diabetes is significantly associated with increasing severity of hard exudates. Central subfield macular thickness increases with increasing severity of hard exudates in diabetic retinopathy., (© 2024. The Author(s).)

Autoimmune (or rheumatic) diseases are increasing in prevalence but selecting the best therapy for each patient proceeds in trial-and-error fashion. This strategy can lead to ineffective therapy resulting in irreversible damage and suffering; thus, there is a need to bring the promise of precision medicine to patients with autoimmune disease. While host factors partially determine the therapeutic response to immunosuppressive drugs, these are not routinely used to tailor therapy. Thus, non-host factors likely contribute. Here, we consider the impact of the human gut microbiome in the treatment of autoimmunity. We propose that the gut microbiome can be manipulated to improve therapy and to derive greater benefit from existing therapies. We focus on the mechanisms by which the human gut microbiome impacts treatment response, provide a framework to interrogate these mechanisms, review a case study of a widely-used anti-rheumatic drug, and discuss challenges with studying multiple complex systems: the microbiome, the human immune system, and autoimmune disease. We consider open questions that remain in the field and speculate on the future of drug-microbiome-autoimmune disease interactions. Finally, we present a blue-sky vision for how the microbiome can be used to bring the promise of precision medicine to patients with rheumatic disease., (© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)

Within the scope of this review, our exploration spans diverse facets of amphiphilic glycolipid-based low-molecular-weight gelators (LMWGs). This journey explores glycolipid synthesis, self-assembly, and gelation with tailorable properties. It begins by examining the design of glycolipids and their influence on gel formation. Following this, a brief exploration of several gel characterization techniques adds another layer to the understanding of these materials. The final section is dedicated to unraveling the various applications of these glycolipid-based supramolecular gels. A meticulous analysis of available glycolipid gelators and their correlations with desired properties for distinct applications is a pivotal aspect of their investigation. As of the present moment, there exists a notable absence of a review dedicated exclusively to glycolipid gelators. This study aims to bridge this critical gap by presenting an overview that provides novel insights into their unique properties and versatile applications. This holistic examination seeks to contribute to a deeper understanding of molecular design, structural characteristics, and functional applications of glycolipid gelators by offering insights that can propel advancements in these converging scientific disciplines. Overall, this review highlights the diverse classifications of glycolipid-derived gelators and particularly emphasizes their capacity to form gels., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The present investigation was planned to bridge the knowledge gap on spatiotemporal variations of pesticide pollution in small streams adjacent to paddy fields, and to visualize the associated risks in the aquatic ecosystems. We screened 106 pesticides using GCMSMS and LCMSMS from 10 small streams (n = 212, surface water samples) adjacent to paddy fields over seven months. Fifty-five pesticides were detected across different streams and months. The highest mean concentration was detected for fenobucarb (272 ng L -1 ), followed by thiamethoxam (199 ng L -1 ). The highest maximum concentration was detected for thiamethoxam ( 13,264 ng L -1 ), followed by triflumezopyrim ( 11,505 ng L -1 ). The highest detection frequency was recorded for fenobucarb (80.00%), followed by pretilachlor (79.00%). Out of the ten streams, Attabira stream had the highest mean number of pesticides detected in each sample. Maximum number of pesticides were detected in October followed by September. Pesticides namely, hexaconazole, pretilachlor, tricyclazole, fenobucarb and thiamethoxam were consistently detected across all streams. The risk assessment against the fishes, micro-invertebrates and algae were measured by risk quotient index (RQ). Twenty-five pesticides out of the detected pesticides (n = 55) had risk quotient values greater than 1. The highest RQ max values were observed in case of fenpropathrin followed by cyfluthrin-3. The highest RQ mean value was observed in case of cyfluthrin, indicating its higher toxicity to fishes. The present study reveals that small streams are polluted with pesticides and there is a need to develop strategies and policy interventions in regularizing the pesticide uses for reducing the pesticide pollution in aquatic systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (β-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms., (© Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research 2024.)

In developing countries like India, Linezolid is widely used for the treatment of Multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Long-term administration of Linezolid is reported to cause toxic optic neuropathy causing bilateral, progressive visual loss in patients. We report case details of three patients on anti-tubercular therapy presented to us with sudden, progressive, painless blurring of vision of both eyes the cause of which was confirmed to be toxic optic neuropathy due to linezolid. Subsequently, cessation of the drug resulted in complete visual recovery in two patients whereas one patient had minimal visual improvement due to secondary optic atrophy. Clinicians and health care workers need to be aware of sight threatening complications of Linezolid., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Malnutrition is a universal problem that has many forms. It affects all geographies, all age groups, and rich and poor people.The link between food insecurity and the health of populations has been established. Malnutrition commonly affects all groups in a community, but infants and young children are the most vulnerable because of their high requirements for growth and development. Hence, this study is taken up to assess existing household food insecurity, nutritional status, and various factors influencing the same among preschool children., Material and Methods: This was a cross-sectional study conducted in Anganwadis in the rural field practice area attached to Bangalore Medical College and Research Institute (BMCRI), Bengaluru. Based on the probability proportional to size (PPS) sampling method, 500 Anganwadi children aged three to six years were included in the study from nine Integrated Child Development Scheme (ICDS) blocks in Nelamangala, Bengaluru. Data were collected using a pre-validated, semi-structured questionnaire., Results: Among 500 study participants, 274 (54.8%) were boys and 226 (45.2%) were girls. Moderate underweight was seen in 13.87% of boys and 28.32% of girls. Severe underweight was seen in 6.57% of boys and 4.4% of girls. Moderate stunting was seen in 6.2% of boys and 21.68% among girls. Severe stunting was seen in 1.44% of boys and 0.88% of girls. Moderate wasting was seen in 12.41% of boys and 16.81% of girls. Severe wasting was seen in 2.19% of boys and 0.88% of girls. Mild food insecurity was seen in 11.65% of households, and moderate food insecurity was seen in 5.2% of households. There was a significant association between wasting and household food insecurity (p < 0.05), stunting, and household food insecurity (p < 0.05). There was a significant correlation between age and stunting, gender and stunting, and gender and underweight. On regression analysis, moderate food insecurity was 2.08 times higher and significantly associated with stunting., Conclusion: The prevalence of malnutrition was less than the NFHS 5 statistics in this study. Regular monitoring and analysis of food insecurity and malnutrition among children and women need to be done at the national, state, and regional levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, L et al.)

Recovery, recycling, and reuse of metal waste have been re-intensified in the current era to build a sustainable future. In this context, gel nanocomposites were formulated by in situ reduction of gold within the low molecular weight gel matrix of synthetic glycolipid amphiphiles without using any external reducing/stabilizing agents. This strategy aroused the interest in formulating gel nanocomposites with preferential uptake of gold. The exclusive advantages owned by gold nanoparticle (GNP) embedded hydrogel offer an alternative to decorate the electrode surface without physical deposition/plating of the catalyst. Formation of GNP within the gel matrix was confirmed by the SPR peak in the UV-Visible spectrum. The particle size of 5-7 nm with zeta potential value in the range of -30.5 to -41.4 mV displayed good stability of nanoparticles in the gel matrix. Due to the encapsulation of nanoparticles within supramolecular assemblies of gel, a noteworthy increase in viscoelastic strength was observed, whereas the gelation behavior, melting temperature, and original fibrillar morphology of hydrogel remained intact. This hybrid gel exhibited good ionic conductivity (2.36 × 10 -5 S cm -1 ) with appreciable ionic transport, remarkable oxygen reduction reaction (ORR) augmentation in reduction potential from 0 V to -0.12 V vs. Ag/AgCl as reference electrode, and excellent thermal stability in a wide temperature range. This green and efficient approach can pave the way for creating GNP-embedded hierarchical architecture that can act as bifunctional electrolyte/electrocatalyst material.

The environment and public health are currently being threatened by the water pollution caused by dyes. Finding eco-friendly and economically viable photocatalysts has been a hot issue in recent years, as photocatalytic dye degradation is essential for eliminating dye from contaminated water as compared to other methods because of the cost factor and efficiency in removing organic contaminants. Using un-doped ZnSe for degrading activity has very seldom been attempted up to this point. Therefore, the current research focuses on the use of zinc selenide nanomaterials, which are produced via a green synthesis process from the organic waste peels of orange and potato using the hydrothermal method, and utilizes them as photocatalysts for the degradation of dyes using sunlight as a natural source of light. The crystal structure, bandgap, and surface morphology and analysis of the synthesized materials serve as indicators of their characteristics. Citrate in orange peel-mediated synthesis assists in forming a particle size of 1.85 nm and a large surface area of 17.078 m 2 /g enabling more surface-active sites resulting in degradation efficiency of 97.16% and 93.61% for methylene blue and Congo red dye, respectively, which outperforms commercial ZnSe in the dye degradation. The presented work maintains overall sustainability in real-practical applications by utilizing sunlight in photocatalytic degradation activity instead of sophisticated equipment and using waste peels as a capping and stabilizing agent in the green synthesis method for the preparation of photocatalysts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time-consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein S imilarity algorithms that I dentify M icrobio M e E nzymatic R eactions (SIMMER). We show that SIMMER accurately predicts the responsible species and enzymes for a queried reaction, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. We validate these predictions on external datasets and provide an in vitro validation of SIMMER's predictions for metabolism of methotrexate, an anti-arthritic drug. After demonstrating its utility and accuracy, we made SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher's toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds., Competing Interests: AB, RN, AA No competing interests declared, PT Reviewing editor, eLife, KP is a consultant for Phylagen Inc, (© 2023, Bustion et al.)

Purpose: Increased screen time has been a major concern among the students who have adopted the online curriculum amid the pandemic. The study was conducted to shed light on the changing trends of symptoms pertaining to dry eye disease and digital eyestrain due to the online curriculum and its negative implications on the ocular health of students., Methods: A cross-sectional study was conducted among students of Manipal Academy of Higher Education who are currently following the E-learning curriculum amid the COVID-19 pandemic the participants were surveyed using a pre-validated structured questionnaire., Results: The mean age of study participants was 23.33 ± 4.604 years. In total, 97.9% (321/352) of the respondents experienced at least three symptoms associated with the usage of digital devices. 88.1% of the participants were exposed to an average screen time of more than 4 hours per day. An increased number of hours of digital device usage was found to be associated with higher total symptom scores (P = 0.04). The total symptom scores were found to be considerably higher for those with continuous contact with the screen (P = 0.02). Headache (69.9%, n = 246) is the most commonly reported symptom followed by neck pain (65.3%, n = 230), tearing (44.6%, n = 157), eye pain (40.9%, n = 144), and burning sensation (40.1%, n = 141)., Conclusion: This study highlights a tremendous increase in the prevalence of symptoms related to dry eye and digital eyestrain among students attending online classes during the COVID-19 pandemic. Eye care professionals need to be aware of this emerging public health threat and the appropriate measures for its prevention., Competing Interests: None

Background: Stroke vastly contributes to death and disability worldwide. Acute ischemic stroke (AIS) is caused by a reduction in supply of blood to the brain. Accumulation of unnecessary intracellular serum calcium in AIS induces the cytotoxic actions that activates enzymes involved in cell death. The present investigation assessed the relationship of total serum calcium level (at admission) and initial diffusion weighted imaging (DWI) infarct volume and correlated with National Institute of Health Stroke Scale (NIHSS) scores., Methods: A hospital-based observational study was conducted on 74 consecutive patients identified with AIS fulfilling the inclusion criteria. NIHSS scores and serum ionized calcium were calculated in every patient and compared with DWI infarct volume for assessing correlation between these three. Statistical software R Version 4.0.2 and Microsoft Excel were used for statistical analysis., Results: Out of the 74 patients, most of them were in age group of 50-69 years, with a male preponderance (68.9%). A significant association was noticed between diabetes and dyslipidemia with age (P=0.01499). A strong negative correlation was observed between NIHSS scores (at admission & discharge) with ionized calcium, while a strong positive correlation was noticed between stroke scores with infarct volume. A statistically significant negative correlation was recorded between serum calcium (on admission) and infarct size (r=-0.851755, P=0.0001). The mean of NIHSS scores on admission (8.24±5.19) has been remarkably higher when compared with NIHSS scores at discharge (5.25±3.89)., Conclusion: In patients with AIS examined within 6-24 hours of symptoms onset, serum ionized calcium and volume of infarct on DWI showed inverse association. Serum calcium serves as a marker of severity and acts as prognostic factor in AIS., Competing Interests: None declared.

A multicentric study is being conducted in which children with severe acute malnutrition (SAM) aged 6-59 months are identified with only weight-for-height z-score (WHZ) < - 3 criteria. The present study aimed to assess associations of anthropometric parameters and body composition parameters, to improve treatment of SAM. We conducted a cross-section assessment using the enrolment data of children who participated in a multi-centric longitudinal controlled study from five Indian states. Fat-free mass (FFM) and fat mass (FM) were determined by bio-electrical impedance analysis (BIA). Six hundred fifty-nine children were enrolled in the study using WHZ < -3 criteria. Available data shows that WHZ, WAZ and BMIZ were significantly associated with FFMI while MUACZ was significantly associated with both FMI and FFMI. Children with both severe wasting and severe stunting had significantly lower FFMI compared to those who were only severely wasted. All forms of anthropometric deficits appear to adversely impact FFM and FM.Trial registrationThe study is registered with Clinical Trial Registration of India (Registration No.: CTRI/2020/09/028013 dated 24/09/2020)., (© 2022. The Author(s).)

Designing of supramolecular hydro-/organogels having desired properties, biocompatibility, and stimuli responsiveness is a challenging task. Herein, the gelation ability of amphiphilic glycolipid-based gelators in a wide range of solvents is explored. The structure-function relationship was established by varying the chain length and polar headgroup size of amphiphilic gelators. The prepared hydro-/organogels were characterized by employing several techniques such as differential scanning calorimetry (DSC), rheology, field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), etc. The thermal stability of hydro-/organogels increased with an increase in chain length. Rheological analysis depicted that variation in chain length and headgroup size of amphiphilic gelators significantly affected the gel strength and stability. The self-assembled morphology of hydro-/organogel samples revealed the compact entangled fibrillar network structures. After comparing the energy-minimized molecular length with the d -spacing value obtained by XRD, interdigitated bilayer packing in the gel network was established. The bioactive encapsulation and enzymatic release study of hydro-/organogels portrayed their potential application in the biomedical field. To our delight, glycolipid 16M (C16 chain length) formed a molecular hydrogel with injectable and thixotropic behaviors. High critical strain value, thixotropy, injectability, thermoreversibility, and faster bioactive release for the 16M-W hydrogel proved crucial to predict its future applications. Overall, glycolipid amphiphiles designed by upholding proper hydrophilic-lipophilic balance can form multifunctional supramolecular hydrogels with excellent implementation in the drug delivery system.

Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity., Competing Interests: Declaration of interests P.J.T. is on the scientific advisory board for Kaleido, Pendulum, and SNIPRbiome. K.S.P. is on the scientific advisory board of Phylagen. S.V.L. is a co-founder, board member, and consultant for Siolta Therapeutics Inc. This work was partially supported by a MedImmune research grant., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Severe acute malnutrition (SAM) is a major underlying cause of mortality among children. Around one third of the world's acutely malnourished children live in India. The WHO recommends community-based management of acute malnutrition (CMAM) for managing children with SAM. In India, different states are implementing community-based SAM treatment programme, hereinafter called CSAM, using varieties of locally produced nutrient dense food items with different nutrient compositions. The study will assess the effectiveness of these state specific CSAM interventions., Methods: The longitudinal quasi-experimental study will be undertaken in two purposively selected blocks of one district each in the four intervention states and one comparison state. From each state, 200 SAM children identified using weight-for-length/height z-score (WHZ) < - 3 criteria will be enrolled in the study. Their anthropometric data and skinfold thickness will be taken on admission, at sixth week and at discharge by trained field investigators. Other child details, incidence of morbidity and socio-economic details will be collected on admission. To assess food consumption pattern including consumption of locally produced nutrient dense food supplements, dietary assessment, using 24-h dietary recall will be conducted on admission, at sixth week and at discharge. In addition, body composition parameters will be assessed for a sub-set of children using bio-electrical impedance analysis on admission and at discharge to analyse changes in total body water, fat-free mass, and fat mass. Post discharge, all study participants will be followed up monthly until 6 months. Atleast 10% of the sample will be checked for quality assessment. The study's primary outcome is cure rate defined as children attaining WHZ ≥ -2. Secondary outcomes include mean weight gain, mean length of stay, body composition parameters, relapse and mortality rates. Additionally, process evaluation and cost effectiveness analysis will be conducted., Discussion: There is a shortage of robust evidence regarding the effectiveness of locally produced nutrient dense food supplements provided as part of the CSAM intervention in India. This study will contribute to evidence on effective strategies to manage children with uncomplicated SAM in India. The study protocol has all necessary ethical approvals. Written informed consent will be obtained from caregivers of the children., Trial Registration: The study is registered with Clinical Trial Registration of India (Registration No.: CTRI/2020/09/028013 ) Date of registration 24/09/2020., (© 2021. The Author(s).)

Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest., Competing Interests: Declaration of interests K.N.L., P.S., and P.J.T. are listed inventors on a US provisional patent application related to this work (33167/55262P1). P.J.T. is on the scientific advisory boards for Kaleido, Pendulum, and SNIPRbiome. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the urine protein (UP) and urine creatinine (UC) ratio in diabetes mellitus and report its influence as a risk factor for the presence and severity of diabetic retinopathy (DR)., Methods: In total, 150 diabetic patients presenting to the outpatient department were included. Detailed history with informed consent and ophthalmic examination, including visual assessment, external ocular examination, anterior segment evaluation, dilated fundus examination by slit-lamp biomicroscopy, and indirect ophthalmoscopy, was done. The early morning spot urine sample was used to determine spot urine protein creatinine ratio. Association with hypertension, fasting blood sugar (FBS), and HBA1C (glycosylated Hb) were also noted., Results: Urinary PCR increased with the severity of the diabetic retinopathy (P < 0.001). HbA1c, FBS, and duration of diabetes had a direct correlation with urine PCR. ROC curve analysis showed that the optimal PCR cut-off value for predicting the risk of onset DR was 0.65. Retinopathy progressed with increasing urine PCR. Spot urine PCR strongly correlates with stages of diabetic retinopathy and proteinuria measured in 24-h urine samples., Conclusion: The study showed that urine PCR can be a marker for risk and progression of diabetic retinopathy.

Economically motivated adulteration of expensive coconut oil with low cost oil, like palm kernel oil and palmolein is difficult to detect and quantify by available methods primarily due to their overlapping physicochemical properties with coconut oil. In the present work, a HPLC method has been developed to detect and quantify the degree of adulteration of coconut oil with palmolein and palm kernel oil based on triglyceride structure. The normalized area percentage of trilaurin (C36) among the three major TAG molecular species dilaurin-monocaprin/myristin-caprylin-laurin (C34), trilaurin (C36) and dilaurin-monomyristin (C38) of coconut oil was chosen as detection index for quantifying degree of adulteration of coconut oil with palm kernel oil, while the area ratio of dipalmitoyl-monoolein: trilaurin was chosen as detection index for quantifying adulteration of coconut oil with palmolein. The RP-HPLC based method developed in the present work is effective with a 2-4% minimum detection limit of adulterant oils and 78-98% detection accuracy depending on the degree of adulteration and types of oil., Competing Interests: Conflict of interestThe Authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2021.)

Shi et al. (2021) in "Short-term Western diet intake promotes IL-23-mediated skin and joint inflammation accompanied by changes to the gut microbiota in mice" show that Western diet (WD) exacerbates an IL-23 minicircle‒mediated model of psoriasis and psoriatic arthritis, with an expansion of IL-17A‒expressing γδ T cells and shifts to the gut microbial community. WD-associated inflammation is mitigated by diet manipulation or antibiotic administration. These results suggest that dietary manipulation may be useful in the treatment of IL-23‒mediated disease, possibly through the modulation of the gut microbiota., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

We hereby report a successfully salvaged eye due to mycotic keratitis by Cylindrocarpon lichenicola in a 60-year-old female from Kasaragod (Kerala). The patient came with a history of pain, photophobia and decreased vision of the right eye. The microbiological investigations of the corneal scraping revealed C. lichenicola. C. lichenicola is a soil saprophyte. Since the ulcer worsened paracentesis followed by therapeutic keratoplasty and adjunct therapy with natamycin drops, voriconazole drops and oral ketoconazole was given. We stress that evidence-based timely medical and surgical intervention helped in the restoration of the vision in an infected eye., Competing Interests: None

Designing of multifunctional soft and smart materials from natural sources is a useful strategy for producing safer chemicals having potential applications in biomedical research and pharmaceutical industries. Herein, eight glycolipids with variation in unsaturation of hydrophobic tail and polar headgroup size were designed. The effect of unsaturation in the tail group and headgroup size on gelation ability, and mechanical and thermal stability of glycolipid hydro/organogels was studied to understand structure and property relationship. Glycolipids are functional amphiphilic molecules having potential applications in the field of drug delivery and metal removal. The encapsulation capacity and kinetic release behavior of hydrophobic/hydrophilic bioactives like curcumin/riboflavin from the hydrophobic/hydrophilic pockets of glycolipids hydro/organogels was examined. A significant observation was that the glucamine moiety of the glycolipid headgroup plays a vital role in removal of Cr and Cu from oil/water biphasic systems. Typical functions of the glycolipid hydrogels are metal chelation and enzyme-triggered release behavior, enabled them as promising material for Cr, Cu removal from edible oils and controlled release of water soluble/insoluble bioactives.

Biosourced surfactants are endeavored as a green alternative to biosurfactants and petrochemical surfactants having industrial utilization. Nine glycolipids with headgroup and chain length variation were derived from renewable resources like vegetable oils, carbohydrates, and amino acids. The concentration-dependent interfacial activity, foamability, wetting power, emulsification power, and solubilization capacities of glycolipids were investigated to provide a structure-activity relationship. Later, the metal flotation and emulsification experiments were performed. In general, for metal flotation, the surfactant should contain a hydrophobic tail, hydrophilic head, and chelating function. In the present investigation, it was observed that the headgroup of a glycolipid can serve as a hydrophilic head as well as perform a chelating function. Moreover, heat energy generated from the sunlight was utilized for metal flotation. Additionally, these glycolipids are capable to form stable sunflower oil-water (W/O and O/W) emulsions. The mechanical and thermal stabilities and hydrophobic chain length dependency of the prepared emulsions at different water volume fractions are explored. Furthermore, encapsulation and release of water-soluble (riboflavin and l-ascorbic acid) and oil-soluble (curcumin and α-tocopherol) bioactives in glycolipid emulsions were monitored. Thus, glycolipids under investigation had shown the possibility for pretreatment of chromium-containing wastewaters and bioactive-loaded emulsions toward the controlled release.

Encapsulation of a hydrophobic guest molecule inside a micelle and its stimuli-sensitive release is a useful strategy for target-specific drug delivery. Herein, nine biobased glycolipids were derived from plant sources. The influence of headgroup on the stability and aggregation pattern in water with different alkyl chain lengths was investigated to deduce the structure-property relationship. External factors, such as temperature, pH, and NaCl and urea concentrations, were employed to explore stimuli response of glycolipid nanoassemblies. Furthermore, solvatochromic dyes, such as pyrene, N-phenyl-1-naphthylamine, and curcumin, were utilized to examine hydrophobe loading capacities of these glycolipid assemblies. A fluorescence study was performed to investigate the enzyme-sensitive hydrophobe release. Interestingly, the pH-sensitive hydrophobic guests showed pH-responsive release from dynamic micelles. Finally, the synthesized glycolipids revealed their nanoassemblies as smart carriers for hydrophobic cargo.

Bacillus tequilensis strain CH had been previously shown to produce a biosurfactant. In this study, chemical structure of the purified biosurfactant was determined by using high performance liquid chromatography and liquid chromatography-mass spectroscopy as a 10 amino acid cyclic lipopeptide (CL). The cyclic lipopeptide was found to be active against Anopheles culicifacies larvae with a LC 50 of 110 µg/ml in 2 days. 1 ppm cadmium (Cd) which had a profound mutagenic effect on the cell division of onion ( Allium cepa ) root tip cell resulting in abnormal metaphase, abnormal anaphase and nuclei elongation was partially reversed in the presence of 0.1 mg/ml of CL (52% cells dividing normally and 8% with abnormal division) and was comparable to control experiment where no Cd was present. Thus, the CL described in this report may have applications in eliminating larvae from water repository systems and in reversing the effects of cadmium pollution., Competing Interests: Compliance with ethical standardsNo conflict of interest.

Silver nanoparticles are produced by a novel biosynthesis technique using fungus Penicillium purpurogenum NPMF (MTCC 7356). The biomass when subjected to heat treatment up to 700 °C produces the nanoparticles of silver due to the presence of free carbon which acts as encapsulation for silver nanoparticles. Increase in temperature above 700 °C causes a reduction in concentration of free carbon so that the nanoparticles come close to each other and form clusters in the shape of tetrapods to polypods. The micro-Raman analysis supports the formation of mesoporous carbon with increase in the calcined temperature. The formation of Ag nanostructures has been explained in terms of free energy diagram i.e., the crystal favors more to grow on (100) facet or (110) facet rather than on (111) facet by the addition of silver atoms and thereby, it releases more energy. The release of energy has been confirmed from the differential thermo gravimetric analysis. In fact, it is the dynamics of the minimization of the free energy of the system which governs the reorientation and rearrangement of Ag themselves leading to formation of various types of polypods. A formation mechanism is presented schematically.

Objective: Previous studies have shown that differential DNA methylation is associated with SLE susceptibility. How DNA methylation affects the clinical heterogeneity of SLE has not been fully defined. We conducted this study to identify differentially methylated CpG sites associated with nephritis among women with SLE., Methods: The methylation status of 428 229 CpG sites across the genome was characterised for peripheral blood cells from 322 women of European descent with SLE, 80 of whom had lupus nephritis, using the Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting for population substructure and leucocyte cell proportions was used to identify differentially methylated sites associated with lupus nephritis. The influence of genetic variation on methylation status was investigated using data from a genome-wide association study of SLE. Pathway analyses were used to identify biological processes associated with lupus nephritis., Results: We identified differential methylation of 19 sites in 18 genomic regions that was associated with nephritis among patients with SLE (false discovery rate q<0.05). Associations for four sites in HIF3A , IFI44 and PRR4 were replicated when examining methylation data derived from CD4+ T cells collected from an independent set of patients with SLE. These associations were not driven by genetic variation within or around the genomic regions. In addition, genes associated with lupus nephritis in a prior genome-wide association study were not differentially methylated in this epigenome-wide study. Pathway analysis indicated that biological processes involving type 1 interferon responses and the development of the immune system were associated with nephritis in patients with SLE., Conclusions: Differential methylation of genes regulating the response to tissue hypoxia and interferon-mediated signalling is associated with lupus nephritis among women with SLE. These findings have not been identified in genetic studies of lupus nephritis, suggesting that epigenome-wide association studies can help identify the genomic differences that underlie the clinical heterogeneity of SLE., Competing Interests: Conflicts of Interest: None declared.

Aim: To assess the intraocular penetration of 0.5% moxifloxacin hydrochloride into aqueous humour after oral and topical administration., Methods: A prospective, interventional study of 42 patients scheduled to undergo cataract surgery was carried out. Out of the 42 subjects, 21 were randomly categorised into Group I and received one drop of 0.5% topical moxifloxacin four times, at 15 min intervals starting 75 min before the surgery. Another 21 subjects were categorised into Group II and all subjects in this group were administered a single tablet of 400 mg of moxifloxacin, 12 h before the surgery. Estimation of moxifloxacin in aqueous samples was carried out using high-performance liquid chromatography. Results were analysed using Student unpaired 't' test and analysis of variance. The value of p<0.05 was considered to be significant., Results: Mean aqueous concentration of moxifloxacin attained in the oral group (n=21) was 0.504±0.30 μg/mL while that in the topical group (n=21) was 2.04±0.72 μg/mL, and this difference in levels was statistically significant (p<0.005). The levels attained by both the groups well exceeded the MIC90 (minimum inhibitory concentration of antibiotic required to inhibit growth of 90% of bacteria strains) levels for most of the organisms causing endophthalmitis. Penetration of moxifloxacin in aqueous in both the groups was not affected by gender, intraocular pressure or comorbidities significantly. However, aqueous levels were found to be higher among the younger subjects within the topical group., Conclusions: Moxifloxacin has an impressive spectrum of coverage and this pharmacokinetic study reinforces its potential as a prophylactic drug against intraocular infections, given the high aqueous levels post topical administration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Bionanotechnology has revolutionized nanomaterial synthesis by providing a green synthetic platform using biological systems. Among such biological systems, microalgae have tremendous potential to take up metal ions and produce nanoparticles by a detoxification process. The present study explores the intracellular and extracellular biogenic syntheses of silver nanoparticles (SNPs) using the unicellular green microalga Scenedesmus sp. Biosynthesized SNPs were characterized by AAS, UV-Vis spectroscopy, TEM, XRD, FTIR, DLS, and TGA studies and finally checked for antibacterial activity. Intracellular nanoparticle biosynthesis was initiated by a high rate of Ag(+) ion accumulation in the microalgal biomass and subsequent formation of spherical crystalline SNPs (average size, 15-20 nm) due to the biochemical reduction of Ag(+) ions. The synthesized nanoparticles were intracellular, as confirmed by the UV-Vis spectra of the outside medium. Furthermore, extracellular synthesis using boiled extract showed the formation of well scattered, highly stable, spherical SNPs with an average size of 5-10 nm. The size and morphology of the nanoparticles were confirmed by TEM. The crystalline nature of the SNPs was evident from the diffraction peaks of XRD and bright circular ring pattern of SAED. FTIR and UV-Vis spectra showed that biomolecules, proteins and peptides, are mainly responsible for the formation and stabilization of SNPs. Furthermore, the synthesized nanoparticles exhibited high antimicrobial activity against pathogenic gram-negative and gram-positive bacteria. Use of such a microalgal system provides a simple, cost-effective alternative template for the biosynthesis of nanomaterials in a large-scale system that could be of great use in biomedical applications.

Cells respond to variable environments by changing gene expression and gene interactions. To study how human cells response to stress, we analyzed the expression of >5000 genes in cultured B cells from nearly 100 normal individuals following endoplasmic reticulum stress and exposure to ionizing radiation. We identified thousands of genes that are induced or repressed. Then, we constructed coexpression networks and inferred interactions among genes. We used coexpression and machine learning analyses to study how genes interact with each other in response to stress. The results showed that for most genes, their interactions with each other are the same at baseline and in response to different stresses; however, a small set of genes acquired new interacting partners to engage in stress-specific responses. These genes with altered interacting partners are associated with diseases in which endoplasmic reticulum stress response or sensitivity to radiation has been implicated. Thus, our findings showed that to understand disease-specific pathways, it is important to identify not only genes that change expression levels but also those that alter interactions with other genes.

The present study offers the demonstration and rational design of two synthesized single chain pyridyl carboxylic acid (nicotinic acid) based amphiphilic gelators named the sodium salt of 2-dodecylpyridine-5-carboxylic acid (SDDPC) and the sodium salt of [2-dodecylpyridine-5-carboxylic]glycine (SDDPCG). The gelation abilities were tested in a series of organic solvents, by a number of physical methods including X-ray diffraction, FTIR spectroscopy, rheology, DSC, optical and electron microscopy. The minimum gelation concentration and gelation number of the gelators in different solvents were determined. No gelation was observed when pure solvents were employed. The gelation properties of these two compounds found that the gelation depends on H-bonding of the amide linkage. X-ray diffraction study indicates the presence of two recognizable morphologies for SDDPC in a gel-emulsion, whereas for SDDPCG a single type of aggregate is predominant. FTIR spectra suggest that the presence of intermolecular hydrogen bonding facilitates the gelation process. Rheological measurements demonstrated that the gel-emulsions are mechanically stable and exhibit typical viscoelastic properties. Optical microscopy images show a network structure in the gel phase and a fibril structure in the xerogel. SEM images confirmed the presence of network as well as a flex-like thick fibrous network for both the amphiphiles, forming three dimensional (3-D) networks. Both the gelators showed a remarkable response toward external pH. The gel-emulsions were used in the controlled and/or pH triggered release of entrapped (within the gel-emulsions) vitamin B 12 at different pHs.

Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq) and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated) genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past., Competing Interests: The authors have declared that no competing interests exist.

Two-photon absorption properties of 1,4-bis{4'-[N,N-bis(6''-trimethylammoniumhexyl)amino]styryl}benzene tetrabromide (C1) and its inclusion complexes (ICs) with cyclodextrins (CDs) have been studied. Upon complexation with CDs, the absorption spectra of C1 showed a slight red shift, whereas the emission spectra showed a blue shift with concomitant increase in the fluorescence quantum efficiency. A Stern-Volmer study using K(3)Fe(CN)(6) as a quencher revealed significant reduction in the photoinduced charge transfer quenching, in accord with the IC formation. Comparison of the spectroscopic results reveals that C1 forms increasingly more stable ICs in the order C1/beta-CD < C1/gamma-CD < C1/(3gamma:beta)-CD (gamma-CD/beta-CD 3:1, mole ratio). Moreover, the two-photon action cross section of C1 increased from 200 GM for C1 to 400 GM for C1/beta-CD, 460 GM for C1/gamma-CD, and 650 GM for C1/(3gamma:beta)-CD, respectively. Furthermore, the two-photon microscopy images of HeLa cells stained with C1 emitted strong two-photon excited fluorescence in the plasma membrane. These results provide a useful guideline for the development of efficient two-photon materials for bioimaging applications.

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in the condition called "ER stress," which induces the unfolded protein response (UPR), a complex cellular process that includes changes in expression of many genes. Failure to restore homeostasis in the ER is associated with human diseases. To identify the underlying changes in gene expression in response to ER stress, we induced ER stress in human B cells and then measured gene expression at ten time points. We followed up those results by studying cells from 60 unrelated people. We rediscovered genes that were known to play a role in the ER-stress response and uncovered several thousand genes that are not known to be involved. Two of these are VLDLR and INHBE, which showed significant increase in expression after ER stress in B cells and in primary fibroblasts. To study the links between UPR and disease susceptibility, we identified ER-stress-responsive genes that are associated with human diseases and assessed individual differences in the ER-stress response. Many of the UPR genes are associated with Mendelian disorders, such as Wolfram syndrome, and complex diseases, including amyotrophic lateral sclerosis and diabetes. Data from two independent samples showed extensive individual variability in ER-stress response. Additional analyses with monozygotic twins revealed significant correlations within twin pairs in their responses to ER stress, thus showing evidence for heritable variation among individuals. These results have implications for basic understanding of ER function and its role in disease susceptibility., (Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

We have synthesized amphiphilic copolymers using ring-opening metathesis polymerization (ROMP), a copper-catalyzed dipolar click reaction, and osmium-catalyzed dihydroxylation. The resulting copolymers were easily conjugated with folate and dye (indocyanine green) moieties, using a transamidation method. The copolymers exhibited high water solubility and formed nanometer-sized self-assemblies in aqueous medium. The amphiphilic copolymers modified by dihydroxylation of the polymer backbone exhibited much lower cmc values than the non dihydroxylated copolymer. Copolymers conjugated with folate moieties reduced the fluorescence intensity of aqueous polymer solutions both in vitro and in vivo, but their self-assemblies efficiently accumulated at tumor sites because of folate-receptor recognition at tumor tissue. The PEGylation of copolymers improved the stability of the self-assemblies in aqueous medium as well as the tumor site selectivity in vivo. Furthermore, the fluorescent nanoparticles consisting of PEG- and folate-conjugated ROMP-based copolymers accumulated in tumor tissue selectively and efficiently, whereas accumulation in all other normal organs was reduced. The PEGylation and folate conjugation can synergistically improve the in vivo tumor site selectivity of ROMP-based copolymers.

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes.

A polymer-surfactant micellar complex has been studied as a fluorescence resonance energy transfer (FRET) donor to fluorescein-labeled DNA (ssDNA-Fl). In water, the molar absorptivity and fluorescence quantum efficiency of cationic poly(fluorene-co-phenylene) (c-PFP) are substantially increased in the presence of non-ionic surfactants. A TEM microscopic study shows the formation of a nanowire micellar complex of c-PFP and the surfactants. About a 400% enhancement of the FRET signal is measured in c-PFP/ssDNA-Fl with Brij 30, relative to that without surfactants. The signal amplification is successfully modulated using different types of non-ionic surfactants which perturb the complexation, fine-structure of the complex (i.e., donor-acceptor separation), and the resulting energy transfer process., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

1. Frequency of Campylobacter detection was monitored in three flocks of turkeys. The effect of week of production was evaluated for hens in flocks 1 and 2, and the effect of week, gender and litter (fresh or used) was assessed for flock 3. 2. Gastrointestinal tracts, poult box liners, drinkers and faecal droppings were sampled. Conventional microbiological procedures were used to isolate and identify the presence of Campylobacter. Campylobacter latex agglutination tests were used for confirmation. 3. Peak colonisation occurred at approximately 3 weeks of production. Frequency of Campylobacter isolation from bird sources paralleled isolation from waterers. Frequency of detection from birds placed on used litter was lower than detection from birds placed on fresh litter (2% vs 58%). Gender did not affect frequency of detection. 4. Minimising peak colonisation at 3 weeks and managing litter are opportunities to reduce the occurrence of this organism in turkeys.