Exploring laccase: a sustainable enzymatic solution for the paper recycling domain.

The global advocacy of resource conservation and waste management emphasizes the significance of sustainable practices, particularly in sectors such as paper manufacturing and recycling. Currently, conventional chemical methods are predominant for paper production, necessitating the use of substantial amount of toxic chemicals. This chemical-intensive approach compromises the recycled fiber quality, generates hazardous effluent causing serious ecological threats which triggers regulatory complexities for the mills. To address these challenges modern research suggests adopting sustainable eco-friendly practices such as employing enzymes. This review aims to explore the applicability of 'laccase' enzyme for paper recycling, investigating its properties and contribution to improved recycling practices. By delving into the potential application of laccase integration into the papermaking process, this article sheds light on the limitations inherent in traditional methods surmounted within both research and translational landscapes. Culture and process optimization studies, supporting the technological improvements and the future prospects have been documented.

Chemical characteristics, morphology and source apportionment of PM10 over National Capital Region (NCR) of India.

The present study frames the physico-chemical characteristics and the source apportionment of PM10 over National Capital Region (NCR) of India using the receptor model's Positive Matrix Factorization (PMF) and Principal Momponent Mnalysis/Absolute Principal Component Score-Multilinear Regression (PCA/APCS-MLR). The annual average mass concentration of PM10 over the urban site of Faridabad, IGDTUW-Delhi and CSIR-NPL of NCR-Delhi were observed to be 195 ± 121, 275 ± 141 and 209 ± 81 µg m-3, respectively. Carbonaceous species (organic carbon (OC), elemental carbon (EC) and water-soluble organic carbon (WSOC)), elemental constituents (Al, Ti, Na, Mg, Cr, Mn, Fe, Cu, Zn, Br, Ba, Mo Pb) and water-soluble ionic components (F-, Cl-, SO42-, NO3-, NH4+, Na+, K+, Mg2+, Ca2+) of PM10 were entrenched to the receptor models to comprehend the possible sources of PM10. The PMF assorted sources over Faridabad were soil dust (SD 15%), industrial emission (IE 14%), vehicular emission (VE 19%), secondary aerosol (SA 23%) and sodium magnesium salt (SMS 17%). For IGDTUW-Delhi, the sources were SD (16%), VE (19%), SMS (18%), IE (11%), SA (27%) and VE + IE (9%). Emission sources like SD (24%), IE (8%), SMS (20%), VE + IE (12%), VE (15%) and SA + BB (21%) were extracted over CSIR-NPL, New Delhi, which are quite obvious towards the sites. PCA/APCS-MLR quantified the similar sources with varied percentage contribution. Additionally, catalogue the Conditional Bivariate Probability Function (CBPF) for directionality of the local source regions and morphology as spherical, flocculent and irregular were imaged using a Field Emission-Scanning Electron Microscope (FE-SEM).

ARL6IP5 Ameliorates α-Synuclein Burden by Inducing Autophagy via Preventing Ubiquitination and Degradation of ATG12.

Recent advanced studies in neurodegenerative diseases have revealed several links connecting autophagy and neurodegeneration. Autophagy is the major cellular degradation process for the removal of toxic protein aggregates responsible for neurodegenerative diseases. More than 30 autophagy-related proteins have been identified as directly participating in the autophagy process. Proteins regulating the process of autophagy are much more numerous and unknown. To address this, in our present study, we identified a novel regulator (ARL6IP5) of neuronal autophagy and showed that the level of ARL6IP5 decreases in the brain with age and in Parkinson's disease in mice and humans. Moreover, a cellular model of PD (Wild type and A53T mutant α-synuclein overexpression) has also shown decreased levels of ARL6IP5. ARL6IP5 overexpression reduces α-synuclein aggregate burden and improves cell survival in an A53T model of Parkinson's disease. Interestingly, detailed mechanistic studies revealed that ARL6IP5 is an autophagy inducer. ARL6IP5 enhances Rab1-dependent autophagosome initiation and elongation by stabilizing free ATG12. We report for the first time that α-synuclein downregulates ARL6IP5 to inhibit autophagy-dependent clearance of toxic aggregates that exacerbate neurodegeneration.

Design, Synthesis, Molecular Docking Study and Biological Evaluation of Novel γ-Carboline Derivatives of Latrepirdine (Dimebon) as Potent Anticancer Agents.

A series of novel γ-Carboline derivatives were designed and synthesized using the Suzuki coupling reaction to identify the leads for the activity against cancer. Interestingly, these compounds were tested for their anticancer activity against the cell lines, particularly human cancer cell lines MCF7 (breast), A549 (lung), SiHa (cervix), and Colo-205 (colon). Most of the γ-Carboline derivatives showed potent inhibitory activity in four cancer cell lines, according to in vitro anticancer activity screening. Two compounds, specifically LP-14 and LP-15, showed superior activity in cancer cell lines among the γ-Carboline derivatives from LP-1 to LP-16. Additionally, the compound LP-14, LP-15 and Etoposide carried out molecular docking studies on human topoisomerase II beta in complex with DNA and Etoposide (PDB ID: 3QX3). The docking studies' results showed that the derivative LP-15 was strongly bound with the receptor amino acid residues, including Glu477 and DC8 compared with the marked drug Etoposide.

Functional Characterization of Non-Ankyrin Repeat Domains of Orientia tsutsugamushi Ank Effectors Reveals Their Importance for Molecular Pathogenesis.

Orientia tsutsugamushi is a genetically intractable obligate intracellular bacterium, causes scrub typhus, and has one of the largest known armamentariums of ankyrin repeat-containing effectors (Anks). Most have a C-terminal F-box presumed to interact with the SCF ubiquitin ligase complex primarily based on their ability to bind overexpressed Skp1. Whether all F-box-containing Anks bind endogenous SCF components and the F-box residues essential for such interactions has gone unexplored. Many O. tsutsugamushi Ank F-boxes occur as part of a PRANC (pox protein repeats of ankyrin-C-terminal) domain. Roles of the non-F-box portion of the PRANC and intervening sequence region (ISR) that links the ankyrin repeat and F-box/PRANC domains are unknown. The functional relevance of these effectors' non-ankyrin repeat domains was investigated. The F-box was necessary for Flag-tagged versions of most F-box-containing Anks to precipitate endogenous Skp1, Cul1, and/or Rbx1, while the ISR and PRANC were dispensable. Ank toxicity in yeast was predominantly F-box dependent. Interrogations of Ank1, Ank5, and Ank6 established that L1, P2, E4, I9, and D17 of the F-box consensus are key for binding native SCF components and for Ank1 and Ank6 to inhibit NF-κB. The ISR is also essential for Ank1 and Ank6 to impair NF-κB. Ectopically expressed Ank1 and Ank6 lacking the ISR or having a mutagenized F-box incapable of binding SCF components performed as dominant-negative inhibitors to block O. tsutsugamushi NF-κB modulation. This study advances knowledge of O. tsutsugamushi Ank functional domains and offers an approach for validating their roles in infection.

AdipoRon induces AMPK activation and ameliorates Alzheimer's like pathologies and associated cognitive impairment in APP/PS1 mice.

Alzheimer's disease (AD) is a progressive devastating neurodegenerative disorder characterized by extracellular amyloid beta (Aß42) plaque formation, hyperphosphorylation of tau protein leading to intracellular neurofibrillary tangle formation. Recently discovered hallmark features responsible for AD pathogenesis are neuronal insulin resistance, dysregulation in adiponectin and AMPK signaling. The presence of adiponectin and its receptor in the brain with its unique anti-diabetic effects and association with neurodegenerative diseases has raised our interest in exploring orally active small molecule adiponectin receptor agonist, AdipoRon. To date, all the available drugs for the treatment of AD provides symptomatic relief and do not stall the progression of the disease. Indeed, it is becoming increasingly apparent to find appropriate targets. Here, we attempt to shed lights on adiponectin receptor agonist, AdipoRon and its downstream molecular targets in reducing disease pathogenesis and insulin resistance. In brain, AdipoRon induced AMPK activation, increased insulin sensitivity, reduced amyloid beta plaque deposition and improved cognitive impairment. Levels of BACE were also downregulated while LDLR, APOE and neprilysin were upregulated promoting amyloid beta clearance from brain. AdipoRon further reduced the chronic inflammatory marker, GFAP and improved synaptic markers PSD-95 and synaptophysin in APP/PS1 mice. Our in-vitro studies further confirmed the potential role of AdipoRon in improving insulin sensitivity by increasing GLUT 4 translocation, glucose uptake and insulin signaling under hyperinsulinemic condition. Our findings suggest that AdipoRon could be a promising lead in the future treatment strategies in the development of effective AD treatment.

Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease.

In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure-activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC50 = 0.96 ± 0.14 µM, BChE IC50 = 1.23 ± 0.23 µM) compared to earlier identified lead molecule EJMC-G (AChE IC50 = 5.74 ± 0.13 µM, BChE IC50 = 14.05 ± 0.10 µM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC50 = 20.25 ± 0.26 µM) over the earlier identified EJMC-B (IC50 = 61.98 ± 0.30 µM) and it also was able to chelate iron. Co-treatment of 13b with H2O2, significantly attenuated and reversed H2O2-induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management.

Role of neuroimaging in children with first unprovoked seizure: A prospective observational study.

OBJECTIVE: To evaluate the incidence and type of neuroimaging abnormalities in first unprovoked seizure (FUS) in children. To investigate the association of neuroimaging abnormalities with clinical variables. METHODS: A prospective observational study enrolled children aged 6 months-14 years with FUS over one year at a tertiary-care teaching hospital, Northern India and subjected them to neuroimaging. Factors associated with abnormal neuroimaging were assessed using Chi square/Fischer Exact test. RESULTS: Out of 115 cases, 40 (34.8%) had abnormal neuroimaging. Frequent findings were inflammatory granuloma (70%) including Neurocysticercosis (NCC) (40%), ill-defined granuloma, calcified nodule and tuberculoma followed by white matter signal alterations. Inflammatory granuloma was significantly associated with age >2 years and focal seizures. Calcified nodule was more common in children >10 years. Other neuro-abnormalities like cerebral atrophy, gliosis, infarcts, and white matter changes were significantly prevalent with generalized seizures, perinatal asphyxia, and developmental delay. CONCLUSION: High prevalence of abnormalities in FUS, especially focal seizures, due to NCC warrants neuroimaging in all children with FUS in India.

Lactate Measurements and Their Association With Mortality in Pediatric Severe Sepsis in India: Evidence That 6-Hour Level Performs Best.

PURPOSE: To investigate association of static and dynamic lactate indices with early mortality (within 48 hours of admission), as well as need for vasopressors and mechanical ventilation in pediatric severe sepsis/shock. To explore optimal cutoffs of lactate indices. We hypothesized that dynamic indices are superior to static indices in predicting early mortality. METHODS: This prospective cohort study involved children (aged <14 years) admitted in emergency department, tertiary care teaching hospital in North India with severe sepsis/shock (2015-2016). Arterial lactate was measured at admission (X0) and after 6 hours (X6). Primary outcome of the measurement was early mortality. Association between lactate indices- lactate at 0 hours (Lac0), lactate after 6 hours (Lac6), time-weighted average (LacTW), delta (ΔLac), clearance (LacCl%) and early mortality, need for vasopressors, and mechanical ventilation-was assessed using Student t test/Mann-Whitney test. Area under the receiver operating characteristic curve (AUROC) for early mortality deduced for all lactate indices and compared with reference (Lac0). Optimal cutoffs (maximizing both sensitivity and specificity) and their positive predictive value (PPV) and negative predictive value (NPV) were determined. RESULTS: During the study period, 116 children were assessed. Septic shock was present at admission in 56.9% children; 50% of children died during the next 48 hours. Lac0, Lac6, and LacTW were significantly higher, and LacCl% was lower in nonsurvivors versus survivors (all P < .001). Lac6 (0.837 [0.76-0.91]) had significantly higher AUROC (95% confidence interval) than Lac0 (0.77; P = .03). Abnormal lactate metrics (higher Lac0, Lac6, LacTW, and lower LacCl%) were associated with vasopressors need and mechanical ventilation. On logistic regression, Lac6 emerged as an independent predictor of early mortality as well as vasopressor and mechanical ventilation need. The optimal cutoff of Lac6 for identifying early mortality with good sensitivity, specificity, PPV, and NPV was ≥2.65 (76, 85, 83, 78). CONCLUSIONS: Lactate6 is the best marker associated with early mortality and higher level of care in severe sepsis/septic shock in resource-poor regions.

Assessment of prevailing practices for identification of tuberculosis in children admitted in nutritional rehabilitation centres: A multicentre study.

Background & objectives: To eliminate tuberculosis (TB), the National TB Elimination Programme (NTEP) has given an algorithm for diagnosis and treatment of TB in children. This study was carried out to assess the prevailing practices to identify TB in severely malnourished children admitted to various nutrition rehabilitation centres (NRCs). Methods: A retrospective chart review of 41 NRCs across five States having a maximum number of NRCs was carried out. Details of children admitted to the NRCs and the investigations carried out in the form of obtaining X-ray film, tuberculin skin test (TST) and gastric aspirate for cartridge-based nucleic acid amplification test (CBNAAT) for diagnosis of TB over three months were collected. Results: A total of 2121 children with severe acute malnourished (SAM) across 41 NRCs (Bhopal, Jodhpur, Patna, Kolkata, Lucknow and Ratlam) were evaluated. X-ray of the chest was done in 473 (22%), TST was done in 135 (6%) and gastric aspirate was collected in 56 (3%) children. CBNAAT was done in only 56 SAM children. Ten children among those screened were confirmed to have pulmonary TB and were linked to treatment as per the National TB guidelines. Interpretation & conclusions: Although NTEP suggests universal screening of all malnourished children admitted in the NRCs, but the prevailing practices indicate that the NRCs are grossly under-utilizing molecular diagnostic tests for diagnosis of TB. There is a gap between prevailing practices and suggested guidelines for the identification of TB in children admitted in the NRCs.

Shock index is better than conventional vital signs for assessing higher level of care and mortality in severe sepsis or shock.

BACKGROUND: Conventional vital signs alone have limitations in determining the physiological status. Age-adjusted shock-index (SIPA), a comprehensive physiological variable, defined as the ratio of heart rate (HR) and systolic blood pressure (SBP) may be better at predicting hemodynamic stability and outcome than vital signs. OBJECTIVES: To compare discriminatory power of SIPA against vital signs in assessing higher level of care (vasopressor use and mechanical ventilation) and early mortality in severe sepsis/septic shock. METHODS: Prospective cohort study of 116children <14 years with severe sepsis/septic shock admitted at emergency department of a tertiary care hospital. Association between abnormal signs (raised heart-rate; HR, lower systolic blood-pressure; SBP, high SIPA) and higher level of care and early mortality at 0 and completed 6 hours (t0, t6) were assessed using univariate/multivariate analysis. Area-under-receiver-operating-characteristic curves (AUROC) of SIPA and conventional vital signs for outcome variables and their correlation with arterial lactate using Pearson's-coefficient were noted. RESULTS: High SIPA was independently associated with higher level of care i.e. vasopressor use, mechanical ventilation (AUROC t0: 0.698, 0.730; AUROC t6; 0.733, 0.735) as well as early mortality (AUROC t0: 0.638; AUROC t6:0.721) at t0 and t6. At t0, only high SIPA (r2 = 0.313) fairly correlated with arterial lactate (4.5 mmol/L). At t6, HR and SBP showed weak and SIPA (r2 = 0.434) demonstrated moderate correlation with arterial lactate. CONCLUSIONS: SIPA performs better than conventional vital-signs in recognising higher-level-of-care and early mortality.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

Identification of a HSP14-3-3 in Setaria cervi and its cross-reactivity with W bancrofti-infected human sera.

AIM: Identification of a 29 kDa heat stress protein in filarial parasite Setaria cervi and evaluation of its diagnostic potential against lymphatic filariasis. METHODS AND RESULTS: The Heat shock proteins (HSPs) were induced in filarial parasite S cervi by incubated at 42°C for 2 hours. The 10% SDS-PAGE of cytosolic extract showed several over-expressed bands. The MALDI-LC/MS analysis of 29 kDa band showed 100% similarity with Bm14-3-3 like protein 2. Multiple sequence alignment of Bm14-3-3 like protein 2 sequence with W bancrofti, Caenorhabditis elegans; Loa loa and Homo sapiens showed 100%, 86%, 83% and 78%, sequence similarity respectively. The antigenic efficacy of Sc14-3-3 protein was evaluated with different filarial sera using ELISA which showed cross-reactivity in order to Endemic Normal (EN) < Microfilaraemic (MF) < Chronic(CH) with IgG1 and EN < CH < MF in IgG4 ELISA. IgG1- and IgG4-specific immunoblotting with CH and MF sera further explicated its specific antigenic cross-reactivity. CONCLUSION: A 29 kDa heat shock protein of S cervi was identified as 14-3-3 protein having 100% homology to human filarial parasite B malayi. It showed strong reactivity with IgG1 and IgG4 subclass antibodies of W bancrofti-infected human sera suggesting that 14-3-3 protein could be used as a vaccine/ diagnostic marker.

Shock Index-A Useful Noninvasive Marker Associated With Age-Specific Early Mortality in Children With Severe Sepsis and Septic Shock: Age-Specific Shock Index Cut-Offs.

BACKGROUND: Aim of the study was to analyze the association of shock index (SI) from 0 to 6 hours with early mortality in severe sepsis/septic shock and to explore its age-specific cut-off values. To investigate association of change in SI over first 6 hours with early mortality. METHODS: A prospective cohort study of children (<14 years) admitted in emergency department, tertiary care hospital with severe sepsis or septic shock, divided into 3 groups: group 1: 1 month to <1 year; group 2: 1 to <6 years; group 3: 6 to 12 years. Shock index (SI = heart rate/systolic blood pressure) measured at admission (X0) and hourly till 6 hours (X1-6). Primary outcome was death within 48 hours of admission. Area under receiver operating characteristic curves were constructed for SI (0-6). Optimal cut-offs of SI 0 and SI 6, maximizing both sensitivity and specificity were determined and positive and negative predictive values (PPV, NPV) were calculated. RESULTS: From 2015 to 2016, 120 children were recruited. Septic shock was present at admission in 56.7% children. Early mortality was 50%. All hourly shock indices (SI 0-6) were higher among nonsurvivors in group 2 (P ≤ .03) and group 3 (P < .001). In group 1, SI after 2 hours was higher in nonsurvivors (P 2-6: ≤ .02). Area under receiver operating characteristic curves (95% CI) for SI at 0 hour was 0.72 (0.5-0.9), 0.66 (0.5-0.8), and 0.77 (0.6-0.9) and at 6 hours was 0.8 (0.6-1), 0.75 (0.6-0.9), and 0.8 (0.7-1) in 3 groups. The cut-off values of SI 0 (sensitivity; specificity; PPV; NPV) in 3 groups: 1.98 (77; 75; 67; 83), 1.50 (65; 65; 68; 63), and 1.25 (90; 67; 77; 83) and SI6: 1.66 (85; 80; 73; 89), 1.36 (73; 70; 73; 70), and 1.30 (74; 73; 78; 69). Improvement of SI over 6 hours was associated with better outcome. Children with higher SI at both time points had higher mortality than those with SI score below the cut-offs (P = .001). CONCLUSIONS: Age-specific SI cut-off values may identify children at high risk of early mortality in severe sepsis/septic shock and allow for better targeted management.

Community attitudes and gendered influences on decision making around contraceptive implant use in rural Papua New Guinea.

BACKGROUND: Despite targeted interventions to improve contraceptive implant acceptability and uptake in rural Papua New Guinea (PNG), ongoing use of this method remains limited. Previous literature has suggested community attitudes and intrinsic factors within the decision-making process may be negatively impacting on implant uptake, however these elements have not previously been studied in detail in this context. We set out to explore community attitudes towards the contraceptive implant and the pathways to decision making around implant use in a rural community on Karkar Island, PNG. METHODS: We conducted 10 focus-group (FGD) and 23 in-depth interviews (IDI) using semi-structured topic guides. Key sampling characteristics included age, exposure or non-exposure to implants, marital status, education and willingness to participate in discussion. Four FGDs were held with women, four with men and two with mixed gender. IDIs were carried out with five women (current implant users, former implant users, implant never users), five men, five religious leaders (Catholic and non-Catholic), four village leaders and four health workers. Two in-depth interviews (four participants) were analysed as dyads and the remaining participant responses were analysed individually. RESULTS: Men were supportive of their wives using family planning but there was a community-wide lack of familiarity about the contraceptive implant which influenced its low uptake. Men perceived family planning to be 'women's business' but remained strongly influential in the decision making processes around method use. Young men were more receptive to biomedical information than older men and had a greater tendency towards wanting to use implants. Older men preferred to be guided by prominent community members for decisions concerning implants whilst young men were more likely to engage with health services directly. CONCLUSIONS: In communities where a couple's decision to use the contraceptive implant is strongly coloured by gendered roles and social perceptions, having a detailed understanding of the relational dynamics affecting the decision-making unit is useful in targeting future healthcare interventions. Engaging groups who are reluctant to connect with health information, as well as those who are most influential in the decision making process, will have the greatest impact on increasing implant acceptability and uptake.

Hypophosphataemia in severe acute malnutrition: a prospective observational study.

Severe acute malnutrition (SAM) is a major cause of child mortality and morbidity. Children treated for SAM are at risk of refeeding hypophosphataemia (HP). The study was done to find out the incidence and various predictors of moderate/severe HP in SAM among North Indian children. This prospective observational study was conducted from August 2014 to July 2015 in the inpatients' department of Department of Paediatrics at King George's Medical University, Lucknow, Uttar Pradesh, North India, a tertiary care teaching hospital. Before inclusion, ethical approval and written informed consent was obtained. Included in the study were sixty-five children aged 6-59 months of age, who were admitted to the hospital with SAM as per the WHO guidelines. SAM was defined as a mid-upper arm circumference <115 mm and/or weight-for-height/length <-3 z-scores of the WHO growth standards and/or have bilateral oedema. Serum P levels were measured on admission and for five consecutive days after starting feed. HP was defined as mild, moderate and severe with a cut-off of 1·19-0·65, 0·65-0·32 and <0·32 mmol/l, respectively. About 60 % children had HP, with 20 % having moderate/severe HP at admission. The proportion of HP increased to 83·1 %, with 38·5 % having moderate/severe HP on day 3 after feeding. It was concluded that HP is a common biochemical abnormality in SAM. Considering its impact on the health of the child, serum P levels should be monitored in patients with SAM who are treated with enteral feeding.

Modulation of prion polymerization and toxicity by rationally designed peptidomimetics.

Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-ß2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity.

Benzothiophenes as Potent Analgesics Against Neuropathic Pain.

Neuropathic pain arises because of neuronal injury. Unlike inflammatory pain which can be managed by classical nonsteroid anti-inflammatory drugs (NSAIDs), neuropathic pain is difficult to treat. The classical NSAIDs work through inhibition of cyclooxygenase 2 (COX2) enzyme. However, COX2 inhibitors are insufficient to treat neuropathic pain. Hence, it becomes important to explore for novel molecules acting through cell surface molecules like ion channels, for the treatment of neuropathic pain. We investigated multiple bromobenzothiophene carboxamides for their efficacy against neuropathic pain. Interestingly, AS6 was found to be very effective in treating neuropathic pain through inhibition of Kv4.3 ion channel. AS6 also reduced the COX2 overexpression associated with neuropathic pain. These results as well as results from our previous study indicate that AS6 can be a potent antinociceptive agent against both inflammatory and neuropathic pain.

Temporal Variation of Phthalic Acid Esters (PAEs) in Ambient Atmosphere of Delhi.

Phthalic acid esters (PAEs) are a group of chemical species, ubiquitously present in the environment and pose a serious risk to humans. In the present study, the average concentrations of PAEs in PM10 (particulate matter ≤ 10 µm) are reported at a densely populated site in Delhi. The average concentration of PAEs was reported to be 703.1 ± 36.2 ng m-3 with slightly higher concentrations in winter than in summer; suggesting that sources are relatively stable over the whole year. The average concentration of PAEs was 35.7 ± 30.5 ng m-3 in winter, 35.4 ± 27.0 ng m-3 in summer, 3.4 ± 1.5 ng m-3 in monsoon and 7.5 ± 5.2 ng m-3 in post-monsoon. Principal component analysis was performed, which suggested that emissions were mainly due to plasticizers, cosmetics and personal care products, municipal solid waste, thermal power stations, industrial wastewater, cement plants and coke ovens.

Educating the handicraft factory workers about tobacco cessation and to assess its effectiveness by motivational interviewing: An Intervention study.

INTRODUCTION: Tobacco use is considered to be global pandemic. The study was done to assess the effectiveness of smoking cessation intervention among workers by motivational interviewing among handicraft factories, Jodhpur, Rajasthan. METHODOLOGY: An interventional study was carried out among 400 handicraft factory workers on the basis of inclusion and exclusion criterion. Twenty one handicraft factories were taken into consideration. Training, Standardization and Calibration of Examiners was carried out in the public health department. The structured pre-tested proforma and Fagerstrom questionnaire was used to record the data. Four sessions of intervention were given to workers. Follow ups were carried out after 1 month, 3month and 6month. Paired t-test was used to compare Fagerstrom/smoking analysis mean scores among study and control groups before and after intervention. RESULTS: showed that in study group, a percentage change of +1.2%, seen in high dependence category and -1.5 in very high dependence and after 6 months the change was+14.2%, 18.7%, -19.2% in Very low dependence, Low dependence, Medium dependence, -11.8% was seen in high dependence category and -1.8 in very high dependence. When comparison was done among Fagerstrom/smoking analysis mean scores among study subjects before and after intervention. It was found that there was a significant difference between the mean scores of Fagerstrom/smoking analysis between baseline - 3 months, 3 months to 6 months and 6 months to 9 months among study group as compared to control group. CONCLUSION: Tobacco addiction produces neurological and behavioural change, optima; approach involving behavioural change and pharmacotherapy are needed.