Role of Amyloidogenic and Non-Amyloidogenic Protein Spaces in Neurodegenerative Diseases and their Mitigation Using Theranostic Agents.

Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60-80 % of all dementia cases. Currently, there are no curative or disease-reversing/modifying molecules for many of the NDDs except a few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa which treat the disease-associated symptoms. Similarly, there are very few FDA-approved tracers such as flortaucipir (Tauvid) for tau fibril imaging and florbetaben (Neuraceq), flutemetamol (Vizamyl), and florbetapir (Amyvid) for amyloid imaging available for diagnosis. Recent advances in the cryogenic electron microscopy reported distinctly different microstructures for tau fibrils associated with different tauopathies highlighting the possibility to develop tauopathy-specific imaging agents and therapeutics. In addition, it is important to identify the proteins that are associated with disease development and progression to know about their 3D structure to develop various diagnostics, therapeutics and theranostic agents. The current article discusses in detail the disease-associated amyloid and non-amyloid proteins along with their structural insights. We comprehensively discussed various novel proteins associated with NDDs and their implications in disease pathology. In addition, we document various emerging chemical compounds developed for diagnosis and therapy of different NDDs with special emphasis on theranostic agents for better management of NDDs.

Intravoxel incoherent motion and diffusion kurtosis imaging and their machine-learning-based texture analysis for detection and assessment of prostate cancer severity at 3 T.

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

Determination of optimum levels of binding antibody units (BAU) of new quantitative chemiluminescent immuno-assay (CLIA) in COVID-19 vaccinated volunteer blood donors.

BACKGROUND: For assessment of COVID-19 vaccine efficacy, neutralization activity of anti-SARS-CoV-2 antibody is measured. This study was undertaken to determine optimum levels of binding antibody units (BAU/ml) in new quantitative chemiluminescent assay (CLIA) that corresponded to neutralizing potential (30% inhibition) of sVNT assay. METHODS: Ninety-one blood samples were analyzed by CLIA and sVNT assays. Test samples (n = 75) were collected from blood donors post-2nd vaccination dose, while control samples (n = 16) were archived pre-COVID donor samples. Correlation between CLIA and sVNT was calculated and receiver operating characteristic (ROC) curve was drawn and analyzed. RESULTS: Results indicated excellent correlation between 57.5 BAU/ml on CLIA and 30%inhibition on sVNT assay. ROC curve analysis revealed that the area under the curve (AUC) was 0.971. DISCUSSION: The present study determined that 57.5 BAU/ml on CLIA corresponded to 30% inhibition on sVNT assay. Periodic quantitative analysis.

Toll like receptor 4 (TLR4) gene polymorphism and its association with somatic cell score and milk production traits in Indian dromedary camels.

Our study aimed to explore the genetic variation in the Toll-like receptor 4 (TLR4) gene and establish its association with somatic cell score (SCS) and milk production traits in four Indian camel breeds namely Bikaneri, Kachchhi, Jaisalmeri and Mewari. TLR4 gene fragment of 573 bp spanning 5' UTR, exon-1 and partial intron-1 region was amplified and genotyped using the PCR-sequence based typing method. Only one SNP located at position C472T was identified. Genotyping revealed two alleles (C and T) and three genotypes: CC, CT and TT. The genotype frequencies for CC, CT and TT were 0.116, 0.326 and 0.558 and allele frequencies for C and T alleles were 0.279 and 0.721, respectively. Association study inferred that the effect of genotype on SCS, lactation yield (LY) and peak yield (PY) was non-significant however heterozygote (CT) genotypes recorded lower SCS and higher LY and PY. It can be concluded that the TLR4 gene possesses limited genetic variation, depicting polymorphism at a single locus in Indian camel breeds with a predominance of the TT genotype. The association study indicated that heterozygote animals possess better udder health and production performance, the statistical significance of which needs to be established using a large data set.

Point-of-care devices based on fluorescence imaging and spectroscopy for tumor margin detection during breast cancer surgery: Towards breast conservation treatment.

OBJECTIVE: Fluorescence-based methods are highly specific and sensitive and have potential in breast cancer detection. Simultaneous fluorescence imaging and spectroscopy during intraoperative procedures of breast cancer have great advantages in detection of tumor margin as well as in classification of tumor to healthy tissues. Intra-operative real-time confirmation of breast cancer tumor margin is the aim of surgeons, and therefore, there is an urgent need for such techniques and devices which fulfill the surgeon's priorities. METHODS: In this article, we propose the development of fluorescence-based smartphone imaging and spectroscopic point-of-care multi-modal devices for detection of invasive ductal carcinoma in tumor margin during removal of tumor. These multimodal devices are portable, cost-effective, noninvasive, and user-friendly. Molecular level sensitivity of fluorescence process shows different behavior in normal, cancerous and marginal tissues. We observed significant spectral changes, such as, red-shift, full-width half maximum (FWHM), and increased intensity as we go towards tumor center from normal tissue. High contrast in fluorescence images and spectra are also recorded for cancer tissues compared to healthy tissues. Preliminary results for the initial trial of the devices are reported in this article. RESULTS: A total 44 spectra from 11 patients of invasive ductal carcinoma (11 spectra for invasive ductal carcinoma and rest are normal and negative margins) are used. Principle component analysis is used for the classification of invasive ductal carcinoma with an accuracy of 93%, specificity of 75% and sensitivity of 92.8%. We obtained an average 6.17 ± 1.66 nm red shift for IDC with respect to normal tissue. The red shift and maximum fluorescence intensity indicates p < 0.01. These results described here are supported by histopathological examination of the same sample. CONCLUSION: In the present manuscript, simultaneous fluorescence-based imaging and spectroscopy is accomplished for the classification of IDC tissues and breast cancer margin detection.

IVIM-DKI for differentiation between prostate cancer and benign prostatic hyperplasia: comparison of 1.5 T vs. 3 T MRI.

OBJECTIVE: To implement an advanced spatial penalty-based reconstruction to constrain the intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model and investigate whether it provides a suitable alternative at 1.5 T to the traditional IVIM-DKI model at 3 T for clinical characterization of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Thirty-two patients with biopsy-proven PCa were recruited for MRI examination (n = 16 scanned at 1.5 T, n = 16 scanned at 3 T). Diffusion-weighted imaging (DWI) with 13 b values (b = 0 to 2000 s/mm2 up to 3 averages, 1.5 T: TR = 5.774 s, TE = 81 ms and 3 T: TR = 4.899 s, TE = 100 ms), T2-weighted, and T1-weighted imaging were used on the 1.5 T and 3 T MRI scanner, respectively. The IVIM-DKI signal was modeled using the traditional IVIM-DKI model and a novel model in which the total variation (TV) penalty function was combined with the traditional model to optimize non-physiological variations. Paired and unpaired t-tests were used to compare intra-scanner and scanner group differences in IVIM-DKI parameters obtained using the novel and the traditional models. Analysis of variance with post hoc test and receiver operating characteristic (ROC) curve analysis were used to assess the ability of parameters obtained using the novel model (at 1.5 T) and the traditional model (at 3 T) to characterize prostate lesions. RESULTS: IVIM-DKI modeled using novel model with TV spatial penalty function at 1.5 T, produced parameter maps with 50-78% lower coefficient of variation (CV) than traditional model at 3 T. Novel model estimated higher D with lower D*, f and k values at both field strengths compared to traditional model. For scanner differences, the novel model at 1.5 T estimated lower D* and f values as compared to traditional model at 3 T. At 1.5 T, D and f values were significantly lower with k values significantly higher in tumor than BPH and healthy tissue. D (AUC: 0.98), f (AUC: 0.82), and k (AUC: 0.91) parameters estimated using novel model showed high diagnostic performance in cancer lesion detection at 1.5 T. DISCUSSION: In comparison with the IVIM-DKI model at 3 T, IVIM-DKI signal modeled with the TV penalty function at 1.5 T showed lower estimation errors. The proposed novel model can be utilized for improved detection of prostate lesions.

Predictors of mortality in children admitted with SARS-CoV-2 infection to a tertiary care hospital in North India.

AIM: To compare the demographic, clinical, laboratory and radiological parameters of patients with different clinical outcomes (death or discharge) and analyse them to find out the potential predictors for mortality in children hospitalised with SARS-CoV-2 infection. METHODS: Retrospective chart review of all patients less than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and requiring hospital admission between 16 April 2020 and 31 October 2020. RESULTS: Of 255 children with SARS-CoV-2 infection, 100 patients (median age 62.5 months, 59% males, 70% with moderate to severe disease) were hospitalised, of whom 27 died (median age 72 months, 59% males and 30% severely underweight). The subgroup with comorbidities (n = 14) was older (median age 126 months) and had longer duration of stay (median 10 days). Fever and respiratory symptoms were comparable while gastrointestinal symptoms were more common among non-survivors. Hypoxia at admission (odds ratio (OR) 5.48, P = 0.001), multiorgan dysfunction (OR 75.42, P = 0.001), presence of acute kidney injury (OR 11.66, P = 0.001), thrombocytopenia (OR 4.40, P = 0.003) and raised serum C-reactive protein (CRP) (OR 4.69, P = 0.02) were independently associated with mortality. The median time from hospitalisation to death was 3 days. The deceased group had significantly higher median levels of inflammatory parameters and a higher incidence of complications (myocarditis, encephalitis, acute respiratory distress syndrome and shock). CONCLUSIONS: Hypoxia at admission, involvement of three or more organ systems, presence of acute kidney injury, thrombocytopenia and raised serum C-reactive protein were found to be independently associated with increased odds of in-hospital mortality in children admitted with SARS-CoV-2 infection.

Comparison of clinical and laboratory profile of survivors and non-survivors of SARS-CoV-2-related multisystem inflammatory syndrome of childhood in India: An observational study.

AIM: The SARS-CoV-2 pandemic is characterised by multiple reports of paediatric multisystem inflammatory disease or multisystem inflammatory syndrome in children (MIS-C) with Kawasaki disease-like features often complicated by myocarditis, shock and macrophage activation syndrome. Certain clinical and laboratory markers may be used to identify high risk cases. METHODS: All sequentially admitted patients hospitalised between April 2020 and October 2020, who met the WHO case definition for MIS-C were included. Data included patient demographic information, presenting symptoms, organ dysfunction and laboratory parameters. SARS-CoV-2 infection was diagnosed by nasopharyngeal swab real-time reverse transcription-polymerase chain reaction and/or rapid antibody test for SARS-CoV-2 as recommended. The clinical and laboratory criteria were compared in the survival and non-survival groups. RESULTS: A total of 29 patients with MIS-C were treated during the study period. There were 21 survivors and 8 non-survivors. The non-survivors had more neurocognitive and respiratory symptoms along with increased incidence of myocarditis compared with survivors. The serum levels of CPK-MB, D-dimer, ferritin and triglyceride were significantly raised in non-survivors as compared to survivors. CONCLUSION: The non-survivor group had higher CPK and greater proportion of children with troponin-T elevation indicating higher incidence of myocardial injury and necrosis. The D-dimer, ferritin and triglyceride were also higher in the mortality group, indicating the greater extent of inflammatory damage in this group.

Site-directed dual bioprobes inducing single-step nano-sandwich assay for the detection of cardiac troponin I.

Bioreceptor functionalized metallic nano-colloids have been identified as effective nanobioprobes to realize the detection of an analyte based on a common phenomenon of salt-induced aggregation. In marked contrast to this, we describe a nano-sandwich assay integrating the novel match-pair of aptamer and peptide functionalized gold nanoparticles. The site-directed biomolecular interaction of high affinity aptamer and peptide bioreceptors directed towards distinct sites of cardiac biomarker troponin I; this was found to form a nano-sandwich assay in a peculiar manner. The gold nanoconjugates interact with specific and distant regions of troponin I to result in collision of probes upon target identification. In the presence of TnI, both nanobioprobes bind at their respective sites forming a nano-sandwich pair providing a visual color change from red to blue. Thus, the presence of target TnI itself causes instant agglomeration in just a single-step without addition of any external aggregator. The assay imparts 100% specificity and 90% sensitivity in a dynamic concentration range of 0.1-500 ng/mL troponin I with detection limit as low as 0.084 ng/mL. The applicability of the assay has been validated in clinical samples of acute myocardial infarction patients thus establishing a promising point-of-care detection of TnI.

Acute Intermittent Porphyria in Prepubertal Child-diagnostic and Therapeutic Challenges in India: A Case Report and Literature Review.

Acute intermittent porphyria (AIP) is autosomal dominant metabolic disorder of adulthood with limited case reports in children. Literature review from Western countries shows that most children present with non-specific gastrointestinal and neuropsychiatric symptoms with no family history. Moreover, the attacks are recurrent and precipitated by various factors (drugs/infection). We describe the case of 11-year-old male child who presented with acute abdominal pain, seizures, hypertension, quadriparesis, neuropathy, and respiratory weakness necessitating ventilatory and intensive care. Diagnosis of AIP was suspected on basis of bedside urine testing and confirmed with hydroxymethylbilane synthase gene mutation study. Besides supportive therapy, child was managed successfully with intravenous hemin, an orphan drug, which was procured with great difficulty. This case is presented for highlighting the diagnostic and therapeutic challenges faced in management of such cases in a developing country. We also review Indian literature for similar cases and discuss the clinical presentation, diagnosis, and management of AIP in children. How to cite this article: Sharma AG, Pandit K, Gupta S, Kumar V. Acute Intermittent Porphyria in Prepubertal Child-diagnostic and Therapeutic Challenges in India: A Case Report and Literature Review. Indian J Crit Care Med 2022;26(3):390-394.

Characterisation of prostate cancer using texture analysis for diagnostic and prognostic monitoring.

Automated classification of significant prostate cancer (PCa) using MRI plays a potential role in assisting in clinical decision-making. Multiparametric MRI using a machine-aided approach is a better step to improve the overall accuracy of diagnosis of PCa. The objective of this study was to develop and validate a framework for differentiating Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) grades (grade 2 to grade 5) of PCa using texture features and machine learning (ML) methods with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC). The study cohort included an MRI dataset of 59 patients with clinically proven PCa. Regions of interest (ROIs) for a total of 435 lesions were delineated from the segmented peripheral zones of DWI and ADC. Six texture methods comprising 98 texture features in total (49 each of DWI and ADC) were extracted from lesion ROIs. Random forest (RF) and correlation-based feature selection methods were applied on feature vectors to select the best features for classification. Two ML classifiers, support vector machine (SVM) and K-nearest neighbour, were used and validated by 10-fold cross-validation. The proposed framework achieved high diagnostic performance with a sensitivity of 85.25% ± 3.84%, specificity of 95.71% ± 1.96%, accuracy of 84.90% ± 3.37% and area under the receiver-operating characteristic curve of 0.98 for PI-RADS v2 grades (2 to 5) classification using the RF feature selection method and Gaussian SVM classifier with combined features of DWI + ADC. The proposed computer-assisted framework can distinguish between PCa lesions with different aggressiveness based on PI-RADS v2 standards using texture analysis to improve the efficiency of PCa diagnostic performance.

Acute Kidney Injury in Hospitalized Children with COVID19.

BACKGROUND: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection. AIM: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting. METHODS: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group. RESULTS: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality. CONCLUSION: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.

Correction to: Biomethanol Production from Methane by Immobilized Co-cultures of Methanotrophs.

[This corrects the article DOI: 10.1007/s12088-020-00883-6.].

Biotin and Zn2+ Increase Xylitol Production by Candida tropicalis.

In this study, the medium requirements to increase the production of xylitol by using Candida tropicalis (CT) have been investigated. The technique of single addition or omission of medium components was applied to determine the nutritional requirements. The addition of amino acids such as Asp, Glu, Gln, Asn, Thr, and Gly had no significant effect on CT growth. However, in the absence of other metal ions, there was a higher concentration of cell growth and xylitol production when only Zn2+ was present in the medium. The analysis of various vitamins unveiled that biotin and thiamine were the only vitamins required for the growth of CT. Surprisingly, when only biotin was present in the medium as a vitamin, there was less growth of CT than when the medium was complete, but the amount of xylitol released was significantly higher. Overall, this study will increase the xylitol production using the single omission or addtion technique.

Practices of Initiation of Vasoactive Drugs in Relation to Resuscitation Fluids in Children with Septic Shock: A Prospective Observational Study.

Background: The role of vasoactive medications in septic shock is well-defined, but the appropriate time of initiation of these medications in reference to fluid boluses is not clear. We planned to study prospectively the practices and outcome of initiation of vasoactive infusions with respect to resuscitation fluids boluses in pediatric septic shock. Patients and methods: Children aged 1 month to 18 years diagnosed with septic shock were enrolled to receive fluid resuscitation boluses along with vasoactive drugs. The primary outcome was to look at various practices of the initiation of vasoactive infusions; accordingly, patients were categorized into three groups: N1 received vasoactive infusions after completion of the first bolus (20 mL/kg), N2 after the second (40 mL/kg), and N3 after the third fluid (60 mL/kg) bolus. Secondary outcomes were to compare the time taken, amount of fluid required to achieve hemodynamic stability, total fluid required, and complications in the first 24 hours of treatment and mortality. Results: Hundred children were enrolled and grouped into N1, N2, and N3 with 46, 10, and 44 patients, respectively. The volume of fluid required to achieve the resolution of shock in N1 (40 ± 10 mL/kg) was significantly less than in N2 (70 ± 10 mL/kg) and N3 (70 ± 20 mL/kg); p = 0.02. The time taken to achieve hemodynamic stability was significantly less in N1 (115 ± 45 minutes) than in N2 (196 ± 32 minutes) and N3 (212 ± 44 minutes); p = 0.02. The volume of intravenous fluid required in the first 24 hours (p = 0.02) and complications were lower in the N1 group (p = 0.04). No statistical difference in mortality was seen. Conclusion: Early initiation of vasoactive infusions (after the first bolus) resulted in less total fluid volume, lesser time to achieve hemodynamic stability, less fluid boluses, less length of stay in the pediatric intensive care unit, and lesser complications in the first 24 hours. Highlight: Early initiation of vasoactive infusions-after completion of the first fluid bolus resulted in less need for further fluid boluses, lesser time for shock resolution, lesser fluid overload, and less PICU stay-in pediatric septic shock. How to cite this article: Karanvir, Gupta S, Kumar V. Practices of Initiation of Vasoactive Drugs in Relation to Resuscitation Fluids in Children with Septic Shock: A Prospective Observational Study. Indian J Crit Care Med 2021;25(8):928-933.

Biomethanol Production from Methane by Immobilized Co-cultures of Methanotrophs.

Methanol production by co-culture of methanotrophs Methylocystis bryophila and Methyloferula stellata was examined from methane, a greenhouse gas. Co-culture exhibited higher methanol yield of 4.72 mM at optimum ratio of M. bryophila and M. stellata (3:2) compared to individual cultures. The immobilized co-culture within polyvinyl alcohol (PVA) showed relative efficiency of 90.1% for methanol production at polymer concentration of 10% (v/v). The immobilized co-culture cells within PVA resulted in higher bioprocess stability over free cells at different pH, and temperatures. Free and encapsulated co-cultures showed maximum methanol production of 4.81 and 5.37 mM under optimum conditions, respectively. After five cycles of reusage under batch conditions, free and encapsulated co-cultures retained methanol production efficiency of 23.8 and 61.9%, respectively. The present investigation successfully revealed the useful influence of co-culture on the methanol production over pure culture. Further, encapsulation within the polymeric matrix proved to be a better approach for the enhanced stability of the bioprocess.

A Metal-Free Domino Process for Regioselective Synthesis of 1,2,4-Trisubstituted Pyrroles: Application toward the Formal Synthesis of Ningalin B.

A new one-pot, transition-metal, acid/base-free domino process is developed for the regioselective synthesis of 1,2,4-trisubstituted pyrroles. The process involves 1,3-dipolar cycloaddition of unsymmetrical azomethine ylide resulting from the thermal C-C bond cleavage of unactivated aziridines with ß-bromo-ß-nitrostyrene, followed by a cascade of elimination and aromatization reaction sequence to preferentially furnish 1,2,4-trisubstituted pyrroles instead of the expected 1,2,3-trisubstituted pyrroles, in good to excellent yields. Further, the application of the methodology for the formal synthesis of ningalin B is delineated.

Scalable Total Syntheses of Some Natural and Unnatural Lamellarins: Application of a One-Pot Domino Process for Regioselective Access to the Central 1,2,4-Trisubstituted Pyrrole Core.

Short and scalable total syntheses of lamellarin G trimethyl ether, lamellarin D trimethyl ether, lamellarin H, lamellarin η, dihydrolamellarin η, and lamellarin U have been realized in four to six linear steps with an overall yield of ≤22%. Highlights of the synthesis include single-step access to the central 1,2,4-trisubstituted pyrrole core in a highly regioselective manner via a one-pot [3+2] cycloaddition/elimination/aromatization sequence-based domino process. Subsequent, palladium-mediated double C-H oxidative coupling in a single-pot operation provides access to the pentacyclic coumarin-fused pyrrolo-dihydroisoquinoline core present in lamellarins.

Relationship between mid-upper arm circumference and BMI for identifying maternal wasting and severe wasting: a cross-sectional assessment.

OBJECTIVE: To assess the strength of correlation and agreement between mid-upper arm circumference (MUAC) and BMI, and determine suitable MUAC cut-offs, to detect wasting and severe wasting among non-pregnant adult women in India. DESIGN: Cross-sectional studies were conducted in five high-burden pockets of four Indian states. SETTING: Prevalence of malnutrition among women and children is very high in these pockets and the government plans to implement community-based pilot projects to address malnutrition in these areas. PARTICIPANTS: Anthropometric measurements were carried out on 1716 women with children <5 years of age. However, analyses were conducted on 1538 non-pregnant adult women. RESULTS: The results showed a strong correlation between MUAC and BMI in the non-pregnant women, with correlation coefficient of 0·860 (95 % CI 0·831, 0·883; P < 0·001). Cohen's κ of 0·812 and 0·884 also showed good agreement between MUAC and BMI in identifying maternal wasting and severe wasting, respectively. The univariate regression model between MUAC and BMI explained 0·734 or 73 % of the variation in BMI. The MUAC cut-offs for wasting (BMI < 18·5 kg/m2) and severe wasting (BMI < 16·0 kg/m2) were calculated as 232 and 214·5 mm, respectively. CONCLUSIONS: MUAC is a strong predictor of maternal BMI among non-pregnant women with children <5 years in high-burden pockets of four Indian states. In a resource-constrained setting where BMI may not be feasible, the MUAC cut-offs could reliably be used to screen wasting and severe wasting in non-pregnant women for providing appropriate care.

Laser-line-driven phosphor-converted extended white light source with uniform illumination.

We report the development of laser-driven extended white light source designed as a light sheet for general illumination. This light sheet is made of two large diffused glass plates. A Ce:YAG phosphor layer was coated and sandwiched between the two diffusing sheets. The blue laser beam was first converted into a uniform laser line using a cylindrical lens, and a laser line was made incident parallel to the edges of the designed light sheet. The blue photons are waveguided inside the glass sheet via total internal reflection and scattered from the diffused surface. Some of the blue photons are absorbed by the Ce:YAG phosphor and down-converted into yellow light of longer wavelength. The white light emanating from the diffuse surface is the combined effect of yellow light with original blue light. The developed light sheet with the combination of laser line generation and total internal reflection is a unique and low-cost method for generating white light with uniform illumination. The details of the development of the light sheet and laser line generation are described. The experimental parameters, such as correlated color temperature and color coordinates, are reported.