Interrogating the Mechanistic Features of Ni(I)-Mediated Aryl Iodide Oxidative Addition Using Electroanalytical and Statistical Modeling Techniques.

While the oxidative addition of Ni(I) to aryl iodides has been commonly proposed in catalytic methods, an in-depth mechanistic understanding of this fundamental process is still lacking. Herein, we describe a detailed mechanistic study of the oxidative addition process using electroanalytical and statistical modeling techniques. Electroanalytical techniques allowed rapid measurement of the oxidative addition rates for a diverse set of aryl iodide substrates and four classes of catalytically relevant complexes (Ni(MeBPy), Ni(MePhen), Ni(Terpy), and Ni(BPP)). With >200 experimental rate measurements, we were able to identify essential electronic and steric factors impacting the rate of oxidative addition through multivariate linear regression models. This has led to a classification of oxidative addition mechanisms, either through a three-center concerted or halogen-atom abstraction pathway based on the ligand type. A global heat map of predicted oxidative addition rates was created and shown applicable to a better understanding of the reaction outcome in a case study of a Ni-catalyzed coupling reaction.

Evaluation of Mitral-Aortic Flow Velocity Integral Ratio as a Tool to Differentiate Between Severe and Nonsevere Mitral Regurgitation.

OBJECTIVES: To evaluate mitral-aortic flow velocity integral ratio (MAVIR) as an echocardiographic tool to differentiate between severe and nonsevere mitral regurgitation (MR), compared with regurgitant volume (RVol) and effective regurgitant orifice area (EROA), with subgroup analysis in patients with calcific mitral valve, both by transthoracic (TTE) and transesophageal (TEE) echocardiography. Also, whether MAVIR can be used as a screening tool for severe MR. DESIGN: Prospective, cross-sectional, observational. SETTING: Cardiac operating room of a tertiary-care hospital. PARTICIPANTS: One hundred adult patients with chronic mitral regurgitation with at least mild MR by two-dimensional Doppler and with absence of mitral stenosis, aortic valve disease, and rhythm other than sinus scheduled for cardiac surgery. The subgroup (n = 24) consisted specifically of patients with a calcific mitral valve. INTERVENTIONS: Preinduction TTE and postinduction TEE in the operating room. MEASUREMENTS AND RESULTS: MAVIR, RVol, and EROA were measured in all patients both by TTE and TEE. Cohen's kappa statistics was employed to quantify concordance among RVol, EROA, and MAVIR. Diagnostic indices of MAVIR toward diagnosis of severe MR also were quantified. The results showed a strong agreement, in differentiating severe from nonsevere MR, between MAVIR and both RVol and EROA in the whole cohort (n = 100) and the subgroup (n = 24), both by TTE and TEE. Diagnostic indices were high for MAVIR compared with RVol and EROA in detecting severe MR, both by TTE and TEE. CONCLUSION: MAVIR may be used as an echocardiographic tool to differentiate between severe and nonsevere MR, even in patients with calcific valves. It also can be used to screen patients for severe MR.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Investigating Oxidative Addition Mechanisms of Allylic Electrophiles with Low-Valent Ni/Co Catalysts Using Electroanalytical and Data Science Techniques.

The catalysis by a π-allyl-Co/Ni complex has drawn significant attention recently due to its distinct reactivity in reductive Co/Ni-catalyzed allylation reactions. Despite significant success in reaction development, the critical oxidative addition mechanism to form the π-allyl-Co/Ni complex remains unclear. Herein, we present a study to investigate this process with four catalysis-relevant complexes: Co(MeBPy)Br2, Co(MePhen)Br2, Ni(MeBPy)Br2, and Ni(MePhen)Br2. Enabled by an electroanalytical platform, Co(I)/Ni(I) species were found responsible for the oxidative addition of allyl acetate. Kinetic features of different substrates were characterized through linear free-energy relationship (Hammett-type) studies, statistical modeling, and a DFT computational study. In this process, a coordination-ionization-type transition state was proposed, sharing a similar feature with Pd(0)-mediated oxidative addition in Tsuji-Trost reactions. Computational and ligand structural analysis studies support this mechanism, which should provide key information for next-generation catalyst development.

Prebiotic Membranes and Micelles Do Not Inhibit Peptide Formation During Dehydration.

Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first protocells would have hinged upon colocalization of these biopolymers with fatty acid membranes. Using atomic force microscopy, we find that a prebiotic fatty acid (decanoic acid) forms stacks of membranes after dehydration. Using LC-MS-MS (liquid chromatography-tandem mass spectrometry) with isotope internal standards, we measure the rate of formation of serine dipeptides. We find that dipeptides form during dehydration at moderate temperatures (55 °C) at least as fast in the presence of decanoic acid membranes as in the absence of membranes. Our results are consistent with the hypothesis that protocells could have formed within evaporating environments on the early Earth.

Acute onset movement disorders in diabetes mellitus: A clinical series of 59 patients.

BACKGROUND AND PURPOSE: No previous study has assessed the frequency and clinical-radiological characteristics of patients with diabetes mellitus (DM) and acute onset nonchoreic and nonballistic movements. We conducted a prospective study to investigate the spectrum of acute onset movement disorders in DM. METHODS: We recruited all the patients with acute onset movement disorders and hyperglycemia who attended the wards of three hospitals in West Bengal, India from August 2014 to July 2021. RESULTS: Among the 59 patients (mean age = 55.4 ± 14.3 years, 52.5% men) who were included, 41 (69.5%) had choreic or ballistic movements, and 18 (30.5%) had nonchoreic and nonballistic movements. Ballism was the most common movement disorder (n = 18, 30.5%), followed by pure chorea (n = 15, 25.4%), choreoathetosis (n = 8, 13.6%), tremor (n = 5, 8.5%), hemifacial spasm (n = 3, 5.1%), parkinsonism (n = 3, 5.1%), myoclonus (n = 3, 5.1%), dystonia (n = 2, 3.4%), and restless leg syndrome (n = 2, 3.4%). The mean duration of DM was 9.8 ± 11.4 years (89.8% of the patients had type 2 DM). Nonketotic hyperglycemia was frequently (76.3%) detected. The majority (55.9%) had no magnetic resonance imaging (MRI) changes; the remaining showed striatal hyperintensity. Eight patients with MRI changes exhibited discordance with sidedness of movements. Most of the patients (76.3%) recovered completely. CONCLUSIONS: This is the largest clinical series depicting the clinical-radiological spectrum of acute onset movement disorders in DM. Of note was that almost one third of patients had nonchoreic and nonballistic movements. Our findings highlight the importance of a capillary blood glucose measurement in patients with acute or subacute onset movement disorders, irrespective of their past glycemic status.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Premedication with Fentanyl for Less Invasive Surfactant Application (LISA): A Randomized Controlled Trial.

INTRODUCTION: Currently, there is no consensus regarding analgesic premedication before the surfactant administration by less invasive surfactant application (LISA) procedure. In this randomized controlled trial, we compared the level of comfort of preterm infants receiving fentanyl as analgesic and sedative versus no fentanyl during LISA procedure. METHODS: We randomized 34 preterm infants of 28+0-33+6 weeks of gestation with respiratory distress syndrome (RDS) within 6 h of birth to receive either fentanyl (1 µg/kg intravenous) or no premedication during surfactant administration by LISA procedure. Primary objective was to assess the proportion of preterm infants to be comfortable during the procedure [revised premature infant pain profile (R-PIPP) score ≤12] and secondarily complications occurring during the procedure, hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular hemorrhage (IVH) (≥ grade 3), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. RESULTS: Proportion of preterm infants with a R-PIPP score ≤12 during LISA was significantly higher in the fentanyl group [15/17 (88.23%) vs. 8/17 (47.05%); p value 0.025]. There were no differences in secondary outcome parameters. CONCLUSION: Low-dose fentanyl during LISA procedure resulted in more comfort in preterm infants and without increased complication of both the LISA procedure and fentanyl administration. Further studies are needed to determine the safest and most effective pharmacologic measures to prevent pain and discomfort during LISA.

Respiratory distress syndrome (RDS) in neonates is associated with prematurity, and surfactant administration is essential for its management. Surfactant instillation through a thin intratracheal catheter in spontaneously breathing infants with nasal continuous positive airway pressure (nCPAP) is known as less invasive surfactant application (LISA). Till date, there is no consensus regarding analgesic premedication before the surfactant administration by LISA procedure. In this randomized controlled trial, we compared the level of comfort of preterm infants receiving fentanyl as analgesic and sedative versus no fentanyl during LISA procedure. We reported that proportion of preterm infants with severe pain during LISA was significantly lower in the fentanyl group. There were no differences in clinical outcome parameters. So, we concluded that low-dose fentanyl during LISA procedure resulted in more comfort in preterm infants and without increased complication of both the LISA procedure and fentanyl administration.

Blood Pressure Variation with Altitudes in Children: A Cross-Sectional Observational Study from Himalayan Hills.

OBJECTIVES: We aimed to evaluate blood pressure (BP) in Indian children who had similar demographic characteristics but hailed from different altitudes. METHODS: BP of school going children, aged 5 to 12 years, at five different locations varying in altitude (near sea level: n = 425; 2000 feet: n = 244; 4000 feet: n = 248; 6000 feet: n = 242 and 8000 feet: n = 250) was measured in a mountainous district in Himalaya. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by aneroid sphygmomanometer in the sitting posture using a calibrated instrument and four trained resident doctors. The average of three readings was taken. RESULTS: Of the 1229 children whose data were analyzed, 50.4% were boys. SBP showed a progressive rise from 99.5 (4.00) mmHg [mean (standard deviation)] at near sea level to 106.7 (4.17) mmHg at 8000 feet. Similarly, DBP showed a rise from 60.1 (3.67) mmHg to 66.8 (4.58) mmHg over the same altitude range. Analysis of covariance for BP variation with altitude, with age as covariate, indicated a modest but statistically significant rise in both SBP and DBP with altitude. Higher BP values was noted among children residing at higher than at lower altitude (0.8% at sea level to 18.8% at 8000 feet). Correlations between SBP and DBP values and height and weight, though positive and significant at p < 0.01 level, were weak. CONCLUSIONS: These data will help in correct interpretation of BP readings in children residing at high altitude.

Hydroalkylation of Alkynes: Functionalization of the Alkenyl Copper Intermediate through Single Electron Transfer Chemistry.

We have developed a method for the stereoselective coupling of terminal alkynes and α-bromo carbonyls to generate functionalized E-alkenes. The coupling is accomplished by merging the closed-shell hydrocupration of alkynes with the open-shell single electron transfer (SET) chemistry of the resulting alkenyl copper intermediate. We demonstrate that the reaction is compatible with various functional groups and can be performed in the presence of aryl bromides, alkyl chlorides, alkyl bromides, esters, nitriles, amides, and a wide range of nitrogen-containing heterocyclic compounds. Mechanistic studies provide evidence for SET oxidation of the alkenyl copper intermediate by an α-bromo ester as the key step that enables the cross coupling.

A multicentre point prevalence survey (PPS) of antimicrobial use amongst admitted patients in tertiary care centres in India.

OBJECTIVES: Data from point prevalence surveys (PPSs) in India are scarce. Conducting PPSs is especially challenging in the absence of electronic medical records, a lack of dedicated resources and a high patient load in resource-poor settings. This multicentre survey was conducted to provide background data for planning and strengthening antimicrobial stewardship programmes across the country. METHODS: This inpatient PPS was conducted over 2 weeks in May 2019 simultaneously across five study centres in India. Data about patient characteristics, indications for antimicrobials use and details of each antimicrobial prescribed including supportive investigation reports were collected in predesigned forms. RESULTS: A total of 3473 admitted patients in wards and ICUs were covered across five study centres. Of these, 1747 (50.3%) patients were on antimicrobials, with 46.9% patients being on two or more antimicrobials. Out of the total antimicrobials prescribed, 40.2% of the antimicrobials were prescribed for community-acquired infection requiring hospitalization followed by surgical prophylaxis (32.6%). Third-generation cephalosporins and drugs from the 'Watch' category were prescribed most commonly. Only 22.8% of the antimicrobials were based on microbiology reports. CONCLUSIONS: The survey demonstrated a high use of antimicrobials in admitted patients with a considerable proportion of drugs from the 'Watch' category. The targets for interventions that emerged from the survey were: improving surgical prophylaxis, decreasing double anaerobic cover, initiating culture of sending cultures and de-escalation with targeted therapy.

Nasal HFOV versus nasal IPPV as a post-extubation respiratory support in preterm infants-a randomised controlled trial.

Early and successful extubation prevents several morbidities in preterm newborns. Several secondary non-invasive respiratory modalities exist but with their merits and demerits. Given the benefits of nasal high-frequency oscillatory ventilation (nHFOV), we tried to examine whether nHFOV could reduce reintubation rates compared to nasal intermittent positive pressure ventilation (NIPPV) during the post-extubation phase in preterm infants. Stratified randomisation based on gestational age was done for 86 mechanically ventilated preterm infants between 26 and 36+6 weeks of gestation within 2 weeks of age to receive either nHFOV or NIPPV post-extubation. The main objective was to compare extubation failure within 72 h following extubation and secondarily feed intolerance, intraventricular haemorrhage (IVH) (> grade 3), composite bronchopulmonary dysplasia (BPD)/mortality, composite duration of oxygen supplementation/ventilation support and SpO2/FiO2 ratio. No statistical difference was noted for primary outcome (RR 0.8, 95% CI: 0.23 to 2.78; p = 1.00) and secondary outcomes. However, nHFOV appeared possibly better in respect to feed tolerance rates and pCO2 washout.Conclusion: Extubation failure within 72 h in infants less than 37 weeks of gestation did not differ between the two groups. However, nHFOV seems promising in reducing enteral feeding issues and pCO2 elimination. Larger multicentre studies are required for exploring benefits of nHFOV.Trial registration: www.ctri.nic.in id CTRI/2019/07/020055, registration date July 5, 2019 What is Known: • NIPPV is superior to nCPAP as a secondary mode of respiratory support. • Synchronisation is preferred for optimum ventilation. What is New: • nHFOV, a novel non-invasive respiratory modality without need for synchronisation, appears promising as a secondary mode subject to further trials. • It seems promising in reducing enteral feeding issues and pCO2 elimination.

COVID-19 and Co-infection in Children: The Indian Perspectives.

BACKGROUND AND OBJECTIVES: Assessing the co-infections with COVID-19 is crucial to delineate its true clinical impact. Pediatric information in this aspect is limited. Our study aims to analyze the spectrum of co-infections in pediatric COVID-19 patients and determine the clinical as well as laboratory parameters predicting co-infection. METHODOLOGY: In this prospective observational study conducted from June to December 2020 in a single tertiary care institution, data pertaining to demographic, illness and treatment-related variables were analyzed among two subsets of pediatric patients of age 1 month-12 years with RT-PCR-confirmed COVID-19 infection-Group A: those with confirmed co-infection and Group B: moderate to severe disease without co-infection. Among Group A, etiology of co-infection was characterized through relevant microbiological examination within 48 h admission. RESULT: Among our study population, 15.03% and 20.6% had co-infections and moderate to severe disease respectively. Among those with confirmed co-infection, 32.5%, 11.6% and 6.97% recorded blood culture, respiratory secretion and CSF growth, respectively, the picture being dominated by Methicillin resistant and sensitive Staphylococcus aureus. Serum serology demonstrated Scrub typhus infection to be most prevalent. Concurrent respiratory viral infections were seen in 11.6%. Children with co-infection had significantly higher morbidity and need for supportive therapy. Predictors of co-infection were localization of infection, Neutrophil count ≥10×109, age-specific lymphopenia, CRP > 100 mg/dl and hyperferritinemia. CONCLUSION: Co-infections are an important factor prognosticating pediatric COVID infection. Their early detection, prompt and appropriate treatment is of paramount importance.

The disease presentation of Moyamoya angiopathy in Eastern India.

INTRODUCTION: Clinical spectrum of Moyamoya angiopathy (MMA) differs across populations with different ethnicity. This study, the largest one done among Indian population was undertaken to assess clinico-radiological profile of MMA patients in eastern India. METHODS: A single centre cross-sectional study was undertaken among 76 MMA cases. Each patient was evaluated for epidemiological, clinical and radiological characteristics. SPSS 25 was used for statistical analysis. P < 0.05 was taken as statistically significant. RESULTS: 36 (47.4%) were children without gender preponderance. There were female predominance among adults (male:female = 1:2.33). Mean age at onset of first neurological symptoms for children was 4.2 ± 2.0years, followed by 34.9 ± 58.2months of latency with final diagnosis at the mean age of 7.4 ± 3.5years. For adults, mean age of onset of first neurological symptoms was 31.5 ± 12.3years, followed by 14.7 ± 41.7months time gap and diagnosed at the mean age of 33.5 ± 12.5years. There was a statistically significant difference between child and adult regarding the diagnostic latency (p = 0.035). Fixed motor weakness (FMW) was the predominant symptom across the whole disease course. Among children predominant first neurological symptom was fixed motor weakness (FMW) (52.8%), followed by seizures (22.2%). FMW was predominant (55%) first neurological complaint, followed by headache (22.5%) among adults. Seizure was more prevalent among children both as first (p = 0.002) and presenting symptom at the time of diagnosis (p = 0.048). Over the course of the disease seizure was more common among children (p = 0.001), while headache was more common among adults (p = 0.017). Recurrence of symptoms was more common among children (p = 0.059). Infarcts were more common among children (91.7%) than adults (72.5%), while hemorrhage was seen only among adults (25%) (p = 0.004). Isolated cerebral cortex was involved more commonly among children (59.4%) than adults (36.1%), while isolated subcortical involvement was seen only among adults (19.4%) (p = 0.016). Majority of the MMA cases were of Suzuki stage 4 (39.5%) and 5 (27.6%). Brain atrophy was associated with diagnostic latency (p = 0.009). CONCLUSION: Indian Moyamoya presents similar to disease presentation in Caucasian and Japanese patients. It is a frequently overlooked cause of stroke in young, often with various non-motor presentations, failure to recognize which leads to delay in diagnosis. Radiological burden disproportionate to number of acute vascular events, with subtle neurological manifestations like headache or seizure, often with cognitive decline, should raise suspicion of MMA.

Stereospecific Synthesis of E-Alkenes through Anti-Markovnikov Hydroalkylation of Terminal Alkynes.

We have developed a method for stereospecific synthesis of E-alkenes from terminal alkynes and alkyl iodides. The hydroalkylation reaction is enabled by a cooperative action of copper and nickel catalysts and proceeds with excellent anti-Markovnikov selectivity. We demonstrate the broad scope of the reaction, which can be accomplished in the presence of esters, nitriles, aryl bromides, ethers, alkyl chlorides, anilines, and a wide range of nitrogen-containing heteroaromatic compounds. Mechanistic studies provide evidence that the copper catalyst activates the alkyne by hydrocupration, which controls both the regio- and diastereoselectivity of the overall reaction. The nickel catalyst activates the alkyl iodide and promotes cross coupling with the alkenyl copper intermediate.

Clinical Profile and Therapeutic Response of Scrub Typhus in Children: A Recent Trend from Eastern India.

OBJECTIVE: The aim of this study was to assess the clinico-laboratory parameters, complications and therapeutic responses in children with scrub typhus in Eastern India. MATERIALS AND METHODS: In this prospective, observational study, all children (age, <12 years) with suspected scrub typhus with a compatible clinical scenario were enrolled consecutively over six months. Cases confirmed by means of a positive IgM serology or a positive Weil-Felix reaction (OXK = 1/80 or above) were administered enteral doxycycline (4.5 mg/kg/day). RESULTS: Out of 94 recruited children, 61 had confirmed scrub typhus (mean age = 6.1 years, M:F = 1.1:1) with or without complications and having a considerably higher incidence of neurological presentation (meningoencephalistis n = 21, 34.4%). The most frequent manifestations included vomiting (n = 39, 63.9%), abdominal pain (n = 33, 54.1%), lymphadenopathy (n = 36, 59%), hepatosplenomegaly (n = 32, 52.5%), pedal edema (n = 32, 52.5%) and eschar formation (n = 30, 49.2%). Low hemoglobin levels, leukocytosis, thrombocytopenia, hypoalbuminemia, hyponatremia, increased liver enzymes and increased C-reactive protein were associated with delayed defervescence (>48 h). CONCLUSION: Scrub meningoencephalitis, with a notably higher incidence, showed favorable therapeutic response. Prompt and empiric doxycycline therapy could be lifesaving.

Photoinduced Copper-Catalyzed Coupling of Terminal Alkynes and Alkyl Iodides.

We have developed a photoinduced copper-catalyzed alkylation of terminal alkynes with primary, secondary, or tertiary alkyl iodides as electrophiles. The reaction has a broad substrate scope and can be successfully performed in the presence of ester, nitrile, aryl halide, ketone, sulfonamide, epoxide, alcohol, and amide functional groups. The alkylation is promoted by blue light (λ≈450 nm) and proceeds at room temperature in the absence of any additional metal catalysts. The use of a terpyridine ligand is essential for the success of the reaction and is shown to prevent photoinduced copper-catalyzed polymerization of the starting materials.

Catalytic Anti-Markovnikov Hydroallylation of Terminal and Functionalized Internal Alkynes: Synthesis of Skipped Dienes and Trisubstituted Alkenes.

We have developed catalytic anti-Markovnikov hydroallylation of terminal and functionalized internal alkynes. In this article, we describe the development of the reaction, exploration of the substrate scope, and a study of the reaction mechanism. Synthesis of skipped dienes through the hydroallylation of terminal alkyl and aryl alkynes with simple allyl phosphates and 2-substituted allyl phosphates is described. The hydroallylation of functionalized internal alkynes leads to the formation of skipped dienes containing trisubstituted alkenes. We demonstrate that the hydroallylation of internal alkynes can be used in the regio- and diastereoselective synthesis of complex trisubstituted alkenes. A mechanism of the hydroallylation reaction is proposed, and experimental evidence is provided for the key steps of the catalytic cycle. Stoichiometric experiments demonstrate an unexpected role of lithium alkoxide in the carbon-carbon bond-forming step of the reaction. A study of the hydrocupration of internal alkynes provides new insight into the structure, stability, and reactivity of alkenyl copper intermediates, as well as insight into the source of the regioselectivity in reactions of internal alkynes.

Detailed Mechanistic Studies on Palladium-Catalyzed Selective C-H Olefination with Aliphatic Alkenes: A Significant Influence of Proton Shuttling.

Directing group-assisted regioselective C-H olefination with electronically biased olefins is well studied. However, the incorporation of unactivated olefins has remained largely unsuccessful. A proper mechanistic understanding of olefination involving unactivated alkenes is therefore essential for enhancing their usage in future. In this Article, detailed experimental and computational mechanistic studies on palladium catalyzed C-H olefination with unactivated, aliphatic alkenes are described. The isolation of Pd(II) intermediates is shown to be effective for elucidating the elementary steps involved in catalytic olefination. Reaction rate and order determination, control experiments, isotopic labeling studies, and Hammett analysis have been used to understand the reaction mechanism. The results from these experimental studies implicate ß-hydride elimination as the rate-determining step and that a mechanistic switch occurs between cationic and neutral pathway. Computational studies support this interpretation of the experimental evidence and are used to uncover the origins of selectivity.

Epidemiology of dementia and its burden in the city of Kolkata, India.

OBJECTIVES: Increase in aging population is expected to lead to increasing prevalence of dementia in India. In this study, we aimed to determine prevalence, incidence, and mortality of dementia and its subtypes and assess dementia burden in terms of disability-adjusted life years (DALY). METHODS: A community study was conducted over 5 years (2003-2008) in Kolkata, India, on 100,802 (males 53,209) randomly selected subjects to assess prevalence and capture data on incident cases and deaths. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, based on Global Burden of Disease 2010 approach. RESULTS: During 2003-2004, there were 103 (men 55) cases of dementia. The prevalence was 1.53% (age adjusted 1.12%) at age ≥65 years. In those ≥55 years age, average annual incidence rate of dementia was 72.57 per 100,000. All-cause standardized mortality ratio in dementia cases was 4.74 (men 6.19, women 3.03). The burden of dementia in 2007-2008 revealed that overall YLL was 47.13 per 100,000 and YLD ranged from 1.87 to 16.95 per 100,000 depending on the clinical severity of dementia. The overall DALY lost per 100,000 due to dementia for the year 2007-2008 was 74.19. CONCLUSIONS: This community study revealed a low prevalence and incidence of dementia with consequent low DALY-derived burden of illness compared with many industrialized nations. YLL formed major component of DALY indicating premature mortality to be an outcome of dementia burden. Copyright © 2016 John Wiley & Sons, Ltd.