Molecular detection of Orientia tsutsugamushi in ectoparasites & their small mammal hosts captured from scrub typhus endemic areas in Madurai district, India.

BACKGROUND OBJECTIVES: Scrub typhus, caused by Orientia tsutsugamushi present in small mammals harbouring the ectoparasites. A study was undertaken to detect the pathogen present in small mammals and its ectoparasites in the scrub typhus-reported areas. METHODS: The small mammals (rodents/shrews) and its ectoparasites were screened for O. tsutsugamushi using nested PCR amplification of the groEL gene. Small mammals were collected by trapping and screened for ectoparasites (mites, ticks and fleas) by combing method. RESULTS: All the chigger mites collected were tested negative for O. tsutsugamushi . Interestingly, adult non-trombiculid mites ( Oribatida sp., Dermanyssus gallinae ), fleas ( Xenopsylla astia, X. cheopis, Ctenophalides felis and Ctenophalides sp.) and ticks ( Rhipicephalus sanguineus , R. haemaphysaloides ) screened were found to be positive for O. tsutsugamushi , which the authors believe is the first report on these species globally. Bandicota bengalensis with O. tsutsugamushi infection is reported for the first time in India. The O. tsutsugamushi groEL sequences from the positive samples were similar to the reference strains, Karp and Ikeda and phylogenetically clustered in clade IV with less evolutionary divergence. The blood samples of Rattus rattus , Suncus murinus and B. bengalensis collected from this area were tested positive for O. tsutsugamushi ; interestingly, the sequence similarity was much pronounced with their ectoparasites indicating the transmission of the pathogen to host or vice versa . INTERPRETATION CONCLUSIONS: The outcome of the present investigations widened our scope on the pathogens present in ectoparasites and rodents/shrews from this area. This will help to formulate the required vector control methods to combat zoonotic diseases.

Oxygen transfer reactivity mediated by nickel perfluoroalkyl complexes using molecular oxygen as a terminal oxidant.

Nickel perfluoroethyl and perfluoropropyl complexes supported by naphthyridine-type ligands show drastically different aerobic reactivity from their trifluoromethyl analogs resulting in facile oxygen transfer to perfluoroalkyl groups or oxygenation of external organic substrates (phosphines, sulfides, alkenes and alcohols) using O2 or air as a terminal oxidant. Such mild aerobic oxygenation occurs through the formation of spectroscopically detected transient high-valent NiIII and structurally characterized mixed-valent NiII-NiIV intermediates and radical intermediates, resembling O2 activation reported for some Pd dialkyl complexes. This reactivity is in contrast with the aerobic oxidation of naphthyridine-based Ni(CF3)2 complexes resulting in the formation of a stable NiIII product, which is attributed to the effect of greater steric congestion imposed by longer perfluoroalkyl chains.

Current status of mites and mite-borne diseases in India.

Mites act as the vectors of zoonotic vector-borne disease scrub typhus caused by the rickettsial pathogen Orientia tsutsugamushi. In India, scrub typhus is transmitted by the mite Leptotrombidium deliense. Rodents are the reservoirs and support the spread of this disease. Sarcoptes scabiei or the itch mite is causing scabies which is a common skin infection in India. Dermatitis, trombiculosis, and mite dust allergy are common mite-borne diseases transmitted by Pyemotidae family. D. brevis folliculorum and Demodex brevis are two major mite species found on humans also causing a disease; "Demodicosis", common in India. Dermanyssus gallinae, fowl mite causes pruritis in poultry birds, transmits infections to poultry workers when they come into contact with birds. There is a re-emergence of mite-borne diseases, especially scrub typhus, in many parts of India requiring urgent attention for its control. This review is aimed to update the available information on mites and mite transmitted diseases prevalent in India to highlight the importance of rodent and chigger mite vector control to prevent forthcoming mite-borne diseases in India.

Heterometallic bond activation enabled by unsymmetrical ligand scaffolds: bridging the opposites.

Heterobi- and multimetallic complexes providing close proximity between several metal centers serve as active species in artificial and enzymatic catalysis, and in model systems, showing unique modes of metal-metal cooperative bond activation. Through the rational design of well-defined, unsymmetrical ligand scaffolds, we create a convenient approach to support the assembly of heterometallic species in a well-defined and site-specific manner, preventing them from scrambling and dissociation. In this perspective, we will outline general strategies for the design of unsymmetrical ligands to support heterobi- and multimetallic complexes that show reactivity in various types of heterometallic cooperative bond activation.

A review of public health important fleas (Insecta, Siphonaptera) and flea-borne diseases in India.

Fleas (Insecta, Siphonaptera) are important vectors of plague and murine typhus in many parts of the world. Currently, about 2700 flea species were described in the world. The most common vector flea Xenopsylla cheopis is found throughout India, but X. astia, and X. brasiliensis are found less and limited in distribution associated with the domestic rats such as Rattus rattus, R. norvegicus, Mus musculus, and Bandicota bengalensis. Bubonic plague is a major flea-borne disease caused by the bacterial pathogen Yersinia pestis, transmitted from rats to humans via the rodent flea, X. cheopis. A major outbreak of plague and high mortality occurred in India. After 1966 with the 3 decadal intervals, plague cases occurred only during the year 1994 reported in 5 different states (Gujarat, Maharashtra, Karnataka, Uttar Pradesh, Madhya Pradesh and New Delhi and subsequently plague cases occurred during 2002 and 2004 after the one-decade interval in Himachal Pradesh (2002). Another outbreak of bubonic plague was reported in Dangud village, Barkhot tehsil, Uttarkashi district, Uttarakhand during October 2004. Ctenocephalides fleas are common in cats and dogs, which are the main vectors of bacteria rickettsiae, such as Rickettsia typhi, R. felis, R. conorii, and Bartonella henselae. Molecular and serological evidence also confirms the presence of R. typhi, R. conorii R. felis and B. henselae pathogens in cats and other fleas in India. Flea bites and flea-borne dermatitis are common in men and pet animals. Because of the re-emergence of the plague, updated information on fleas and flea-borne diseases are essential to control the flea vectors and flea-borne diseases in India. Hence, this comprehensive review updates the available information on fleas and fleas transmitted diseases in India.

Seasonal Diversity of mosquito species in Dakshina Kannada district, Karnataka, India.

BACKGROUND & OBJECTIVES: Dakshina Kannada is one of the districts of Karnataka state of India with high incidences of mosquito-borne diseases, especially malaria and dengue. The larval stages of the mosquitoes are very important in determining the prevalence of adult mosquitoes and associated diseases. Hence, the occurrence of mosquito species was investigated by sampling different water bodies present in the Dakshina Kannada district from June 2014 to May 2017. METHODS: Random sampling was carried out from permanent and temporary, artificial and natural water bodies belonging to 11 types of microhabitats using dippers and suction pumps. RESULTS: A maximum of 37 mosquito species belonging to 12 genera were recorded with the dominant genera being Culex. Most species have been recorded from temporary bodies of water with the highest number of species in receptacles. Monsoon is the most productive season, both in terms of occurrence and abundance followed by post-monsoon and pre-monsoon. The abundance of mosquito larvae was significantly higher in temporary water bodies compared to the permanent. INTERPRETATION & CONCLUSION: Abundant rainfall in the study area which produces many natural and domestic temporary water bodies accounts for mosquito breeding throughout the year.

Dengue infection among tribal population in the Nilgiris district, Tamil Nadu, India.

BACKGROUND & OBJECTIVES: Dengue emerged as an important public health problem in Tamil Nadu from 2000 onwards, reported in all the districts as an endemic disease of Tamil Nadu except Nilgiris district. So this study was carried out to understand the dengue epidemiology in Nilgiris district. METHODS: Block-wise study was made at the Nilgiris district. The clinicians at the Nilgiris Adivasi Welfare Association hospitals (NAWA) situated in Kotagiri, Kozhikarai and Primary Health Centers from Kunjpannai, Arayoor, and Soloor Mattam, examined and recorded symptoms and collected blood samples from the dengue-suspected patients. These samples were centrifuged at 4°C and stored. Serum samples (267 nos.) collected from dengue-suspected patients for two years period from 2014 to 2016 were screened for dengue infection. RESULTS: First year study conducted during 2014-15 showed 13 dengue positives (8.39%) mainly from Kotagiri block (9 nos. - 69.2%) and the second year study conducted during 2015-16 showed 12 dengue positives (10.71%) found mostly from Udagamandalam block (6 nos.- 50%). People belonging to 6 different tribes - Irular, Toda, Kota, Kurumba, Kattunaickan, and Paniya were found infected with dengue and more Irular positives were recorded in both the years (5 Irular-2014-15 & 11 Irular -2015-16). First year detected more female positives (92.3%) whereas the second year showed 5 males (41.7%) and 7 females (58.3%). INTERPRETATION & CONCLUSION: This study unearthed the hidden disease dengue to be prevalent among the tribal community and emphasized the need for the establishment of a permanent dengue surveillance system with improved disease diagnostics, to initiate effective vector control efforts to stop dengue transmission from this hilly region.

Physician Health in the Times of COVID-19.

BACKGROUND AND OBJECTIVES: A virtual registry study evaluating real world evidence on physicians' use of prophylactic regimens for protection against SARS-CoV-2. This paper summarizes the interim results. METHODS: Asymptomatic physicians at risk of acquiring SARS-CoV-2 responded to online questions at baseline and 7 weeks post-baseline. Baseline data included demographics, prophylaxis regimen (including "no prophylaxis") and start date. Participants who provided complete week-7 data (information on type of health facility [COVID/Non-COVID], number of presumed/confirmed cases exposed to, PPE use, SARS-CoV-2 testing and symptoms, regimen adherence and intercurrent illness) comprised the Completer population. Limited data (regimen adherence, SARS-CoV-2 testing) was collected for participants who failed to provide complete week7 data. Those providing limited/complete information comprised the Evaluable population. RESULTS: Of 369 enrolled participants, 182 (mean age 42±11.05 years) comprised the Evaluable population. They showed a male preponderance (67.6%). Practitioners from Maharashtra (59.9%) and specialties of Pediatrics, Internal Medicine, Anesthesiology and Critical Care (63.2%) accounted for the majority. ICMR's HCQ prophylaxis regimen was initiated by 125 (68.7%) participants with 31 (17%) initiating 'No prophylaxis'. The highest adherence was for the ICMRregimen (87.2%). In the Completer population comprising 150 participants, 87 were exposed to presumed (81) and/or confirmed cases (60). Most exposures to confirmed cases (49, 81.7%) were high-risk. PPE use was generally high (75-100%). Most participants (94.7%) did not report an AE. The proportions with an AE was similar with ICMR regimen (5.9%) and no prophylaxis (6.5%). INTERPRETATION AND CONCLUSIONS: Physicians in India preferred ICMR's HCQ regimen. The regimen appears to be safe and associated with a high level of adherence.

A K-arylacetylide complex for catalytic terminal alkyne functionalization using KOtBu as a precatalyst.

Herein we report a transition metal free catalytic terminal alkyne functionalization across the C-X triple bond (X = CH and N) with E-selective homo (alkyne-alkyne) and head-to-tail selective hetero (alkyne-nitrile) dimerization. A series of stoichiometric reactions enabled us to crystallize a reactive organometallic intermediate K-arylacetylide complex which was characterized by X-ray crystallography, indicating that an ionic mechanism is operative.

Transition-Metal-Free Catalytic Carboalkoxylation of Styrenes at Room Temperature.

Herein, we describe the first transition-metal-free catalytic carboalkoxylation of styrenes with aryl diazonium salts by Meerwein addition in the presence of a phenalenyl ligand at room temperature without requiring any light stimulation. This three-component reaction allows facile difunctionalization of styrene derivatives with various alcohols (such as 1, 2, and 3°) as the source of alkoxy group during this transformation. The key intermediates and the transition states involved in this reaction path were unraveled by a series of control experiments coupled with density functional theory calculations. The full mechanistic investigation provides an understanding of the selectivity toward carboalkoxylation (Meerwein arylation addition elimination) in the presence of various alcohols over the simple arylation to multiple bond (Meerwein arylation-elimination) reaction.

Transforming atmospheric CO2 into alternative fuels: a metal-free approach under ambient conditions.

This work demonstrates the first-ever completely metal-free approach to the capture of CO2 from air followed by reduction to methoxyborane (which produces methanol on hydrolysis) or sodium formate (which produces formic acid on hydrolysis) under ambient conditions. This was accomplished using an abnormal N-heterocyclic carbene (aNHC)-borane adduct. The intermediate involved in CO2 capture (aNHC-H, HCOO, B(OH)3) was structurally characterized by single-crystal X-ray diffraction. Interestingly, the captured CO2 can be released by heating the intermediate, or by passing this compound through an ion-exchange resin. The capture of CO2 from air can even proceed in the solid state via the formation of a bicarbonate complex (aNHC-H, HCO3, B(OH)3), which was also structurally characterized. A detailed mechanism for this process is proposed based on tandem density functional theory calculations and experiments.

Emergence of dengue in the tribal pockets of Nilgiris district, Tamil Nadu.

As original tribal ways of living have morphed from a forest dweller existence, dengue is no longer an urban infection but is now also found in rural hilly areas. The spread of dengue is enhanced by the frequent movement of people to endemic areas where there is a vector mosquito presence. The impact of the virus is known to be great in the immunologically naive population. Our study reports on the threat of the dengue virus in these hilly areas.

Drug Transporters: Advances and Opportunities.

Drug transporter research conducted over the last several decades has led to a greatly advanced understanding of the mechanisms underlying the principles of drug absorption and disposition. Although many transporters remain poorly characterized, there is ample evidence that the drug transporter field will ultimately provide vital support to routine patient management, and will play a key role in the discovery, development, and evaluation of innovative, cutting-edge therapies.

Lysosomal solute carrier transporters gain momentum in research.

Emerging evidence indicates that lysosome function extends beyond macromolecular degradation. Genetic and functional defects in components of the lysosomal transport machinery cause lysosomal storage disorders implicating the lysosomal solute carrier (SLC) transporters as essential to vital cell processes. The pathophysiology and therapeutic potential of lysosomal SLC transporters are highlighted here, focusing on recent discoveries in autophagic amino acid sensing (SLC38A9), phagocytic regulation in macrophages (SLC29A3, SLC15A3/A4), adenosine triphosphate (ATP) exocytosis in neurotransmission (SLC17A9), and lysosomal transport of maytansine catabolites into the cytoplasm (SLC46A3).

Flow around a rotating, semi-infinite cylinder in an axial stream.

This paper concerns steady, high-Reynolds-number flow around a semi-infinite, rotating cylinder placed in an axial stream and uses boundary-layer type of equations which apply even when the boundary-layer thickness is comparable to the cylinder radius, as indeed it is at large enough downstream distances. At large rotation rates, it is found that a wall jet appears over a certain range of downstream locations. This jet strengthens with increasing rotation, but first strengthens then weakens as downstream distance increases, eventually disappearing, so the flow recovers a profile qualitatively similar to a classical boundary layer. The asymptotic solution at large streamwise distances is obtained as an expansion in inverse powers of the logarithm of the distance. It is found that the asymptotic radial and axial velocity components are the same as for a non-rotating cylinder, to all orders in this expansion.

Synthesis, Structural Characterization, and Host-Guest Studies of Aminoquinonato-Bridged Re(I) Supramolecular Rectangles.

Aminoquinonato bridged Re(I)-based metallarectangles have been constructed via an orthogonal bonding approach. Self-assembly of Re2(CO)10 and aminoquinone ligands in the presence of ditopic linear pyridyl ligands has resulted in the formation of metallarectangles of the general formula [{(CO)3Re(µ-η(4)-L)Re(CO)3}2(µ-N-L'-N)2] (1-4), wherein 1, L = 2,5-bis(n-butylamino)-1,4-benzoquinonato (bbbq) and N-L'-N = 4,4'-bipyridine (bpy); 2, L = 2,5-bis(phenethylamino)-1,4-benzoquinonato (bpbq) and N-L'-N = 4,4'-bipyridine; 3, L = 2,5-bis(n-butylamino)-1,4-benzoquinonato (bbbq) and N-L'-N = trans-1,2-bis(4-pyridyl)ethylene (bpe) and 4, L = 2,5-bis(phenethylamino)-1,4-benzoquinonato (bpbq) and N-L'-N = trans-1,2-bis(4-pyridyl)ethylene (bpe). Metallarectangles 1-4 have been characterized by elemental analysis, IR, NMR, and UV-vis absorption spectroscopic techniques. The molecular structures of 1 and 4 were determined by single-crystal X-ray diffraction methods. The molecular recognition capability of 1 and 3 with pyrene and triphenylene has been investigated using UV-vis absorption and emission spectroscopic techniques. The formation of host-guest complex has been further corroborated by the single-crystal X-ray structural evidence of carceplex system (3⊃pyrene)·(DMF).

One-pot synthesis of oxamidato-bridged hexarhenium trigonal prisms adorned with ester functionality.

Oxamidato-bridged Re(I)-based hexanuclear trigonal prisms with ester functionality have been synthesised via a multicomponent self-assembly process under solvothermal conditions. The self-assembly of Re2(CO)10, oxamide ligands (H2L1 = N,N'-dibutyloxamide, H2L2 = N,N'-dioctyloxamide, H2L3 = N,N'-didodecyloxamide and H2L4 = N,N'-dibenzyloxamide) and phenyl-1,3,5-tris(isonicotinate) (ptin) resulted in the formation of metallaprisms with the general formula [{(CO)3Re(µ­Î·(4)-L)Re(CO)3}3(µ3-ptin)2] (1­4). The metallaprisms 1­4 have been characterised using spectroscopic techniques, and the molecular structure of 4 has been elucidated by single-crystal X-ray diffraction methods. Investigations on the guest binding ability of 2 with a few aromatic alcohols and L-tryptophan using UV­vis and fluorescence spectroscopic titration experiments revealed strong host­guest interactions. The luminescence enhancement studies of 2 and 3 have been carried out using organic-aqueous solvent mixtures.

[Process management in the hospital pharmacy for the improvement of the patient safety]. / La gestión por procesos en la farmacia hospitalaria para la mejora de la seguridad del paciente.

OBJECTIVES: To define a process management model for a hospital pharmacy in order to measure, analyse and make continuous improvements in patient safety and healthcare quality. MATERIAL AND METHODS: In order to implement process management, Igualada Hospital was divided into different processes, one of which was the Hospital Pharmacy. A multidisciplinary management team was given responsibility for each process. For each sub-process one person was identified to be responsible, and a working group was formed under his/her leadership. With the help of each working group, a risk analysis using failure modes and effects analysis (FMEA) was performed, and the corresponding improvement actions were implemented. Sub-process indicators were also identified, and different process management mechanisms were introduced. RESULTS: The first risk analysis with FMEA produced more than thirty preventive actions to improve patient safety. Later, the weekly analysis of errors, as well as the monthly analysis of key process indicators, permitted us to monitor process results and, as each sub-process manager participated in these meetings, also to assume accountability and responsibility, thus consolidating the culture of excellence. CONCLUSIONS: The introduction of different process management mechanisms, with the participation of people responsible for each sub-process, introduces a participative management tool for the continuous improvement of patient safety and healthcare quality.