A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India.

BACKGROUND: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. METHODS: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. DISCUSSION: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. TRIAL REGISTRATION: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.

The Role of Computed Tomography and Radiographs in the Management of Intertrochanteric Fractures.

Introduction: The Intertrochanteric fracture is a common hip trauma encountered in elderly patients. There is a lack of general agreement regarding its surgical management and choice of implant. Purpose of this study to conclude the final decision matrix regarding surgical management of intertrochanteric fractures based on parameters assessed on plain radiographs and CT scan. Materials and methods: We have retrospectively evaluated 55 patients with intertrochanteric fractures presented to our institute after informed consent with radiographs and CT scans between July 2017 to July 2018. Assessment of various parameters regarding fracture geometry and classification as well as measurement was done. Results: Mean lateral wall thickness in present study was 20.76mm. Incidence of coronal fragments was 90.9% and absence of coronal fragment in 5 patients. We noted the cases with anterior comminution had also a posterior comminution rendered the fracture unstable in almost 20 % cases. Conclusion: Better understanding of fracture geometry by combined used of radiograph and CT scan enhanced preoperative planning, choice of suitable implant, helps in reduction manoeuvre and improving quality of osteosynthesis.

A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya.

On 7 February 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. More than 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27 × 106 cubic meters of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders greater than 20 meters in diameter and scoured the valley walls up to 220 meters above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.

A selective hydrolytic and restructuring approach through a Schiff base design on a coumarin platform for "turn-on" fluorogenic sensing of Zn2.

A new Schiff base, CMD, designed based on a coumarin platform was synthesized and fully characterized through single crystal X-ray diffraction studies. CMD underwent selective Zn2+-triggered hydrolysis in ethanolic medium followed by restructuring of its fragments, resulting in a "turn-on" green fluorogenic response. This response was confirmed through various physico-chemical measurements along with single crystal X-ray diffraction studies. This selective hydrolytic fluorogenic event was exploited for the successful optical detection and live cell imaging of Zn2+ in SiHa cells. The above restructured products were characterized as two new Schiff bases, viz.CM and NSA, of which NSA was highly fluorescent (green). Hence, the formation of this green fluorogenic product accounted for the above fluorogenic "turn-on" sensing of Zn2+ with a sub-nanomolar detection limit. Spectroscopic evidence along with mass determinations indicated that the Zn-CMD ensemble took the form of CM-Zn-CM in solution, supporting our above proposal of hydrolysis and restructuring. However, the X-ray diffraction studies of the Zn-CMD ensemble further revealed it to consist of NSA and CM-Zn-CM', where CM' is yet another new Schiff base formed in situ during the process of developing single crystals.

Large-scale synthesis of free-standing N-doped graphene using microwave plasma.

Direct assembling of N-graphene, i.e. nitrogen doped graphene, in a controllable manner was achieved using microwave plasmas at atmospheric pressure conditions. The synthesis is accomplished via a single step using ethanol and ammonia as carbon and nitrogen precursors. Tailoring of the high-energy density plasma environment results in a selective synthesis of N-graphene (~0.4% doping level) in a narrow range of externally controlled operational conditions, i.e. precursor and background gas fluxes, plasma reactor design and microwave power. Applying infrared (IR) and ultraviolet (UV) irradiation to the flow of free-standing sheets in the post-plasma zone carries out changes in the percentage of sp2, the N doping type and the oxygen functionalities. X-ray photoelectron spectroscopy (XPS) revealed the relative extension of the graphene sheets π-system and the type of nitrogen chemical functions present in the lattice structure. Scanning Electron microscopy (SEM), Transmission Electron microscopy (TEM) and Raman spectroscopy were applied to determine morphological and structural characteristics of the sheets. Optical emission and FT-IR spectroscopy were applied for characterization of the high-energy density plasma environment and outlet gas stream. Electrochemical measurements were also performed to elucidate the electrochemical behavior of NG for supercapacitor applications.

Biallelic mutations in FLNB cause a skeletal dysplasia with 46,XY gonadal dysgenesis by activating ß-catenin.

Filamin B (FLNB) functions as a switch that can affect chrondrocyte development and endochondral bone formation through a series of signaling molecules and transcription factors that also affect Sertoli cell development. Here, we report a subject with a novel skeletal dysplasia and co-existing 46,XY gonadal dysgenesis and biallelic mutations in FLNB. Whole exome sequencing was performed to identify mutations. Quantitative polymerase chain reaction (qPCR) and flow variant assays were performed to quantify RNA, proteins and phosphorylated proteins. The TOPFLASH reporter was performed to quantify ß-catenin activity. Mutations were identified in the FLNB gene (FLNB:p.F964L, FLNB:p.A1577V). These mutations increased binding of FLNB protein to the MAP3K1 and RAC1 signal transduction complex and activated ß-catenin and had different effects on phosphorylation of MAP kinase pathway intermediates and SOX9 expression. Direct activation of ß-catenin through the FLNB-MAP3K1-RAC1 complex by FLNB mutations is a novel mechanism for causing 46,XY gonadal dysgenesis. The mechanism of action varies from those reported previously for loss of function mutations in SOX9 and gain-of-function mutations in MAP3K1.

Brightening Quinolineimines by Al3+ and Subsequent Quenching by PPi/PA in Aqueous Medium: Synthesis, Crystal Structures, Binding Behavior, Theoretical and Cell Imaging Studies.

Recent years have witnessed an upsurge of Al3+ selective optical sensors involving simple Schiff bases to other complex organic frameworks. However, more than ∼95% of such reports lack crystallographic evidence, and proposals of binding sites for Al3+ are based upon spectroscopic evidence only. We herein synthesized and fully characterized a quinolineimine derivative (CMO) and explored its potential toward efficient detection of Al3+ with crystallographic evidence. The ongoing nonradiative photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) processes in CMO got inhibited via the chelation enhanced fluorescence (CHEF) effects induced by Al3+, and consequently turn-on fluorescence response was observed with 18-fold emission enhancements. The theoretical calculations performed were in good consonance with experimental results. We also explored further the applicability of the CMO·Al3+ complex toward highly sensitive and selective detection of inorganic phosphate (PPi) and an explosive picric acid (PA) via fluorescence quenching processes through two different chemical routes. The bioimaging of Al3+ and PPi were carried out in the living human cancer cells (MCF-7).

A multi writable thiophene-based selective and reversible chromogenic fluoride probe with dual -NH functionality.

A chromogenic fluoride probe bearing bis imine groups having dual -NH functionality (BSB) has been designed, synthesised and structurally characterized by its single crystal X-ray diffraction studies. The BSB could visually and spectroscopically recognise F(-) with high selectivity over other anions by exhibiting intense chromogenic response (from colourless to red) for F(-) in acetonitrile solution. The UV-visible titration and (1)H NMR titration experiments indicated that the observed changes occur via a combined process including hydrogen bonding and deprotonation between the BSB and F(-). Moreover theoretical calculations at the Density Functional Theory (DFT) level shed further light upon probe design strategy and the nature of interactions between BSB and F(-). The limit of detection and binding constant of BSB towards F(-) were found to be 6.9×10(-7)M and 1.42±0.069×10(8)M(-2) respectively. Finally, by using F(-)and H(+) as chemical inputs and the absorbance as output, a INHIBIT logic gate was constructed, which exhibits "Multi-write" ability without obvious degradation in its optical output.

A pyrene-benzthiazolium conjugate portraying aggregation induced emission, a ratiometric detection and live cell visualization of HSO3(.).

The present study deals with the photophysical property of a pyrene-benzthiazolium conjugate R1, as a strong intramolecular charge transfer (ICT) probe exhibiting long wavelength emission in the red region. Unlike traditional planar polyaromatic hydrocarbons whose aggregation generally quenches the light emission, the pyrene based R1 was found to display aggregation-induced emission (AIE) property along with simultaneous increase in its quantum yield upon increasing the water content of the medium. The R1 exhibits high specificity towards HSO3(-)/SO3(2-) by interrupting its own ICT producing there upon a large ratiometric blue shift of ∼220 nm in its emission spectrum. The lowest detection limit for the above measurement was found to be 8.90 × 10(-8) M. The fluorescent detection of HSO3(-) was also demonstrated excellently by test paper strip and silica coated TLC plate incorporating R1. The live cell imaging of HSO3(─) through R1 in HeLa cells was studied using fluorescence microscopic studies. The particle size and morphological features of R1 and R1-HSO3(-) aggregates in aqueous solution were characterized by DLS along with SEM analysis.

Efficient visualization of H2S via a fluorescent probe with three electrophilic centres.

H2S is a reactive nucleophilic species with toxic effects towards human beings. Its efficient detection and marking is still a challenging job due to its similar nucleophilic character to a number of biothiols, like glutathione, cysteine, homocysteine etc. We report herein the first ever use of a chemosensor incorporating three electrophilic centres to achieve high sensitivity and very fast response time (40 s) towards H2S.

A radical approach for fluorescent turn 'on' detection, differentiation and bioimaging of methanol.

A simple Schiff base (RC) has been explored as a smart example of fluorescent material for the selective detection, differentiation and bioimaging of methanol. The nucleophilic attack of methanol on the cyclic control unit of RC leads to its opening and formation of a highly fluorescent moiety, RO. The RC displays a good sensitivity for MeOH with a detection limit of 0.042 wt% in water.

Outcomes of neonates with birth weight⩽500 g: a 20-year experience.

OBJECTIVE: Ethical dilemmas continue regarding resuscitation versus comfort care in extremely preterm infants. Counseling parents and making decisions regarding the care of these neonates should be based on reliable, unbiased and representative data drawn from geographically defined populations. We reviewed survival and morbidity data for our population at the edge of viability. STUDY DESIGN: A retrospective review of our perinatal database was carried out to identify all infants born alive and admitted to the neonatal intensive care unit (NICU) with BW⩽500 g between 1989 and 2009. Data from the initial hospital stay and follow-up at 24 months were collected. RESULT: Out of 22 672 NICU admissions, 273 were eligible: 212 neonates were reviewed after excluding infants with comfort care. BW ranged from 285 to 500 g (mean 448 g) and gestational age range 22 to 28 weeks (median 24 week). Sixty-one (28.8%) survived until discharge. Only 13.8% males survived compared with 39.2% females (P<0.05). Half (49%) were discharged with home oxygen/monitor. Fifty (82%) patients' charts were available to review at the 24-month follow-up. Thirty-three percent of surviving infants had a normal neurodevelopmental assessment at 24 months. Forty-three percent had weight/head circumference<5th percentile at 24 months. CONCLUSION: About a third of neonates admitted to NICU with ⩽500 g BW survived, with 33% of those surviving, demonstrating age-appropriate development at a 24-month follow-up visit.

Bioinformatics in otolaryngology research. Part two: other high-throughput platforms in genomics and epigenetics.

OBJECTIVES: This second segment of the two-part review summarises several modern high-throughput methods in genomics, epigenetics and molecular biology. Many principles from nucleotide sequencing and transcriptomics can be applied to other high-throughput molecular biology techniques. Specifically, this manuscript reviews: array comparative genome hybridisation; single nucleotide polymorphism arrays; microarray technology, used to study epigenetics; and methodology applied in proteomics. Finally, the review describes current methods for the integration of multiple molecular biology platforms. CONCLUSION: Progress in treating human disease in general will require close collaboration with experts in bioinformatics. Improved understanding, by clinicians and physician-scientists in our field, of the concepts presented in both parts of this review will advance diagnosis and therapy for diseases of the head and neck.

Bioinformatics in otolaryngology research. Part one: concepts in DNA sequencing and gene expression analysis.

BACKGROUND: Advances in high-throughput molecular biology, genomics and epigenetics, coupled with exponential increases in computing power and data storage, have led to a new era in biological research and information. Bioinformatics, the discipline devoted to storing, analysing and interpreting large volumes of biological data, has become a crucial component of modern biomedical research. Research in otolaryngology has evolved along with these advances. OBJECTIVES: This review highlights several modern high-throughput research methods, and focuses on the bioinformatics principles necessary to carry out such studies. Several examples from recent literature pertinent to otolaryngology are provided. The review is divided into two parts; this first part discusses the bioinformatics approaches applied in nucleotide sequencing and gene expression analysis. CONCLUSION: This paper demonstrates how high-throughput nucleotide sequencing and transcriptomics are changing biology and medicine, and describes how these changes are affecting otorhinolaryngology. Sound bioinformatics approaches are required to obtain useful information from the vast new sources of data.

A remarkable effect of N,N-diethylamino functionality on the optoelectronic properties of a salicylimine-based probe for Al(3+).

A new live-cell permeable, fluorescent probe comprised of a simple salicylimine-based Schiff base (SA1) has been developed for Al3+ with nano-molar sensitivity in aqueous media. SA1 was synthesized through a simple structural modification of a recently reported receptor SA2 by the incorporation of the N,Ndiethylamino (DEA) group as a fine controllable unit. This modification affects the performance of SA1 remarkably in terms of its sensitivity, water compatibility and efficiency as well as its mechanistic aspect. The presence of the DEA group in SA1 led to its dual channel emission due to the TICT state and at the same time its hydrophobic nature was also responsible for controlling the strong hydration of Al3+ ions in aqueous media which ultimately led to the high sensitivity of SA1 for Al3+. The structure of SA1 was confirmed by single crystal X-ray diffraction and its binding with Al3+ was studied in detail using UVvisible, fluorescence and 1H NMR spectral studies along with mass determination. The effort of getting a single crystal of Al3+­SA1 led to single crystals of Cl−/NO3 − complexes of protonated SA1 which were fully characterized by their XRD studies.

Solvent viscosity tuned highly selective NIR and ratiometric fluorescent sensing of Fe3+ by a symmetric chalcone analogue.

The present communication outlined for the first time a novel combination of chromogenic near-infrared (NIR) and ratiometric fluorescence responses for Fe(3+) by a symmetric chalcone analogue (receptor 1). The key step behind NIR chromogenic response was attributed to chelation of Fe(3+) with receptor 1 upon its unfolding in aprotic, low viscosity solvents. The receptor 1 also exhibited Fe(3+) selective ratiometric changes at 538 nm and 463 nm. The chromogenic detection limit of the receptor 1 for Fe(3+) is the lowest ever (5.8 × 10(-8) M). The mechanistic details of NIR/fluorescence sensing of receptor 1 along with its solvent dependency have been discussed in detail.

A Zn(2+)-responsive highly sensitive fluorescent probe and 1D coordination polymer based on a coumarin platform.

A coumarin-based Schiff base (receptor 1) exhibited fluorescence enhancement selectively with Zn(2+) at a nanomolar level in near-aqueous medium (EtOH-H2O; 1:1, v/v). The response was instantaneous with a detection limit of 3.26 × 10(-9) M. The sensing event is supposed to incorporate a combinational effect of intramolecular charge transfer (ICT), chelation-enhanced fluorescence (CHEF) and C[double bond, length as m-dash]N isomerization mechanisms. Various spectroscopic methods, viz. IR, UV-visible, fluorescence and NMR in association with single crystal XRD studies, were used for thorough investigation of the structure of receptor 1 as well as of the sensing event. The Zn(2+) complex of receptor 1 exhibited a very nice 1D chain coordination polymeric framework in its single crystal XRD.

An Al3+ and H2PO4(-)/HSO4(-) selective conformational arrest and bail to a pyrimidine-naphthalene anchored molecular switch.

A pyrimidine-naphthalene anchored Schiff base (receptor 1) showed Al(3+) selective conformational arrest by inhibition of its C=N isomerization (cis-trans) leading to its fluorescent switching in aqueous medium. Nevertheless the H(2)PO(4)(-)/HSO(4)(-) bailed receptor 1 from the Al(3+) arrest leading to its switching 'off'. This conformational arrest and bail of receptor 1 were highly specific as no other ion pairs were able to do the same. The detection limit of the receptor 1 towards Al(3+) is 1.49 × 10(-9) M and is the second highest for the same reported to date in the literature, while the same for H(2)PO(4)(-) and HSO(4)(-) were found to be 2.27 × 10(-7) and 2.91 × 10(-6), respectively. The mechanistic details of 'on-off' switching of the receptor 1 by the analytes have been explored through various spectroscopic studies along with theoretical calculations at density functional theory (DFT) level. The 'on-off' switching of receptor 1 through inputs Al(3+) and H(2)PO(4)(-)/HSO(4)(-) led it to mimic with INH logic function.

Uncovering the true mechanism of optical detection of HSO4- in water by Schiff-base receptors--hydrolysis vs. hydrogen bonding.

The mechanism of optical detection of HSO(4)(-) in aqueous medium by Schiff-base receptors has previously been proposed to depend on selective hydrogen-bond interactions. Here, we clearly demonstrate for the first time that the acidic nature of this anion gives rise to hydrolysis of the Schiff base, which leads to the optical changes observed in this family of receptors.

A zinc(II) directed triple-stranded helicate incorporating a nine membered metallamacrocycle: supramolecular cylinders mimicking P1 nuclease.

We report herein the first small molecule based self-assembled fluorescent trinuclear Zn(II) supramolecular cylindrical motif as a structural and functional model of the active site of P1 nuclease. The DNA binding of the same was investigated through UV-Vis, fluorescence and circular dichroism studies.