L-Tryptophan-based pyrene conjugate for intracellular zinc-guided excimer emission and controlled nano-assembly.

This article describes intracellular zinc-induced excimer emission and tuning of self-assembly from L-tryptophan-pyrene conjugate (1). The zinc-guided excimer formation is due to the interaction of the pyrene moiety in an excited state. AFM studies show the structural modification in the supramolecular nano-assembly of 1 from dome-shaped to porous surface after complexation with zinc ions. Further, the interaction of 1 with Zn(II) ion is also studied using DFT, Job's plot, NMR titration and HRMS. The results of Zn(II) ion determination in natural water samples and RAW 264.7 cells demonstrate the practical utility of 1.

Dimensionality-Tailored Ferromagnetism in Quasi-Two-Dimensional MnSe2 for the Magnetoelectrochemical Hydrogen Evolution Reaction in Alkaline Media.

The application of an external magnetic field to the cathode shows great promise in facilitating the hydrogen evolution reaction (HER) via water electrolysis. However, the criteria for designing such cathodes are still under investigation. Among various aspects, understanding the effect of different magnetic states of the cathode material is crucial, especially for the HER in alkaline conditions, which possesses different reaction steps compared to that in acidic conditions. Herein, we present MnSe2 as a cathode material for the magneto-electrocatalytic HER in alkaline media, utilizing its dimension-dependent magnetic phase transition. By tailoring its dimensionality, we have achieved room-temperature ferromagnetism in its quasi-two-dimensional (2D) form, whereas its bulk counterpart exhibits paramagnetism. Upon being subjected to a low external magnetic field of 0.4 T at -182 mV (vs RHE) overpotential, quasi-2D MnSe2 exhibited a 120% improvement in current density compared to itself at zero magnetic field, while negligible changes were observed in the bulk material. This performance enhancement under a magnetic field could originate from the higher spin polarization of the ferromagnetic catalyst. This work signifies a conceptual advancement of the catalyst's spin state in magnetically enhanced electrocatalytic reaction kinetics.

Atypical Extraoral Presentation of a Heterotopic Gastrointestinal Cyst on the Face: A Case Report.

Heterotopias and choristomas are congenital lesions characterized by the presence of histologically normal tissues at non-physiological anatomic sites. The presence of gastrointestinal tissue in the oral cavity has been recognized as a heterotopic gastrointestinal cyst (HGIC) of the oral cavity. An intestinal heterotopia on the face, in relation to the parotid gland, is extremely rare. Highlighting this possibility is the case of a 42-year-old, non-habitué female with swelling in the parotid region of the face for two years. Clinical examination and radiographic investigations ruled out the possibility of a salivary gland tumor, epidermal inclusion cyst, and enlarged parotid lymph node while confirming the cystic nature of the presenting pathology. Further evaluation was carried out using an excisional biopsy. Histopathological evaluation revealed a cystic space lined by simple columnar epithelium with an abundance of goblet cells. The cystic epithelium was noted to form finger-like projections and crypts. An eosinophilic mucinous content was noted in the cystic space. Using Alcian blue-periodic acid-Schiff (PAS) staining, a distinct Alcian blue positivity of the mucinous material and the goblet cells was noted. This feature confirms the acidic nature of the mucinous content being liberated by the goblet cells. The histopathological features, along with histochemical assessment, were confirmatory for the diagnosis of an HGIC. The patient remains disease-free at the end of a 12-month follow-up. This is the first report of an HGIC at an extraoral site on the face in association with the parotid gland. It highlights the possible presentation of heterotopias in adult patients and warrants clinicopathological vigilance due to its benign nature and late presentation.

Narrative review on artificially intelligent olfaction in halitosis.

Halitosis, commonly known as oral malodor, is a multifactorial health concern that significantly impacts the psychological and social well-being of individuals. It is the third most frequent reason for individuals to seek dental treatment, after dental caries and periodontal diseases. For an in-depth exploration of the topic of halitosis, an extensive literature review was conducted. The review focused on articles published in peer-reviewed journals and only those written in the English language were considered. The search for relevant literature began by employing subject headings such as 'halitosis, oral malodor, volatile sulfur compounds, artificial intelligence, and olfaction' in databases such as PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE. Additionally, a thorough hand search of references was conducted to ensure the comprehensiveness of the review. After amalgamating the search outcomes, a comprehensive analysis revealed the existence of precisely 134 full-text articles that bore relevance to the study. Abstracts and editorial letters were excluded from this study, and almost 50% of the full-text articles were deemed immaterial to dental practice. Out of the remaining articles, precisely 54 full-text articles were employed in this review. As primary healthcare providers, dentists are responsible for diagnosing and treating oral issues that may contribute to the development of halitosis. To effectively manage this condition, dentists must educate their patients about the underlying causes of halitosis, as well as proper oral hygiene practices such as tongue cleaning, flossing, and selecting appropriate mouthwash and toothpaste. This narrative review summarises all possible AI olfaction in halitosis.

Assessment approaches for hemiplegic shoulder pain in people living with stroke - A scoping review.

PURPOSE: Hemiplegic shoulder pain (HSP) is reported in up to 40% of people with stroke. Causes of HSP are often multifactorial. To inform appropriate treatment, reliable/valid assessments are critical. The aim of this scoping review was to collate assessment approaches used in studies where the primary outcome was HSP, and to identify how frequently each assessment approach was used. METHODS: A systematic search, including studies from 2000-2023 was conducted of the MEDLINE, EMBASE, CINAHL, AMED, Biomed Central, and Cochrane Library databases, with four key terms used: "assess", "stroke", "pain" and "shoulder". All primary studies published in English language fulfilling the reviews inclusion criteria were included. Six reviewers extracted the data. RESULTS: A total of 29 assessment methods for HSP were identified from 124 studies. The common assessments were: Visual Analogue Scale (n = 75, 60%), Passive Range of Movement (n = 65, 52%), Fugl-Meyer Assessment (n = 32, 26%), glenohumeral subluxation (n = 30, 24%) and Numerical Rating Scale (n = 27, 22%). CONCLUSION: A wide range of assessment approaches was identified for HSP, and some are used more than others. A fully comprehensive assessment that considers different aspects of pain including severity and timing, functioning, and the psychological burden, is needed in this area of practice to be able to guide appropriate treatment.

Hemiplegic shoulder pain is reported in up to 40% of people with stroke and a wide range of assessments approaches are reported in the literature.Simple questioning about shoulder pain may not be adequate for providing the best clinical care to patients and an ideal assessment approach would be one that takes into consideration both quantitative and qualitative information.Until a new measure is developed, the four common assessments reported (Visual Analogue Scale; Passive Range of Movement; Fugl-Meyer Assessment and Numerical Rating Scale) should be used in combination.

Comparison of ultrasound-guided sacral erector spinae plane block and caudal epidural block for analgesia in paediatric patients undergoing hypospadias repair: A double-blind, randomised controlled trial.

Background and Aims: Caudal block is more frequently used in children for postoperative analgesia. However, its disadvantage is its short duration. Erector spinae plane block (ESPB) at the sacral level can potentially block the pudendal nerve. It may prove an alternative to caudal block for hypospadias repair regarding time to first rescue analgesia. Methods: Fifty children of 2-7 years of age were included. After induction of general anaesthesia, Group I (n = 25) was given ultrasound-guided sacral ESPB with 1 ml/kg of 0.25% bupivacaine and Group II (n = 25) was given caudal block with 0.5 ml/kg of 0.25% bupivacaine. Postoperatively at face, leg, activity, cry, consolability (FLACC) score ≥4, rescue analgesia was given using intravenous 15 mg/kg paracetamol. The primary outcome was to compare time to first rescue analgesia, and secondary outcomes were intraoperative haemodynamic parameters, fentanyl consumption, postoperative FLACC score and analgesic consumption in 24 h. Continuous variables were compared using the independent sample t-test or Mann-Whitney test, and categorical variables were compared using the Chi-square test. Results: The mean time to first rescue analgesia was 21.30 (standard deviation [SD]: 3.06) h in Group I and 9.36 (SD: 1.71) h in Group II (P < 0.001) (mean difference -11.94 [95% CI: -13.39, -10.48]). The FLACC score was significantly higher (P < 0.05) postoperatively at 8, 10, 12 and 18 h in Group II. Mean postoperative analgesic consumption was 310.5 (SD: 72.69) mg in Group I and 615.6 (SD: 137.51) mg in Group II (P < 0.001) (mean difference 30.5 [95% CI: 236.41, 373.78]). Conclusion: Sacral ESPB is better regarding time to first rescue analgesia than caudal block in paediatric patients undergoing hypospadias repair.

Comprehensive rheological and mechanistic evaluation of an asphalt binder and mixture modified with warm mix additives.

Though warm mix asphalt (WMA) technology has been introduced for a long time, there is still reluctance in the industry to utilize it in practice. In regions like India, where WMA incorporation into road construction has been limited over the past two decades, building confidence in local binders is imperative for widespread adoption. Thus, the present study appraises the effect of three commonly used WMA additives in India, namely Sasobit®, Evotherm®, and Zycotherm®, with base binder VG-30 on the rheological and mixture performance parameters. Three dosages of each WMA additive were blended with the control binder to give ten binder combinations. Different binder evaluations such as Superpave grading and parameters, frequency sweep testing, multiple stress creep recovery test, and linear amplitude sweep test were conducted for comparative dynamic mechanical analysis. Based on the binder testing results, suitable dosages of WMA additives were established, and mixture testing was carried out using these specific additive dosages. Binder evaluations showed improvement in high-temperature characteristics with Sasobit® and better fatigue performance with Evotherm®, while Zycotherm® did not alter binder properties significantly. The asphalt mixture testing results indicated satisfactory performance with the three additives based on Marshall stability and flow testing. The WMA additives also showed enhancement in moisture susceptibility based on the modified Lottman test with Zycotherm® demonstrating the best performance. Overall, the study underscores promising effects of the three WMA additives across different parameters, signaling their potential for widespread application in real-world scenarios.

Comparative Efficacy of Interventions for Analgesia During Heel Prick in Newborn Infants - A Systematic Review and Network Meta-Analysis.

CONTEXT: Heel prick is one among the common painful procedures in neonates. We performed a systematic review and network meta-analysis (NMA) to compare the efficacy of different interventions for analgesia during heel prick in neonates. EVIDENCE ACQUISITION: Medline, Cochrane, Embase and CINAHL databases were searched from inception until February 2023. Randomized and quasi-randomized trials that evaluated different pharmacological and non-pharmacological interventions for analgesia during heel prick for neonates were included. Data from the included trials were extracted in duplicate. A NMA with a frequentist random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. We adhered to the PRISMA-NMA guidelines. RESULTS: One-hundred-and-three trials comparing 51 different analgesic measures were included. Among the 38 interventions, for pain "during" heel prick, non-nutritive suckling (NNS) plus sucrose [SMD -3.15 (-2.62, -3.69)], followed by breastfeeding, glucose, expressed breast milk (EBM), sucrose, NNS and touch massage, had a high certainty of evidence (CoE) to reduce pain scores when compared to no intervention. Among the 23 interventions for pain at 30 seconds after heel-prick, moderate CoE was noted for facilitated tucking plus NNS plus music, glucose, NNS plus sucrose, sucrose plus swaddling, mother holding, EBM, sucrose and NNS. CONCLUSIONS: Oral sucrose 2 minutes before combined with NNS during the procedure, was the best intervention for reducing pain during heel prick. It also effectively reduced pain scores 30 seconds and 1 minute after the procedure. Other interventions with moderate to high CoE for a significant reduction in pain during and at 30 seconds after heel prick are oral sucrose, oral glucose, EBM and NNS. All these are low-cost and feasible interventions for most of the settings.

Applicability of the External Genitalia Score (EGS) in Indian neonates and children up to 2 years of age.

OBJECTIVES: To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia. METHODS: This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia. RESULTS: Median EGS values in newborn males with typical genitalia were 9.5 at 28-31 weeks, 10.5 at 32-33 weeks, 11 at 34 weeks and 11.5 in males at 35-42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**). CONCLUSIONS: The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate).

Odd Sites of Parathyroid Adenomas: 18F-fluorocholine PET/CT Pointing to the Right Place.

Primary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and 99mTc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration. 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) can help in the localization of these ectopic adenomas due to its superior detection rates and spatial resolution. Herein, we report a case of ectopic parathyroid adenomas that were localized on FCH PET/CT.

Controlled Environment Ecosystem: A Cutting-Edge Technology in Speed Breeding.

The controlled environment ecosystem is a meticulously designed plant growing chamber utilized for cultivating biofortified crops and microgreens, addressing hidden hunger and malnutrition prevalent in the growing population. The integration of speed breeding within such controlled environments effectively eradicates morphological disruptions encountered in traditional breeding methods such as inbreeding depression, male sterility, self-incompatibility, embryo abortion, and other unsuccessful attempts. In contrast to the unpredictable climate conditions that often prolong breeding cycles to 10-15 years in traditional breeding and 4-5 years in transgenic breeding within open ecosystems, speed breeding techniques expedite the achievement of breeding objectives and F1-F6 generations within 2-3 years under controlled growing conditions. In comparison, traditional breeding may take 5-10 years for plant population line creation, 3-5 years for field trials, and 1-2 years for variety release. The effectiveness of speed breeding in trait improvement and population line development varies across different crops, requiring approximately 4 generations in rice and groundnut, 5 generations in soybean, pea, and oat, 6 generations in sorghum, Amaranthus sp., and subterranean clover, 6-7 generations in bread wheat, durum wheat, and chickpea, 7 generations in broad bean, 8 generations in lentil, and 10 generations in Arabidopsis thaliana annually within controlled environment ecosystems. Artificial intelligence leverages neural networks and algorithm models to screen phenotypic traits and assess their role in diverse crop species. Moreover, in controlled environment systems, mechanistic models combined with machine learning effectively regulate stable nutrient use efficiency, water use efficiency, photosynthetic assimilation product, metabolic use efficiency, climatic factors, greenhouse gas emissions, carbon sequestration, and carbon footprints. However, any negligence, even minor, in maintaining optimal photoperiodism, temperature, humidity, and controlling pests or diseases can lead to the deterioration of crop trials and speed breeding techniques within the controlled environment system. Further comparative studies are imperative to comprehend and justify the efficacy of climate management techniques in controlled environment ecosystems compared to natural environments, with or without soil.

Nanostructured transition metal dichalcogenides-based colorimetric sensors: Synthesis, characterization, and emerging applications.

Nanostructured transition metal dichalcogenides (TMDCs) have garnered significant attention as prospective materials for the development of highly sensitive and versatile colorimetric sensors. This work explores the synthesis, characterization, and emerging applications of TMDC-based sensors, focusing on their unique structural aspects and inherent properties. The synthesis methods involve tailored fabrication techniques, such as chemical vapor deposition and hydrothermal processes, aimed at producing well-defined nanostructures that enhance sensor performance. Characterization techniques, including microscopy, spectroscopy, and surface analysis, are employed to elucidate the structural and chemical features of the nanostructured TMDCs. These analyses provide insights into the correlation between the material's morphology and its sensing capabilities. The colorimetric sensing mechanism relies on the modulation of optical properties in response to specific analytes, enabling rapid and visual detection. The emerging applications of TMDC-based colorimetric sensors span diverse fields, including environmental monitoring, healthcare, and industrial processes. The sensors exhibit high sensitivity, selectivity, and real-time response, making them ideal candidates for detecting various target analytes. Furthermore, their integration with complementary technologies such as microfluidics, can facilitate the development of on-site and point-of-care applications. This work highlights the interdisciplinary significance of nanostructured TMDC-based colorimetric sensors and underscores their potential contributions to addressing contemporary challenges in sensing technology.

Design of C2-symmetric pseudopeptides for in vivo detection of Cu(II) through controlled supramolecular nano-assembly.

Pseudopeptides are emerging next-generation soft bioinspired materials for biological applications. Therefore, a new class of C2-symmetric L-valine-derived pseudopeptides has been designed and developed. The newly developed pseudopeptides exhibit intracellular Cu(II) ion detection in live-cell fluorescence studies on RAW264.7 cells. We find that the changes in the amino acid side chain in desired pseudopeptidic moieties lead to a drastic change in their selectivity towards different metal ions. The L-valine-derived pseudopeptides exhibit selectivity towards Cu(II) ions through turn-off fluorescence, and the L-phenylalanine-derived pseudopeptides exhibit selectivity towards Zn(II) ions through turn-on fluorescence. In addition, the L-valine-derived pseudopeptides show an increase in spherical-shaped structures upon incubation with Cu(II) ions during supramolecular nano-assembly formation. In contrast, the L-phenylalanine-derived pseudopeptides show a decrease in spherical-shaped structures upon adding Zn(II) ions. The judiciously designed L-valine-derived and L-phenylalanine-derived bioinspired pseudopeptides are promising for exploring similar effects in various peptidomimetics in advanced biological applications.

Poly(l-glutamic acid) augments the transfection performance of lipophilic polycations by overcoming tradeoffs among cytotoxicity, pDNA delivery efficiency, and serum stability.

Polycations are scalable and affordable nanocarriers for delivering therapeutic nucleic acids. Yet, cationicity-dependent tradeoffs between nucleic acid delivery efficiency, cytotoxicity, and serum stability hinder clinical translation. Typically, the most efficient polycationic vehicles also tend to be the most toxic. For lipophilic polycations-which recruit hydrophobic interactions in addition to electrostatic interactions to bind and deliver nucleic acids-extensive chemical or architectural modifications sometimes fail to resolve intractable toxicity-efficiency tradeoffs. Here, we employ a facile post-synthetic polyplex surface modification strategy wherein poly(l-glutamic acid) (PGA) rescues toxicity, inhibits hemolysis, and prevents serum inhibition of lipophilic polycation-mediated plasmid (pDNA) delivery. Importantly, the sequence in which polycations, pDNA, and PGA are combined dictates pDNA conformations and spatial distribution. Circular dichroism spectroscopy reveals that PGA must be added last to polyplexes assembled from lipophilic polycations and pDNA; else, PGA will disrupt polycation-mediated pDNA condensation. Although PGA did not mitigate toxicity caused by hydrophilic PEI-based polycations, PGA tripled the population of transfected viable cells for lipophilic polycations. Non-specific adsorption of serum proteins abrogated pDNA delivery mediated by lipophilic polycations; however, PGA-coated polyplexes proved more serum-tolerant than uncoated polyplexes. Despite lower cellular uptake than uncoated polyplexes, PGA-coated polyplexes were imported into nuclei at higher rates. PGA also silenced the hemolytic activity of lipophilic polycations. Our work provides fundamental insights into how polyanionic coatings such as PGA transform intermolecular interactions between lipophilic polycations, nucleic acids, and serum proteins, and facilitate gentle yet efficient transgene delivery.

Red luminescent water stable lead-free 2D tin halide perovskite nanocrystals for photodetectors.

In this report, we have synthesized an environmentally friendly hybrid organic-inorganic layered two-dimensional (2D) lead-free perovskite nanomaterial. The synthesized perovskites, namely (OleylAm)2SnI4 (MHP1), exhibit outstanding water stability and emit luminous red light. The photodetector constructed using our material showcases superior characteristics, including a faster response than comparable devices and improved rise and fall times compared to other 2D perovskite nanomaterials.

Observation of oxygenated intermediates in functional mimics of aminophenol dioxygenase.

Aminophenol dioxygenases (APDO) are mononuclear nonheme iron enzymes that utilize dioxygen (O2) to catalyze the conversion of o-aminophenols to 2-picolinic acid derivatives in metabolic pathways. This study describes the synthesis and O2 reactivity of two synthetic models of substrate-bound APDO: [FeII(TpMe2)(tBu2APH)] (1) and [FeII(TpMe2)(tBuAPH)] (2), where TpMe2 = hydrotris(3,5-dimethylpyrazole-1-yl)borate, tBu2APH = 4,6-di-tert-butyl-2-aminophenolate, and tBuAPH2 = 4-tert-butyl-2-aminophenolate. Both Fe(II) complexes behave as functional APDO mimics, as exposure to O2 results in oxidative CC bond cleavage of the o-aminophenolate ligand. The ring-cleaved products undergo spontaneous cyclization to give substituted 2-picolinic acids, as verified by 1H NMR spectroscopy, mass spectrometry, and X-ray crystallography. Reaction of the APDO models with O2 at low temperature reveals multiple intermediates, which were probed with UV-vis absorption, electron paramagnetic resonance (EPR), Mössbauer (MB), and resonance Raman (rRaman) spectroscopies. The most stable intermediate at -70 °C in THF exhibits multiple isotopically-sensitive features in rRaman samples prepared with 16O2 and 18O2, confirming incorporation of O2-derived atom(s) into its molecular structure. Insights into the geometric structures, electronic properties, and spectroscopic features of the observed intermediates were obtained from density functional theory (DFT) calculations. Although functional APDO models have been previously reported, this is the first time that an oxygenated ligand-based radical has been detected and spectroscopically characterized in the ring-cleaving mechanism of a relevant synthetic system.

The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside.

Depression is a complicated neuropsychiatric condition with an incompletely understoodetiology, making the discovery of effective therapies challenging. Animal models have been crucial in improving our understanding of depression and enabling antidepressant medication development. The CUMS model has significant face validity since it induces fundamental depression symptoms in humans, such as anhedonia, behavioral despair, anxiety, cognitive impairments, and changes in sleep, food, and social behavior. Its construct validity is demonstrated by the dysregulation of neurobiological systems involved in depression, including monoaminergic neurotransmission, the hypothalamic-pituitary-adrenal axis, neuroinflammatory processes, and structural brain alterations. Critically, the model's predictive validity is demonstrated by the reversal of CUMS-induced deficits following treatment with clinically effective antidepressants such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. This review comprehensivelyassesses the multifarious depressive-like phenotypes in the CUMS model using behavioral paradigms like sucrose preference, forced swim, tail suspension, elevated plus maze, and novel object recognition tests. It investigates the neurobiological mechanisms that underlie CUMS-induced behaviors, including signaling pathways involving tumor necrosis factor-alpha, brain-derived neurotrophic factor and its receptor TrkB, cyclooxygenase-2, glycogen synthase kinase-3 beta, and the kynurenine pathway. This review emphasizes the CUMS model's importance as a translationally relevant tool for unraveling the complex mechanisms underlying depression and facilitating the development of improved and targeted interventions for this debilitating neuropsychiatric disorder by providing a comprehensive overview of its validity, behavioral assessments, and neurobiological underpinnings.

Epilepsy-associated Kv1.1 channel subunits regulate intrinsic cardiac pacemaking in mice.

The heartbeat originates from spontaneous action potentials in specialized pacemaker cells within the sinoatrial node (SAN) of the right atrium. Voltage-gated potassium channels in SAN myocytes mediate outward K+ currents that regulate cardiac pacemaking by controlling action potential repolarization, influencing the time between heartbeats. Gene expression studies have identified transcripts for many types of voltage-gated potassium channels in the SAN, but most remain of unknown functional significance. One such gene is Kcna1, which encodes epilepsy-associated voltage-gated Kv1.1 K+ channel α-subunits that are important for regulating action potential firing in neurons and cardiomyocytes. Here, we investigated the functional contribution of Kv1.1 to cardiac pacemaking at the whole heart, SAN, and SAN myocyte levels by performing Langendorff-perfused isolated heart preparations, multielectrode array recordings, patch clamp electrophysiology, and immunocytochemistry using Kcna1 knockout (KO) and wild-type (WT) mice. Our results showed that either genetic or pharmacological ablation of Kv1.1 significantly decreased the SAN firing rate, primarily by impairing SAN myocyte action potential repolarization. Voltage-clamp electrophysiology and immunocytochemistry revealed that Kv1.1 exerts its effects despite contributing only a small outward K+ current component, which we term IKv1.1, and despite apparently being present in low abundance at the protein level in SAN myocytes. These findings establish Kv1.1 as the first identified member of the Kv1 channel family to play a role in sinoatrial function, thereby rendering it a potential candidate and therapeutic targeting of sinus node dysfunction. Furthermore, our results demonstrate that small currents generated via low-abundance channels can still have significant impacts on cardiac pacemaking.

RAM Cannula versus Short Binasal Prongs for Non-invasive Ventilation in Preterm Infants: An Updated Systematic Review and Meta-analysis.

OBJECTIVES: To compare the efficacy and safety of RAM cannula with short binasal prongs (SBPs) as nasal interfaces in preterm infants requiring nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV). METHODS: The authors searched electronic databases (Medline, Embase, and Web of Science) and trial registries from inception until March 15, 2024, for randomized controlled trials (RCTs) comparing the RAM cannula with SBP for delivering nCPAP/NIPPV. They performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was failure of nCPAP/NIPPV. Secondary outcomes included nasal injury, mechanical ventilation, air leaks, and mortality. RESULTS: Five RCTs (825 participants) were included. There was no significant difference in nCPAP/NIPPV failure (RR: 1.04; 95% CI: 0.58 to 1.87) or the need for invasive mechanical ventilation (RR: 1.23; 95% CI: 0.75 to 2.01) between the RAM cannula and SBP groups (low to very low certainty). Compared with infants in the SBP group, those in the RAM cannula group had a significantly lower incidence of moderate to severe nasal injury [(5 RCTs, 825 participants; RR: 0.34; 95% CI: 0.18 to 0.66); low certainty] and any nasal injury [(RR: 0.44; 95% CI: 0.26 to 0.76; very low certainty)]. There was no significant difference in the other clinical outcomes. CONCLUSIONS: In comparison to SBP, the RAM cannula may have little to no effect on nCPAP/NIPPV failure, but the evidence is very uncertain. Low-certainty evidence suggests that the use of RAM cannula possibly results in reduction in moderate to severe nasal trauma in preterm infants receiving nCPAP/NIPPV.

Cancer Trials Ecosystem in India-Ready for Prime Time?

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.