Mapping malaria vectors and insecticide resistance in a high-endemic district of Haryana, India: implications for vector control strategies.

BACKGROUND: Achieving effective control and elimination of malaria in endemic regions necessitates a comprehensive understanding of local mosquito species responsible for malaria transmission and their susceptibility to insecticides. METHODS: The study was conducted in the highly malaria prone Ujina Primary Health Center of Nuh (Mewat) district of Haryana state of India. Monthly entomological surveys were carried out for adult mosquito collections via indoor resting collections, light trap collections, and pyrethrum spray collections. Larvae were also collected from different breeding sites prevalent in the region. Insecticide resistance bioassay, vector incrimination, blood meal analysis was done with the collected vector mosquitoes. RESULTS: A total of 34,974 adult Anopheles mosquitoes were caught during the survey period, out of which Anopheles subpictus was predominant (54.7%). Among vectors, Anopheles stephensi was predominant (15.5%) followed by Anopheles culicifacies (10.1%). The Human Blood Index (HBI) in the case of An. culicifacies and An. stephensi was 6.66 and 9.09, respectively. Vector incrimination results revealed Plasmodium vivax positivity rate of 1.6% for An. culicifacies. Both the vector species were found resistant to DDT, malathion and deltamethrin. CONCLUSION: The emergence of insecticide resistance in both vector species, compromises the effectiveness of commonly used public health insecticides. Consequently, the implementation of robust insecticide resistance management strategies becomes imperative. To effectively tackle the malaria transmission, a significant shift in vector control strategies is warranted, with careful consideration and adaptation to address specific challenges encountered in malaria elimination efforts.

Concentration-Dependent Diffusion of Monoclonal Antibodies: Underlying Mechanisms of Anomalous Diffusion.

The development, storage, transport, and subcutaneous delivery of highly concentrated monoclonal antibody formulations pose significant challenges due to the high solution viscosity and low diffusion of the antibody molecules in crowded environments. These issues often stem from the self-associating behavior of the antibody molecules, potentially leading to aggregation. In this work, we used a dissipative particle dynamics-based coarse-grained model to investigate the diffusion behavior of IgG1 antibody molecules in aqueous solutions with 15 and 32 mM NaCl and antibody concentrations ranging from 10 to 400 mg/mL. We determined the coarse-grained interaction parameters by matching the calculated structure factor with the computational and experimental data from the literature. Our results indicate Fickian diffusion for antibody concentrations of 10 and 25 mg/mL and anomalous diffusion for concentrations exceeding 50 mg/mL. The anomalous diffusion was observed for ∼0.33 to 0.4 µs, followed by Fickian diffusion for all antibody concentrations. We observed a strong linear correlation between the diffusion behavior of the antibody molecules (diffusion coefficient D and anomalous diffusion exponent α) and the amount of aggregates present in the solution and between the amount of aggregates and the Coulomb interaction energy. The investigation of underlying mechanisms for anomalous diffusion revealed that in crowded environments at high antibody concentrations, the attractive interaction between electrostatically complementary regions of the antibody molecules could further bring the neighboring molecules closer to one another, ultimately resulting in aggregate formation. Further, the Coulomb attraction can continue to draw more molecules together, forming larger aggregates.

Road accidents on Indian National highways, ambulance reachability and transportation of injured to trauma facility: Survey-based introspection of golden hour.

Background: The transportation system plays a crucial role in the context of socioeconomic development, whereas the highway infrastructure acts as a base for the transportation system. In recent years, a rich impetus has been given to the development of road infrastructure by Indian governance. There is a need to introspect how well the prevailing highway infrastructure is equipped with emergency rescue management during road accidents. Lack of ambulance service and trauma facilities along the highways results in a steady loss of lives and injuries and increases people's exposure to risks. Objective: This study aims to determine the response time of ambulance reachability to the accident spot on Indian national highways associated with heavy commercial transportation. Also, determining the time to transport the injured to the nearest trauma facility is another factor included as an objective in this investigation. Methods: The study adopted survey-based research, whereby the variables in the questionnaire were designed to record and assess the time for an ambulance to reach the accident spot and, from there, to transport the injured to the trauma management facility on Indian highways. Two hundred twenty-five participants who were either victims/relatives of victims or those involved in the rescue of the injured have participated in the survey. The dates of the accident events were 2017 and 2022. Results: The survey resulted in the identification of two categories of highway accidents. The first category of accidents happened on the highways near city limits/dense settlements, and the second category occurred on the core highways. The percentage of accidents caused on the highways either adjacent to or passing through the city limits/dense settlements was reported to be higher than the accidents on the core highways. Ninety percent of the participants reported successful contact with the ambulance call/service centre, but only ~75% success rate exists for ambulances to reach the accident scene. On the core highways, the time taken for the ambulance to arrive at the accident scene is 25-35 minutes. The results from the survey ascertained that the patients were prioritised for treatment in the nearest hospitals (irrespective of having a trauma facility) at a distance of ~12-20 km, for which the time taken is ~15-25 minutes. Importantly, from the interviews, it is understood that in many cases, these hospitals have further referred to specialty hospitals located in nearby cities or trauma centres with greater facilities. Occasions exist where the injured were taken directly to hospitals 30-40 km from the accident spot, for which the time was more than 40 minutes. Conclusions: The results provide evidence that in either of the accident cases on the highways that are adjacent to/passing through the city limits or on the core highways, the total time for emergency care accessibility is nearly 60 minutes or greater; this implies that in the majority of cases, there is very meagre time left to provide emergency medical care to the needy and injured on the Indian highways to abide by the concept of golden hour. Plausible reforms backed by technology for enabling highways into 'emergency rescuable highways' are highly needed to guarantee a safer and more sustainable transportation system in India.

Unraveling the Photoionization Dynamics of Indole in Aqueous and Ethanol Solutions.

The photoionization dynamics of indole, the ultraviolet-B chromophore of tryptophan, were explored in water and ethanol using ultrafast transient absorption spectroscopy with 292, 268, and 200 nm excitation. By studying the femtosecond-to-nanosecond dynamics of indole in two different solvents, a new photophysical model has been generated that explains many previously unsolved facets of indole's complex solution phase photochemistry. Photoionization is only an active pathway for indole in aqueous solution, leading to a reduction in the fluorescence quantum yield in water-rich environments, which is frequently used in biophysical experiments as a key signature of the protein-folded state. Photoionization of indole in aqueous solution was observed for all three pump wavelengths but via two different mechanisms. For 200 nm excitation, electrons are ballistically ejected directly into the bulk solvent. Conversely, 292 and 268 nm excitation populates an admixture of two 1ππ* states, which form a dynamic equilibrium with a tightly bound indole cation and electron-ion pair. The ion pair dissociates on a nanosecond time scale, generating separated solvated electrons and indole cations. The charged species serve as important precursors to triplet indole production and greatly enhance the overall intersystem crossing rate. Our proposed photophysical model for indole in aqueous solution is the most appropriate for describing photoinduced dynamics of tryptophan in polypeptide sequences; tryptophan in aqueous pH 7 solution is zwitterionic, unlike in peptides, and resultantly has a competitive excited state proton transfer pathway that quenches the tryptophan fluorescence.

Early-Onset Takayasu Arteritis in Childhood: A Case Report.

Takayasu arteritis is a chronic, idiopathic, inflammatory disease mainly affecting medium and large vessels with a significant rate of morbidity and mortality. The vessels most frequently affected are the aorta and its branches; branches originating from the aortic arch include right brachiocephalic trunk and its branches, left common carotid artery, left subclavian artery, coronary arteries from the ascending aorta, celiac trunk, right and left renal arteries, superior and inferior mesenteric arteries from the descending aorta, and right and left iliofemoral arteries. Local and systemic inflammation along with end organ ischemia is attributed to severe clinical manifestations associated with this condition. Although Takayasu arteritis is more commonly diagnosed in adults, this study highlights the unusual occurrence of childhood-onset Takayasu arteritis (TAK), presenting a unique set of diagnostic challenges. We present a case of a seven-year-old female patient who manifested atypical symptoms, such as absent pulses and malignant hypertension at an early age, leading to a delayed diagnosis. The patient's clinical course, including diagnostic workup and imaging studies such as CT or MR angiography, is thoroughly discussed. This study emphasizes the importance of recognizing the subtleties of Takayasu arteritis in children. The disease may initially masquerade as other common conditions, such as peripheral arterial disease, coarctation of aorta, renal artery stenosis, chronic renal disease, and increased intracranial pressure, thereby hindering timely diagnosis and appropriate intervention. This case underscores the importance of considering Takayasu arteritis as a differential diagnosis in children, presenting with unexplained constitutional symptoms or signs of systemic vasculitis, emphasizing the need for multidisciplinary collaboration and tailored therapeutic intervention to optimize the outcome in this rare and potentially debilitating condition.

SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.

SARS-CoV-2, the causative agent of COVID-19, uses the host endolysosomal system for entry, replication, and egress. Previous studies have shown that the SARS-CoV-2 virulence factor ORF3a interacts with the lysosomal tethering factor HOPS complex and blocks HOPS-mediated late endosome and autophagosome fusion with lysosomes. Here, we report that SARS-CoV-2 infection leads to hyperactivation of the late endosomal and lysosomal small GTP-binding protein Rab7, which is dependent on ORF3a expression. We also observed Rab7 hyperactivation in naturally occurring ORF3a variants encoded by distinct SARS-CoV-2 variants. We found that ORF3a, in complex with Vps39, sequesters the Rab7 GAP TBC1D5 and displaces Rab7 from this complex. Thus, ORF3a disrupts the GTP hydrolysis cycle of Rab7, which is beneficial for viral production, whereas the Rab7 GDP-locked mutant strongly reduces viral replication. Hyperactivation of Rab7 in ORF3a-expressing cells impaired CI-M6PR retrieval from late endosomes to the trans-Golgi network, disrupting the biosynthetic transport of newly synthesized hydrolases to lysosomes. Furthermore, the tethering of the Rab7- and Arl8b-positive compartments was strikingly reduced upon ORF3a expression. As SARS-CoV-2 egress requires Arl8b, these findings suggest that ORF3a-mediated hyperactivation of Rab7 serves a multitude of functions, including blocking endolysosome formation, interrupting the transport of lysosomal hydrolases, and promoting viral egress.

A Rare Case of Isolated Congenital Facial Nerve Aplasia in an Infant.

Facial nerve aplasia is an exceptionally rare condition, with only a few reported cases in the existing medical literature. Congenital facial palsy (CFP) is characterized by the clinical manifestation of facial paralysis involving the seventh cranial nerve, either evident at birth or shortly thereafter. This condition is categorized based on various parameters, including the presence of trauma or developmental origins, unilateral or bilateral involvement, and whether the paralysis is complete or incomplete. While CFP is uncommon, its occurrence can pose multiple challenges for newborns, such as difficulties in nursing and incomplete closure of the affected eye. In cases where the paralysis persists, there is the potential for a long-term impact on the child's speech, emotional expressions, and mastication. Here we present the case of a six-month-old male child who experienced lower motor neuron palsy of the facial nerve on the left side since birth. This case contributes to the limited knowledge surrounding facial nerve aplasia and CFP, emphasizing the importance of early diagnosis and intervention to mitigate potential long-term complications.

Doxorubicin catalyses self-assembly of p53 by phase separation.

Liquid-liquid phase separation plays a crucial role in cellular physiology, as it leads to the formation of membrane-less organelles in response to various internal stimuli, contributing to various cellular functions. However, the influence of exogenous stimuli on this process in the context of disease intervention remains unexplored. In this current investigation, we explore the impact of doxorubicin on the abnormal self-assembly of p53 using a combination of biophysical and imaging techniques. Additionally, we shed light on the potential mechanisms behind chemoresistance in cancer cells carrying mutant p53. Our findings reveal that doxorubicin co-localizes with both wild-type p53 (WTp53) and its mutant variants. Our in vitro experiments indicate that doxorubicin interacts with the N-terminal-deleted form of WTp53 (WTp53ΔNterm), inducing liquid-liquid phase separation, ultimately leading to protein aggregation. Notably, the p53 variants at the R273 position exhibit a propensity for phase separation even in the absence of doxorubicin, highlighting the destabilizing effects of point mutations at this position. The strong interaction between doxorubicin and p53 variants, along with its localization within the protein condensates, provides a potential explanation for the development of chemotherapy resistance. Collectively, our cellular and in vitro studies emphasize the role of exogenous agents in driving phase separation-mediated p53 aggregation.

An interventional study evaluating the NTCP (NATIONAL TOBACCO CONTROL PROGRAM) guidelines-based education model in semi-urban school population.

Background: The present study was carried out to assess the awareness of the adverse consequences of tobacco use in the semi-urban school population in Wardha district because tobacco use in schools is a significant concern and is rising at an alarming rate. The purpose of the current study was to assess the prevalence of tobacco use among students and teachers as well as their knowledge of the negative effects of tobacco use. It also aimed to educate students and teachers about these effects and assess the effectiveness of the intervention. Methodology: A total of 350 students from a semi-urban school in the Wardha area participated in this study. Pre-tests were administered to a group of chosen kids and instructors to gauge their familiarity with tobacco. After the pre-test data were analyzed, teachers were offered intervention. PowerPoint presentations, posters, and models were used to educate them about the dangers of tobacco usage for dental health. There were discussions, role plays, and skits done. After the instruction, the students took a post-test to gauge how well they understood what they had learned. Results: The recent study is a significant step toward the semi-urban school population quitting smoking. Overall, the study involves testing participants' knowledge, teaching them about tobacco's negative consequences, and inspiring habitual smokers to completely kick the habit. The majority of the NTCP questionnaire's elements were significant when compared to knowledge of tobacco use and its components (*p0.05; significant). Conclusion: The suggested study is a significant step toward the semi-urban school population quitting smoking. The research will provide a genuine and dependable change and help promote optimal dental health.

Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants.

Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.

Effect of tertiary processing on physical, optical, phytochemical as well as rheological properties of high-protein rice.

The first high-protein rice variety of India, CR Dhan 310, developed at ICAR-NRRI, Cuttack is being selected for the study. It contains 10.1% protein in milled rice as compared to 6-7% protein content in the milled rice of any other normal variety. It has intermediate amylose content (25.1%), medium bold grains rich in protein (10.1%) The significant changes in properties of raw and parboiled rice on processing were studied at statistical differences of p ≤ 0.05. These properties included physical, optical, antioxidant and rheological properties which changed with different processing techniques. All the three processes namely, puffing, popping and flaking increased the dimensions as compared to the raw rice. Peak viscosity measurements demonstrated the breakdown of starch molecules, with white rice having the greatest value (4145 cP) and popped rice having the lowest value (2017 cP) as a result of the starch granules being gelatinized during the production of popped rice. Highest anthocyanin content (2.93 mg/100 g) was observed in puffed rice, phenolic content (347.93 mg/100 g) was highest in popped rice and flaked/flattened rice showed highest flavonoid content (127.12 mg/100 g) indicating that tertiary processing of rice obtained higher values of phytochemicals when compared to the plain high-protein rice. This indicates that the processed products of rice can be consumed directly as ready-to-eat or can be used in preparation of other functional foods to combat malnutrition and build nutritional security. The study indicates that processing could improve the nutritional quality of the rice products.

Site-specific electronic structure of covalently linked bimetallic dyads from nitrogen K-edge x-ray absorption spectroscopy.

A nitrogen K-edge x-ray absorption near-edge structure (XANES) survey is presented for tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2‴,3‴-j]phenazine (tpphz)-bridged bimetallic assemblies that couple chromophore and catalyst transition metal complexes for light driven catalysis, as well as their individual molecular constituents. We demonstrate the high N site sensitivity of the N pre-edge XANES features, which are energetically well-separated for the phenazine bridge N atoms and for the individual metal-bound N atoms of the inner coordination sphere ligands. By comparison with the time-dependent density functional theory calculated spectra, we determine the origins of these distinguishable spectral features. We find that metal coordination generates large shifts toward higher energy for the metal-bound N atoms, with increasing shift for 3d < 4d < 5d metal bonding. This is attributed to increasing ligand-to-metal σ donation that increases the effective charge of the bound N atoms and stabilizes the N 1s core electrons. In contrast, the phenazine bridge N pre-edge peak is found at a lower energy due to stabilization of the low energy electron accepting orbital localized on the phenazine motif. While no sensitivity to ground state electronic coupling between the individual molecular subunits was observed, the spectra are sensitive to structural distortions of the tpphz bridge. These results demonstrate N K-edge XANES as a local probe of electronic structure in large bridging ligand motifs, able to distinctly investigate the ligand-centered orbitals involved in metal-to-ligand and ligand-to-ligand electron transfer following light absorption.

Assessment of Differences in Oral Health Knowledge, Attitudes, and Behavior Among Preclinical and Clinical Dental Students.

Aim To assess and compare differences in oral health knowledge, attitudes, and behavior among preclinical and clinical dental students of Dental Institute, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India. Material and methods A total of 175 students responded to a total of 37 questions regarding their knowledge, attitudes, and behavior regarding dentistry and oral health. The mean percentage scores and standard deviation were calculated to assess the relation between knowledge, attitude, and behavior. Results It was observed that the students in the clinical phase had significantly better knowledge and attitude towards oral health than preclinical undergraduates. There was no significant difference in mean and SD among clinical and preclinical students in behavior while statistically significant differences were observed in their responses to questions related to knowledge (p = 0.000) and attitude (p = 0.007). Female students had better knowledge than male students (p = 0.029). Conclusion Clinical dental students of the institute showed a marginally higher KAP regarding oral health than preclinical students. This might reveal an ineffective transition of the students from the preclinical to the clinical stage. On intergender comparison, the females were better oriented than males towards oral health.

Secreted IgM modulates IL-10 expression in B cells.

IL-10+ B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10+ B cell differentiation are ill-defined. Here we find that IL-10+ B cells expand in mice lacking secreted IgM ((s)IgM-/-) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10+ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10+ B cells. Lack of the high affinity receptor for sIgM, FcµR, in B cells translates into an intermediate IL-10+ B cell phenotype relative to WT or sIgM-/- mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcµR, thereby revealing a function of sIgM in regulating immune homeostasis.

An Emerging Foodborne Pathogen Spotlight: A Bibliometric Analysis and Scholarly Review of Escherichia coli O157 Research.

Foodborne infections pose a substantial global threat, causing an estimated 600 million illnesses and resulting in approximately 420,000 deaths annually. Among the diverse array of pathogens implicated in these infections, Escherichia coli (E. coli), specifically the O157 strain (E. coli O157), emerges as a prominent pathogen associated with severe outbreaks. This study employs a comprehensive bibliometric analysis and scholarly review focused on E. coli O157 research. The bibliometric analysis highlights the significant role played by the United States in the E. coli O157 research domain. Further exploration underscores the noteworthy contributions of the researcher Doyle MP, whose body of work, consisting of 84 documents and an impressive H-Index of 49, reflects their substantial impact in the field. Recent research trends indicate a discernible shift towards innovative detection methods, exemplified by the adoption of CRISPR-CAS and Loop-Mediated Isothermal Amplification. Moreover, high-throughput whole-genome sequencing techniques are gaining prominence for the expeditious analysis of pathogenic E. coli strains. Scientists are increasingly exploring antimicrobial agents, including phage therapy, to address the challenges posed by antibiotic-resistant E. coli strains, thereby addressing critical concerns related to multi-drug resistance. This comprehensive analysis provides vital insights into the dynamic landscape of E. coli O157 research. It serves as a valuable resource for researchers, policymakers, and healthcare professionals dedicated to mitigating E. coli O157 outbreaks and advancing global public health strategies.

Leaching of Phytochemicals from Beans during Hydration, Kinetics, and Modeling.

In the current era, there is a growing emphasis on the circular economy and the valorization of waste products. Bean processing industries generate substantial nutrient-rich waste laden with valuable phytochemicals. Understanding the leaching patterns and kinetics of major phytochemicals is key to designing better processes leading to increased sustainability. This review investigates phytochemical leaching mechanisms and kinetic modeling methods. Firstly we lay the foundation with a broad theoretical framework, and later deal with kinetic modeling approaches and promising areas for future research. Currently, the composition of industrial-scale bean wastewater remains undocumented in the open literature. Nonetheless, drawing from existing studies and general bean composition knowledge, we proposed a multi-phase leaching process. We hypothesize three distinct phases: initial leaching of phytochemicals from the outer seed coat, followed by a second phase involving polysaccharides, and concluding with a third phase wherein phenolic acids within the cotyledons leach into the hydration water. This review aims to shed light on the complex process of phytochemical leaching from common beans during hydration. By combining theoretical insights and practical modeling strategies, this work seeks to enhance our understanding of this phenomenon and ultimately contribute to the optimization of food processing methods with reduced environmental impact.

Synthesis of Pectin and Eggshell Biowaste-Mediated Nano-hydroxyapatite (nHAp), Their Physicochemical Characterizations, and Use as Antibacterial Material.

The current study reports the synthesis of sustainable nano-hydroxyapatite (nHAp) using a wet chemical precipitation approach. The materials used in the green synthesis of nHAp were obtained from environmental biowastes such as HAp from eggshells and pectin from banana peels. The physicochemical characterization of obtained nHAp was carried out using different techniques. For instance, X-ray diffractometer (XRD) and FTIR spectroscopy were used to study the crystallinity and synthesis of nHAp respectively. In addition, the morphology and elemental composition of nHAP were studied using FESEM equipped with EDX. HRTEM showed the internal structure of nHAP and calculated its grain size which was 64 nm. Furthermore, the prepared nHAp was explored for its antibacterial and antibiofilm activity which has received less attention previously. The obtained results showed the potential of pectin-bound nHAp as an antibacterial agent for various biomedical and healthcare applications.