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Background: Carpal coalition referes to the fusion of two or more carpal bones in the wrist. This has a prevalence of 0.1 % in Caucasian populations, where lunotriquetral coalition is reported as the most common type. The incidence in Asian populations is not known. Most of lunotriquetral coaliations are asymptomatic and are incidently diagnosed, however, they can be the cause of wrist pain at times. Case report: We hereby present a case of 45 years old male with previously asymptomatic lunotriquetral coaliation with fracture through it post-injury. Classification, diagnostic methodology along with management of leunotriquetral coaliation and fracture have been discussed. Conclusion: Most of symptomatic patients with leunotriquetral coalition can be managed conservatively, however at times, symptomatology, instability or associated fractures may warrant for surgical procedures.

IntroductionRenal cell carcinoma (RCC) represents cancer originating from the renal epithelium and accounts for > 90% of cancers in the kidney. Prostate-specific membrane antigen (PSMA) is overexpressed in tumor-associated neovascular endothelial cells of many solid tumors, including metastatic RCC. Although studied in several small clinical studies, PSMA-based imaging and therapy have not been pursued rigorously in preclinical RCC. This study aimed to evaluate the preclinical performance of PSMA-based radiotheranostic agents in a relevant murine model.MethodsA PSMA-overexpressing murine cell line, PSMA+ RENCA, was developed by lentiviral transduction. PSMA-based theranostic agents, 68Ga-L1/177Lu-L1/225Ac-L1, were synthesized in high radiochemical yield and purity following our reported methods. Immunocompetent BALB/c mice were used for flank and orthotopic tumor inoculation. 68Ga-L1 was evaluated in small animal PET/CT imaging in flank and PET/MR imaging in orthotopic models. Cell viability studies were conducted for 177Lu-L1 and 225Ac-L1. Proof-of-concept treatment studies were performed using 225Ac-L1 (0, 37 kBq, 2 kBq × 37 kBq, 1 week apart) using PSMA+ RENCA in the flank model.ResultsCellular uptake of 68Ga-L1, 177Lu-L1, and 225Ac-L1 confirmed the specificity of the agents to PSMA+ RENCA cells rather than to RENCA (wt) cells, which are low in PSMA expression. The uptake in PSMA+ RENCA cells at 1 h for 68Ga-L1 (49.0% incubated dose [ID] ± 3.6%ID/million cells), 177Lu-L1 (22.1%ID ± 0.5%ID)/million cells), and 225Ac-L1 (4.1% ± 0.2% ID)/million cells), respectively, were higher than the RENCA (wt) cells (~ 1%ID–2%ID/million cells). PET/CT images displayed > 7-fold higher accumulation of 68Ga-L1 in PSMA+ RENCA compared to RENCA (wt) in flank implantation at 1 h. A twofold higher accumulation of 68Ga-L1 was observed in orthotopic tumors than in normal kidneys during 1–3 h postinjection. High lung uptake was observed with 68Ga-L1 PET/MR imaging 3 weeks after orthotopic implantation of PSMA+ RENCA due to spontaneous lung metastases. The imaging data were further confirmed by immunohistochemical characterization. 225Ac-L1 (0-37 kBq) displayed a dose-dependent reduction of cell proliferation in the PSMA+ RENCA cells after 48 h incubation; ~ 40% reduction in the cells with treated 37 kBq compared to vehicle (p < 0.001); however, no effect was observed with 177Lu-L1 (0–3700 kBq) up to 144 h postinoculation, suggesting lower efficacy of β-particle-emitting radiations in cellular studies compared to α-particle-emitting 225Ac-L1. Animals treated with 225Ac-L1 at 1 week posttumor inoculation in flank models displayed significant tumor growth delay (p < 0.03) and longer median survival of 21 days and 24 days for the treatment groups 37 kBq and 2 kBq × 37 kBq, respectively, compared to the vehicle group (12 days).ConclusionThe results suggest that a theranostic strategy targeting PSMA, employing PET and α-emitting radiopharmaceuticals, enabled tumor growth control and enhanced survival in a relevant immunocompetent murine model of RCC. These studies provide the rationale for clinical studies of PSMA-targeted theranostic agents in patients with RCC.

Two of the main challenges in origami antenna designs are creating a reliable hinge and achieving precise actuation for optimal electromagnetic (EM) performance. Herein, a waterbomb origami ring antenna is introduced, integrating the waterbomb origami principle, 3D‐printed liquid metal (LM) hinges, and robotic shape morphing. The approach, combining 3D printing, robotic actuation, and innovative antenna design, enables various origami folding patterns, enhancing both portability and EM performance. This antenna's functionality has been successfully demonstrated, displaying its communication capabilities with another antenna and its ability to navigate narrow spaces on a remote‐controlled wheel robot. The 3D‐printed LM hinge exhibits low DC resistance (200 ± 1.6 mΩ) at both flat and folded state, and, with robotic control, the antenna achieves less than 1° folding angle accuracy and a 66% folding area ratio. The antenna operates in two modes at 2.08 and 2.4 GHz, ideal for fixed mobile use and radiolocation. Through extensive simulations and experiments, the antenna is evaluated in both flat and folded states, focusing on resonant frequency, gain patterns, and hinge connectivity. The findings confirm that the waterbomb origami ring antenna consistently maintains EM performance during folding and unfolding, with stable resonant frequencies and gain patterns, proving the antenna's reliability and adaptability for use in portable and mobile devices.

Background:. Standard breast reduction dressings such as Prineo are used to cover surgical wounds, in combination with a binder or support bra. The Prevena Restor BellaForm is a negative pressure wound therapy dressing that covers the entirety of the breast mound and is purported to provide further support and reduce swelling. The aim of this study was to compare the Restor to standard-of-care dressings. Methods:. The study was a randomized control trial of women undergoing bilateral breast reduction with one breast being dressed with the Prevena Restor BellaForm dressing and the other having standard of care (Prineo). Outcomes measured were drain outputs, postoperative length of stay, quality of scarring, patient preference for dressings, and adverse events. Follow-up was at 1, 2–6, and 26 weeks. Results:. The results show a reduction in postoperative days 1 and 2 average drain output on the Restor side compared with standard dressings. Patient-reported outcome measures showed less bruising. There was no difference in postoperative length of stay and no difference in appearance of scars at the 26-week follow-up period. One patient required removal of the dressing due to irritation and one patient required assistance with resealing of the vacuum. Conclusions:. We have shown benefits to drain output and comfort using close incisional negative pressure therapy in breast reduction mammaplasty. We plan to continue to investigate close incisional negative pressure therapy in larger comparative trials for other breast procedures including implant-based reconstruction, where a reduction in drain output could be of great benefit to both healing and reduction of infection risk.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Impaired mucociliary clearance due to altered respiratory physiology in COPD presents an exceptional opportunity for bacterial proliferation. Sampling the respiratory tract using sputum or Bronchoalveolar Lavage (BAL) can be labourious and inconvenient, particularly in chronically debilitated patients. Saliva offers an interesting and non invasive method for assessing COPD patients and preventing exacerbations. Aim: To use saliva to analyse the association between the frequency of positive Potentially Pathological Bacterial Isolates (PPBI) and COPD exacerbations in relation to the frequency of exacerbations and the severity of the disease. Materials and Methods: This cross-sectional study was conducted over a period of one year (July 2022 to June 2023) among COPD patients attending the outpatient department at the Department of Respiratory Medicine, GMERS Medical College, Gotri, Vadodara, Gujarat, India. A total of 60 patients with COPD, diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 guidelines, were included. The patients were categorised based on the severity of airflow limitation, GOLD “ABCD” assessment tool, and number of exacerbations. Salivary samples were collected and subjected to microbiological analysis using laboratory conventional culture techniques. Analysis of Variance (ANOVA) and t-tests were applied. Results: The mean age was 64±5.1 years. S. pneumoniae and H. influenza were common bacterial findings in all stages of COPD, while E. coli and A. baumannii were isolated in GOLD Group D patients. Disease severity also showed a significant association with oral bacterial composition (p=0.010) and the frequency of exacerbations (p=0.03). Conclusion: The current study demonstrates an association between oral bacteria and COPD, especially in patients with severe symptoms (GOLD Group D). Additionally, patients with repeated exacerbations exhibited a different oral bacterial composition, thus supporting the use of saliva as a non invasive specimen for assessing heterogeneous diseases like COPD and designing an empiric antibiotic regimen for those PPBI.

Abstract Background Oral health of preschool children remains a concern globally. Primary healthcare providers are in a vital position to support preventive oral care programmes. This study explored current practices, perception and barriers of primary health care professionals towards oral health promotion program of children in Qatar. Methods The qualitative research used focus group discussions and interviewed a total of 108 participants that were audio recorded and transcribed verbatim. Four major themes emerged and were analysed to explore contextual patterns within the data. Results Participants acknowledged the high prevalence of caries in children and identified the causes in the local context which included parental practices, poor dietary habits, impact of culture lack of oral health knowledge, limitations in the healthcare system, and negative role of the media. However, complex barriers were exposed, including lack of time and ownership, system coordination between organizations, and lack of policy. Conclusion Health professionals and bureaucrats involved in decision-making held a positive attitude towards oral health prevention programs and were enthusiastic to initiate and support these programs.

Land surface temperature (LST) and its diurnal variability are key to understanding the land-atmosphere interactions, hydrological processes and climate change. However, at any given point in time approximately half of the Earth's surface is covered by clouds. This restricts the availability of LST through satellite remote sensing, which works best under clear skies. However, in situ observations continue to monitor atmospheric conditions beneath the clouds that could complement satellite measurements during cloudy conditions. The present study explores a novel approach to estimate hourly LST during the daylight hours using remotely sensed surface solar absorption and in situ observations of daily LST extremes (maximum and minimum) together with an adaptive non-linear fitting approach. A learning algorithm trained against in-situ measurements of LST extrema and diurnal cycle of surface solar absorption together with the associated linear correlation between the two parameters, is used to estimate an optimized set of parameters to approximate hourly LST for each day during the daylight hours between sunrise and sunset. Results show that the method captures the intra-day variability of LST very well under most sky conditions with rms errors below 1.5 K.

BackgroundSoil- and water-transmitted helminths are a major concern in the developing world due to their high prevalence. More than a quarter of the population were estimated to be infected with helminths in these endemic zones.Research designAn in silico approach was used to design a vaccine construct against the Taenia genus utilizing the proteomic information and evaluation of the construct using immune-informatics.ResultsOur study identified 451 conserved proteins in Taenia spp. using the existing proteome; out of these, 141 were found to be expressed in cysticerci. These proteins were screened for antigenic epitopes and a multi-subunit vaccine was constructed. The constructed vaccine was assessed for its efficacy in mounting the appropriate immune response. Our constructed vaccine showed stability and optimal performance against the TLR 4 receptor, which is reported to be upregulated in Taenia infections in hosts.ConclusionImmune-informatics tools help design vaccines for neglected diseases such as those attributed to helminths, which are known to cause widespread morbidity. Our vaccine construct holds tremendous potential in conferring protection against all Taenia spp. of clinical relevance to human.

The present study aims to develop a novel hybrid composite by incorporating clamshell as a secondary reinforcing filler into a bamboo-epoxy composite. The primary objective of this hybridization is to optimize the synergistic benefits of each component, harnessing the strength of bamboo fibres, the durability of epoxy, and the cost-effective repurposing of the waste clamshell. Compression moulding was employed to develop composites with varying filler content (0- 9 wt%). The effect of filler on the physical and mechanical properties of bamboo-epoxy composites was evaluated by conducting tests as per ASTM standards. Experimental results show that the addition of clamshell filler significantly improved composites' properties, but there was a limitation to the addition. Hardness, tensile, and flexural properties were increased, whereas impact strength was reduced. Composites with 6 wt% clamshell exhibited optimum properties, enhancing tensile strength by 20.5% and flexural strength by 24.4 % compared to composites without filler. SEM analysis of fractured tensile and bending specimens revealed an enhanced fibre-matrix bonding with the inclusion of filler and supported the experimental results obtained. The outcome of this study contributes to sustainable development by using natural resources like bamboo fibre and repurposing seashell waste to create cost-effective composite material with enhanced properties.

Abstract Background Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. Results We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. Conclusion The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world’s population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers.

Schizophrenia is a neurological disorder known to influence the motor region. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique being investigated as a treatment for schizophrenia. Resting motor threshold (RMT) is the dosage parameter for TMS treatment protocols and is known to vary between participants with limited understanding of the drivers of this variance. Previous investigations have used functional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and individual level neuroanatomy to explain RMT variability. Our previous investigation showed neuroanatomy influences RMT in both schizophrenia and healthy populations and this relationship was weakened by the presence of schizophrenia. In this study, 54 participants with schizophrenia-diagnosed, who were antipsychotic naive and 43 non-impaired controls underwent single pulse TMS, structural magnetic resonance imaging, and fMRI. An independent component analysis (ICA) was used to process fMRI data into 25 distinct channels where correlations were derived between channels. Linear and multiple regression models were used to evaluate first, the influence of these channel interactions on RMT followed by their influence when individual level neuroanatomy was also considered. We found that between-channel functional connectivity was altered in individuals with schizophrenia and that fMRI can contribute to prediction of RMT, but differently in both cohorts and to a lesser degree than individual level neuroanatomical measures. This suggests that functional connectivity influences TMS response and fMRI might help in dosage calculations of clinical TMS protocols.

In this comprehensive review, an extensive analysis has been conducted on paleoclimate datasets from climatically sensitive regions in the Indian Himalaya and Indo-Gangetic plain. Our main objective was to gain valuable insights into the broad palaeoclimatic variability during the Late Quaternary-Holocene period. To achieve this, careful categorization was focused for various archives from multi-proxy studies into three groups: glacial moraine, glacio-fluvial and lake records, and speleothems. The compilation of climate records from different geographical settings has revealed an overall coherence during warm and humid phases, with minor variations influenced by variable moisture sources and topographic changes. The analysis reveals that Indian Summer Monsoon (ISM) reached its peak during approximately 9-5 ka BP and subsequently weakened around the Mid-Holocene (ca. 4–5 ka BP). Notably, the Last Glacial Maximum (LGM) and early Holocene were characterized by significant glacial advances in the Himalayan region. Furthermore, the sedimentation rates derived from lacustrine records in different regions exhibit considerable variability. In conclusion, the compilation and comparisons of diverse palaeoclimate records have significantly improved our understanding of the regions palaeoclimate. These findings hold substantial value for planning future focused studies in the crucial climatic zone. By refining our understanding of past climate dynamics in the Indian Himalaya and Indo-Gangetic alluvium, a better comprehension of the regions susceptibility to climate change can be achieved. This, in turn, facilitates informed decisions for sustainable development and environmental management.

Prolonged low-dose administration (PLDA) of several FDA-approved drugs for noncancer conditions or dietary compounds is associated with a lower incidence of specific types of cancers and with the lower formation of metastasis. However, the underlying mechanism is unknown; there is a discrepancy between the concentration of drugs needed to kill cancer cells in vitro and the actual serum levels (10 and >1000 times lower) found in patients. In this study, we evaluated the hypothesis that clonogenicity may be the target of PLDA. We compared the effect of nigericin (NIG) and menadione (MEN) on the human A549 and H460 lung and MCF-7 and MDA-MB-231 breast cancer cell lines using routine MTT and colony forming assays (CFA). The ability of both NIG and MEN to eliminate 100% of cancer cells was at least 2-10 times more potent in CFA compared to MTT assays. Our results revealed the existence of a short post-reattachment window of time when cancer cells growing at low density are more sensitive to PLDA of specific drugs likely by targeting clonogenic rather than proliferation pathways. This short ultrasensitive window of time (SUSWoT) was cell- and drug-type specific: the SUSWoT for NIG was present in H460, A549, and MDA-MB-231 cells but not evident in MCF-7 cells. Conversely, a similar SUSWoT for MEN was present in MCF-7, MDA-MD-231, and A549 cells but not evident in H460 cells. Our findings partially explain the decreased incidence of specific types of cancer by PLDA of FDA-approved drugs (or dietary compounds) for noncancer conditions.

Background and Aims: Modified electroconvulsive therapy is routinely used to treat complicated psychiatric disorders. Its therapeutic effect is directly proportional to induced seizure duration but it is associated with hemodynamic disturbances. The aim of this study was to evaluate the effect of a ketamine + propofol combination (“ketofol”) for electroconvulsive therapy and to compare these with the effects of propofol alone. Methods: In this prospective study, 60 patients aged 18–60 years with American Society of Anesthesiologists (ASA) Ι and ΙΙ for psychiatric disorders were included. Patients were divided into two groups (30 each). Group P received propofol at 10 mg/ml and group K received ketofo at 10 mg/ml (ketamine 5 mg/ml and propofol 5 mg/ml in a 1:1 ratio). Motor/electroencephalography (EEG) seizure duration, induction time, hemodynamic variables, recovery time, agitation score, and complications were recorded. Standard qualitative and quantitative tests were used to compare the data (e.g., unpaired student t-test, Chi-squared test, etc). A P value of < 0.05 was considered to be significant. Results: The mean duration of (motor/EEG) seizure was statistically significantly high in the ketofol group compared to the propofol group (P = 0.0001/0.0001). The mean induction time was significantly less in the ketofol group compared to propofol group (P = 0.0001). The recovery time was significantly early in group K patients compared to group P (P = 0.004). The ketofol group was more hemodynamically stable with comparable agitation score and side effects than patients in the propofol group. Conclusion: In modified ECT, ketofol was associated with longer seizure duration, lesser induction time, better hemodynamic stability, early recovery with comparable post ECT agitation and adverse effects compared to propofol alone.

Ksheerabdhi Sankar, Kuppusamy Anand, Swetha Ramani, Balasubramaniam Gayathri Department of Anesthesiology, SRM Medical College Hospital and Research Centre, Potheri, 603203, IndiaCorrespondence: Kuppusamy Anand, Department of Anesthesiology, SRM Medical College Hospital and Research Centre, Room No. 206, B Block, Second Floor, Potheri, 603203, India, Tel +91-98652 82288, Email anandk@srmist.edu.inBackground and Aim: Percutaneous nephrolithotomy (PCNL) under epidural anesthesia has been reported to have few advantages over general anesthesia, like lower postoperative pain and less need for analgesics. There are limited studies on PCNL being performed under neuraxial anesthesia in supine position. Hence the present study was conceived to compare hemodynamic parameters in patients undergoing percutaneous nephrolithotomy (PCNL) in the supine position under combined spinal-epidural with general anesthesia (GA).Material and Methods: A prospective, randomized control trial was conducted among 90 patients who were posted to undergo elective percutaneous nephrolithotomy in the the supine position, after obtaining Institutional Ethical Committee (IEC) approval and CTRI (Clinical Trial Registry - India) registration. Patients were randomly allotted to undergo surgery either under general anesthesia (group GA) or combined spinal epidural anesthesia (group CSE) by computer-generated random number method. Hemodynamic parameters, postoperative analgesic requirement and incidence of blood transfusion were recorded and analyzed.Results: There was no significant difference between the two groups with respect to gender, ASA grade, surgery duration, calculus size and pulse rate. There was a statistically significant reduction in mean arterial pressure from 5 to 50 minutes of surgery and less incidence of blood transfusion in patients in the CSE group. Patients who underwent PCNL in the supine position under CSE required lesser analgesics postoperatively compared to those under general anesthesia.Conclusion: Combined spinal epidural analgesia can be used as an alternative to general anesthesia for patients undergoing PCNL in the supine position in view of less MAP and reduced postoperative analgesic and blood transfusion requirement.Keywords: pulse rate, mean arterial pressure, percutaneous nephrolithotomy, ureteroscopy, supine position

The 2:1 co-crystal of nadifloxacin [systematic name: 9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid] with oxalic acid, C19H21FN2O4·0.5C2H2O4, was prepared by slow evaporation from a chloroform:acetone solvent system. Nadifloxacin belongs to the group of antibacterial drugs. The co-crystal is stabilized through an intramolecular O—H...O bond and intermolecular hydrogen bonds. It was studied by FT–IR spectroscopy, differential scanning calorimetry and X-ray diffraction. Hirshfeld surface analysis indicated that the major contribution to the packing is from O...H/H...O interactions.

Abstract Globalisation has facilitated different industries to eliminate geographical boundaries and equipped organisations to work collectively to produce goods. Pharmaceuticals is one such industry which has majorly benefited from globalisation to reduce costs and increase profitability at different aspects of research, development, manufacturing of drugs and finally distribution of drugs. Globalisation not only reduces costs and increases profits for the industry, it also makes essential medication available to all individuals even at remote areas of undeveloped, developing and developed countries. As the number of entities or participants grew in the Pharmaceutical Supply Chain (PSC), the complexity and abstractness of the drug delivery from manufacturer to consumer has increased, which raised new concerns like counterfeit medication, incorrect, incomplete or no information about the drug reaching the consumer thus undermining customer confidence and most importantly distribution delays which can cause serious impact on the life of the consumer as well as business growth. Considering all these challenges, there is a dire need for a robust PSC which can eliminate blind parties and provide a transparent chain. A transparent PSC will eliminate data fragmentation between different participating entities by creating a trail of secure, single source of truth for the entire life cycle of a medicine, thereby eliminating the introduction of counterfeits and ensuring the consumer safety. This article proposes a novel Distributed Ledger Technology (DLT) based transparent supply chain for PSC and proof‐of‐concept is implemented to analyse the scalability and efficiency of the proposed architecture. Distributed Ledger Technology (DLT) is one of the technologies which can provide such transparent PSC and Smart Contracts (SC) are the most commonly used component in such systems to implement business logic and access control mechanisms. The proposed PharmaChain model investigates all the interactions between the main entities in PSC and also addresses smart contract issues such as re‐entrance, randomness and lacking trustworthy data feed. Results are compared with other proposed solutions for PSC based on DLT.

BackgroundWeak nystagmus with fixation removed can be seen both in normal individuals and in recovery from a unilateral vestibular insult, thus its clinical significance is unclear in patients with dizziness. We thus sought to compare features of nystagmus at various stages following unilateral vestibular loss (UVL).MethodsWe enrolled thirty consecutive patients after acute UVL with impaired vestibulo-ocular reflex (VOR) gain. The patients were allocated into three groups according to time from onset of symptoms: acute (1–7 days), subacute (8–30 days), and chronic (>30 days). Patients underwent video-oculography (with and without fixation) and video head impulse testing (vHIT) to determine VOR gain. We examined the relationships amongst SPV, VOR gain, and time from symptom onset across groups.ResultsThere were 11, 10, and 9 patients in the acute, subacute, and chronic stages of UVL, respectively. With visual fixation, only 8 patients (26.7%) demonstrated nystagmus, all from the acute group. With fixation removed, 26 patients (86.7%) exhibited spontaneous nystagmus, including 90.9%, 90%, and 77.8% of the patients from the acute, subacute, and chronic groups, respectively. Horizontal nystagmus was paralytic (i.e., fast phase contralesional) in 25 (96.7%) cases. Horizontal SPV was negatively correlated with logarithm of time from onset to examination (r = −0.48, p = 0.007) and weakly negatively correlated with ipsilesional VOR gain (r = −0.325, p = 0.08).ConclusionIn the subacute or chronic stages of UVL, paralytic nystagmus with fixation removed persisted at a low intensity. Therefore, weak nystagmus in the dark may have diagnostic value in chronic dizziness.

BackgroundHelminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis.MethodologyT. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level.ConclusionWe found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite's survival and delay their recognition by host immune system.

BackgroundThe BlueStar (Welldoc) digital health solution for people with diabetes incorporates data from multiple devices and generates coaching messages using artificial intelligence. The BlueStar app syncs glucose data from the G6 (Dexcom) real-time continuous glucose monitoring (RT-CGM) system, which provides a glucose measurement every 5 minutes. ObjectiveThe objective of this real-world study of people with type 2 diabetes (T2D) using the digital health solution and RT-CGM was to evaluate change in glycemic control and engagement with the program over 3 months. MethodsParticipants were current or former enrollees in an employer-sponsored health plan, were aged 18 years or older, had a T2D diagnosis, and were not using prandial insulin. Outcomes included CGM-based glycemic metrics and engagement with the BlueStar app, including logging medications taken, exercise, food details, blood pressure, weight, and hours of sleep. ResultsParticipants in the program that met our analysis criteria (n=52) were aged a mean of 53 (SD 9) years; 37% (19/52) were female and approximately 50% (25/52) were taking diabetes medications. The RT-CGM system was worn 90% (SD 8%) of the time over 3 months. Among individuals with suboptimal glycemic control at baseline, defined as mean glucose >180 mg/dL, clinically meaningful improvements in glycemic control were observed, including reductions in a glucose management indicator (–0.8 percentage points), time above range 181-250 mg/dL (–4.4 percentage points) and time above range >250 mg/dL (–14 percentage points; all P

The Internet of Everything (IoE) is a bigger picture that tries to fit the Internet of Things (IoT) that is widely deployed in smart applications. IoE brings people, data, processes, and things to form a network that is more connected and increases overall system intelligence. A further investigation of the IoE can really mean creating a distributed network focusing on edge computing instead of relying on the cloud. Blockchain is one of the recently distributed network technologies which by structure and operations provide data integrity and security in trust-less P2P networks such as IoE. Blockchain can also remove the need for central entities which is the main hurdle for the wide adoption of IoT in large networks. IoT “things” are resource-constrained both in power and computation to adopt the conventional blockchain consensus algorithms that are power and compute-hungry. To solve that problem, this paper proposes EasyChain, a blockchain that is robust along with running on a lightweight authentication-based consensus protocol that is known as Proof-of-Authentication (PoAh). This blockchain based on the lightweight consensus protocol replaces the power-hungry transaction, blocks validation steps, and provides ease of usage in resource-constrained environments such as IoE. The proposed blockchain is designed using the Python language for an easy understanding of the functions and increased ease of integration into IoE applications. The designed blockchain system is also deployed on a single-board computer to analyze its feasibility and scalability. The latency observed in the simulated and experimental evaluations is 148.89 ms which is very fast compared to the existing algorithms.

Betaine acts as a methyl donor in metabolism and serves as an organic osmolyte, which is used by cells for protection against osmotic stress and high temperatures. The present study was carried out to investigate the effect of betaine on physiological parameters and serum electrolyte changes in postpartum lactating Murrah buffaloes during the hot-humid season. The study was performed at the Livestock Farm Complex, N.D.V.S.U., Jabalpur, in 2019. Eighteen postpartum Murrah buffaloes were randomly divided into three groups for the experiment. T1 was a control group. T2 and T3 groups were supplemented with betaine at 50 g/animal/day and 100 g/animal/day, respectively. Betaine was supplemented in the feed from day 5 postpartum and continued up to 4 months. The rectal temperature was found to be significantly lower in the T2 and T3 groups as compared to the T1 group on day 90 postpartum. The pulse rate was lower in the T2 and T3 groups as compared to the control group on day 105 postpartum. It was concluded that betaine improves serum sodium, potassium, and the chloride concentration as compared to the control group and reduces heat stress in lactating buffaloes.

Abstract A container provides an environment where applications are packaged and run with the supporting libraries and dependencies. Due to scalability and efficient software deployment, the popularity of container technology has increased and its services are also available on cloud platforms. The container environment is prone to a variety of threats and vulnerabilities that lead to security breaches and attacks. Investigation is required to analyze the attack and the digital forensics processes have also been implemented in the container environment. In this paper, we present a systematic evaluation of container artifacts. An interface named CONTAIN4n6 is developed to collect data from container environment that extracts the data using introspection libraries, container file systems, and is also capable to trace the system call of running container. The functionality of system calls traces is implemented in an open source containerization software, i.e, Moby project. Container’s artifacts are associated with environmental information, log files, directories, link files, repositories, etc. Data collected from multiple sources are stored in a database and created a hash values to maintain the integrity of collected data. A case study of privilege escalation attacks has been demonstrated which is used to validate the data collection tool, called, CONTAIN4n6. Research challenges associated with security and forensic investigations on containerized applications are also presented.

The automotive industry has undergone a transformation with the growing popularity of electrical vehicles, which provide an eco-friendlier and cleaner substitute for conventional fuel-powered cars. However, the scarcity of EV charging stations is impeding the widespread use of electric vehicles. This research offers a novel wireless EV charging technology that runs on solar energy as a solution to this problem, providing EV owners worldwide with affordable and environmentally friendly options. The wireless power transmission technology at the centre of the suggested system allows EVs to charge without the need for physical hookups. This technology improves user accessibility and safety while doing away with the need for cords. By using solar energy, one can lessen their reliance on traditional power sources increasing the cost- and environmentally-effectiveness of the charging. Comparing this strategy to the conventional plug-in EV charging techniques reveals a number of benefits. The system's ability to charge electric vehicles (EVs) while they are in motion further improves user convenience and reduces discharge time. Solar power offers a sustainable and renewable energy source, minimizing reliance on the power grid and environmental impact. Wireless charging also eliminates the need for physical connections, improving safety and convenience. The purpose of this study is to solve the shortcomings of the conventional electric vehicle systems and offer an innovative solution that will further the development of sustainable transportation. The combination of solar energy and wireless charging for electric vehicles not only promotes the use of sustainable energy. It also encourages the growth of an energy ecosystem that is more flexible and interconnected, paving the path for more environmentally friendly and effective city transport in the future.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Where implant history is known, all confirmed cases to date have occurred in patients with exposure to textured implants. The etiopathogenesis of BIA-ALCL is likely to be multifactorial, with current evidence-based theories recognising the combination of chronic infection in setting of textured implants, gram-negative biofilm formation, chronic inflammation, host genetics (e.g. JAK/STAT, p53) and time in tumorigenesis. Proposed triggers for the development of malignancy are mechanical friction, silicone implant shell particulates, silicone leachables and bacteria. Of these, the bacterial hypothesis has received significant attention, supported by a plausible biological model. In this model, bacteria form an adherent biofilm in the favourable environment of the textured implant surface, producing a bacterial load that elicits a chronic inflammatory response. Bacterial antigens, primarily of gram-negative origin, may trigger innate immunity and induce T-cell proliferation with subsequent malignant transformation in genetically susceptible individuals. Future research, investigating BIA-ALCL genetic mutations and immunological modulation with Gram-negative biofilm in BIA-ALCL models is warranted to establish a unifying theory for the aetiology of BIA-ALCL.

Plant identification has applications in ethnopharmacology and agriculture. Since leaves are one of a distinguishable feature of a plant, they are routinely used for identification. Recent developments in deep learning have made it possible to accurately identify the majority of samples in five publicly available leaf datasets. However, each dataset captures the images in a highly controlled environment. This paper evaluates the performance of EfficientNet and several other convolutional neural network (CNN) architectures when applied to a combination of the LeafSnap, Middle European Woody Plants 2014, Flavia, Swedish, and Folio datasets. To normalize the impact of imbalance resulting from combining the original datasets, we used oversampling, undersampling, and transfer learning techniques to construct an end-to-end CNN classifier. We placed greater emphasis on metrics appropriate for a diverse-imbalanced dataset rather than stressing high performance on any one of the original datasets. A model from EfficientNet’s family of CNN models achieved a highly accurate F-score of 0.9861 on the combined dataset.

Thrombin is a key enzyme involved in the development and progression of many cardiovascular diseases. Direct thrombin inhibitors (DTIs), with their minimum off-target effects and immediacy of action, have greatly improved the treatment of these diseases. However, the risk of bleeding, pharmacokinetic issues, and thrombotic complications remain major concerns. In an effort to increase the effectiveness of the DTI discovery pipeline, we developed a two-stage machine learning pipeline to identify and rank peptide sequences based on their effective thrombin inhibitory potential. The positive dataset for our model consisted of thrombin inhibitor peptides and their binding affinities (KI) curated from published literature, and the negative dataset consisted of peptides with no known thrombin inhibitory or related activity. The first stage of the model identified thrombin inhibitory sequences with Matthew’s Correlation Coefficient (MCC) of 83.6%. The second stage of the model, which covers an eight-order of magnitude range in KI values, predicted the binding affinity of new sequences with a log room mean square error (RMSE) of 1.114. These models also revealed physicochemical and structural characteristics that are hidden but unique to thrombin inhibitor peptides. Using the model, we classified more than 10 million peptides from diverse sources and identified unique short peptide sequences (KI. Based on the binding energies of the interaction of the peptide with thrombin, we identified a promising set of putative DTI candidates. The prediction pipeline is available on a web server.

The excitation cross-sections of the 3D and 4D states of atomic hydrogen at low incident energies (from 0.90 to 5.00 Ry) were calculated using the variational polarized orbital method, which is also called the hybrid theory. Up to 12 partial waves (L = 2 to 13) were used to obtain converged cross-sections at high energies. The importance of the long-range forces near the threshold region and the behavior of the cross-sections in that region are indicated. The S, P, and D cross-sections are needed if the total excitation cross-sections are measured in addition to the elastic cross-sections. These cross-sections are also useful if the cascade from the D to the P to the S states is considered in the diagnostics of solar and astrophysical observations.

This paper presents reliability, availability, and maintainability (RAM) analysis framework for evaluating the performance of a circulation system of water (WCS) used in a coal-fired power plant (CFPP). The performance of WCS is evaluated using a reliability block diagram (RBD), fault tree analysis (FTA), and Markov birth–death probabilistic approach. In this work, the system under study consists of five subsystems connected in series and parallel configuration namely condensate extraction pump (CEP), low-pressure feed water heater (LPH), deaerator (DR), boiler feed pump (BFP), high-pressure feed water heater (HPH). The reliability block diagram (RBD) and fault tree approach (FTA) have been employed for the performance evaluation of WCS. The Markov probabilistic approach based simulation model is developed. The transition diagram of the proposed model represented several states with full working capacity, reduced capacity, and failed state. The ranking of critical equipment is decided on the basis of criticality level of equipment. The study results revealed that the boiler feed pump affects the system availability at most, while the failure of deaerator affects it least. The availability of the system is optimized using the particle swarm optimization method. The optimized availability parameter (TBF, TTR) based modified maintenance strategy is recommended to enhance the availability of the plant system. The optimized failure rate and repair rate parameters of the subsystem are used to suggest a suitable maintenance strategy for the water circulation system of the thermal power plant. The proposed RAM framework helps the decision-makers to plan the maintenance activity as per the criticality level of subsystems and allocate the resources accordingly.

Abstract Background In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Methods Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Results Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. Conclusion The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .

Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease.

Deep learning (DL) applied to whole dermoscopic images has shown unprecedented accuracy in differentiating images of melanoma from benign lesions. We hypothesize that accuracy in whole-image deep learning suffers because whole lesion analysis lacks an evaluation of dermoscopic structures. DL also suffers a “black box” characterization because it offers only probabilities to the physician and no visible structures. We propose the detection of structures called dots and globules as a means to improve precision in melanoma detection. We compare two encoder-decoder architectures to detect dots and globules: UNET vs. UNET++. For each of these architectures, we compare three pipelines: with test-time augmentation (TTA), without TTA, and without TTA but with checkpoint ensembles. We use an SE-RESNEXT encoder and a symmetric decoder. The pixel-based F1-scores for globule and dot detection based on UNET++ and UNET techniques with checkpoint ensembles were found to be 0.632 and 0.628, respectively. The blob-based UNET++ and UNET F1-scores (50 percent inter-section) were 0.696 and 0.685, respectively. This agreement score is over twice the statistical correlation score measured among specialists. We propose UNET++ globule and dot detection as a technique that offers two potential advantages: increased diagnostic accuracy and visible structure detection to better explain DL results and mitigate deep learning's black-box problem. We present a public globule and dot database to aid progress in automatic detection of these structures.

ObjectiveTo study the long-term treatment outcome of vestibular paroxysmia (VP).Study designRetrospective study.SettingTertiary referral hospital.MethodsWe analyzed records of 29 consecutive patients who were diagnosed with VP and who were treated with VP-specific anticonvulsants for at least 3 months. Patients were followed for a minimum of 6 months. We recorded and assessed starting and target dosage of medications, time to achieve adequate therapeutic response, adverse effects, and the rates of short-term and long-term remission without medication.ResultsAll 29 patients were started on oxcarbazepine as first-line treatment, and 93.1% and 100% of patients reported good-to-excellent therapeutic response within 2 and 4 weeks, respectively. Three patients switched to other anticonvulsants at 3 months. At long-term follow-up (8–56 months), most (84.6%) oxcarbazepine-treated patients maintained good therapeutic response at doses between 300 and 600 mg/day. Eleven (37.9%) patients experienced complete remission without medication for more than 1 month, of which six (20.7%) had long-term remission off medication for more than 12 months. Nineteen (65.5%) patients had neurovascular compression (NVC) of vestibulocochlear nerve on MRI, but its presence or absence did not predict treatment response or remission.ConclusionLow-dose oxcarbazepine monotherapy for VP is effective over the long term and is generally well-tolerated. About 20% of patients with VP in our study had long-term remission off medication.

BackgroundDiagnosis of acute vestibular syndrome (AVS) with hearing loss is challenging because the leading vascular cause—AICA territory stroke—can appear benign on head impulse testing. We evaluated the diagnostic utility of various bedside oculomotor tests to discriminate imaging-positive and imaging-negative cases of AVS plus hearing loss.MethodWe reviewed 13 consecutive inpatients with AVS and acute unilateral hearing loss. We compared neurologic findings, bedside and video head impulse testing (bHIT, vHIT), and other vestibular signs (including nystagmus, skew deviation, and positional testing) between MRI+ and MRI– cases.ResultsFive of thirteen patients had a lateral pontine lesion (i.e., MRI+); eight did not (i.e., MRI–). Horizontal-canal head impulse test showed ipsilateral vestibular loss in all five MRI+ patients but only in three MRI– patients. The ipsilesional VOR gains of horizontal-canal vHIT were significantly lower in the MRI+ than the MRI– group (0.56 ± 0.11 vs. 0.87 ± 0.24, p = 0.03). All 5 MRI+ patients had horizontal spontaneous nystagmus beating away from the lesion (5/5). One patient (1/5) had direction-changing nystagmus with gaze. Two had skew deviation (2/5). Among the 8 MRI– patients, one (1/8) presented as unilateral vestibulopathy, four (4/8) had positional nystagmus and three (3/8) had isolated posterior canal hypofunction.ConclusionThe horizontal-canal head impulse test poorly discriminates central and peripheral lesions when hearing loss accompanies AVS. Paradoxically, a lateral pontine lesion usually mimics unilateral peripheral vestibulopathy. By contrast, patients with peripheral lesions usually present with positional nystagmus or isolated posterior canal impairment, risking misdiagnosis as central vestibulopathy.

Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1–T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1–T3 lesions treated with surgery or radiotherapy (p = 0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p

Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but the persistence of white patches in stable disease is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. We combine noninvasive multiphoton microscopy (MPM) imaging and single-cell RNA-Seq (scRNA-Seq) to identify subpopulations of keratinocytes in stable vitiligo patients. We show that, compared with nonlesional skin, some keratinocyte subpopulations are enriched in lesional vitiligo skin and shift their energy utilization toward oxidative phosphorylation. Systematic investigation of cell-to-cell communication networks show that this small population of keratinocyte secrete CXCL9 and CXCL10 to potentially drive vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. Further MPM imaging of patients undergoing punch grafting treatment showed that keratinocytes favoring oxidative phosphorylation persist in nonresponders but normalize in responders. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cell-to-cell communication networks and keratinocyte cell states that can perpetuate inflammation and prevent repigmentation.

Background: Post thyroidectomy hypocalcemia is a common complication. Post thyroidectomy PTH estimation at varying cut offs and time have been used to predict hypocalcemia and aid in early and safe discharge. Single post thyroidectomy PTH values may be spuriously normal or high in a patient that subsequently develops unanticipated low calcium levels. This study aimed to evaluate the percentage change in preoperative and postoperative PTH (Gradient) in predicting post thyroidectomy hypocalcemia. Methods: Forty-one patients of thyroidectomy had PTH preoperatively, postoperatively one-hour (PTH0) and day 1 (PTH1). PTH gradient was calculated as percentage change in postoperative PTH to preoperative (PTHG0, PTHG1). Hypocalcemia was categorized into mild or severe based on corrected calcium values and presence of clinical signs and/or symptoms of hypocalcemia. Results: Ten (24.3%) and 11 (26.8%) patients had mild and severe hypocalcemia, respectively. PTHG0 and PTHG1 were significantly associated with risk for hypocalcemia (P-0.006 vs P-0.002). Higher PTH0 and PTH1 gradients were significantly associated with risk of hypocalcemia (PTH0 gradient OR-0.006, 95% CI 0.00–0.175, P-0.006; PTH1 gradient OR- 0.008, 95% CI 0.00–0.166, P-0.002). PTH0 gradient was the best predictor of hypocalcemia (AUC 0.855, SE-0.065, 95% CI0.710 to 0.945, P value 75% correlates with high risk of severe/clinical post thyroidectomy hypocalcemia.

Pandi Boomi,1 Ramalingam Ganesan,2 Gurumallesh Prabu Poorani,3 Sonamuthu Jegatheeswaran,4 Chandrasekaran Balakumar,5 Halliah Gurumallesh Prabu,6 Krishnan Anand,7 Narayanasamy Marimuthu Prabhu,8 Jeyaraman Jeyakanthan,1 Muthupandian Saravanan9 1Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India; 2Department of Chemistry, Arumugam Seethaiyammal Arts and Science College, Tiruppattur, Tamil Nadu, India; 3Kumaraguru College of Technology, Coimbatore, Tamil Nadu, India; 4The Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China; 5Faculty of Pharmacy, Philadelphia University, Amman, Jordan; 6Department of Industrial Chemistry, School of Chemical Sciences, Alagappa University, Karaikudi, Tamil Nadu, India; 7Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences and National Health Laboratory Service, University of the Free State, Bloemfontein, South Africa; 8Disease Control and Prevention Lab, Department of Animal Health and Management, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India; 9Department of Medical Microbiology and Immunology, Division of Biomedical Sciences, School of Medicine, College of Health Science, Mekelle University, Mekelle, EthiopiaCorrespondence: Pandi Boomi; Muthupandian Saravanan Email pboomi1983@gmail.com; saravanan.muthupandian@mu.edu.etBackground: A diabetic ulcer is one of the major causes of illness among diabetic patients that involves severe and intractable complications associated with diabetic wounds. Hence, a suitable wound-healing agent is urgently needed at this juncture. Greener nanotechnology is a very promising and emerging technology currently employed for the development of alternative medicines. Plant-mediated synthesis of metal nanoparticles has been intensively investigated and regarded as an alternative strategy for overcoming various diseases and their secondary complications like microbial infections. Hence, we are interested in developing phyto-engineered gold nanoparticles as useful therapeutic agents for the treatment of infectious diseases and wounds effectively.Methods and Results: We have synthesized phyto-engineered gold nanoparticles from the aqueous extract of Acalypha indica and characterized using advanced bio-analytical techniques. The surface plasmon resonance feature and crystalline behavior of gold nanoparticles were revealed by ultraviolet-visible spectroscopy and X-ray diffraction, respectively. High-performance liquid chromatography analysis of the extract demonstrated the presence of different constituents, while major functional groups were interpreted by the Fourier-transform infrared spectroscopy as the various stretching vibrations appeared for important O-H (3443 cm− 1), C=O (1644 cm− 1) and C-O (1395 cm− 1) groups. Scanning electron microscopy, high-resolution transmission electron microscopy results revealed a distribution of spherical and rod-like nanostructures with 20 nm of size. The gold nanoparticle-coated cotton fabric was evaluated for the antibacterial activity against Staphylococcus epidermidis and Escherichia coli bacterial strains which revealed remarkable inhibition at the zone of inhibition of 31 mm diameter against S. epidermidis. Further, antioxidant activity was tested for their free radical scavenging property, and the maximum antioxidant activity of the extract containing gold nanoparticles was found to be 80% at 100 μg/mL. The potent free radical scavenging property of the nanoparticles is observed at IC50 value 16.25 μg/mL. Moreover, in vivo wound-healing activity was carried out using BALB/c mice model with infected diabetic wounds and observed the stained microscopic images at different time intervals (day 2, day 7 and day 15). It was noted that in 15 days, the wound area is completely re-epithelialized due to the presence of different morphologies such as spherical, needle and triangle nanoparticles. The re-epithelialization layer is fully covered by nanoparticles on the wound area and also collagen filled in the scar tissue when compared with the control group.Conclusion: The pharmacological evaluation results of the study indicated an encouraging antibacterial and antioxidant activity of the greener synthesized gold nanoparticles tethered with aqueous extract of Acalypha indica. Moreover, we demonstrated enhanced in vivo wound-healing efficiency of the synthesized gold nanoparticles through the animal model. Thus, the outcome of this work revealed that the phyto-engineered gold nanoparticles could be useful for biomedical applications, especially in the development of promising antibacterial and wound-healing agents.Keywords: gold nanoparticles, antibacterial, antioxidant, wound healing, in vivo mice model

Objective:Compared with other countries in the Middle East, Qatar has one of the highest breast cancer incidence and mortality rates. Poor quality mammography images may be associated with advanced stage breast cancer, however there is limited information about the quality of breast imaging in Qatar. Our purpose was to evaluate the clinical image quality of mammography examinations performed at a tertiary care center in Doha, Qatar using a standardized assessment tool.Materials and Methods: Bilateral mammograms from consecutive patients from a tertiary care cancer center in Doha, Qatar were obtained. Proportions of examinations deemed adequate for interpretation were estimated. Standardized clinical image quality assessment form was utilized to evaluate image quality components. For each image, image quality components were given grades on a 1-5 scale (5- excellent, 4- good, 3- average, 2- fair, 1- poor). Mean scores with 95% confidence intervals were estimated for each component.Results: Consecutive sample of 132 patients was obtained representing 528 mammographic images. Overall, 99.2% of patients underwent examinations rated as acceptable for interpretation. Mean scores for each image quality component ranged from 4.045 to 5.000 (lowest score for inframammary fold). Image quality component scores were 93.0% excellent, 5.2% good, 1.1% average, 0.6% fair, and 0.1% poor.Conclusion: Overall image quality at a tertiary care center in Doha, Qatar was acceptable for interpretation with minimal areas identified for improvement.

Summary: CDC42 family GTPases (RHOJ, RHOQ, CDC42) are upregulated but rarely mutated in cancer and control both the ability of tumor cells to invade surrounding tissues and the ability of endothelial cells to vascularize tumors. Here, we use computer-aided drug design to discover a chemical entity (ARN22089) that has broad activity against a panel of cancer cell lines, inhibits S6 phosphorylation and MAPK activation, activates pro-inflammatory and apoptotic signaling, and blocks tumor growth and angiogenesis in 3D vascularized microtumor models (VMT) in vitro. Additionally, ARN22089 has a favorable pharmacokinetic profile and can inhibit the growth of BRAF mutant mouse melanomas and patient-derived xenografts in vivo. ARN22089 selectively blocks CDC42 effector interactions without affecting the binding between closely related GTPases and their downstream effectors. Taken together, we identify a class of therapeutic agents that influence tumor growth by modulating CDC42 signaling in both the tumor cell and its microenvironment.