Lecanemab blocks the effects of the Aß/fibrinogen complex on blood clots and synapse toxicity in organotypic culture.

Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (Aß) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aß plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aß protofibrils, preventing Aß/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aß/fibrinogen complex and prevents fibrinogen from exacerbating Aß-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.

The ß2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.

While the existence and functional role of class C G-protein-coupled receptors (GPCR) dimers is well established, there is still a lack of consensus regarding class A and B GPCR multimerization. This lack of consensus is largely due to the inherent challenges of demonstrating the presence of multimeric receptor complexes in a physiologically relevant cellular context. The C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR that is a promising target of anticancer therapy. Here, we investigated the potential of CXCR4 to form multimeric complexes with other GPCRs and characterized the relative size of the complexes in a live-cell environment. Using a bimolecular fluorescence complementation (BiFC) assay, we identified the ß2 adrenergic receptor (ß2AR) as an interaction partner. To investigate the molecular scale details of CXCR4-ß2AR interactions, we used a time-resolved fluorescence spectroscopy method called pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS can resolve membrane protein density, diffusion, and multimerization state in live cells at physiological expression levels. We probed CXCR4 and ß2AR homo- and heteromultimerization in model cell lines and found that CXCR4 assembles into multimeric complexes larger than dimers in MDA-MB-231 human breast cancer cells and in HCC4006 human lung cancer cells. We also found that ß2AR associates with CXCR4 multimers in MDA-MB-231 and HCC4006 cells to a higher degree than in COS-7 and CHO cells and in a ligand-dependent manner. These results suggest that CXCR4-ß2AR heteromers are present in human cancer cells and that GPCR multimerization is significantly affected by the plasma membrane environment.

Comparison of laparoscopic port site skin closure techniques (CLOSA): transcutaneous suturing versus subcuticular sutures versus adhesive strips: a prospective single-blinded randomized control trial.

BACKGROUND: Cosmesis is an essential aspect of laparoscopic surgery. Various methods of skin closure techniques have been described. We conducted a study to evaluate the cosmesis and patient satisfaction with the scars three months after laparoscopic surgery using transcutaneous suture (TS) vs. adhesive strips (AS) and subcuticular suturing (SS). METHODS: A randomized, controlled, prospective study was conducted at AIIMS, Bhubaneswar. The included patients were randomly assigned among the three arms. The time for skin closure was measured. Wounds were assessed till discharge, at 14 days, one month, and three months. Cosmesis was measured by the Hollander Wound evaluation scale (HWES) for each incision separately, and patient satisfaction by a 10- point Visual analog scale (VAS). RESULTS: One hundred six patients were assessed for eligibility, and 90 patients were randomized. Three-month follow-up data was obtained from 83 patients (92.22%). Baseline characteristics were similar among the groups. Cosmetic outcome was assessed in 312 incisions across 83 patients, and 206 (66.03%) incisions had an HWE Score of 0, but there was no significant difference (p = 0.86). Patient satisfaction was highest in the TS group (TS = 1.29, SS = 1.79, AS = 2.04, p = 0.03). Time for skin closure was the least in the AS arm (41.4 secs, p = 0.00). Skin dehiscence was significantly more in the AS arm. Four (4.44%) patients had port site infections. CONCLUSION: This study demonstrates that skin closure by transcutaneous, subcuticular, or adhesive strip methods had comparable cosmetic outcomes at three months. However, the transcutaneous closure method showed better patient satisfaction and minimal post-operative complications.

On-demand (SOS) analgesia through Transversus Abdominis Plane (TAP) catheter route for post-operative pain relief in Emergency Laparotomies-a non-randomised interventional study (STAPLE trial).

INTRODUCTION: This study aimed to compare the efficacy and safety of on-demand bupivacaine infusion via transversus abdominis plane (TAP) catheter in emergency laparotomy patients. METHODS: A non-randomised interventional study was conducted on patients undergoing emergency midline laparotomy. The intervention group received an on-demand infusion of 10 ml 0.5% bupivacaine through TAP catheters, whilst the control group received standard analgesic care. The primary outcome was the amount of rescue analgesic consumption. Secondary outcomes included the post-operative, measured by visual analogue scores (VAS), side effects, time to first flatus, post-operative nausea and vomiting, and pulmonary complications. RESULTS: One-hundred-twenty patients (58 in the TAP-SOS group, 62 in the control group) were included in the final analysis. The TAP-SOS group showed significantly reduced rescue analgesic requirement by 91% (p < 0.001) and lower VAS scores at 3, 6, 12, and 24 h (adjusted p < 0.00). Time to out-of-bed mobilisation was significantly shorter in the TAP-SOS group by 12.47 h (p < 0.001), and post-operative pulmonary complications were lower by 75% (p < 0.05). There were no significant differences in bowel recovery, catheter-related complications, or post-operative morbidity. No incidences of catheter-site infection were reported on follow-up; however, the catheter tip-culture was positive in 3 (5.17%) patients. CONCLUSION: On-demand bupivacaine infusion through a TAP catheter effectively reduced post-operative pain and opioid requirements in emergency laparotomy patients without complications. If an epidural is not an option, the TAP-SOS approach can be a helpful adjunct in implementing the ERAS protocol in an emergency since it allows for early ambulation and better pain management.

Comparison of surgical site infection (SSI) between negative pressure wound therapy (NPWT) assisted delayed primary closure and conventional delayed primary closure in grossly contaminated emergency abdominal surgeries: a randomized controlled trial.

PURPOSE: NPWT has been tried in many surgical fields, including colorectal, thoracic, vascular, and non-healing wounds, for the prevention of SSI. However, its efficacy in the prevention of SSI-grade IV closed abdominal wounds is yet to be explored. METHODS: All patients with grade IV abdominal wounds were included in the study. They were randomized into the conventional arm and the VAC arm after confirming the diagnosis intra-operatively. The sheath was closed, and the skin was laid open in the postoperative period. In the VAC arm, the NPWT dressing was applied on postoperative day (POD)-1 and removed on POD-5. In the conventional arm, only regular dressing was done postoperatively. The skin was closed with a delayed primary intention on POD-5 in both arms. The sutures were removed after 7 to 10 days of skin closure. RESULTS: The rate of SSI (10% in the VAC arm vs. 37.5% in the conventional arm, p-value = 0.004) was significantly lower in the VAC arm, as were the rates of seroma formation (2.4% in the VAC arm vs. 20% in the conventional arm, p = 0.014) and wound dehiscence (7.3% vs. 30%, p = 0.011). The conventional arm had a significant delay in skin closure beyond POD5 due to an increased rate of SSI, which also led to a prolonged hospital stay (5 days in the VAC arm vs. 6.5 days in the conventional arm, p-value = 0.005). CONCLUSION: The VAC dressing can be used routinely in grade IV closed abdominal wounds to reduce the risk of SSI and wound dehiscence.

Defending the Defender: Adversarial Learning Based Defending Strategy for Learning Based Security Methods in Cyber-Physical Systems (CPS).

Cyber-Physical Systems (CPS) are prone to many security exploitations due to a greater attack surface being introduced by their cyber component by the nature of their remote accessibility or non-isolated capability. Security exploitations, on the other hand, rise in complexities, aiming for more powerful attacks and evasion from detections. The real-world applicability of CPS thus poses a question mark due to security infringements. Researchers have been developing new and robust techniques to enhance the security of these systems. Many techniques and security aspects are being considered to build robust security systems; these include attack prevention, attack detection, and attack mitigation as security development techniques with consideration of confidentiality, integrity, and availability as some of the important security aspects. In this paper, we have proposed machine learning-based intelligent attack detection strategies which have evolved as a result of failures in traditional signature-based techniques to detect zero-day attacks and attacks of a complex nature. Many researchers have evaluated the feasibility of learning models in the security domain and pointed out their capability to detect known as well as unknown attacks (zero-day attacks). However, these learning models are also vulnerable to adversarial attacks like poisoning attacks, evasion attacks, and exploration attacks. To make use of a robust-cum-intelligent security mechanism, we have proposed an adversarial learning-based defense strategy for the security of CPS to ensure CPS security and invoke resilience against adversarial attacks. We have evaluated the proposed strategy through the implementation of Random Forest (RF), Artificial Neural Network (ANN), and Long Short-Term Memory (LSTM) on the ToN_IoT Network dataset and an adversarial dataset generated through the Generative Adversarial Network (GAN) model.

131I dose coefficients for a reference population using age-specific models.

Age-specific dose coefficients are required to assess internal exposure to the general public. This study utilizes reference age-specific biokinetic models of iodine to estimate the total number of nuclear disintegrations ã(rS,τ) occurring in source regions (rS) during the commitment time (τ). Age-specific S values are estimated for 35 target regions due to131I present in 22rSusing data from 10 paediatric reference computational phantoms (representing five ages for both sexes) published recently by the International Commission of Radiation Protection (ICRP). Monte Carlo transport simulations are performed in FLUKA code. The estimated ã(rS,τ) and S values are then used to compute the committed tissue equivalent dose HT(τ) for 27 radiosensitive tissues and dose coefficients e(τ) for all five ages due to inhalation and ingestion of131I. The derived ã(rS,τ) values in the thyroid source are observed to increase with age due to the increased retention of iodine in the thyroid. S values are found to decrease with age, mainly due to an increase in target masses. Generally, HT(τ) values are observed to decrease with age, indicating the predominant behaviour of S values over ã(rS,τ). On average, ingestion dose coefficients are 63% higher than for inhalation in all ages. The maximum contribution to dose coefficients is from the thyroid, accounting for 96% in the case of newborns and 98%-99% for all other ages. Furthermore, the estimated e(τ) values for the reference population are observed to be lower than previously published reference values from the ICRP. The estimated S, HT(τ) and e(τ) values can be used to improve estimations of internal doses to organs/whole body for members of the public in cases of131I exposure. The estimated dose coefficients can also be interpolated for other ages to accurately evaluate the doses received by the general public during131I therapy or during a radiological emergency.

Identification and validation of a key genomic region on chromosome 6 for resistance to Fusarium stalk rot in tropical maize.

KEY MESSAGE: A key genomic region was identified for resistance to FSR at 168 Mb on chromosome 6 in GWAS and haplotype regression analysis, which was validated by QTL mapping in two populations. Fusarium stalk rot (FSR) of maize is an economically important post-flowering stalk rot (PFSR) disease caused by Fusarium verticillioides. The pathogen invades the plant individually, or in combination with other stalk rot pathogens or secondary colonizers, thereby making it difficult to make accurate selection for resistance. For identification and validation of genomic regions associated with FSR resistance, a genome-wide association study (GWAS) was conducted with 342 maize lines. The panel was screened for FSR in three environments using standard artificial inoculation methodology. GWAS using the mixed linear model corrected for population structure and kinship was done, in which 290,626 SNPs from genotyping-by-sequencing were used. A total of 7 SNPs, five on chromosome 6 showing strong LD at 168 Mb, were identified to be associated with FSR. Haplotype regression analysis identified 32 haplotypes with a significant effect on the trait. In a QTL mapping experiment in two populations for validating the identified variants, QTLs were identified with confidence intervals having overlapped physical coordinates in both the populations on chromosome 6, which was closely located to the GWAS-identified variants on chromosome 6. It makes this genomic region a crucial one to further investigate the possibility of developing trait markers for deployment in breeding pipelines. It was noted that previously reported QTLs for other stalk rots in maize mapped within the same physical intervals of several haplotypes identified for FSR resistance in this study. The possibility of QTLs controlling broad-spectrum resistance for PFSR in general requires further investigation.

Clinical Profile and Prevalence of H Pylori, Iga-Ttg, and Spectrum of Duodenal Abnormalities in Non Ulcer Dyspepsia.

The Rome IV criterion for a diagnosis of NUD is chronic or recurrent epigastric pain within the last 3 months and an onset of symptoms at least 6 months prior to presentation. The term functional Dyspepsia and idiopathic dyspepsia are often used as well. Symptoms include ulcer-like dyspepsia; gastroparetic-like (nausea, early satiety, and post-prandial pain), and undifferentiated. Pathogenesis of NUD is not completely known yet. Several mechanisms have been proposed to be responsible for these symptoms. Although there is strong evidence of an association between H. pylori infection and NUD, Celiac Disease and NUD. Being a tropical country, the prevalence of infections is parasitic cause. Dyspepsia is likely to be more in India. However, the present data from India as scares in literature. Hence the present study was planned to decipher the clinical profile, prevalence of H. pylori, IgA tTG, spectrum of duodenal biopsy abnormalities in NUD patients. MATERIAL: This Descriptive Observational study was carried out in the Gastro Enterology center in GOI research institute from August 2020 to March 2021. Initially, 200 dyspepsia patients were selected. 50 patients were excluded due to various reasons. Finally, 150 patients who met the Rome 4 criteria for NUD/Functional Dyspepsia were recruited. The inclusion criteria were patients above 18 years of age, dyspepsia for >/- 6 months, and no evidence of underlying malignancy, pan gastritis, previous gastric ulcers, and pancreatitis. The patients underwent routine blood investigations like haemogram and biochemistry, Rapid Urease Test (RUT), Upper Gastro-Intestinal Endoscopy, Duodenal Biopsy, and Serum IgA-tTG antibody. OBSERVATION: The mean age was 46.3 yrs. +/- 14.12 yrs, of which 49.3% were females and 50.70% were males. The prevalence of Epigastric Pain Syndrome (EPS) was found in 37.3%, Post Prandial Distress Syndrome (PDS) in 30.7%, and 32% had both EPS+PDS. 38% of the NUD patients were positive on Rapid Urease Test (RUT) suggesting H. pylori infection. 88.7% of NUD patients were IgA-tTG antibody negative and 11.3% serologically positive. The Duodenal biopsy was normal in 48% of patients, 21.3% had mild inflammation/duodenitis, 8% chronic duodenitis and 22.7% had various grades of Celiac Disease (as per Marsh Grading). These 22.7% showing evidence of Celiac Disease on histopathological examination showed Marsh Grade 1 in 12.7%, Grade-2 in 2%, Grade 3A in 6.7%, and Grade 3B in 1.3%. Only 17.6% of biopsy positive had IgA-tTG antibody positivity but only 4% of total cases were positive for both biopsy and IgA-tTG antibody (p-value 0.05). Eosinophilic infiltration in duodenum common in NUD patients. It was observed that 17.33% (26/150) NUD patients had duodenal eosinophilia. Further, look for the association of duodenal eosinophilia with various diseases. 33.33% (19/57) H. pylori patients had duodenal eosinophilia with p-value < 0.001. It was also observed that 7.52% (7/93) others like normal individual, Chronic duodenitis, mild inflammation/ duodenitis had Duodenal eosinophilia. CONCLUSION: The prevalence of H. pylori and IgA-tTG antibodies in non-ulcer dyspepsia patients was 38% and 11.3% respectively. The spectrum of Duodenum biopsy abnormalities in NUD patients included mild inflammation/ duodenitis, Chronic duodenitis, and Celiac Disease. 22.7% of NUD patients had various degrees of celiac disease morphology on D2 biopsy and only 17.6% of these biopsy positive patients were positive for IgA-tTG. Only 4% of total NUD patients were positive for both biopsy and IgA-tTG antibody labeled as Celiac Disease (CeD). There is a significant association between H. pylori and duodenal eosinophilia.

Autoinducer N-(3-oxododecanoyl)-l-homoserine lactone induces calcium and reactive oxygen species-mediated mitochondrial damage and apoptosis in blood platelets.

Acylated homoserine lactones (AHL) such as N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-l-homoserine lactone (C4 HSL) are the most common autoinducer molecules in Pseudomonas aeruginosa. These AHL molecules not only regulate the expression of virulence factors but also have been shown to interfere with the host cell and modulate its functions. Recently, we reported that 3-oxo-C12 HSL but not C4 HSL causes cytosolic Ca2+ rise and ROS production in platelets. In this study, we examined the potential of AHLs to induce apoptosis in the human blood platelet. Our result showed that 3-oxo-C12 HSL but not C4 HSL causes phosphatidylserine (PS) exposure, mitochondrial dysfunction (mitochondrial transmembrane potential loss, and mitochondrial permeability transition pore (mPTP) formation). Besides, 3-oxo-C12 HSL also inhibited thrombin-induced platelet aggregation and clot retraction. The pretreatment of an intracellular calcium chelator BAPTA-AM or ROS inhibitor (DPI) significantly attenuated the 3-oxo-C12 HSL induced apoptotic characters such as PS exposure and mitochondrial dysfunctions. These data, including our previous findings, confirmed that 3-oxo-C12 HSL induced intracellular Ca2+ mediated ROS production results in the activation and subsequent induction of apoptotic features in platelets. Our results demonstrated that the 3-oxo-C12 HSL modulates the functions of platelets that may cause severe thrombotic complications in P. aeruginosa infected individuals.

Cardiac Diagnostic Feature and Demographic Identification (CDF-DI): An IoT Enabled Healthcare Framework Using Machine Learning.

The incidence of cardiovascular diseases and cardiovascular burden (the number of deaths) are continuously rising worldwide. Heart disease leads to heart failure (HF) in affected patients. Therefore any additional aid to current medical support systems is crucial for the clinician to forecast the survival status for these patients. The collaborative use of machine learning and IoT devices has become very important in today's intelligent healthcare systems. This paper presents a Public Key Infrastructure (PKI) secured IoT enabled framework entitled Cardiac Diagnostic Feature and Demographic Identification (CDF-DI) systems with significant Models that recognize several Cardiac disease features related to HF. To achieve this goal, we used statistical and machine learning techniques to analyze the Cardiac secondary dataset. The Elevated Serum Creatinine (SC) levels and Serum Sodium (SS) could cause renal problems and are well established in HF patients. The Mann Whitney U test found that SC and SS levels affected the survival status of patients (p < 0.05). Anemia, diabetes, and BP features had no significant impact on the SS and SC level in the patient (p > 0.05). The Cox regression model also found a significant association of age group with the survival status using follow-up months. Furthermore, the present study also proposed important features of Cardiac disease that identified the patient's survival status, age group, and gender. The most prominent algorithm was the Random Forest (RF) suggesting five key features to determine the survival status of the patient with an accuracy of 96%: Follow-up months, SC, Ejection Fraction (EF), Creatinine Phosphokinase (CPK), and platelets. Additionally, the RF selected five prominent features (smoking habits, CPK, platelets, follow-up month, and SC) in recognition of gender with an accuracy of 94%. Moreover, the five vital features such as CPK, SC, follow-up month, platelets, and EF were found to be significant predictors for the patient's age group with an accuracy of 96%. The Kaplan Meier plot revealed that mortality was high in the extremely old age group (χ2 (1) = 8.565). The recommended features have possible effects on clinical practice and would be supportive aid to the existing medical support system to identify the possibility of the survival status of the heart patient. The doctor should primarily concentrate on the follow-up month, SC, EF, CPK, and platelet count for the patient's survival in the situation.

Internet of Things: Evolution, Concerns and Security Challenges.

The escalated growth of the Internet of Things (IoT) has started to reform and reshape our lives. The deployment of a large number of objects adhered to the internet has unlocked the vision of the smart world around us, thereby paving a road towards automation and humongous data generation and collection. This automation and continuous explosion of personal and professional information to the digital world provides a potent ground to the adversaries to perform numerous cyber-attacks, thus making security in IoT a sizeable concern. Hence, timely detection and prevention of such threats are pre-requisites to prevent serious consequences. The survey conducted provides a brief insight into the technology with prime attention towards the various attacks and anomalies and their detection based on the intelligent intrusion detection system (IDS). The comprehensive look-over presented in this paper provides an in-depth analysis and assessment of diverse machine learning and deep learning-based network intrusion detection system (NIDS). Additionally, a case study of healthcare in IoT is presented. The study depicts the architecture, security, and privacy issues and application of learning paradigms in this sector. The research assessment is finally concluded by listing the results derived from the literature. Additionally, the paper discusses numerous research challenges to allow further rectifications in the approaches to deal with unusual complications.

Injuries in survivors of elephant attack: Report of three cases.

Human-elephant conflict (HEC) in India is becoming a growing health problem causing many fatalities every year. Elephants produce injuries by trampling, stomping, squeezing, tossing in the air, or crushing/targeting the head and chest commonly. The adult elephants are most aggressive in their mating season, leading to maximum incidences of HECs in this period. These attacks are mostly unprovoked, though most HECs are provoked. In this case series, the authors described the injuries sustained by three survivors in a short span of one month due to the sudden and unprovoked elephant attack. All the injuries were mild to moderate in severity and involved the chest in common. Timely rescue and prompt initiation of treatment were pivotal in their survival. The authors also want to create awareness about the mating season of elephants to minimize these unfortunate events in the future.

Pattern of injuries due to wild animal attack among patients presenting to the emergency department: A retrospective observational study.

PURPOSE: The human-wildlife conflicts (HWCs) causing nuisances and injuries are becoming a growing public health concern over recent years worldwide. We aimed to study the demographic profile, mode of injury, pattern of injury, and outcome of wild animal attack victims presented to the emergency department. METHODS: This retrospective cross-sectional study was conducted in the emergency department of a tertiary-care hospital in Eastern India. Data were retrieved from the medical records from May 2017 to May 2021. Patients of all ages and genders attacked by wild animals and secondary injuries were included in this study. Patients with incomplete data, injuries due to the attack of stray and domestic animals and trauma due to other causes were excluded. Demographic profile, mode of injury, the pattern of injury, injury severity score (ISS), radiological pattern, and outcome were recorded. Statistical analysis with R (version 3.6.1.) was conducted. RESULTS: A total of 411 wild animal attack victims were studied, of which 374 (90.9%) were snakebite injuries and 37 (9.1%) were wild mammalian (WM) attack injuries. The mean age of WM attack victims was 46 years, and the male-to-female ratio was 4:1. Elephant attack injury (40.5%) was the most common WM attack injury reported. Most WM attacks (43.2%) occurred between 4:00 a.m. to 8:00 a.m. The median ISS was 18.5 (13-28), where 54.2% of patients had polytrauma (ISS>15). Elephant attack was associated with a higher ISS, but the difference was not significant compared to other animal types (p = 0.2). Blunt trauma was common pattern of injury in the elephant attack injury cases. Lacerations and soft tissue injuries were common patterns in other animal attacks. Among snakebites, neurotoxic was the most common type (55.4%), and lower extremity was the most common site involved. CONCLUSION: The young male population is the major victim of HWCs; and elephant is the most common animal involved. There is a need to design scientifically sound preventive strategies for HWCs and to strengthen the preparedness in health establishments to manage victims effectively.

Outbreak of Dirkmeia churashimaensis Fungemia in a Neonatal Intensive Care Unit, India.

Bloodstream infections caused by uncommon or novel fungal species are challenging to identify and treat. We report a series of cases of fungemia due to a rare basidiomycete yeast, Dirkmeia churashimaensis, in neonatal patients in India. Whole-genome sequence typing demonstrated that the patient isolates were genetically indistinguishable, indicating a single-source infection.

An Intelligent Opportunistic Routing Algorithm for Wireless Sensor Networks and Its Application Towards e-Healthcare.

The lifetime of a node in wireless sensor networks (WSN) is directly responsible for the longevity of the wireless network. The routing of packets is the most energy-consuming activity for a sensor node. Thus, finding an energy-efficient routing strategy for transmission of packets becomes of utmost importance. The opportunistic routing (OR) protocol is one of the new routing protocol that promises reliability and energy efficiency during transmission of packets in wireless sensor networks (WSN). In this paper, we propose an intelligent opportunistic routing protocol (IOP) using a machine learning technique, to select a relay node from the list of potential forwarder nodes to achieve energy efficiency and reliability in the network. The proposed approach might have applications including e-healthcare services. As the proposed method might achieve reliability in the network because it can connect several healthcare network devices in a better way and good healthcare services might be offered. In addition to this, the proposed method saves energy, therefore, it helps the remote patient to connect with healthcare services for a longer duration with the integration of IoT services.

Blastomycosis Misdiagnosed as Tuberculosis, India.

Chronic pulmonary blastomycosis is often misdiagnosed and treated as tuberculosis in disease-endemic and non-disease-endemic areas. We report the case of a 32-year-old man who after visiting Chicago, Illinois, USA, returned to India and received treatment for tuberculosis for 12 months before receiving the correct diagnosis of blastomycosis.

A unique multidrug-resistant clonal Trichophyton population distinct from Trichophyton mentagrophytes/Trichophyton interdigitale complex causing an ongoing alarming dermatophytosis outbreak in India: Genomic insights and resistance profile.

There has been a considerable upsurge of extensive, treatment recalcitrant, dermatophytosis presenting as tinea corporis and tinea cruris in India since the past few years. Genome analysis of Trichophytonspecies causing severe superficial dermatophytosis in North India confirmed a unique clade related to the T.mentagrophytes/interdigitale complex, seeming to belong to an early diverging clade of the complex. The Indian Trichophyton species genomes were highly related showing only up to 42 SNPs between any two isolates confirming their clonal origin. Other genetic approaches such as ITS sequencing and multigene phylogeny used in this study were contradictory or inconclusive to show the differentiation of these isolates from T. mentagrophytes/T. interdigitale. Remarkably, high rates of resistance to all three commonly used oral antifungals, i.e., 36% for terbinafine (MICs 4 to ≥32 mg/L), 39.5% for fluconazole (MIC range 32 to ≥64 mg/L) and griseofulvin (Geometric mean MIC ≥ 4 mg/L) were observed. Two important amino acid substitutions (Leu393Phe or Phe397Leu) leading to a terbinafine resistant phenotype were found in the squalene epoxidase protein of all tested terbinafine resistant isolates. All 20 examined genomes presented a high mobility group (HMG) domain transcription factor gene corresponding to mating type (+). Of these, three isolates also showed positivity for both alpha-box and HMG in the genome which might indicate hybridization or an incomplete sexual cycle. Therefore, we highlight the potential of this organism to rapidly spread alleles that might be driving antifungal resistance among its population. This new population of Trichophyton with high rates of in vitro antifungal resistance seems to be driving an ongoing outbreak of dermatophytosis in India. Our study highlights difficulties in identifying isolates from the Trichophyton mentagrophytes/interdigitale clade of the genus using currently available molecular tools. High resistance rates of terbinafine warrant further clinical studies to assess its utility in the treatment of dermatophytosis caused by this clonal strain.

Mechanism underlying N-(3-oxo-dodecanoyl)-L-homoserine lactone mediated intracellular calcium mobilization in human platelets.

Acyl-homoserine lactones (AHLs), are the key autoinducer molecules that mediate Pseudomonas aeruginosa associated quorum sensing. P. aeruginosa produces two types of AHLs; N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-L-homoserine lactone (C4 HSL). AHLs are not only regulating the virulence gene of bacteria but also influence the host cell functions by interkingdom signaling. In this study, we explored the mechanism of AHLs induced calcium mobilization in human platelets. We found that 3-oxo-C12 HSL but not C4 HSL induces intracellular calcium release. 3-oxo-C12 HSL induced calcium mobilization was majorly contributed from the dense tubular system (DTS). Furthermore, 3-oxo-C12 HSL also stimulates the store-operated Ca2+ entry (SOCE) in platelet. Intracellular calcium rise was significantly lowered in rotenone, and bafilomycin pre-treated platelets suggesting partial involvement of mitochondria and acidic vacuoles. The significant effect of 3-oxo-C12 HSL on calcium mobilization can alter the platelet functions that might results in thrombotic disorders in individuals infected with P. aeruginosa.

Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-L-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling.

Pseudomonas aeruginosa is an opportunistic pathogen that utilizes the quorum-sensing (QS) process to regulate the production of different virulence factors and biofilm. N-3-oxo-dodecanoyl-L-homoserine lactone (C12) is a key QS molecule of P. aeruginosa which interacts with the mammalian immune cells and modulates their function. Here, we investigated the molecular mechanism of C12-induced apoptosis in neutrophils. Our data show that C12 causes apoptosis in neutrophils through an elevation in cytosolic and mitochondrial Ca2+ levels. Besides, C12 induces phosphatidylserine (PS) exposure, mitochondrial membrane potential (MMP) depolarization, mitochondrial permeability transition pore (MPTP) formation and mitochondrial reactive oxygen species (mROS) generation. C12-induced rise in intracellular Ca2+ level is majorly contributed by endoplasmic reticulum store through the activation of inositol 1, 4, 5-triphosphate receptor. Intracellular calcium chelation inhibited C12-induced mitochondrial dysfunction and apoptosis. Further, inhibition of mitochondrial Ca2+ uniporter by ruthenium red or Ru360 abrogated C12-induced mitochondrial Ca2+ uptake, MMP loss, MPTP opening, mROS production, and PS exposure. These mechanistic insights are expected to provide a better understanding of the role of C12 in P. aeruginosa pathogenesis.