Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

Recent Advances in Nanomaterials Based Optical Sensors for the Detection of Melatonin and Serotonin.

In this review paper we discussed the detection of melatonin and serotonin by using various optical methods. Melatonin and serotonin are very necessary body hormones these are also called neuroregulatory hormones secreted by pineal gland in brain by pinealocytes and shape of pineal gland is cone like. Sensitive detection of melatonin and serotonin in pharmacological samples and human serum is crucial for human beings, lots of research publications available in literature for melatonin and serotonin and we overviewed these papers. We have deeply reviewed many research papers where sensitively sensing of melatonin and serotonin occurs, by using of various interfering agents and nanomaterials. This review aims presenting colorimetry, fluorometry and spectrophotometric detection of melatonin (MEL) and serotonin (SER) by using different metal oxides, carbon nanomaterials (nanosheets, nanorods, nanofibers) and many other agents. Nanomaterials typically possess favourable optical, electrical and mechanical characteristics, they provide up new avenues for enhancing the efficacy of sensors. It is crucial to provide an optical sensors platform that is dependable, sensitive and low price. The development of sensors and biosensors to use nanomaterials for neurotransmitters has advanced significantly in recent years. There are currently many developing biomarkers in biological fluids, and bionanomaterial-based biosensor systems, as well as clinical and pharmacological settings, have garnered significant interest. Biomarkers have been found using optical devices in a quick, selective and sensitive manner. Our aim is to compile all the data that already published on MEL, SER sensing and comparison of each method, we mainly focused on principle, observations, sensitivity, selectivity, limit of detection, mechanism behind the reaction, effect of temperature, pH and concentration. In the last of this paper, we discuss some challenges of these methods and future projects.

Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.

OBJECTIVES: To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. METHODS: This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. RESULTS: The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. CONCLUSIONS: The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.

Polyvinyl alcohol-derived-carbon quantum dots based fluorometric "On-Off" probe for moxifloxacin detection in milk and egg samples.

Unconditional use of antibiotics triggered the process of bacterial resistance and causes major health problems. Nowadays, antibiotics majorly used in animals not only for infection treatment but also as mass promotor. The excess amount of antibiotics residue in animal derived foods which accelerate antibiotic resistance (ABR). So, here, a simple and quick carbon quantum dots(CQDs) based fluorometric "On-Off" probe was developed for detection of moxifloxacin (MOXI) in milk and egg samples. The CQDs emits blue emission and are uniformly distributed with average particle size 5.9 ± 0.22 nm. With MOXI, fluorescence intensity of CQDs at 372 nm decreased due to inner filter effect (IFE) and a new peak appeared at 508 nm correspondence to MOXI. The probe shows linear response with MOXI concentration varies as 0.025 µM - 15.0 µM with lower detection limit (LOD) of 6.34 nM. The real sample applicability test proved that the sensors have excellent efficacy for food applications.

Current Landscape of Therapeutics for the Management of Hypertension - A Review.

Hypertension is a critical health problem. It is also the primary reason for coronary heart disease, stroke, and renal vascular disease. The use of herbal drugs in the management of any disease is increasing. They are considered the best immune booster to fight against several types of diseases. To date, the demand for herbal drugs has been increasing because of their excellent properties. This review highlights antihypertensive drugs, polyphenols, and synbiotics for managing hypertension. Evidence is mounting in favour of more aggressive blood pressure control with reduced adverse effects, especially for specific patient populations. This review aimed to present contemporary viewpoints and novel treatment options, including cutting-edge technological applications and emerging interventional and pharmaceutical therapies, as well as key concerns arising from several years of research and epidemiological observations related to the management of hypertension.

Interplay of host and viral factors in inflammatory pathway mediated cytokine storm during RNA virus infection.

RNA viruses always have been a serious concern for human health by causing several outbreaks, often pandemics. The excessive mortality and deaths associated with the outbreaks caused by these viruses were due to the excessive induction of pro-inflammatory cytokines leading to cytokine storm. Cytokines are important for cell-to-cell communication to maintain cell homeostasis. Disturbances of this homeostasis can lead to intricate chain reactions resulting in a massive release of cytokines. This could lead to a severe self-reinforcement of several feedback processes, which could eventually cause systemic harm, multiple organ failure, or death. Multiple inflammation-associated pathways were involved in the cytokine production and its regulation. Different RNA viruses induce these pathways through the interplay with their viral factors and host proteins and miRNAs regulating these pathways. This review will discuss the interplay of host proteins and miRNAs that can play an important role in the regulation of cytokine storm and the possible therapeutic potential of these molecules for the treatment and the challenges associated with the clinical translation.

Bistable Aryl Azopyrazolium Ionic Photoswitches in Water.

We report a new class of arylazopyrazolium-based ionic photoswitches (AAPIPs). These AAPIPs with different counter ions have been accessed through a modular synthetic approach in high yields. More importantly, the AAPIPs exhibit excellent reversible photoswitching and exceptional thermal stability in water. The effects of solvents, counter ions, substitutions, concentration, pH, and glutathione (GSH) have been evaluated using spectroscopic investigations. The results revealed that the bistability of studied AAPIPs is robust and near quantitative. The thermal half-life of Z isomers is extremely high in water (up to years), and it can be lowered electronically by the electron-withdrawing groups or highly basic pH.

Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy's cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.

Machine learning-driven blood transcriptome-based discovery of SARS-CoV-2 specific severity biomarkers.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by rapidly evolving variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2), continues to be a global health threat. SARS-CoV-2 infection symptoms often intersect with other nonsevere respiratory infections, making early diagnosis challenging. There is an urgent need for early diagnostic and prognostic biomarkers to predict severity and reduce mortality when a sudden outbreak occurs. This study implemented a novel approach of integrating bioinformatics and machine learning algorithms over publicly available clinical COVID-19 transcriptome data sets. The robust 7-gene biomarker identified through this analysis can not only discriminate SARS-CoV-2 associated acute respiratory illness (ARI) from other types of ARIs but also can discriminate severe COVID-19 patients from nonsevere COVID-19 patients. Validation of the 7-gene biomarker in an independent blood transcriptome data set of longitudinal analysis of COVID-19 patients across various stages of the disease showed that the dysregulation of the identified biomarkers during severe disease is restored during recovery, showing their prognostic potential. The blood biomarkers identified in this study can serve as potential diagnostic candidates and help reduce COVID-19-associated mortality.

Impulsivity Classification Using EEG Power and Explainable Machine Learning.

Impulsivity is a multidimensional construct often associated with unfavorable outcomes. Previous studies have implicated several electroencephalography (EEG) indices to impulsiveness, but results are heterogeneous and inconsistent. Using a data-driven approach, we identified EEG power features for the prediction of self-reported impulsiveness. To this end, EEG signals of 56 individuals (18 low impulsive, 20 intermediate impulsive, 18 high impulsive) were recorded during a risk-taking task. Extracted EEG power features from 62 electrodes were fed into various machine learning classifiers to identify the most relevant band. Robustness of the classifier was varied by stratified [Formula: see text]-fold cross validation. Alpha and beta band power showed best performance in the classification of impulsiveness (accuracy = 95.18% and 95.11%, respectively) using a random forest classifier. Subsequently, a sequential bidirectional feature selection algorithm was used to estimate the most relevant electrode sites. Results show that as little as 10 electrodes are sufficient to reliably classify impulsiveness using alpha band power ([Formula: see text]-measure = 94.50%). Finally, the Shapley Additive exPlanations (SHAP) analysis approach was employed to reveal the individual EEG features that contributed most to the model's output. Results indicate that frontal as well as posterior midline alpha power seems to be of most importance for the classification of impulsiveness.

BQ-AurIPr: a redox-active anticancer Au(i) complex that induces immunogenic cell death.

Immunogenic Cell Death (ICD) is a unique cell death mechanism that kills cancer cells while rejuvenating the anticancer immunosurveillance, thereby benefiting the clinical outcomes of various immuno-chemotherapeutic regimens. Herein, we report development of a library of benzo[a]quinolizinium-based Au(i) complexes through an intramolecular amino-auration reaction of pyridino-alkynes. We tested 40 candidates and successfully identified BQ-AurIPr as a novel redox-active Au(i) complex with potent anticancer properties. BQ-AurIPr efficiently triggered generation of DAMPs - the hallmarks of ICD - and was superior in terms of efficiency compared to FDA-approved drugs known to induce ICD. BQ-AurIPr significantly increased immunogenicity of cancer cells enhancing their phagocytosis when co-cultured with immune cells. Our investigation reveals that BQ-AurIPr induces oxidative stress inside mitochondria leading to mitophagy, as the mechanism for immunogenic cell death in A549 cells.

A case report on anesthetic challenges in the post-Covid complication of active mucormycosis: Patient preparedness for family physicians.

Mucormycosis is a well-known yet complicated illness that seems benign but behaves malignantly. This article discusses the anesthesia challenges in providing care for a 49-year-old male who presented with post-Covid pneumonia and uncontrolled diabetes along with active mucormycosis and scheduled for functional endoscope sinus surgery (FESS) and debridement of necrotic tissue. We want to illustrate the importance of anticipated difficult airway, while highlighting the toxicity of intravenous amphotericin-B and its combination against anesthesia drugs.

An Unusual Case of Acute Confusion in an Elderly Man: Pituitary Apoplexy With Lateral Rectus Palsy.

Often, the provisional diagnosis for an elderly patient who arrives at the hospital with confusion is presumed to be delirium stemming from confusion usually caused by an infectious cause. The famous mnemonic PINCH ME signifies the ruling out of pain, infection (that usually has a urinary cause), constipation, dehydration, medication (particularly narcotics), and the environment (factors triggering confusion in a patient with a background of dementia). However, we report a rare case of sudden confusion in an elderly male with no previous history of cognitive impairment. This is the first ever reported case to the best of our knowledge of a patient that presented with sudden confusion, impaired extraocular mobility, and spontaneous cranial hemorrhage that was ultimately determined to be due to a hypothalamic and/or a pituitary cause. It signifies a need for prompt evaluation to arrive at an early diagnosis. Additionally, we hope this case report would serve as a guide to look beyond the current mnemonic of PINCH ME and instead to a new mnemonic of 'PINCH ME HOT' where the latter most mnemonic connotes the need to look at a hypothalamic/pituitary, ocular, or traumatic origin for the delirium.

Assessment of emotional states in EEG signals using multi-frequency power spectrum and functional connectivity patterns.

In this work, an attempt has been made to characterize arousal and valence emotional states using Electroencephalogram (EEG) signals and Phase lag index (PLI) based functional connectivity features. For this, EEG signals are considered from a publicly available DEAP database. Signals are decomposed into four frequency bands, namely theta (θ, 4-7 Hz), alpha (a, 8-12 Hz), beta (ß, 13-30 Hz), and gamma (γ, 30-45 Hz). Two features, namely relative PSD and PLI, are calculated from each band of signals with Welch's periodogram. Four classifiers, namely Random Forest (RF), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), and K-Nearest Neighbor (KNN), are employed to discriminate the emotional states. Results show that the proposed approach can differentiate emotional states using EEG signals. It is observed that there is strong functional connectivity in Fp1-02 and Fp2-Pz in all emotional states for different frequency bands. SVM classifier yields the highest classification performance for arousal, and RF yields the highest performance for valence in the y band. The combination of all features performs the best for the valence dimension. Thus, the proposed approach could be extended for classifying various emotional states in clinical settings. Clinical Relevance- This establishes PLI based approach for improved classification (fl = 74.77% for Arousal fl = 74.94 for valence) of emotional states.

A Rare Case of Kostmann Syndrome Presenting Difficult Airway Challenges and Patient Preparedness for Anesthesiologists.

Severe congenital neutropenia (SCN), commonly known as the Kostmann syndrome, is a rare and complex set of disorders defined by a lack of neutrophil maturation in the bone marrow, leading to life-threatening complications. This case report discusses a young adult patient scheduled for elective laparoscopic cholecystectomy. The patient presented with skin lesions which are a common scenario of Kostmann syndrome, but along with that, our patient posed challenges of short neck, limited neck extension, and gynecomastia. These additional conditions dramatically increased the challenges for anesthesiologists to address the anticipated difficult airway. The anticipated difficult airway challenges were handled by following the protocols of difficult airway guidelines 2022.

Essential role of Rnd1 in innate immunity during viral and bacterial infections.

Intracellular and cell surface pattern-recognition receptors (PRRs) are an essential part of innate immune recognition and host defense. Here, we have compared the innate immune responses between humans and bats to identify a novel membrane-associated protein, Rnd1, which defends against viral and bacterial infection in an interferon-independent manner. Rnd1 belongs to the Rho GTPase family, but unlike other small GTPase members, it is constitutively active. We show that Rnd1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms. Rnd1 counteracts intracellular calcium fluctuations by inhibiting RhoA activation, thereby inhibiting virus internalisation. On the other hand, Rnd1 also facilitates pro-inflammatory cytokines IL-6 and TNF-α through Plxnb1, which are highly effective against intracellular bacterial infections. These data provide a novel Rnd1-mediated innate defense against viral and bacterial infections.

Host and viral non-coding RNAs in dengue pathogenesis.

Dengue virus (DENV) is a mosquito-borne flavivirus that causes frequent outbreaks in tropical countries. Due to the four different serotypes and ever-mutating RNA genome, it is challenging to develop efficient therapeutics. Early diagnosis is crucial to prevent the severe form of dengue, leading to mortality. In the past decade, rapid advancement in the high throughput sequencing technologies has shed light on the crucial regulating role of non-coding RNAs (ncRNAs), also known as the "dark matter" of the genome, in various pathological processes. In addition to the human host ncRNAs like microRNAs and circular RNAs, DENV also produces ncRNAs such as subgenomic flaviviral RNAs that can modulate the virus life cycle and regulate disease outcomes. This review outlines the advances in understanding the interplay between the human host and DENV ncRNAs, their regulation of the innate immune system of the host, and the prospects of the ncRNAs in clinical applications such as dengue diagnosis and promising therapeutics.