Clinical magnetic resonance imaging evaluation of glymphatic function.

The glymphatic system is a system of specialized perivascular spaces in the brain that facilitates removal of toxic waste solutes from the brain. Evaluation of glymphatic system function by means of magnetic resonance imaging (MRI) has thus far been largely focused on rodents because of the limitations of intrathecal delivery of gadolinium-based contrast agents to humans. This review discusses MRI methods that can be employed clinically for glymphatic-related measurements intended for early diagnosis, prevention, and the treatment of various neurological conditions. Although glymphatic system-based MRI research is in its early stages, recent studies have identified promising noninvasive MRI markers associated with glymphatic system alterations in neurological diseases. However, further optimization in data acquisition, validation, and modeling are needed to investigate the glymphatic system within the clinical setting.

Functional alterations in cortical processing of speech in glioma-infiltrated cortex.

Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity in a manner similar to normal-appearing cortex but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. Here, we use subdural electrocorticography to sample both normal-appearing and glioma-infiltrated cortex during speech. We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but recruits a diffuse spatial network. On a temporal scale, we show that signals from glioma-infiltrated cortex have decreased entropy, which may affect its ability to encode information during nuanced tasks such as production of monosyllabic versus polysyllabic words. Furthermore, we show that temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex but not from glioma-infiltrated cortex. These findings inform our understanding of cognitive processing in chronic disease states and have implications for neuromodulation and prosthetics in patients with malignant gliomas.

Telephone Virtual Versus In-Person Pharmacotherapy-Based Obesity Care: A COVID-19-Related Experience at a Veterans Administration Facility.

Background: Most of the Veterans Administration (VA) population is either overweight or obese, which is a serious health concern. Medical weight management visits have traditionally occurred through in-person clinics. However, the COVID-19 pandemic forced care delivery to virtual platforms. Methods: We compared weight loss with in-person versus telephone-based medical weight management (lifestyle counseling coupled with pharmacotherapy) delivered by physician and nurse practitioner visits during the pandemic. We designed a program evaluation utilizing a naturalistic (pragmatic) observational study structure, including both newly enrolled and previously established participants in the Minneapolis VA MOVE! program between 2017 and 2021. A "transition" cohort (n = 74) received in-person care from March 2019 to March 2020, and then transitioned to virtual care. A "new start" virtual care cohort (n = 149) enrolled after March 2020 was compared to a separate historical group (n = 180) that received in-person care between January 2017 and December 2019. Weight loss was accessed over a 9-month period in both cohorts. Results: Mean weight loss over 9 months was -6.5 ± 18.2 and -2.5 ± 13.3 lbs in the in-person and virtual phases of the transition cohort, respectively, without significant difference between the two phases (p = 0.22). Mean weight loss over 9 months in the new start (virtual) cohort was -14.4 ± 17.0 lbs compared to -16.7 ± 21.0 lbs in the historical cohort, without significant difference between groups (p = 0.44). Conclusions: In our naturalistic study in a single-site VA clinic setting, weight loss with telephone-based medical weight management during the pandemic was comparable to in-person care. These findings are important for veterans living in rural and/or underserved areas.

An Effective Flux Framework for Linear Irreversible Heat Engines: Case Study of a Thermoelectric Generator.

We consider an autonomous heat engine in simultaneous contact with a hot and a cold reservoir and describe it within a linear irreversible framework. In a tight-coupling approximation, the rate of entropy generation is effectively written in terms of a single thermal flux that is a homogeneous function of the hot and cold fluxes. The specific algebraic forms of the effective flux are deduced for scenarios containing internal and external irreversibilities for the typical example of a thermoelectric generator.

Encaved optical fiber nano-probe exciting whispering gallery mode resonance with focused far off-axis beam.

This paper demonstrates whispering gallery mode (WGM) resonance with the help of an encaved optical nano-probe developed inside an optical fiber tip cavity. The nano-probe generates a tightly focused beam with a spot-size of ∼3 µm. A barium titanate microsphere is placed besides the optical axis inside the cavity. The focused beam remains off-axis of the microresonator and excites the WGM. The off-axis excitation shows unique resonating properties depending on the location of the resonator. A resonant peak with quality factor as high as Q ∼7 × 104 is achieved experimentally. Another design with a shorter cavity length for a bigger resonator is also demonstrated by embedding a bigger microsphere on the cleaved fiber tip surface. The optical probe holds great potential for photonic devices and is ideal for studying morphology-based scattering problems.

An ESIPT solvatochromic fluorescent and colorimetric probe for sensitive and selective detection of copper ions in environmental samples and cell lines.

Copper is one of the most important transition metals in our body for various physiological functions. An imbalance in the homeostasis of copper in our body can lead to various neurological disorders such as Alzheimer's disease, Parkinson's, and Menkes disease. As a result, there is a need for the detection of excess copper present in the environment and the human system. In this work, we have designed a quinoline-based fluorescent/colorimetric probe (QHS) for rapid and selective detection of copper ions via quenching of fluorescence/color change from yellow to peach which is visible to the naked eye. The probe displayed high selectivity towards copper(II), i.e., Cu(II) in the presence of different metal analytes in water samples. The sensing mechanism of the probe was confirmed by NMR, HRMS, IR spectroscopy, and SEM. The detection limit of Cu(II) ions was found to be 0.493 µM which is lower than the tolerable limit of copper (20 µM) in drinking water as per the EPA. The probe was also utilized for the visualization of Cu(II) in cell lines. The probe was also demonstrated for its application in real-time detection of aqueous samples using portable paper strips.

Tweeting for Health Using Real-time Mining and Artificial Intelligence-Based Analytics: Design and Development of a Big Data Ecosystem for Detecting and Analyzing Misinformation on Twitter.

BACKGROUND: Digital misinformation, primarily on social media, has led to harmful and costly beliefs in the general population. Notably, these beliefs have resulted in public health crises to the detriment of governments worldwide and their citizens. However, public health officials need access to a comprehensive system capable of mining and analyzing large volumes of social media data in real time. OBJECTIVE: This study aimed to design and develop a big data pipeline and ecosystem (UbiLab Misinformation Analysis System [U-MAS]) to identify and analyze false or misleading information disseminated via social media on a certain topic or set of related topics. METHODS: U-MAS is a platform-independent ecosystem developed in Python that leverages the Twitter V2 application programming interface and the Elastic Stack. The U-MAS expert system has 5 major components: data extraction framework, latent Dirichlet allocation (LDA) topic model, sentiment analyzer, misinformation classification model, and Elastic Cloud deployment (indexing of data and visualizations). The data extraction framework queries the data through the Twitter V2 application programming interface, with queries identified by public health experts. The LDA topic model, sentiment analyzer, and misinformation classification model are independently trained using a small, expert-validated subset of the extracted data. These models are then incorporated into U-MAS to analyze and classify the remaining data. Finally, the analyzed data are loaded into an index in the Elastic Cloud deployment and can then be presented on dashboards with advanced visualizations and analytics pertinent to infodemiology and infoveillance analysis. RESULTS: U-MAS performed efficiently and accurately. Independent investigators have successfully used the system to extract significant insights into a fluoride-related health misinformation use case (2016 to 2021). The system is currently used for a vaccine hesitancy use case (2007 to 2022) and a heat wave-related illnesses use case (2011 to 2022). Each component in the system for the fluoride misinformation use case performed as expected. The data extraction framework handles large amounts of data within short periods. The LDA topic models achieved relatively high coherence values (0.54), and the predicted topics were accurate and befitting to the data. The sentiment analyzer performed at a correlation coefficient of 0.72 but could be improved in further iterations. The misinformation classifier attained a satisfactory correlation coefficient of 0.82 against expert-validated data. Moreover, the output dashboard and analytics hosted on the Elastic Cloud deployment are intuitive for researchers without a technical background and comprehensive in their visualization and analytics capabilities. In fact, the investigators of the fluoride misinformation use case have successfully used the system to extract interesting and important insights into public health, which have been published separately. CONCLUSIONS: The novel U-MAS pipeline has the potential to detect and analyze misleading information related to a particular topic or set of related topics.

Digital Parenting Interventions for Fathers of Infants From Conception to the Age of 12 Months: Systematic Review of Mixed Methods Studies.

BACKGROUND: Digital interventions help address barriers to traditional health care services. Fathers play an important parenting role in their families, and their involvement is beneficial for family well-being. Although digital interventions are a promising avenue to facilitate father involvement during the perinatal period, most are oriented toward maternal needs and do not address the unique needs of fathers. OBJECTIVE: This systematic review describes the digital interventions that exist or are currently being developed for fathers of infants from conception to 12 months postpartum. METHODS: A systematic search of the MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, Embase (using Ovid), and CINAHL (using EBSCO) databases was conducted to identify articles from database inception to June 2022, of which 39 met the inclusion criteria. Articles were included if they were peer-reviewed and described a digital intervention that targeted fathers of fetuses or infants aged ≤12 months. Systematic reviews, meta-analyses, and opinion pieces were excluded. Data from these studies were extracted and themed using a narrative synthesis approach. Quality appraisal of the articles was conducted using the Mixed Methods Appraisal Tool. RESULTS: A total of 2816 articles were retrieved, of which 39 (1.38%) met the inclusion criteria for eligibility after removing duplicates and screening. Eligible articles included 29 different interventions across 13 countries. Most articles (22/29, 76%) described interventions that were exclusively digital. There were a variety of digital modalities, but interventions were most commonly designed to be delivered via a website or web-based portal (14/29, 48%). Just over half (21/39, 54%) of the articles described interventions designed to be delivered from pregnancy through the postpartum period. Only 26% (10/39) of the studies targeted fathers exclusively. A wide range of outcomes were included, with 54% (21/39) of the studies including a primary outcome related to intervention feasibility. Qualitative and mixed methods studies reported generally positive experiences with digital interventions and qualitative themes of the importance of providing support to partners, improving parenting confidence, and normalization of stress were identified. Of the 18 studies primarily examining efficacy outcomes, 13 (72%) reported a statistically significant intervention effect. The studies exhibited a moderate quality level overall. CONCLUSIONS: New and expecting fathers use digital technologies, which could be used to help address father-specific barriers to traditional health care services. However, in contrast to the current state of digital interventions for mothers, father-focused interventions lack evaluation and evidence. Among the existing studies on digital interventions for fathers, there seem to be mixed findings regarding their feasibility, acceptability, and efficacy. There is a need for more development and standardized evaluation of interventions that target father-identified priorities. This review was limited by not assessing equity-oriented outcomes (eg, race and socioeconomic status), which should also be considered in future intervention development.

Analysis of Fluoride-Free Content on Twitter: Topic Modeling Study.

BACKGROUND: Although social media has the potential to spread misinformation, it can also be a valuable tool for elucidating the social factors that contribute to the onset of negative beliefs. As a result, data mining has become a widely used technique in infodemiology and infoveillance research to combat misinformation effects. On the other hand, there is a lack of studies that specifically aim to investigate misinformation about fluoride on Twitter. Web-based individual concerns on the side effects of fluoridated oral care products and tap water stimulate the emergence and propagation of convictions that boost antifluoridation activism. In this sense, a previous content analysis-driven study demonstrated that the term fluoride-free was frequently associated with antifluoridation interests. OBJECTIVE: This study aimed to analyze "fluoride-free" tweets regarding their topics and frequency of publication over time. METHODS: A total of 21,169 tweets published in English between May 2016 and May 2022 that included the keyword "fluoride-free" were retrieved by the Twitter application programming interface. Latent Dirichlet allocation (LDA) topic modeling was applied to identify the salient terms and topics. The similarity between topics was calculated through an intertopic distance map. Moreover, an investigator manually assessed a sample of tweets depicting each of the most representative word groups that determined specific issues. Lastly, additional data visualization was performed regarding the total count of each topic of fluoride-free record and its relevance over time, using Elastic Stack software. RESULTS: We identified 3 issues by applying the LDA topic modeling: "healthy lifestyle" (topic 1), "consumption of natural/organic oral care products" (topic 2), and "recommendations for using fluoride-free products/measures" (topic 3). Topic 1 was related to users' concerns about leading a healthier lifestyle and the potential impacts of fluoride consumption, including its hypothetical toxicity. Complementarily, topic 2 was associated with users' personal interests and perceptions of consuming natural and organic fluoride-free oral care products, whereas topic 3 was linked to users' recommendations for using fluoride-free products (eg, switching from fluoridated toothpaste to fluoride-free alternatives) and measures (eg, consuming unfluoridated bottled water instead of fluoridated tap water), comprising the propaganda of dental products. Additionally, the count of tweets on fluoride-free content decreased between 2016 and 2019 but increased again from 2020 onward. CONCLUSIONS: Public concerns toward a healthy lifestyle, including the adoption of natural and organic cosmetics, seem to be the main motivation of the recent increase of "fluoride-free" tweets, which can be boosted by the propagation of fluoride falsehoods on the web. Therefore, public health authorities, health professionals, and legislators should be aware of the spread of fluoride-free content on social media to create and implement strategies against their potential health damage for the population.

Transforming entomology to adapt to global concerns: 2021 student debates.

The 2021 Student Debates of the Entomological Society of America (ESA) were held at the Annual Meeting in Denver, CO. The event was organized by the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC). The theme of the 2021 Student Debates was "Transforming Entomology to Adapt to Global Concerns", with 3 topics. Each topic had an unbiased introduction and 2 teams. The debate topics were (i) Nonnative insect introduction is an ethical approach for counteracting proliferation and overpopulation of consumers, (ii) What is the best technology to control undesirable insect pests in urban and agricultural settings? and (iii) Compared to other solutions, like plant-based diets, insect farming is the best method to address rising human global food and nutrient supply demands. Unbiased introduction speakers and teams had approximately 6 months to prepare for their presentations.

Combination of TRP channel dietary agonists induces energy expending and glucose utilizing phenotype in HFD-fed mice.

BACKGROUND: Bioactive dietary constituents activating Transient receptor potential (TRP) channels have emerged as promising candidates for the prevention of metabolic disorders. OBJECTIVE: The present study is an attempt to evaluate anti-obesity potential of a dietary TRP-based tri-agonist, combination of sub-effective doses of capsaicin (TRPV1 agonist), menthol (TRPM8 agonist), and cinnamaldehyde (TRPA1 agonist) in high-fat diet (HFD)-fed mice. DESIGN: Male C57BL/6 J mice divided into three groups (n = 8), were fed on normal pellet diet (NPD), or high-fat diet (HFD) (60% energy by fat) and HFD + CB (combination of capsaicin 0.4 mg/Kg, menthol 20 mg/Kg, and cinnamaldehyde 2 mg/Kg; p.o) for 12 weeks. Effects on HFD-induced weight gain, biochemical, histological and genomic changes in the WAT, BAT, liver and hypothalamus tissues were studied. RESULTS: Administration of tri-agonist prevented HFD-induced increase in weight gain, improved altered morphometric parameters, glucose homeostasis, and adipose tissue hypertrophy. Tri-agonist supplementation was found to induce browning of white adipose tissue and promote brown adipose tissue activation. Enhanced glucose utilization and prevention of lipid accumulation and insulin resistance in the liver was observed in mice supplemented with a tri-agonist. CONCLUSION: The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.

Cytodiagnosis of giant cell tumour presenting at unusual age and site with review of literature.

Giant cell tumour (GCT), also known as osteoclastoma, is an osteolytic tumour. It involves the epiphyseal and metaphyseal regions of long bones in adults. On rare occasions, these may occur in paediatric patients, and may involve uncommon locations such as the sternum, pelvis and, particularly infrequently, rib bones. We present a rare case of GCT in the rib of a child, diagnosed on fine needle aspiration.

Organogel mediated co-delivery of nisin and 5-fluorouracil: a synergistic approach against skin cancer.

AIM: The present study aimed to develop topical combinatorial therapy of nisin and 5-fluorouracil in a single nanosized formulation against skin cancer. METHODS: Nisin and 5-fluorouracil were encapsulated in an organogel system (NF-OG) and investigated for morphology, physicochemical properties, cytotoxicity, encapsulation and release. NF-OG was evaluated against DMBA/TPA murine skin cancer in terms of tumour statistics, histoarchitecture, TUNEL and M1/M2 macrophages. RESULTS: The optimised NF-OG formulation exhibited particle size of 185.1 ± 11.24 nm, zeta potential of -7.93 ± 0.60 mV, offered substantial drug loading and temporal release. NF-OG therapy led to improved cytotoxicity of nisin and 5-FU against B16-F10 cells, significant decrease in tumour volume (84.983 mm3) in treated group as compared to untreated group (490.482 mm3) accompanied by restoration of histoarchitecture and repolarization of macrophages. CONCLUSION: The study yielded a promising delivery system exhibiting potent anticancer activity and forms the bases for further applications in clinical settings.

Vector and rodent surveillance for Orientia tsutsugamushi in north India.

BACKGROUND & OBJECTIVES: Scrub typhus or chigger borne typhus, caused by Orientia tsutsugamushi is an emerging vector-borne disease as large numbers of cases have been reported in various tropical countries. It is transmitted to humans through bites of infected chiggers (larval mites). The knowledge about the vector, its distribution, density and habitat are important so as to understand the epidemiology of scrub typhus in a given area. To control rickettsial infections, regular rodent-vector surveillance should be planned in areas where the disease transmission is occurring and it will also help to strengthen the existing entomological data related to the vector of scrub typhus in northern India. METHODS: In the present study, rodent-vector surveillance was planned for one whole year, covering both mite active and non-active seasons (October 2019-December 2020) in selected areas of Chandigarh and Punjab in north India. Rodent tissues and mites were also examined for the presence of O. tsutsugamushi by nested PCR for 56 kDa gene and real-time PCR for 47 kDa outer membrane protein gene. 18S gene PCR was performed for molecular identification of mites. RESULTS: In the surveillance, three types of ectoparasite, viz. mites, fleas and ticks were obtained in rodents. All mites found were of Laelapidae family. None of the pooled rodent tissue samples as well as mite samples were found positive for O. tsutsugamushi by nested PCR for rickettsial DNA. INTERPRETATION & CONCLUSION: In the present study, we did not get any evidence of carriage of O. tsutsugamushi in either mites or rodents collected and sampled in selected regions in Chandigarh and Punjab. We need to strengthen the entomological surveillance over a broader region and increase the frequency of trapping rodents to increase clarity on vector-reservoir dynamics in this geographical region.

An Overview of Recent Advances in Biomedical Applications of Click Chemistry.

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a modular and bio-orthogonal approach that is being adopted for the efficient synthesis of organic and bioorganic compounds. It leads to the selective formation of 1,4-disubstituted 1,2,3-triazole units connecting readily accessible building blocks via a stable and biocompatible linkage. The vast array of the bioconjugation applications of click chemistry has been attributed to its fast reaction kinetics, quantitative yields, minimal byproducts, and high chemospecificity and regioselectivity. These combined advantages make click reactions quite suitable for the lead identification and the development of pharmaceutical agents in the fields of medicinal chemistry and drug discovery. In this review, we have outlined the key aspects, the mechanistic details and merits and demerits of the click reaction. In addition, we have also discussed the recent pharmaceutical applications of click chemistry, ranging from the development of anticancer, antibacterial, and antiviral agents to that of biomedical imaging agents and clinical therapeutics.

Nisin loaded carbopol gel against Pseudomonas aeruginosa infected third-degree burns: A therapeutic intervention.

The emergence of multidrug resistant strains of Pseudomonas aeruginosa necessitates the exploration of novel therapeutic intervention (s). The present study aimed to develop a nisin loaded carbopol gel formulation (NLCG) and explore its therapeutic efficacy against P. aeruginosa infected burn wounds. The formulation was prepared using Carbopol 940 as a polymer and characterized in terms of its appearance, stability, pH, rheology, spreadability, release, and permeation profiles. Disc diffusion assay and field emission scanning electron microscopy were carried out to establish in vitro antibacterial activity while the in vitro cytotoxicity was evaluated by hemolytic and trypan blue exclusion assay. Furthermore, in vivo efficacy was investigated by developing P. aeruginosa infected third-degree murine burn wound model followed by evaluation of parameters like bacterial loads, skin restoration, histopathological architecture, levels of hydroxyproline, myeloperoxidase and cytokines. Our studies yielded a stable formulation with pH, viscosity and drug release flux values as 6.5 ± 0.02, 382.4 p and 160.55 ± 3.64 µg h-1  cm-2 , respectively. Approximately, 84.02 ± 1.63% of nisin was found to permeate into murine skin, further, affirmed by confocal microscopic observations. Interestingly, no in vitro cytotoxicity of NLCG (to erythrocytes and/or to peritoneal macrophages) could be observed. The log units decrease (s) in CFUs of Pseudomonas in skin were found to be 1.5137, 4.2257, 6.456 after 12, 24 and 72 h of topical gel therapy, respectively. Percentage wound closure, tensile strength, histological, and scanning electron microscopic studies further provided a healing evidence with skin showing restoration of the epithelium. The gel therapy also led to a significant modulation (p ≤ 0.05) in hydroxyproline content, myeloperoxidase levels, and serum levels of IL-1, IL-10, and TNF-α. Our formulation revealed anti-Pseudomonas, wound healing, and immunomodulatory efficacy of NLCG. Further investigations are warranted to determine the underlying mechanism (s) of these displayed antibacterial and immunomodulatory effects.

Synthesis, proteolytic stability, and in vitro evaluation of DOTA conjugated p160 peptide based radioconjugates: [177Lu]Lu-DOTA-p160.

In this work, we describe the synthesis, in vitro stability, and preliminary biological evaluation of [177Lu]Lu-DOTA-p160 peptide-based radiopharmaceuticals. Our findings highlight that all DOTA-p160-peptide radioconjugates exhibit favorable proteolytic and enzymatic stability with a prolonged half-life in human plasma and serum. Cell uptake studies carried out on MCF-7 cell line revealed saturable binding of the radioconjugates in the nanomolar range, thereby demonstrating their promising potential in the imaging and therapy of breast tumors.

Is there a correlation between viral load and olfactory & taste dysfunction in COVID-19 patients?

OBJECTIVES: To evaluate the correlation between cycle threshold (Ct) value and occurrence of olfactory and taste dysfunction in COVID-19 patients. METHODS: This comparative study included COVID-19 patients diagnosed by reverse transcription- polymerase chain reaction (RT-PCR) based test at our hospital with mild to moderate disease. The demographic details and detailed clinical history of the patient, including history of loss of smell and taste was taken at the time of presentation. The patients were divided into 2 groups, group A: COVID-19 patients with OTD; group B: COVID-19 patients without OTD. 100 contiguous patients were recruited in each group. The COVID-19 test by RT-PCR was done and Ct value of the 3 genes: E (Envelope encoding) gene, N (Nucleocapsid encoding) gene, and RdRp (RNA-dependent RNA polymerase) gene, was used for data analysis. The Ct values of each of the three genes were compared between groups A and B. RESULTS: Group A and B did not differ significantly in terms of basic demographics. The differences in the Ct values of the 3 genes E gene, N gene and RdRp gene, of group A and B were found to be statistically significant (p = 0.005, p = 0.001 and p = 0.002, respectively). CONCLUSION: The patients with OTD had a lower Ct value at diagnosis, and hence, a higher viral load than those without OTD. The evaluation of Ct value and viral load in COVID-19 patients may help in further reducing the transmission of the virus in the community.

Assessment of alpha glucosidase inhibitors produced from endophytic fungus Alternaria destruens as antimicrobial and antibiofilm agents.

Diabetes is considered as a major health concern worldwide and patients with diabetes are at high risk for infectious diseases. Therefore, α-glucosidase inhibitors possessing antibacterial activity along with the ability to inhibit biofilms would be better therapeutic agents for diabetic patients. In the present study, two fractions (AF1 and AF2) possessing α-glucosidase inhibitory activity were purified from an endophytic fungus Alternaria destruens (AKL-3) isolated from Calotropis gigantea. These were evaluated for their antimicrobial and antibiofilm potential against human pathogens. AF1 exhibited broad spectrum antimicrobial activity against all the tested pathogens. It also significantly inhibited biofilm formation and dispersed the preformed biofilm at sub-optimal concentrations. AF2 possessed lesser activity as compared to AF1. The active compounds were purified using semi preparative HPLC. Some of the active compounds were identified to be phenolic in nature. The active fractions were also determined to be non-mutagenic and non-cytotoxic in safety analysis. The study highlights the role of endophytic fungi as sources of α-glucosidase inhibitors with antimicrobial potential which can have application in management of diabetes.

Human Gut Microbiota and Mental Health: Advancements and Challenges in Microbe-Based Therapeutic Interventions.

Gut microbes play prime role in human health and have shown to exert their influence on various physiological responses including neurological functions. Growing evidences in recent years have indicated a key role of gut microbiota in contributing to mental health. The connection between gut and brain is modulated by microbes via neural, neuroendocrinal and metabolic pathways that are mediated through various neurotransmitters and their precursors, hormones, cytokines and bioactive metabolites. Impaired functioning of this connection can lead to manifestation of mental disorders. Around 1 billion of the world population is reported to suffer from emotional, psychological and neurological imbalances, substance use disorders and cognitive, psychosocial and intellectual disabilities. Thus, it becomes imperative to understand the role of gut microbes in mental disorders. Since variations occur in the conditions associated with different mental disorders and some of them have overlapping symptoms, it becomes important to have a holistic understanding of gut dysbiosis in these disorders. In this review, we consolidate the recent data on alterations in the gut microbes and its consequences in various neurological, psychological and neurodegenerative disorders. Further, considering these evidences, several studies have been undertaken to specifically target the gut microbiota through different therapeutic interventions including administration of live microbes (psychobiotics) to treat mental health disorders and/or their symptoms. We review these studies and propose that an integrative and personalized approach, where combinations of microbe-based therapeutic interventions to modulate gut microbes and in-use psychological treatment practices can be integrated and based on patient's gut microbiome can be potentially adopted for effective treatment of the mental disorders.