The influence of time-restricted eating/feeding on Alzheimer's biomarkers and gut microbiota.

OBJECTIVES: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting approximately 55 million individuals globally. Diagnosis typically occurs in advanced stages, and there are limited options for reversing symptoms. Preventive strategies are, therefore, crucial. Time Restricted Eating (TRE) or Time Restricted Feeding (TRF) is one such strategy. Here we review recent research on AD and TRE/TRF in addition to AD biomarkers and gut microbiota. METHODS: A comprehensive review of recent studies was conducted to assess the impact of TRE/TRF on AD-related outcomes. This includes the analysis of how TRE/TRF influences circadian rhythms, beta-amyloid 42 (Aß42), pro-inflammatory cytokines levels, and gut microbiota composition. RESULTS: TRE/TRF impacts circadian rhythms and can influence cognitive performance as observed in AD. It lowers beta-amyloid 42 deposition in the brain, a key AD biomarker, and reduces pro-ininflammatory cytokines. The gut microbiome has emerged as a modifiable factor in AD treatment. TRE/TRF changes the structure and composition of the gut microbiota, leading to increased diversity and a decrease in harmful bacteria. DISCUSSION: These findings underscore the potential of TRE/TRF as a preventive strategy for AD. By reducing Aß42 plaques, modulating pro-inflammatory cytokines, and altering gut microbiota composition, TRE/TRF may slow the progression of AD. Further research is needed to confirm these effects and to understand the mechanisms involved. This review highlights TRE/TRF as a promising non-pharmacological intervention in the fight against AD.

Synthesis, biological evaluation and in silico studies of some new analogues of 3,5-vdisubstituted thiazolidin-2,4-dione.

Background: A new series of 3,5-disubstituted thiazolidin-2,4-dione molecules were derived and characterized using various spectral techniques (1H NMR, IR, carbon, hydrogen, nitrogen, etc.) and physicochemical parameters. Materials & methods: The molecules were derived using Knoevenagel condensation followed by Mannich reaction and further synthesized analogues were screened for their antioxidant and antimicrobial potential using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method and serial tube dilution method, respectively, along with in silico studies (docking and absorption, distribution, metabolism and excretion parameters) to explore the drug-receptor interaction and druglikeness. Results & conclusion: In antimicrobial screening, the analogs MP2, MM6, MM7 and MM8 displayed promising activity while molecule MM4 exhibited better antioxidant potential in the series. In molecular docking analysis, the best-fitted analogs, namely, MM6 and MM7, showed good interactions.

Identification of Aztreonam as a potential antibacterial agent against Pasteurella multocida sialic acid binding protein: A combined in silico and in-vitro analysis.

Pasteurella multocida, a Gram-negative zoonotic bacterial pathogen, interacts with the host environment, immune response, and infection through outer membrane proteins, adhesins, and sialic acid binding proteins. Sialic acids provide nutrition and mask bacterial identity, hindering the complement system, facilitates tissue access and biofilm formation. Sialic acid binding protein (SAB) enable adhesion to host cells, immune evasion, and nutrient acquisition, making them potential targets for preventing Pasteurella multocida infections. In this study, in silico molecular docking assessed 11 antibiotics targeting SAB (4MMP) comparing their docking scores to Amoxicillin. As SAB (4MMP) exhibits a highly conserved sequence in various Pasteurella multocida strains, including the specific strain PMR212 studied in this article, with a 96.09% similarity score. Aztreonam and Gentamicin displayed the highest docking scores (-6.025 and -5.718), followed by a 100ns molecular dynamics simulation. Aztreonam exhibited stable simulation with protein RMSD fluctuations of 1.8-2.2 Å. The ligand initially had an RMSD of 1.6 Å, stabilizing at 4.8 Å. Antibiotic sensitivity testing confirmed Aztreonam's efficacy with the largest inhibition zone of 42 mm, while Amoxicillin and Gentamicin had inhibition zones of 32 mm and 25 mm, respectively. According to CLSI guidelines, all three antibiotics were effective against Pasteurella multocida. Aztreonam's superior efficacy positions it as a promising candidate for further investigation in targeting Pasteurella multocida.

2-Substituted-3-(5-Substituted-1,3,4-oxadiazol/thiadiazol-2-yl) Thiazolidin-4-one Derivatives: Synthesis, Anticancer, Antimicrobial, and Antioxidant Potential.

In this innovative research, a novel series of thiazolidin-4-one analogues having a 1,3,4-oxadiazole/thiadiazole moiety were derived and the structures of all the newly obtained molecules were established using different physicochemical and analytical means (1H-NMR, FTIR, mass spectra, and elemental analyses). The synthesized molecules were then investigated for their antiproliferative, antimicrobial, and antioxidant potential. The cytotoxicity screening studies revealed that analogues D-1, D-6, D-15, and D-16 possessed comparable efficacy, within the IC50 range (1 to 7 µM), when taking doxorubicin as a reference drug (IC50 = 0.5 µM). The antimicrobial activity was assessed using different Gram-(+) and Gram-(-) bacterial and fungal strains and the results revealed that molecules D-2, D-4, D-6, D-19, and D-20 possessed potent activity against selective strains of microbes with MIC ranges of 3.58 to 8.74 µM. The antioxidant evaluation was performed using the DPPH assay and the screening results revealed that analogue D-16 was the most potent derivative (IC50 = 22.3 µM) when compared with the positive control, ascorbic acid (IC50 = 111.6 µM). Structure-activity relationship (SAR) studies of the synthesized novel derivatives revealed that para-substituted halogen and hydroxy derivatives have remarkable potential against the MCF-7 cancer cell line and antioxidant potential. Similarly, electron-withdrawing groups (Cl/NO2) and -donating groups at the para position possess moderate to promising antimicrobial potential.

Quinoxaline: A Chemical Moiety with Spectrum of Interesting Biological Activities.

Quinoxaline (C8H6N2), commonly called 1,4-diazanaphthalene, 1,4-benzodiazine, or benzopyrazine, is a very potent nitrogenous heterocyclic moiety consisting of a benzene ring fused with the pyrazine ring. A number of different methods for the synthesis of quinoxaline derivatives have been reported in the literature, but the most effective method, commonly used for the synthesis of quinoxaline analogues involves the condensation of substituted o-phenylenediamines with 1, 2- dicarbonyl compounds in the presence of different catalyst(s). The presence of different types of catalysts and their concentration affects the overall yield of the product. Quinoxaline not only plays an important role as an organic reaction intermediate but also has a wide spectrum of interesting biological activities viz. antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal activity, etc. Some commercially available drug molecules containing quinoxaline moiety are echinomycin (as antibacterial, antineoplastic, and nucleic acid inhibitor), triostins (cyclic desipeptide as an antibacterial agent), dioxidine and mequindox (as antibacterial agents), carbadox (controlling swine dysentery), desoxycarbadox (as swine growth promoter) and panadipion (as hepatoprotective agent), etc. A large number of quinoxaline analogues possessing different biological activities and their synthetic procedures have been patented worldwide.

Carrier-Specific Hot Phonon Bottleneck in CH3NH3PbI3 Revealed by Femtosecond XUV Absorption.

Femtosecond carrier cooling in the organohalide perovskite semiconductor CH3NH3PbI3 is measured using extreme ultraviolet (XUV) and optical transient absorption spectroscopy. XUV absorption between 44 and 58 eV measures transitions from the I 4d core to the valence and conduction bands and gives distinct signals for hole and electron dynamics. The core-to-valence-band signal directly maps the photoexcited hole distribution and provides a quantitative measurement of the hole temperature. The combination of XUV and optical probes reveals that upon excitation at 400 nm, the initial hole distribution is 3.5 times hotter than the electron distribution. At an initial carrier density of 1.4 × 1020 cm-3 both carriers are subject to a hot phonon bottleneck, but at 4.2 × 1019 cm-3 the holes cool to less than 1000 K within 400 fs. This result places significant constraints on the use of organohalide perovskites in hot-carrier photovoltaics.

Dermoscopic Assessment of Microneedling Alone versus Microneedling with Platelet-Rich Plasma in Cases of Male Pattern Alopecia: A Split-Head Comparative Study.

INTRODUCTION: Male pattern alopecia (MPA) is a common disorder hugely impacting the quality of life of affected individuals. The meager number of options available for treatment has their own limitations. Novel therapies are continuously being researched for. MATERIALS AND METHODS: The present study included thirty male patients with Hamilton Grade II to Grade V. All patients received four sequential treatments with microneedling (MN) on one half of the scalp and platelet-rich plasma (PRP) with MN (MN + PRP) on the other half for 4 months. Three months following the last session, evaluation was done from the vertex and temporal sites in both the groups by dermoscopic microphotographs by a blinded evaluator. In addition, the patients were asked about their satisfaction score on the basis of treatment outcome. RESULTS: Overall hair thickness showed significant increase in both MN and MN + PRP group. Furthermore, the increase in thickness was almost double in the MN group as compared to MN + PRP group (0.006 and 0.003 mm, respectively). Overall hair density also increased significantly in both the study groups but more in MN + PRP group (14.6 hair/cm2) than the MN group (10.8 hair/cm2). However, the difference between the results of both the groups was not statistically significant. CONCLUSION: To the best of our knowledge, this is the first split scalp study for MPA. We conclude that MN and PRP are both effective in treatment of androgenetic alopecia and improve the hair parameters and patient satisfaction. However, no additional effect of PRP over MN was observed. Both these therapies are safe and well tolerated without any major side effects. Limitations of our study were small sample size and lack of long-term follow-up.

Eruptive pseudoangiomatosis - cherry angiomas with perilesional halo.

Eruptive pseudoangiomatosis is a rare viral exanthem characterized by acute onset of hemangiomata-like lesions, however, histological findings are distinct from that of true angiomas. This entity has been reported from Europe, North America, Japan, and Korea till date. Here, we report 12 cases of eruptive pseudoangiomatosis from a tertiary care hospital in Punjab.

Altered resting state functional connectivity in early course schizophrenia.

Impaired connectivity is proposed to underlie pathophysiology of schizophrenia. Existing studies on functional connectivity show inconsistent results. We examined functional connectivity in a clinically homogenous sample of 34 early course schizophrenia patients compared with/to 19 healthy controls using resting state functional magnetic resonance imaging (rsfMRI). Mean duration of illness for schizophrenia patients was 4 ± 1.78 years. Following a comprehensive clinical assessment, rsfMRI data were acquired using a 3.0 T magnetic resonance imaging scanner, and analyzed using FSL version 5.01 software (FMRIB's Software Library, www.fmrib.ox.ac.uk/fsl). Compared to healthy controls, schizophrenia patients had significantly decreased functional connectivity in the left fronto-parietal network, lateral and medial visual network, motor network, default mode network and auditory network. Our data suggests significant functional hypoconnectivity in selected brain networks in early schizophrenia patients compared to controls. It is likely that the observed functional hypoconnectivity may be associated with features of schizophrenia other than those examined in this study. It is possible that hypoconnectivity is necessary but not sufficient to the clinical manifestation of schizophrenia. The examination of functional connectivity as a biomarker should be extended to a wider array of disease phenotypes to better understand its significance.

"Psychiatric assessment of deaf and mute patients - A case series".

Deafness is negatively associated with higher distress, depression, somatization, and loneliness in patients of all age groups. The psychiatric presentation of patient also varies. Due to lack of proper communication, clinical approach often becomes quite difficult. We will be discussing various psychiatric presentations in 3 different deaf mute patients. We will also be highlighting the different clinical approach applied to all the patients. This case series might help in giving an insight into the psychiatric symptoms of deaf mute patients which might pave way for new diagnostic guidelines for future research and in clinical practice.

Unusual Sites of Cutaneous Tuberculosis: A Report of Two Cases.

Cutaneous tuberculosis (CTB) is an uncommon small subset of extrapulmonary tuberculosis, comprising 1-1.5% of all extrapulmonary tuberculosis manifestations, which manifests only in 8.4-13.7% of all tuberculosis cases. Lupus vulgaris (LV) and tuberculosis verrucosa cutis (TBVC) are forms of reinfection tuberculosis and often occur in presensitized patients, by exogenous inoculation. We report two cases of cutaneous tuberculosis at unusual sites. A 35-year-old female having a forehead lesion for 2 years was diagnosed as having tuberculosis verrucosa cutis and another 16-year-old girl with lesion in left axilla for 10 years was proven to have lupus vulgaris. The delayed diagnosis was possibly due to lower clinical suspicion due to the presentation of CTB at unusual sites. This highlights the importance of keeping TB as an important differential as misdiagnosis or delayed diagnosis of this entity can lead to prolonged morbidity.

Primary Delusion and the Sociopolitical Milieu in India - A Case Report & Short Review.

Delusion has always been a central topic for psychiatric research with regard to its etiology, pathogenesis, diagnosis, treatment, and forensic relevance. Among these, primary delusion seems to be the interest of many psychiatrists. Content of delusion has always been the area of interest of cultural psychiatry. We have tried to discuss the various aspects of primary delusion and also tried to explain how cultural and sociopolitical environment in a country like India can shape the formation of primary delusion and influence its psychopathology.