A Retrospective Study of Imaging of Invasive Rhino-Orbital-Cerebral Mucormycosis in the COVID-19 Pandemic in a Tertiary Care Center.

Aim The study aims to analyze the imaging findings of invasive rhino-orbital-cerebral mucormycosis (ROCM) in patients who had COVID-19. Materials and methods This retrospective descriptive study was done on confirmed (culture and histopathology) patients who had a COVID-19 infection. The data was collected from the record section from May 2021 to June 2021. Imaging data were analyzed, and findings were tabulated according to statistical methods. Results Radiological evaluation, including CT and MRI, was done in 48 cases. The ethmoid sinus was the most common sinus involved in 60.41% of cases, followed by the maxillary sinus (52.09%). Unilateral pansinusitis was observed in 21 cases (43.75%). Among periantral extensions, retroantral fat involvement was the most common finding, seen in 24 cases (50%). Lamina papyracea and the walls of the maxillary sinus were involved in eight cases (16.67%). A total of 38 cases (79.17%) exhibited involvement of the extraconal compartment, while 32 cases (66.67%) showed involvement of the intraconal compartment. In intracranial involvement, infarct was noted in 13 cases (27%), and cavernous sinus involvement in nine cases (18.75%). Conclusions ROCM is a life-threatening fungal infection in immunocompromised patients, especially diabetics. Imaging of ROCM plays a pivotal role in early diagnosis, the extent of disease, surgical planning, prognosis, and the response to treatment. Radiologists must know the imaging features and patterns of extension of ROCM.

Dynamic Endocannabinoid-mediated Neuromodulation of Retinal Circadian Circuitry.

Circadian rhythms are biological rhythms that originate from the "master circadian clock," called the suprachiasmatic nucleus (SCN). SCN orchestrates the circadian rhythms using light as a chief zeitgeber, enabling humans to synchronize their daily physio-behavioral activities with the Earth's light-dark cycle. However, chronic/ irregular photic disturbances from the retina via the retinohypothalamic tract (RHT) can disrupt the amplitude and the expression of clock genes, such as the period circadian clock 2, causing circadian rhythm disruption (CRd) and associated neuropathologies. The present review discusses neuromodulation across the RHT originating from retinal photic inputs and modulation offered by endocannabinoids as a function of mitigation of the CRd and associated neuro-dysfunction. Literature indicates that cannabinoid agonists alleviate the SCN's ability to get entrained to light by modulating the activity of its chief neurotransmitter, i.e., γ-aminobutyric acid, thus preventing light-induced disruption of activity rhythms in laboratory animals. In the retina, endocannabinoid signaling modulates the overall gain of the retinal ganglion cells by regulating the membrane currents (Ca2+, K+, and Cl- channels) and glutamatergic neurotransmission of photoreceptors and bipolar cells. Additionally, endocannabinoids signalling also regulate the high-voltage-activated Ca2+ channels to mitigate the retinal ganglion cells and intrinsically photosensitive retinal ganglion cells-mediated glutamate release in the SCN, thus regulating the RHT-mediated light stimulation of SCN neurons to prevent excitotoxicity. As per the literature, cannabinoid receptors 1 and 2 are becoming newer targets in drug discovery paradigms, and the involvement of endocannabinoids in light-induced CRd through the RHT may possibly mitigate severe neuropathologies.

Diverse role, structural trends, and applications of fluorinated sulphonamide compounds in agrochemical and pharmaceutical fields.

Our knowledge of fluorine's unique and complex properties has significantly increased over the past 20 years. Consequently, more sophisticated and innovative techniques have emerged to incorporate this feature into the design of potential drug candidates. In recent years, researchers have become interested in synthesizing fluoro-sulphonamide compounds to discover new chemical entities with distinct and unexpected physical, chemical, and biological characteristics. The fluorinated sulphonamide molecules have shown significant biomedical importance. Their potential is not limited to biomedical applications but also includes crop protection. The discovery of novel fluorine and Sulfur compounds has highlighted their importance in the chemical sector, particularly in the agrochemical and medicinal fields. Recently, several fluorinated sulphonamide derivatives have been developed and frequently used by agriculturalists to produce food for the growing global population. These molecules have also exhibited their potential in health by inhibiting various human diseases. In today's world, it is crucial to have a steady supply of innovative pharmaceutical and agrochemical molecules that are highly effective, less harmful to the environment, and affordable. This review summarizes the available information on the activity of Fluorine and Sulphonamide compounds, which have proven active in pharmaceuticals and agrochemicals with excellent environmental and human health approaches. Moreover, it focuses on the current literature on the chemical structures, the application of fluorinated sulphonamide compounds against various pathological conditions, and their effectiveness in crop protection.

Impact of the heartfulness program on stress and sleep among healthcare professionals: Pre experimental study.

Background: Healthcare professionals (HCPs) worldwide suffer from stress and poor sleep and the COVID-19 pandemic has further raised these issues. This study sought to determine whether HCPs had reduced stress and increased sleep quality while participating in a heartfulness meditation program. Subjects and Methods: For a 2-month (8 weeks) heartfulness meditation program, we included 41 individuals in a prospective one-group pretest post-test intervention design from February 2023 to April 2023. Scores on the Perceived Stress Scale and Pittsburgh Sleep Quality Index were gathered at baseline and 8 weeks. Forty-one (76%) of the 54 participants completed this study for 8 weeks. Results: Results showed a substantial decline in stress (preintervention mean ± standard deviation [SD] = 20.54 ± 4.46; postintervention mean ± SD = 18.42 ± 6.14; t-value = -1.947 [0.05*]) and improvement in sleep quality (preintervention mean ± SD = 6.63 ± 3.82; postintervention mean ± SD = 5.29 ± 2.44) among HCPs after following this 8-week heartfulness meditation program. In the end, a substantial decrease in perceived stress score and an improvement in the sleep quality index was found. Conclusion: Additionally, practicing heartfulness meditation may aid in developing the traits of empathy, acceptance, and inner serenity. We draw the conclusion that more extensive research is required to fully understand the impact of heartfulness meditation practice.

HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.

Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.

Efficacy of lignocaine nebulization in patients with COVID-19 respiratory infection: An exploratory randomized double-blinded controlled trial.

Background and Aims: Coronavirus disease (COVID-19)-related pneumonia is proposed to be an inflammatory process. The treatment currently includes supportive therapy and low-dose steroids. Anti-inflammatory drugs have been proposed to prevent cytokine storms and improve oxygenation in such cases. The study aimed to assess the efficacy of nebulized lignocaine in COVID-19 patients with pneumonia. Material and Methods: This was an exploratory randomized double-blinded control trial conducted in COVID-19 patients with respiratory failure requiring oxygen therapy either by face mask or non-invasive mechanical ventilation. Patients included were of the age of more than 18 years of either gender. The patients were randomized to receive either lignocaine or distilled water nebulization. The outcomes assessed were PaO2/FiO2 ratio, hemodynamics, respiratory parameters, and sequential organ failure score (SOFA). Results: The two groups were comparable concerning demographic variables. The PaO2/FiO2 were significantly higher in the lignocaine group from day 2 onward. The SPO2 was significantly higher on day 3 in the lignocaine group and thereafter there was no significant difference. Other hemodynamic, respiratory parameters, and SOFA scores showed no difference in both the groups. Conclusion: Lignocaine nebulization improved oxygenation in COVID-19 patients and can be used as adjunctive therapy along with other supportive medications.

The efficacy of ultrasound-guided upper thoracic erector spinae plane block for postoperative analgesia in proximal shoulder surgery and its effect on phrenic nerve function: A prospective exploratory study.

Background and Aims: The upper thoracic (T2) erector spinae plane block (UT-ESPB) has been proposed as an alternative to interscalene brachial plexus block for postoperative analgesia in shoulder surgery. The current study was conducted to evaluate the same. Material and Methods: Patients scheduled for shoulder surgery under general anesthesia (GA) received ultrasound-guided UT-ESPB. The outcomes measured were diaphragmatic movements, block characteristics, and quality of recovery at 24 h. Results: A total of 43 patients were recruited. The incidence of phrenic nerve palsy was 0%. The sensory level achieved by the maximum number of patients at the end of 30 min was C7-T5 level, and none had a motor block. Forty-two percent of patients did not require rescue analgesia till 24 h postoperative. In the rest of the patients, the mean (SD) duration of analgesia was 724.2 ± 486.80 min, and the mean postoperative requirement of fentanyl was 98.80 ± 47.02 µg. The median pain score (NRS) during rest and movement is 2 to 3 and 3 to 4, respectively. The median quality of recovery score at the end of 24 h after the block was 14 (15-14). Conclusion: The upper thoracic ESPB resulted in a sensory loss from C7-T5 dermatomes without any weakness of the diaphragm and upper limb. However, the block was moderately effective in terms of the total duration of analgesia, postoperative pain scores, analgesic requirement, and quality of recovery in patients undergoing proximal shoulder surgeries under GA. Further studies are required to establish its role due to its poor correlation with sensory spread.

Facile synthesis and in silico studies of benzothiazole-linked hydroxypyrazolones targeting α-amylase and α-glucosidase.

Aim: The objective of the present investigation was to design and synthesize new heterocyclic hybrids comprising benzothiazole and indenopyrazolone pharmacophoric units in a single molecular framework targeting α-amylase and α-glucosidase enzymatic inhibition. Materials & methods: 20 new benzothiazole-appended indenopyrazoles, 3a-t, were synthesized in good yields under environment-friendly conditions via cycloaddition reaction, and assessed for antidiabetic activity against α-amylase and α-glucosidase, using acarbose as the standard reference. Results: Among all the hydroxypyrazolones, 3p and 3r showed the best inhibition against α-amylase and α-glucosidase, which finds support from molecular docking and dynamic studies. Conclusion: Compounds 3p and 3r have been identified as promising antidiabetic agents against α-amylase and α-glucosidase and could be considered valuable leads for further optimization of antidiabetic agents.

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Debate on direct-anterior vs posterior approach for hip hemiarthroplasty: The authors' insights.

We read and discussed the study entitled "Complication rates after direct anterior vs posterior approach for Hip Hemiarthroplasty in elderly individuals with femoral neck fractures" with great interest. The authors have done justice to the topic of comparison of anterior and posterior surgical approaches for bipolar hemiarthroplasty which has been an everlasting debate in the existing literature. However, there are certain aspects of this study that need clarification from the authors.

Retraction: Metal-ion batteries for electric vehicles: current state of the technology, issues and future perspectives.

[This retracts the article DOI: 10.1039/D1NA00214G.].

Electrocardiographic changes in pneumothorax: an updated review.

ECG changes in pneumothorax have gained recognition as important indicators of cardiopulmonary interactions. This narrative review examines the existing literature to provide insights into the various ECG abnormalities observed in patients with pneumothorax, their underlying mechanisms, and clinical implications. The review highlights the commonly reported changes, including alterations in the electrical axis, ST segment deviations, T-wave abnormalities, and arrhythmias. The rightward shift of the electrical axis is attributed to cardiac displacement caused by increased intrathoracic pressure. ST segment deviations may reflect the influence of altered intrathoracic pressure on myocardial oxygen supply and demand. T-wave abnormalities may result from altered myocardial repolarization and hypoxemia. Arrhythmias, although varying in incidence and type, have been associated with pneumothorax. The clinical implications of these ECG changes are discussed, emphasizing their role in diagnosis, risk stratification, treatment optimization, and prognostication. Additionally, future research directions are outlined, including prospective studies, mechanistic investigations, and the integration of artificial intelligence. Enhancing our understanding of ECG changes in pneumothorax can lead to improved patient care, better management strategies, and the development of evidence-based guidelines. The objective of this review is to demonstrate the presence of various ECG abnormalities in patients with pneumothorax.

Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia.

Splicing factor 3b subunit 1 (SF3B1) is the largest subunit and core component of the spliceosome. Inhibition of SF3B1 was associated with an increase in broad intron retention (IR) on most transcripts, suggesting that IR can be used as a marker of spliceosome inhibition in chronic lymphocytic leukemia (CLL) cells. Furthermore, we separately analyzed exonic and intronic mapped reads on annotated RNA-sequencing transcripts obtained from B cells (n = 98 CLL patients) and healthy volunteers (n = 9). We measured intron/exon ratio to use that as a surrogate for alternative RNA splicing (ARS) and found that 66% of CLL-B cell transcripts had significant IR elevation compared with normal B cells (NBCs) and that correlated with mRNA downregulation and low expression levels. Transcripts with the highest IR levels belonged to biological pathways associated with gene expression and RNA splicing. A >2-fold increase of active pSF3B1 was observed in CLL-B cells compared with NBCs. Additionally, when the CLL-B cells were treated with macrolides (pladienolide-B), a significant decrease in pSF3B1, but not total SF3B1 protein, was observed. These findings suggest that IR/ARS is increased in CLL, which is associated with SF3B1 phosphorylation and susceptibility to SF3B1 inhibitors. These data provide additional support to the relevance of ARS in carcinogenesis and evidence of pSF3B1 participation in this process.

Clinical characteristics and outcomes in pseudomonas endocarditis: a systematic review of individual cases : Systematic review of pseudomonas endocarditis.

BACKGROUND: The landscape of Pseudomonas infective endocarditis (IE) is evolving with the widespread use of cardiac implantable devices and hospital-acquired infections. This systematic review aimed to evaluate the emerging risk factors and outcomes in Pseudomonas IE. METHODS: A literature search was performed in major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords and combinations till November 2023. We recorded data for risk factors, diagnostic and treatment modalities. This study is registered with PROSPERO, CRD42023442807. RESULTS: A total of 218 cases (131 articles) were included. Intravenous drug use (IDUs) and prosthetic valve endocarditis (PVE) were major risk factors for IE (37.6% and 22%). However, the prosthetic valve was the predominant risk factor in the last two decades (23.5%). Paravalvular complications (paravalvular leak, abscess, or pseudoaneurysm) were described in 40 cases (18%), and the vast majority belonged to the aortic valve (70%). The mean time from symptom onset to presentation was 14 days. The incidence of difficult-to-treat resistant (DTR) pseudomonas was 7.4%. Valve replacement was performed in 57.3% of cases. Combination antibiotics were used in most cases (77%), with the aminoglycosides-based combination being the most frequently used (66%). The overall mortality rate was 26.1%. The recurrence rate was 11.2%. Almost half of these patients were IDUs (47%), and most had aortic valve endocarditis (76%). CONCLUSIONS: This review highlights the changing epidemiology of Pseudomonas endocarditis with the emergence of prosthetic valve infections. Acute presentation and associated high mortality are characteristic of Pseudomonas IE and require aggressive diagnostic and therapeutic approach.

Comparative transcriptome profile of embryos at different developmental stages derived from somatic cell nuclear transfer (SCNT) and in-vitro fertilization (IVF) in riverine buffalo (Bubalus bubalis).

Somatic cell nuclear transfer (SCNT) is a very important reproductive technology with many diverse applications, such as fast multiplication of elite animals, the production of transgenic animals and embryonic stem (ES) cells. However, low cloning efficiency, a low live birth rate and the abnormally high incidence of abnormalities in the offspring born are attributed to incomplete or aberrant nuclear reprogramming. In SCNT embryos, the aberrant expression pattern of the genes throughout embryonic development is responsible for the incomplete nuclear reprogramming. The present study was carried out to identify the differential gene expression (DEGs) profile and molecular pathways of the SCNT and IVF embryos at different developmental stages (2 cell, 8 cell and blastocyst stages). In the present study, 1164 (2 cell), 1004 (8 cell) and 530 (blastocyst stage) DEGs were identified in the SCNT embryos as compared to IVF embryos. In addition, several genes such as ZEB1, GDF1, HSF5, PDE3B, VIM, TNNC, HSD3B1, TAGLN, ITGA4 and AGMAT were affecting the development of SCNT embryos as compared to IVF embryos. Further, Gene Ontology (GO) and molecular pathways analysis suggested, SCNT embryos exhibit variations compared to their IVF counterparts and affected the development of embryos throughout the different developmental stages. Apart from this, q-PCR analysis of the GDF1, TMEM114, and IGSF22 genes were utilized to validate the RNA-seq data. These findings contribute valuable insights about the different genes and molecular pathways underlying SCNT embryo development and offer crucial information for improving SCNT efficiency.

Insight in Quinazoline-based HDAC Inhibitors as Anti-cancer Agents.

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

Alkanols Regulate the Fluidity of Phospholipid Bilayer in Accordance to Their Concentration and Polarity.

In spite of the widespread use of alkanols as penetration enhancers, their effect on vesicular formulations remains largely unexplored. These can affect the stability and integrity of the phospholipid bilayers. In this study, we have investigated the interaction of linear (ethanol, butanol, hexanol, octanol) and branched alkanols (t-amylol and t-butanol) with three phospholipids (soya lecithin, SL; soy L-α-phosphatidylcholine, SPC; and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC). Thermodynamic and structural aspects of these interactions were studied as a function of the alkanol concentration and chain length. Our interpretations are based on isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) experiments. We observed one-site interactions wherein hydroxyl and acyl groups interacted with the polar and nonpolar regions of the phospholipid, respectively. The stability and structural integrity of bilayers appeared to be dependent upon (a) the hydrocarbon chain length and concentration of alcohols, and (b) the degree of unsaturation in the phospholipid molecule. We found that these interactions triggered a reduction in the enthalpy which was compensated by increased entropy, keeping free energy negative. Drop in enthalpy indicates reversible disordering of the bilayer which enables the diffusion of alcohol without triggering destabilization. Ethanol engaged predominantly with the interface, and it resulted in higher enthalpic changes. Interactions became increasingly unfavorable with longer alcohols - a cutoff point was recorded with hexanol. The overall sequence of membrane disordering capability was recorded as follows: ethanol < butanol < octanol < hexanol. Octanol's larger size restricted its penetration in the bilayer, and hence it caused less enthalpic changes relative to hexanol. This could also be verified from the trends in the area ratio of these vesicles obtained from the DLS data. Branched alkanols displayed a lower binding affinity with the phospholipids relative to their linear counterparts. These data are useful while contemplating the inclusion of short-chain alcohols as penetration enhancers in phospholipid vesicles.

Case Report: Salmonella typhi Iliopsoas Abscess with Concomitant Sacroiliitis in a Young Immunocompetent Male: A Rare Case.

Iliopsoas abscess is an infrequent condition characterized by the collection of pus in the iliopsoas compartment. The prevalence of the disease has been increasing in recent years with the emergence of various comorbidities and risk factors. The availability of newer imaging modalities has also improved the detection of new cases. Salmonellosis is an uncommon etiology in iliopsoas abscess and sacroiliitis. Most cases reported in the literature are associated with Staphylococcus aureus, Streptococci species, and Escherichia coli. Diabetes, hematological malignancies, HIV, and other immunocompromised states are important comorbidities/risk factors for iliopsoas abscess. We report a case of an 18-year-old male who presented with a history of fever and right hip pain for 10 days. Radioimaging revealed right sacroiliitis and iliopsoas abscess. Blood culture revealed pan-sensitive Salmonella typhi. After the prolonged course of antibiotics (intravenous ceftriaxone followed by oral levofloxacin), the patient improved with no further relapse in symptoms. Salmonella typhi should be an important differential of iliopsoas abscess in endemic regions after ruling out the common etiology such as S. aureus and Mycobacterium tuberculosis.

Associations of pain sensitivity and conditioned pain modulation with physical activity: findings from the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. DESIGN: We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. RESULTS: Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. CONCLUSIONS: In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA.