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.

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.

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.

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.

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.

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.

[Box: see text].

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.

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).

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.

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.

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

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

Seed endophytic bacterium Lysinibacillus sp. (ZM1) from maize (Zea mays L.) shapes its root architecture through modulation of auxin biosynthesis and nitrogen metabolism.

Seed endophytic bacteria have been shown to promote the growth and development of numerous plants. However, the underlying mechanism still needs to be better understood. The present study aims to investigate the role of a seed endophytic bacterium Lysinibacillus sp. (ZM1) in promoting plant growth and shaping the root architecture of maize seedlings. The study explores how bacteria-mediated auxin biosynthesis and nitrogen metabolism affect plant growth promotion and shape the root architecture of maize seedlings. The results demonstrate that ZM1 inoculation significantly enhances root length, root biomass, and the number of seminal roots in maize seedlings. Additionally, the treated seedlings exhibit increased shoot biomass and higher levels of photosynthetic pigments. Confocal laser scanning microscopy (CLSM) analysis revealed extensive colonization of ZM1 on root hairs, as well as in the cortical and stellar regions of the root. Furthermore, LC-MS analysis demonstrated elevated auxin content in the roots of the ZM1 treated maize seedlings compared to the uninoculated control. Inoculation with ZM1 significantly increased the levels of endogenous ammonium content, GS, and GOGAT enzyme activities in the roots of treated maize seedlings compared to the control, indicating enhanced nitrogen metabolism. Furthermore, inoculation of bacteria under nitrogen-deficient conditions enhanced plant growth, as evidenced by increased root shoot length, fresh and dry weights, average number of seminal roots, and content of photosynthetic pigments. Transcript analysis indicated upregulation of auxin biosynthetic genes, along with genes involved in nitrogen metabolism at different time points in roots of ZM1-treated maize seedlings. Collectively, our findings highlight the positive impact of Lysinibacillus sp. ZM1 inoculation on maize seeds by improving root architecture through modulation of auxin biosynthesis and affecting various nitrogen metabolism related parameters. These findings provide valuable insights into the potential utilization of seed endophytic bacteria as biofertilizers to enhance plant growth and yield in nutrient deficient soils.

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.

Nano Encapsulation of An Essential Oil Transpire the Therapeutic Approach.

Essential oils are natural compounds extracted from plants that are volatile and sensitive to heat. Due to their therapeutic value, essential oils are now used in many industries, including the sanitary, cosmetic, agricultural, food, and pharmaceutical industries. These are complex mixtures of a wide range of volatile molecules, including phenol-derived aliphatic and aromatic compounds and terpenoids. Essential oils have been used medicinally since ancient times for their antibacterial, antifungal, antiviral, antiparasitic, insecticidal, sedative, antiinflammatory, and anaesthetic properties. However, essential oils come with inherent limitations; thus, nanoencapsulation is advocated as a remedy as it has the potential to enhance the stability, solubility, and effectiveness of formulations based on essential oils, all while preserving the therapeutic drug blood levels. It is not always viable to use essential oils independently in treatment due to several restrictions; however, nanodelivery technologies appear capable of overcoming these challenges. The therapeutic efficacy that is achieved can be affected by several factors, including the selection of the essential oil as well as the system of nanodelivery. Today, nanoencapsulation is capable of enabling the simultaneous delivery of multiple oils, providing synergistic effects, and facilitating the development of combinational therapies. Additionally, they may have potential applications in preserving food to prolong the shelf life of quickspoiling items and their fragrances. While there is already much research on the characterisation of EOs, this review evaluates the features of the nanoparticles employed for the delivery of essential oils and their impact on the functionality of nano-delivered essential oils and their beneficial uses.

Rarest of the Rare - Malignant Solitary Fibrous Tumour of the Breast: Case Report and Literature Review.

Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far. Here we have presented such a case from India, where a 52-year-old lady presented with a 10 cm x 8 cm breast lump. Diagnosis was achieved with the help of FDG PET, histopathology and immunohistochemistry, which showed nuclear positivity for STAT6. Fluorescent in situ hybridization (FISH) molecular study for SS18-SSX was used to rule out the differential diagnosis of synovial sarcoma. Guidelines for the management of this type of breast malignancy still do not exist. We have done a review of the literature in order to discuss which might be the best management in such cases. Evidence on this very rarest type of breast malignancy is still evolving. The interest in the case described here relies on its rarity, difficulties in achieving diagnosis and formulation of the proper management.

The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.