Chronic Morphine Treatment and Antiretroviral Therapy Exacerbate HIV-Distal Sensory Peripheral Neuropathy and Induce Distinct Microbial Alterations in the HIV Tg26 Mouse Model.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individuals, leading to chronic pain and reduced quality of life. Even with antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16S rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain pathways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine- and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mouse model to be a relevant system that can help elucidate the pathogenic mechanisms of the opioid- and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate interplay between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

Characterizing genetic diversity of Sclerotium rolfsii isolates by biomapping of mycelial compatibility groupings and multilocus sequence analysis.

Genetic diversity in Sclerotium rolfsii is useful for understanding its population structure, identifying different mycelial compatibility groups (MCGs), and developing targeted strategies for disease management in affected crops. In our study, a comprehensive genetic analysis was conducted on 50 isolates of S. rolfsii, collected from various geographic regions and host plants. Two specific genes, TEF1α and RPB2, were utilized to assess the genetic diversity and relationships among these isolates. Notably, out of 1225 pairings examined, only 154 exhibited a compatible reaction, while the majority displayed antagonistic reactions, resulting in the formation of a barrier zone. The isolates were grouped into 10 distinct MCGs. These MCGs were further characterized using genetic sequencing. TEF1α sequences distinguished the isolates into 17 distinct clusters, and RPB2 sequences classified them into 20 clusters. Some MCGs shared identical gene sequences within each gene, while others exhibited unique sequences. Intriguingly, when both TEF1α and RPB2 sequences were combined, all 10 MCGs were effectively differentiated, even those that appeared identical with single-gene analysis. This combined approach provided a comprehensive understanding of the genetic diversity and relationships among the S. rolfsii isolates, allowing for precise discrimination between different MCGs. The results shed light on the population structure and genetic variability within this plant pathogenic fungus, providing valuable insights for disease management and control strategies. This study highlights the significance of comprehending the varied virulence characteristics within S. rolfsii isolates, categorizing them into specific virulence groups based on disease severity index (DSI) values. The association with MCGs provides additional insights into the genetic underpinnings of virulence in this pathogen. Furthermore, the identification of geographical patterns in virulence implies the influence of region-specific factors, with potential implications for disease control and crop protection strategies.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [G. M. Sandeep] Last name [Kumar]. Author 2 Given name: [Praveen Kumar] Last name [Singh]. Also, kindly confirm the details in the metadata are correct.I confirm that the given names are accurate and presented in the correct sequence.

Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.

Immunogenicity of measles-rubella vaccine administered under India's Universal Immunization Programme in the context of measles-rubella elimination goal: A longitudinal study.

Background & objectives: There is a paucity of data regarding immunogenicity of recently introduced measles-rubella (MR) vaccine in Indian children, in which the first dose is administered below one year of age. This study was undertaken to assess the immunogenicity against rubella and measles 4-6 wk after one and two doses of MR vaccine administered under India's Universal Immunization Programme (UIP). Methods: In this longitudinal study, 100 consecutive healthy infants (9-12 months) of either gender attending the immunization clinic of a tertiary care government hospital affiliated to a medical college of Delhi for the first dose of routine MR vaccination were enrolled. MR vaccine (0.5 ml, subcutaneous) was administered to the enrolled participants (1st dose at 9-12 months and 2nd dose at 15-24 months). On each follow up (4-6 wk post-vaccination), 2 ml of venous blood sample was collected to estimate the antibody titres against measles and rubella using quantitative ELISA kits. Seroprotection (>10 IU/ml for measles and >10 WHO U/ml for rubella) and antibody titres were evaluated after each dose. Results: The seroprotection rate against rubella was 97.5 and 100 per cent and against measles was 88.7 per cent and 100 per cent 4-6 wk after the first and second doses, respectively. The mean (standard deviation) titres against rubella and measles increased significantly (P<0.001) after the second dose in comparison to the levels after the first dose by about 100 per cent and 20 per cent, respectively. Interpretation & conclusions: MR vaccine administered below one year of age under the UIP resulted in seroprotection against rubella and measles in a large majority of children. Furthermore, its second dose resulted in seroprotection of all children. The current MR vaccination strategy of two doses, out of which the first is to be given to infants below one year of age, appears robust and justifiable among Indian children.

Comparing the Efficacy of Postoperative Antibiotic Regimens in the Treatment of Maxillofacial Fractures: A Prospective Study.

AIM: The present study was designed to investigate the difference in the effectiveness of a 3 day postoperative course and a single perioperative dose of antibiotics on the incidence of postoperative infection in the management of maxillofacial trauma patients. MATERIALS AND METHODS: About 183 maxillofacial trauma patients requiring open reduction and internal fixation (ORIF) under general anesthesia were divided based on the type of fracture sustained, i.e., mandibular fractures, Le Fort fractures, and zygomaticomaxillary complex fractures. Patients from each fracture type were randomized into two groups, A and B. All patients were administered amoxicillin/clavulanate 1.2 grams intravenously 8 hours from the time of admission till the patient was taken up for surgery. Once the patients were taken up for surgery, a perioperative dose was administered. No antibiotics beyond this point were given to patients in Group A. Patients in Group B were administered the same antibiotic for 3 postoperative days additionally. Outcomes in terms of purulent discharge from the surgical site, an abscess or any other sign of infection, and wound dehiscence requiring reopening of the surgical site were considered. Patients were reviewed at 1 week, 2 weeks, 1 month, 2 months, and 3 months. RESULTS: No statistically significant difference was found between the two groups across all three fracture types in terms of postoperative outcomes. However, increased numbers of complications were noted in the patients treated with an intra-oral approach in each fracture type irrespective of group. All complications were managed with local measures. CONCLUSION: A single perioperative dose of antibiotics is effective in minimizing postoperative complications following ORIF of maxillofacial fractures and there is no significant benefit in prolonging the course of antibiotics postoperatively with the need for further studies to be conducted considering comminuted, complex fractures and old fractures. CLINICAL SIGNIFICANCE: In maxillofacial trauma, fractures frequently communicate with contaminated indigenous flora on the skin surface, oral cavities, or sinus cavities. Surgery is frequently performed using an approach across a contaminated area, even in closed fractures. Postoperative infections can be significantly decreased by using antibiotics in surgical procedures to treat facial fractures.

Comparative Assessment of Three Different Alveolar Ridge Dimension Measurement Methods before Implant Placement: An In Vivo Study.

AIM: The purpose of this study was to compare the three various techniques for measuring the alveolar ridge's dimensions prior to implant insertion. MATERIALS AND METHODS: For this study, a total of 36 participants were chosen. To prepare a surgical stent, a study model was created from an alginate impression. A first point (reference point) was marked on the crest of the ridge in relation to the adjacent teeth. Then, one point (point 1) and another point (point 2) were marked at distances of 3 and 6 mm, respectively, from the reference point. Based on the procedure for measuring the size of the alveolar ridge, the study was divided into the following groups. Group I: Cone-beam computed tomography (CBCT) measurement method; Group II: Ridge mapping measurement method; Group III: Direct caliper measurements method. Descriptive statistics were used to estimate the mean and standard deviation (SD). The Student's unpaired t-test was utilized for the statistical analysis. The 5% level of significance was used. RESULTS: There was no significant difference found between CBCT with ridge mapping and direct caliper measurements. However, on comparison of ridge mapping and direct caliper measurements technique, at point 1, the ridge mapping was 3.88 ± 0.12 and the direct caliper measurement was 3.62 ± 0.08. At point 2, the ridge mapping was 6.58 ± 0.06 and the direct caliper measurement was 6.32 ± 0.04. There was a statistically significant difference found between these two measurement methods. CONCLUSION: Within the limitation, the current study came to the conclusion that when CBCT and ridge mapping measurements were individually compared with the gold standard-the surgical open method, CBCT-demonstrated to be a highly specific and sensitive method for detecting the residual alveolar ridge width in the treatment planning of dental implants. CLINICAL SIGNIFICANCE: Evaluation of alveolar bone is necessary during treatment planning for dental implant placement. Using simply panoramic and/or periapical radiographs to evaluate the bone may not be sufficient because it only provides two-dimensional information regarding the implant locations. Therefore, for better implant placement, three-dimensional information of the implant site, such as CBCT and ridge mapping technique, should be assessed.

Angiotensin-Converting Enzyme Gene Polymorphism Influences Gastrointestinal Motility in Type 2 Diabetes Mellitus.

Uncontrolled diabetes mellitus may affect any part of the gastrointestinal tract (GIT) and impact negatively the quality of life. Angiotensin-converting enzyme (ACE) gene polymorphism can have direct effect on circulating level of ACE which further modifies the degradation of substance P and thus may influence the gut motility. Hence, it could be hypothesised that ACE gene polymorphism would influence the gut motility. An observational analytical study was conducted at PGIMER, Chandigarh. 300 Type2 diabetes mellitus (T2DM) and 200 age and sex matched healthy individuals were enrolled. After taking written consent, 5 ml blood sample was collected for measurement of substance P by ELISA method and for ACE gene polymorphism (insertion[I]/deletion[D]) by polymerase chain reaction. Orocecal transit time (OCTT) was measured using non-invasive lactulose breath test. Out of 300 diabetic patients, 32.7%, 44% and 23.3% belonged to II, ID and DD genotypes, respectively. The frequency of D allele (OR = 1.39) and DD genotype (OR = 2.17) was significantly higher in patients than in controls and was associated with increased risk. Moreover, more number of diabetes patients with constipation (90%) belonged to DD genotype and their OCTT was significantly delayed (166.7 ± 7.3 min) as compared to ID (143.5 ± 4.2 min) or II (121.8 ± 4.9 min) genotype. From this study, it could be concluded that ACE gene polymorphism could be an important contributing factor to influence the gut motility and thus giving rise to the GI symptoms for T2DM patients.

The interplay among Th17 and T regulatory cells in the immune dysregulation of chronic dermatophytic infection.

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17  cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research.

Oxidative stress and inflammatory markers in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is most demanding public health problem of 21st century. Uncontrolled diabetes may cause complications affecting any part of gut from mouth to rectum presenting as vomiting, nausea, bloating, abdominal pain, constipation and diarrhoea. The aim of this study was to compare levels of oxidative stress and inflammatory markers in small intestinal bacterial overgrowth (SIBO)-positive and negative diabetic patients. SUBJECTS AND METHODS: An observational analytical study was conducted on 300 T2DM (>5 years' duration) attending Diabetic Clinic. A total of 200 age- and sex-matched healthy individuals were enrolled as controls. Noninvasive glucose hydrogen breath test was used to diagnose SIBO. A total of 5 mL blood was taken. Plasma was used for measurement of inflammatory cytokines (TNF-α, IL-6 and IL-10) by ELISA. Hemolysate was used for measurement of lipid peroxidation, reduced GSH, superoxide dismutase and catalase. RESULTS: It was observed that constipation was present in 59.6% T2DM patients. SIBO was observed significantly higher (P < .0001) in T2DM patients than controls. Inflammatory and oxidative stress markers were significantly (P < .001) higher in diabetic and SIBO-positive patients than controls and SIBO negative. Reduced GSH was significantly (P < .05) lower whereas superoxide dismutase (SOD) and catalase antioxidant enzymes were significantly (<.05) higher in diabetic and SIBO-positive patients than controls and SIBO-negative patients. CONCLUSION: From this study, it could be concluded that SIBO in T2DM patients can cause oxidative stress and inflammation. Therefore, SIBO should be taken care to prevent further damage to intestine.

TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis.

BACKGROUND: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. RESULTS: The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-ß levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. CONCLUSIONS: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

Patient Specific Three-Dimensional Implant for Reconstruction of Complex Mandibular Defect.

This study was planned to evaluate the improvement in mandibular function, facial esthetics and quality of life after reconstruction of complex mandibular defects using patient-specific three-dimensional (3D) titanium implant. A total of 7 patients, who visited our outpatient clinic for reconstruction of mandibular defects after removal of their primary mandibular lesion and refused treatment with autologous bone grafts were treated with patient-specific implant for reconstruction of mandible. Three-dimensional virtual treatment planning was carried out using their 3D computed-tomographic data. The unaffected contralateral side of mandible was superimposed on the defect side and a customized implant was designed in the desired size and shape on the virtual model using computer aided designing and milled in titanium using selective laser melting, for precise anatomic mandibular reconstruction. There was significant improvement in their esthetics, function, and quality of life. The symmetry of the face and occlusion was restored with adequate mouth opening, closing, and lateral movements of the mandible with no deviation of jaw during movements. The patient specific implants appear to be very useful for precise reconstruction of mandible with greater accuracy. The concept of using customized implant with the help of 3D virtual treatment planning, stereolithographic models and computer aided designing greatly improves mandibular restoration and helps to achieve good facial profile, aesthetics and dental rehabilitation preventing severe complications related to autologous grafts.

Over-expression of Arabidopsis thaliana SFD1/GLY1, the gene encoding plastid localized glycerol-3-phosphate dehydrogenase, increases plastidic lipid content in transgenic rice plants.

Lipids are the major constituents of all membranous structures in plants. Plants possess two pathways for lipid biosynthesis: the prokaryotic pathway (i.e., plastidic pathway) and the eukaryotic pathway (i.e., endoplasmic-reticulum (ER) pathway). Whereas some plants synthesize galactolipids from diacylglycerol assembled in the plastid, others, including rice, derive their galactolipids from diacylglycerols assembled by the eukaryotic pathway. Arabidopsis thaliana glycerol-3-phosphate dehydrogenase (G3pDH), coded by SUPPRESSOR OF FATTY ACID DESATURASE 1 (SFD1; alias GLY1) gene, catalyzes the formation of glycerol 3-phosphate (G3p), the backbone of many membrane lipids. Here SFD1 was introduced to rice as a transgene. Arabidopsis SFD1 localizes in rice plastids and its over-expression increases plastidic membrane lipid content in transgenic rice plants without any major impact on ER lipids. The results suggest that over-expression of plastidic G3pDH enhances biosynthesis of plastid-localized lipids in rice. Lipid composition in the transgenic plants is consistent with increased phosphatidylglycerol synthesis in the plastid and increased galactolipid synthesis from diacylglycerol produced via the ER pathway. The transgenic plants show a higher photosynthetic assimilation rate, suggesting a possible application of this finding in crop improvement.

Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors.

A series of novel aminomethyl-piperidones were designed and evaluated as potential DPP-IV inhibitors. Optimized analogue 12v ((4S,5S)-5-(aminomethyl)-1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-4-(2,5-difluorophenyl)piperidin-2-one) showed excellent in vitro potency and selectivity for DPP-IV over other serine proteases. The lead compound 12v showed potent and long acting antihyperglycemic effects (in vivo), along with improved pharmacokinetic profile.

Semiquinone fraction isolated from Bacillus sp. INM-1 protects hepatic tissues against γ-radiation induced toxicity.

Present study was focused on evaluation of a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 for its ability against γ radiation induced oxidative stress in irradiated mice. Animals were divided into four group, i.e., (i) untreated control mice; (ii) SQGD treated (50 mg/kg b. wt. i.p.) mice; (iii) irradiated (10 Gy) mice; and (iv) irradiated mice which were pre-treated (-2 h) with SQGD (50 mg/kg b. wt. i.p.). Following treatment, liver homogenates of the treated mice were subjected to endogenous antioxidant enzymes estimation. Result indicated that SQGD pre-treatment, significantly (P < 0.05) induced superoxide dismutase (SOD) (19.84 ± 2.18% at 72 h), catalase (CAT) (26.47 ± 3.11% at 12 h), glutathione (33.81 ± 1.99% at 24 h), and glutathione-S-transferase (24.40 ± 2.65% at 6 h) activities in the liver of mice as compared with untreated control. Significant (P < 0.05) induction in SOD (50.04 ± 5.59% at 12 h), CAT (62.22 ± 7.50 at 72 h), glutathione (42.92 ± 2.28% at 24 h), and glutathione-S-transferase (46.65 ± 3.25 at 12 h) was observed in irradiated mice which were pre-treated with SQGD compared with only irradiated mice. Further, significant induction in ABTS(+) radicals (directly proportional to decrease mM Trolox equivalent) was observed in liver homogenate of H2 O2 treated mice which were found to be significantly inhibited in H2 O2 treated mice pre-treated with SQGD. Thus, it can be concluded that SQGD treatment neutralizes oxidative stress caused by irradiation not only by enhancing endogenous antioxidant enzymes but also by improving total antioxidant status of cellular system and thus cumulative effect of the phenomenon may contributes to radioprotection.

Immunomodulating and antiproteinuric effect of Hippophae rhamnoides (Badriphal) in idiopathic nephrotic syndrome.

OBJECTIVE: The treatment of idiopathic nephrotic syndrome is still not well settled and at times is very frustrating. Number of protocols have been reported with variable results outcome in various conditions. The main pillar of treatment of idiopathic nephrotic syndrome is use of immunomodulating and suppressive drugs in various combinations. The herbal preparations have also been reported to have immunomodulating property. The study has been planned to record Immunomodulating and antiproteinuric effect of Hippophae rhamnoides. MATERIAL AND METHODS: In the present study had 2 groups having 28 patients of idiopathic nephrotic syndrome in each group have been included. The patients were subjected to haematological, biochemical, immunological investigation at 0, 1, 2 and 3 months interval with dietic advise. Group A have been put on standard treatment, whereas group B on Badriphal in the well worked up doses. The hydroalcoholic extract of 350 mg twice daily of Badriphal was given to group B as add on treatment. Patients were followed up with definite protocol at monthly interval for 3 months. RESULTS: At the end of 3 month patients showed improvement in the symptoms of oedema, anorexia, oliguria in the herbal group. The urinary estimation of protein showed significant decrease in Group B with elevation of S. albumin levels. The inflammatory cytokines has showed significant decrease at the end of 3 month. CONCLUSION: Thus the pilot study showed beneficial effect of the herbal preparation Hippophae rhamnoides as add on treatment. A large perspective study is recommended to establish these findings.

Enhancement of dielectric and electro-optical characteristics of liquid crystalline material 4'-octyl-4-cyano-biphenyl with dispersed functionalized and nonfunctionalized multiwalled carbon nanotubes.

For recent applications, liquid crystal-carbon nanotube based nanocomposite systems have been proven to be highly attractive. In this paper, we give a thorough analysis of a nanocomposite system made of both functionalized and nonfunctionalized multiwalled carbon nanotubes that are disseminated in a 4'-octyl-4-cyano-biphenyl liquid crystal medium. Thermodynamic study reveals a decrease in the nanocomposites' transition temperatures. In contrast to nonfunctionalized multiwalled carbon nanotube dispersed systems, the enthalpy of functionalized multiwalled carbon nanotube dispersed systems has increased. In comparison to the pure sample, the dispersed nanocomposites have a smaller optical band gap. A rise in the longitudinal component of permittivity and, consequently, the dielectric anisotropy of the dispersed nanocomposites has been observed by dielectric studies. When compared to the pure sample, the conductivity of both dispersed nanocomposite materials has increased by two orders of magnitude. For the system with dispersed functionalized multiwalled carbon nanotubes, the threshold voltage, splay elastic constant, and rotational viscosity all decreased. For the dispersed nanocomposite of nonfunctionalized multiwalled carbon nanotubes, the value of the threshold voltage is somewhat decreased but the rotational viscosity and splay elastic constant both are enhanced. These findings show the applicability of the liquid crystal nanocomposites for display and electro-optical systems with appropriate tuning of the parameters.

Assessment of the Impact of Commonly used Beverages on Durability of Suture Materials: An In Vitro Study.

Aim: The current study was conducted to evaluate the influence of frequently ingested beverages on the stability of suture materials. Materials and Methods: This research comprised of two kinds of chromic catgut, polyglactin 910 (4-0) absorbable suture materials. Every specimen was subjected to tying using a square surgeon's knot. Subsequent to pretensioning, 80 suture samples (40 of every material) were employed in this research. Every specimen was subjected to immersion in artificial saliva to replicate the oral atmosphere. Specimens were sunken in the acidic drink (Coca Cola) and tea for 10 min every day. Tensile strengths of the suture specimens were subjected to test at particular time periods: before immersion and 1, 7, and 14 days after immersion. Tensile strength evaluation of the suture specimens was performed employing the microtensile tester at a cross-head speed of 2.0 mm/60 s. Results: When subjected to exposure to acidic beverages, the tensile strength of chromic catgut suture before immersing was 25.14 ± 0.16, 25.02 ± 0.08 on the first day, 16.34 ± 0.23 on the seventh day, and 9.18 ± 0.28 on the fourteenth day. When the suture substance made contact with tea, the tensile strength before immersing was 24.48 ± 0.02, 24.14 ± 0.16 on the first day, 18.26 ± 0.11 on the seventh day, and 12.39 ± 0.14 on the fourteenth day. When subjected to exposure to acidic beverages, the tensile strength of polyglactin 910 sutures before immersing was 25.21 ± 0.02, 25.08 ± 0.01 on the first day, 18.12 ± 0.06 on the seventh day, and 10.06 ± 0.32 on the fourteenth day. When the suture substance made contact with tea, the tensile strength before immersing was 25.02 ± 0.14, 24.96 ± 0.04 on the first day, 20.48 ± 0.18 on the seventh day, and 14.10 ± 0.08 on the fourteenth day. The differences between the groups were statistically significant. Conclusion: In conclusion, polyglactin 910 exhibited a maintained strength superior than chromic catgut sutures subsequent to 14 days.

BODIPY-Based Mitochondrial Targeted NIR-Responsive CO-Releasing Platform for the On-Demand Release of CO to Treat Cancer.

It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered meso-substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two meso-substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of ∼50 µM.

Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition.

BACKGROUND AND PURPOSE: Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine-mediated gastric inflammation. EXPERIMENTAL APPROACH: Mice were implanted with 25 mg slow-release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ-free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole. KEY RESULTS: Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine-mediated gastric pathology was significantly attenuated in germ-free mice, and reconstitution of morphine gastric microbiome in germ-free mice resulted gastric inflammation. In addition, morphine-mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine-induced gastric dysbiosis and preventing inflammation. CONCLUSION AND IMPLICATIONS: This study attributes morphine-induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine-associated pathophysiology.

Multi-omics analysis revealing the interplay between gut microbiome and the host following opioid use.

Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.