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Abstract Background This study aims to evaluate the efficacy and safety of tranexamic acid (TXA) administered via the I/V (Intravenous) route and irrigation fluid route during TURP to directly target the bleeding site. Methods A total of 105 cases undergoing bipolar–TURP with gland size 40–100 g were randomized into three groups—control/placebo group (n = 35), I/V group (n = 35) (received 1gm TXA 20 min before the procedure) and irrigation group (n = 35) (received 500 mg TXA in every 3000 ml irrigation fluid up to a maximum of 2 g). Blood loss was estimated by recording haemoglobin and hematocrit at 4 h after the procedure and on first postoperative day. Other parameters such as resection time, intraoperative endoscopic vision, irrigation fluid volume and complications were noted. Results When measured at 4 h postoperatively, the drop in haemoglobin and haematocrit, respectively, was maximum in the control group (ΔHb = 0.78 g/dl, ΔHCT = 1.23%) followed by the irrigation group (ΔHb = 0.51 g/dl, ΔHCT = 0.72%) and was least in the I/V group (0.27 g/dl, 0.62%). The intergroup analysis showed significant difference only between the control vs I/V group (ΔHb p = 0.0163, ΔHCT p = 0.0253). On postoperative day 1, the drop in haemoglobin and haematocrit, respectively, was maximum in the control group (1.10 g/dl, 1.63%) followed by the irrigation group (0.828 g/dl, 0.911%) and was least in the I/V group (0.811 g/dl, 0.948%). The intergroup analysis showed significant difference between the control vs irrigation group (ΔHb p = 0.026, ΔHCT p = 0.0001) and control vs I/V group (ΔHb p = 0.016, ΔHCT p = 0.0003). Total resection time, average volume of irrigation fluid and average postoperative stay were comparable. No significant complications were observed. Conclusions TXA, given either via I/V or irrigation fluid route, reduces postoperative blood loss associated with TURP. Both routes are superior to placebo, but neither is superior to the other. TXA via the intravenous route also reduces intraoperative blood loss, but the same advantage is not observed with administration through irrigation fluid. TXA via either route has no impact on endoscopic vision. Both routes of administration are safe with no reported side effects.

Co-agglomeration unique crystal engineering approach; in which the co-precipitated micro-particles of nitramines with other energetic materials co-agglomerated by the slurry method; to modify the energetic properties of attractive nitramines like CL20, HMX, BCHMX, and RDX etc. The interesting properties and structural modifications in newly prepared co-agglomerated crystals (CACs) interesting one are discussed here. There are notable variations in the crystal morphologies and packing of crystals, including key properties like relatively high density, melting point, impact sensitivity, and detonation properties. These CACs are in the overwhelming and majority showing properties like co-crystals. Apart from these aspects, co-agglomeration provides a huge opportunity to tune the key properties and performance of existing energetic materials and is easy to scale-up for the industrial level. These preliminary results also suggest that chemical engineering factors are involved in the preparation of CACs and have tremendous improvements than the conventional crystallization. With technological optimization this method can be employable industrial scale production.

Background: Diode laser is known for its biostimulatory effects on various cell populations such as osteoblasts and fibroblasts. The usage of low-level laser therapy for photobiomodulation depends on its type, emission wavelength, and energy selected. Previously performed in vitro studies have determined its effect on cell proliferation and cytotoxicity; however, the results were inconsistent. Objectives: The objectives of this study were to evaluate and compare diode laser effect on mouse embryonic fibroblasts (MEFs) and human gingival fibroblasts (HGFs) for proliferation and cytotoxicity. Materials and Methods: 32 samples, 16 wells of MEF cells (Group I) and HGF cells (Group II) each with 8 subgroups containing control (no laser irradiation) and experimental (laser irradiated) groups were cultured after being seeded at 4000 cells/ well with 4cm inter-well distance. Experimental group cell cultures were irradiated with a single dose of 810 nm diode laser (energy 1J/cm2, 12.5 mW, 80 s/well) using continuous wave mode after 1 day of incubation. Spectrophotometric analysis was done after 24 h of laser irradiation for cell proliferation and cell cytotoxicity on the 2nd, 3rd, and 7th days on all groups. Results: Human and mouse fibroblast groups showed positive results when irradiated with an 810 nm laser. A hundred percent proliferation was seen for MEF in 7 days and HGF in 2 days. Two percent cytotoxicity was seen on the 2nd and 3rd day in MEF. Increased cell proliferation and minimal cytotoxic effects were seen with diode laser usage. Conclusion: Low-level laser irradiation indicates an increase in cell proliferation with less cytotoxicity on mouse and human fibroblasts.

Abstract Cyclotriazadisulfonamide (CADA) is a macrocyclic compound known for its unique mechanism in inhibiting HIV infection by downregulating the CD4 T-cell receptor, a crucial entry point for the virus. Unlike other antiretrovirals, CADA exhibits activity against a wide range of HIV strains, as all HIV variants require CD4 binding for infection. Furthermore, CADA has shown a synergistic effect with clinically approved anti-HIV drugs, offering potential for enhanced therapeutic strategies (Vermeire & Schols, [65]). One proposed mechanism for CADA’s inhibition of the CD4 receptor involves blocking the gates of the Sec61 channel, thereby preventing its translocation. However, CADA suffers from poor solubility and bioavailability. To address this, the study aimed to design CADA analogs with improved binding to the Sec61 channel, enhanced bioavailability, and reduced toxicity. The analogs were designed using SeeSAR, with Avogadro and Meeko used for 3D configuration and pseudoatom placement, respectively. AutoDock Vina version 1.2.4 was employed to predict the binding energies of these analogs. Of the 113 analogs designed, 93 demonstrated a more negative binding energy to the Sec61 channel compared to CADA. Structure-binding energy analyses were done to the top-binding analogs to show favorable structural modifications. Enzyme-ligand interactions were analyzed to elucidate the forces contributing to these binding energies. Additionally, 33 of the 113 analogs were deemed bioavailable using a bioavailability criteria specific for macrocycles. Toxicity predictions using PASS Online and StopTox identified analogs JGL023, JGL024, JGL032, and JGL047 as potential drug candidates. Molecular dynamics simulations using Gromacs-2020.4 revealed that JGL023 and JGL032 exhibited the most favorable binding to the Sec61 channel, as determined by evaluating ligand and residue flexibility, compactness, contact frequency, motion pathways, free energy, and other relevant parameters. Synthetic routes for these four analogs were proposed for future studies. The results of this study offer a new perspective on developing drugs to inhibit HIV entry.

Abstract Viral nervous necrosis (VNN) poses a significant threat to the aquaculture industry, causing substantial losses and economic burdens. The disease, attributed to nervous necrosis viruses within the Betanodavirus genus, is particularly pervasive in the Mediterranean region, affecting various fish species across all production stages with mortality rates reaching 100%. Developing effective preventive measures against VNN is imperative. In this study, we employed rigorous immunoinformatics techniques to design a novel multi-epitope vaccine targeting VNN. Five RNA-directed RNA polymerases, crucial to the lifecycle of Betanodavirus, were selected as vaccine targets. The antigenicity and favorable physicochemical properties of these proteins were confirmed, and epitope mapping identified cytotoxic T lymphocyte, helper T lymphocyte, and linear B lymphocyte epitopes essential for eliciting a robust immune response. The selected epitopes, characterized by high antigenicity, non-allergenicity, and non-toxicity, were further enhanced by adding PADRE sequences and hBD adjuvants to increase immunogenicity. Two vaccine constructs were developed by linking epitopes using appropriate linkers, demonstrating high antigenicity, solubility, and stability. Molecular dynamics simulations revealed stable interactions between the vaccine constructs and Toll-like receptors (TLRs), essential for pathogen recognition and immune response activation in fish. Notably, vaccine construct V2 exhibited superior stability and binding affinity with TLR8, suggesting its potential as a promising candidate for VNN prevention. Overall, our study presents a comprehensive approach to VNN vaccine design utilizing immunoinformatics, offering safe, immunogenic, and effective solutions across multiple Betanodavirus species. Further experimental validation in model animals is recommended to fully assess the vaccine’s efficacy. This research contributes to improved vaccine development against diverse fish pathogens by addressing emerging challenges and individualized immunization requirements in aquaculture.

The literature widely reported information about apparent high impact sensitivities of both the pure 2,4,6-trinitrotoluene (TNT; i.e. of 14–16 J) and ɛ-2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (ɛ-CL20; i.e. of 2–4.4 J), which mostly correspond to the BAM method of determination. This brief overview discusses the reasons of these error data. The physical organic chemistry approach to this problem has confirmed the Beijing Inst. of Technology value of 13.2 J for ɛ-CL20 and the LANL value of 39.2 J for TNT. The morphological instability of ɛ-CL20, when in contact with polar binders or plasticizers, might not have much influence on its application in propellants. The stabilization of ɛ- to β-CL20 upon its entry into a cocrystal with a coformer having the character of a polynitro compound (especially with nitramines) could be of practical importance. The high impact sensitivity of TNT and ɛ-CL20 is important for handling and processing safety when related to the specific practical samples. However, they cannot be used for molecular-structural analyses and predictions or as a comparative standard, which is currently widespread in the literature.

Graphene oxide (GO) and mesoporous silica nanoparticle (MSN) have been documented as advanced nanocarriers for drug delivery due to their unique and versatile properties. The design of GO–MSN nanocomposite offers a large surface area, adjustable pore size, biocompatibility, and low cytotoxicity. The application of acyclovir (ACV) (BCS: III) is suffering from poor permeability, low bioavailability, etc. Hence, the use of GO–MSN nanocomposite for the delivery of ACV may overcome the limitations of ACV. Therefore, the present work aims to design the lipid-coated ACV-loaded GO–MSN (LC-ACV-GO–MSN) nanocomposites. In brief, the design of experiments (DoE, 32 response surface methodology) approach was preferred for the development of GO–MSN nanocomposite. The loading of ACV in nanocomposite was done passive loading whereas the coating of lipids was done using a modified thin film hydration technique. At last, different spectral characterizations were performed. The output demonstrated that the entrapment efficiency of ACV-MSN and ACV-GO–MSN was 51.13% and 71.86%, respectively. Afterward, the designed LC-ACV-GO–MSN and ACV-GO–MSN nanocomposite shows 93.40% and 80.74% in vitro drug release, respectively. In conclusion, the design of LC-ACV-GO–MSN nanocomposite using optimized GO–MSN followed lipid coating offers the modified release. Therefore, in the future, LC-ACV-GO–MSN nanocomposite can be used for the delivery of ACV and other drug molecules with a high payload and enhanced release profile. We hope the current proof of concept may provide advantages over existing methods and emphasize the significance of protocells in cargo delivery systems.

PHACE syndrome was first described by Dr. Ilonia Frieden and colleagues in 1996. It is an under-recognized rather than a very rare condition among patients with large facial hemangiomas. It is challenging as it has significant neurological, vascular and airway implications. Vascular malformations compromising cerebral blood flow predispose the patient to strokes and seizures. Subglottic hemangiomas, if present, could bleed during intubation. Meticulous neurological monitoring is mandatory in those undergoing repair of the great vessels. We describe the perioperative management of a child with PHACE syndrome subjected to dental treatment under general anesthesia.

The widespread occurrence of Type 2 Diabetes Mellitus (T2DM) is a significant public health issue in India. Diabetes severely impedes the wound healing process. Delayed wound healing in diabetes is caused by a decrease in nitric oxide generation, the presence of Advanced Glycation End products (AGEs), and impaired epithelial cell motility. In this case, a 38-year-old diabetic male presented seeking Ayurvedic treatment for a wound on his right lower limb, which resulted from a prick injury sustained 10 days earlier. He also had varicose veins in both legs and had been living with diabetes for five years. His medical history included slow wound healing. The condition was diagnosed as “Dushtvrana” associated with “Prameha” and was treated with Ayurvedic medicines in addition to oral hypoglycaemics. The Ayurvedic treatment included Panchavalkala Kwatha Vranadhavan, followed by the local application of Yashtimadhu Ghrita every third day, along with the oral administration of Nishadhatri Yoga (5 g) twice daily. Additionally, he was prescribed a daily evening dose of 500 mg metformin tablets for 25 days. There was no pain or inflammation observed, and the wound fully healed. This case demonstrates the effectiveness of Ayurvedic treatment-Panchavalkala Kwatha Vranadhavan, Yashtimadhu Ghrita for local application, and oral Nishadhatri Yoga-as an adjunct to the oral hypoglycaemic drug metformin in treating diabetic wounds.

UASD Bt cotton Event-78 based early segregating generations (F2 & F3) derived from three diverse crosses were evaluated for field incidence of cotton leaf hopper during kharif-2021 & 2022 at Agricultural Research Station, UAS, Dharwad. A total 600 F2 plants from the crosses viz., UASD Bt-78 х DHS-29, UASDBt-78 х Suvin and Suvin х UASD Bt-78 were screened of which 103,100 and 102 plants respective to the three crosses were found to be resistant. The segregation of F2 population for the jassid tolerance deciphered the implicit “Inhibitory epistasis” mechanism of host plant resistance. Further evaluation of F3 families of these crosses leads to identification of 103 resistant lines from all the three crosses, the mean leafhopper population ranges from 0.67- 2.67 leafhoppers / 3 leaves with the LHRI score of 1.

Background Kite string injuries (manja cut injuries), particularly those caused by Chinese manja, are new culprit of emergencies especially in the month of January in Maharashtra region. These injuries commonly affect the neck, face, hands, and legs, especially among individuals traveling on two wheelers. The visibility challenge, where the kite's thread is difficult to see, further exacerbates the risk.

Abstract Cyprinid herpesvirus is a causative agent of a destructive disease in common and koi carp (Cyprinus carpio), which leads to substantial global financial losses in aquaculture industries. Among the strains of C. herpesvirus, C. herpesvirus 1 (CyHV-1) and C. herpesvirus 3 (CyHV-3) are known as highly pathogenic to carp fishes in Europe, Asia, and Africa. To date, no effective vaccine has been developed to combat these viruses. This study aimed to develop unique multi-epitope subunit vaccines targeting the CyHV-1 and CyHV-3 using a reverse vaccinology approach. The study began with a comprehensive literature review to identify the most critical proteins, which were then subjected to in silico analyses to predict highly antigenic epitopes. These analyses involved assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. We constructed two multi-epitope-based vaccines incorporating a suitable adjuvant and appropriate linkers. It revealed that both the vaccines are non-toxic and immunogenic. The tertiary structures of the vaccine proteins were generated, refined, and validated to ensure their suitability. The binding affinity between the vaccine constructs and TLR3 and TLR5 receptors were assessed by molecular docking studies. Molecular dynamics simulations indicated that vaccine construct V1 exhibited greater stability with both TLR3 and TLR5 based on RMSD analysis. Hydrogen bond analysis revealed a stronger binding affinity between the vaccine constructs and TLR5 compared to TLR3. Furthermore, MM-PBSA analysis suggested that both vaccine constructs exhibited a better affinity for TLR5. Considering all aspects, the results suggest that in silico development of CyHV vaccines incorporating multiple epitopes holds promise for management of diseases caused by CyHV-1 and CyHV-3. However, further in vivo trials are highly recommended to validate the efficacies of these vaccines.

Cerebral palsy (CP) is a group of permanent clinical syndromes which are characterized by motor and postural dysfunction. Urolithiasis is a unique challenge in children with neurologic disorders and those with CP. It is very important to formulate a safe and effective anesthetic plan for CP patients. A teenage male of around 17 years, diagnosed with CP for ten years, presented with complaints of pain abdomen for four years. Investigations revealed a vesical calculus of 14 mm. The patient underwent transurethral cystolithotripsy under spinal anesthesia and sedation. During the procedure, there were many difficulties faced, such as inability to place patient in lithotomy position and also challenges in administering anesthesia. In this article, we will discuss how we overcame the difficulties and successfully performed the case. When encountering such a case, it is better to pre-plan the procedure with the anesthetist due to the challenges that might be faced in managing such a case. Also, if conventional cystolithotripsy cannot be performed for any reason, and then percutaneous cystolithotripsy can also be performed.

The aim of the present study was to evaluate the effect of the ethyl acetate fraction of amla (EAFA) extract on valproic acid (VPA)-induced postnatal autism in BALB/c mice. Our study revealed that mice treated with VPA on postnatal day 14 (PND14) showed significant abnormal behaviours such as social interaction, social affiliation, anxiety, and motor coordination compared to the control group, while EAFA extract treatment (100 mg/kg) ameliorated these symptoms. Our study highlights the protective effect of EAFA extract on improving behavioural alterations, significantly restoring anti-oxidative enzymes such as GST and GR, and reducing MDA and NO levels. Furthermore, the EAFA-treated group significantly lowered the proinflammatory markers (IL-1β and TNF-α) and the expression of up-regulated 5-HT1D, 5-HT2A, and D2 receptor proteins. Based on histopathological studies, the percentage of neuronal injury in the EAFA-treated group as well as cellular structural changes were reduced using SEM analysis. In conclusion, the present study suggests that treatment with EAFA extract ameliorates VPA-induced autism due to its anti-oxidant and neuroprotective activity.

Objective: Orbital apex syndrome (OAS) is a rare condition with multiple cranial nerve involvement caused by varied etiologies. It is not only a threat to the patient’s vision but also life-threatening due to the intracranial spread of infection, if not diagnosed early and treated accurately. To study the outcome of endoscopic sinus surgery (ESS) for OAS secondary to sinusitis concerning resolution of ptosis, improvement of ophthalmoplegia, visual prognosis, intracranial spread of infection, and mortality. Methods: A retrospective review of patients with OAS secondary to sinusitis who underwent ESS from 2011 to 2021 was tabulated and analyzed. Results: Twenty-seven patients (mean age: 55.11+/-16 years; male 62%) were included in this study. At presentation, blurring of vision (81%), headache (66%), diplopia (63%) ptosis (63%) were the most common symptoms, and ophthalmoplegia (100%) was the most common sign. Five patients had no perception of light and the rest had various degrees of vision impairment. The most common etiopathology of sinusitis was fungal sinusitis (12 mucormycosis and four aspergillus). The final visual prognosis at three months follow-up post-ESS showed vision stabilization (no improvement or worsening) in 13 (48%) patients, improvement in seven (26%) patients, and vision deterioration in two (7%) patients. There was a significant improvement in ptosis (70%) and ophthalmoplegia (85%). There was no intracranial spread of infection or recurrence with a mortality rate of 3.7% (one patient). Conclusion: ESS coupled with appropriate antimicrobials effectively treats OAS secondary to sinusitis with decreased morbidity and mortality.

In this systematic investigation of Abutilon indicum extracts for antidiabetic activity, using TLC and HPTLC were employed to analyze bioactive compounds. The ethanolic extract (EA) exhibited specific RF values: 0.16 for catechin, 0.57 for gallic acid, and 0.70 for quercetin, with Abutilon indicum (EA) containing the highest percentages—48.87% catechin, 27.45% gallic acid, and 7.25% quercetin. The robustly developed and validated HPTLC process, applied to ethanolic extracts, demonstrated clear bands and sharp peaks, ensuring precise separation of bioactive compounds. Similar methodologies were employed for chloroform extract (CA) and aqueous extract (AA), revealing RF values of 0.10, 0.36, and 0.54 for CA, and 0.087, 0.36, and 0.53 for AA, corresponding to catechin, gallic acid, and quercetin, respectively. Fingerprinting analysis confirmed the simultaneous presence of these compounds, highlighting the method's utility for quality control. Statistical analysis supported the reliability and cost-effective suitability of HPTLC for quantitative analysis in assessing herbal material and formulations. GC-MS exploration of Abutilon indicum extracts revealed over 20 compounds in each, including flavonoids, alkaloids, and terpenoids in the ethanolic extract, and phytosterols, alkaloids, and terpenoids in the chloroform extract. The aqueous extract displayed a diverse phytochemical composition, affirming medicinal potential. These results collectively endorse Abutilon indicum's versatility and therapeutic potential in herbal medicine and pharmaceutical formulations. Keywords Pharmacognosy, Bioactive Compounds, Analytical Study, Abutilon indicum etc

Abstract Global trends show that the rapid increase in maize production is associated more with the expansion of maize growing areas than with rapid increases in yield. This is possible through achieving possible higher productivity through maize production practices intensification to meet the sustainable production. Therefore, a field experiment on “Ecological intensification of climate-resilient maize–chickpea cropping system” was conducted during consecutive three years from 2017–2018 to 2019–2020 at Main Agricultural Research Station, Dharwad, Karnataka, India. Results of three years pooled data revealed that ecological intensification (EI) treatment which comprises of all best management practices resulted in higher grain yield (7560 kg/ha) and stover yield compared to farmers’ practice (FP) and all other treatments which were deficit in one or other crop management practices. Similarly, in the succeeding winter season, significantly higher chickpea yield (797 kg/ha) was recorded in EI. Further EI practice recorded significant amount of soil organic carbon, available nitrogen, phosphorus, potassium, zinc, and iron after completion of third cycle of experimentation (0.60%, 235.3 kg/ha,21.0 kg/ha,363.2 kg/ha,0.52 ppm and 5.2 ppm respectively). Soil enzymatic activity was also improved in EI practice over the years and improvement in each year was significant. Lower input energy use was in FP (17,855.2 MJ/ha). Whereas total output energy produced was the highest in EI practice (220,590 MJ ha−1) and lower output energy was recorded in EI–integrated nutrient management (INM) (149,255 MJ/ha). Lower energy productivity was noticed in EI-INM. Lower specific energy was recorded in FP and was followed by EI practice. Whereas higher specific energy was noticed is EI–INM. Each individual year and pooled data showed that EI practice recorded higher net return and benefit–cost ratio. The lower net returns were obtained in EI-integrated weed management (Rs. 51354.7/ha), EI-recommended irrigation management (Rs. 56,015.3/ha), integrated pest management (Rs. 59,569.7/ha) and farmers’ practice (Rs. 67,357.7/ha) which were on par with others.

In the previous study, the synthesis and characterization of 4-(3-fluorophenyl)-3-thiosemicarbazide and benzaldehyde derivatives based thiosemicarbazone ligands and their Co(II), Ni(II), Cu(II), Zn(II) complexes were carried out to evaluate their malarial and oxidant and inflammatory inhibition abilities, demonstrating that these compounds have robust efficacy for these ailments. In the present research, to find out a combating agent against breast cancer, tuberculosis, bacterial and fungal ailments, the compounds were tested through MTT, microplate alamar blue and serial dilution protocols. ADMET and DFT investigation were analyzed against highly bioactive compounds (2, 7–10) to give a new insight about compound's reactivity, stability and drug likeness properties. Furthermore, activity results shows that the ligand (2) and its complexes demonstrate greater efficacy compared to ligand (1) and its complexes. The Cu(II) (9) and Zn(II) (10) complexes were observed as highly efficient for breast cancer (MCF-7 cell line), TB (H37Rv strain), bacterial and fungal ailments in comparison of standard drugs with 0.029 ± 0.001 μM IC50 value for (9) in anticancer activity and 0.0034 ± 0.0017 μmol/mL MIC value for (10) in anti-tuberculosis activity. In the molecular docking investigation, the various kind of binding interactions and lowest binding affinity of (9) (against 4RJ3 (−10.0 kcal/mol), 2VCJ (−7.9 kcal/mol)) and (10) (−7.8 and −8.3 kcal/mol for 5V3Y and 3PTY protein) support their bioactivity. This research highlights the pharmaceutical importance of transition metal complexes having thiosemicarbazones, presenting a significant approach for the discovery of potent anti-infectious agent.

Background: Majority of the AIDS patients will get opportunistic infections due to their low immune system and as result, these opportunistic infections incurs sever health issue among the HIV patients. Methods: The study was conducted on 370 immunocompromised patients selected from government civil hospital ART centre, Vijayapur district Karnataka. Results: majority 302(81.6%) had CD4 count less than 500 cell/ mm3.Metabolic disorder ,PPD and Photosend were considered to be significant opportunist infections and were significant correlation with CD4 count of the patients. Conclusion: It was concluded that some of the opportunistic infections such as metabolic disorder, PPD and photosend was highly correlated with CD4 count among the autoimmunocompromised patients.

Background: Cleft lip chelioplasty can be approached with a wide array of different techniques.The ultimate goal of all techniques is to restore sphincter competence and aesthetically favorable outcome. Dr.C. Balakrishnan of Government medical college,Nagpur devised an original triple wedge technique,a form of three triangular flap,that was evolved independently of the triangular flap technique.Unfortunately he did not publish his technique,even today many of his 4th and 5th generation trainees perform triple wedge technique for cleft lip repair.[1],[2,],[3] The history of cleft lip repair in Nagpur and it's growth can not be dissociated from modern plastic surgery in India by the father of modern plastic surgery in India Dr. C.Balakrishnan himself,who established the first department of plastic surgery in India at GMC Nagpur,credited it with a new classification of cleft lip and palate, a new technique of cleft lip repair and propagated the principles of comprehensive cleft care. In our institute triple wedge repair for cleft lip is the repair of choice since 1950, although many modifications have been done in original technique since then. I was trained in KEM hospital,Mumbai and learned Millard's repair there. After coming to Nagpur,I joined the department as lecturer under respected Dr S.M. Kale sir and I got the opportunity to learn triple wedge technique from him. Over the last 20 years I have added few modifications like changing the orientation of triangles,using the mucosal element for anterior palate repair which used to be discarded in original triple wedge technique and primary rhinoplasty. Aims and Objectives: In this original article we are describing the original triple wedge technique invented by father of modern plastic surgery in India Dr.C. Balakrishnan 2 and its evolution since then in the first department of plastic surgery in India. Materials and Methods: Patients operated in last 50 years at Government Medical college,Nagpur and data available in department. Results: Early and late postoperative pictures showing result of the technique. Conclusion: The purpose of this article is illuminating unpublished work of legend of plastic surgery in India Dr. C. Balakrishnan.

Abstract Background Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. Methods endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. Discussion This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. Trial registration ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Abstract This paper aims to introduce a custom-designed multiband planar inverted-F antenna (PIFA) suitable for automotive applications in LTE/5G schemes operating under 6 GHz, as well as Vehicle-to-Everything (V2X) communications. The PIFA antenna has a broad bandwidth capability, resonating from 950 MHz to 6 GHz. The proposed PIFA antenna is divided into three parts: the top, front, and back, resulting in a unique and effective antenna structure. The antenna is fabricated using a substrate made of FR4 material with a dielectric constant of 4.4. The whole measurements of the antenna are 54 × 38 × 25 mm3.The proposed PIFA antenna has been tested and has achieved a voltage standing wave ratio (VSWR) of less than 2 across the entire frequency range of 950 MHz to 6 GHz. Additionally, the maximum gain achieved by the antenna is 7.08 dBi at a frequency of 5.5 GHz, 6.81 dBi at 5.2 GHz, and 6.65 dBi at 5.9 GHz. The antenna also achieved a gain of 6.67 dBi at 3.8 GHz and a gain of 3.31 dBi at 1.7 GHz. Overall, this paper presents a well-designed and effective multiband PIFA antenna that is appropriate for use in vehicular applications. The antenna ability to cover a wide range of bandwidth and achieve high gain makes it an excellent candidate for use in LTE/5G systems and V2X communications.

Abstract Background Site-specific transport of medicinal products to malignant cells and tissues is an intriguing area since it has an ability to safeguard healthy cells. Selective upregulation of folate receptors on colon cancer cells is usual. Consequently, folate receptors have become one of extensively studied target moieties for targeting the delivery of chemotherapeutics. Hence, the study aimed to anchor folic acid, chitosan and oxaliplatin to the functionalized nanotube (FA-CHI-FSWCNT-OXA) for targeting folate receptors on colon cancer cells. The purification process of single-walled carbon nanotubes (SWCNTs) involved the use of an ultrasonic-assisted acid digestion method. The developed complex was evaluated using FTIR, DSC, SEM, XRD and in vitro dissolution studies. SRB and MTT assays were used to assess in vitro cytotoxicity of oxaliplatin and FA-CHI-FSWCNT-OXA) against HT29 and COLO320DM cell lines. Further, progression of apoptosis in cells was investigated using flow cytometry. Results The FTIR results corroborated drug attachment over carbon nanotube (CNT), whereas the TEM results validated the nanosizing (1–300 nm) of the developed system. Drug entrapment in CNT was found to be 93.43 ± 1.65%, and in vitro drug release was found to be 94.73 ± 0.90% after 24 h. The complex reduced viability of 92.35 ± 0.942% cells than oxaliplatin’s 66.58 ± 0.38% inhibition, revealed by MTT assay. In the SRB assay, the developed system showed 91.22 ± 0.90% inhibition, whereas oxaliplatin showed 76.69 ± 0.52% inhibition against HT29 cells. Conclusions Conclusively, the developed system exhibited better cytotoxicity effects as compared with plain oxaliplatin. Our findings are suggestive of the potential development of CNT-anchored antineoplastic agents for target-specific delivery.

Abstract Heat waves, and an increased number of warm days and nights, have become more prevalent in major agricultural regions of the world. Although well adapted to semi-arid regions, cotton is vulnerable to high temperatures, particularly during flowering and boll development. To maintain lint yield potential without compromising its quality under high-temperature stress, it is essential to understand the effects of heat stress on various stages of plant growth and development, and associated tolerance mechanisms. Despite ongoing efforts to gather data on the effects of heat stress on cotton growth and development, there remains a critical gap in understanding the distinct influence of high temperatures during the day and night on cotton yield and quality. Also, identifying mechanisms and target traits that induce greater high day and night temperature tolerance is essential for breeding climate-resilient cotton for future uncertain climates. To bridge these knowledge gaps, we embarked on a rigorous and comprehensive review of published literature, delving into the impact of heat stress on cotton yields and the consequential losses in fiber quality. This review encompasses information on the effects of heat stress on growth, physiological, and biochemical responses, fertilization, cotton yield, and quality. Additionally, we discuss management options for minimizing heat stress-induced damage, and the benefits of integrating conventional and genomics-assisted breeding for developing heat-tolerant cotton cultivars. Finally, future research areas that need to be addressed to develop heat-resilient cotton are proposed.

The genus Xanthomonas primarily comprises phytopathogenic species. By carrying out deep phylo-taxonogenomics, we recently reported that the genera Xylella, Stenotrophomonas, and Pseudoxanthomonas are misclassified and belong to the genus Xanthomonas. Considering the importance of Xanthomonas/Xylella as plant pathogens and to further determine the taxonomic and phylogenetic breadth of this genus, we extended our earlier study by including all the reported genera and families in the order. This investigation revealed that at least four more genera belong to the genus Xanthomonas, with a notable case being Lysobacter, after which the family and order are named. Similarly, our investigation also allowed us to reveal the expanded taxonomic breadth of the related genus Rhodanobacter. This finding of a major related genus that lacks plant pathogenic species will allow for taxonomy-based comparative studies. The phylo-taxonogenomic revelations were further supported by complete 16S rRNA-based sequence boundaries proposed for genus delineation. Accordingly, we propose a taxonomic revision of these major and closely related genera along with their constituent families within the order Lysobacteraceae (Xanthomonadaceae). The identification of a major related genus lacking plant pathogenic species will be important in investigating the origin and success of pathogenic species/lineages in the genus Xanthomonas.

Wireless Sensor Networks (WSNs) play a critical role in data transmission and reception across a multitude of applications. A primary challenge in WSNs is managing scalability and latency due to the deployment of numerous sensor nodes, each with limited memory and energy resources. Moreover, understanding the randomness in node distribution across the WSN is complex. A commonly employed technique to address this issue is clustering, which groups distributed nodes within the network. A node with high energy, preferably located near the cluster's center, is selected as the cluster head to enhance latency. This paper primarily focuses on developing an efficient routing protocol to improve the scalability of WSNs. An ideal routing protocol should adapt to network topology changes. In this proposal, a Genetic Algorithm-based routing mechanism, the Cluster-based Genetic Routing Protocol (CGRP), is established. CGRP is particularly suitable for highly distributed and rapidly expanding networks, performing well even with an increase in workload. A mathematical evaluation is conducted to elucidate the scalability of the network. To demonstrate CGRP's efficiency, it was compared with various conventional state-of-the-art routing algorithms. Experimental results indicate that CGRP outperforms these algorithms, achieving lower latency and proving robust in highly scalable WSNs.

Abstract Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups—a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Aim and background: Jaundice is a clinical condition characterized by transient bilirubin conjugation deficiency resulting in neonatal hyperbilirubinemia. Hyperbilirubinemia is defined as a serum total bilirubin concentration greater than 95th centile for the hour of life. Approximately 60% of term and 80% of preterm infants are affected with hyperbilirubinemia, which may lead to complications such as brain neuron damage after several years. Early discharge of healthy-term newborns after delivery has become a common practice, which may be the cause for readmission during the early neonatal period. Universal follow-up within 1–2 days of early discharge, pre-discharge serum total bilirubin, transcutaneous bilirubin measurement, and universal clinical assessment of risk factors of developing jaundice are various strategies to predict significant neonatal hyperbilirubinemia. An association between cord blood bilirubin levels and subsequent risk of neonatal hyperbilirubinemia has been reported. However, the utility of cord blood bilirubin as a screening test to predict subsequent hyperbilirubinemia has been widely debated. We aimed to verify whether cord blood bilirubin at birth could be used as a predictor of significant neonatal hyperbilirubinemia requiring phototherapy among full-term neonates. Materials and methods: Cord blood bilirubin was estimated in 110 neonates immediately after delivery. These neonates were followed up for the next 3 days and serum total bilirubin was estimated on the third day of life. Neonates with significant hyperbilirubinemia requiring phototherapy were designated as cases and those without hyperbilirubinemia as controls. The association between cord blood bilirubin and serum total bilirubin was determined followed by the identification of the cut-off level of cord blood bilirubin that could predict significant neonatal hyperbilirubinemia requiring phototherapy among term neonates. Results: Among 100 neonates followed up, 50 developed significant hyperbilirubinemia requiring phototherapy. The mean ± SD of cord blood bilirubin was 2.66 ± 0.65 and serum total bilirubin estimated on day 3 of life was 16.16 ± 1.6 and the difference was statistically highly significant at a p-value of t-test. The cord blood bilirubin and day 3 serum bilirubin were positively correlated with an r-value of 0.087. The specificity and sensitivity with cord blood bilirubin of 2.5 mg/dL were 98 and 56%, and with day 3 bilirubin of 11.5 mg/dL was 72 and 100%, respectively. Conclusion: A cut-off of 2.5 mg/dL in cord blood bilirubin can be used to predict significant neonatal hyperbilirubinemia requiring phototherapy among full-term neonates. Clinical significance: Umbilical cord blood bilirubin measurement is a simple, economical, and non-invasive method to predict subsequent neonatal hyperbilirubinemia which can aid clinicians in early discharge of normal neonates and selective follow-up of high-risk infants.

Cryptococcosis is a lethal mycosis instigated by the pathogenic species Cryptococcus neoformans and Cryptococcus gattii, primarily affects the lungs, manifesting as pneumonia, and the brain, where it presents as meningitis. Mortality rate could reach 100% if infections remain untreated in cryptococcal meningitis. Treatment options for cryptococcosis are limited and and there are no licensed vaccines clinically available to treat or prevent cryptococcosis. Our study utilizes an integrated bioinformatics approaches to develop a polyvalent multiepitope subunit vaccine focusing on the key virulent proteins Heat shock transcription factor and Chaperone DnaK of both C. neoformans and C. gatti. Then in silico analysis was done to predict highly antigenic epitopes by assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. Following this analysis, we designed two vaccine constructs integrating a compatible adjuvant and suitable linkers. These constructs exhibited notable characteristics including high antigenicity, non-toxicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). The interaction between both vaccine constructs and TLR2, TLR3, and TLR9 was assessed through molecular docking analysis. Molecular dynamics simulations and MM-PBSA calculations suggest the substantial stabilizing property and binding affinity of Vaccine Construct V1 against TLR9. Both the vaccines revealed to have a higher number of interchain hydrogen bond with TLR9. These findings serve as a crucial stepping stone towards a comprehensive solution for combating cryptococcus infections induced by both C. neoformans and C. gattii. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of cryptococcosis. Subsequent validation through in vivo studies is paramount to confirm the effectiveness and potential of the vaccine in reducing the spread of cryptococcosis.

Parkinson disease is a neurogenerative disease common in adults and results in different kinds of memory dysfuntions. This study evaluated the monoamine oxidase B (MAO-B) inhibitory potential of kaurane diterpenoids previously isolated from Xylopia aethiopica through comprehensive computational approaches. Molecular docking study and molecular dynamics simulation were used to access the binding mode and interaction of xylopic acid and MAO-B enzyme. The ADMET properties of the phytochemical were evaluated to provide information on its druggability. The molecular docking and molecular dynamics simulation revealed xylopic acid as potential MAO-B inhibitor due to the good binding energy elicited and stability throughout the 100 ns simulation period. The ADMET properties of the ligand showed it as a promising drug candidate. The study recommend further comprehensive in vitro investigation towards the development of xylopic acid as potent MAO-B inhibitor.

Type 2 diabetes is a major health concern contributing to most of diabetic cases worldwide. Mangiferin and its congeners are known for their diverse pharmacological properties. This study sought to investigate the inhibitory property of naturally occurring mangiferin congeners on sodium-glucose co-transporter 2 protein (SGLT-2) using comprehensive computational methods. The naturally occurring mangiferin congeners were subjected to molecular docking, molecular dynamics (MDs) simulation (100 ns), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy, density functional theory calculations (B3LYP 6-31G basis set), and ADMET approaches to identify potential SGLT-2 inhibitor. The molecular docking studies revealed neomangiferin (−9.0 kcal/mol) as the hit molecule compared with dapagliflozin (−8.3 kcal/mol). Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) plots from the MD simulations established that neomangiferin stabilizes SGLT-2 better than the dapagliflozin, a standard drug. The MM-PBSA binding free energy calculations showed that neomangiferin (−26.05 kcal/mol) elicited better binding affinity than dapagliflozin (−17.42 kcal/mol). The electronic studies showed that neomangiferin (3.48 eV) elicited high electrophilicity index compared with mangiferin (3.31 eV) and dapagliflozin (2.11 eV). Also, the ADMET properties showed that the hit molecule is safe when administered to diabetic subjects. The current in silico studies suggest that neomangiferin could emerge as a promising lead molecule as a SGLT-2 inhibitor.

This report provides an efficient, environment-friendly, and greener approach to synthesizing azomethines using carbonic acid (H2CO3) as a catalyst formed by passing dry ice (CO2 gas) in water. Carbonic acid is a nontoxic, greener, and readily available catalyst. Various aldehydes reacted well with isoniazid in shorter reaction time in EtOH: water (1:1) as a greener solvent at room temperature. Immersing CO2 (g) in the reaction mixture incorporated to generate carbonic acid provides economic and environmental benefits by accessing the reaction at room temperature. The key benefits of the method are shorter reaction time, higher product yield, and a hassle-free and straightforward experimental process under mild reaction conditions.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.

Background: One of the most prevalent cancers in women worldwide is breast cancer. Breast cancer therapy is preferable to prevention. Breast cancer occurs for a variety of molecular reasons, making chemotherapy and/or radiotherapy treatment highly difficult and frequently creating unfavorable side effects. For millennia, practically every disease has been treated using plant extracts, and breast cancer is no exception. Because of their minimal toxicity, herbal medications are reliable for the treatment of cancer. In addition, the majority of breast cancer-stricken women readily embrace herbal treatments due to their accessibility and affordability. Many plants and the chemicals found in them have been found to exhibit promising anticancer properties versus breast cancer cells in both in vivo and in vitro studies over the past ten years. The poor stability, water solubility, and bioavailability of natural products usually prevent the clinical translation of these drugs, despite the positive preclinical outcomes. There have been efforts to get beyond these restrictions, especially by using nano-based drug delivery methods (NDDSs). The present work aims to comprehensively review the formulation, challenges, and advantages in the development of Nano formulation of Phytoconstituents for Breast Cancer. Main text: This study focuses on the tumor-targeting mechanisms of NDDSs, the benefits, and drawbacks of the main classes of NDDSs for treating breast cancer, as well as the pathophysiology of breast cancer, modern treatments, and phytoconstituents that have shown promise in treating breast cancer. Conclusion: The current review gathered information on the latest treatments, advantages, and disadvantages of NDDS in Breast Cancer. The review also elaborates on the importance of developing of a Targeted delivery system of Phytoconstituents for Breast Cancer.

The FIDES Guide is a reliability prediction handbook published by a group of European defense and aerospace manufacturers under the supervision of the French Ministry of Defense. This paper evaluates the suitability of FIDES for predicting reliability. The evaluation is based on the fitness of the model used in FIDES for calculating the failure rate and the accuracy of its reliability predictions. The assessment makes use of the questionnaire in the IEEE Standard 1413, “IEEE Standard Framework for Reliability Prediction of Hardware.” The foundation of FIDES on the erroneous assumption of a constant failure rate for electronics, its omission of critical attributes (e.g., materials and geometry of components), and the subjectivity of certain inputs to the model make it inadequate for producing an accurate prediction.

Environmental remediation is challenged by the removal of harmful heavy metal contaminants from industrial waste streams. Because of its low cost and great effectiveness, adsorption is a commonly used separation method, particularly in environmental cleanup. Inexpensive, biodegradable orange peel-chitosan and Fe3O4 magnetic particles (Fe3O4-OP-CS) were combined in a simple process to create an innovative composite. Their structure and morphology were studied using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analyses. At room temperature, adsorption experiments were conducted, and variables such pH, initial metal ion concentration, and contact time were tuned to maximize Cd(II) removal. The results of harmful Cd(II) sorption using the synthesized composite showed that its adsorption kinetics and sorption isotherm confirm to the pseudo-second-order and Langmuir models, respectively. The thermodynamic analysis showed that Cd(II) adsorption is exothermic and spontaneous. In comparison to previously reported materials, the new composite also displayed a high adsorption capacity (qmax) of 251.88 mg/g. The composite showed three cycles of reuse and might still be able to promise a maximum saturated adsorption capacity of more than 92%, and tolerance to related metal ions (Mn, Fe, Pb, and Cr) present in Cd (II). In addition to Cd(II) sorption for preconcentration and remediation before Cd testing from waste, digested tobacco, and battery samples, the proposed method is also credible for Cd(II) sorption.