Increasing trends of non-tuberculous mycobacteria clinical isolates in Guangzhou, China.

Non-tuberculous mycobacteria (NTM) are one of major public health concern. The current study aimed to find the prevalence trends of NTM in Guangzhou, China from January 2018 to December 2023. A total of 26,716 positive mycobacterial cultures were collected. Thirty-six specimens with incomplete personal information were excluded. The remaining 26,680 specimens were identified using a gene chip method. 16,709 isolates were Mycobacterium tuberculosis (MTB) (62.63 %), and 9,971 were NTM (37.37 %). 43.43 % (4,330/9,971) of NTM isolates were male, and 56.57 % (5,641/9,971) were female (χ2 = 24.36, P < 0.05), a male to female ratio of approximately 1:1.30. Infections in individuals with aged 40 years and above was higher (77.63 %) than below 40 years (22.37 %) (χ2 = 4.94, P = 0.026). The annual NTM isolation rates from 2018 to 2023 were 32.03 %, 34.00 %, 36.27 %, 38.58 %, 38.99 %, and 43.24 %, respectively, showing an increasing trend (χ2 for trend = 0.097, P < 0.05) (R = 0.097, P < 0.05). Out of 9,971 NTM isolates, 8,881 cases include only five common NTM species (MAC, M. abscessus/M. chelonae, M. kansasii, M. fortuitum, and M. gordonae). The overall NTM isolation rate was 37.37 %. The NTM isolation rate was significantly higher than the national average, showing an increasing trend over the last six years.

Unveiling the complexity of rifampicin drug susceptibility testing in Mycobacterium tuberculosis: comparative analysis with next-generation sequencing.

Introduction. The discordance between phenotypic and molecular methods of rifampicin (RIF) drug susceptibility testing (DST) in Mycobacterium tuberculosis poses a significant challenge, potentially resulting in misdiagnosis and inappropriate treatment.Hypothesis/gap statement. A comparison of RIF phenotypic and molecular methods for DST, including whole genome sequencing (WGS), may provide a better understanding of resistance mechanisms.Aim. This study aims to compare RIF DST in M. tuberculosis using two phenotypic and molecular methods including the GeneXpert RIF Assay (GX) and WGS for better understanding.Methodology. The study evaluated two phenotypic liquid medium methods [Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT)], one targeted molecular method (GX), and one WGS method. Moreover, mutational frequency in ponA1 and ponA2 was also screened in the current and previous RIF resistance M. tuberculosis genomic isolates to find their compensatory role.Results. A total of 25 RIF-resistant isolates, including nine from treatment failures and relapse cases with both discordant and concordant DST results on LJ, MGIT and GX, were subjected to WGS. The phenotypic DST results indicated that 11 isolates (44%) were susceptible on LJ and MGIT but resistant on GX. These isolates exhibited multiple mutations in rpoB, including Thr444>Ala, Leu430>Pro, Leu430>Arg, Asp435>Gly, His445>Asn and Asn438>Lys. Conversely, four isolates that were susceptible on GX and MGIT but resistant on LJ were wild type for rpoB in WGS. However, these isolates possessed several novel mutations in the PonA1 gene, including a 10 nt insertion and two nonsynonymous mutations (Ala394>Ser, Pro631>Ser), as well as one nonsynonymous mutation (Pro780>Arg) in PonA2. The discordance rate of RIF DST is higher on MGIT than on LJ and GX when compared to WGS. These discordances in the Delhi/CAS lineages were primarily associated with failure and relapse cases.Conclusion. The WGS of RIF resistance is relatively expensive, but it may be considered for isolates with discordant DST results on MGIT, LJ and GX to ensure accurate diagnosis and appropriate treatment options.

The development of anti-freezing and anti-evaporating conductive organohydrogel for flexible strain-sensing electronic devices.

The hydrogels got hot attention from the researchers due to their excellent flexibility, mechanical properties, conductivity, and response to external stimuli, however, their applications are hampered due to a lack of water retention properties and anti-freezing ability. In this study, the organohydrogel was designed from the two solvents system (DMSO and water) in which acrylamide (Amm) and acrylic acid (AA) work as monomers and Arabic gum (AG) works as biopolymers. The functional groups, surface morphology, mechanical properties, rheological properties, anti-freezing properties, and strain-sensing properties of the fabricated organohydrogel were studied. The DMGA6 organohydrogel showed good mechanical properties with fracture stress of 197 kPa, fracture strain of 593%, cyclic stability to five cycles at 400% strain without relaxation time, excellent rheological performance (elastic behavior), anti-freezing properties (-54.6 °C), the response time of 65 ms with a gauge factor of 8.86 at 500% strain. The organohydrogel can detect different human motions like bending of the finger, elbow, neck, and wrist at normal and harsh temperatures. Additionally, the organohydrogel can also detect the mood of humans, etc. The designed organohydrogels can be used in strain-sensing smart electronic devices for writing, drawing, etc. as an electronic pen.

Diffusible signal factor (DSF)-mediated quorum sensing modulates swarming in Xanthomonas albilineans.

Xanthomonas spp. are plant pathogens known for significantly impacting crop yields. Among them, Xanthomonas albilineans (Xal) is notable for colonizing the xylem and causing sugarcane leaf scald disease. This study employed homologous recombination to mutate quorum sensing (QS) regulatory genes (rpf) to investigate their role in Xal pathogenicity. Deletions of rpfF (ΔrpfF), rpfC (ΔrpfC), and rpfG (ΔrpfG) led to reduced swarming, growth, and virulence. However, DSF supplementation restored swarming and growth in the ΔrpfF mutant. Deleting rpfC, rpfG, and rpfF also reduced twitching motility and affected Type IV Pilus (T4P) expression. Transcriptomic analysis revealed that ΔrpfF positively regulates flagellar genes. DSF supplementation in ΔrpfF (ΔrpfF-DSF) modulated the expression of flagellar, chemotaxis, and T4P genes. These findings elucidate the DSF-mediated swarming pathway in Xal and provide valuable insights into its regulatory mechanisms.

Sources, transmission and hospital-associated outbreaks of nontuberculous mycobacteria: a review.

Nontuberculous mycobacteria (NTM) are widespread environmental organisms found in both natural and man-made settings, such as building plumbing, water distribution networks and hospital water systems. Their ubiquitous presence increases the risk of transmission, leading to a wide range of human infections, particularly in immunocompromised individuals. NTM primarily spreads through environmental exposures, such as inhaling aerosolized particles, ingesting contaminated food and introducing it into wounds. Hospital-associated outbreaks have been linked to contaminated medical devices and water systems. Furthermore, the rising global incidence, prevalence and isolation rates highlight the urgency of addressing NTM infections. Gaining a thorough insight into the sources and epidemiology of NTM infection is crucial for devising novel strategies to prevent and manage NTM transmission and infections.

Non-tuberculous mycobacteria (NTM) are environmental pathogens affecting humans and animals, with a substantial public health impact. These bacteria have been frequently identified in various natural and human-engineered settings, contributing to their potential transmission.

Adsorption and solar light activity of noble metal adatoms (Au and Zn) on Fe(111) surface: a first-principles study.

Noble metals such as gold (Au), zinc (Zn), and iron (Fe) are highly significant in both fundamental and technological contexts owing to their applications in optoelectronics, optical coatings, transparent coatings, photodetectors, light-emitting devices, photovoltaics, nanotechnology, batteries, and thermal barrier coatings. This study presents a comprehensive investigation of the optoelectronic properties of Fe(111) and Au, Zn/Fe(111) materials using density functional theory (DFT) first-principles method with a focus on both materials' spin orientations. The optoelectronic properties were obtained employing the generalized gradient approximation (GGA) and the full-potential linearized augmented plane wave (FP-LAPW) approach, integrating the exchange-correlation function with the Hubbard potential U for improved accuracy. The arrangement of Fe(111) and Au, Zn/Fe(111) materials was found to lack an energy gap, indicating a metallic behavior in both the spin-up state and the spin-down state. The optical properties of Fe(111) and Au, Zn/Fe(111) materials, including their absorption coefficient, reflectivity, energy-loss function, refractive index, extinction coefficient, and optical conductivity, were thoroughly examined for both spin channels in the spectral region from 0.0 eV to 14 eV. The calculations revealed significant spin-dependent effects in the optical properties of the materials. Furthermore, this study explored the properties of the electronic bonding between several species in Fe(111) and Au, Zn/Fe(111) materials by examining the density distribution mapping of charge within the crystal symmetries.

Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission. METHODS: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts. RESULTS: Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB. CONCLUSIONS: This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Effect of smoking cessation interventions on abstinence and tuberculosis treatment outcomes among newly diagnosed patients: a randomized controlled trial.

The study evaluates the effectiveness of smoking cessation interventions [Behavioral Change Communication (BCC) and Behavioral Change Communication plus bupropion (BCC+)] compared to conventional Directly Observed Therapy Short Course (DOT) treatment in improving pulmonary tuberculosis treatment outcomes and abstinence among newly diagnosed pulmonary tuberculosis (PTB) patients, highlighting the scarcity of robust experimental studies. The current randomized controlled trial, conducted at Ojha Institute of Chest Diseases between October 2017 and June 2019, randomized 292 patients who were current smokers with newly diagnosed pulmonary tuberculosis into three arms: control (n = 97), BCC (n = 97), and BCC+ (n = 98) arms. The outcomes of the interventions were compared in terms of favorable treatment outcomes and abstinence achieved at the end of 6 months. Baseline characteristics were compared between groups. Cox regression quantified the effect size of interventions for both outcome variables and reported as (crude and adjusted) hazard ratios with 95% confidence intervals (CI). No statistically significant difference was observed in baseline characteristics in each arm. Both BCC+ and BCC showed a statistically significant effect in achieving favorable PTB outcomes at 6 months (aHR 2.37, 95% CI 1.52-3.70 and aHR 2.34, 95% CI 1.51-3.60), as well as for abstinence from smoking at 6 months (BCC+: aHR 4.03, 95% CI 2.18-7.44 and BCC: aHR 3.87, 95% CI 2.12-7.05) compared to the control arm. Both BCC and BCC+ aided by pharmacologic agents such as bupropion when incorporated with conventional DOTs were found to be significantly effective in attaining favorable tuberculosis treatment outcomes as well as in attaining smoking abstinence at the end of the 6-month treatment.This study shows that adding smoking cessation programs (with or without extra drugs like bupropion) to standard Directly Observed Treatment Short Course (DOTs) treatment for people who have recently been diagnosed with pulmonary tuberculosis has a great positive impact on how well the overall antituberculosis treatment works. Our trial shows very promising results for such a combined therapy (DOTs and smoking cessation) in a country where the burden of both tuberculosis and smoking is very high.

Evaluation of blood minerals and oxidative stress changing pattern in prepartum and postpartum Achai and Holstein Friesian dairy cows.

This research focused on evaluating blood mineral levels and malondialdehyde (MDA) as an indicator of oxidative stress before and after giving birth in Achai and Holstein Friesian (HF) dairy cows. Blood samples were obtained from a total of 50 cows representing both breeds on the third, second, and first week prior to calving, as well as on the day of calving (day 0). Subsequently, samples were collected on the 1-3 weeks postpartum to allow a comprehensive evaluation of blood parameters throughout the peripartum period. Results showed a significant (p < .01) decrease in serum zinc (Zn) levels on the day of parturition in both breeds. Additionally, HF cows exhibited higher (p < .01) Zn levels on week 2 before giving birth. Interestingly, blood selenium (Se) concentration increased (p < .01) in HF cows on weeks 2 and 3 after calving. In contrast, Achai cows showed a rise (p < .01) in blood Se on week 3 of parturition. Blood copper (Cu) levels were higher (p < .01) on weeks 2 and 3 after parturition in HF cows and on third week before parturition compared to Achai cows, where serum Cu remained high on week 1 of parturition. The findings indicated that blood magnesium (Mg) was higher (p < .01) on third week before parturition in Achai cows and on weeks 2 and 3 after parturition. Serum calcium (Ca) was higher (p < .01) in both HF and Achai cows on weeks 2 and 3 after parturition, and lower (p < .01) on third week before giving birth in both breeds. The mean blood MDA levels in Achai cows were lower (p < .01) on weeks 1 to 3 postpartum or 3 weeks before giving birth. In HF cows, serum MDA increased (p < .01) just before 2 weeks of parturition and remained elevated until 3 weeks of parturition. Thus, both breeds exhibited a similar pattern of mineral fluctuations; yet, Achai cows demonstrated greater resilience to oxidative stress compared to HF cows during the transition period.

Tuning the Magnetic Behavior of Zinc Ferrite via Cobalt Substitution: A Structural Analysis.

Cobalt-doped zinc ferrite is a contemporary material with significant structural and magnetic characteristics. Our study explores the magnetic properties of cobalt-substituted zinc ferrite (ZnxCo1-xFe2O4), synthesized via a simple sol-gel method. By varying the cobalt ratio from 0 to 0.5, we found that zinc substitution impacts both the magnetization and lattice parameters. FTIR analysis suggested the presence of functional groups, particularly depicting an M-O stretching band, within octahedral and tetrahedral clusters. X-ray diffraction analysis confirmed the phase purity and cubic structure. The synthesized materials exhibited an average particle size of 24-75 nm. Scanning electron microscopy revealed the morphological properties, confirming the formation of truncated octahedral particles. In order to determine the stability, mass loss (%), and thermal behavior, a thermal analysis (thermogravimetric analysis (TGA)/differential thermal analysis (DTA)) was performed. The magnetic properties of the synthesized ferrites were confirmed via a vibrating sample magnetometer (VSM). Finally, the highest saturated magnetization and lowest coercivity values were observed with higher concentrations of the cobalt dopant substituting zinc. The synthesized nanomaterials have good stability as compared to other such materials and can be used for magnetization in the near future.

Fungal community dynamics associated with the outbreaks of sugarcane root rot disease.

Sugarcane is a critical sugar and bioenergy crop in China. However, numerous factors, including root rot disease, hamper its yield. Root rot disease is a severe agricultural issue, reducing yield and threatening sustainable crop production. The current study aimed to explore the fungal community structure, identify and characterize the primary pathogen for sugarcane root rot in Guangzhou, China. Eighty-nine samples of sugarcane root, stalk, rhizosphere soil, and irrigation water were collected from five sites in Guangzhou, China. Subsequently, 276 fungal strains were isolated to identify the primary pathogens. The five most common genera identified were Penicillium, Fusarium, Gongronella, Trichoderma, and Cladosporium. Fusarium was more prevalent in the infected soil samples than in healthy ones. Pathogenic assays of the strains revealed that the strain GX4-46 caused 80% of the disease. The strain was confirmed as Fusarium commune through phylogenetic and genome sequence analysis. Rhizosphere soil samples from different regional crops were collected to better understand the fungal community structure and the primary pathogen. We observed a significant presence of Fusarium in irrigation water, indicating that the root rot disease could originate from the irrigation water and then spread as a soil-borne disease. This research is pioneering and one of the most comprehensive investigations on the occurrence and prevalence of sugarcane root rot disease. This study will serve as a reference for expanding the sugarcane industry and a foundation for further exploration and control of root rot.IMPORTANCESugarcane, a significant economic crop, faces challenges due to root rot pathogens that accumulate each year in plants and soil through ratoon planting. This disrupts soil microbial balance and greatly impedes sugarcane industry growth. Symptoms range from wilting and yellowing leaves to stunted growth and reduced seedling tillers. The rhizosphere microbiota plays an important role in plant development and soil health. Little is known about root rot fungal community structure, especially in sugarcane. Here, we focused on exploring the main causative pathogen of root rot in the area alongside a detailed survey of the rhizosphere soil of different severity sugarcane cultivars and rotation crops of the region. To validate the findings, we also investigated the irrigation water of the area. Our study revealed Fusarium commune as the causative pathogen of root rot in the area, primarily originating from water and later as soil-borne. Using Trichoderma can control the disease effectively.

Cellulose nanocrystals boosted hydrophobically associated self-healable conductive hydrogels for the application of strain sensors and electronic devices.

Currently, hydrogel-based flexible devices become hot areas for scientists in the field of electronic devices, artificial intelligence, human motion detection, and electronic skin. These devices show responses to external stimuli (mechanical signals) and convert them into electrical signals (resistance, current, and voltage). However, the applications of the hydrogel-based sensor are hampered due to low mechanical properties, high time response, low fatigue resistance, low self-healing nature, and low sensing range. Herein, a strain sensing conductive hydrogel constructed from the CNCs (cellulose nanocrystal) reinforced, in which acrylamide and butyl acrylate work as hydrophilic and hydrophobic monomers respectively. The incorporation of CNCs in the polymeric system has a direct effect on their mechanical properties. The hydrogel having a high amount of CNCs (C4), its fracture stress and fracture strain reached 371.2 kPa and 2108 % respectively as well as self-healing of C4 hydrogel Broke at 499 % strain and bore 197 kPa stress. The elastic behavior of the hydrogels was confirmed by the rheological parameter frequency sweep and strain amplitude. Besides this our designed hydrogel shows an excellent response to deformation with conductivity 420 mS m-1, shows response to small strain (10 %) and large (400 %) strain, and has excellent anti-fatigue resistance with continuous stretching for 700 s at 300 % strain, with 140 msec response time, and gauge factor 7.4 at 750 % strain. The C4 hydrogel can also work as electronic skin when it is applied to different joints like the finger, elbow, neck, etc. The prepared hydrogel can also work as an electronic pen when it is worn to a plastic pen cover.

Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.

IMPORTANCE: An accurate diagnosis of drug resistance in clinical isolates is an important step for better treatment outcomes. The current study observed a higher discordance rate of rifampicin resistance on Mycobacteria Growth Indicator Tube (MGIT) drug susceptibility testing (DST) than Lowenstein-Jenson (LJ) DST when compared with the rpoB sequencing. We detected a few novel mutations and their combination in rifampicin resistance isolates that were missed by MGIT DST and may be useful for the better management of tuberculosis (TB) treatment outcomes. Few novel deletions in clinical isolates necessitate the importance of rpoB sequencing in large data sets in geographic-specific locations, especially high-burden countries. We explored the discordance rate on MGIT and LJ, which is important for the clinical management of rifampicin resistance to avoid the mistreatment of drug-resistant TB. Furthermore, MGIT-sensitive isolates may be subjected to molecular methods of diagnosis for further confirmation and treatment options.

Effect of body weight at photostimulation on productive performance and welfare aspects of commercial layers.

OBJECTIVE: Due to current selection practices for increased egg production and peak persistency, the production profile, age at maturity, and body weight criteria for commercial layers are constantly changing. Body weight and age at the time of photostimulation will thus always be the factors that need to be adequately addressed among various production systems. The current study was carried out to determine the effects of pullets' body weight (low, medium, and heavy) on their performance, welfare, physiological response, and hormonal profile. METHODS: With regard to live weight, 150 16-week-old pullets were divided into three groups using a completely randomized design (CRD) and held until the 50th week. One-way analysis of variance was used to evaluate the data under the CRD, and the least significant difference test was used to distinguish between treatment means. RESULTS: In comparison to the medium and light birds, the heavy birds had higher body weight at maturity, an earlier age at maturity, and higher egg weight, eggshell weight, eggshell thickness, egg yolk index, breaking strength, egg surface area, egg shape index, egg volume, and hormonal profile except corticosterone. However, the medium and light birds had lower feed consumption rates per dozen eggs and per kilogram of egg mass than the heavy birds. Light birds showed greater body weight gain, egg production, and egg specific gravity than the other categories. At 20 weeks of age, physiological response, welfare aspects, and catalase were non-significant; however, at 50 weeks of age, all these factors-aside from catalase-were extremely significant. CONCLUSION: The findings of this study indicate that layers can function at lower body weights during photostimulation; hence, dietary regimens that result in lighter pullets may be preferable. Additionally, the welfare of the birds was not compromised by the lighter weight group.

Malocclusion: Prevalence and Determinants among Adolescents of Karachi, Pakistan.

OBJECTIVES: The aim of this study was to determine the prevalence of malocclusion and its associated demographic and clinical factors in young adolescents (13-15 years) of Karachi, Pakistan. MATERIALS AND METHODS: An epidemiological survey included 500 young adolescents of registered schools, madrassas (Islamic education system), and shop workers of Gulshan-e-Iqbal Town. It was a cross-sectional analytical study design. Multistage random sampling technique was used to enroll participants. The pattern of occlusion was recorded with other related features using Angle's classification. Health status was recorded through World Health Organization-guided indices (decayed, missing, and filled permanent teeth [DMFT], community periodontal index of treatment needs [CPITN], and body mass index [BMI]). The information, thus, obtained was analyzed through SPSS using the chi-squared test and regression models. RESULTS: Forty four percent of the participants were female, while overall estimated prevalence of malocclusion in young adolescents of Karachi was 57.4%. After adjustments, participants going to any kind of education system had less malocclusion in comparison to those who were not going to any education system (adjusted odds ratio [aOR] = 0.305, 95% confidence interval [CI] = 0.12-0.73); mother's education especially higher level (aOR = 2.02, 95% CI = 1.08-3.75) and presence of periodontal disease (aOR = 1.57, 95% CI = 1.06-2.33) were significantly associated with malocclusion. CONCLUSION: This study showed that the class I malocclusion is prevalent in the local community. Demographic factors like gender, age, self-reported ethnicity, and BMI did not show any significant role. Education or knowledge of parents and young adolescents does play an influential role in decreasing malocclusion. Young adolescents, who are more prone to oral health problems at an early age, would have more chances to develop occlusal discrepancies.

Alzheimer's Disease; Mechanism, Mutations, and Applications of Nano-Medicine.

BACKGROUND: In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of ß-amyloid (Aß) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Aß peptide is cleaved by the α-secretase, ß-secretase, and γ-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site. METHODS: In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies. RESULTS: Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (APP). However, the A673>T mutation has been shown to confer protection against AD. CONCLUSION: More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD.

Demographic and clinical variables in the dengue epidemic in Punjab, Pakistan.

Objectives: To identify the latest trends in the clinical picture and severity of the disease, which will help better understand and manage dengue. Methodology: It was a cross-sectional, hospital-based study performed in the tertiary care hospitals of Punjab from August 21 to December 2022, in which serologically and polymerase chain reaction (PCR) confirmed patients with dengue infection, were enrolled. Demographic and clinical variables were recorded on a pre-tested Performa, processed and presented in frequency and percentages, and graphs were generated. Mean and standard deviation was used to present continuous variables. Results: Out of a total of 580 patients, 472 were diagnosed with Dengue Fever (DF) and 108 with Dengue Hemorrhagic Fever (DHF). About 79.31% of the patients were male and 20.69% were females. The mean age of patients was 32.5±9 years. Among the clinical features the percentage of high-grade fever, body aches, and vomiting were the highest. The liver function profile showed that serum bilirubin, Serum aspartate transaminase (AST), serum alanine transaminase (ALT,) and alkaline phosphatase (ALP) levels were markedly raised. Conclusion: This study showed that with time the trends in the presentation of dengue are slowly shifting, which will help us better manage the disease burden in the future.

Inclusion of the fungus Pleurotus florida in the diet affects performance and feed efficiency traits in calves: a case study on Ravi buffalo.

The objective of the study was to investigate the effects of inclusion of Pleurotus florida treated wheat straw in the total mixed rations (TMRs) on feed intake, growth performance, nutrient digestibility, and nitrogen retention in male buffalo calves. As a pilot study, four TMRs, i.e., TMR1 having 0% P. florida treated wheat straw (FTWS), TMR2 (20% FTWS), TMR3 (40% FTWS), and TMR4 (60% FTWS) with berseem hay as basal diet, were formulated. Sixteen Nili-Ravi male buffalo calves (aged 10-12 months, weighing 73 ± 2.50 kg) were divided into four equal groups and randomly assigned one of four TMRs. A significant increase (P < 0.05) was observed in all nutrients intake, their digestibility, weight gain, and nitrogen retention with TMRs incorporated with FTWS. Highest feed conversion ratio (FCR) of 2.63 was noted with TMR1-0% and the lowest FCR (1.80) with TMR4-60%, on the other hand. In conclusion, the TMR4 (60% FTWS) has the potential to increase the weight gain, nutrient digestibility, nitrogen retention, and feed efficiency in buffalo calves. Therefore, inclusion of 60% Pleurotus florida treated wheat straw is recommended as TMRs with berseem hay based basal diet for feeding buffaloes calves.