Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

A two-stage grasp detection method for sequential robotic grasping in stacking scenarios.

Dexterous grasping is essential for the fine manipulation tasks of intelligent robots; however, its application in stacking scenarios remains a challenge. In this study, we aimed to propose a two-phase approach for grasp detection of sequential robotic grasping, specifically for application in stacking scenarios. In the initial phase, a rotated-YOLOv3 (R-YOLOv3) model was designed to efficiently detect the category and position of the top-layer object, facilitating the detection of stacked objects. Subsequently, a stacked scenario dataset with only the top-level objects annotated was built for training and testing the R-YOLOv3 network. In the next phase, a G-ResNet50 model was developed to enhance grasping accuracy by finding the most suitable pose for grasping the uppermost object in various stacking scenarios. Ultimately, a robot was directed to successfully execute the task of sequentially grasping the stacked objects. The proposed methodology demonstrated the average grasping prediction success rate of 96.60% as observed in the Cornell grasping dataset. The results of the 280 real-world grasping experiments, conducted in stacked scenarios, revealed that the robot achieved a maximum grasping success rate of 95.00%, with an average handling grasping success rate of 83.93%. The experimental findings demonstrated the efficacy and competitiveness of the proposed approach in successfully executing grasping tasks within complex multi-object stacked environments.

Tripeptides Ghk and GhkCu-modified silver nanoparticles for enhanced antibacterial and wound healing activities.

Bacterial skin infections represent a major healthcare concern that can delay healing and threaten human health. Silver nanoparticles (AgNPs) have been widely used for antimicrobial purposes; however, their high toxicity limits their applications. Therefore, there is an urgent need to develop simple and efficient therapeutic approaches for treating bacterial infections and promoting wound healing. Here, novel tripeptide (Ghk and GhkCu)-modified AgNPs were developed and subsequently evaluated their antibacterial efficacy against four pathogenic bacterial isolates, cytotoxic properties, and therapeutic effects as a topical treatment for infected wounds. Spherical GhkAgNPs and GhkCuAgNPs with average sizes of 45.92 nm and 56.82 nm exhibited potential antibacterial activity, with a MIC concentration of 8 µg/ml against S. aureus and E. coli. Both AgNPs showed superior bactericidal effects against S. aureus, with complete inhibition after 7 days of treatment. Cytotoxicity assays revealed IC50 (half maximal inhibitory concentrations) values ranging from 6.75 to 6.99 µg/ml in L929 cells. GhkAgNPs displayed accelerated cell migration and facilitated healing up to 92% after 12 h. Furthermore, topical applications of GhkAgNPs and GhkCuAgNPs to S. aureus-infected wounds demonstrated enhanced in vivo wound healing efficacy compared to control groups, as evidenced by increased regenerated epidermal thickness, improved collagen deposition, and downregulation of TNF-α expression. Hence concluded that these novel tripeptides Ghk and GhkCu-modified AgNPs exhibited potent antibacterial effects and significantly promoted wound healing properties.

Epidemiology and antifungal susceptibilities of clinically isolated Aspergillus species in South China.

Aspergillosis is a rising concern worldwide; however, its prevalence is not well documented in China. This retrospective study determined Aspergillus's epidemiology and antifungal susceptibilities at Meizhou People's Hospital, South China. From 2017 to 2022, the demographic, clinical, and laboratory data about aspergillosis were collected from the hospital's records and analysed using descriptive statistics, chi-square test, and ANOVA. Of 474 aspergillosis cases, A. fumigatus (75.32%) was the most common, followed by A. niger (9.92%), A. flavus (8.86%), and A. terreus (5.91%). A 5.94-fold increase in aspergillosis occurred during the study duration, with the highest cases reported from the intensive care unit (52.74%) - chronic pulmonary aspergillosis (79.1%) and isolated from sputum (62.93%). Only 38 (8.02%) patients used immunosuppressant drugs, while gastroenteritis (5.7%), haematologic malignancy (4.22%), and cardiovascular disease (4.22%) were the most prevalent underlying illnesses. In A. fumigatus, the wild-type (WT) isolates against amphotericin B (99.1%) were higher than triazoles (97-98%), whereas, in non-fumigatus Aspergillus species, the triazole (95-100%) WT proportion was greater than amphotericin B (91-95%). Additionally, there were significantly fewer WT A. fumigatus isolates for itraconazole and posaconazole in outpatients than inpatients. These findings may aid in better understanding and management of aspergillosis in the region.

Surface water quality, public health, and ecological risks in Bangladesh-a systematic review and meta-analysis over the last two decades.

Water quality has recently emerged as one of the utmost severe ecological problems being faced by the developing countries all over the world, and Bangladesh is no exception. Both surface and groundwater sources contain different contaminants, which lead to numerous deaths due to water-borne diseases, particularly among children. This study presents one of the most comprehensive reviews on the current status of water quality in Bangladesh with a special emphasis on both conventional pollutants and emerging contaminants. Data show that urban rivers in Bangladesh are in a critical condition, especially Korotoa, Teesta, Rupsha, Pashur, and Padma. The Buriganga River and few locations in the Turag, Balu, Sitalakhya, and Karnaphuli rivers have dissolvable oxygen (DO) levels of almost zero. Many waterways contain traces of NO3, NO2, and PO4-3 pollutants. The majority of the rivers in Bangladesh also have Zn, Cu, Fe, Pb, Cd, Ni, Mn, As, and Cr concentrations that exceed the WHO permissible limits for safe drinking water, while their metal concentrations exceed the safety threshold for irrigation. Mercury poses the greatest hazard with 90.91% of the samples falling into the highest risk category. Mercury is followed by zinc 57.53% and copper 29.16% in terms of the dangers they pose to public health and the ecosystem. Results show that a considerable percentage of the population is at risk, being exposed to contaminated water. Despite hundreds of cryptosporidiosis cases reported, fecal contamination, i.e., Cryptosporidium, is totally ignored and need serious considerations to be regularly monitored in source water.

Molecular docking and in vitro antibacterial activity of chiral phthalimide on ESBL producing gram negative bacteria.

Antibiotic resistance is tricky enemy that challenges our healthcare system. It is a stealthy, adaptive and ever evolving opponent, which can take years to develop but can spread like wildfire. In this study, derivatives of chiral phthalimides were developed with this aim to control the growth of resistant strains of Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa by targeting their resistance causing proteins and explore their binding interaction focal points through computational docking. Total 8 novel chiral phthalimides were synthesized and its antibiogram analysis was done on Muller-Hinton Agar by disc diffusion method. Cytotoxicity studies were made to check efficacy of tested compounds on human RBCs and monitor release of hemoglobin absorbance at 540nm. By using in silico molecular approach, crystal structure of target protein was retrieved from Protein Data Bank and docked through Autodock vina and PyRx. The obtained results revealed that seven out of eight compounds have active inhibitory effects against virulent strains. Minimum Inhibitory Concentration (MIC) was measured for most potent compounds i.e., 2-(1,3-dioxoisoindolin-2-yl)-3-(4-hydroxyphenyl) propanoic acid (compound 7) and 3-(1,3-dioxoisoindolin-2-yl) propanoic acid (compound 8). Docking studies displayed a report of highest affinity binding points i.e., amino acids LYS315, ALA318, TYR150, THR262, HIS314 and ARG148 for compound 7 while ALA 318, LYS 315, ARG14 and ILE291 for compound 8.

Cryptococcosis in Southern China: Insights from a Six-Year Retrospective Study in Eastern Guangdong.

Objective: Cryptococcosis is a fatal infection that can affect both immunocompetent and immunocompromised patients, and it is little understood in China's various regions. This research aimed to look at the epidemiology, risk factors, and antifungal susceptibility pattern of Cryptococcus neoformans in eastern Guangdong, China. Methods: A six-year (2016-2022) retrospective study was conducted at Meizhou People's Hospital, China. Demographical, clinical, and laboratory data of cryptococcal patients were collected from hospital records and statistically analyzed using the chi-square and ANOVA tests. Results: Overall, 170 cryptococcal infections were recorded, of which meningitis accounted for 78 (45.88%), cryptococcemia for 50 (29.41%), and pneumonia for 42 (24.7%). The number of cases increased 8-fold during the study duration. The median age of patients was 58 years (Inter quartile range: 47-66), and the high proportion of cases was from the male population (n = 121, 71.17%). The underlying diseases were identified only in 60 (35.29%) patients, of which 26 (15.29%) were severely immunocompromised, and 26 (15.29%) others were mildly immunocompromised. A statistically significant difference was reported for chronic renal failure, and anemia (p < 0.05) persisted in cases of three infection types. A high number of non-wild type (NWT) isolates were found against amphotericin B (n=13/145, 8.96%), followed by itraconazole (n=7/136, 5.15%) and voriconazole (n=4/158, 2.53%). Only six isolates (3.79%) were multidrug-resistant, four of which were from cryptococcemia patients. Compared to meningitis and pneumonia, cryptococcemia revealed a higher percentage of NWT isolates (p < 0.05). Conclusion: In high-risk populations, cryptococcal infections require ongoing monitoring and management.

Six-Year Retrospective Analysis of Epidemiology, Risk Factors, and Antifungal Susceptibilities of Candidiasis from a Tertiary Care Hospital in South China.

Candidiasis is a life-threatening disease that increases mortality in critically ill patients. However, such epidemiological data are still lacking in underdeveloped regions of China. A retrospective analysis (2016 to 2021) was conducted in Meizhou People's Hospital, China to study the burden of candidiasis, particularly candidemia, and antifungal susceptibilities of the species among hospitalized patients. Of the 7,864 candidiasis cases, 461 (5.86%) were candidemia cases. Candida albicans (64.25%) was the most identified species, followed by C. tropicalis (12.61%), C. glabrata (10.79%), and C. parapsilosis (9.79%). In non-C. albicans (NCA) candidemia cases, the number of C. glabrata cases was higher (102/461, 22.37%) than C. tropicalis (64/461, 14.04%). Gastrointestinal pathology, respiratory dysfunctions, septic shock, and malignancies were common underlying comorbidities, respectively. A central venous catheter was an independent risk factor for both C. albicans and NCA candidemia. The mortality rate was not statistically significant for either C. albicans or NCA. Amphotericin B and 5-flucytosine were highly effective (98 to 100%), while azoles were least effective (67.74 to 95.66%). Candidemia cases caused by C. tropicalis and C. glabrata had significantly lower azole susceptibility than non-candidemia-causing isolates. This study provides valuable information for prescribers to choose the right empirical therapy, for researchers to explore different resistance mechanisms, and for health care managers to control candidiasis better. IMPORTANCE This study provides important information on the burden of candidiasis, particularly candidemia, and the antifungal susceptibility of Candida species among hospitalized patients in an underdeveloped region of China. First, the finding that azoles were least effective against Candida species causing candidemia is particularly noteworthy, as it suggests the possibility of resistance to this class of antifungal agents. This information can guide the choice of empirical therapy and help in the selection of appropriate antifungal agents for the treatment of candidemia, thereby reducing the risk of resistance development. Second, the study provides important information for researchers to explore different resistance mechanisms in Candida species. Finally, the study has important implications for health care managers in controlling the spread of candidiasis. The high prevalence of candidemia cases in the study highlights the need for appropriate infection control measures to prevent the spread of the disease.

Characterization of antibiotic resistance genes and mobile elements in extended-spectrum ß-lactamase-producing Escherichia coli strains isolated from hospitalized patients in Guangdong, China.

AIM: This study aimed to investigate the high-resolution phenotypic and genotypic characterization of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli strains isolated from hospitalized patients to explore the resistance genes and mobile genetic elements (MGEs) involved in horizontal dissemination. METHODS: Between May and September 2021, a total of 216 ESBL-producing E. coli isolates were recovered from multiple departments. The identification of strains was performed using MALDI-TOF mass spectrometry and PCR, while antibiotic susceptibility testing was carried out using the Vitek 2 COMPACT system to determine resistance patterns, while PCR was used to detect different resistance genes and MGEs. In addition, a conjugation assay was performed to investigate the horizontal gene transfer of resistance genes. Selected isolates underwent whole-genome sequencing (WGS) using the Illumina MiSeq platform. RESULTS: A total of 216 out of 409 E. coli isolates recovered from a tertiary hospital were observed to be ESBL-producing, giving a carriage rate of 52.8%, as determined by phenotypic screening. The most frequent sources of ESBL-producing E. coli isolates were urine (129/216, 59.72%) and blood (50/216, 23.14%). The most prevalent ESBL genes identified were blaCTX-M (60.18%), blaTEM (40.27%), and blaSHV (18.05%). Three E. coli isolates were found to carry the genes blaNDM, mcr-1, and fosA3 genes. The most prevalent MGEs were IS26 (95.37%), Int (87.03%), and IncFIB (76.85%). WGS analysis of eight MDR E. coli strains revealed that these isolates belonged to eight different sequence types (STs) and serotypes and were found to harbor multiple plasmid replicons and virulence factors. CONCLUSION: This study highlights a high incidence of antibiotic resistance genes and MGEs associated with the dissemination of ESBLs and other resistance genes.

Efficacy of orthotic support in mitigating low back pain and disability in low back pain sufferers.

BACKGROUND: Low back pain (LBP) is a prevalent disabling ailment that affects people all over the world. A wide variety of orthotic designs, ranging from lumbosacral corsets to rigid thermoplastic thoraco-lumbosacral orthosis are used for managing LBP. OBJECTIVE: Explore and summarize quality literature on the efficacy of orthotic devices in the management of LBP. METHODS: A systematic review and meta-analysis of the literature on the efficacy of orthosis in low back pain management conducted using electronic databases. Studies utilizing orthotic management alone or combined with other therapies for 2 weeks or above were included. A meta-analysis was performed on primary and secondary variables using Mean difference (MD), Inverse variance (IV), and fixed effect model with 95% CI, Physiotherapy Evidence Database (PEDro) scale, Cochrane Risk of Bias 2 (RoB2) tool were used to assess the quality of evidence and the risk bias. RESULTS: Out of 14671 studies, only 13 Randomized Controlled Trials (RCT) were deemed eligible for inclusion in this study, all level 1 evidence. We found that orthotics could significantly mitigate LBP (P-value < 0.00001). Similarly, a significant reeducation in LBP-associated disability was observed after orthotic intervention (P-value 0.004). CONCLUSION: Lumber orthosis plays a significant role in LBP and associated disability mitigations in sufferers of LBP.

Clinical tests accuracy in diagnosing subacromial impingement syndrome: A systematic review.

OBJECTIVE: To determine the sensitivity and specificity of the clinical diagnostic tests of subacromial impingement syndrome. METHODS: The systematic review comprised search on PubMed, PEDro, Cochrane Library and Google Scholar databases. For prospective cohort studies published in peer-reviewed English-language journals without any time limit, at least fully describing one clinical test. Only studies with free full text available were included. Data extracted included sensitivity and specificity for each clinical test, and variations were sorted out by the 3 reviewers by discussion. RESULTS: Of the 4137 studies identified, 2951(71.3%) were on PubMed, 119(2.9%) PEDro, 5(0.1%) Cochrane Library and 1062(25.7%) Google Scholar. After screening out all the studies that did not match the detailed inclusion criterion, 3(0.07%) studies were selected for review; 1(33.3%) each done in Spain, Turkey and France. Overall, there were 181 aged 15-82 years; 85(47%) males and 96(53%) females. Supraspinatus palpation test had a sensitivity of 92%, while the modified Neer test had specificity of 95.56% in terms of ruling out subacromial impingement syndrome. CONCLUSIONS: Supraspinatus palpation and modified Neer tests were found to be the most effective in the diagnosis of subacromial impingement syndrome.

Stabilization of Acne Vulgaris-Associated Microbial Dysbiosis with 2% Supramolecular Salicylic Acid.

Facial microbiota dysbiosis is an important factor in causing acne vulgaris. The present study aimed to analyze the effect of 2% Supramolecular Salicylic Acid (SSA) on acne-associated facial bacteria. In the current study, 30 acne vulgaris patients (treated with 2% SSA for eight weeks) and ten volunteers with no facial acne were selected. Samples from acne patients (before and after treatment) and volunteers (not treated) were analyzed via high throughput sequencing, Deblur algorithm, and R microbiome package. After treatment with 2% SSA, the total lesion count and global acne grading system (GAGS) score reduced significantly (p < 0.001). Metagenomic sequencing analysis revealed that the pre-treated acne group had low α and deviated ß diversity compared to the control and post-treated acne groups. Due to the treatment with 2% SSA, α diversity index was increased and ß diversity was stabilized significantly (p < 0.001). The relative abundance of bacterial genera in the pre-treated acne group was uneven and had a high proportion of Staphylococcus, Ralstonia, and Streptococcus. The proportion of these three genera was significantly decreased in the post-treated group, and overall bacteria genera distribution tends toward the healthy individual. It is concluded that 2% SSA normalizes the microbial communities associated with the skin.

Seawall-induced impacts on large river delta wetlands and blue carbon storage under sea level rise.

Coastal wetlands have been enclosed by thousands of kilometers of seawalls in China to obtain extra land for rapid socio-economic development in the coastal region. Although understanding seawall-induced impacts on delta wetlands and their ecosystem can provide valuable decision-making information to support coastal management, quantifying and measuring long-term, cumulative ecological impacts of harden seawall under sea level rise (SLR) remains a vital research gap. In this study, by combining the land-use transformation trajectory analysis, ecosystem services assessment, and the SLAMM (Sea Level Affecting Marshes Model), we have explored the seawall-induced effects on temporal-spatial dynamics of tidal wetlands and the Coastal Blue Carbon storage (CBCs) in the Yellow River Delta (YRD) under the SLR by 2050 and 2100. Our study revealed that the delta wetland area would have increased by 2327.87 km2 after seawall removal without regard for SLR while increasing by 3050 km2 in 2100 in both seawall scenarios under SLR. The effects of driving processes trajectory on the changes in CBCs indicated two-sided seawall-induced impacts on the delta wetlands in the YRD, i.e., functioning as a physical coastal defense to prevent coastal erosion (before 2050) while intensifying coastal squeeze effects and quickening the loss in delta wetlands and the CBCs by hindering their inland migration under SLR. For example, the gap of CBCs between the seawall-impacting and seawall-removal scenarios would have reached at 9.94 × 106 Mg by 2050 under the SLR, and the magnitude of the final decrease effect on CBCs induced by the seawall-impacting would be nearly 5 times higher than its gain after seawall-removal in the regressive succession, while the same magnitudes in the salinization process on both scenarios. Our study has provided valuable insights for shoreline management by mitigating seawall-induced impacts on the delta wetlands and their ecosystem services such as CBCs.

Coexistence of bla NDM-5 and tet(X4) in international high-risk Escherichia coli clone ST648 of human origin in China.

The emergence of pathogens is conferring resistance to last-resort therapies such as tigecycline, colistin, and carbapenems, limiting the therapeutic options, and raising concerns about the emergence of new "superbugs." This study reports the first incident of a bla NDM-5 and tet(X4) co-harboring Escherichia coli with resistance to carbapenem and tigecycline recovered as the causative agent of a urinary tract infection in a 94-year-old patient. The E. coli strain ECCL209 carries multiple resistance genes [i.e., bla TEM-1B , bla NDM-5, bla CMY-2, aadA22, florR, erm(B), mph(A), erm(42), lnuG, qnrS1, and sul2] and exhibits resistance to almost all clinically used antibiotics. MLST analysis found that the strain belongs to ST648, considered a worldwide high-risk pandemic clone. Moreover, multiple plasmid incompatibility types were detected, i.e., IncHI1A, IncHI1B, IncFII, IncFIA, IncFIB, IncQ1, Col, and IncX4. Genetic analysis revealed that bla NDM-5 and tet(X4) genes were localized on two hybrid plasmids with multiple replicons. Continuous monitoring studies are suggested to quantify the antimicrobial resistance and assess the dissemination of such superbugs into a human healthcare setting.

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli.

Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.

Distribution and antifungal susceptibility pattern of Candida species from mainland China: A systematic analysis.

Antifungal resistance to Candida pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the Candida prevalence and antifungal susceptibility pattern is necessary to control and treat candidiasis. We aimed to systematically analyse the susceptibility profiles of Candida species published in the last ten years (December 2011 to December 2021) from mainland China. The studies were collected from PubMed, Google Scholar, and Science Direct search engines. Out of 89 included studies, a total of 44,716 Candida isolates were collected, mainly comprising C. albicans (49.36%), C. tropicalis (21.89%), C. parapsilosis (13.92%), and C. glabrata (11.37%). The lowest susceptibility was detected for azole group; fluconazole susceptibilities against C. parapsilosis, C. albicans, C. glabrata, C. tropicalis, C. guilliermondii, C. pelliculosa, and C. auris were 93.25%, 91.6%, 79.4%, 77.95%, 76%, 50%, and 0% respectively. Amphotericin B and anidulafungin were the most susceptible drugs for all Candida species. Resistance to azole was mainly linked with mutations in ERG11, ERG3, ERG4, MRR1-2, MSH-2, and PDR-1 genes. Mutation in FKS-1 and FKS-2 in C. auris and C. glabrata causing resistance to echinocandins was stated in two studies. Gaps in the studies' characteristics were detected, such as 79.77%, 47.19 %, 26.97%, 7.86%, and 4.49% studies did not mention the mortality rates, age, gender, breakpoint reference guidelines, and fungal identification method, respectively. The current study demonstrates the overall antifungal susceptibility pattern of Candida species, gaps in surveillance studies and risk-reduction strategies that could be supportive in candidiasis therapy and for the researchers in their future studies.

Antifungal susceptibility pattern of Candida isolated from cutaneous candidiasis patients in eastern Guangdong region: A retrospective study of the past 10 years.

Cutaneous candidiasis is one of the most prevalent mycotic infections caused by Candida species. The severity of infection mounts faster when the species shows antifungal resistance. In the current retrospective study, we aimed to analyze the occurrence, causes of cutaneous candidiasis, and antifungal susceptibility pattern of Candida isolates from Skin and Venereal Diseases Prevention and Control Hospital of Shantou, located in eastern Guangdong, China. The laboratory data of all patients (n = 3,113) suffering from various skin and venereal infections during January 2012 to December 2021 was analyzed through Excel and GraphPad prism. Our analysis indicate that cutaneous candidiasis was 22.29% (n = 694), of which 78.53% (n = 554) of patients were males and 21.47% (n = 149) of patients were females. The median age of patients with cutaneous candidiasis was 38-year [interquartile range (30-48)]. Most cases occurred in the adult age group (19-50 years). Regarding the species type, the Candida albicans were prominently detected (n = 664, 95.68%), while non-C. albicans were found only in 30 (4.32%) patients, which were C. glabrata (n = 18), C. krusei (n = 8), C. tropicalis (n = 3), and C. parapsilosis (n = 1). The C. albicans susceptibility rate for terbinafine, miconazole, voriconazole, itraconazole, fluconazole, ketoconazole, nystatin, 5-flucytosine and amphotericin B were 10.83, 29.32, 59.39, 78.53, 85.28, 87.75, 99.59, 99.41, and 100%, respectively. Finally, all C. glabrata isolates were found susceptible to all tested azole drugs with exception to miconazole against which 8.33% of isolates showed resistance. The findings of this study will help healthcare officials to establish better antifungal stewardship in the region.

Neonatal Cholestasis: The Changing Etiological Spectrum in Pakistani Children.

OBJECTIVES: To determine the frequency of clinical presentation and laboratory profile in the diagnosis of the etiological spectrum of neonatal cholestasis. MATERIAL AND METHODS:  In this prospective cross-sectional study, we recruited children who presented with jaundice and direct hyperbilirubinemia with onset in the first three months of life. The study was conducted between April 2019 to March 2021 (24 months) at the Government Lady Reading Hospital of Khyber Pakhtunkhwa province in Pakistan. The diagnosis was based on history and clinical findings that included jaundice, stool color, itching, abdominal distention, and deranged liver function tests and confirmed on liver biopsy and specific diagnostic tests. Data was recorded and analyzed using SPSS version 20 (IBM Corp., Armonk, NY). RESULTS: A total of 90 children were included in the study, out of which 65.6% were male. The average age was recorded as 118.01 days + 118.1 SD. Jaundice, dark urine, and hepatomegaly were found in 85.6% of children while ophthalmologic disorder, congenital heart disease, and itching were the least common symptoms. Laboratory findings of the cholestasis patients showed high bilirubin (mean: 8.88 mg/dL), alanine transaminase (ALT) (mean: 177.48 IU/mL), aspartate transaminase (AST) (mean: 187.11 IU/mL), gamma-glutamyl transpeptidase (GGT) (mean: 187.66 IU/mL) and prolonged international normalized ratio (INR) (mean: 2.20) in majority of patients. The genetic and metabolic disorder was the leading cause found in the majority of children, which was 43.8%. CONCLUSION: The common causes of neonatal cholestasis in this study are galactosemia, idiopathic hepatitis, and biliary atresia. The common presentation includes jaundice, hepatomegaly, direct hyperbilirubinemia, raised liver enzymes, and INR.

An analysis of the success of fiscal adjustment in reducing public debt: Evidence from Pakistan.

This study seeks answers to questions such as: what is fiscal adjustment? Which fiscal strategy will result in a reduction in public debt liabilities? In the pursuit of answers to these questions, the study has defined two objectives. Firstly, the fiscal adjustment episodes must be identified in order to detach the discretionary fiscal stance; secondly, the success of these adjustment episodes in reducing public debt liabilities must be assessed. As a result, attempts will be made to undertake analyses that would simplify the issues underlying Pakistan's practical policy options. A total of eleven adjustment episodes have been observed in a sample, ranging from 1976 to 2017, following Alesina and Ardagna's definition. The descriptive analysis reveals that five episodes succeeded in reducing the public debt, while six episodes failed to reduce the ratio. Out of the five successful episodes, four are found to be spending-based and one is tax-based. To quantify the success of fiscal adjustment, the empirical model has been calibrated on Leibrecht and Scharler's model and estimation is done via both the Ordinary Least Squares (OLS) and Robust Least Squares (RLS) methods. The RLS method produces better outcomes than the OLS method. Under RLS, all variables are significant except GDP growth, whereas in the OLS model, the election year and regime shift, together with GDP growth, are statistically insignificant. The fiscal adjustment's composition reveals that spending-based consolidation boosts the chances of the fiscal adjustment's success. Fiscal authorities should, therefore, adopt spending-based austerity measures to ensure the sustainability of public finances and prevent the negative macroeconomic consequences of unsustainable public debt.