Molecular detection and diversity of tick-borne rickettsial pathogens in ticks collected from camel (Camelus dromedarius) in Upper Egypt.

Tick-borne rickettsial pathogens pose significant threats to public and animal health. In Upper Egypt, limited information exists regarding the prevalence and diversity of such tick-borne pathogens. Therefore, this study aimed to conduct a comprehensive investigation to elucidate the presence and variety of tick-borne rickettsial pathogens in Upper Egyptian camels. Our results revealed a prevalence of 2.96 % for Anaplasma marginale and 0.34 % for Candidatus Anaplasma camelii among Hyalomma ticks. However, Ehrlichia spp. weren't detected in our study. The identification of Ca. A. camelii in H. dromedari ticks was documented for the first time, suggesting a potential mode of transmission in camels. Notably, this study marks the first documentation of Rickettsia aeschlimannii with a prevalence of 6.06 % in the study area. Furthermore, we detected Coxiella burnetii in a prevalence of 8.08 % in Hyalomma ticks, indicating a potential risk of Q fever transmission. Molecular techniques results were confirmed by sequencing and phylogenetic analysis and provided valuable insights into the epidemiology of these pathogens, revealing their diversity. This study is vital in understanding tick-borne rickettsial pathogens' prevalence, distribution, and transmission dynamics in Upper Egypt. In conclusion, our findings emphasize the importance of continued research to enhance our understanding of the epidemiology and impact of these pathogens on both animal and human populations.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the KEEPsAKE 2 Randomized Clinical Trial.

INTRODUCTION: Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE 2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1-2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100 weeks of treatment. METHODS: KEEPsAKE 2 is a global phase 3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, and 16). At week 24, all patients received open-label risankizumab every 12 weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. RESULTS: At the cutoff date, 345/443 (77.9%) patients were ongoing in the study. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week 100 and in 60.0% and 55.8%, respectively, at week 52. In week 52 responders, maintenance of ACR20 at week 100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week 100 and by 27.2% and 33.8% at week 52. Among MDA responders at week 52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week 100. CONCLUSIONS: Risankizumab demonstrated durable efficacy and tolerability through 100 weeks; most patients who achieved ACR20 and MDA responses at week 52 maintained this achievement through week 100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671148.

Risankizumab, a biologic disease-modifying antirheumatic drug, helps control the body's immune system to reduce symptoms of psoriatic arthritis (a disease that inflames the joints of people who have the skin condition psoriasis). The ongoing KEEPsAKE 2 study is evaluating how well risankizumab works and how safe it is for treating adult patients with active psoriatic arthritis who previously experienced inadequate response to one or more specific types of disease-modifying anti-arthritis drugs. Patients were randomly assigned to receive either risankizumab or an inactive drug; after 24 weeks, all patients received risankizumab. At study week 100, 57% of patients who were assigned to receive continuous risankizumab since the start of the study experienced a 20% or more improvement in a measure of psoriatic arthritis symptoms using criteria established by the American College of Rheumatology (ACR20); a similar proportion of patients achieved a 20% improvement at both weeks 24 and 52. Similarly, 56% and 53% of patients who switched from inactive drug to risankizumab achieved ACR20 at weeks 52 and 100 (more than before switching to risankizumab at week 24). Minimal disease activity (MDA) was evaluated by assessing joint and skin symptoms, affected body surface area, pain, and physical function. At week 100, 33% of patients achieved MDA (both groups), which was similar to week 52. Most patients who achieved ACR20 or MDA at week 52 maintained responses at week 100. Improvements with risankizumab were seen in several other measures of treatment outcomes through week 100. Risankizumab was generally safe through 100 weeks.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the Phase 3 KEEPsAKE 1 Randomized Clinical Trial.

INTRODUCTION: Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). METHODS: KEEPsAKE 1 (NCT03675308) is a global phase 3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150 mg or placebo at baseline and weeks 4 and 16. After week 24, all patients received open-label risankizumab every 12 weeks thereafter. Patients were evaluated through 100 weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures. RESULTS: Overall, 828/964 (85.9%) patients completed week 100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks 24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week 24 but increased after switching to active treatment at weeks 52 (63.7%) and 100 (62.1%). In ACR20 responders at week 52, 81.2% of both treatment cohorts maintained response at week 100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks 24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week 24, increasing at weeks 52 (28.0%) and 100 (35.2%). MDA response was maintained at week 100 in week 52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100 weeks. CONCLUSIONS: For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03675308.

Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians.

Impact of dietary-nucleotides and Saccharomyces cerevisiae-derivatives on growth-performance, antioxidant-capacity, immune-response, small-intestine histomorphometry, caecal-Clostridia, and litter-hygiene of broiler-chickens treated with florfenicol.

Stress in poultry production is energy-demanding. Nucleotides and yeast cell-wall products are essential nutrients for broiler performance, gut function, and immune response. Antibiotics, like florfenicol, negatively affect the immune system. A total of 600 one-d-old broiler chickens (Cobb-500) were weighed and randomly allotted into four groups with three replicates each. The control group (G1) received the basal diet, G2 received a diet supplemented with a combination of nucleotides and Saccharomyces cerevisiae derivatives (250 g/Ton), G3 received the basal diet and medicated with florfenicol (25 mg/Kg body weight) in drinking water for 5 days, while G4 received a combination of nucleotides and Saccharomyces cerevisiae-derivatives (250 g/Ton) and medicated with florfenicol in drinking water. Growth performance criteria were recorded weekly. Blood, intestinal contents, small-intestine sections, and litter samples were collected to measure birds' performance, carcass yields, leukocytic counts, antioxidant capacity, antibody titres, phagocytic index, caecal Clostridia, intestinal histomorphometry, and litter hygiene. Nucleotide-supplemented groups (G2 and G4) revealed significant (p ≤ 0.05) improvements in feed conversion, and body weight, but not for carcass yields in comparison to the control. Dietary nucleotides in G2 elevated blood total proteins, leucocytic count, antioxidant capacity, and phagocytic index, while they lowered blood lipids and litter moisture and nitrogen (p ≤ 0.05). Dietary nucleotides in G4 ameliorated the immunosuppressive effect of florfenicol (p ≤ 0.05) indicated in reducing caecal Clostridia, improving duodenal and ileal villi length, and increasing blood albumin and globulin levels, and phagocytosis%. Supplementing diets with nucleotides and yeast products has improved the immune system and provided a healthier gut for broilers.

Guanidine dicycloamine-based analogs: green chemistry synthesis, biological investigation, and molecular docking studies as promising antibacterial and antiglycation leads.

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

Emergence and Genomic Characterization of a spa Type t4407 ST6-SCCmec Type IVa Methicillin-Resistant Staphylococcus aureus Strain Isolated from Al-Karak Hospital, Jordan.

Background and Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major concern in Jordanian hospitals in terms of infection control. The purpose of this study was to identify the resistance patterns of Staphylococcus aureus strains isolated from surfaces of critical locations within the Al-Karak Governmental Hospital in 2019. Additionally, the study aimed to conduct whole-genome sequencing on the isolates. Materials and Methods: In February 2019, fourteen S. aureus strains were isolated from surfaces in critical sites in the Al-Karak Governmental Hospital. These isolates underwent antibiogram testing to determine their resistance profile. Genome sequencing using the Illumina MiSeq platform was applied to the extracted DNA from these isolates. The genomic data, including coding sequences, were analyzed to identify lineage, resistance genes, and plasmids. Results: The antibiogram results revealed that 11 of the 14 isolates were resistant to oxacillin, 6 to linezolid, and 1 to rifampicin, while none showed resistance to chloramphenicol. Eleven isolates were identified as MRSA, with a novel spa type (t4407) not previously reported in Jordan. High-quality sequencing data were obtained for only one isolate, i.e., A29, the genome showed 2,789,641 bp with a 32.7% GC content and contained 2650 coding sequences. Genomic analysis indicated the ST6 lineage, mecA gene (SCCmec type IVa(2B)), and a hybrid plasmid (pJOR_blaZ) carrying the blaZ gene for ß-lactam resistance. Genomic data were deposited in NCBI (CP104989). The A29 genome closely resembled an MRSA genome isolated from a Danish hospital in 2011. The SNP analysis revealed identical antimicrobial resistance genes in these two genomes. Conclusions: This study unveils the first genomic sequence of an MRSA isolate from Jordan, marked by distinctive genotypic traits. The findings enhance our understanding of the MRSA types circulating in Jordan and the region and substantiate the phenomenon of intercontinental MRSA transmission.

Influence of titanium dioxide nanoparticles and/or cadmium chloride oral exposure on testicular morphology, oxidative stress, and apoptosis in rats: Ameliorative role of co-enzyme Q10.

Background and objectives: Little is known about the implications of titanium dioxide nanoparticles (TiO2NPs) and cadmium chloride (Cd) co-exposure on the male reproductive system in mammals. As a result, this study researched the effects of oral TiO2NPs and/or Cd exposure on male reproduction and testicular functions. Additionally, a mitigation trial with co-enzyme Q10 (CoQ10) has also been conducted. Methods: In a 60-day experiment, seven experimental groups, each containing 10 male Sprague Dawley rats, were orally given distilled water (control), corn oil (vehicle control), CoQ10 (10 mg/kg b.wt), TiO2NPs (50 mg/kg b.wt), Cd (5 mg/kg b.wt), TiO2NPs + Cd, and TiO2NPs + Cd + CoQ10. Then, sperm quality, male sex hormones, oxidative stress indications, Ti and Cd testicular residues, testes and accessory gland architecture, and apoptotic and inflammatory markers in rat testes were assessed. Results: TiO2NPs and/or Cd exposure negatively impacted body weight, weight gain, testicular weights, semen quality, serum reproductive hormones, oxidative stress parameters, and Caspase-3 and tumor necrosis factor (TNF-α) immunoreactions. Histopathological changes were recorded in testicular, seminal vesicle, and prostatic tissues. Yet, co-administration of CoQ10 with TiO2NPs and Cd substantially mitigated these adverse consequences. The most notable aspect is that it effectively lowered testicular tissue Ti and Cd levels. It also improved oxidant status, hormonal profile, and sperm picture. CoQ10 minimized the testicular damage implied by histological examination. Furthermore, CoQ10 significantly diminished TiO2NPs and Cd-induced Caspase-3 and TNF-α immunoexpression in testicular tissue. Conclusion: As a result, CoQ10 could be utilized as a safe remedy to protect male reproductive physiology from TiO2NPs and Cd damage.

Real-World Discontinuation and Switching Patterns for Interleukin-Inhibitor Treatments in Patients with Moderate-to-Severe Psoriasis in Japan.

INTRODUCTION: Patients with moderate-to-severe psoriasis (PsO) treated with interleukin (IL)-inhibitors may require treatment modification to achieve disease control. This study evaluated discontinuation and switching of IL-inhibitors for PsO patients in Japan. METHODS: Japan Medical Data Center claims (1/2005-5/2022) were used to identify patients with PsO diagnosis preceding a first IL-inhibitor claim (index date) with ≥ 6 months of eligibility prior. Treatment switch (claim for another biologic) and discontinuation (gap in care ≥ 150% of the days' supply of the preceding prescription) were assessed up to 24 months following initiation. Censored Kaplan-Meier time-to-event analyses calculated rates, and Cox proportional hazards models estimated hazard ratios (HRs) adjusting for baseline characteristics. RESULTS: The study included 1481 unique patients treated with brodalumab (BRO; n = 159), guselkumab (GUS; n = 360), ixekizumab (IXE; n = 279), risankizumab (RIS; n = 327), secukinumab (SEC; n = 366), tildrakizumab (n = 40; excluded due to limited data), and ustekinumab (UST; n = 262). At 12/24 months, 25.9%/38.6% of patients overall had discontinued their index IL-inhibitor and 13.5%/21.2% had switched to another biologic. Discontinuation at 12/24 months was lowest for RIS (11.2%/17.4%), followed by UST (17.9%/32.2%), IXE (27.0%/37.0%), GUS (29.8%/43.0%), SEC (35.6%/53.8%), and BRO (37.2%/47.2%). Switching showed a similar trend: RIS (5.7%/10.7%), UST (11.2%/19.9%), SEC (14.7%/25.7%), IXE (14.8%/21.5%), GUS (16.9%/23.2%), and BRO (19.7%/26.8%). HRs of discontinuation relative to RIS were 2.07 for UST, 2.59 for IXE, 2.70 for GUS, 3.65 for BRO, and 3.69 for SEC (all P ≤ 0.001). HRs of switching relative to RIS were 2.05 for IXE, 2.45 for GUS, 2.67 for SEC, 2.73 for UST, and 2.77 for BRO (all P ≤ 0.01). CONCLUSION: Treatment modification of IL-inhibitors for PsO was commonly observed and could indicate insufficient disease control and/or incremental economic burden. Discontinuation and switching rates were lowest for RIS regardless of time point and adjustment for patient characteristics.

Economic Burden among Patients with Vitiligo in the United States: A Retrospective Database Claims Study.

Patients with vitiligo incur direct and indirect costs associated with their condition; however, data regarding the economic burden of vitiligo are scarce and outdated. In this retrospective cohort analysis of the Merative MarketScan Commercial Database, healthcare costs and healthcare resource utilization (HCRU) were evaluated among United States patients with vitiligo. Patients with vitiligo were matched (1:2) with individuals without vitiligo (controls) between January 2007 and December 2021. Outcomes included all-cause and vitiligo-related costs (2021 dollars) and all-cause HCRU, including mental health-related HCRU, during a 1-year postindex period. Subgroup analyses were completed for patients on vitiligo treatments with systemic effects (such as phototherapy and oral steroids) or a new mental health diagnosis. The analysis was focused solely on direct costs. Baseline demographics were well-balanced between matched vitiligo (49,512) and control (99,024) cohorts. Patients with vitiligo incurred significantly higher all-cause ($15,551 vs $7735) and vitiligo-related ($3490 vs $54) costs than controls (P < .0001). All-cause and mental health-related HCRU were also significantly higher among patients with vitiligo (P < .0001). Differences in all-cause and vitiligo-related healthcare costs remained significantly higher in patients on treatments with systemic effects/mental health diagnoses than in controls (P < .0001). Taken together, healthcare costs and HCRU were significantly higher among patients with vitiligo than among controls.

Interactive effects of cadmium and titanium dioxide nanoparticles on hepatic tissue in rats: Ameliorative role of coenzyme 10 via modulation of the NF-κB and TNFα pathway.

This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd2+) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd2+-induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd2+ (5 mg/kg b.wt), TNPs + Cd2+, or TNPs + Cd2++CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd2+ content were increased considerably in TNPs and/or Cd2+-exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd2+-exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd2+ on the liver. The study concluded that TNPs and Cd2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd2+ hepatotoxic impacts.

Comorbidity Burden Among Patients with Vitiligo in the United States: A Large-Scale Retrospective Claims Database Analysis.

INTRODUCTION: Vitiligo is often associated with comorbid conditions that may increase economic burden and affect patients' health-related quality of life. No large-scale study has been published to date using claims databases to evaluate the burden of comorbidities among patients with vitiligo. Herein, we evaluate the comorbidity burden among patients diagnosed with vitiligo from the US. METHODS: This retrospective cohort analysis used the Merative MarketScan Commercial Database. Eligible patients were diagnosed with vitiligo between January 2008 and December 2020 and matched 1:4 (vitiligo:control) with control subjects with no diagnosis of vitiligo between January 2007 and December 2021. Study outcomes were the incidence of comorbidities after matching, adjusted hazard ratios of comorbidity incidence among patients with vitiligo relative to matched control subjects, and time to comorbidity diagnosis or incidence. RESULTS: Baseline demographics were well balanced between matched vitiligo (n = 13,687) and control cohorts (n = 54,748). Incidence rates of comorbidities were higher among patients compared with control subjects (psychiatric, 28.4% vs 22.8%; autoimmune, 13.4% vs 5.1%; and non-autoimmune, 10.0% vs 7.0%). The most common psychiatric and autoimmune comorbidities in patients with vitiligo compared with control subjects included anxiety (14.3% vs 11.0%, respectively), sleep disturbance (9.1% vs 7.1%), depression (8.0% vs 6.3%), atopic dermatitis (3.1% vs 1.1%), psoriasis (2.7% vs 0.6%), and linear morphea (1.5% vs 0.1%). The risk of developing any psychiatric (hazard ratio 1.31; P < 0.01), autoimmune (hazard ratio 2.77; P < 0.01), or non-autoimmune (hazard ratio 1.45; P < 0.01) comorbidity was significantly higher among patients with vitiligo. Time to diagnosis of most vitiligo comorbidities was 1-3 years, although linear morphea was diagnosed at < 1 year. CONCLUSION: Results of this retrospective analysis demonstrated that patients were much more likely to be diagnosed with autoimmune or psychiatric comorbidities following a vitiligo diagnosis, which likely contributed to increased economic burden and lower quality of life.

Vitiligo, a long-lasting disorder in which patches of the skin lose color, is often associated with other medical conditions that may lower a patients' quality of life and increase the cost of caring for patients with the disorder. No large-scale studies are currently available that look at how other medical conditions affect patients with vitiligo. In this study, we determine the occurrence and timing of other medical conditions among patients from the US who have vitiligo. We used the Merative MarketScan Commercial Database, which captures medical and prescription drug data for 145.5 million people in the US. Patients in this study had vitiligo diagnosed between January 2008 and December 2020 and were matched with subjects who did not have vitiligo between January 2007 and December 2021. We looked at the occurrence of other medical conditions among patients with vitiligo compared with subjects without vitiligo and the time it took for another medical condition associated with vitiligo to happen. The authors found that among 13,687 patients with vitiligo and 54,748 subjects without vitiligo, patients with vitiligo were much more likely to have an autoimmune (disorders in which the body's immune system attacks healthy tissue) or psychiatric (mental, emotional, or behavioral) disorder, which likely contributed to the amount of money needed to care for the condition and reduced quality of life.

Real-World Treatment Patterns in Patients with Vitiligo in the United States.

INTRODUCTION: Vitiligo is an autoimmune disorder resulting in skin depigmentation, with limited approved treatment options. This study evaluated medication utilization and treatment patterns among patients in the first year following vitiligo diagnosis. METHODS: This retrospective analysis of claims data from the Merative® MarketScan Research Databases included patients aged ≥ 12 years newly diagnosed with vitiligo. Patients were identified between October 1, 2016, and April 30, 2021, and had ≥ 12 months of continuous enrollment pre- and post-vitiligo diagnosis. Medication use, treatment line of therapy, time to and number of medication claims, and length of therapy were reported in the 12 months post-vitiligo diagnosis. Results are reported separately for treatment initiators post-vitiligo diagnosis, patients with moderate-to-severe vitiligo, and adolescents (aged 12-17 years). RESULTS: A total of 19,335 patients were included in the analysis, with half (N = 9648, 49.9%) not receiving any treatment during the 12-month follow-up. Switching was minimal among treatment initiators (N = 5845) in the 12 months post-vitiligo diagnosis, with the most frequent first-line treatments being high-potency topical corticosteroids (25.4%), oral corticosteroids (23.1%), and topical calcineurin inhibitors (TCI, 14.7%). Adolescents initiating treatment (N = 486) most frequently received TCI (30.9%) as first-line therapy. Patients with moderate-to-severe vitiligo (N = 3462) were very likely to receive treatment during follow-up, with only 1.5% not receiving treatment. Among patients with no vitiligo treatment prior to diagnosis, time to first medication claim ranged from 51.9 days (standard deviation [SD], 84.0) for TCI to 178.6 days (SD 116.0) for systemic immunosuppressants; mean total days supplied ranged from 14.4 days (SD 27.1) for oral corticosteroids to 121.0 (SD 114.0) for immunosuppressants. CONCLUSION: In this real-world study, a high proportion of patients did not receive any treatment. Among those receiving treatment, most were unlikely to switch or use a combination of treatments within the first year of vitiligo diagnosis.

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. OBJECTIVE: To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. METHODS: LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150 mg every 12 weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304 weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256 weeks. RESULTS: Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. LIMITATIONS: Open-label study with no placebo or active-comparator group. CONCLUSIONS: Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy.

Vendor evaluation platform for acquisition of medical equipment based on multi-criteria decision-making approach.

The purchase of medical equipment is a critical issue that should be planned properly. The selection of the most appropriate vendor impacts time, effort, and expenses. Therefore, the challenge is to strike a balance between the available budget and the required equipment. The study aims to select the best vendor for supplying medical equipment based on Emergency Care Research Institute (ECRI) standards. The multi-criteria decision-making approach has been adopted through three methods; Multi-Objective Optimization by Ratio Analysis (MOORA), Simple Additive Weighting (SAW), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). The criteria of selection are divided into general, technical, and financial. The criteria are weighted using three methods: CRITIC, entropy, and expert judgment. The Vendor Evaluation Program for Medical Equipment (VEPME) is designed to automatically select the best vendor. Medical imaging equipment is selected to test the program by four modalities: X-ray equipment, CT, MRI, and ultrasound. The best scenario was given by the entropy-TOPSIS. As a result, this methodology was adopted by the program. The results demonstrate the robustness of the proposed methodology by comparing the VEPME output to expert judgment.

Antiviral Activity of Chitosan Nanoparticles and Chitosan Silver Nanocomposites against Alfalfa Mosaic Virus.

Plant viruses are a global concern for sustainable crop production. Among the currently available antiviral approaches, nanotechnology has been overwhelmingly playing an effective role in circumventing plant viruses. Alfalfa mosaic virus (AMV) was isolated and identified from symptomatic pepper plants in Egypt using symptomatology, serological tests using the direct ELISA technique, differential hosts and electron microscopy. The virus was biologically purified from a single local lesion that developed on Chenopodium amaranticolor. The AMV infection was further confirmed using an AMV coat protein-specific primer RT-PCR. We further evaluated the antiviral potential of chitosan nanoparticles (CS-NPs) and chitosan silver nanocomposites (CS-Ag NC) in different concentrations against AMV infections in pepper plants. All tested concentrations of CS-NPs and CS-Ag NC induced the inhibition of AMV systemically infected pepper plants when applied 24 h after virus inoculation. The foliar application of 400 ppm CS-NPs or 200 ppm CS-Ag NC produced the highest AMV inhibitory effect (90 and 91%) when applied 24 h after virus inoculation. Treatment with CS-NPs and CS-Ag NC considerably increased the phenol, proline and capsaicin contents compared to the infected plants. Moreover, the agronomic metrics (plant height, fresh and dry pod weights and number of pods per plant) were also significantly improved. According to our results, the potential applications of CS-NPs and CS-Ag NC may provide an effective therapeutic measure for better AMV and other related plant virus management.

Identification of sulphonamide-tethered N-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease.

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel triazolo-isatins for inhibiting main protease (Mpro) of the virus, a crucial enzyme for its replication in the host cells. Particularly, sulphonamide 6b showed promising inhibitory activity with an IC50= 0.249 µM. Additionally, 6b inhibited viral cell proliferation with an IC50 of 4.33 µg/ml, and was non-toxic to VERO-E6 cells (CC50 = 564.74 µg/ml) displaying a selectivity index of 130.4. In silico analysis of 6b disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained in vitro findings.

Comparison of risankizumab and apremilast for the treatment of adults with moderate plaque psoriasis eligible for systemic therapy: results from a randomized, open-label, assessor-blinded phase IV study (IMMpulse).

BACKGROUND: Treatment of psoriasis with risankizumab has demonstrated superior efficacy to other treatments, such as adalimumab, ustekinumab and secukinumab. OBJECTIVES: This study compared the efficacy and safety of risankizumab and apremilast in adults with moderate plaque psoriasis eligible for systemic therapy. It also evaluated the efficacy and safety of switching to risankizumab vs. continuing apremilast in patients who did not achieve ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75 nonresponders) after 16 weeks of treatment with apremilast. METHODS: This 52-week, phase IV, multicentre, randomized, open-label, efficacy assessor-blinded study (NCT04908475) enrolled patients (aged ≥ 18 years) with a diagnosis of moderate chronic plaque psoriasis (≥ 6 months) and who were candidates for systemic therapy. The enrolled patients (randomized 1 : 2) received subcutaneous risankizumab (150 mg at weeks 0 and 4) or oral apremilast (30 mg twice daily). At week 16, all patients treated with apremilast were re-randomized (1 : 1) to risankizumab or apremilast, stratified by week-16 PASI 75 response. The co-primary outcomes in period A at week 16 were the achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and static Physician's Global Assessment (sPGA) 0/1 with a two-grade or better improvement from baseline. At week 52, the primary endpoint in period B was the achievement of PASI 90 in PASI 75 nonresponders with apremilast at week 16. Safety was monitored throughout the study. All patients who received one dose of treatment were included in the efficacy and safety analysis. RESULTS: At baseline, 118 and 234 patients were assigned to receive risankizumab and apremilast, respectively. At week 16, PASI 90 was achieved by 55.9% [95% confidence interval (CI) 47.0-64.9] and 5.1% (95% CI 2.3-8.0), and sPGA 0/1 by 75.4% (95% CI 67.7-83.2) and 18.4% (95% CI 13.4-23.3), respectively. In period B, among PASI 75 nonresponders with apremilast at week 16, 83 switched to risankizumab and 78 continued apremilast. At week 52, 72.3% (95% CI 62.7-81.9) who switched to risankizumab achieved PASI 90 vs. 2.6% (95% CI 0.0-6.1) who continued apremilast. The most frequent adverse events (reported in ≥ 5%) in risankizumab-treated patients were COVID-19 infection and nasopharyngitis. Diarrhoea, nausea and headache were most frequent among apremilast-treated patients. CONCLUSIONS: For patients with moderate psoriasis, treatment with risankizumab demonstrated superior efficacy to those treated with apremilast, including those who did not benefit from prior treatment with apremilast. The safety profile of risankizumab was similar to prior studies, and no new safety signals were identified. These results show that, compared with apremilast, risankizumab treatment can significantly improve clinical outcomes in systemic-eligible patients with moderate psoriasis.

Construction of novel polybenzoxazine coating precursor exhibiting excellent anti-corrosion performance through monomer design.

In this study, we utilized salicylaldehyde (SA) and p-toluidine (Tol-NH2) to synthesize 2-(Z)[(4-methylphenyl)imino]methylphenol (SA-Tol-SF), which was then reduced to 2-[(4-methylphenyl)amino]methylphenol, producing SA-Tol-NH. SA-Tol-NH was further reacted with formaldehyde to create SA-Tol-BZ monomer. Poly(SA-Tol-BZ) was produced by thermally curing it at 210 °C, after synthesizing it from SA-Tol-BZ. The chemical structure of SA-Tol-BZ was analyzed using various analytical techniques such as FT-IR, 1H NMR spectroscopy, and 13C NMR spectroscopy TGA, SEM, DSC, and X-ray analyses. Afterward, we applied the obtained poly(SA-Tol-BZ) onto mild steel (MS) using thermal curing and spray coating techniques. To examine the anticorrosion attributes of MS coated with poly(SA-Tol-BZ), electrochemical characterization was employed. The study proved that poly(SA-Tol-BZ) coating had a high level of effectiveness in preventing corrosion on MS, with an efficacy of 96.52%, and also exhibited hydrophobic properties.

Optimal Concentration and Duration of Endotracheal Tube Coating to Achieve Optimal Antimicrobial Efficacy and Safety Balance: An In Vitro Study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common and genuine complication in fundamentally sick patients accepting mechanical ventilation. Silver nitrate sol-gel (SN) has been proposed as a potential preventative measure against VAP. Be that as it may, the arrangement of SN with distinctive concentrations and pH values remains a basic factor influencing its effectiveness. METHODS: Silver nitrate sol-gel was arranged with distinctive concentrations (0.1852%, 0.03496%, 0.1852%, and 0.01968%) and pH values (8.5, 7.0, 8.0, and 5.0) separately. The antimicrobial action of the silver nitrate and NaOH arrangements were assessed against Escherichia coli as a reference strain. The thickness and pH of the arrangements were measured, and biocompatibility tests were performed on the coating tube. The auxiliary changes in the endotracheal tube (ETT) tests after treatment were analyzed utilizing electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: The pH estimations of the diverse arrangements showed that the pH values shifted depending on the test conditions, with pH values extending from 5.0 to 8.5. The consistency estimations of the arrangements showed that the thickness values expanded as the pH values drew closer to 7.5 and diminished when the pH values went over 7.5. The antimicrobial action of the silver nitrate and NaOH arrangements were successful against Escherichia coli, with microbial checks decreasing in concentration (0.03496%, 0.1852% (pH: 8), and 0.01968%). The biocompatibility tests revealed tall cell reasonability rates, demonstrating that the coating tube was secure for therapeutic utilization and did not hurt typical cells. The SEM and TEM investigation gave visual proof of the antibacterial impacts of the silver nitrate and NaOH arrangements on the bacterial surface or interior of the bacterial cells. Moreover, the investigation revealed that a concentration of 0.03496% was the foremost successful in hindering the development of ETT bacterial colonization at the nanoscale level. CONCLUSIONS: We propose that cautious control and alteration of the pH and thickness of the arrangements are essential to guaranteeing the reproducibility and quality of the sol-gel materials. The silver nitrate and NaOH arrangements may serve as a potential preventative degree against VAP in sick patients, with a concentration of 0.03496% appearing to show the most elevated viability. The coating tube may serve as a secure and viable preventative measure against VAP in sick patients. Further investigation is required to optimize the concentration and introduction time of the arrangements to maximize their adequacy in avoiding VAP in real-world clinical settings.