Non-significant Increase Research Articles

Haematological toxicity of PARP inhibitors in advanced ovarian cancer: A systematic review and meta-analysis.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials. In total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8%) and ≥G3 (12.1%) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR)=2.44], neutropenia (RR=3.15) and thrombocytopenia (RR=4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR=5.73) and thrombocytopenia (RR=5.44), and a non-significant increase in the risk of neutropenia (RR=3.41) were detected. In patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.

A prospective evaluation of cellular bone matrix for posterolateral lumbar fusion.

Autograft bone is the gold standard graft used in posterolateral lumbar intertransverse fusion (PLF) but can be limited by supply and donor site morbidity. Cadaveric cellular allografts represent an alternative source of graft material that avoids these limitations. To assess the safety and efficacy of ViviGenRCellular Bone Matrix in comparison to autograft bone in PLF. We performed a prospective study of 20 subjects who underwent PLF including 55 segmental levels. Each patient received ViviGen over the decorticated posterolateral gutter on one side an autograft bone on the other side. Fusion grading was assigned by a blinded independent neuroradiologist using a CT-based modified Lenke radiographic classification at 12 months. There was a nonsignificant increase in surgical levels showing grade A fusion for ViviGen as compared to autograft bone (62 % vs. 44 %, p = 0.056). There was a nonsignificant decrease for Vivigen compared to autograft bone in grade B (16.4 % vs 25.5 %, p = 0.241) and fusion failure (21.8 % vs 30.9 %, p = 0.279). 69 % of subjects had significant improvement in back pain numeric rating and Oswestry scores. 73 % of patients had improvement in their leg pain scores. There were no significant changes in lumbar lordosis (p = 0.611) or mean segmental lordosis (p = 0.417). At 12 months, 35 % of all levels had a > 2-degree change on flexion versus extension views while 21 % of all levels had a > 3-degree change. ViviGen cellular bone matrix demonstrates its theoretical bone-generative properties by showing non-inferiority relative to autograft with regards to fusion rates and similarity regarding patient reported outcome measures. Cellular bone matrix agents may represent a safe and noninferior alternative to autograft bone while circumventing potential drawbacks of the latter.

Magnitude of effect of low dose colchicine, a newly food and drug administration approved treatment for stroke prevention.

As the Food and Drug Administration in June 2023 approved low dose colchicine for primary prevention of stroke and other cardiovascular events, an updated meta-analysis of stroke outcomes in randomized trials would help inform clinical practice.**** METHODS: Systematic, study-level meta-analysis of randomized clinical trials of long-term colchicine in patients with established atherosclerotic cardiovascular disease (ASCVD, preponderantly primary prevention for stroke) or following non-cardioembolic ischemic stroke/transient ischemic attack (secondary prevention). Heterogeneity was assessed with the I2 statistic and Cochrane's Q and potential bias assessed with the Risk of Bias 2.0 scale. Six randomized control trials met selection criteria, enrolling 14,987 patients (7495 colchicine, 7492 placebo), with median follow-up 26.3 months. Colchicine dosage in all trials was 0.5 mg once-daily. Across all trials, colchicine treatment produced a 28 % relative risk reduction in stroke (1.77 % vs 2.54 %, risk ratio (RR)=0.72, 95 %CI: 0.58-0.89; p = 0.003) and a comparable relative reduction on major adverse cardiovascular events. There was potential heterogeneity by subgroup (pinteraction = 0.06), with a stronger relative reduction for stroke in the five ASCVD trials (RR=0.48, 95 %CI:0.30-0.77; p = 0.003) than the non-cardioembolic ischemic stroke/TIA population (RR=0.80, 95 %CI:0.63-1.02; p = 0.07). Colchicine was associated with a small, non-significant increase in all-cause mortality (RR: 1.09; 95 %Cl: 0.85-1.40, p = 0.49) but not cardiovascular death (RR: 0.92; 95 %Cl: 0.65-1.29, p = 0.61). Low-dose colchicine treatment decreases stroke and major adverse cardiovascular event risk in patients with ASCVD and potentially in patients following a non-cardioembolic ischemic stroke/TIA. Among every 1000 patients treated over 2 years, approximately 6.6 strokes and 24 major adverse cardiovascular events are avoided.

Assessment of the Rainfed Wheat Productivity in a Changing Climate in Irbid, Jordan Using Statistical Downscaling and Random Forest Regression Prediction Under RCP4.5 & 8.5 Pathways.

Jordan faces risks associated with climate change and endeavors to sustain resources through the SDGs. This study examines the impacts of climate change on rainfed wheat productivity in Irbid Governorate during the historical period (1994-2021) and simulated for the future (2024-2100) using climate models (SDGs 1, 2, 11, 12, 13, & 15). Monthly precipitation, mean temperature, and annual wheat yield data were collected for the period (1994-2021) and analyzed using the Mann-Kendall test with Sen’s slope to investigate the historical trends and elaborate Phi-k correlation coefficient to determine their association. Monthly precipitation and mean temperature projections were collected from CSIRO-MK3.6.0 & GFDL-ESM2M CMIP5 ensemble models under two concentration pathways: RCP4.5 and RCP8.5. The projections were biased and corrected by the dynamic bilinear interpolation method and Delta, EQM, and QM statistical downscaling to enhance the projections' reliability and performance in capturing the region's climate. Taylor diagram was utilized to choose the best model to represent observed data. Cumulative Distribution Function and Probability Density Function Curves were plotted to describe the changes over decades based on climate models. Future wheat yields were predicted using the Random Forest Regression model. The results revealed a non-significant increase in total annual precipitation of 1.8% and 13.8% and a rise in annual mean temperature of 5.4% and 2.7% for Irbid and Baqura stations, respectively during the baseline timeframe on which wheat yield increased by 21.3%. The CSIRO model outperformed the GFDL model with greater fidelity in simulating historical monthly precipitation and mean temperatures. The CSIRO-MK3.6.0 model indicates precipitation and temperature shifts for near and far future periods. Temperature increases are expected to have more severe impacts in the far future (2073-2100) while projected decreases in precipitation of 0.06 mm/day and 0.10 mm/day under RCP4.5 and RCP8.5 affect yield reductions by 11.42 kg/ha and 12.21 kg/ha. Temperature increases of 2.7°C and 4.1°C under RCP 4.5 & 8.5 correspond to yield decreases of 24.825 kg/ha and 33.395 kg/ha, respectively. The study highlights the need for enhanced adaptation strategies; cultivating resilient wheat varieties, promoting crop rotation, improving meteorological monitoring and risk response approaches, and providing timely weather forecasts to mitigate the adverse effects of climate change on wheat productivity and ensure sustainable agriculture in Jordan.

Abstract A010: PARP1 selective inhibition sensitize triple-negative breast cancers to photon and alpha-particle therapy regardless of homologous recombination proficiency status

Abstract The association of Poly (ADP-ribose) polymerase (PARP) inhibitors with radiotherapy (RT) increase RT-induced DNA damage and radiosensitize tumors regardless deficiency in DNA repair pathways. Although PARP1 is the main protein responsible for PARP-mediated DNA repair, all first-generation PARP inhibitors act on both PARP1 and PARP2, which the latter is associated with hematological toxicity. The RT ability to induce DNA damage can be influenced by the radiation linear energy transfer (LET). High-LET radiation, such as alpha particles (LET: 60-200 keV/μm), induces more complex DNA damage than does low-LET radiation (photon, LET: 0.2 keV/μm). Thus, high-LET radiation combined with selective PARP1 inhibitors may be a promising strategy to radiosensitize tumors. The purpose of this study was to investigate if the selective PARP1 inhibition could radiosensitize BRCA1 mutant and wild-type triple-negative breast cancers (TNBC) to photons and alpha particles. The radiosensitization effect in vitro was assessed using TNBC cells: MDA-MB-436 (BRCA1 mutated), and its isogenic pair with BRCA1 recovered, MDA-MB-436 BRCA1, and 4T1. The IC50 of the PARP1 selective inhibitor (AZD5305) was determined across all cell lines by the clonogenic assay, and concentrations of AZD5305 that did not affect the colony formation ability without radiation were chosen for the radiopotentiation evaluation (clonogenic assay). Mice were inoculated with 4T1 cells in the hind leg. Diffusing Alpha-emitter Radiation Therapy (Alpha DaRT) was used to deliver alpha particles intratumorally, by the implantation of 224Ra-loaded sources. AZD5305 (1 mg/kg) was daily administered by oral gavage for 6 consecutive days, starting 24 h before Alpha DaRT implantation. Tumor growth delay and survival were assessed. AZD5305 significantly radiosensitized all the evaluated cell lines in vitro. AZD5305 alone (mice implanted with inert seeds) did not affect the tumor growth in mice (p=0.12) in comparison with inert+vehicle. Alpha DaRT delayed tumor growth in comparison with mice treated with inert+vehicle (p=0.03), but the Alpha DaRT+AZD5305 reduced tumor growth in comparison with Alpha DaRT+vehicle (p=0.05). Alpha DaRT promoted a non-significant (p=0.09) increase in survival when compared with inert+vehicle, but Alpha DaRT+AZD5305 increased survival in comparison with inert+vehicle (p=0.002), and Alpha DaRT+vehicle (p=0.06). Our findings demonstrate that AZD5305 significantly radiosensitizes TNBC to photons and alpha particles, regardless of the homologous recombination proficiency status. These results are novel because there no studies investigating selective PARP1 inhibition in combination with photons and alpha particles. Our work is relevant because the combination of AZD5305 with Alpha DaRT offers a promising strategy to minimize the adverse effects of PARP inhibition. AZD5305 presents less off-target effects than non-selective PARP inhibitors, while Alpha DaRT delivers alpha particles directly into the tumor, limiting radiosensitization of normal tissue. Citation Format: Poliana C. Marinello, Marco Tulio Freitas Reis, Walison Augusto Da Silva Brito, Amy Wu, Alexandre Rubinstein, Mark D. Wasley, Mandira Manandhar, Scott J. Bright, Yogesh Rai, Seyed Mojtaba Hosseini Ghahfarokhi, Ronen Segal, Vered Domankevich, Gabriel O. Sawakuchi. PARP1 selective inhibition sensitize triple-negative breast cancers to photon and alpha-particle therapy regardless of homologous recombination proficiency status. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A010.

Analysis of choroidal markers of activity in pachychoroid disease spectrum.

To detect choroidal markers of disease activity in eyes with chronic active unilateral pachychoroid disease spectrum (PDS) compared to the non-active contralateral eyes, based on multimodal imaging and particularly indocyanine green angiography (ICGA). An observational retrospective case-control study. The study evaluated individuals diagnosed with chronic active unilateral PDS (group 1) by comparing the eyes with the non-active fellow eyes (group 2). Imaging was performed using fundus photographs, ICGA, and spectral-domain optical coherence tomography (SD-OCT). Choroidal thickness, choroidal vascular density, choroidal vasodilation, choroidal vascular leakage, and choroidal meridian breakdown were evaluated. Of the 90 patients with chronic PDS with ICGA at our database, 27 Caucasians (mean age: 55.9 years) were identified with active unilateral PDS. Group 1 showed a higher prevalence of the following parameters compared to Group 2: choroidal meridian breakdown (81.5% vs. 25.9%; p < 0.001), choroidal vasodilation (88.9% vs. 48.1%; p < 0.001), greater subfoveal choroidal thickness (420 ± 79.8μm vs. 346 ± 78.5μm; p = 0.002), ICGA choroidal vascular leakage (96.3% vs. 29.6%; p < 0.001), and choroidal hyperpermeability (100% vs. 29.6%; p < 0.001), with a nonsignificant increase in choroidal vascular density (55.4%±13.4 vs. 49.3%±13.5 in the contralateral eye; p = 0.167). Choroidal meridian breakdown, thicker choroid, choroidal vasodilation, and ICGA choroidal vascular leakage are potential posterior choroidal markers of disease activity in PDS.

Efficacy of a clinical decision support tool to promote guideline concordant evaluations in patients with high-risk microscopic hematuria: a cluster randomized quality improvement project.

We aimed to determine whether implementation of clinical decision support (CDS) tool integrated into the electronic health record (EHR) of a multi-site academic medical center increased the proportion of patients with American Urological Association (AUA) "high risk" microscopic hematuria (MH) who receive guideline concordant evaluations. We conducted a two-arm cluster randomized quality improvement project in which 202 ambulatory sites from a large health system were randomized to either have their physicians receive at time of test results an automated CDS alert for patients with 'high-risk' MH with associated recommendations for imaging and cystoscopy (intervention) or usual care (control). Primary outcome was met if a patient underwent both imaging and cystoscopy within 180 days from MH result. Secondary outcomes assessed individual completion of imaging, cystoscopy or placement of imaging orders. There were 917 patients randomized to intervention (n=476) or control (n=441) arms between October-December 2021. The percentage of eligible patients for whom the alert correctly triggered in the intervention arm was 83%. Primary outcome was achieved in 0.6% vs. 0.9% (RR: 0.69; 95% CI 0.15, 3.10) of patients in the intervention and control arms, respectively. Patients in the intervention and control groups had similar rates of completed imaging (17.7% vs. 14.7%) and cystoscopy (1.5% vs. 0.9%). Those in the intervention arm had a higher likelihood of CT urogram order (5.5% vs. 1.1%, p=0.003) and a non-significant increase in urology evaluation (11.1% vs. 7.5%, p=0.09). Implementing an EHR-integrated CDS tool to promote evaluation of patients with high-risk MH did not lead to improvements in patient completion of a full guideline-concordant evaluation. The development of an algorithm to trigger a CDS alert was demonstrated to be feasible and effective. Further multi-level assessment of barriers to evaluation are necessary to continue to improve the approach to evaluating high risk patients with MH.

Safety and efficacy of cellular therapy with mesenchymal stromal cells in sepsis, meta-analysis

BackgroundSepsis is a major cause of death in hospitalised patients. Dysregulated immune response is the driving pathophysiologic phenomenon underlying tissue damage and organ failure. Due to immune-modulatory properties of mesenchymal stromal cells (MSCs) several trials experimented their efficacy in sepsis. In-vitro and preclinical studies are quite promising however, clinical trials showed inconsistent results.Methods and resultsWe gathered available evidence in a meta-analysis to figure out if clinical advantage of cellular therapy in sepsis. Eleven trials were included with total of 360 patients, 191 received MSCs and 169 as control. The overall mortality was 0.248 with 95% CI 0.191–0.316. Relative to control, mortality Odds ratio (OR) was 0.54, 95% CI 0.294–1.006 and P = 0.05. Frequent MSCs infusions showed better survival, OR = 0.3, 95% CI 0.1–0.87 and P = 0.03. While survival in the cohort that received infrequent MSCs infusions was comparable with the control, OR = 0.7, 95% CI 0.35–1.41 and P = 0.3. Also, survival benefit was associated with the 1 × 106 cell/kg dose, OR = 0.31, 95% CI 0.14–0.68 and P = 0.004. While the cohort that received higher doses had OR 1.22, 95% CI 0.54–2.75 and P = 0.6. Length of hospitalisation in the MSCs cohort was significantly shorter. The standardized difference in means (d) was − 0.443, 95% CI − 0.743 to − 0.144, P = 0.004. Also, MSCs therapy was associated with significantly shorter ICU stay, d = − 0.349 with 95% CI of − 0.647 to − 0.051 and P = 0.022. Furthermore, MSCs therapy was associated with significant reduction of the proinflammatory cytokines IL-6 and IL-8 but non-significant increase of the anti-inflammatory cytokine IL-10.ConclusionCellular therapy with MSCs is a promising therapeutic modality in sepsis. Positive effects are mainly associated with frequent infusions and the dose of 1 × 106 cell/kg. Larger scale studies are needed to address the pending questions about the optimal indications and cell manipulation conditions.

Efficacy of Ceftazidime-avibactam in treating Gram-negative infections: a systematic review and meta-analysis.

Ceftazidime-avibactam (CAZ-AVI) has emerged as a promising treatment option for Gram-negative infections, particularly those caused by CAZ-Non-Susceptible (NS) pathogens. This systematic review and meta-analysis aim to assess the efficacy and safety of CAZ-AVI in these challenging infections. We systematically queried EMBASE, Cochrane CENTRAL, and PubMed/Medline for studies published until September 15, 2024. Randomized Controlled Trials (RCTs) evaluating CAZ-AVI against Gram-negative infections were included. A meta-analysis was performed to calculate pooled odds ratios (OR) for both clinical and microbiological success. A total of 146 studies were identified through database searches, leading to the inclusion of 17 studies. Among the efficacy studies for Gram-negative pathogens, there was no significant difference in clinical success rates for CAZ-AVI compared to comparators (pooled OR: 0.90, p = 0.22), and a non-significant increase in microbiological success was observed (pooled OR: 1.20, p = 0.41). In contrast, for CAZ-NS pathogens, six studies reported no significant difference in clinical cure rates (pooled OR: 0.77, p = 0.24), while four studies indicated a non-significant increase in microbiological cure rates (pooled OR: 1.83, p < 0.02). This study suggests that CAZ-AVI is a viable option for treating Gram-negative infections, including CAZ-NS pathogens. While it has shown promising activity against these resistant pathogens, its clinical and microbiological success rates are comparable to other antibiotics in the overall analysis. However, CAZ-AVI may offer an advantage in managing resistant infections. These findings underscore the need to consider CAZ-AVI in treatment guidelines and emphasize the importance of antibiotic stewardship programs to optimize its use and prevent resistance. Ongoing monitoring of resistance patterns and patient outcomes is essential to ensure its long-term efficacy.

P1033 The decrease of 6-TGN concentrations during pregnancy is not associated with an increase in fecal calprotectin in female patients with IBD on thiopurine-treatment

Abstract Background Thiopurines, such as azathioprine (AZA), mercaptopurine (MP) and thioguanine (TG), are commonly used to maintain disease remission in inflammatory bowel disease (IBD). AZA and MP are metabolized to form the active 6-thioguanine nucleotides (6-TGN) and the 6-methylmercaptopurine ribonucleotides (6-MMPR), associated with intolerable adverse drug reactions. Previous studies report a shift in thiopurine metabolism during pregnancy, characterized by a decrease in 6-TGN and an increase in 6-MMPR levels 1,2. The influence of these changes on clinical outcomes remains unclear. This study aims to explore the association of changes in 6-TGN and 6-MMPR levels during pregnancy with disease activity and toxicity markers in women with IBD. Methods A retrospective cohort study was conducted recruiting patients with IBD from six Dutch medical centers. Adult women who were pregnant between 2017 and 2022, using thiopurines for IBD, and with at least one thiopurine metabolite measurement during pregnancy were included. Linear mixed effects models assessed 6-TGN and 6-MMPR levels during pregnancy (categorized to half trimesters) and within 6 months postpartum, compared to preconceptional levels, adjusting for dosage and repeated measurements. The influence of percentual changes in 6-TGN and 6-MMPR on disease activity (calprotectin &amp;gt;250μg/g), hepatotoxicity (alanine aminotransferase (ALT) &amp;gt;2xULN) and myelotoxicity (leukocytes &amp;lt;4.0x109/L) were analyzed, adjusting for dosage and trimester. Results A total of 87 women with 100 pregnancies were included, of whom 64.4% were diagnosed with Crohn’s disease and 32.2% with ulcerative colitis. An adverse pregnancy outcome occurred in 13 pregnancies (13%), with rates comparable to the healthy Dutch population. Subtherapeutic levels of 6-TGN were measured in 32 pregnancies (32%). There were no instances of leukopenia; transient hepatotoxicity occurred thrice (3%). There was active disease in 30 pregnancies, corresponding to 37 metabolite measurements. Analysis showed a significant reduction in 6-TGN levels in the second trimester (Figure 1), with non-significant increases in 6-MMPR. Though disease activity coincided with subtherapeutic 6-TGN-levels 21 times (56.8%), the reduction in 6-TGN was not associated with changes in calprotectin (Estimated marginal mean difference (EMM) =5.435, p=0.104), ALT (EMM=-0.025, p=0.858) or leukocytes (EMM=0.068, p=0.536, Table 1). Conclusion Our study results indicate that despite that 6-TGN levels decrease and 6-MMP may increase during pregnancy, these fluctuations do not seem to associate with markers of disease activity, hepatotoxicity and myelotoxicity. Larger, prospective studies are needed to re-evaluate the postulated need for thiopurine monitoring in the third trimester.

Effects of tongue tamers and customized bonded spurs as an early treatment of anterior open bite: a randomized clinical study

BackgroundAnterior open bite is a challenging condition for pediatric dentists and orthodontists as it causes aesthetic, speech, feeding, and psychological problems; this emphasizes the need for early diagnosis and interception of this malocclusion.AimThis study aimed to evaluate the effects of prefabricated metal-bonded tongue tamers and customized bonded spurs in the early treatment of anterior open bite.Materials and methodsA sample of seventy-five children aged 7–9 years were assigned into three groups in which anterior open bite was treated using tongue tamers (group-I), customized composite bonded spurs(group-II), and conventional fixed palatal cribs (group-III). Study model and cephalometric x-ray evaluations were done before and after a three-month follow-up. Data was gathered and statistically analyzed using ANOVA and Bonferroni tests.ResultsModel overbite at central and lateral incisors was increased in all groups. The highest increase was found in group-I(3.16 ± 1.17, 2.81 ± 0.94)and group-III(3.08 ± 1.10,2.99 ± 1.00) though the difference was not statistically significant. Also, cephalometric overbite was non-significantly increased in all groups with a high increase in group-III(3.13 ± 1.10). Overjet decreased in all groups, with the greatest reduction observed in group-I(-2.58 ± 1.02 and -2.47 ± 0.80 in model and cephalometric respectively) and was significantly different from group-II using pairwise analysis. There was a decrease in SNA and ANB in all groups with more significant improvement in groups-I(-1.20 ± 0.88,-1.65 ± 0.74) and -III(-1.31 ± 0.92, -1.62 ± 0.75) than group-II(-0.63 ± 0.46, -0.90 ± 0.43). Moreover, FMA measurements decreased significantly in group-I (-2.6 ± 1.11). Regarding SNB measurement, there was a non-significant increase in all three groups with the highest increase in group-I(0.49 ± 0.48) followed by group-III(0.34 ± 0.63). The U1/FHP and L1/GoGn angles were non-significantly decreased in all tested groups with the highest decrease in group-I(-1.76 ± 1.00 and-2.54 ± 0.87 respectively).ConclusionEarly treatment of anterior open bite, along with tongue tamers' simplicity and aesthetics promoted the malocclusion correction and occlusal function restoration.Trial registrationClinicalTrials.gov, NCT05792553, “Effects of Tongue Tamers as an Early Treatment of Anterior Open Bite”, Retrospectively registered: 31/03/2023.

Impact of trypanosomiasis on male camel infertility

IntroductionBlood parasitism is a significant clinical disease that silently undermines the livestock industry, particularly affecting camels. This study aimed to assess the prevalence of Trypanosoma evansi in Arabian camels (Camelus dromedarius) and its impact on infertility by examining serum protein fractions, lipids, reproductive indices, and the expression of heat shock protein (HSP70) during breeding season.MethodsA total of 107 male post-pubertal camels, aged between 5 and 10 years, were collected randomly from slaughtering house in Assiut Governorate, Egypt.ResultsMicroscopic and serological examinations revealed that 23.4% (25/107) of the camels were infected with T. evansi. Infected camels exhibited a highly significant increase in total serum protein. The assessment of dyslipidemia, measure as binary variables for lipid profiles (cholesterol, triglycerides, HDL, and LDL), indicated a nonsignificant increase in risk of dyslipidemia in infected camels compared to healthy camels. Proteomic analysis identified four major protein fractions in the infected camels compared to healthy camels with molecular weights of 181.72, 87.59, 30.5, and 19.5 kDa using SDS electrophoresis. Testicular tissue of the infected camels showed degeneration and necrotic changes in seminiferous tubules and interstitial tissue, along with edema and congestion. There was a significant reduction in the diameter of seminiferous tubules and germinal epithelium height. A marked reduction in testosterone levels and a high expression of HSP70 in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells were observed.DiscussionConsequently, a combination of physiological and hormonal analyses may serve as a reliable indicator of Trypanosoma infection.

Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities

Macrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein Sorbs2 promotes the development of the second heart field, with its deficiency resulting in atrial septal defects (ASD). In analyzing RNA-seq data, we noted an upregulation of macrophage-related genes in Sorbs2−/− hearts. Immunostaining and lineage-tracing confirmed an increase in macrophage numbers, underscoring a macrophage response to myocardial abnormalities. Partial depletion of macrophages led to downregulation of genes involved in lipid metabolism, muscle development and organ regeneration, alongside upregulation of genes associated with DNA damage-induced senescence and cardiomyopathy. Additionally, a non-significant increase in septal defects in macrophage-depleted Sorbs2−/− hearts suggests a potential reparative function for macrophages in maintaining structural integrity. Valve formation, however, remained unaffected. Our findings suggest that embryonic macrophages might sense abnormalities in embryonic cardiomyocytes and could adaptively support cardiac structure and function development in response to myocardial abnormalities.

Impact of a new case-based payment scheme on volume distribution across public hospitals in Zhejiang, China: does ‘Same disease, same price’ matter

BackgroundWith the implementation of the hierarchical medical system (HMS) in China, Zhejiang Province introduced an innovative payment scheme called “payment method by disease types with point counting”. This scheme was initially adopted in Jinhua in July 2017, and was later integrated with the “same disease, same price” policy in Hangzhou in January 2020. This study aimed to investigate the impact of these reforms on the distribution of health service volume.MethodsData were obtained from 104 hospitals, including 12 tertiary and 14 secondary hospitals from each of four regions: Jinhua (intervention) vs. Taizhou (control), and Hangzhou (intervention) vs. Ningbo (control). A total of 3848 observation points were examined using two sets of controlled interrupted time series analyses to assess the effects of this new case-based payment, without and with “same disease, same price”, on the proportion of discharges, total medical revenue and hospitalization revenue. The Herfindahl–Hirschman Index (HHI) were analyzed to evaluate changes in market competition.ResultsFollowing the introduction of the new case-based payment without “same disease, same price”, secondary hospitals in Jinhua experienced a significant decline in the proportion of discharges (β6 = -0.1074, p = 0.047), total medical revenue (β6 = -0.0729, p = 0.026), and hospitalization revenue (β6 = -0.1062, p = 0.037) compared to those in Taizhou, while tertiary hospitals showed a non-significant increase. After incorporating “same disease, same price”, the proportion of discharges (β6 = 0.2015, p = 0.031), total medical revenue (β6 = 0.1101, p = 0.041) and hospitalization revenue (β6 = 0.1248, p = 0.032) in Hangzhou’s secondary hospitals increased compared with Ningbo’s, yet the differences in both the level and trend changes between tertiary hospitals in the two cities were not statistically significant. The HHI in Jinhua (β7 = 0.0011, p = 0.043) presented an upward trend during the pilot period of the case-based payment, while the HHI in Hangzhou (β6 = -0.0234, p = 0.021) decreased immediately after the introduction of “same disease, same price”.ConclusionThis new case-based payment scheme may worsen the disproportionate distribution of service volume across hospitals of different levels. While “same disease, same price” shows potential benefits, further evidence is needed to assess its effectiveness in promoting HMS. Policymakers should consider hospital interests in payment design and address unintended strategic behaviors.

Economics of Seed Spices in Gujarat: Analyzing Parity of Cost, Price, and Income

This study analyzes the cost, price, and income parity in three major seed spices cultivated in Gujarat by examining indices of average input prices, Farm Harvest Prices, cost of production, and gross income to evaluate the profitability and challenges faced by farmers. The secondary data on input cost, cost of production and gross income were collected for the period of eleven years from 2011-12 to 2021-22 from the reports of “The Scheme for Farm Cost Studies of Important Crops in Gujarat State” and “The Scheme for Creating a Permanent Machinery for studying Cost of Cultivation/ Production of Principal crops grown in Gujarat state, further analysis of parity indices were estimated by taking 2011-12 as base year. The results indicate that for cumin crop, input prices grew significantly, while farm harvest prices exhibited a non-significant increase. Parity indices between Farm Harvest Prices and input prices remained below 100, indicating that farm harvest prices did not cover rising input costs. However, in years like 2016-17, 2018-19, and 2021-22, the farm harvest price and gross income were favorable, indicating profitability for farmers. In fennel, input prices and production costs showed significant growth, while farm harvest prices and gross income had minimal increases. Parity indices suggested that farm harvest prices were insufficient to cover rising costs in most years, though 2012-13 and 2021-22 were favorable for farmers in terms of both price and income. Coriander, with significant growth in input prices, showed a slight increase in farm harvest prices and a decrease in production costs. Parity indices indicated that the farm harvest price consistently exceeded input prices and the cost of production, ensuring favorable profitability and encouraging investment in coriander cultivation. Overall, the findings underscore the need for policy interventions to stabilize farm harvest prices and control input cost inflation, ensuring sustained profitability for farmers growing seed spices.

Trend analysis and change point detection in precipitation time series over the Eastern Province of Rwanda during 1981–2021

This study examines trends and change points in agroclimatic variables at 56 meteorological stations’ locations and region levels in Rwanda’s Eastern Province from 1981 to 2021. We used the Mann–Kendall and Regional Kendall tests, along with Sen’s Slope and Sequential Mann–Kendall Rank Statistic tests, to analyse six key agricultural indicators: seasonal rainfall totals, number of rainy days, rainfall intensity (light, moderate, heavy), onset and cessation dates, and season duration. In the March to May (MAM) season, 39 out of 56 stations recorded a decreasing rainfall trend, with significant trends observed at eight stations in the south. Conversely, 17 stations showed increasing trends, with only one in the north being significant. Regionally, the trend was a non-significant decrease. In the September to December (SOND) season, 31 stations (one significant) experienced decreasing rainfall trends. Among the 25 stations showing increasing trends, only one was significant. The regional trend indicates a non-significant increase. Onset days showed a decreasing trend at 41 stations (12 significant) in both MAM and SOND and a significant regional trend in SOND. Season duration increased at 43 stations in MAM (five significant) and 48 stations in SOND (six significant), with the regional trend being significant only in SOND. Heavy rainy days indicate a significantly regional decreasing trend in MAM. The change point of most stations with decreasing and increasing trends occurred between 2000–2020 and 1980–2000, respectively. These fluctuations have affected agricultural practices and led to crop failures, emphasizing the region’s need for better climate information services and adaptation strategies.

The feasibility and efficacy of a psychospiritual intervention with the insights from Bhagavad Gītā and Yin Yoga on a Turkish population: A mixed method approach

ABSTRACT This pilot study examines the feasibility of a psychospiritual intervention integrating Bhagavad Gītā and Yin Yoga to reduce anxiety and enhance meaning in life and resilience among 20 Turkish women. Amidst challenges like COVID-19 and earthquakes, this novel approach, using quasi-experimental single-group mixed-methods pre-test/post-test design, aimed to assess the intervention’s adaptability and effectiveness within a cultural context unfamiliar with such methods. The online intervention used the Beck Anxiety Inventory, Meaning in Life Questionnaire, and Brief Resilience Scale and semi-structured interviews. SPSS was used for quantitative data analysis, and thematic analysis was applied to qualitative responses. Results showed a significant reduction in anxiety, with participants reporting improved coping strategies and a deeper sense of life’s meaning. While resilience scores showed only a slight, non-significant increase, qualitative feedback suggested subtle improvements in handling adversity. Additionally, the presence and search for meaning scores showed nuanced changes, with qualitative responses indicating a refined understanding of meaning in life post-intervention. This study underscores the value of mixed-methods research in psychospirituality, demonstrating the potential of integrating ancient spiritual teachings with modern psychological practices to support mental health and coping strategies in diverse cultural contexts.

Testing the Recruitment Frequency, Implementation Fidelity, and Feasibility of Outcomes of the Heart Failure Activity Coach Study (HEALTHY): Pilot Randomized Controlled Trial.

Heart failure (HF) is a common and deadly disease, precipitated by physical inactivity and sedentary behavior. Although the 1-year survival rate after the first diagnosis is high, physical inactivity and sedentary behavior are associated with increased mortality and negatively impact the health-related quality of life (HR-QoL). We tested the recruitment frequency, implementation fidelity, and feasibility of outcomes of the Activity Coach app that was developed using an existing mobile health (mHealth) tool, Optilogg, to support older adults with HF to be more physically active and less sedentary. In this pilot clinical randomized controlled trial (RCT), patients with HF who were already using Optilogg to enhance self-care behavior were recruited from 5 primary care health centers in Sweden. Participants were randomized to either have their mHealth tool updated with the Activity Coach app (intervention group) or a sham version (control group). The intervention duration was 12 weeks, and in weeks 1 and 12, the participants wore an accelerometer daily to objectively measure their physical activity. The HR-QoL was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), and subjective goal attainment was assessed using goal attainment scaling. Baseline data were collected from the participants' electronic health records (EHRs). We found 67 eligible people using the mHealth tool, of which 30 (45%) initially agreed to participate, with 20 (30%) successfully enrolled and randomized to the control and intervention groups in a ratio of 1:1. The participants' daily adherence to registering physical activity in the Activity Coach app was 69% (range 24%-97%), and their weekly adherence was 88% (range 58%-100%). The mean goal attainment score was -1.0 (SD 1.1) for the control group versus 0.6 (SD 0.6) for the intervention group (P=.001). The mean change in the overall HR-QoL summary score was -9 (SD 10) for the control group versus 3 (SD 13) in the intervention group (P=.027). There was a significant difference in the physical limitation scores between the control (mean 45, SD 27) and intervention (mean 71, SD 20) groups (P=.04). The average length of sedentary bouts increased by 27 minutes to 458 (SD 84) in the control group minutes and decreased by 0.70 minutes to 391 (SD 117) in the intervention group (P=.22). There was a nonsignificant increase in the mean light physical activity (LPA): 146 (SD 46) versus 207 (SD 80) minutes in the control and intervention groups, respectively (P=.07). The recruitment rate was lower than anticipated. An active recruitment process is advised if a future efficacy study is to be conducted. Adherence to the Activity Coach app was high, and it may be able to support older adults with HF in being physically active. ClinicalTrials.gov NCT05235763; https://clinicaltrials.gov/study/NCT05235763.

Morbid obesity among Crohn's disease patients is on the rise and is associated with a higher rate of surgical complications after ileocolic resection.

Crohn's disease (CD) is regarded as a wasting disease, yet there is a growing population of CD patients with a body mass index (BMI) of 35 and above. The rate of postoperative complications is relatively high in CD patients but might be even higher in CD with morbid obesity (MO). This was a retrospective study using a prospectively maintained database of all patients undergoing Ileocolic resection for CD between 2014 and 2021 in two referral centres, comparing postoperative complication rates according to BMI. Three hundred and forty-six patients were identified. Sixty patients (17%) had a BMI over 30 kg/m2, and 28 (8.1%) had a BMI of over 35 kg/m2 (>35 group). The BMI >35 group had more women (78.6% vs. 52%, P < 0.1), a higher rate of patients not receiving an anastomosis (7.1% vs. 2.5%, P = 0.02), a higher rate of any postoperative surgical complication (32.1% vs. 25.2%, P = 0.4), with a higher rate of Clavien-Dindo ≥3 (14.3% vs. 7.2%, P = 0.25), a higher rate of stoma creation on reoperation for complications (7.2% vs. 1.7%, P = 0.04), a higher rate of 30-day readmission due to intra-abdominal abscess (10.7% vs. 4.7%, P = 0.2), but a lower rate of postoperative medical complications (3.6% vs. 15.7%, P < 0.01). The rate of MO among CD patients requiring ileocolonic resection is on the rise. MO in this setting is associated with statistically non-significant increases in all surgical complications, severe complications, readmission, and a higher chance for a bailout stoma creation upon reoperation. However, MO seems to be a protective factor for medical postoperative complications, which might suggest better nutritional status.

Evaluation of corneal epithelial changes after corneal collagen cross-linking by using anterior segment optical coherence tomography

Background The thickness of the corneal epithelium can be precisely measured using anterior segment optical coherence tomography (AS-OCT). Aim This study aimed to conduct an AS-OCT evaluation of changes in the corneal epithelial thickness following collagen cross-linking (CXL). Patient and methods This prospective interventional study utilized 23 eyes from 13 cases who underwent treatment for progressive keratoconus (KC) with epi-off corneal CXL according to the Dresden’s Protocol. Results After 6 months postoperative the central minimum epithelial thickness (0.0–2.0 mm) showed a statistically significant increase, while the mid-peripheral (5.0–7.0 mm) showed a statistically significant decrease compared with the preoperative level. The central average epithelial thickness (0.0–2.0 mm) showed statistically nonsignificant increase, while the mid-peripheral and peripheral (5.0–7.0, 7.0–9.0 mm) showed a statistically significant decrease in comparison to the level before the operation. At 6 months postoperative, a decrease in Mean k was associated with statistically significant elevation in average central and paracentral epithelial thickness (0.0–2.0, 2.0–5.0 mm) as compared with the preoperative level (negative correlation). At 6 months postoperative, reduction in thinnest pachymetry was associated with statistically significant increase in central and paracentral average epithelial thickness (0.0–2.0, 2.0–5.0 mm) (negative correlation) as compared with the preoperative and 3 months postoperative. Conclusions With AS-OCT, it is simple to track changes in the epithelium over time. Epithelial remodeling occurs after CXL in the areas of protrusion and thinning. The thickness of the epithelium is greatest at the cone’s base and diminishes as one moves away from it.