Post Treatment Research Articles

Th17 and T Regulatory Cytokines in Serum, Lesional Skin, and Stimulated Peripheral Blood Mononuclear Cell Culture Supernatants from Type 1 Leprosy Reaction Patients

There are conflicting reports regarding the roles of T helper-17 (Th17) and T regulatory (Treg) cells in type 1 leprosy reactions (T1Rs). Also, literature on the correlation of immunological parameters with a validated scoring system and the effect of treatment on cytokines is lacking. Adult patients with untreated T1R and nonreactional spectrum–matched controls were included in the study for comparison of levels of Th17 and Treg pathway cytokines in serum, skin lesions (reactional), and peripheral blood mononuclear cells (PBMCs) culture supernatants. Venous blood samples were collected at baseline and after resolution of reaction (post treatment with nonsteroidal anti-inflammatory drugs [NSAIDs] or steroids) for serum cytokine estimation and PBMC stimulation assays, and lesional (reactional) skin biopsy for cytokine messenger RNA (mRNA) estimation. Thirty-two cases of T1R were recruited (23 patients completed follow-up). Serum levels of cytokines were not significantly different between cases and controls or between pre- and post-treatment samples. Tissue mRNA and Mycobacterium leprae (M. leprae) antigen–stimulated PBMC culture supernatant levels of Interleukin (IL)-17A, IL-17F, IL-6, and IL-23 were significantly higher in T1R than in controls. Levels of IL-10 and Transforming Growth Factor-beta (TGF-β) were comparable among the two groups. The levels of all cytokines were significantly reduced after treatment. There was no significant difference in magnitude of the fall between those treated with steroids versus NSAIDs. This study suggests heightened Th17 response in T1R, with a prominent inability of the regulatory cytokines IL-10 and TGF-β to control the associated inflammation. The dynamics of change after resolution of T1R were comparable between NSAID and oral steroid treatment groups.

The effect of 6-month treatment with coenzyme Q10 on endothelial, vascular and myocardial function in patients with nonalcoholic fatty liver disease

Abstract Background Patients with Non-alcoholic fatty liver disease (NAFLD) hold an increased cardiovascular risk and present impaired markers of vascular, endothelial and myocardial function. Coenzyme Q10 (CQ10) is a powerful antioxidant that enhances mitochondrial function. Patients/methods: 52 patients (52±10 years old) with NAFLD were randomized to 240 mg CQ10 (n=25) or placebo (n=27). We measured at baseline and at six months post-treatment: i) Perfused boundary Region (PBR) of the sublingual arterial microvessels (Microscan, Glycocheck), ii) Carotid femoral pulse wave velocity - PWV (Complior ALAM), iii) Flow-mediated dilation (FMD) of the brachial artery, iv) Global left ventricular longitudinal strain (GLS) by speckle tracking imaging, v) Controlled attenuation parameter (CAP) measurement (FibroScan, Echosens). Results Six months post treatment with cQ10, values of PBR (2.12±0.19 vs. 2.28±0.23 μm), PWV (9.5±2.3 vs. 10.5±2.4m/s), CAP score (278.1±50, 2 vs. 305.3±44.5dB/m), FMD (6.61±4 vs. 5.02±2.6 %) and GLS (-19.3±1.9 vs -18.2±2 %) were improved (p<0.05 for all comparisons). On the contrary, the patients who were treated with placebo did not show statistically significant differences in PBR, PWV, CAP score, FMD and GLS after from 6 months (p>0.05). In the patients who received cQ10, the percentage reduction of CAP score at 6 months was directly proportional to the percent reduction in PWV (r=0.31, p=0.045) and inversely proportional to the percentage increase in FMD (r=-0.58, p=0.014). Conclusion Six-month treatment with CoQ10 reduces liver steatosis in patients with NAFLD. CoQ10 is associated with improved endothelial, vascular and LV myocardial function in patients with NAFLD.

Efficacy and safety of ambulatory, weekly, high-intensity intravenous diuretic strategy for congestion-refractory heart failure patients: insights from the DEA-HF prospective randomized clinical trial

Abstract Background Congestion and volume overload are strongly associated with low quality of life and pose a significant risk for both rehospitalization and mortality in heart failure (HF) patients. Despite the widespread use of diuretics in HF, the use of weekly, intravenous (IV), high-intensity diuretic treatment has not been prospectively studied in the setting of ambulatory congestion-refractory patients. Purpose To assess the efficacy and safety of weekly high-intensity diuresis regimens in a practical setting of ambulatory day care for chronically congested HF patients. Methods We performed a sub-analysis on data from a prospective, randomized, cross-over controlled study (DEA-HF) originally designed to compare diuresis regimens in the setting of an HF ambulatory daycare unit who had signs of congestion or volume overload despite adherence to guideline-directed medical therapy. Each patient received three different IV diuretic regimens, in one of six randomized sequences: IV furosemide 250mg; IV furosemide 250mg + oral metolazone 5mg; and IV furosemide 250mg + IV acetazolamide 500mg. All regimens given on the same chronological week were pooled, and diuresis efficacy was assessed by measuring excreted urine volume and sodium weight 6 hours post treatment initiation. Additional assessment at one week post each treatment included serum levels of NT-ProBNP, body weight and creatinine as well as congestion score based on the presence of ascites, pleural effusion and pedal edema. Statistical analysis was based on linear mixed models while accounting for the random effect of patient identity. Results A total of 42 patients were recruited. The mean age was 72±9 years, twenty-one subjects (50%) had LVEF ≥ 50%. 74% of patients were NYHA III class. All patients were on contemporary guidelines-directed HF therapy. Analysis of excreted sodium weight and urine volume revealed values of 4202.1±180.1 mg (Mean±SEM) and 1.77±0.07 liter per visit, respectively. No significant differences in efficacy were detected among treatments given in consecutive weeks (P= 0.80 and 0.69 for differences in sodium weight and urine volume, respectively). After 4 weeks, log(NT-ProBNP) was significantly decreased (P=0.044), accompanied by a significant decrease of 2.4±0.62 kg in body weight (P=0.0004) and of 0.92±0.44 points in congestion score (P=0.037). Serum creatinine level was only slightly increased by 0.19±0.04 mg/dl (P=0.0001), demonstrating the overall safety of the high-intensity diuresis strategy. Conclusions In ambulatory, congestion refractory HF patients a strategy based on high-intensity, weekly diuresis therapy was safe and effective for three consecutive weeks. The natriuresis response to the treatments was maintained, NT-ProBNP levels and congestion score were decreased. The strategy may be instrumental for ambulatory HF patients that require diuretic therapy intensification and may allow to prevent hospitalization.

Effect of antiretroviral treatment on myocardial work and arterial function of treatment-naive patients with HIV

Abstract Background/Aim HIV infection is related with cardiovascular adverse events. We investigated the effects of antiretroviral treatment in myocardial and vascular function of newly diagnosed patients with HIV. Patients and methods A total of 70 newly diagnosed HIV patients (41.2±8.7 years old, 87 % male) were enrolled. Patients were randomized to the newer integrase inhibitor Dolutegravir or to the older protease inhibitor Darunavir/Cobicistat. We measured at baseline and 12 months posttreatment: (a) Left Ventricular (LV) Global Longitudinal Strain (GLS), (b) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE), (c) Coronary Flow Reserve (CFR) of Left Anterior Descending Artery. At baseline, we compared the HIV patients with 35 healthy matched controls. Results At baseline patients with HIV had impaired myocardial function, endothelial function and endothelial glycocalyx compared with healthy controls. Twelve months after intervention HIV patients improved myocardial function, as assessed by GLS, GWI, GCW, GWW and GWE (p<0.05). Moreover, twelve months after intervention HIV patients improved endothelial function, as evaluated by an increase in CFR and a decrease in PBR5-25 (p<0.05). Response to therapy was similar between the two groups of treatment. Nevertheless, in HIV patients 12 months post treatment myocardial, endothelial function and endothelial glycocaylyx was impaired in comparison with healthy controls. Conclusions Treatment with antiretroviral therapy partially improves myocardial and arterial function 12 months post treatment.

Aerobic exercise capacity improvement of patients with human immunodeficiency virus one year post-treatment initiation by integrase inhibitors

Abstract Background Infection by Human Immunodeficiency Virus (HIV) leads to chronic inflammation and subsequently to the early development of cardiovascular (CV) disease in young adults. Initiation of antiretroviral therapy (ART) usually leads to patient’s body weight and blood pressure increase. Cardiopulmonary exercise test (CPET) evaluates aerobic exercise capacity and subsequently cardiovascular and respiratory function. Aim of this study is the investigation of any treatment-induced changes in aerobic exercise capacity in treatment naïve young HIV patients’ at 1-year post HIV treatment initiation by different ART agents. Methods We studied 46 recently diagnosed and treatment naïve young HIV patients (37+10 years, 87% males, 62% smokers) at baseline and 1-year post ART initiation (integrase or protease inhibitors). Twenty-six (26) patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age=36+9 years, 100% males, 77% smokers) while 19 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age=37+10 years, 90% males, 47% smokers). All patients were submitted in CPET at baseline and 1-year post ART initiation. We estimated any changes in body mass index (BMI), systolic blood pressure (SBP) and CPET parameters (peak VO2, Oxygen pulse, WorkLoad, VE/VCO2) at 1-year post ART initiation. Results At baseline and 1-year re-evaluation, we found no differences between groups regarding age, BMI and CPET parameters. In the whole HIV population, we found an increase in body weight (76+12 vs. 82+15kg, p<0.001), SΒΡ (124+12 vs. 132+14mmHg, p<0.001), WorkLoad (176+35 vs. 186+35watt, p<0.001) and peak VO2 (2171+437 vs. 2299+491ml/min, p=0.03) at 1-year re-evaluation. In Group A, body weight (p<0.001), SBP (p=0.07), WorkLoad (p=0.006) and peak VO2 (p=0.01) were increased while in Group B, body weight (p<0.001), SBP (p=0.001) και WorkLoad (p=0.01) were also increased. Conclusions Aerobic exercise capacity is improved 1-year post-treatment initiation by the newer integrase inhibitor Dolutegravir in treatment-naïve HIV patients despite the adverse BMI and SBP increase. The newer Dolutegravir probably exhibits a more favorable CV profile in HIV patients compared to the older Darunavir/Cobicistat.Re-evaluation 1-year post ART initiation

Comparing the real-world and clinical trial bleeding rates associated with oral anticoagulation treatment for atrial fibrillation

Abstract Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOAC). However, it comes with an increased risk of bleeding and therefore, counselling patients on their individual risk is important. Although majority of patients initiated on DOAC have been represented within the clinical trials, there are some cohorts which are under-represented in whom clinicians are unable to practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, 5 recent open-label industry sponsored AF trials were compared with Real-World data (RWD) was sourced from the HealthVerity Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs 65.3 ±10.7 years old, p<0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs 2.87 ± 1.73, p<0.001) and HAD-BLED scores (2.13 ± 1.02 vs 1/04 ± 0.93, p<0.001) when compared to the trial data. When comparing the incidence of first major bleed at 12 months post treatment initiation, rates in the RWD cohort was significantly higher (10.69 vs 18.97 per 100 person-years). The impact of comorbidities such as age, CHA2DS2VASc and HAD-BLED scores were similar in both cohorts, however, there was an under-representation of older, females and more co-morbid patients within the clinical trial cohort. Conclusion DOAC treated patients have higher bleeding incidence rate in the RWD cohort as compared to clinical trials. This can be explained by the older patient age group with more complex medical histories and higher HAS-BLED scores. The under-representation of higher risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real world clinical practice.

Interferon as an immunoadjuvant to enhance antibodies following influenza B infection and vaccination in ferrets

Despite annual vaccination, influenza B viruses (IBV) continue to cause significant morbidity and mortality in humans. We have found that IBV infection resulted in a weaker innate and adaptive immune response than influenza A viruses (IAV) in ferrets. To understand and overcome the weak immune responses to IBV in ferrets, we administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination and evaluated their effects on the immune response. IFN signaling following viral infection plays an important role in the initial innate immune response and affects subsequent adaptive immune responses. In the respiratory tract, IFN lambda (IFNL) has regulatory effects on adaptive immunity indirectly through thymic stromal lymphopoietin (TSLP), which then acts on immune cells to stimulate the adaptive response. Following IBV infection or vaccination, IFN treatment (IFN-Tx) upregulated gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained following challenge or vaccination in IFN-Tx animals. Serum IFNL and TSLP levels were enhanced in IFN-Tx animals following challenge/rechallenge over mock-Tx; however, this difference was not observed following vaccination. Antibody responses in serum of IFN-Tx animals following IBV infection or vaccination increased more quickly and to higher titers and were sustained longer than mock-Tx animals over 3 months. Following rechallenge of infected animals 3 months post treatment, antibody levels remained higher than mock-Tx. However, IFN-Tx did not have an effect on antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses following challenge-rechallenge and vaccination-challenge indicating it as a useful tool for predicting adaptive immune responses following IBV infection or vaccination. The effects of IFN on strengthening both innate and adaptive responses to IBV may aid in development of more effective treatments following infection and improved influenza vaccines.

Cognitive processing biases of social anxiety in adults who do and do not stutter

PurposeAdults who stutter are at risk of developing high levels of social anxiety, leading to negative outcomes and contributing towards stuttering relapse post treatment. To ensure that psychological treatments for social anxiety in stuttering adults are relevant and effective, a broader empirical understanding of the mechanisms of social anxiety in stuttering populations is required. Four key cognitive processing biases identified as maintenance factors in cognitive behavioral models of social anxiety were examined: self-focused attention, safety behavior use, negative self-imagery, and interpretation bias. MethodsAdults who stutter and non-stuttering adults (N = 186) were assessed via an online survey. Participants were categorised into two groups based on stuttering: formally diagnosed stuttering and non-stuttering. Within those groups, participants were further categorised as having low or high levels of social anxiety. Cognitive processing bias was assessed in response to two hypothetical social scenarios (i.e., social interaction and social performance). ResultsAs predicted, in both adults who stutter and who are non-stuttering, high social anxiety was related to greater self-focused attention, safety behavior use and negative self-imagery compared to low social anxiety. No significant effect of social anxiety or stuttering was found in relation to interpretation bias. A significant effect of social anxiety upon negative self-imagery was observed in formally-diagnosed adults who stutter compared to non-stuttering adults. ConclusionThe results support the use of cognitive behavioral models of social anxiety as a framework for research and treatment development within stuttering populations.

A Preliminary Study on Structural and Optical Properties of Heat Treated Nb2O5 Nanostructure

Annealing is a heat treatment that alters the physical and sometimes chemical properties of a material to improve their crystalline structure and other important properties. This work presents the effect of post heat treatment on optical, structural, morphological, and surface roughness of Nb2O5 thin films at different temperatures (200-700oC) which to the best of our knowledge not been extensively studied yet. A clear modification in surface morphology and other studied properties was obtained. XRD results show a significant enhancement in the film’s structural properties such as a reduction in the dislocation densities and stress. The optical properties of the treated films show a clear decrease in the transmission and energy gap values which their values were found to reduce from (4.35 to 2.9) eV with heat treatment up to 600oC and re-increase at 700oC. The surface roughness was also enhanced as a result of increasing the grain size from (9.95 – 34.7) nm Finally, SEM images of the films show an obvious change in their morphology and an increase in film uniformity as a result of heat treatment. Therefore, heat treatment could be considered as a helpful method to control film characteristics. Main result should be presented quantitatively.

Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?

Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission. Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 (ccr5Δ32), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response. Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.

Comparative Bio Assay of New Generation Insecticides against Invasive Southeast Asian Thrips, Thrips parvispinus (Karny) (Thripidae:Thysanoptera)

Aims: Management of invasive southeast Asian thrips, Thrips parvispinus under laboratory conditions. Study Design: Completely Randomized Design. Place and Duration of Study: Regional Agricultural Research Station, Guntur, Andhra Pradesh during 2023. Methodology: Bio assays study was conducted with eleven insecticides for the Management of Thrips parvispinus under laboratory conditions following leaf dip method replicated thrice. Mortality and corrected mortality were assessed at 24 and 48 hours after treatment imposition by counting the number of dead and live adults. Results: Bio assay study revealed that the insecticide broflanilide 300 DC @ 64.0 ml/ha recorded significant high percent mortality of 93.3 at 48 hours after exposure. The insecticides fluxametamide 10 EC @ 400 ml/ha, tolfenpyrad 15 EC@ 1000 ml/ha, spinoterom 11.7 SC @ 500 ml/ ha and fipronil 5 SC @1000 ml/ha were at par with broflanilide 300 DC with 90.0, 90.0, 86.7 and 86.7 percent mortality, respectively. Lowest mortality of 6.0 percent was observed in untreated control where the leaves were agitated in distilled water. The corrected mortality was calculated and the insecticides broflanilide 300 DC (92.59 %), fluxametamide 10 EC (88.9), tolfenpyrad 15 EC (89.3), spinetoram 11.7 SC (85.9) and fipronil 5 SC @400 ml/acre (85.2) recorded high corrected mortality at 48 hours of post treatment.

Role of artificial intelligence in staging and assessing of treatment response in MASH patients.

The risk of disease progression in MASH increases proportionally to the pathological stage of fibrosis. This latter is evaluated through a semi-quantitative process, which has limited sensitivity in reflecting changes in disease or response to treatment. This study aims to test the clinical impact of Artificial Intelligence (AI) in characterizing liver fibrosis in MASH patients. The study included 60 patients with clinical pathological diagnosis of MASH. Among these, 17 received a medical treatment and underwent a post-treatment biopsy. For each biopsy (n = 77) a Sirius Red digital slide (SR-WSI) was obtained. AI extracts >30 features from SR-WSI, including estimated collagen area (ECA) and entropy of collagen (EnC). AI highlighted that different histopathological stages are associated with progressive and significant increase of ECA (F2: 2.6% ± 0.4; F3: 5.7% ± 0.4; F4: 10.9% ± 0.8; p: 0.0001) and EnC (F2: 0.96 ± 0.05; F3: 1.24 ± 0.06; F4: 1.80 ± 0.11, p: 0.0001); disclosed the heterogeneity of fibrosis among pathological homogenous cases; revealed post treatment fibrosis modification in 76% of the cases (vs 56% detected by histopathology). AI characterizes the fibrosis process by its true, continuous, and non-categorical nature, thus allowing for better identification of the response to anti-MASH treatment.

Precise Construction of the Triple-Phase Boundary and Its Antiphosphate Poisoning Effect in the Confined Region.

As a critical component for the oxygen reduction reaction (ORR), platinum (Pt) catalysts exhibit promising catalytic performance in High-temperature-proton exchange membrane fuel cells (HT-PEMFCs). Despite their success, HT-PEMFCs primarily utilize phosphoric acid-doped polybenzimidazole (PA-PBI) as the proton exchange membrane, and the phosphoric acid within the PBI matrix tends to leach onto the Pt-based layers, easily causing toxicity. Herein, we first propose UiO-66@Pt3Co1-T composites with precisely engineered interfacial structures. The UiO-66@Pt3Co1-T exhibits an octahedral porous framework with uniform structural dimensions and even distribution of surface nanoparticles, which demonstrate superior ORR performance compared to commercial Pt/C. The unique structure and morphology of the composites also exhibit a favorable half-wave potential in different concentrations of phosphoric acid electrolyte, regulated by the phosphoric acid adsorption site and intensity.This finding suggests that the incorporation of Co could effectively modulate the Pt d-band center, thereby enhancing the ORR performance. Furthermore, the selective adsorption of phosphoric acid by ZrO2 enables precise control over the phosphoric acid distribution. Notably, the retention of the octahedral framework post high-temperature treatment facilitates the establishment of dual transport pathways for gases and protons, leading to a stable and efficient triple-phase boundary.

Biologically informed deep neural networks provide quantitative assessment of intratumoral heterogeneity in post treatment glioblastoma.

Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p < 2e-26). In cross-validation, BioNet achieved AUCs of 0.80 (Pro) and 0.81 (Inf), with accuracies of 80% and 75%, respectively. In blind tests, BioNet achieved AUCs of 0.80 (Pro) and 0.76 (Inf), with accuracies of 81% and 74%. Competing methods had AUCs lower or around 0.6 and accuracies lower or around 70%. BioNet's voxel-level prediction maps reveal intratumoral heterogeneity, potentially improving biopsy targeting and treatment evaluation. This non-invasive approach facilitates regular monitoring and timely therapeutic adjustments, highlighting the role of ML in precision medicine.

Exogenously Applied Gibberellic Acid Alters Cannabinoid Profile in Cannabis sativa L.

Cannabis sativa (C. sativa L.) has garnered significant attention worldwide due to its widespread use as a pharmaceutical agent. With the increasing clinical application of C. sativa and cannabinoid therapeutics, there is strong interest in the development of superior plant varieties and optimisation of growth conditions to enhance secondary metabolite yield. Our RNA sequencing analysis revealed differential expression of hormone-related transcripts in developing C. sativa trichomes, suggesting the involvement of hormone signalling pathways in cannabinoid production. Leveraging the potency of exogenous hormones on plants, this study sought to determine if the application of cytokinin (CK), gibberellic acid (GA) and jasmonic acid (JA) modified trichome morphology and the cannabinoid profile over an 8-week period following the induction of flowering. Exogenous hormone application led to alterations in trichome morphology, with each treatment significantly reducing trichome head width by the final week of assessment. Interestingly, GA application also resulted in a significant reduction in the concentration of Δ-9-tetrahydrocannabinol (THC), Δ-9-tetrahydrocannabinolic acid (THCA), cannabidiol (CBD) and cannabidiolic acid (CBDA) by week 8 post floral induction, however, JA and CK treatment did not consistently modulate the accumulation of these cannabinoids. The minor cannabinoids, cannabidivaranic acid (CBDVA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabichromene (CBC), cannabigerolic acid (CBGA) and cannabigerol (CBG), were also affected by hormone treatments, with varying degrees of accumulation observed. These findings underscore the intricate interplay between phytohormones and secondary metabolite biosynthesis in C. sativa. Our study highlights the potential of hormone modulation as a strategy to enhance cannabinoid yield and offers some insights into the regulatory mechanisms governing cannabinoid biosynthesis in C. sativa trichomes.

Introduction of the distribution of Cs in Cu(In,Ga)Se2 photovoltaic absorbers following post-deposition treatment with CsF

In recent years, the device performance of Cu(In,Ga)Se2 (CIGS) solar cells has been improved by heavy alkali element post-deposition treatment (Alkali-PDT). Therefore, it is of great significance to study the mechanism of enhancing CIGS device performance through Alkali-PDT. One aspect to be studied is the distribution of heavy alkali elements in the absorber. In this work, the distribution of the heavy alkali element Cs in the absorber after post deposition treatment of CsF (CsF-PDT) and its effect on the device performance are investigated. The experimental results indicate that Cs can enter both the grain interior (GI) and grain boundaries (GB) via the Cu vacancy (VCu). By comparing the distribution of Na and Cs in the film, it can be noticed that Na is mainly distributed at the GB, while Cs is not differently distributed between the GB and GI. This is mainly due to the fact that the presence of Na at GB inhibits the accumulation of Cs there. The distribution of Cs is beneficial in improving the device’s performance by passivating defects, such as InCu.

Comparative Efficacy of Biodentine® and Calcium Hydroxide in Pulp Capping Treatment

Background: This study is focused on — Assessing Biodentine and Calcium hydroxide in indirect pulp capping procedures. Various materials have been used in indirect pulp capping but this comparative study may help appreciate which material produces better results: Biodentine or Calcium hydroxide. Objective: To compare treatment outcomes post indirect pulp capping treatment using Biodentine® and Calcium hydroxide (Ca(OH)2) . Materials and Methods: A blinded, randomized clinical control trial involving 50 consenting subjects, comparing Biodentine® (test) and Ca(OH)2 (control). Cavity preparation was done and the cavity was dressed with either Biodentine® or Ca(OH)2 and then restored with Glass ionomer cement. The subjects’ teeth were later examined clinically and radiographically at 3, 6, and 9 months post treatment. The indicators of clinical success were absence of pain, swellings, sinus, fistula, abscess, mobility, tenderness to percussion, normal response to electric pulp tester, and Endo-ice cold test. The indicator of radiographic success was absence of periapical pathosis. The probability level of p&lt;0.05 was considered significant. Results: The success rate at three months was 100% for both groups; at six months, it was 92% for both groups and at nine months, 92% of subjects were successful in the Biodentine® group while the Ca(OH)2 group recorded 88% which was statistically insignificant (P=0.74). Conclusion: Biodentine® and Calcium hydroxide have shown comparable effectiveness in improving treatment outcomes, thus, contributing to the longevity of the teeth, and the period of optimum efficaciousness of the pulp capping materials in this study was three months.

AN ANALYSIS OF THE PATIENT REPORT OUTCOMES OF A JOINT CNS / AHP NEURO-ONCOLOGY CLINIC ON PATIENTS QUALITY OF LIFE

Abstract AIMS Velindre Cancer Centre established a successful model of collaborative working between CNS and AHP services for neuro-oncology patients to holistically support their complex needs throughout treatment. Building on this success, the clinic has introduced a recognised reliable and valid patient reported outcome measure (PROM) to be completed pre and post clinic intervention. This is in addition to the patient reported experience measure that is already established within the pathway. This PROM will enable an analysis of the clinics impact on patients quality of life. METHOD A quantitative methodology will be utilised to enable a objective evaluation of the impact of the clinic on patients quality of life. An EQ-5D-5L PROM is completed with patients prior to their involvement with the clinic enabling an overview of key aspects related to quality of life including mobility, self-care, participation in usual activities, pain and anxiety / depression. Following interventions within the clinic, patient are provided with a post treatment EQ-5D-5L to enable a comparison of these key indicators of quality of life. RESULTS The data will build on the resounding success of collaborative working between CNS and AHP’s in the neurooncology MDT clinic. An analysis of the pre and post data will demonstrate the impact of having access to this unique and integrated way of working, enabling patient access to specialist timely support throughout their treatment. CONCLUSION This innovative model of working is now established in the patient pathway and findings from patient experience measures have recognised that patients experience of the clinic is extremely highly valued. Findings from this additional dataset will further evidence the impact on patients quality of life. It will add to findings from a proposed gap analysis to evidence the benefits of developing an outreach service for this patient cohort.

Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is more than an insulin-deficiency disease-it is an autoimmune disease, and the field is moving towards adopting disease-modifying immunotherapy as part of clinical care during T1D development. Recent successful immunotherapies as well as therapies that missed the mark are reviewed. T cell-directed therapies may allow for the greatest preservation of β cell function but also come with more side effects. Anti-cytokine therapies are very promising but likely need chronic administration. Antigen-specific therapies while safe have not produced meaningful results. Most successful trials have been conducted in adolescents and adults with stage 3 T1D (clinical T1D) with preserved C-peptide (up to 60% more compared to placebo) demonstrated 1-2 years post treatment. HbA1c and total insulin dose are less likely to be significantly different between treated and placebo groups because most participants in studies are meeting glycemic targets and because of the heterogeneous nature of these measures. In the prevention space (delaying progression from stage 2 to stage 3 T1D) the outcome is more discrete, and a T cell-directed therapy, teplizumab, has received FDA approval. Even negative studies with promising mechanistic and safety profiles have added value. What is clear, a single administration or short course of an immunotherapy is unlikely to provide sustained freedom from exogenous insulin.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide

Background: Non-arteritic anterior ischemic optic neuropathy is the most common acute optic neuropathy in patients older than 50 years. Risk factors for NAION are structural crowding of disc, diabetes, systemic hypertension, hyperlipidaemia, smoking. Patients present with sudden monocular vision loss, dyschromatopsia, visual field defect, disc edema diffuse or segmental. Objectives: To evaluate risk of non arteritic anterior ischemic optic neuropathy after routine treatment. Method: This Longitudinal observational study was carried out from January 2016 to June 2016 at Department of Neuro-Ophthalmology, National Institute of Ophthalmology &amp; Hospital, Sher -E-Bangla Nagar, Dhaka among Sixty cases. Detailed information were obtained in each cases according to protocol. A complete history was taken from the patient. Relevant investigation reports were collected. Selected patients were undergone detailed ophthalmological and systemic evaluation. They were treated at NIO&amp;H with following measure like proper counseling, controlling of risk factors like diabetes, hypertension, hyperlipidaemia and were advised to take tablet vitamin B1, B6 &amp; B12. They were followed up at 1st week, 4th week &amp; 8th week. In each visit visual acuity, color vision, field of vision, RAPD &amp; optic disc changes were recorded in a pre- designed data collection sheet. All the information’s were recorded according to fixed protocol. Results: Among the 60 cases, mean age was 55.67 (±4.89) years, minimum age was 51 and maximum age 69 years. Majority 32(53.3%) were male and 28(46.67%) were female. Associated risk factor like diabetes, hypertension, hyperlipidaemia and sleep apnea which were 53.3%, 36.67%, 30% and 13.3% respectively. Different disc changes of the study population were segmental disc swelling 36(60%) and diffuse disc swelling 24(40%) respectively. Regarding distant visual acuity patients were grouped into 6/6 to 6/12 group, 6/18-6/36 group, 6/60- 1/60 group and counting finger to hand movement group. At presentation most of the patient belongs to 6/6- 6/12 group which was 26(43.33%) followed by 6/18-6/36 group, it was 18(30%), 10(16.67%) were included in (6/60-1/60) group and the rest 06(10%) were included in counting finger to hand movement group. At final visit on 8th week 20(35.7%) patients remain in 6/6-6/12 group and also 6/18-6/36 group includes 20(35.7%) patients, 10(16.67%) were included in (6/60-1/60) group and the rest 06(10%) were included in counting finger to hand movement group. RAPD present in pretreatment 52(86.7%) and in post treatment were 46(82.14%). (p&gt;0.05) that was not statistically significant. Color vision dyschromatopsia in pretreatment 46(76.7%) and in post treatment were 37(60%). In post treatment 06(10.71%) were normal color vision. (p&lt;0.5) that was statistically significant. ocular involvement 52(86.67%) were 1st eye and 08(13.3%) were 2nd eye. Comparison of pre-treatment and post treatment visual field were Arcuate scotoma 12(20%) vs 09(16.07%), Inferior Altitudinal field defect 32(53.33%) vs 31(57.14%), Superior Altitudinal field defect 02(3.3%) vs 02(3.57%) respectively. Conclusion: In study no significant change found on visual acuity, colour vision and field of vision after treatment of non-arteritic anterior ischemic optic neuropathy.