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Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration., (© 2024. The Author(s).)

The knowledge of pollen morphology, suitable storage condition, and species compatibility is vital for a successful grapevine improvement programme. Ten grape genotypes from three different species, viz. , Vitis vinifera L., Vitis parviflora Roxb., and Vitis champini Planc., were studied for their pollen structure and pollen storage with the objective of determining their utilization in grape rootstock improvement programs. Pollen morphology was examined through the use of a scanning electron microscope (SEM). The viability of the pollen was assessed using 2,3,5-triphenyltetrazolium chloride (TTC). In vitro pollen germination was investigated using the semi-solid medium with 10 % sucrose, 100 mg/L boric acid, and 300 mg/L calcium nitrate. The results revealed variations in pollen micro-morphology in 10 genotypes, with distinct pollen dimensions, shapes, and exine ornamentation. However, species-wise, no clear difference was found for these parameters. Pollen of V. parviflora Roxb. and Dogridge was acolporated and did not germinate. The remaining eight genotypes exhibited tricolporated pollen and showed satisfactory in vitro pollen germination. Storage temperature and duration interactions showed that, at room temperature, pollen of most of the grape genotypes can be stored for up to 1 day only with an acceptable pollen germination rate (>30 %). However, storage for up to 7 days was successfully achieved at 4 °C, except for 'Pearl of Csaba'. The most effective storage conditions were found to be at -20 °C and -196 °C (in liquid N 2 ), enabling pollen storage for a period of up to 30 days, and can be used for pollination to overcome the challenge of asynchronous flowering. Four interspecific combinations were studied for their compatibility, among which V. parviflora Roxb. × V. vinifera L. (Pusa Navrang) and V. parviflora Roxb. × V. champini Planc. (Salt Creek) showed high cross-compatibility, offering their potential use for grape rootstock breeding. However, V. parviflora Roxb. × V. vinifera L. (Male Hybrid) recorded the lowest compatibility index among studied crosses. In the case of self-pollinated flowers from V. parviflora Roxb. and V. parviflora Roxb. × V. champini Planc. (Dogridge), pollen failed to germinate on the stigma due to male sterility caused by acolporated pollen. As a result, the flowers of these genotypes functioned as females, which means they are ideal female parents for grape breeding without the need for the tedious process of emasculation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rane, Thakre, Verma, Kumar, Prakash, Srivastava, P. R., Murukan, Chawla, Mandal, Kumar, Jadhav, Varghese, Patel and Singh.)

Many premedication agents with opioid-sparing properties have been used in patients undergoing various elective surgeries. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used by many researchers as an opioid-sparing strategy. Various databases like PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched after registering the review protocol in PROSPERO for randomized-controlled trials (RCTs) that investigated the efficacy and safety of memantine premedication in adult patients undergoing various elective surgeries. The risk of bias (RoB-2) scale was used to assess the quality of evidence. From the 225 articles that were identified after a database search, 3 studies were included for a qualitative systematic review and a quantitative meta-analysis. The pooled analysis revealed that the use of memantine provided better pain scores at 2nd (mean difference: -0.82, 95% CI: -1.60, -0.05, P = 0.04) with significant heterogeneity ( P = 0.06; I² =71%), and 6 hours postoperatively (mean difference: -1.80, 95% CI: -2.23, -1.37, P < 0.00001), but not at 1 hour. The sedation scores at 1 hour were higher in the memantine group but comparable in the 2nd hour. The number of doses of rescue analgesia and nausea/vomiting in the postoperative period was comparable in both groups. The results of this review suggest that memantine premedication could provide better pain scores in the immediate postoperative period with acceptable adverse effects. However, the current evidence is insufficient to suggest the routine use of memantine as a premedication before elective surgeries., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Anesthesia.)

Background and Aims: Patients undergoing hysterectomy by open or laparoscopic approach experience moderate to severe postoperative pain. A multimodal analgesic approach is recommended for these patients. This study reviews the analgesic efficacy of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor used as an adjuvant for opioid-sparing postoperative analgesia., Methods: After registering the protocol in the international prospective register of systematic reviews (PROSPERO), databases like PubMed, Ovid, Scopus, Cochrane Library and clinicaltrials.gov were searched for randomised controlled trials using relevant keywords to find studies in which duloxetine premedication was compared to a placebo in patients undergoing hysterectomy. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess the quality of evidence., Results: The qualitative systematic review included five of the 88 studies identified. The overall risk of bias in the included studies was very high. In all the studies, 60 mg oral duloxetine was used, and the control group was placebo. In two studies, duloxetine premedication was administered 2 h before and 24 h after surgery. In the other three studies, a single dose of 60 mg duloxetine was only administered 2 h before surgery. A pooled meta-analysis was not performed due to fewer studies that fulfilled the inclusion criteria and even fewer studies with consistent reporting of various outcomes., Conclusion: The evidence is insufficient to advocate routine duloxetine premedication in patients undergoing hysterectomy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Introduction: Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf., Methods: This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent., Results: Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0-82.6]), ease of use (87.4 [83.7-91.0]), tolerability (94.2 [91.0-97.3]) and effectiveness (76.2 [71.6-80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 10 9 /L and 1.3 ± 0.3 × 10 9 /L, respectively., Conclusions: Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment., (© 2023. The Author(s).)

Amid environmental crises, a galloping population, and changing food habits, increasing fruit production with nutritional quality is a global challenge. To address this, there is a necessity to exploit the germplasm accessions in order to develop high-yielding varieties/hybrids with good adaptability and high quality fruit under changing environmental and biological conditions. In the study, a total of 33 morpho-biochemical traits enabled an assessment of the genetic variability, diversity, and structure in a collection of 28 diverse germplasm lines of guava. Results showed that highly significant genetic variability existed in the studied traits in the guava germplasm. The coefficient of variation values for the qualitative and quantitative traits varied from 23.5-72.36 to 1.39-58.62%, respectively. Germplasm Thai, Lucknow-49, Punjab Pink, Psidium friedrichsthalianum , and Shweta had the highest fruit weight (359.32 g), ascorbic acid content (197.27 mg/100 g fruit), total phenolic content (186.93 mg GAE/100 g), titratable acidity (0.69 percent), and antioxidant capacity (44.49 μmolTrolox/g), respectively. Fruit weight was positively correlated with ascorbic acid content; however, titratable acidity was negatively correlated with fruit weight. The principal component analysis (PCA) was 84.2% and 93.3% for qualitative and quantitative traits, respectively. Furthermore, K-mean clustering was executed; the population was grouped into three clusters for both traits. Additionally, the dendrogram using agglomerative hierarchical clustering (AHC), where all the germplasm were grouped into four clusters, revealed that among the clusters, clusters III and IV were highly divergent. The high variability, diversity, and structure could be utilized for the breeding programme of guava and also explored for molecular analysis using next-generation technology to enhance the guava yield and nutrition properties and also develop the climate resilient technology to fulfill the existing demand gap and nutrition availability, which could not only mitigate the nutrition requirement but also enhance the easy availability of fruits year-round., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gangappa, Singh, Verma, Thakre, Sevanthi, Singh, Srivastav, Raghunandan, Anusha, Yadav and Nagaraja.)

Objective: To compare the efficacy and safety of avanafil as compared with sildenafil in the management of patients with erectile dysfunction., Methods: It was a prospective, randomized, double-blind, two-arm, active-controlled, parallel, multicenter, non-inferiority clinical study carried out in patients with erectile dysfunction for at least 3 months and International Index of Erectile Function - Erectile Function domain score of <26 at enrolment., Results: A total of 220 patients were randomized to receive either avanafil tablets 100 mg or sildenafil tablets 50 mg in 1:1 ratio. After 4 weeks of treatment, 40.0% of patients in the avanafil group and 45.6% of patients in the sildenafil group required dose escalation to a high dose (avanafil 200 mg/sildenafil 100 mg). The difference in the mean change of International Index of Erectile Function - Erectile Function score from baseline in the two groups increased from week 4 (1.1, 95% confidence interval -0.2 to 2.5) to week 8 (1.4, 95% confidence interval 0.1-2.7) and week 12 (2.1, 95% confidence interval 0.8-3.5), showing non-inferiority at week 4, and superiority at week 8 and week 12. Avanafil showed a faster onset of action as shown by a significantly better response to modified Sexual Encounter Profile 1 in the avanafil group (84.8%) as compared with that in the sildenafil group (28.2%; P < 0.001). Both avanafil and sildenafil were well tolerated by all the patients in the study; the most common adverse event reported during the study was headache in both the groups., Conclusion: Avanafil is superior to sildenafil in improving the International Index of Erectile Function - Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action., (© 2022 Zydus Healthcare Limited. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: The prevalence of multiple sclerosis (MS) is increasing in Gulf Cooperation Council (GCC) countries. Multiple sclerosis contributes to significant burden on patients and caregivers. The pharmacological treatment in MS involves treating acute exacerbations and preventing relapses and disability progression using disease-modifying therapies. Clinical evidence suggests that teriflunomide is one of the therapeutic choices for patients with relapsing-remitting MS (RRMS). However, genetic and cultural differences across different regions may contribute to variations in drug use. Therefore, it is necessary to consider real-world evidence for teriflunomide usage in GCC countries., Methods: An expert group for MS gathered from GCC countries in December 2020. The consensus highlighting role of teriflunomide in MS management has been developed using clinical experiences and evidence-based approach., Results: The expert-recommended patient profile for teriflunomide usage includes individuals aged 18 years and above, both men and women (on effective contraceptives) with clinically isolated syndrome or RRMS. The factors considered were cost-effectiveness of the drug, patient preference, adherence, monitoring, established safety profile, and coronavirus disease 2019 status., Conclusion: Expert recommendations based on their clinical experience will be more helpful to clinicians in clinical settings regarding the usage of teriflunomide and provide valuable insights applicable in day-to-day practice., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)