The regulation and function of the crucial cell cycle regulator cyclin E (CycE) remains elusive. Unlike other cyclins, CycE can be uniquely controlled by mitochondrial energetics, the exact mechanism being unclear. Using mammalian cells (in vitro) and Drosophila (in vivo) model systems in parallel, we show that CycE can be directly regulated by mitochondria through its recruitment to the organelle. Active mitochondrial bioenergetics maintains a distinct mitochondrial pool of CycE (mtCycE) lacking a key phosphorylation required for its degradation. Loss of the mitochondrial fission protein dynaminrelated protein 1 (Drp1, SwissProt O00429 in humans) augments mitochondrial respiration and elevates the mtCycE pool allowing CycE deregulation, cell cycle alterations and enrichment of stem cell markers. Such CycE deregulation after Drp1 loss attenuates cell proliferation in low-cell-density environments. However, in high-celldensity environments, elevated MEK-ERK signaling in the absence of Drp1 releases mtCycE to support escape of contact inhibition and maintain aberrant cell proliferation. Such Drp1-driven regulation of CycE recruitment to mitochondria might be a mechanism to modulate CycE degradation during normal developmental processes as well as in tumorigenic events.

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Pemphigus poses a therapeutic challenge and rituximab is increasingly used in its treatment. Long-term data regarding efficacy and safety of rituximab in pemphigus is limited.This study was a retrospective analysis of 76 pemphigus patients with primary endpoint being the percentage of patients achieving complete remission (CR) on/off therapy. Secondary endpoints were time to relapse, mean cumulative dose of prednisolone after rituximab infusion, mean duration of follow up, and adverse events to rituximab if any. A total of 62 (82.7%) attained complete remission on/off treatment, out of which 42 were off therapy. Mean interval between rituximab administration and complete remission off treatment was 6.9 ± 3.7 months. Complete remission off treatment was sustained for a mean duration of 21.4 ± 17.8 months before relapse. Over a mean follow-up duration of 42.7 ± 24.9 months (median 41, maximum 83 months), 22 of 62 patients (35.5%) who had achieved complete remission after the first cycle of rituximab relapsed. A mean total cumulative dose of 8716.3 ± 10533.8 mg prednisolone was prescribed over a mean duration of 18.05 ± 15.64 months after the first cycle of rituximab. Adverse events were noted in 18 out of 76 patients (23.7%) which included infusion reactions (n = 3), minor infections (n = 7), transitory disease flare (n = 6), and mortality (n = 2). No statistically significant correlation was found between remission/relapse rates and age, gender or pemphigus subtype. This study substantiates the long-term efficacy and safety of single cycle of rituximab in pemphigus.

The management of dermatophytosis is challenging in India and there are reports of using systemic antifungals at higher doses. But there are multiple reports of increased treatment failures with terbinafine at standard dosage as well, hence we conducted this study to compare efficacy and safety of high dose of terbinafine with itraconazole at standard dose. Topical ciclopirox olamine was used in both arms.This was randomized, open label, comparative study where 80 patients with tinea corporis et cruris infection were included. Patients were either prescribed terbinafine 250mg twice a day or itraconazole 100mg twice a day for 4 weeks. Efficacy was assessed based on complete, clinical and mycological cure rate. Safety was assessed by evaluating adverse events and monitoring liver function of patients.Total 76 patients completed the study with 38 in each group. 81.5% patients achieved complete cure in terbinafine group compared to 76.31% patients in itraconazole group. At the end of six weeks, there was a statistically significant improvement (p value<0.05) in the total symptom score (erythema, scaling, and pruritus) in Group I as well as in Group II compared to baseline. None of the patients showed any significant side effect in both Itraconazole and Terbinafine groups. No changes in liver function were observed in both the groups. This study shows that the high dose of terbinafine in combination with topical ciclopirox is effective and safe in management of tinea corporis et cruris.

Introduction Though second-generation antihistamines (SGAH) are first-line drugs in chronic spontaneous urticaria (CSU), 50% of patients do not respond to them. In such patients, guidelines recommend either up-dosing of SGAH or combination of different antihistamines. However, the studies comparing these treatment regimens are limited. Methods In this comparative, three-arm study, CSU patients were randomized to receive standard dose of either bilastine, fexofenadine, or levocetirizine for 2 weeks. After 2 weeks of treatment, non-responders received double dose of either bilastine or fexofenadine, while hydroxyzine 25 mg once daily was added in the levocetirizine group. Patients were primarily evaluated for improvement in CSU, quality of life, and somnolence. Results A total of 110 patients with CSU were recruited. At the end of 4 weeks, 33/39, 26/35, and 22/36 patients in the bilastine, fexofenadine, and levocetirizine groups showed improvement in urticaria symptoms. At week 2, there was no statistical difference in urticaria activity score (UAS7) improvement between any of the groups; however, at week 4, there was a statistical difference between the bilastine and levocetirizine groups ( p <0.05). Somnolence was significantly lower in the bilastine group ( p <0.05). Bilastine was statistically significant ( p <0.05) in the improvement of quality of life as compared to both groups. No major adverse events were reported during study period; however, bilastine was associated with significantly lower levels of AEs compared to levocetirizine ( p <0.05). Conclusion Two-fold up-dosing of bilastine improves CSU symptoms without compromising safety as compared to two-fold up-dosing of fexofenadine and combination of first- and second-generation antihistamines.