Fixed drug combination (levosulpiride and rabeprazole)-induced atypical Parkinsonian's disorders with associated anxiety and low-lying depression.

We hereby describe a rare case of levosulpiride-induced atypical parkinsonism presenting with sluggish movements, atypical kinetic tremors (tremors with voluntary movement), periorbital tremors, dystonia, difficulty in speech and coordination, postural imbalance, with additional features of difficulty in swallowing and drooling with associated recent onset psychiatric disturbances such as anxiety and low-lying depression. The dechallenge of levosulpiride and medications for associated anxiety and low-lying depression caused a complete remission of the disease within 2 ½ months.

Does Coronavirus Disease 2019 Kill More Elderly Men than Women Due to Different Hormonal Milieu.

Preliminary data depicts a much greater prevalence and high case-fatality rate in advanced age males as compared to age-matched women with severe acute respiratory syndrome-coronavirus-2 infections with high morbidity, mortality, high referral, and admission to intensive care unit with severe sequelae. However, the literature search revealed both for and against studies in this context. Thus, at present, in light of the mixed studies, it cannot be established whether low testosterone levels in aging hypogonadal males create a permissive environment for severe response to coronavirus disease 2019 (COVID-19) infection and can it increase the morbidity or mortality, or on the contrary if the virus inhibits androgen formation. Hence, it is highly warranted to establish the said hypothesis by conducting large statistically powered clinical studies in future. Further, it is highly indicated that impact of sex hormones and gender on the incidence and case fatality of the disease and hormones as a treatment according to sex and gender for COVID requires further scientific research by the research community before it is actually recommended to mitigate the COVID-19 disease course among elderly men and women at large.

Menopause and Sleep Disorders.

Women are likely to suffer from sleep disorders more in comparison to men during menopause and with advancing age. The incidence of sleep disorders ranges from 16% to 47% at peri-menopause and 35%-60% at postmenopause. Insomnia with or without associated anxiety or low lying depression and Mood disorder is most common associated manifestations. Sleep disorders and insomnia largely remain a clinical diagnosis based on the subjective complaints of patients. Benzodiazepines remain the mainstay of the treatment in majority of the sleep disorders including chronic or acute insomnia. Treatment of associated anxiety, depression, or psychosis is most important. Tricyclic antidepressant, Selective Serotonin Reuptake Inhibitors (SSRI), Melatonin, Duloxetine, Fluoxetine, Imipramine, Nortriptyline or Amitriptyline and other drugs such as Eszopiclone, Escitalopram, Gabapentin, Quiteiapine, Citalopram, Mirtazapine followed by long-acting Melatonin and Ramelteon, also are very useful for the management of various sleep disorders. Hormone replacement therapy presently lacks concrete evidence to be used in menopausal women for sleep disorder. Sleep hygiene practices, self-hypnosis, meditation, and exercise play a very important role.

Improvement in Quality of Life of Postmenopausal Women with Depression with commonly used Antidepressants (Escitalopram vs. Desvenlafaxine): A Randomized Controlled Trial in a Tertiary Care Teaching Hospital of North India.

Introduction: The postmenopausal symptoms affect the quality of life (QoL) of women. Depression and anxiety too have been associated with diminished QoL. It is known that antidepressants escitalopram and desvenlafaxine are effective in the treatment of depression and anxiety. However, to the best of our knowledge, their comparative effect on the QoL of postmenopausal women with depression and anxiety has not been studied in the Indian setup. Materials and Methods: The present study was a randomized, intention to treat, open-label trial undertaken in North India's a tertiary care teaching hospital. Postmenopausal women attending the psychiatry outpatient department and newly diagnosed with depression and anxiety were randomized in two groups to receive Tab. Escitalopram 10-20 mg and Tab. Desvenlafaxine 50-100 mg. Their QoL was assessed using the WHOQOL BREF scale at baseline, 3 weeks and 6 weeks. Results: Escitalopram was observed to be statistically better than desvenlafaxine in improving the overall QoL score of the WHOQOL-BREF scale. Individually, escitalopram significantly improved the scores of the physical health domain, psychological and environmental domains except for the social relationship domain. Desvenlafaxine significantly improved scores of all four domains. Conclusion: Escitalopram was observed to be significantly better than desvenlafaxine in improving the overall QoL scores. Both the drugs were well tolerated.

High-throughput continuous-flow microfluidic electroporation of mRNA into primary human T cells for applications in cellular therapy manufacturing.

Implementation of gene editing technologies such as CRISPR/Cas9 in the manufacture of novel cell-based therapeutics has the potential to enable highly-targeted, stable, and persistent genome modifications without the use of viral vectors. Electroporation has emerged as a preferred method for delivering gene-editing machinery to target cells, but a major challenge remaining is that most commercial electroporation machines are built for research and process development rather than for large-scale, automated cellular therapy manufacturing. Here we present a microfluidic continuous-flow electrotransfection device designed for precise, consistent, and high-throughput genetic modification of target cells in cellular therapy manufacturing applications. We optimized our device for delivery of mRNA into primary human T cells and demonstrated up to 95% transfection efficiency with minimum impact on cell viability and expansion potential. We additionally demonstrated processing of samples comprising up to 500 million T cells at a rate of 20 million cells/min. We anticipate that our device will help to streamline the production of autologous therapies requiring on the order of 10[Formula: see text]-10[Formula: see text] cells, and that it is well-suited to scale for production of trillions of cells to support emerging allogeneic therapies.

Correction: A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions.

Correction for 'A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions' by Kelly Tan et al., Lab Chip, 2019, 19, 1556-1566, DOI: .

Comparative Efficacy and Safety of Clonazepam versus Nortrptilline on Menopausal Symptom among Forty Plus Women: A Prospective, Open-Label Randomized Study.

AIMS AND OBJECTIVES: The aim of this study is to compare the effect of clonazepam and nortryptiline on menopausal symptoms in above 40 years women. MATERIALS AND METHODS: A prospective, randomized, open-label comparative study was conducted in a tertiary care teaching hospital for 1 year. Patients were randomized into two groups. Both the groups had 60 patients, out of which Group A had 39 menopausal patients and Group B had 31 menopausal patients, respectively. Group 1 received tablet clonazepam 0.5 mg bed time orally daily. Group 2 received tablet nortryptiline 25 mg bed time orally daily. The primary efficacy end points were effect on menopausal symptoms evaluated by at 0, 4, and 8 weeks. RESULTS: Mean age since menopause was 45 ± 4.06 years, and the mean number of years since menopause was 9.18 ± 7.59 years clonazepam and nortryptiline recorded statistically comparable effect with numerical superiority of nortryptiline both at 4 and 8 weeks on mean Menopausal Symptom Score, thereby indicating that both the drugs may have directly/indirectly improved the mean menopausal symptoms equally. Improvement in the clonazepam group was numerically and statistically more than nortryptiline group at 4 and 8 weeks on mean Vasomotor Symptom Score with P < 0.01 in clonazepam group and P < 0.05 in nortryptiline group both at 4 and 8 weeks. Both the drugs showed comparable results on psychosocial symptom score both at 4 and 8 weeks with numerical superiority in nortryptiline group. Clonazepam group showed more improvement on mean physical score than nortryptiline group numerically and statistically. Both the drugs showed comparable results on mean sexual symptom score at 4 weeks, but nortryptiline proved to be statistically better at 8 weeks P < 0.01 versus P < 0.05 in clonazepam group. CONCLUSION: Clonazepam and nortryptiline recorded statistically comparable effect at 4 and 8 weeks on mean menopausal symptom. Both the drugs were equally safe and did not recorded any serious Adverse Drug Reaction (ADRs).

A Microfluidic Device to Enhance Viral Transduction Efficiency During Manufacture of Engineered Cellular Therapies.

The development and approval of engineered cellular therapies are revolutionizing approaches to treatment of diseases. However, these life-saving therapies require extensive use of inefficient bioprocessing equipment and specialized reagents that can drive up the price of treatment. Integration of new genetic material into the target cells, such as viral transduction, is one of the most costly and labor-intensive steps in the production of cellular therapies. Approaches to reducing the costs associated with gene delivery have been developed using microfluidic devices to increase overall efficiency. However, these microfluidic approaches either require large quantities of virus or pre-concentration of cells with high-titer viral particles. Here, we describe the development of a microfluidic transduction device (MTD) that combines microfluidic spatial confinement with advective flow through a membrane to efficiently colocalize target cells and virus particles. We demonstrate that the MTD can improve the efficiency of lentiviral transduction for both T-cell and hematopoietic stem-cell (HSC) targets by greater than two fold relative to static controls. Furthermore, transduction saturation in the MTD is reached with only half the virus required to reach saturation under static conditions. Moreover, we show that MTD transduction does not adversely affect cell viability or expansion potential.

Comparative Efficacy and Safety of Escitalopram versus Desvenlafaxine in Postmenopausal Women with Depression and Anxiety: A Randomized, Open-Label, Comparative Trial.

AIMS AND OBJECTIVES: The aim was to evaluate the comparative efficacy and safety of escitalopram versus desvenlafaxine in postmenopausal women with depression and anxiety in our study cohort. MATERIALS AND METHODS: A randomized, open-label, intention-to-treat, comparative study was conducted over a period of 1 year. Group 1 (n = 20) patients received tablet escitalopram 10 mg once daily orally which was increased to 20 mg/day when needed at the first follow-up. Group 2 (n = 20) patients received tablet desvenlafaxine 50 mg once daily orally which was increased to 100 mg/day when needed at the first follow-up. Patients were followed at 3 and 6 weeks. Primary endpoints were change in baseline scores (recorded as mean ± standard deviation) of Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A), and safety was also assessed and compared. RESULTS: Forty patients completed the study. Escitalopram was statistically better than desvenlafaxine in reducing depression after 6 weeks of treatment (P < 0.05). Both the drugs were found to be equally effective in treating anxiety. Furthermore, they showed comparable safety and tolerability. CONCLUSION: Escitalopram appears to be more effective on short-term basis in treating depression, and both the drugs appear equally effective in combating anxiety. Furthermore, they appear to be equally safe and well tolerated in postmenopausal women with depression and anxiety.

Acoustophoretic rapid media exchange and continuous-flow electrotransfection of primary human T cells for applications in automated cellular therapy manufacturing.

Autologous cellular therapies based on modifying T cells to express chimeric antigen receptor genes have been highly successful in treating hematological cancers. Deployment of these therapies is limited by the complexity and costs associated with their manufacturing. Transitioning these processes from virus-based methods for gene delivery to a non-viral method, such as electroporation, has the potential to greatly reduce cost and manufacturing time while increasing safety and efficacy. Major challenges with electroporation are the negative impacts on cell health associated with exposure to high-magnitude electric fields, and that most commercial bulk electroporators are low-precision instruments designed for manually-operated, lower-throughput batch processing of cells. Negative effects on cell health can be mitigated by use of specialized electroporation medias, but this adds processing steps, and long-term exposure to these medias can reduce transfection efficiency and post-transfection viability. To enable automated, clinical-scale production of cellular therapies using electrotransfection in specialized medias, we developed a high-precision microfluidic platform that automatically and continuously transfers cells from culture media into electroporation media using acoustophoresis, and then immediately applies electric fields from integrated electrodes. This limits cell residence time in electroporation media to seconds, and enables high transfection efficiency with minimum impact on cell viability. We tested our system by transferring primary human T cells from a standard cell media to electroporation media, and then transfecting them with mRNA encoding an mCherry fluorescent protein. We achieved a media exchange efficiency of 86% and transfection efficiency of up to 60%, with less than a 5% reduction in viability.

Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania: A Randomized Controlled Trial.

BACKGROUND: Atypical antipsychotics are used for the treatment of acute mania, either as monotherapy or in combination with lithium or divalproex, which have a better tolerability profile as compared with typical antipsychotics. Asenapine, a newer atypical antipsychotic, has been found to be effective for the treatment of mania, with efficacy similar to olanzapine. The objective of the study was to compare the efficacy and safety of asenapine and olanzapine when used in combination with divalproex in patients with acute mania. METHODS: One hundred twenty patients aged 18 to 55 years, diagnosed with manic episode, were randomized to receive either flexible dose of sublingual asenapine (10-20 mg/d) or tablet olanzapine (10-20 mg/d), in combination with valproate 20 mg/kg per day for a period of 6 weeks. Efficacy was measured as change in Young Mania Rating Scale and Clinical Global Impression-Bipolar using intention-to-treat analysis with last observation carried forward, and safety was measured using Udvalg for Kliniske Undersøgelser scale and Modified Simpson-Angus Extrapyramidal Side Effects Scale. RESULTS: There was a significant reduction in Young Mania Rating Scale and Clinical Global Impression-Bipolar scores over time in both groups, with a significantly higher reduction in the olanzapine group as shown by the group × time interaction effect. Higher weight gain, increased sleep and appetite, and tremors were seen in the olanzapine-treated patients as compared with asenapine-treated patients; however, tongue hypesthesia was seen in the asenapine group only. CONCLUSIONS: This study found that asenapine was an effective and well-tolerated atypical antipsychotic alternative to olanzapine in combination with divalproex for the short-term management of acute mania.