d for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.

This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.From peptide hormones to monoclonal antibodies, advances in biotherapeutic medicines, or biologics, have brought incalculable benefits to patients, especially for conditions where previous classes of therapy were ineffective or non-existent. At the same time, the development of biologics has been accompanied by questions of access and cost. The advent of biosimilars, molecules highly similar to their reference biologics, has offered the promise of ameliorating cost and access challenges. However, issues regarding biosimilar uptake remain. Multiple factors impact the utilization of biosimilars by healthcare providers and perhaps the best recognized of these is education. This paper discusses the importance of education to biosimilar adoption and lists action-items that various stakeholders in healthcare can adopt to improve the overall understanding of this important class of therapeutics.

Women aged ≥  45years are known to experience various menopausal symptoms due to reduced oestrogen levels. Changes associated with cutaneous ageing, such as wrinkles and sagging, are also prominent in women in this age group. Numerous studies have evaluated the usefulness of individual basic nutrients and essential components, such as amino acids and vitamins, in menopausal women. The aim of this study was to comprehensively assess the effects of supplements containing amino acid and vitamin combinations on menopausal symptoms and age-related changes in the skin.

This is a randomised, placebo-controlled study on the effects of a supplement containing three types of amino acids [leucine, glutamine and arginine (LGA)] and 11 types of vitamins in 37 middle-aged women. The participants ingested either the test substance or a placebo twice daily for 8 consecutive weeks, at the end of which time the efficacy and safety of the test substance were assessed based on subjective symptoms of fatigue, Simplified Menopausal Index (SMI) score, the grade and number of wrinkles at the corners of the eyes, results of an analysis of the stratum corneum of the cheek and blood test results.

None of the participants experienced adverse events, and all items assessed in our survey of subjective symptoms of fatigue showed a significant decrease in the test substance group (LGA group). Additionally, the SMI score of the LGA group was significantly lower than that of the placebo group. The LGA group showed significant improvement in the grade of the wrinkles in the corners of the eyes and the number of wrinkles, and the stratum corneum cell area declined significantly in the LGA group compared to the placebo group at the end of the study.

These results indicate that the vitamin-containing amino acid supplement improved menopausal symptoms and age-related changes in the skin (wrinkles).

UMIN000029830.

UMIN000029830.

Hereditary spastic paraplegias (HSPs), a genetically heterogeneous group of neurodegenerative diseases, have an incidence of around 3 to 9 individuals every 100,000. Due to the broad clinical and genetic variability of HSPs, it is challenging to diagnose the disorder quickly and precisely. Hereditary spastic ataxias (HSAs) and HSPs are overlapping diseases, and their intersection has been gradually identified by next-generation sequencing. The idea of the spasticity-ataxia phenotype (SAP) spectrum is further substantiated by the similarities in phenotypes and underlying genes in ataxias and inherited spastic paraplegias and the related cellular processes and disease mechanisms these disorders exhibit.

Whole-exome sequencing was performed on the 25 spastic or spastic-ataxic gait patients.

Twenty-two specific HSPs-HSAs-SAP mutations, including 14 novel mutations, were found in 25 cases from 18 Turkish and 2 Syrian families. This research discovers many novel hereditary spastic paraplegia (HSP) mutations and shows a robust genotype-phenotype heterogeneity in the disease.

This research helped expand the clinical and molecular scope of HSP and clarified the concept of the spasticity-ataxia phenotype, further enhancing our understanding of the complicated form of HSP and its association with ataxia. Our data broadens the spectrum of HSPs and HSAs related gene mutations and provides insights for genotype-phenotype correlations for HSPs and HSAs.

This research helped expand the clinical and molecular scope of HSP and clarified the concept of the spasticity-ataxia phenotype, further enhancing our understanding of the complicated form of HSP and its association with ataxia. Our data broadens the spectrum of HSPs and HSAs related gene mutations and provides insights for genotype-phenotype correlations for HSPs and HSAs.Patients with adipsic hypernatremia present with chronic hypernatremia because of defects in thirst sensation and dysregulated salt appetite, without demonstrable hypothalamic structural lesions. The involvement of autoantibodies directed against the sodium channel, Nax in the subfornical organ (SFO) has recently been reported. However, the pathophysiology of water and electrolyte imbalance underlying the disease has yet to be elucidated. We describe the case of a 5-year-old boy who complained of headaches and vomiting that gradually worsened. Brain magnetic resonance imaging detected no abnormal lesions. Blood laboratory testing revealed a serum sodium (Na) concentration of 152 mmol/L and a serum osmolarity of 312 mOsm/L. His body weight had slightly decreased, and his thirst sensation was absent. His plasma vasopressin concentration was 0.9 pg/mL, despite the high serum osmolarity. He was encouraged to drink water, and oral 1-deamino-8-D-arginine-vasopressin was administered. When serum sodium concentrations were normalized, plasma vasopressin concentrations were apparently normal and ranged from 0.8 to 2.0 pg/mL. He did not present with polyuria at any time. Immunohistochemical study using mouse brain sections and the patient’s serum revealed the deposition of human immunoglobulin G (IgG) antibody in the mouse SFO. In conclusion, our observations suggested that water and electrolyte imbalance in adipsic hypernatremia is characterized by a certain amount of vasopressin release regardless of serum sodium concentrations with no response to hyperosmolarity.Renin-angiotensin-aldosterone system (RAAS) is primarily involved with pathological mechanism of developing hypertensive emergencies. However, none of clinical practice guidelines mention RAAS blockers for the treatment of hypertensive emergencies. A 44 year-old woman presented with severe hypertension, brain stem posterior reversible encephalopathy syndrome and severe acute kidney injury (AKI). We started anti-hypertensive therapy with continuous intravenous nitroglycerin and oral calcium channel blocker (CCB) and spironolactone. Since severe AKI persisted despite this therapy, we administered losartan potassium, which resulted in improvement in her blood pressure and creatinine. Clinical course of our patient suggests that timely initiation of ARB and spironolactone for hypertensive emergencies could be beneficial in terms of blood pressure control and for protection of target organs from this condition.The outcomes associated with pediatric acute myeloid leukemia (AML) have improved over the last few decades, with the implementation of intensive chemotherapy, hematopoietic stem cell transplant, and improved supportive care. However, even with intensive therapy and the use of HSCT, both of which carry significant risks of short- and long-term side effects, approximately 30% of children are not able to be cured. The characterization of AML in pediatrics has evolved over time and it currently involves use of a variety of diagnostic tools, including flow cytometry and comprehensive genomic sequencing. Given the adverse effects of chemotherapy and the need for additional therapeutic options to improve outcomes in these patients, the genomic and molecular architecture is being utilized to inform selection of targeted therapies in pediatric AML. This review provides a summary of current, targeted therapy options in pediatric AML.Trimethoprim and sulfamethoxazole are prescribed for a broad spectrum of bacteria. However, the use of these medicines is restricted due to the risk of microbial resistance in the body. Nanotechnology is a strategy for overcoming this problem by helping develop novel drug delivery systems. This study aims to assess the ability of Fe3O4/Ag and Fe3O4@SiO2/Ag nanoparticles to improve efficiency of the traditional formulation of trimethoprim and sulfamethoxazole. Fe3O4/Ag and Fe3O4@SiO2/Ag were found to have sphere-like morphologies with average sizes of 33.2 and 35.1 nm, respectively. The values of the zeta potential for the pure sulfamethoxazole and trimethoprim were -30.6 and -10.0 mV, respectively, which increased to zero or even larger positive values after being conjugated with the NPs. The study of the release kinetics showed that 64.7% of the medicines were released from the carriers within 40 days. The values of MIC for sulfamethoxazole, trimethoprim, Fe3O4/Ag/sulfamethoxazole, Fe3O4/Ag/trimethoprim, Fe3O4@SiO2/Ag/sulfamethoxazole, and Fe3O4@SiO2/Ag/trimethoprim against Escherichia coli were calculated to be 12, 9, 4, 4, 4, and 4 μg/mL, respectively. Besides, the relevant values against Staphylococcus aureus were measured to be 12, 9, 4, 4, 3, and 2 μg/mL, respectively. The use of synthesized nanomaterials for the delivery of these antibiotics leads to smaller doses compared to their traditional forms.Infection is one of the major causes of death in hematopoietic stem cell transplantation (HSCT) survivors. Precise assessments of immune function after HSCT will be critical in establishing appropriate treatment and prophylaxis, such as re-vaccination. Although several surrogate markers for prediction of clinical outcomes after HSCT have been proposed, definitive markers of immune reconstitution and data on those markers in long-term survivors are lacking. In this study, cellular response to mitogens was assessed and clinical features associated with a poor response to mitogens were investigated in long-term allogeneic HSCT survivors. Age at transplantation and age at the time of mitogen stimulation test were each identified as significant risk factors for poor response to phytohemagglutinin and concanavalin A, respectively (P  less then  0.001 each). However, time elapsed since transplantation was not found to be correlated with responsiveness to mitogens in this study. Prospective, in-depth studies on immune reconstitution are needed to establish appropriate prophylaxis against infections after HSCT and a schedule for re-vaccination.