The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles.

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.

Spatial predictors of immunotherapy response in triple-negative breast cancer.

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell-cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer-immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.

Constraint-induced movement therapy versus bimanual intensive therapy in children with hemiplegia showing low/very low bimanual functional performance: A randomized clinical trial.

INTRODUCTION: Children with infantile hemiplegia with low or very low bimanual functional performance have great impediments to spontaneously use their affected upper limb, which affects their performance of day-to-day activities and their quality of life. OBJECTIVE: To determine whether the order of application and the dose of modified constraint-induced movement therapy within a combined (hybrid) protocol influences the results of bimanual functional performance of the affected upper limb and the quality of life of children with congenital hemiplegia (5 to 8 years old) with low/very low bimanual functional performance. DESIGN: Single-blinded randomized controlled trial. PARTICIPANTS: Twenty-one children with congenital hemiplegia (5 to 8 years old) were recruited from two public hospitals and an infantile hemiplegia association in Spain. INTERVENTIONS: The experimental group (n = 11) received 100 hours of intensive therapies for the affected upper limb: 80 hours of modified constraint-induced movement therapy and 20 hours of bimanual intensive therapy. The control group (n = 10) received the same dose with 80 hours of bimanual intensive therapy and 20 hours of modified constraint-induced movement therapy. The protocol was provided 2 hours per day, 5 days per week, for 10 weeks. OUTCOME MEASURES: The primary outcome was bimanual functional performance, measured with the Assisting Hand Assessment, and the second outcome was quality of life, measured with the Pediatric Quality of Life Inventory Cerebral-Palsy module (PedsQL v. 3.0, CP module). Four assessments were performed: Weeks 0, 4, 8, and 10. RESULTS: The experimental group obtained an increase of 22 assisting hand assessment (AHA) units at week 8 with the application of modified constraint-induced movement, in contrast with the control group, which obtained an increase of 3.7 AHA units after bimanual intensive therapy. At week 10, the control group showed its greatest increase in bimanual functional performance, with 10.6 AHA units after modified constraint-induced movement therapy. Regarding quality of life, the greatest improvement occurred after modified constraint-induced movement, with 13.1 points in the experimental group (80 hours) and 6.3 points in the control group (20 hours). The protocol interaction was statistically significant for bimanual functional performance (p = .018) and quality of life (p = .09). CONCLUSIONS: Modified constraint-induced movement therapy is more beneficial than bimanual intensive therapy for improving upper limb functioning and quality of life in children with congenital hemiplegia showing low/very low bimanual performance. GOV IDENTIFIER: NCT03465046.

Partial hydatidiform mole and coexistent live fetus with placenta previa: a case report.

Partial molar pregnancy with a coexistent live fetus is very rare. This type of mole mostly ends in the early termination of pregnancy due to an abnormally developed fetus. Case presentation: Here, we report a case of a 24-year-old Indonesian woman with an ultrasonographic appearance of partial hydatidiform mole with initial placenta covering the internal uterine ostium in the late first trimester which then became marginal placenta previa in the third trimester. The woman decided to continue the pregnancy after considering the risks and benefits. The normal anatomy of the premature infant was vaginally delivered alive with a large and hydropic placenta. Clinical discussion: Proper diagnosis, management, and monitoring remain challenging as this case is still rarely reported. Although embryos from partial mole forms generally do not survive since the first trimester, our case reported the singleton pregnancy with the coexistent normal fetus and the partial mole characteristic of the placenta. Diploid karyotype, few and focal extent of hydatidiform tissue of placenta, low rate of molar degeneration, and the absence of fetal anemia hypothesized as the factors that influenced survival of the fetus. There were two maternal complications such as hyperthyroidism and frequent vaginal bleeding without subsequent anemia in this patient. Conclusions: A rare case of partial hydatidiform mole coexistent with a live fetus with placenta previa was reported in this study. There were also maternal complications. Thus, prompt and regular monitoring of maternal and fetal condition holds an important role.

Epidemiological Pattern of Traumatic Brain Injury in the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

BACKGROUND: Although the incidence of traumatic brain injury (TBI) has decreased since the beginning of the coronavirus disease 2019 (COVID-19) pandemic and severe acute respiratory syndrome coronavirus 2 is still evolving, the number of TBI cases has still greatly increased in multiple countries. In the present systematic review and meta-analysis, we evaluated the epidemiological characteristics of patients with TBI before and during the COVID-19 pandemic. METHODS: We conducted a systematic literature search of original studies, short reports, and research letters from databases on studies that contained data about the severity, mortality, presence of neurological deficits, radiological diagnosis, cause of injury, and type of management of TBI during a specified period within the pandemic compared with before the pandemic. RESULTS: A total of 18,490 subjects from 13 studies were included in the present study. The results of the meta-analysis showed a higher TBI mortality rate during the COVID-19 pandemic in the low-to-middle income countries (odds ratio, 1.65; 95% confidence interval, 1.12-2.41; P < 0.05; I2 = 40.8%; P = 0.18). The proportion of subdural hemorrhage was decreased, and the proportion of subarachnoid hemorrhage was increased in low- to middle-income and high-income countries, respectively. The proportion of assaults as the cause of TBI had increased during the pandemic (odds ratio, 1.40; 95% confidence interval, 1.06-1.86; P = 0.02; I2 = 20.8%; P = 0.28). We did not find any significant differences in the incidence of surgical intervention for TBI during the pandemic. CONCLUSIONS: Our results have indicated that during the COVID-19 pandemic, the TBI mortality rate had increased in low- to middle-income countries. The rate of assault as the cause of TBI had also increased during the pandemic.

The efficacy of virtual reality tools for total knee replacement rehabilitation: A systematic review.

Purpose. To assess the effects of training with virtual reality tools (VRT) during rehabilitation of patients after total knee replacement (TKR). Methods. Systematic review. Six databases were queried. Search criteria included studies in which participants underwent TKR, took part in a rehabilitation protocol with VRT, and clinical outcomes of rehabilitation were considered. Available demographic, interventional and outcome data, along with functional, balance, and pain outcome measures were extracted. Patient satisfaction was also summarized. Results. Six trials were included. Available information shows that multi-modal intervention with VRT is used primarily to augment conventional rehabilitation. The Wii Balance Board is the most frequently used device. Conclusions. Findings suggest that an augmented VRT physical therapy intervention that is specifically-oriented to enhance balance could be more effective for overcoming balance limitations than standard physical therapy. However, rehabilitation with VRT has no advantage over conventional training for enhancing function, resolving pain, or increasing patient satisfaction after TKR. Future studies are needed to confirm the findings, particularly regarding the feasibility of preoperative and continued in-home intervention. Registration: CRD42017057087.