Efficacy/effectiveness and safety of emicizumab prophylaxis of people with hemophilia A: a systematic review and meta-analysis.

BACKGROUND: Emicizumab is a monoclonal antibody approved for prophylaxis against bleeds for people with hemophilia A (PwHA). A systematic review was conducted evaluating the efficacy/effectiveness and the safety of emicizumab as prophylaxis for PwHA compared to prophylaxis with factor VIII (FVIII) or bypassing agents (BPA), respectively in patients without and with inhibitors. RESEARCH DESIGN AND METHODS: Database-directed search strategies were performed in Aug/26/2022 and updated in Mar/16/2023. Studies evaluating the prophylaxis with emicizumab versus prophylaxis with FVIII or BPA in PwHA without or with inhibitors, respectively, were selected by two independent reviewers. Data were extracted by two independent reviewers. Annualized bleeding rates for total treated bleeding events (ABR-all) were evaluated by meta-analysis. The quality of studies and certainty of evidence were assessed. RESULTS: A total of 11 studies were included. The standard mean differences for ABR-all were -0.6 (95%CI -1.0 to -0.2, p-value = 0.0002), among PwHA without inhibitors, and -1.7 (95%CI -2.4 to -0.9, p-value <0.00001), among PwHA with inhibitors. However, there was moderate heterogeneity in both meta-analyses. The most frequent adverse event was injection site reaction. CONCLUSIONS: Emicizumab prophylaxis was superior in reducing the ABR-all when compared with prophylaxis with FVIII or BPA.

Economic Evaluation of Immune Tolerance Induction in Children With Severe Hemophilia A and High-Responding Inhibitors: A Cost-Effectiveness Analysis of Prophylaxis With Emicizumab.

OBJECTIVE: This study aimed to measure the cost-effectiveness of prophylaxis with emicizumab in PsHAhri on ITI in Brazil. METHODS: A cost-effectiveness modeling analysis was used to estimate the costs per PsHAhri on ITI and the number of prevented bleedings from undertaking one intervention (prophylaxis with BpA) over another (prophylaxis with emicizumab), based on the Brazilian Ministry of Health perspective. Costs of ITI with recombinant FVIII, prophylaxis with BpA or emicizumab, and treated bleeding episodes with BpA costs were evaluated for PsHAhri who had ITI success or failure. This study was conducted with the perspective of the Brazilian Ministry of Health (payer). RESULTS: During ITI, prophylaxis with BpA cost US $924 666/PsHAhri/ITI, whereas prophylaxis with emicizumab cost US $488 785/PsHAhri/ITI. During ITI, there was an average of 9.32 bleeding episodes/PsHAhri/ITI when BpA were used as prophylaxis and 0.67 bleeding/PsHAhri/ITI when emicizumab was used. By univariate deterministic sensitivity analysis, emicizumab remained dominant whichever variable was modified. CONCLUSION: In this study, prophylaxis with emicizumab during ITI is a dominant option compared with prophylaxis with BpA during ITI.

Disseminated Mycobacterium avium on HIV/AIDS: Historical and Current Literature Review.

Combination antiretroviral therapy (cART) has changed Mycobacterium avium epidemiology. A significant decrease in the incidence of disseminated M. avium complex: (DMAC) infection was observed between pre-cART and post-cART periods. In contrast, diagnoses of DMAC more than doubled from 1990 to 1996. During this time, DMAC prevalence in people living with AIDS (PLHA) in developed countries reached 20-23% overall and >40% in groups with CD4 cell counts <10 cells/mm3. At present, DMAC in PLHA has an incidence of two events per 1000 patient years. Recently, the centers for disease control changed the criteria for MAC primary prophylaxis, where only patients without immediate cART and CD4 cell counts <50 cells/mm3 are prescribed 1200 mg of azithromycin weekly. Treatment is discontinued when patients initiate effective cART. Diagnosing a disseminated M. avium infection is difficult due to the low accuracy of fluid cultures and a lack of diagnostic processes. However, the usefulness of newer molecular techniques such as whole-genome sequencing has not been evaluated for DMAC and HIV/AIDS. As DMAC has a high mortality rate if not properly diagnosed and treated, we performed a literature review of HIV/AIDS and DMAC epidemiology, risk factors, prophylaxis, clinical manifestation, diagnosis, prognosis, and treatment.

Lupin gamma conglutin protein: effect on Slc2a2, Gck and Pdx-1 gene expression and GLUT2 levels in diabetic rats

ABSTRACT Recently, lupin seed (Lupinus albus L., Fabaceae) products have emerged as a functional food due to their nutritional and health benefits. Numerous reports have demonstrated the hypoglycemic effects of lupin's gamma conglutin protein; nonetheless, its mechanism of action remains elusive. To understand the role of this protein on glucose metabolism, we evaluated the effect of administering L. albus' gamma conglutin on Slc2a2, Gck, and Pdx-1 gene expression as well as GLUT2 protein tissue levels in streptozotocin-induced diabetic rats. While consuming their regular diet, animals received a daily gamma conglutin dose (120 mg/kg per body weight) for seven consecutive days. Serum glucose levels were measured at the beginning and at the end of the experimental period. At the end of the trial, we quantified gene expression in pancreatic and hepatic tissues as well as GLUT2 immunopositivity in Langerhans islets. Gamma conglutin administration lowered serum glucose concentration by 17.7%, slightly increased Slc2a2 and Pdx-1 mRNA levels in pancreas, up-regulated Slc2a2 expression in the liver, but it had no effect on hepatic Gck expression. After gamma conglutin administration, GLUT2 immunopositivity in Langerhans islets of diabetic animals resembled that of healthy rats. In conclusion, our results indicate that gamma conglutin up-regulates Slc2a2 gene expression in liver and normalizes GLUT2 protein content in pancreas of streptozotocin-induced rats.

Dynamical amplification of magnetoresistances and Hall currents up to the THz regime.

Spin-orbit-related effects offer a highly promising route for reading and writing information in magnetic units of future devices. These phenomena rely not only on the static magnetization orientation but also on its dynamics to achieve fast switchings that can reach the THz range. In this work, we consider Co/Pt and Fe/W bilayers to show that accounting for the phase difference between different processes is crucial to the correct description of the dynamical currents. By tuning each system towards its ferromagnetic resonance, we reveal that dynamical spin Hall angles can non-trivially change sign and be boosted by over 500%, reaching giant values. We demonstrate that charge and spin pumping mechanisms can greatly magnify or dwindle the currents flowing through the system, influencing all kinds of magnetoresistive and Hall effects, thus impacting also dc and second harmonic experimental measurements.

GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome.

INTRODUCTION: GATA2 mutations are associated with several conditions, including Emberger syndrome which is the association of primary lymphedema with hematological anomalies and an increased risk for myelodysplasia and leukemia. OBJECTIVE: To describe a family with Emberger syndrome with incomplete penetrance. METHODS: A DNA sequencing of GATA2 gene was performed in the parents and offspring (five individuals in total). RESULTS: The family consisted of 5 individuals with a GATA2 null mutation (c.130G>T, p.Glu44*); three of them were affected (two of which were deceased) while two remained unaffected at the age of 40 and 13 years old. The three affected siblings (two boys and one girl) presented with lymphedema of the lower limbs, recurrent warts, epistaxis and recurrent infections. Two died due to hematological abnormalities (AML and pancytopenia). In contrast, the two other family members who carry the same mutation (the mother and one brother) have not presented any symptoms and their blood tests remain normal. DISCUSSION: Incomplete penetrance may indicate that GATA2 haploinsufficiency is not enough to produce the phenotype of Emberger syndrome. It could be useful to perform whole exome or genome sequencing, in cases where incomplete penetrance or high variable expressivity is described, in order to probably identify specific gene interactions that drastically modify the phenotype. In addition, skewed gene expression by an epigenetic mechanism of gene regulation should also be considered.

[Glucotransporters: clinical, molecular and genetic aspects]. / Glucotransportadores (GLUT): Aspectos clínicos, moleculares y genéticos.

Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches.

Novel integrative virtual rehabilitation reduces symptomatology of primary progressive aphasia--a case report.

PURPOSE: BrightBrainer™ integrative cognitive rehabilitation system evaluation in an Adult Day Program by a subject with Primary Progressive Aphasia (PPA) assumed to be of the mixed nonfluent/logopenic variant, and for determination of potential benefits. METHODS: The subject was a 51-year-old Caucasian male diagnosed with PPA who had attended an Adult Day Program for 18 months prior to BrightBrainer training. The subject interacted with therapeutic games using a controller that measured 3D hand movements and flexion of both index fingers. The computer simulations adapted difficulty level based on task performance; results were stored on a remote server. The clinical trial consisted of 16 sessions, twice/week for 8 weeks. The subject was evaluated through neuropsychological measures, therapy notes and caregiver feedback forms. RESULTS: Neuropsychological testing indicated no depression (BDI 0) and severe dementia (BIMS 1 and MMSE 3). The 6.5 h of therapy consisted of games targeting Language comprehension; Executive functions; Focusing; Short-term memory; and Immediate/working memory. The subject attained the highest difficulty level in all-but-one game, while averaging 1300-arm task-oriented active movement repetitions and 320 index finger flexion movements per session. While neuropsychological testing showed no benefits, the caregiver reported strong improvements in verbal responses, vocabulary use, speaking in complete sentences, following one-step directions and participating in daily activities. This corroborated well with therapy notes. CONCLUSIONS: Preliminary findings demonstrate a meaningful reduction of PPA symptoms for the subject, suggesting follow-up imaging studies to detail neuronal changes induced by BrightBrainer system and controlled studies with a sufficiently large number of PPA subjects.

Complex magnetic structure of clusters and chains of Ni and Fe on Pt(111).

We present an approach to control the magnetic structure of adatoms adsorbed on a substrate having a high magnetic susceptibility. Using finite Ni-Pt and Fe-Pt nanowires and nanostructures on Pt(111) surfaces, our ab initio results show that it is possible to tune the exchange interaction and magnetic configuration of magnetic adatoms (Fe or Ni) by introducing different numbers of Pt atoms to link them, or by including edge effects. The exchange interaction between Ni (or Fe) adatoms on Pt(111) can be considerably increased by introducing Pt chains to link them. The magnetic ordering can be regulated allowing for ferromagnetic or antiferromagnetic configurations. Noncollinear magnetic alignments can also be stabilized by changing the number of Pt-mediated atoms. An Fe-Pt triangularly-shaped nanostructure adsorbed on Pt(111) shows the most complex magnetic structure of the systems considered here: a spin-spiral type of magnetic order that changes its propagation direction at the triangle vertices.

Adaptabilidad y cohesión familiar,implicación parental en conductasautorregulatorias, autoconcepto del estudiante y rendimiento académico / Familiar cohesion and adaptability, parental self-regulatory inducement, children's self-concept, and academic achievement

En este estudio se analiza la relación existente entre la adaptabilidad y la cohesión familiar, así como la conducta autorregulatoria de los padres en relación a su comportamiento con los hijos, en general, y en su implicación en el ámbito del estudio, en particular. También se estudia el tipo de relación que tales variables familiares mantienen con diferentes dimensiones del autoconcepto de los hijos y con su rendimiento académico. Los datos se obtienen a partir de una muestra de 163 estudiantes de Educación Secundaria Obligatoria que han cumplinentado tres escalas (Family Adaptability and Cohesion Evaluation Scales, Parental Inducement of Self-Regulation y Self-Description Questionnaire-II). Los resultados muestran que la percepción que los hijos tienen sobre el grado de implicación de los padres en comportamientos característicos autorregulatorios influye significativamente sobre las diferentes dimensiones que el estudiante tiene sobre sí mismo (privada, social, académica), que este tipo de percepción se encuentra escasamente relacionada con las características de adaptabilidad y cohesión familiar y, finalmente, que la dimensión académica del autoconcepto predice positiva y significativamente el rendimiento académico, mientras que la dimensión social lo predice negativamente (AU)

The present study analyses the relationship between adaptability and parental cohesion and how children’s behaviour towards studying and in general is affected by parental self-regulatory inducement. Furthermore, the relationship between variables like children’s self-concept dimensions and academic achievement are also analysed. Family Adaptability and Cohesion Evaluation Scales, Parental Inducement Self-Regulation and Self-Description Questionnaire II scales were administered in a sample of 133 secondary students. The results indicate that: 1) children’s perception about self-regulatory inducement had a significant influence on the self-concept dimensions (personal, social, academic); 2) this perception was vaguely related to adaptability and familiar cohesion; and, 3) academic self-concept dimensions positively and significantly predicted academic achievement, whereas social dimensions predicted it negatively (AU)