Real-world experience using hydroxyurea in children with sickle cell disease in Lilongwe, Malawi.

Introduction: Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region-specific evidence for safety and efficacy.

Methods: We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi.

Medication adherence in first-episode psychosis and its association with psychopathology.

Background: The purpose of the study was to follow-up the individuals with first-episode psychosis (FEP) for a period of 1 year to assess their medication adherence rates and to identify the association between medication adherence and psychopathology.

Materials And Methods: In a 1 year longitudinal study, 59 individuals with FEP were assessed for their sociodemographic profile and medication adherence at 1 month and 12-month follow-up period using a semi-structured per forma. Positive and negative symptoms were assessed by positive and negative syndrome scale (PANSS) while the functioning by global assessment of functioning (GAF) scale.

The Malawi NCD BRITE Consortium: Building Research Capacity, Implementation, and Translation Expertise for Noncommunicable Diseases.

Africa is experiencing an increasing prevalence of noncommunicable diseases (NCD). However, few reliable data are available on their true burden, main risk factors, and economic impact that are needed to inform implementation of evidence-based interventions in the local context. In Malawi, a number of initiatives have begun addressing the NCD challenge, which have often utilized existing infectious disease infrastructure.

Microcosting Analysis of Diffuse Large B-Cell Lymphoma Treatment in Malawi.

Purpose: To describe the cost of treating diffuse large B-cell lymphoma (DLBCL) in Malawi under the following circumstances: (1) palliation only, (2) first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), (3) salvage etoposide, ifosfamide, and cisplatin (EPIC), and (4) salvage gemcitabine and oxaliplatin (GEMOX).

Methods: We conducted a microcosting analysis from the health system perspective in the context of a prospective cohort study at a national teaching hospital in Lilongwe, Malawi. Clinical outcomes data were derived from previously published literature from the cohort.

Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

Background: Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood.

Objectives: To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice.

Methods: Factor VIII (FVIII)-deficient mice +/- FVIII treatment and hypocoagulable wild-type mice ( BALB/c) were subjected to subpatellar puncture.

Rolling Circle Transcription-Amplified Hierarchically Structured Organic-Inorganic Hybrid RNA Flowers for Enzyme Immobilization.

Programmable nucleic acids have emerged as powerful building blocks for the bottom-up fabrication of two- or three-dimensional nano- and microsized constructs. Here we describe the construction of organic-inorganic hybrid RNA flowers (hRNFs) via rolling circle transcription (RCT), an enzyme-catalyzed nucleic acid amplification reaction. These hRNFs are highly adaptive structures with controlled sizes, specific nucleic acid sequences, and a highly porous nature.

Immunogold FIB-SEM: Combining Volumetric Ultrastructure Visualization with 3D Biomolecular Analysis to Dissect Cell-Environment Interactions.

Volumetric imaging techniques capable of correlating structural and functional information with nanoscale resolution are necessary to broaden the insight into cellular processes within complex biological systems. The recent emergence of focused ion beam scanning electron microscopy (FIB-SEM) has provided unparalleled insight through the volumetric investigation of ultrastructure; however, it does not provide biomolecular information at equivalent resolution. Here, immunogold FIB-SEM, which combines antigen labeling with in situ FIB-SEM imaging, is developed in order to spatially map ultrastructural and biomolecular information simultaneously.

Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia.

Antipsychotics are the mainstay in schizophrenia management, and long-acting injectable (LAI) antipsychotics contribute to the successful maintenance of treatment by improving non-adherence and preventing relapses. Paliperidone palmitate 3-monthly (PP3M) formulation is the only available LAI antipsychotic that offers an extended 3-month window of stable plasma drug concentration, enabling only four injections per year. This paper summarizes clinically relevant endpoints from available evidence for PP3M to bridge translational research gaps and provide measurable outcomes that can be interpreted in clinical practice.

Relationship of metabolic syndrome and neurocognitive deficits in patients with schizophrenia.

This study aimed to evaluate the association of the metabolic syndrome (MS) and its components with neurocognition among patients with schizophrenia. 121 patients with schizophrenia from an outpatient service of two psychiatric centers were assessed on a neurocognitive battery and by metabolic measures. More than half (56.

Giant intrathoracic teratoma presenting with cachexia and severe dyspnea.

Background: This case highlights the challenges of preoperative differential diagnosis and management in a patient with an uncommon clinical presentation of giant intrathoracic teratoma. The age of the patient, location and size of the tumor, and clinical presentation makes this case unique. Typically, intrathoracic teratomas are found between the ages of 20-30, they are located in the anterior mediastinum, and tumors larger than 25 cm clinically present with cough or dysphagia.

Unconventional secretory pathway activation restores hair cell mechanotransduction in an USH3A model.

The pathogenic variant c.144T>G (p.N48K) in the clarin1 gene () results in progressive loss of vision and hearing in Usher syndrome IIIA (USH3A) patients.

The landscape of cancer cell line metabolism.

Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated dependencies remain uncommon. To further understand the metabolic diversity of cancer, we profiled 225 metabolites in 928 cell lines from more than 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) using liquid chromatography-mass spectrometry (LC-MS). This resource enables unbiased association analysis linking the cancer metabolome to genetic alterations, epigenetic features and gene dependencies.

Gingival metastasis of adenocarcinoma with an unknown occult primary.

Metastatic dissemination to the oral cavity is extremely rare and constitutes about 1%-2.1% of all oral malignancies. The very first sign of the metastasis into the oral cavity indicates an occult malignancy in the distant site.

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies.

Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW).

Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase).

Epidemiological and histopathological profile of malignant melanoma in Malawi.

Background: Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype.

A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion.

Appropriate Wnt morphogen secretion is required to control animal development and homeostasis. Although correct Wnt globular structure is essential for secretion, proteins that directly mediate Wnt folding and maturation remain uncharacterized. Here, we report that protein disulfide isomerase-1 (PDI-1), a protein-folding catalyst and chaperone, controls secretion of the Caenorhabditis elegans Wnt ortholog EGL-20.

Psychometric properties of Tamil version of Body Weight Image and Self Esteem questionnaire (BWISE) in severe mental illness in a South Indian population.

Background: Body weight image self-esteem questionnaire (BWISE) has been recently developed to assess psychosocial adjustment related to antipsychotic induced weight gain in Schizophrenia and related disorders. Patients have reported disturbance in body image and poor self esteem due to weight gain leading to treatment non-adherence.

Aim: Assessment of psychometric properties of Tamil version of Body weight image self-esteem questionnaire (BWISE) in our population.

Efficacy and safety of paliperidone palmitate 3-month versus 1-month formulation in patients with schizophrenia: comparison between European and non-European population.

Purpose: This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia.

Patients And Methods: In this randomized, DB, parallel-group study, adult patients (18-70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4-12 weeks) phase.

Nanoneedle-Mediated Stimulation of Cell Mechanotransduction Machinery.

Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments.

Prospective study of Burkitt lymphoma treatment in adolescents and adults in Malawi.

Burkitt lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing nonpediatric BL and no regional standard of care.

Rosette-Forming Glioneuronal Tumor in Opticochiasmatic Region-Novel Entity in New Location.

Background: Rosette-forming glioneuronal tumour [RGNT] is a relatively rare entity first identified as a separate entity in 2002. We are reporting the second case of RGNT in the opticochiasmatic region.

Case Description: We report a case report and literature review of RGNT with syndromic association.