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PurposeThis paper assesses the short-term consequences of the COVID-19 pandemic on the market for childcare and speculates about potential long-term consequences of pandemic-related policy intervention.Design/methodology/approachThe paper uses basic statistics and data to describe changes in the market for childcare.FindingsPolicy responses to the pandemic likely aggravated pre-existing trends in the market for childcare, drove up the cost of production at a time when demand was collapsed because of the pandemic, and ultimately resulted in systematic closures of childcare centers. These closures will be difficult to reverse due to the high cost of entry into the industry and overall low profitability.Research limitations/implicationsThe study is just a preliminary investigation in its current form that points to future areas of research.Originality/valueThis paper summarizes the results of existing studies and draws some basic conclusions about the effects of policy intervention.

Carbon materials displaying electrical double capacitance are widely used in the electrochemical energy storage devices. To enhance the electrochemical performance, compositing carbon with transition metal oxides and conducting polymers have been very much appreciated. A novel and effective approach to prepare a high energy density and high specific capacitance composite electrode material from a biomass is presented in the work. Pyrolysis of biomass at 500 oC in the nitrogen atmosphere yielded a biochar (BC) with well-developed porosity, surface functionality and suitable morphological characteristics. Anchoring ZnO nanoparticles on BC and subsequently coating it with a conducting polymeric material, polyaniline (PANI) obtained the hierarchical BC-ZnO/PANI composite. Both BC-ZnO and BC-ZnO/PANI composites have been characterized by FTIR, UV-Visible, XRD, SEM and TEM studies. The characteristic signals at 2θ values 18.5ᵒ, 28.4ᵒ,24.0ᵒ and 31.4ᵒ in XRD correspond to wurtzite structure of ZnO nanoparticles. ZnO rod like structural morphology was confirmed by SEM analysis. The maximum specific capacitance was found to be 110.0 F/g for BC-ZnO and 198.0 F/g for BC-ZnO/PANI. Furthermore, the ternary composite displayed low solution resistance and charge transfer resistance as evident from the Nyquist plots proved that PANI coating is a promising methodology in the fabrication of electrode materials for energy storage applications.

Pancreatic acinar cells are responsible for the synthesis and secretion of digestive enzymes. In order to sustain high rates of secretory protein production, acinar cells rely on adaptive mechanisms to mitigate endoplasmic reticulum (ER) stress and maintain secretory homeostasis. The adaptive unfolded protein response (UPR), mediated by the IRE1-XBP1s axis, is essential for acinar function and protects against cellular injury. Recent work has demonstrated that the ER acetyl-CoA transporter, AT-1, is necessary for nascent secretory protein acetylation and export out of the ER and is regulated by IRE1-XBP1s. Furthermore, AT-1 is rapidly downregulated during experimental pancreatitis. To investigate the role of AT-1 in exocrine pancreas function, we generated inducible, acinar-specific AT-1 knockout mice (Ela-Cre AT-1-/-). Loss of AT-1 produced a chronic pancreatitis phenotype characterized by inflammation, immune cell infiltration, tissue fibrosis, and aberrant intracellular activation of the proteolytic digestive enzyme trypsin. Despite the histological and biochemical dysfunction observed, Ela-Cre AT-1-/- mice grow normally, have typical lifespans, and do not lose pancreatic mass. Interestingly, XBP1s expression is significantly upregulated in Ela-Cre AT-1-/- and may confer a protective effect with loss of AT-1. Our data suggests a role for AT-1 in the IRE1-XBP1s axis and highlights the previously undescribed role of protein acetylation in exocrine pancreas physiology. Given the numerous potential downstream effects of dysregulated acetyl-CoA transport, this model will advance our understanding of pancreatic function and disease. NIH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Gliomas are the most prevalent type of brain tumors and one of the leading causes of cancer-related death in the adolescent and young adult population (AYA). Two-thirds of glioma AYA patients are affected by low-grade gliomas (LGGs), but there are no specific treatments. Therefore, a percentage of LGG patients experience tumor relapse and malignant progression to high-grade glioma which leads to fatal outcomes. In part, malignant progression is potentiated by the immunosuppressive stromal component of the tumor microenvironment (TME) underscored by M2-macrophages and a paucity of cytotoxic T cells. As a result, first-line immunotherapies have failed to improve outcomes for patients with progressive high-grade gliomas. Here, we report the efficacy of an in vivo approach that demonstrates the potential for a novel cell-mediated innate immunotherapy designed to abrogate immunosuppressive mechanisms within the glioma TME and enhance the recruitment of activated effector T cells. A single dose of engineered bone marrow-derived myeloid cells that release Interleukin-2 (GEMys-IL2) was used systemically to treat mice with LGG tumors systemically. Our results demonstrate that GEMys-IL2 efficiently crossed the blood brain barrier (BBB), infiltrated the glioma microenvironment, and reprogrammed the infiltrating immune cell composition and transcriptome. In addition, GEMys-IL2 impaired tumor progression and extended survival in a LGG immunocompetent mouse model. In conclusion, we demonstrated that GEMys-IL2 have a therapeutic effect in vivo, thus supporting its potential application as a novel immunotherapy that warrants further investigation.

ImportanceInterindividual variability in postprandial glycemic response (PPGR) to the same foods may explain why low glycemic index or load and low-carbohydrate diet interventions have mixed weight loss outcomes. A precision nutrition approach that estimates personalized PPGR to specific foods may be more efficacious for weight loss.ObjectiveTo compare a standardized low-fat vs a personalized diet regarding percentage of weight loss in adults with abnormal glucose metabolism and obesity.Design, Setting, and ParticipantsThe Personal Diet Study was a single-center, population-based, 6-month randomized clinical trial with measurements at baseline (0 months) and 3 and 6 months conducted from February 12, 2018, to October 28, 2021. A total of 269 adults aged 18 to 80 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) ranging from 27 to 50 and a hemoglobin A1c level ranging from 5.7% to 8.0% were recruited. Individuals were excluded if receiving medications other than metformin or with evidence of kidney disease, assessed as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation, to avoid recruiting patients with advanced type 2 diabetes.InterventionsParticipants were randomized to either a low-fat diet (Main Outcomes and MeasuresThe primary outcome was the percentage of weight loss from baseline to 6 months. Secondary outcomes included changes in body composition (fat mass, fat-free mass, and percentage of body weight), resting energy expenditure, and adaptive thermogenesis. Data were collected at baseline and 3 and 6 months. Analysis was based on intention to treat using linear mixed modeling.ResultsOf a total of 204 adults randomized, 199 (102 in the personalized group vs 97 in the standardized group) contributed data (mean [SD] age, 58 [11] years; 133 women [66.8%]; mean [SD] body mass index, 33.9 [4.8]). Weight change at 6 months was −4.31% (95% CI, −5.37% to −3.24%) for the standardized group and −3.26% (95% CI, −4.25% to −2.26%) for the personalized group, which was not significantly different (difference between groups, 1.05% [95% CI, −0.40% to 2.50%]; P = .16). There were no between-group differences in body composition and adaptive thermogenesis; however, the change in resting energy expenditure was significantly greater in the standardized group from 0 to 6 months (difference between groups, 92.3 [95% CI, 0.9-183.8] kcal/d; P = .05).Conclusions and RelevanceA personalized diet targeting a reduction in PPGR did not result in greater weight loss compared with a low-fat diet at 6 months. Future studies should assess methods of increasing dietary self-monitoring adherence and intervention exposure.Trial RegistrationClinicalTrials.gov Identifier: NCT03336411

Major adverse cardiac events (MACE) are a major contributor to morbidity and mortality in patients undergoing major vascular surgeries. We aim to assess the incidence, risk factors, and outcome of MACE in patients with coronary artery disease (CAD) undergoing aortic surgeries.In this retrospective observational study, we included patients with CAD who underwent elective major vascular surgery, namely, thoracoabdominal aortic aneurysm repairs and vascular bypass surgeries for aorto-occlusive disease, in our institute from January 2010 to December 2019. The association of preoperative risk factors including revised cardiac risk index factors, functional status of patients, severity of CAD, and its treatment status and technique of anesthesia with occurrence of MACE was analyzed.Medical records of 141 patients were studied. The incidence of perioperative MACE was 11.3% (16/141) and overall in-hospital mortality was 6.4% (9/141), all of them related to MACE; implicating a 56.2% mortality in patients who develop MACE. The odds of a patient who had undergone preoperative coronary revascularization to develop a MACE was higher than a nonrevascularized patient (odds ratio: 3.9; 95% confidence interval [CI], 1.34-11.34). There was found to be no benefit in the addition of epidural analgesia to general anesthesia in reducing perioperative MACE.Major vascular surgeries in patients with CAD are a highly morbid procedure and a perioperative MACE places them at a significantly high risk of mortality. Early detection of CAD and preoperative medical optimization can play a major role in reducing the risk of MACE.

Background The revised fourth edition of the World Health Organization Classification of Tumors of the Central Nervous System-published in 2016-established 1p19q codeletion as the molecular hallmark for the diagnosis of oligodendrogliomas. Fluorescence in situ hybridization (FISH) is currently the most commonly used modality for 1p19q testing. However, as with most laboratory testing, 1p19q FISH testing has a false-positive rate, potentially resulting in an erroneous diagnosis of oligodendroglioma with significant implications for the choice of therapy and prognosis. Methods The authors describe a case series of 5 patients treated at the Ohio State University James Cancer Center to illustrate the problem of false-positive 1p19q FISH results. Results In our case series, the authors present a spectrum of possibilities for conflicting 1p19q testing results and the clinical consequences. The authors present 4 cases that, in retrospect, are believed to have had a false 1p19q FISH results. One other case may represent a true transformation of oligodendroglioma to glioblastoma or a second malignancy. Neuro-oncologists should pay attention to additional molecular markers, namely ATRX, TP53, and MGMT methylation status, before discussing the pathology with the patient and formulating a treatment plan. Conclusions Pathologists and neuro-oncologists should be aware of false-positive 1p19q FISH results as they can significantly change treatment and prognosis for glioma patients. Moreover, this issue should be taken into account when designing clinical trials specific to this disease cohort.

BACKGROUND: Oncogenic fusions involving neurotrophic tyrosine receptor kinase (NTRK) have been identified across cancer types and represent potential therapeutic targets given availability of TRK inhibitors. Gliomas harboring NTRK fusions have been described most commonly in infants with high-grade histology and hemispheric tumor location, though there is emerging evidence suggesting clinical, histopathologic, and molecular heterogeneity. Herein, we present two cases of NTRK-rearranged suprasellar/ optic pathway gliomas. CASE DESCRIPTIONS: The first patient was diagnosed at 6 months old with an extensive suprasellar/ optic pathway tumor, treated with carboplatin/ vincristine, which initially responded but subsequently progressed. A biopsy was then performed, with pathology consistent with infiltrating piloid astrocytoma with anaplastic features (elevated mitoses and Ki-67 index); a BCAN-NTRK1 fusion was identified by RT-PCR and confirmed by Sanger sequencing. After further disease progression on vinblastine monotherapy, this patient began treatment with entrectinib (NCT02650401), with favorable clinical and radiographic responses thus far. The second patient was diagnosed with a large suprasellar/ optic pathway tumor at 3 years old, and underwent upfront partial resection, revealing similar infiltrating piloid/pilocytic astrocytoma with anaplastic features (elevated mitoses and Ki-67 index). A diagnosis of “midline” infantile high-grade glioma (HGG) was also considered, as with the former case. Sequencing demonstrated a SOX10-NTRK3 rearrangement, resulting in an integrated diagnosis of NTRK-fused infantile HGG, for which the patient recently started treatment with larotrectinib (NCT04655404). Both patients’ fusions retain the entire kinase domain of respective NTRK partners, supporting oncogenicity, and neither tumor harbored additional somatic pathogenic variants (both lacked BRAF alterations). Methylation profiling did not confidently classify either tumor. CONCLUSIONS: NTRK-rearranged gliomas may present with primary suprasellar/ optic pathway involvement in infants. Given the potential to offer targeted therapy, testing for the presence of NTRK fusions should be strongly considered for infantile gliomas in any location, including midline, and across the histologic spectrum.

Carbon developed from biomass is employed in the electrochemical energy storage device. By the development of novel carbon-based substances, especially the cost-effective, abundantly available biomass and its nanocomposite electrodes have gathered significant interest in formulating energy storing devices. The electrochemical energy storage properties of biochar-based composites had been analyzed in the present work. Banana stem (BS), a naturally abundant agricultural waste material was used as raw material for the study. It was pyrolyzed at 500 ℃ for 12 h under nitrogen atmosphere. Biochar (BC) was then converted into a binary composite with manganese (BC-Mn) and then to a ternary composite with PANI (BC-Mn/PANI). The composite formation was confirmed by the electronic transitions at 296 and 396 nm. The prominent peaks in XRD at 2θ values 38.3°, 42.6°, 56.4°, and 65.6° and 20.8° confirmed the presence of γ-type MnO2 and PANI in the composite. SEM images clearly displayed compact granular spherical morphology. The average particle size for BC-Mn and BC-Mn/PANI found to be 21.43 nm and 10.10 nm respectively from TEM images. The charge transfer resistance of BC-Mn (17.5 Ω) was found to be greater than BC-Mn/PANI (10.3 Ω), make the PANI composite a promising electrode material, though derived from a biomass. The specific capacitance values for BC-Mn (138 Fg−1) and BC-Mn/PANI (241.5 Fg−1) composites further proved the potential of the material. To satisfy the high demand for energy density a new concept hybrid supercapacitor came into an existence. By this approach energy density and the capacitance can be increased. In this current period, a composite electrode material-based biomass proved to be more promising one and highlighted as an alternative electrode material. We can combine relatively cheap materials to attain high electrochemical performance.

Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations.The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code.The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts.NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

INTRODUCTION Gliomas are the most prevalent type of brain tumors in the adolescent and young adult population (AYA) and one of the leading causes of cancer- related death. Two-third of glioma AYA patients are affected by low-grade gliomas (LGGs), but yet there are no specific treatments. Therefore, a significant percentage of LGG patients experience tumor recurrence and malignant progression to high-grade glioma (HGG) and the immune microenvironment plays a critical role in mediating mechanisms of tumor progression and treatment resistance. Specifically, tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) have been shown to restrict cytotoxic effector trafficking and activation. To that end, first-line immunotherapies have limited efficacy in improving outcomes for HGGs. HYPOTHESIS We investigated the preclinical efficacy of a novel immunotherapeutic approach for the treatment of LGGs in AYA mice to modulate and reprogram the immunosuppressive tumor microenvironment (TME) and enhance the trafficking of activated effector T cells. METHODS Immunocompetent RCAS n/tv-a LGG bearing animals were treated at day 28 with a single retroorbital dose of bone-marrow derived myeloid cells, engineered for the release of Interlekin-2 (GEMys-IL2). The treatment was well tolerated and no sign of toxicity was noted. RESULTS Our results demonstrated that GEMys-IL2 efficiently crossed the BBB, infiltrate the glioma microenvironment, and activate infiltrating immune cells while altering the TME underscored by an increased CD8+ T cell population. Of note, the RCAS/t-va immunocompetent LGG to HGG progression mouse model treated with a single dose of GEMys-IL2 demonstrated a transient arrest of tumor burden within 14 days post treatment, which was associated with a significant advantage in overall survival. CONCLUSIONS These results highlight the pre-clinical efficacy and anti-tumoral therapeutic activity of GEMYys-IL2 on CD8+ T cell trafficking and activation to the TME in low-grade glioma in vivo, thus supporting its potential as a novel cell-mediated innate immunotherapy.

Background and Aims: Continuous wound infiltration of local anaesthetics provide postoperative analgesia by peripheral nociceptors blockade. The placement of wound infiltration catheter in the optimal anatomical plane of surgical wound may play a significant role in reducing postoperative pain depends on the surgical procedure. We hypothesised that preperitoneal infusion of local anaesthetics will reduce the postoperative opioid consumption as compared to subcutaneous infusion following cesarean section. Methods: This was a randomised, double-blinded clinical trial. Fifty-two pregnant women who underwent lower segment caesarean section by Pfannensteil incision, under spinal anaesthesia, were randomised to group 'subcutaneous' and group 'preperitoneal'. A wound infiltration catheter was placed in the subcutaneous or preperitoneal plane, depending on their randomisation at the end of the surgery. Bupivacaine of 0.25% at 5 mL/h was infused for the next 48 h. Pain was assessed using numerical rating scale at 1, 2, 3, 4, 5, 6, 12, 24, 36 and 48 h after surgery. Cumulative postoperative consumption and adverse effects of morphine and complications of the procedure were looked for. Results: Cumulative 48-h morphine consumption showed no statistical significance between the preperitoneal group (15.96 ± 7.69 mg) and subcutaneous group (21.26 ± 11.03 mg); P = 0.058. Pain score was comparable. Independent T-test and Mann–Whitney test were the statistical tests used for continuous and categorical data, respectively. Conclusion: Postoperative cumulative morphine consumption and pain scores are comparable when bupivacaine is infused continuously through wound infiltration catheter either in the preperitoneal or subcutaneous layer following Caesarean delivery.

BACKGROUND: The B-cell-specific Moloney murine leukemia virus integration site-1 (BMI-1) protein, implicated in self-renewal and DNA-damage signaling, is highly expressed in DIPG and HGG. Preclinically, BMI-1 modulation by unesbulin (PTC596 [which mediates hyperphosphorylation and subsequent degradation of BMI-1]) leads to DIPG/HGG cell proliferation blockade, mitotic abnormalities, and tumor cell sensitization to radiation-induced DNA damage. METHODS: This phase Ib study sought to determine the maximally tolerated dose/ recommended phase 2 dose (RP2D) of unesbulin administered concurrently with radiotherapy and adjuvantly in children with newly diagnosed DIPG or HGG. Patients were enrolled according to a Rolling-6 design and received oral unesbulin twice weekly during radiotherapy and as maintenance therapy. RESULTS: Twenty-seven patients enrolled (median age: 8.5 years [range: 2-18]), including 18 patients with DIPG and nine patients with HGG. Unesbulin was administered in capsule formulation in the first nine patients, then tablet formulation for subsequent patients. Within the capsule formulation group, three dose-limiting toxicities (DLTs) were observed in two patients on dose level 2 (grade 4 neutropenia). Within the tablet formulation group, four DLTs were experienced by three patients on dose level 2 (grade 3 ALT elevation, grade 3 dehydration/vomiting, grade 3 decreased ejection fraction, grade 4 neutropenia). Dose level 1 was declared the RP2D, and six additional patients enrolled in the expansion cohort at this dose without DLTs. Most common drug-related grade 3/4 toxicities were neutropenia (48%), leucopenia (35%), and elevated ALT (26%). Similar pharmacokinetic profiles were observed for capsule and tablet formulations, consistent with adult data. Survival outcomes and genomics results will be shared at time of presentation. CONCLUSIONS: The RP2D of unesbulin in children newly diagnosed with DIPG or HGG is 200mg/m2 twice weekly, concurrent with and following radiotherapy. The recently opened surgical cohort will assess intratumoral pharmacokinetics and inhibition of tumor BMI-1 signaling, with results forthcoming.

Advances in RNA and DNA profiling have identified four core molecular subgroups of medulloblastoma of prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. Infants and young children with SHH medulloblastoma have demonstrated a favorable outcome in clinical trials utilizing either high-dose chemotherapy (“Head Start”) or a combination of intravenous and intraventricular methotrexate (HIT-SKK). Two recently conducted clinical trials (COG ACNS1221 and St. Jude – SJYC07) failed to demonstrate similar survival advantage with conventional dose chemotherapy and without intraventricular methotrexate. “Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare the efficacy of one versus versus three (tandem) cycles of myeloablative therapy. Eligibility includes newly diagnosed children less than six years of age with localized medulloblastoma. Eligible patients with SHH medulloblastoma were considered “low-risk” and non-randomly assigned to receive three cycles of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, etoposide, and high-dose methotrexate) followed by consolidation with single cycle of myeloablative chemotherapy (thiotepa, carboplatin, etoposide) and autologous hematopoietic progenitor cell rescue. Patients with less than a complete response after three induction cycles received two additional cycles prior to consolidation therapy. Only children between 6 -10 years old, or those with confirmed residual tumor post-consolidation, were meant to receive irradiation after consolidation. Twenty-eight children with localized SHH medulloblastoma were enrolled on the trial with a median age of 2.1 years (range: 0.3-5.9 years). Median follow-up for this cohort is 29.6 months (range: 7.0-58.6 months). The estimated 3-year event-free (EFS) and overall survival (OS) is 96% (CI: 89-100%) and 100%, respectively. The estimated 3-year EFS for SHH subtype 1 and 2 patients is 100% and 95%, respectively (p=0.65). None of the M0 SHH medulloblastoma patients received irradiation.

In this work a novel composite, acrylamide β-cyclodextrin grafted silylated bentonite was synthesized for the controlled delivery of tetracycline hydrochloride (TCH). Characterization of the drug delivery system was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis etc. The equilibrium swelling behaviour of the composite was studied and the result showed a maximum at pH 7.4. The in vitro drug release study of tetracycline hydrochloride at pH 7.4 was shown to be divided into three stages, first of which was the initial burst followed by slower release and finally a constant rate of release. In vitro biocompatibility study was performed and the result showed good biocompatibility of the composite in the concentration range of 50–450 μg/mL. Drug delivery study of the composite proved that TCH could be successfully released in a controlled manner in the colon without much loss of drug in the stomach.

Concrete is a major contributor to the environmental impact of the construction industry, due to its cement content but also its reinforcement. Reinforcement has a significant contribution because of construction rationalisation, resorting to regular mats or cages of steel bars, despite layoutoptimisation algorithms and additive-manufacturing technologies. This paper presents an automated framework, connecting design and fabrication requirements for the optimisation of spatial layouts as of reinforcement of concrete structures, by the means of robotic filament winding.

Background The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period. Methods This is a retrospective study of the α-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was performed by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot blot hybridization (Vienna Lab Strip Assay). Results Four hundred samples were characterized and analyzed from individuals aged PA-1α/α PA-1α) in 33.3% of the samples, followed by heterozygosity (αα/α PA-1α) for the same mutation in 32.3%. PA-1 was therefore the most frequent allele (0.59). The frequency of the α0 (−-MED) allele was 0.017. Rare alleles that were found in very low frequencies included α0 (−-FIL) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria. Conclusion There is a wide variety of alpha thalassemia alleles among Kuwaitis, but nondeletional PA-1 is by far the most common cause of the moderate to severe HbH (β4 tetramer) disease phenotype. The α0 (−MED) allele is also encountered, which has implications for premarital counseling, especially for the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).

Editor Richard Gartner is an American expert in the field of understanding the specifically male experience of sexual abuse and has written about this, until recently, ignored or overlooked subject...

Background Acute ischemic stroke is a leading cause of death and disability worldwide. Unlike myocardial infarction, there is no current blood test to diagnose acute ischemic stroke. MicroRNAs (miRNAs) are very stable in the blood and have been suggested as potential diagnostic markers. Materials and Methods This review aimed to systematically assess case–control studies investigating the association of circulating miRNAs with acute ischemic stroke. Medline, CINAHL, Cochrane Library, Web of Science, Scopus, and PubMed were searched for studies that examined the association of circulating miRNAs in patients with acute ischemic stroke. Studies meeting specific inclusion and exclusion criteria (such as blood samples obtained within 24 hours of an acute ischemic stroke) were selected for data extraction. Two authors extracted data from the included studies relevant to the study design, the patient characteristics, and the relative miRNA expression. Results Eight studies were included involving 572 cases and 431 healthy controls. Twenty-two miRNAs (12 upregulated and 10 downregulated) were reported as differentially expressed. Only 1 miRNA, miR-106b, was reported as differentially expressed in at least 2 studies. Significant heterogeneity in the design and methods of the included studies was noted. Conclusions Differential expression of a large number of miRNAs has been reported early following acute ischemic stroke. More research is required in larger patient populations to further evaluate the diagnostic potential of the reported miRNAs.