Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides.

Due to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids, such as RNA transcription, translation, splicing and degradation, or DNA replication and repair, is impaired by the presence of the CPPs. Interestingly, the effects of (PR)n are fully mimicked by protamine, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated with the onset of ALS.

Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells.

Full differentiation potential along with self-renewal capacity is a major property of pluripotent stem cells (PSCs). However, the differentiation capacity frequently decreases during expansion of PSCs in vitro. We show here that transient exposure to a single microRNA, expressed at early stages during normal development, improves the differentiation capacity of already-established murine and human PSCs. Short exposure to miR-203 in PSCs (miPSCs) induces a transient expression of 2C markers that later results in expanded differentiation potency to multiple lineages, as well as improved efficiency in tetraploid complementation and human-mouse interspecies chimerism assays. Mechanistically, these effects are at least partially mediated by direct repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to transient and reversible erasure of DNA methylation. These data support the use of transient exposure to miR-203 as a versatile method to reset the epigenetic memory in PSCs, and improve their effectiveness in regenerative medicine.

Ultrasonographic characteristics of myogenous temporomandibular disorders: A scoping review.

OBJECTIVE: To identify the available evidence on the ultrasonographic characteristics of masticatory muscles in subjects with myogenous TMD, as well as the potential use of ultrasonography as a diagnostic and treatment assessment outcomes tool. METHOD: An electronic search of the PubMed, Web of Science and Scopus databases was performed using the following terms: 'ultrasonography', 'ultrasound', 'masseter', 'temporal', 'masticatory muscles', 'temporomandibular disorders', 'temporomandibular joint disorders'. Full-text articles were obtained from the records after applying the inclusion/exclusion criteria. RESULTS: Thirteen articles were included for analysis: one comparative cross-sectional study, five case-control studies, six clinical trials and one randomised clinical trial. Main ultrasonographic characteristic assessed were local cross-sectional dimension and intramuscular ultrasonographic appearance. Retrieved studies reported the use ultrasonography for diagnosis or treatment assessment purposes showing heterogeneous results. For diagnosis purposes, the results of local cross-sectional dimension are not consistent; therefore, its diagnostic value for myogenous TMD diagnosis is weak. However, more homogeneous results were observed for intramuscular ultrasonographic appearance showing a higher prevalence of type-II pattern in myogenous TMD subjects than non-TMD subjects. On the other hand, for treatment assessment purposes, muscles were observed thinner after treatment compared to pre-treatment. Also, results of intramuscular ultrasonographic appearance show disappearance or reduction of anechoic areas, higher prevalence of type-II pattern and significant distinction of echogenic bands were observed after treating TMD subjects. CONCLUSION: Ultrasonography cannot be considered as a diagnostic instrument, but maybe as a complementary tool for treatment assessment of myogenous TMD subjects, even though future research is required to confirm its utility.

Promoting Justice, Diversity, Equity, and Inclusion Through Caring Communities: Why It Matters to Occupational Therapy.

The global challenges humanity faces today, such as social and economic inequalities, occupational deprivation, racism, exclusion, displacement and migration crises, violence, wars, and political oppression, all contribute to health and participation inequities (Powell & Toppin, 2021). The depth and breadth of these inequities became strikingly evident and were exacerbated with the coronavirus 2019 pandemic (Khanijahani et al., 2021). More than ever before, we need to apply an occupational perspective to create caring communities that strengthen each person's sense of belonging (Beagan, 2015; Lavalley & Johnson, 2020; Mahoney & Kiraly-Alvarez, 2019). In this column, we argue that occupational therapy academic programs have a unique role in advancing justice, equity, diversity, and inclusion through the creation of caring communities.

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

Targeting STAT3 anti-apoptosis pathways with organic and hybrid organic-inorganic inhibitors.

Recurrence and drug resistance are major challenges in the treatment of acute myeloid leukemia (AML) that spur efforts to identify new clinical targets and active agents. STAT3 has emerged as a potential target in resistant AML, but inhibiting STAT3 function has proven challenging. This paper describes synthetic studies and biological assays for a naphthalene sulfonamide inhibitor class of molecules that inhibit G-CSF-induced STAT3 phosphorylation in cellulo and induce apoptosis in AML cells. We describe two different approaches to inhibitor design: first, variation of substituents on the naphthalene sulfonamide core allows improvements in anti-STAT activity and creates a more thorough understanding of anti-STAT SAR. Second, a novel approach involving hybrid sulfonamide-rhodium(ii) conjugates tests our ability to use cooperative organic-inorganic binding for drug development, and to use SAR studies to inform metal conjugate design. Both approaches have produced compounds with improved binding potency. In vivo and in cellulo experiments further demonstrate that these approaches can also lead to improved activity in living cells, and that compound 3aa slows disease progression in a xenograft model of AML.

Tricuspid Regurgitation and Mortality Risk Across Left Ventricular Systolic Function in Acute Heart Failure.

BACKGROUND: Tricuspid regurgitation (TR) is a common echocardiographic finding that has been related to adverse outcome under various clinical scenarios. Nevertheless, evidence supporting its prognostic value in heart failure (HF) is scarce, and, in most cases, contradictory. We evaluated the association of TR grade with 1-year all-cause mortality in acute HF (AHF). METHODS AND RESULTS: We included 1,842 consecutive patients admitted for AHF. Mean age was 72.8±11.3 years, 51% were female and 45.5% had LVEF <50%. The severity of TR was graded in non-TR, mild (1), moderate (2), moderate-severe (3) and severe (4). At 1-year follow-up, 370 patients (20.1%) had died. In patients with LVEF ≥50%, a significant and positive association between TR severity and mortality was noted. Indeed, the HR for mortality for TR 3 and 4 vs. no TR/TR 1 were as follows: hazard ratios (HR), 1.68; 95% confidence intervals (95% CI): 1.08-2.60, P=0.02; and HR, 2.87; 95% CI: 1.61-5.09, P<0.001, respectively. In contrast, no association between TR grade and mortality (P=0.650) was observed in patients with LVEF <50% (P-value for interaction=0.033). CONCLUSIONS: A differential prognostic effect of TR severity on 1-year mortality was observed for LVEF HF status. The association was significant only in patients with LVEF ≥50%, with increasing mortality risk as TR became more severe.

Prognostic implications of tissue Doppler imaging-derived e/ea ratio in acute heart failure patients.

BACKGROUND: Tissue Doppler-derived transmitral to mitral annular early diastolic velocity ratio (E/Ea), as a noninvasive estimation of left ventricular (LV) filling pressures, is a strong prognosticator in various cardiac scenarios including chronic heart failure; nevertheless, its utility for risk stratification in the whole spectrum of acute heart failure (AHF) patients remains elusive. Thus, the aim of this study was to determine the association between E/Ea ratio and 1-year mortality in nonselected patients with AHF. METHODS: The study included 417 consecutive patients admitted for AHF. Twenty-two patients were excluded due to nonaccurate Ea measurements, leaving the final sample to be 395 patients. E-wave, septal, and lateral Ea velocities were measured following initial stabilization and according to current recommendations. The association of mean E/Ea ratio with all-cause mortality was assessed using Cox regression analysis. RESULTS: At a median follow-up of 306 days (interquartile range, 118-564), 89 deaths (22.5%) were registered. Mean age and E/Ea ratio were 72 ± 11.5 and 20 ± 3. Proportion of LV ejection fraction ≥50% was 47%. In multivariate analysis, after adjusting for well-known prognostic factors, including natriuretic peptides, E/Ea ratio was linearly associated with an increase risk of all-cause mortality (HR 1.04, 95% CI 1.03-1.05; P < 0.001, per increase in one unit of E/Ea). The threshold of risk was identified above 20. No significant interactions among the most important subgroups were found. CONCLUSION: In AHF patients, tissue Doppler imaging derived E/Ea ratio is independently associated with an increased risk of all-cause mortality.

Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Relationship between steroid use and superinfections in SARS-CoV-2 patients. A systematic review and meta-analysis.

Introduction: The use of steroids has been proposed as a pharmacological approach to treat the SARS-CoV-2 infection to improve outcomes. However, there are doubts about safety against the development of superinfections and their worse outcomes. Objective: To establish the relative frequency of superinfection associated with using steroids in patients with SARS-CoV-2 infection. Materials and methods: We conducted a systematic literature review and meta-analysis using PRISMA standards in 5 databases (PubMed/Scopus/Cochrane/EMBASE/Google Scholar). The search was carried out between February 2020 and May 2023. The search terms were 'steroids' or 'superinfection' 'and' followed by 'SARS-CoV-2' or 'COVID-19'. Results: We found 77 studies, but only 10 with 3539 patients were included in the systematic review. All patients developed severe disease. The documented OR for superinfection through the meta-analysis was 1.437 (95% IC 0.869-2.378) with a p-value of 0.158 without showing a risk attributed to steroids and the development of superinfections. In the Funnel-plot analysis, no publication biases were found. Conclusion: No relationship was found between using steroids and superinfection in patients with SARS-CoV-2.

Case Report: Kommerell's diverticulum and left aberrant subclavian artery stenosis hybrid treatment with branched aortic stent-graft.

Kommerell's diverticulum in association with left or right aberrant subclavian arteries is a rare finding and is challenging to treat. Contemporary surgical and endovascular techniques provide a broad arsenal of possible treatments. Imaging techniques and modeling technology allow a more personalized strategy for each patient. In this case, we present a symptomatic patient with a Kommerell's diverticulum and a left aberrant subclavian artery complicated by proximal stenosis and poststenotic aneurysm. A hybrid technique using a single-branched thoracic stent-graft (Castor, MicroPort Medical, Shanghai, China) in combination with a surgical left subclavian-carotid bypass and endovascular occlusion of the poststenotic aneurysm using a vascular plug device (Amplatzer Vascular Plug, Abbott, Chicago, United States) was performed. This approach was planned and facilitated by the use of a 3D model. Alternative treatment options and the strengths of this approach are briefly reviewed and discussed.

Baculovirus-mediated expression of a Helicobacter pylori protein-based multiepitope hybrid gene induces a potent B cell response in mice.

Helicobacter pylori is a gram-negative bacterium that is present in over half of the world's population. The colonization of the stomach́s gastric mucosa by H. pylori is related to the onset of chronic gastritis, peptic ulcer, and cancer. The estimated deaths from gastric cancer caused by this bacterial infection are in the 15,000-150,000 range. Current treatment for controlling the colonization of H. pylori includes the administration of two to four antibiotics and a gastric ATPase proton pump inhibitor. Nevertheless, the bacterium has shown increased resistance to antibiotics. Despite an extensive list of attempts to develop a vaccine, no approved vaccine against H. pylori is available. Recombinant viruses are a novel alternative for the control of primary pathogenic agents. In this work, we employed a baculovirus that carries a Thp1 transgene coding for nine H. pylori epitopes, some from the literature, and others were selected in silico from the sequence of H. pylori proteins (carbonic anhydrase, urease B subunit, gamma-glutamyl transpeptidase, Lpp20, Cag7, and CagL). We verified the expression of this hybrid multiepitopic protein in HeLa cells. Mice were inoculated with the recombinant baculovirus Bac-Thp1 using various administration routes: intranasal, intragastric, intramuscular, and a combination of intranasal and intragastric. We identified a strong adjuvant-independent IgG-antibody response in the serum of recombinant baculovirus-Thp1 inoculated mice, which was specific for a strain of H. pylori isolated from a human patient. The bacterium-specific IgG-antibodies were present in sera 125 days after the first vaccine administration. Also, H. pylori-specific IgA-antibodies were found in feces at 82 days after the first inoculation. A baculovirus-based vaccine for H. pylori is promising for controlling this pathogen in humans.

Moraxella nonliquefaciens superinfecting herpes simplex keratitis.

INTRODUCTION: Moraxella nonliquefaciens (M. nonliquefaciens) is a low pathogenicity microorganism, which rarely causes ocular infections, unless there is a predisposing factor. The main clinical manifestation of M. nonliquefaciens ocular infections is endophthalmitis and only five cases of corneal infection have been reported. This work shows an update in M. nonliquefaciens corneal infections, and the first reported case of keratitis due to M. nonliquefaciens superinfecting herpes simplex infection. CASE REPORT: A 84-year old woman with worsening of her herpes simplex keratitis, diagnosed, and treated 2 days before. The slit lamp showed deep paracentral infiltrate and hypopyon. A corneal sample was collected for culture prior to initiation of empiric antibiotic therapy with vancomycin and ceftazidime fortified, oral acyclovir, and cyclopentolate. The strain was identified as M. nonliquefaciens and topical antibiotic therapy was adjusted to ciprofloxacin and ceftazidime. After 2 weeks, the epithelial defect and the infiltrate were resolved and prednisolone was added to the regimen. As the corneal oedema and neovascularization decreased, acyclovir, and prednisolone were slowly tapered. About 4 months later, the visual outcome was 20/50 and the ophthalmic examination showed a clear cornea with a paracentral leucoma. CONCLUSION: Keratitis due to M. nonliquefaciens is rare and should be suspected in patients with local predisposing factors such as corneal damage or previous corneal infection. Prompt and appropriate combined treatment for the predisposing lesions and the keratitis may improve the prognosis and avoid a more aggressive approach.

CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome.

Children with Down syndrome (DS) are 10-fold more likely to develop B-cell acute lymphoblastic leukemia (B-ALL), with a higher frequency of rearrangements resulting in overexpression of cytokine receptor-like factor 2 (CRLF2). Here, we investigated the impact of CRLF2 overexpression on B-cell progenitor proliferation, immunophenotype, and gene expression profile in the Dp(16)1Yey (Dp16) mouse model of DS compared with wild-type (WT) mice. CRLF2 overexpression enhanced immature B-lymphoid colony development and increased the proportion of less differentiated pre-pro-B cells, with a greater effect in Dp16 versus WT. In CRLF2-rearranged (CRLF2-R) B-ALL patient samples, cells with higher CRLF2 expression exhibited a less differentiated B-cell immunophenotype. CRLF2 overexpression resulted in a gene expression signature associated with E2F signaling both in Dp16 B-progenitors and in DS-ALL patient samples, and PI3K/mTOR and pan-CDK inhibitors, which reduce E2F-mediated signaling, exhibited cytotoxicity in CRLF2-R B-ALL cell lines and patient samples. CRLF2 overexpression alone in Dp16 stem and progenitor cells did not result in leukemic transformation in recipient mice. Thus, CRLF2 overexpression results in reduced B-cell differentiation and enhanced E2F signaling in Dp16 B-progenitor cells and DS-ALL patient samples. These findings suggest a functional basis for the high frequency of CRLF2-R in DS-ALL as well as a potential therapeutically targetable pathway.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Morphological and molecular description of Blastocrithidia cyrtomeni sp. nov. (Kinetoplastea: Trypanosomatidae) associated with Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae) from Colombia.

A new trypanosomatid species, Blastocrithidia cyrtomeni, is herein described using morphological and molecular data. It was found parasitising the alimentary tract of the insect host Cyrtomenus bergi, a polyphagous pest. The morphology of B. cyrtomeni was investigated using light and transmission microscopy and molecular phylogeny was inferred from the sequences of spliced leader RNA (SL rRNA) - 5S rRNA gene repeats and the 18S small subunit (SSU) rRNA gene. Epimastigotes of variable size with straphanger cysts adhering to the middle of the flagellum were observed in the intestinal tract, hemolymph and Malpighian tubules. Kinetoplasts were always observed anterior to the nucleus. The ultrastructure of longitudinal sections of epimastigotes showed the flagellum arising laterally from a relatively shallow flagellar pocket near the kinetoplast. SL RNA and 5S rRNA gene repeats were positive in all cases, producing a 0.8-kb band. The amplicons were 797-803 bp long with > 98.5% identity, indicating that they originated from the same organism. According to the sequence analysis of the SL-5S rRNA gene repeats and the 18S SSU rRNA gene, B. cyrtomeni is different from all other known species or isolates of Trypanosomatidae. Both analyses indicate that among known species, it is most closely related to Blastocrithidia triatomae.

Severe diabetic ketoacidosis precipitated by COVID-19 in pediatric patients: Two case reports. / Cetoacidosis diabética severa precipitada por COVID-19 en pacientes pediátricos: reporte de dos casos.

INTRODUCTION: The association of COVID-19 with diabetes mellitus is bidirectional. In one direction, diabetes mellitus is associated with an increased risk of severe COVID-19. In the opposite direction, in patients with COVID-19 new-onset diabetes mellitus, severe diabetic ketoacidosis and severe metabolic complications have been described. CLINICAL CASE: This report describes two patients with diabetes mellitus who came to our hospital with ketoacidosis resulting from new-onset diabetes mellitus. We describe the clinical course and the management approach during the COVID-19 pandemic. CONCLUSION: COVID-19 is associated with metabolic complications such as severe diabetic ketoacidosis.

INTRODUCCIÓN: La relación entre la enfermedad por el coronavirus de 2019 (COVID-19) secundaria a SARS-CoV-2 y la diabetes mellitus es bidireccional. Por un lado, la diabetes mellitus se asocia con un mayor riesgo de COVID-19 grave. Por otro lado, en pacientes con COVID-19 se han observado diabetes mellitus de nueva aparición con presentaciones de cetoacidosis diabética y complicaciones metabólicas graves de dicha presentación. CASOS CLÍNICOS: En este informe, describimos a dos pacientes pediátricos con diabetes mellitus que acudieron a nuestro hospital con cetoacidosis diabética, de debut inicial. Describimos la evolución y el manejo clínico y terapéutico durante la pandemia de COVID-19. CONCLUSIÓN: La infección por COVID-19 puede precipitar complicaciones como cetoacidosis diabética severa.

COVID-19 as a trigger for splenic infarction in a patient with sickle cell trait: A case report.

Sickle cell trait (SCT) is the carrier state for sickle cell disease (SCD) and is usually perceived as a mild condition; however, previous studies have shown that hypoxemia may trigger sickle-cell related complications in these patients, including splenic infarction. Hypoxemia is a common finding in patients with COVID-19 pneumonia. We present the case of a 19-year-old male with a history of epilepsy who presented to the emergency room due to abdominal pain in the left flank that appeared after presenting generalized tonic-clonic seizures and fever. SARS-CoV-2 RT-PCR testing in nasopharyngeal swab was positive and an abdominal computerized tomography (CT) revealed a massive splenic infarction. Hemoglobinopathy study using high-efficiency liquid chromatography demonstrated the presence of 39.7% HbS, thus confirming the diagnosis of SCT. Hypoxemia, endothelial dysfunction and hypercoagulability caused by SARS-CoV-2 infection could lead to complement activation and microangiopathy, triggering the vaso-occlusive crisis that led to splenic infarction.

Prolactin's role in the early stages of liver regeneration in rats.

Liver regeneration after partial hepatectomy (PHx) is a complex process that is regulated by hemodynamic changes, the modulation of cytokines and growth factors, and the activation of immediate early transcription factors that lead to a round of hepatocyte mitosis. Among the factors involved, the pituitary hormone prolactin (PRL) has been shown to induce a hepatotrophic response after partial hepatectomy similar to that caused by phorbol esters; and in isolated hepatocytes PRL triggers a mitogenic response. However, it is becoming clear that PRL exerts a dual role acting in proliferation and differentiation processes. In this work, we have assessed the role of PRL in the early stages of liver regeneration in rats. To this end, three groups of rats were compared: Sham operated, regenerant and regenerant with PRL i.p. administration. Results show that PRL administration prior to partial hepatectomy caused an increase in the binding activity of several transcription factors involved in cell proliferation: AP-1, c-Jun and STAT-3, and in liver-specific differentiation and maintenance of energetic metabolism: CEBPalpha, HNF-1, HNF-4 at early time points and at later time points HNF-3. Hepatic sections show that PRL administration increases the number of proliferating cells within 5 h post-partial hepatectomy. The mRNA of the angiogenic and survival factors VEGF and HIF-1alpha, was also induced by PRL treatment. Data indicate that PRL triggers, either directly or indirectly, an acceleration of liver regeneration, preserving liver function and fulfilling a hepatoprotective role. J. Cell. Physiol. 219: 626-633, 2009. (c) 2009 Wiley-Liss, Inc.

An occupational and rehabilitation perspective for institutional practice.

OBJECTIVE: The article aims to provide an occupational perspective on the lives of people with a serious mental illness who have committed a criminal offense and are incarcerated in a secure environment. PURPOSE: The article focuses on ways that institutions fail to meet occupational needs of such persons and the challenges for mental health and psychiatric rehabilitation professionals, including occupational therapists, in providing psychiatric rehabilitation to facilitate community integration and participation. The concepts of occupational deprivation, occupational imbalance, habits and occupational enrichment provide useful theoretical constructs underpinning practice endeavors. SOURCES USED: Ovid using Medline, PsychINFO, CINAHL, OTDBase, and ProQuest. CONCLUSIONS: There is a priority for research to validate tools to assess outcomes of occupations in secure settings, and the use of these tools to focus on which rehabilitation practices are correlated with establishing positive outcomes after release. Research evidence is also needed that demonstrates that occupational enrichment can result in observable and measurable outcomes that mitigate the negative effects of incarceration and support successful community re-entry of persons with mental illnesses who are offenders.