Type 2 diabetes mellitus, obesity, cesarean section delivery, and lack of exclusive breastfeeding exposure in patients from the Guadalajara Metropolitan Area, Mexico.

INTRODUCTION: the combination of cesarean section delivery and limited exposure to exclusive breastfeeding (EBF) in the first six months of life may increase the risk of obesity and diabetes mellitus. This study aimed to establish an association between type 2 diabetes mellitus (T2DM) in adulthood, cesarean section delivery and incomplete breastfeeding (FBF) in individuals from the metropolitan area of Guadalajara, Mexico. METHODOLOGY: this analytical cross-sectional study included patients over 18 years of age with T2DM and normal weight, overweight or obesity, regardless of sex. Informed consent was obtained. Variables encompassed T2DM, type of delivery method, first-year diet, family history, demographic, socioeconomic, and educational characteristics, and anthropometric measurements. For statistical analysis, Student's t test, chi-square tests and odds ratios were employed. RESULTS: the study evaluated 218 patients with an average age of 57.8 years (± 12.7) and an average age at T2DM diagnosis of 46.2 years (± 12.5). FBF (65.6 %) and partial breastfeeding (PBF) (23.8 %) prevailed in the first six months. The average age at T2DM diagnosis was 46.7 years (± 12.1) for vaginally born patients and 30.7 years (± 15.5) for cesarean-born patients (p = 0.001). Cesarean delivery increased obesity risk by nine times in patients with T2DM [OR = 8.9 (CI, 1.05, 75.2), p = 0.02]. CONCLUSION: prioritizing the limitation of nonmedically justified cesarean section deliveries is crucial to mitigate the risk of obesity and T2DM in adulthood. .

Targeting the immunoproteasome in hypothalamic neurons as a novel therapeutic strategy for high-fat diet-induced obesity and metabolic dysregulation.

OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.

Regulatory T cells administration reduces anxiety-like behavior in mice submitted to chronic restraint stress.

Background: Major depression disorder (MDD) and anxiety are common mental disorders that significantly affect the quality of life of those who suffer from them, altering the person's normal functioning. From the biological perspective, the most classical hypothesis explaining their occurrence relies on neurotransmission and hippocampal excitability alterations. However, around 30% of MDD patients do not respond to medication targeting these processes. Over the last decade, the involvement of inflammatory responses in depression and anxiety pathogenesis has been strongly acknowledged, opening the possibility of tackling these disorders from an immunological point of view. In this context, regulatory T cells (Treg cells), which naturally maintain immune homeostasis by suppressing inflammation could be promising candidates for their therapeutic use in mental disorders. Methods: To test this hypothesis, C57BL/6 adult male mice were submitted to classical stress protocols to induce depressive and anxiety-like behavior; chronic restriction stress (CRS), and chronic unpredictable stress (CUS). Some of the stressed mice received a single adoptive transfer of Treg cells during stress protocols. Mouse behavior was analyzed through the open field (OFT) and forced swim test (FST). Blood and spleen samples were collected for T cell analysis using cell cytometry, while brains were collected to study changes in microglia by immunohistochemistry. Results: Mice submitted to CRS and CUS develop anxiety and depressive-like behavior, and only CRS mice exhibit lower frequencies of circulating Treg cells. Adoptive transfer of Treg cells decreased anxiety-like behavior in the OFT only in CRS model, but not depressive behavior in FST in neither of the two models. In CRS mice, Treg cells administration lowered the number of microglia in the hippocampus, which increased due this stress paradigm, and restored its arborization. However, in CUS mice, Treg cells administration increased microglia number with no significant effect on their arborization. Conclusion: Our results for effector CD4+ T cells in the spleen and microglia number and morphology in the hippocampus add new evidence in favor of the participation of inflammatory responses in the development of depressive and anxiety-like behavior and suggest that the modulation of key immune cells such as Treg cells, could have beneficial effects on these disorders.

Next-generation BCMA-targeted chimeric antigen receptor CARTemis-1: the impact of manufacturing procedure on CAR T-cell features.

PURPOSE: CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives is imperative. We present the preclinical and clinical validation of a new optimized anti-BCMA CAR (CARTemis-1). In addition, we explored how the manufacturing process could impact CAR-T cell product quality and fitness. METHODS: CARTemis-1 optimizations were evaluated at the preclinical level both, in vitro and in vivo. CARTemis-1 generation was validated under GMP conditions, studying the dynamics of the immunophenotype from leukapheresis to final product. Here, we studied the impact of the manufacturing process on CAR-T cells to define optimal cell culture protocol and expansion time to increase product fitness. RESULTS: Two different versions of CARTemis-1 with different spacers were compared. The longer version showed increased cytotoxicity. The incorporation of the safety-gene EGFRt into the CARTemis-1 structure can be used as a monitoring marker. CARTemis-1 showed no inhibition by soluble BCMA and presents potent antitumor effects both in vitro and in vivo. Expansion with IL-2 or IL-7/IL-15 was compared, revealing greater proliferation, less differentiation, and less exhaustion with IL-7/IL-15. Three consecutive batches of CARTemis-1 were produced under GMP guidelines meeting all the required specifications. CARTemis-1 cells manufactured under GMP conditions showed increased memory subpopulations, reduced exhaustion markers and selective antitumor efficacy against MM cell lines and primary myeloma cells. The optimal release time points for obtaining the best fit product were > 6 and < 10 days (days 8-10). CONCLUSIONS: CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00).

Targeted whole-genome recovery of single viral species in a complex environmental sample.

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. We present an experimental method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A unique gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. We demonstrate this method's efficacy by spiking two known viral genomes, Simian virus 40 (SV40, 5,243 bp) and Human Adenovirus 5 (HAd5, 35,938 bp), into a sewage sample with a final abundance in the droplets of around 0.1% and 0.015%, respectively. We achieve 100% recovery of the complete sequence of the spiked-in SV40 genome with uniform coverage distribution. For the larger HAd5 genome, we cover approximately 99.4% of its sequence. Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables single-genome whole-genome amplification and targeting characterizations of rare viral species and will facilitate our ability to access the mutational profile in single-virus genomes and contribute to an improved understanding of viral ecology.

BDNF-TrkB signaling orchestrates the buildup process of local sleep.

Sleep debt accumulates during wakefulness, leading to increased slow wave activity (SWA) during sleep, an encephalographic marker for sleep need. The use-dependent demands of prior wakefulness increase sleep SWA locally. However, the circuitry and molecular identity of this "local sleep" remain unclear. Using pharmacology and optogenetic perturbations together with transcriptomics, we find that cortical brain-derived neurotrophic factor (BDNF) regulates SWA via the activation of tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We map BDNF/TrkB-induced sleep SWA to layer 5 (L5) pyramidal neurons of the cortex, independent of neuronal firing per se. Using mathematical modeling, we here propose a model of how BDNF's effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Proteomic analysis further reveals that TrkB activation enriches ubiquitin and proteasome subunits. Together, our study reveals that local SWA control is mediated by BDNF-TrkB-CREB signaling in L5 excitatory cortical neurons.

Executive dysfunction and cortical variations among intimate partner violence perpetrators and the association with sexism.

Malfunctioning in executive functioning has been proposed as a risk factor for intimate partner violence (IPV). This is not only due to its effects on behavioral regulation but also because of its association with other variables such as sexism. Executive dysfunctions have been associated with frontal and prefrontal cortical thickness. Therefore, our first aim was to assess differences in cortical thickness in frontal and prefrontal regions, as well as levels of sexism, between two groups of IPV perpetrators (with and without executive dysfunctions) and a control group of non-violent men. Second, we analyzed whether the cortical thickness in the frontal and prefrontal regions would explain sexism scores. Our results indicate that IPV perpetrators classified as dysexecutive exhibited a lower cortical thickness in the right rostral anterior cingulate superior frontal bilaterally, caudal middle frontal bilaterally, right medial orbitofrontal, right paracentral, and precentral bilaterally when compared with controls. Furthermore, they exhibited higher levels of sexism than the rest of the groups. Most importantly, in the brain structures that distinguished between groups, lower thickness was associated with higher sexism scores. This research emphasizes the need to incorporate neuroimaging techniques to develop accurate IPV profiles or subtypes based on neuropsychological functioning.

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Study on Behalf of the Spanish Hematopoietic Stem Cell Transplantation and Cellular Therapy Group (GETH).

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). However, its characterization after haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) is scarce. This study aimed to describe characteristics and outcomes of patients with SOS/VOD after haplo-HSCT with PT-Cy. We conducted a retrospective study of 797 patients undergoing a haplo-HSCT with PT-Cy between 2007 and 2019 in 9 centers in Spain. SOS/VOD was defined according to modified Seattle, Baltimore, or revised European Society for Blood and Marrow Transplantation (EBMT) criteria. Severity was graded retrospectively according to revised EBMT severity criteria into 4 categories: mild, moderate, severe, and very severe. From a total of 797 haplo-HSCTs performed, 46 patients (5.77%) were diagnosed with SOS/VOD at a median of 19 days (range, 4 to 84 days) after transplantation. Based on revised EBMT severity criteria, the SOS/VOD cases were classified as mild (n = 4; 8.7%), moderate (n = 10; 21.7%), severe (n = 12; 26.1%), and very severe (n = 20; 43.5%). Overall, 30 patients (65%) achieved SOS/VOD complete response, 25 (83%) of whom were treated with defibrotide. Twenty patients (43%) died before day +100 post-HSCT. Death was attributed to SOS/VOD in 11 patients, and 5 patients died of other causes without resolution of SOS/VOD. The incidence of SOS/VOD after haplo-HSCT with PT-Cy was comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria. Despite a promising SOS/VOD complete response (CR) rate (65%), 100-day mortality remained high (43%), indicating that further improvement in the management of this potentially fatal complication is needed.

Deep learning automatic semantic segmentation of glioblastoma multiforme regions on multimodal magnetic resonance images.

OBJECTIVES: In patients having naïve glioblastoma multiforme (GBM), this study aims to assess the efficacy of Deep Learning algorithms in automating the segmentation of brain magnetic resonance (MR) images to accurately determine 3D masks for 4 distinct regions: enhanced tumor, peritumoral edema, non-enhanced/necrotic tumor, and total tumor. MATERIAL AND METHODS: A 3D U-Net neural network algorithm was developed for semantic segmentation of GBM. The training dataset was manually delineated by a group of expert neuroradiologists on MR images from the Brain Tumor Segmentation Challenge 2021 (BraTS2021) image repository, as ground truth labels for diverse glioma (GBM and low-grade glioma) subregions across four MR sequences (T1w, T1w-contrast enhanced, T2w, and FLAIR) in 1251 patients. The in-house test was performed on 50 GBM patients from our cohort (PerProGlio project). By exploring various hyperparameters, the network's performance was optimized, and the most optimal parameter configuration was identified. The assessment of the optimized network's performance utilized Dice scores, precision, and sensitivity metrics. RESULTS: Our adaptation of the 3D U-net with additional residual blocks demonstrated reliable performance on both the BraTS2021 dataset and the in-house PerProGlio cohort, employing only T1w-ce sequences for enhancement and non-enhanced/necrotic tumor models and T1w-ce + T2w + FLAIR for peritumoral edema and total tumor. The mean Dice scores (training and test) were 0.89 and 0.75; 0.75 and 0.64; 0.79 and 0.71; and 0.60 and 0.55, for total tumor, edema, enhanced tumor, and non-enhanced/necrotic tumor, respectively. CONCLUSIONS: The results underscore the high precision with which our network can effectively segment GBM tumors and their distinct subregions. The level of accuracy achieved agrees with the coefficients recorded in previous GBM studies. In particular, our approach allows model specialization for each of the different tumor subregions employing only those MR sequences that provide value for segmentation.

Migration of the left atrial appendage closure device to the aorta.

Percutaneous closure of the left atrial appendage may be indicated in patients with contraindications to anticoagulation therapy, for example, after recurrent gastrointestinal bleeding. It is an effective and safe procedure but is not without complications. We present a patient who presented with severe aortic insufficiency due to migration of the left atrial appendage closure device, which required urgent cardiac surgery for its removal.

Electrophoretic Mobility Assay to Separate Supercoiled, Catenated, and Knotted DNA Molecules.

Two-dimensional (2D) agarose gel electrophoresis is the method of choice to analyze DNA topology. The possibility to use E. coli strains with different genetic backgrounds in combination with nicking enzymes and different concentrations of norfloxacin improves the resolution of 2D gels to study the electrophoretic behavior of three different families of DNA topoisomers: supercoiled DNA molecules, post-replicative catenanes, and knotted DNA molecules. Here, we describe the materials and procedures required to optimize their separation by 2D gels. Understanding the differences in their electrophoretic behavior can help explain some important physical characteristics of these different types of DNA topoisomers. Key features • Preparative method to enrich DNA samples of supercoiled, catenated, and knotted families of topoisomers, later analyzed by 2D gels (or other techniques, e.g., microscopy). • 2D gels facilitate the separation of the topoisomers of any given circular DNA molecule. • Separation of DNA molecules with the same molecular masses but different shapes can be optimized by modifying the conditions of 2D gels. • Evaluating the roles of electric field and agarose concentration on the electrophoretic mobility of DNA topoisomers sheds light on their physical characteristics.

A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Transcription-coupled repair of DNA-protein cross-links depends on CSA and CSB.

Covalent DNA-protein cross-links (DPCs) are toxic DNA lesions that block replication and require repair by multiple pathways. Whether transcription blockage contributes to the toxicity of DPCs and how cells respond when RNA polymerases stall at DPCs is unknown. Here we find that DPC formation arrests transcription and induces ubiquitylation and degradation of RNA polymerase II. Using genetic screens and a method for the genome-wide mapping of DNA-protein adducts, DPC sequencing, we discover that Cockayne syndrome (CS) proteins CSB and CSA provide resistance to DPC-inducing agents by promoting DPC repair in actively transcribed genes. Consequently, CSB- or CSA-deficient cells fail to efficiently restart transcription after induction of DPCs. In contrast, nucleotide excision repair factors that act downstream of CSB and CSA at ultraviolet light-induced DNA lesions are dispensable. Our study describes a transcription-coupled DPC repair pathway and suggests that defects in this pathway may contribute to the unique neurological features of CS.

Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS.

OBJECTIVES: Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop 'flare criteria'. METHODS: Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop 'clinical' and 'subclinical' flare criteria. Disease flare rates were compared among patients with <25% and >25% dose reductions and during study visits when patients received recommended 'optimized' baricitinib doses (high-dose visits) versus lower than recommended baricitinib doses (low-dose visits) using two-sided χ2 tests. RESULTS: In the 9/10 patients with CANDLE with dose reduction, 7/14 (50%) times the dose was reduced resulted in a disease flare. All four dose reductions of >25% triggered a disease flare (p <0.05). Assessment of clinical and laboratory changes during disease flares allowed the development of disease flare criteria that were assessed during visits when patients received high or low doses of baricitinib. Disease flare criteria were reached during 43.14% of low-dose visits compared with 12.75% of high-dose visits (p <0.0001). Addition of an interferon score as an additional flare criterion increased the sensitivity to detect disease flares. CONCLUSION: We observed disease flares and rebound inflammation with baricitinib dose reductions and proposed flare criteria that can assist in monitoring disease activity and in designing clinical studies in CANDLE/PRAAS.

The contribution of brain volume to explain autonomous imbalance during recovery from acute stress in batterers.

AIM: Many authors have suggested that intimate partner violence (IPV) perpetrators present an imbalance between both branches of the autonomous nervous system when coping with acute stress. Concretely, there is a predominance of the sympathetic branches over the parasympathetic ones when recovering from stress. This imbalance can be explained by their tendency toward anger rumination, and more concretely, by their focus on thoughts of revenge during this period. Unfortunately, there is a gap in the scientific literature in terms of using magnetic resonance imaging (MRI) techniques to assess which brain structures would explain this tendency of IPV perpetrators when coping with acute stress. METHOD: The main objective of this study was to assess whether the gray matter volume (GMV) of relevant brain structures, signaled in previous scientific literature, moderates the association between thoughts of revenge and sympathetic activation during the recovery period, based on skin conductance levels (SCL) after being exposed to stress, in a group of IPV perpetrators (n = 58) and non-violent men (n = 61). RESULTS: This study highlighted that the GMV of the left nucleus accumbens, right lobules of the cerebellum, and inferior temporal gyrus in IPV perpetrators moderated the association between thoughts of revenge and SCL during the recovery period. Accordingly, the higher the thoughts of revenge, the higher the sympathetic predominance (or higher SCL levels), especially among IPV perpetrators with the lowest GMV of these brain structures. Nonetheless, those variables were unrelated in the control group. CONCLUSIONS: Our study highlights the involvement of certain brain structures and how they explain the tendency of some IPV perpetrators to ruminate anger or, more precisely, to focus on thoughts of revenge when they recover from acute stress. These results reinforce the need to incorporate neuroimaging techniques during screening processes to properly understand how IPV perpetrators deal with stress, which in turn helps target their needs and design concrete intervention modules.

Associations of current and childhood socioeconomic status and health outcomes amongst patients with knee or hip osteoarthritis in a Mexico City family-practice setting.

OBJECTIVES: To examine the association of current and childhood socioeconomic status (SES) with patient-reported functional status, quality of life and disability in patients with knee or hip osteoarthritis (OA). METHODS: Cross-sectional study amongst individuals seeking care for any medical reason in a primary care family-practice clinic in Mexico City. We included individuals with self-reported doctor-diagnosed arthritis, recruited through waiting-room posters and invitations by treating family physicians. We administered a survey using validated Spanish language versions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Osteoarthritis of Lower Limbs and Quality of Life (AMICAL), and the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI). To estimate current and childhood SES, we collected data on education level and occupation type for both the patient and their parents, as well as using a validated tool to estimate income quintile. RESULTS: We recruited 154 patients and excluded 8 patients. There was a high correlation between outcome scores. Estimated income and education levels were correlated with WOMAC, AMICAL and HAQ-DI scores, and significant differences were found in all scores by occupation type. The associations for current SES variables and outcome scores remained significant independently of age, sex, BMI, and presence of diabetes or hypertension, and were largely explained by current income in mutually adjusted models. Childhood SES - in particular as measured through maternal education - was best correlated with AMICAL scores, though its effect seemed largely mediated by its association with current SES. CONCLUSIONS: Current Socioeconomic Status impacts functional status, quality of life and disability amongst OA patients in Mexico City. The WOMAC, AMICAL and HAQ-DI scores correlate with each other and are all potentially useful markers of disease severity. More research is needed to elucidate the relationships between childhood SES and OA outcomes. Awareness of life-course SES may be useful in identifying patients at risk for worse outcomes.

COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

The Vicious Cycle of Type 2 Diabetes Mellitus and Skeletal Muscle Atrophy: Clinical, Biochemical, and Nutritional Bases.

Today, type 2 diabetes mellitus (T2DM) and skeletal muscle atrophy (SMA) have become increasingly common occurrences. Whether the onset of T2DM increases the risk of SMA or vice versa has long been under investigation. Both conditions are associated with negative changes in skeletal muscle health, which can, in turn, lead to impaired physical function, a lowered quality of life, and an increased risk of mortality. Poor nutrition can exacerbate both T2DM and SMA. T2DM and SMA are linked by a vicious cycle of events that reinforce and worsen each other. Muscle insulin resistance appears to be the pathophysiological link between T2DM and SMA. To explore this association, our review (i) compiles evidence on the clinical association between T2DM and SMA, (ii) reviews mechanisms underlying biochemical changes in the muscles of people with or at risk of T2DM and SMA, and (iii) examines how nutritional therapy and increased physical activity as muscle-targeted treatments benefit this population. Based on the evidence, we conclude that effective treatment of patients with T2DM-SMA depends on the restoration and maintenance of muscle mass. We thus propose that regular intake of key functional nutrients, along with guidance for physical activity, can help maintain euglycemia and improve muscle status in all patients with T2DM and SMA.

Zoonotic nematode in the city of La Plata, Argentina: Report of a case of Calodium hepaticum in Rattus rattus.

This study describes a case of Calodium hepaticum (Trichinellida: Capillariidae) infection in an adult rat (Rattus rattus) from the periurban area of the city of La Plata in the province of Buenos Aires, Argentina. The rat was found with neurological signs (ataxia, lethargy, and episodes of unresponsiveness) in the food storage of a goat production facility. The liver was observed with hepatomegaly and diffuse and irregular yellowish-white spots appearing in striae or small nodules on the external surface and inside the liver. Subsequent microscopic and histopathological studies were performed. Eggs were observed by direct microscopy of the impression smear of liver tissue. A multifocal granulomatous tissue reaction with different stages of fibrocellular tissue was observed in the liver parenchyma. The granulomas contained adults and degenerated eggs delimited by an intense infiltrate of mononuclear cells. Macro and microscopic observations and histopathological liver lesions were compatible with C. hepaticum infection. To our knowledge, this is the first confirmation of C. hepaticum infection in R. rattus in Argentina, increasing the host record of this parasite and a new record of distribution in goat production systems in the country.

Increased femoral anteversion in females with anterior knee pain relates to both the neck and the shaft of the femur.

INTRODUCTION: Increased femoral anteversion (FAV) can have many clinical manifestations, including anterior knee pain (AKP). To our knowledge, no studies have measured the location of FAV in a cohort of female AKP patients. The objective of this research is to determine whether the increased FAV in AKP females originates above the lesser trochanter, below the lesser trochanter or at both levels. MATERIALS AND METHODS: Thrity-seven consecutive AKP female patients (n = 66 femurs) were recruited prospectively. There were 17 patients (n = 26 femurs; mean age of 28 years) in whom the suspicion for the increased FAV of the femur was based on the clinical examination (pathological group-PG). The control group (CG) consisted of 20 patients (n = 40 femurs; mean age of 29 years) in whom there was no increased FAV from the clinical standpoint. All of them underwent a torsional computed tomography of the lower limbs. FAV was measured according to Murphy´s method. A segmental analysis of FAV was performed using the lesser trochanter as a landmark. RESULTS: Significant differences in the total FAV (18.7 ± 5.52 vs. 42.46 ± 6.33; p < 0.001), the neck version (54.88 ± 9.64 vs. 64.27 ± 11.25; p = 0.0006) and the diaphysis version (- 36.17 ± 8.93 vs. - 21.81 ± 11.73; p < 0.001) were observed between the CG and the PG. The difference in the diaphyseal angle between CG and PG accounts for 60% of the total difference between healthy and pathological groups, while the difference between both groups in the angle of the neck accounts for 40%. CONCLUSION: In chronic AKP female patients with increased FAV, the two segments of the femur contribute to the total FAV, with a different pattern among patients and controls, being the compensation mechanism of the diaphysis much lower in the pathological femurs than in the controls.