Search

Abstract Background Frailty and sarcopenia are important conditions that grow more common as people age. Frailty, a multi-system illness linked to heightened vulnerability to stresses, and sarcopenia, a loss of muscle mass and function, both raise the likelihood of unfavorable health outcomes including disability or death. This work’s objective was to study the clinical utility of sarcopenia and frailty in critically ill elderly patients with multiple comorbidities. Patients and methods Clinical frailty scale and SARC-F scale questionnaire were done in 70 critically ill patients admitted to geriatric ICU in geriatric hospital. Results There was a highly significant effect of frailty on primary outcomes whether sarcopenia was present or not (which means that effect of frailty on primary outcomes is more prominent than sarcopenia). The associated factors of frailty including primary admission cause, type of associated comorbidities, and primary outcome (mortality, prolonged hospital stay, long-term ICU care) were found to be important. There was a highly significant effect on the presence of sarcopenia regarding mean age, associated comorbidities, and degree of frailty, with a higher percentage for the need of noradrenaline treatment in ICU patients, highly significant relation to patient mortality. Conclusions The risk of death in critical illness is increased by sarcopenia and frailty. Clinical examinations should routinely identify the risk factors for frailty and sarcopenia. By providing appropriate therapies, medical professionals in intensive care units may be able to improve patient outcomes. Clinicians may be able to get prognostic information on the survival and recovery of their frail intensive care unit patients by routinely assessing frailty at the time of admission. Crucially, this might assist patients and their families in making well-informed choices on the course of treatment while they are in critical condition. Crucially, more investigation is needed to ascertain whether there are modifiable elements that might enhance the prognosis of critically sick fragile people.

AbstractHighly effective antiobesity and diabetes medications such as glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide/GLP-1 (dual) receptor agonists (RAs) have ushered in a new era of treatment of these highly prevalent, morbid conditions that have increased across the globe. However, the rapidly escalating use of GLP-1/dual RA medications is poised to overwhelm an already overburdened health care provider workforce and health care delivery system, stifling its potentially dramatic benefits. Relying on existing systems and resources to address the oncoming rise in GLP-1/dual RA use will be insufficient. Generative artificial intelligence (GenAI) has the potential to offset the clinical and administrative demands associated with the management of patients on these medication types. Early adoption of GenAI to facilitate the management of these GLP-1/dual RAs has the potential to improve health outcomes while decreasing its concomitant workload. Research and development efforts are urgently needed to develop GenAI obesity medication management tools, as well as to ensure their accessibility and use by encouraging their integration into health care delivery systems.

Abstract Background Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into ‘motor-driven’ and ‘cognitively driven’. RRBI symptomatology depends on the individual’s clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures—involving cortical and subcortical areas. Method A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. Results We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the ‘motor-driven’ RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the ‘cognitively driven’ RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p

Iron and manganese are poorly soluble elements in oxic and alkaline solutions, whereas they are much more soluble under anoxic conditions. As a result, the formation of authigenic mineral phases rich in Fe and/or Mn has traditionally been viewed as diagnostic of global or local anoxic conditions. Here we reveal that some specific cyanobacteria of very small size (< 2 µm, i.e., picocyanobacteria) can biomineralize abundant, authigenic Fe(III)-, Mn(IV)- and Si-rich amorphous phases under oxic conditions in an alkaline lake in Mexico. The resulting biominerals cluster as small globules arranged as rings around the division septum of cyanobacterial cells. These rings are enveloped within an organic, likely polysaccharidic envelope and are partially preserved, at least morphologically, upon sedimentation. Based on their 16S rDNA sequence, these cyanobacteria were affiliated with the Synechococcales order. The high Fe and Mn enrichment of the biominerals questions the systematic inference of anoxic conditions based on their detection. Moreover, this process scavenges iron from the water column, an overlooked biological contribution to the Fe cycle. Finally, it reveals a new case of controlled biomineralization of Si-rich phases by bacteria.

As the field of public health rises to the demands of real-time surveillance and rapid data-sharing needs in a postpandemic world, it is time to examine our approaches to the dissemination and accessibility of such data. Distinct challenges exist when working to develop a shared public health language and narratives based on data. It requires that we assess our understanding of public health data literacy, revisit our approach to communication and engagement, and continuously evaluate our impact and relevance. Key stakeholders and cocreators are critical to this process and include people with lived experience, community organizations, governmental partners, and research institutions. In this viewpoint paper, we offer an instructive approach to the tools we used, assessed, and adapted across 3 unique overdose data dashboard projects in Rhode Island, United States. We are calling this model the “Rhode Island Approach to Public Health Data Literacy, Partnerships, and Action.” This approach reflects the iterative lessons learned about the improvement of data dashboards through collaboration and strong partnerships across community members, state agencies, and an academic research team. We will highlight key tools and approaches that are accessible and engaging and allow developers and stakeholders to self-assess their goals for their data dashboards and evaluate engagement with these tools by their desired audiences and users.

IntroductionFetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic forms (NS-FASD). The neuroanatomical consequences of prenatal alcohol exposure are mainly the reduction in brain size, but also focal abnormalities such as those of the corpus callosum (CC). We previously showed a narrowing of the CC for brain size, using manual measurement and its usefulness to improve diagnostic certainty. Our aim was to automate these measurements of the CC and identify more recurrent abnormalities in FAS subjects, independently of brain size reduction.MethodsWe developed a fast, automated, and normalization-free method based on spectral analysis to generate thicknesses of the CC continuously and at singular points (genu, body, isthmus, and splenium), and its length (LCC). We applied it on midsagittal section of the CC extracted from T1-anatomical brain MRI of 89 subjects with FASD (52 FAS, 37 NS-FASD) and 126 with typically development (6–20 y-o). After adjusting for batch effect, we compared the mean profiles and thicknesses of the singular points across the 3 groups. For each parameter, we established variations with age (growth charts) and brain size in the control group (scaling charts), then identified participants with abnormal measurements (

IntroductionFetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic non-specific forms (NS-FASD) that are still underdiagnosed and could benefit from new neuroanatomical markers. The main neuroanatomical manifestation of prenatal alcohol exposure on developmental toxicity is the reduction in brain size, but repeated imaging observations have long driven the attention on the corpus callosum (CC), without being all convergent. Our study proposed a new segmentation of the CC that relies on both a sulci-based cortical segmentation and the “hemispherotopic” organization of the transcallosal fibers.MethodsWe collected a monocentric series of 37 subjects with FAS, 28 with NS-FASD, and 38 with typical development (6 to 25 years old) using brain MRI (1.5T). Associating T1- and diffusion-weighted imaging, we projected a sulci-based cortical segmentation of the hemispheres on the midsagittal section of the CC, resulting in seven homologous anterior–posterior parcels (frontopolar, anterior and posterior prefrontal, precentral, postcentral, parietal, and occipital). We measured the effect of FASD on the area of callosal and cortical parcels by considering age, sex, and brain size as linear covariates. The surface proportion of the corresponding cortical parcel was introduced as an additional covariate. We performed a normative analysis to identify subjects with an abnormally small parcel.ResultsAll callosal and cortical parcels were smaller in the FASD group compared with controls. When accounting for age, sex, and brain size, only the postcentral (η2 = 6.5%, pFDR = 0.032) callosal parcel and % of the cortical parcel (η2 = 8.9%, pFDR = 0.007) were still smaller. Adding the surface proportion (%) of the corresponding cortical parcel to the model, only the occipital parcel was persistently reduced in the FASD group (η2 = 5.7%, pFDR = 0.014). In the normative analysis, we found an excess of subjects with FASD with abnormally small precentral and postcentral (peri-isthmic) and posterior–splenial parcels (pFDR < 0.05).ConclusionThe objective sulcal and connectivity-based method of CC parcellation proved to be useful not only in confirming posterior–splenial damage in FASD but also in the narrowing of the peri-isthmic region strongly associated with a specific size reduction in the corresponding postcentral cortical region (postcentral gyrus). The normative analysis showed that this type of callosal segmentation could provide a clinically relevant neuroanatomical endophenotype, even in NS-FASD.

Abstract Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40–50%) and the 45,X/46,XX mosaic karyotype (15–25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.

Abstract A wide spectrum of disorders involves the parotid glands, in infancy and childhood. Acute or chronic inflammatory/infectious diseases are predominant. The first branchial cleft anomalies are congenital lesions that typically manifest during childhood. Tumor lesions are more likely to be benign, with infantile hemangioma the most common in infancy and pleomorphic adenoma the most frequent in childhood. Malignant tumors are uncommon, with mucoepidermoid carcinoma the least rare. Infiltrative parotid diseases are rare and have some pediatric clinical specificities. These common and uncommon disorders of parotid glands during childhood and their imaging characteristics are reviewed.

Abstract Neurodegenerative diseases are characterized by chronic neuroinflammation and may perpetuate ongoing fibrotic reactions within the central nervous system. Unfortunately, there is no therapeutic available that treats neurodegenerative inflammation and its sequelae. Here we utilize cromolyn, a mast cell inhibitor with anti-inflammatory capabilities, and its fluorinated analogue F-cromolyn to study fibrosis-related protein regulation and secretion downstream of neuroinflammation and their ability to promote microglial phagocytosis and neurite outgrowth. In this report, RNA-seq analysis shows that administration of the pro-inflammatory cytokine TNF-α to HMC3 human microglia results in a robust upregulation of fibrosis-associated genes. Subsequent treatment with cromolyn and F-cromolyn resulted in reduced secretion of collagen XVIII, fibronectin, and tenascin-c. Additionally, we show that cromolyn and F-cromolyn reduce pro-inflammatory proteins PLP1, PELP1, HSP90, IL-2, GRO-α, Eotaxin, and VEGF-Α, while promoting secretion of anti-inflammatory IL-4 in HMC3 microglia. Furthermore, cromolyn and F-cromolyn augment neurite outgrowth in PC12 neuronal cells in concert with nerve growth factor. Treatment also differentially altered secretion of neurogenesis-related proteins TTL, PROX1, Rab35, and CSDE1 in HMC3 microglia. Finally, iPSC-derived human microglia more readily phagocytose Aβ42 with cromolyn and F-cromolyn relative to controls. We propose the cromolyn platform targets multiple proteins upstream of PI3K/Akt/mTOR, NF-κB, and GSK-3β signaling pathways to affect cytokine, chemokine, and fibrosis-related protein expression.

Abstract Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)‐conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer—melanoma, breast cancer, and lung cancer—with CLC‐PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC‐PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC‐based drug‐conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients.