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Carl Wernicke described the disease bearing his name in 1881 and reported three cases characterized by the presence of mental confusion, ataxia, and ophthalmoplegia. Wernicke’s disease is mainly observed in alcoholic patients, due to decreased vitamin intake as a consequence of an unbalanced diet, and a reduction of absorption due to the effects of alcohol. Likewise, inadequate vitamin intake is prevalent in older patients. Wernicke’s encephalopathy due to inappropriate total parenteral nutrition (TPN) occurs infrequently; recently, there is an increase in the literature concerning Wernicke’s encephalopathy in patients after general and bariatric surgeries. We present two cases of Wernicke’s encephalopathy after oncologic gastrointestinal surgery by failure to administer vitamin B1 during TPN; to our knowledge, these are the first two cases of Wernicke’s encephalopathy after colorectal surgery for cancer. In our opinion, timely diagnosis and treatment are mandatory to avoid nonfunctional recovery and consequent malpractice legal actions as well as an increase in the health-care costs correlated with the prolonged hospital stay and with the nonfunctional recovery.

Abstract Animals’ ability to orient and navigate relies on selecting an appropriate motor response based on the perception and integration of the environmental information. This is the case, for instance, of the optokinetic response (OKR) in Drosophila melanogaster, where optic flow visual stimulation modulates head movements. Despite a large body of literature on the OKR, there is still a limited understanding, in flies, of the impact on OKR of concomitant, and potentially conflicting, inputs. To evaluate the impact of this multimodal integration, we combined in D. melanogaster, while flying in a tethered condition, the optic flow stimulation leading to OKR with the simultaneous presentation of olfactory cues, based on repellent or masking compounds typically used against noxious insect species. First, this approach allowed us to directly quantify the effect of several substances and of their concentration on the dynamics of the flies’ OKR in response to moving gratings by evaluating the number of saccades and the velocity of the slow phase. Subsequently, this analysis was capable of easily revealing the actual effect, i.e. masking vs. repellent, of the compound tested. In conclusion, we show that D. melanogaster, a cost-affordable species, represents a viable option for studying the effects of several compounds on the navigational abilities of insects.

Abstract Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19–2019/20. The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression. The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged

Abstract Background Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. Methods We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. Results We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920–0.952, p

Abstract The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

Abstract Background Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. Methods The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. Results 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). Conclusions Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. Trial Registration Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018

In the last decades, the development of computerized adaptive testing (CAT) has allowed more precise measurements with a smaller number of items. In this study, we develop an item bank (IB) to generate the adaptive algorithm and simulate the functioning of CAT to assess the domains of mathematical knowledge in Argentinian university students (N=773). Data were analyzed from the Rasch model. A simulation design created with the R software was used to determine the necessary items of the IB to estimate examinee ability. Our results indicate that the IB in the domains of mathematical knowledge is adequate to be applied in CAT, especially to estimate average ability levels. The use of CAT is recommended for rapidly generating indicators of the knowledge acquired by students and to design educational strategies that enhance student performance. Results, constrains, and implications of this study are discussed.

ABSTRACT: Objectives: In order to support policymakers in allocating resources, we aimed to assess vaccine effectiveness (VE) of inactivated influenza vaccines (IIVs) available for Italian adults in the 2023/2024 season. Methods: A hospital-based test-negative case-control study was conducted in Genoa between mid-October 2023 and mid-April 2024. Adult (≥18 years) inpatients with prescription of a polymerase chain reaction test for influenza were eligible. Results: Of 1,664 adults analyzed, most (82%) of which were ≥65 years, 114 (6.9%) tested positive for influenza A. Most (92%) cases were caused by subclades 6B.1A.5a.2a and 6B.1A.5a.2a.1 of the A(H1N1)pdm09 subtype. In older adults aged ≥65 years vaccination was effective at 51% (95% CI: 8%, 74%) against any influenza A and 49% (95% CI: 2%, 73%) against A(H1N1)pdm09. Compared with non-vaccinated older adults, VE point estimates for the adjuvanted and, especially, high-dose IIVs were higher than those for the standard-dose non-adjuvanted IIV. Conclusion: The 2023/2024 seasonal influenza vaccination proved moderately effective in preventing hospitalization for laboratory-confirmed influenza. Being more appropriate for older adults, local policymakers and vaccinating physicians should maximize adoption of the enhanced IIVs.

Commuter satisfaction with their chosen mode of transport significantly affects quality of life, well-being, and the sustainability of commuting practices. This study uses a fuzzy-hybrid TOPSIS approach, applied to data from seven functional urban areas in Central Europe. The method effectively creates a composite indicator for assessing satisfaction levels by considering factors such as socioeconomic conditions, geographical features, and mobility-related data. The research analyzes how satisfaction varies according to these factors. Results indicate that commuter satisfaction levels vary across different factors, including age, education, occupation, gender, travel distance, travel time, commuting cost, and income. Notably, those with shorter commuting times and lower expenses tend to report higher satisfaction, while unemployed and low-income commuters, as well as those using active modes of transport, often express lower satisfaction levels. Interestingly, bus riders find their trip more satisfactory than car drivers, but train commuters are the least satisfied of all. Overall, this study provides valuable insights into commuter satisfaction, informing the development of policies and strategies to improve the transport infrastructure and services and promote the choice of sustainable modes.

Abstract Background Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT4) in a cohort of healthy individuals (N = 254) and, for 5-HT4, in a cohort of unmedicated patients with depression (N = 90). To do so, we quantified SLC6A4/TPH2 methylation using bisulfite pyrosequencing and estimated brain 5-HT4 and 5-HTT levels using positron emission tomography. In addition, we explored the association between SLC6A4 and TPH2 methylation and measures of early life and recent stress, depressive and anxiety symptoms on 297 healthy individuals. Results We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity. Conclusions We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms.

Knee stiffness is a widely known and worrying condition in several postoperative knees. Less is known about native stiff knee. The aim of this manuscript is to summarize the available literature on native stiff knee epidemiology, classification and treatment. In 1989 stiff knee was defined as a knee with less than 50° of total range of motion. If range of motion is

Abstract Objective In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement. Methods In 200 ALS patients (ALSpts) and 50 healthy controls (HCs) we measured loneliness, mood, and quality of life (QoL). ALSpts underwent comprehensive clinical, genetic, and neuropsychological assessment to define phenotypes. Seventy‐seven ALSpts performed 3T MRI scans to measure cortical thickness. Between‐group, partial correlation and regression analyses were used to examined clinical, neuropsychological, and cortical signatures of loneliness. Results Feelings of loneliness were documented in 38% of ALSpts (ALS/L+pts) and in 47% of HCs. In both groups loneliness was associated with anxiety (P

Abstract Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.

The measurement of the meshing stiffness in gear pairs is a technological problem. Many studies have been conducted, but a few results are available. A tailored test bench was designed and realized to measure the Static Transmission Error in two mating gears to address this issue. The bench is capable of testing several kinds of gears, e.g., spur, helical, conical, and internal, and it measures the transmission error concerning the applied torque. The Static Transmission Error is due to the variable stiffness of the gear teeth during a mesh cycle. In this paper, a dynamical method for measuring gear mesh stiffness is presented. The tooth stiffness is estimated from the torsional modal behavior of the rotating parts of the test bench. The dynamics of the system are acquired using accelerometers and very precise encoders to measure the angular accelerations and displacements of rotating parts. The torsional mode shapes are identified; those that show a vibrational behavior of the gears that do not follow the transmission ratio’s sign of the mating kinematic condition are selected because they depend on the flexibility of the teeth. In such a way, the engagement stiffness is estimated from the natural frequencies of the selected mode-shapes and the known inertia of gears and shafts. The experimentally identified results are also compared with numerical values computed with a commercial software for mutual validation.

Abstract Objective The resting‐state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. Methods Here we studied the network‐to‐network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72−), and 19 ALS‐mimic patients (ALSm) well‐matched for demographic and clinical variables. Results When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole‐connectome showed greater node degree (P

IntroductionWhile pharmacists-led interventions in hypertension have proven effective in high-income countries, their implementation and impact in low- and middle-income countries (LMIC) remain limited. This study assessed the implementation and outcomes of the hypertension program FarmaTeCuida (FTC), which integrated community pharmacies into the public primary care level using information and communication technologies. The study took place during the pandemic in General Pueyrredón, Buenos Aires, Argentina, so modifications to the implementation strategy and expected outcomes were also analyzed.MethodsA mixed-methods study was conducted using the non-adoption, abandonment, scaling-up, dissemination, and sustainability (NASSS) conceptual model. Qualitative in-depth interviews were conducted with key stakeholders using snowball sampling until thematic saturation was achieved. The quantitative approach employed a quasi-experimental, prospective, longitudinal design in a cohort of hypertensive patients enrolled in the FTC program since October 2020 to March 2022. Adoption, access, adherence to follow-up, and blood pressure levels were assessed. Clinical outcomes were compared to a cohort of hypertensive patients attending primary health care centers (PHCCs) in 2021 but not enrolled in the FTC program. Routine data from this cohort was obtained from the municipal health information system (HIS).ResultsOut of 33 PHCCs, 23 adopted the FTC program, but only four collaborated with community pharmacies. A total of 440 patients were recruited, with 399 (91%) enrolled at PHCCs. Hypertension was detected in 63% (279/440) of cases at the first visit (113 were possible hypertensive patients; 26 new hypertensive patients and 140 already diagnosed). During follow-up, FTC identified 52 new hypertensive patients (12% out of 440). Reduction of systolic blood pressure (SBP) was observed in patients enrolled in both the FTC program and the comparison group over 60 days. In the multivariate analysis that included all hypertensive patient (FTC and HIS) we found strong evidence that for each month of follow up, SBP was reduced by 1.12 mmHg; however, we did not find any significant effect of the FTC program on SBP trend (interaction FTC*months has a p-value = 0.23). The pandemic was identified as the main reason for the program's underperformance; in addition we identified barriers related to technology, patient suitability, implementation team characteristics, and organizational factors.DiscussionOur study, grounded in the NASSS model, highlights the profound complexity of introducing innovative strategies in low- and middle-income settings. Despite substantial challenges posed by the pandemic, these obstacles provided valuable insights, identified areas for improvement, and informed strategies essential for reshaping the care paradigm for conditions like hypertension in resource-constrained environments.

La evaluación de pastizales en regiones áridas y semiáridas de la Patagonia argentina es una herramienta clave tanto para planificar el manejo ganadero como para realizar evaluaciones ambientales y seguir procesos complejos (e.g., desertificación e impacto del cambio climático). Mientras la mayoría de los métodos de evaluación de pastizales asignan esfuerzos a resolver el dato (parcelas de evaluación a campo) o a la extensión de la información (clasificaciones a escala de paisaje usando sensores remotos), la variación temporal de la vegetación concentra menos atención. Las razones de este déficit podrían responder al costo de realizar evaluaciones a campo en el largo plazo o a las cortas series de datos satelitales disponibles hasta hace dos décadas. Una ventaja actual es contar con series de datos satelitales de >20 años, lo cual posibilita estudiar la dinámica (i.e., la variabilidad temporal y espacio-temporal) de la productividad de la vegetación. Nuestro objetivo fue evaluar la aplicación de un método de clasificación funcional de la vegetación, analizando la complementación de información entre aspectos estructurales y funcionales de ambientes de pastizal a escala de un predio ganadero. Comparamos los resultados obtenidos por una clasificación de unidades de paisaje y fisionomía de la vegetación con los de una clasificación y caracterización de la dinámica de la productividad de la vegetación a partir del protocolo que denominamos Arquetipos Funcionales de Pastizal. Los resultados enfatizan la necesidad de incorporar la dinámica de la productividad vegetal como un factor clasificatorio y no como una variable dependiente de una clasificación estructural definida de manera previa. Discutimos la potencialidad y los pasos futuros en la integración de ambos abordajes a escala predial en sistemas ganaderos de Patagonia como herramienta para la evaluación complementaria estructural y funcional de pastizales, orientada a la planificación y al manejo adaptativo.

Background and aimsWe previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors.Approach and resultsWe analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6 , and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A.ConclusionsMetabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.