Fc alpha receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcR gamma adaptor

Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcRgamma adaptor. They express FcRgamma-associated FcalphaRI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of FcalphaRIgamma in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of FcalphaRI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human FcalphaRI(R209L) that cannot associate with FcRgamma. Like FcalphaRI(wt)-Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. FcalphaRI activation in FcalphaRI(wt), but not in FcalphaRI(R209L), Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred FcalphaRI(wt) Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. FcalphaRI(wt) cross-linking on macrophages activated MAP kinases and production of TNF-alpha and MCP-1. Moreover, IgA-IC from IgAN patients activated FcalphaRI and induced TNF-alpha production. Thus, FcalphaRI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage.     

Corticomotor facilitation associated with observation,imagery and imitation of hand actions: a comparative study in young and old adults

In the present report, we extent our previous findings (Clark et al. in Neuropsychologia 42:105–122, 2004) on corticomotor facilitation associated with covert (observation and imagery) and overt execution (action imitation) of hand actions to better delineate the selectivity of the effect in the context of an object-oriented action. A second aim was to examine whether the pattern of facilitation would be affected by age. Corticomotor facilitation was determined in two groups of participants (young n = 21, 24 ± 2 years; old n = 19, 62 ± 6 years) by monitoring changes in the amplitude and latency of motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation. MEP responses were measured from both the first dorsal interosseous (FDI, task selective muscle) and the abductor digiti minimi (ADM) of the right hand while participants attended to four different video presentations. Each of four videos provided specific instructions for participants to either: (1) close their eyes and relax (REST), (2) observe the action attentively (OBS), (3) close their eyes and mentally simulate the action (IMAG), or (4) imitate the action (IMIT). The action depicted in the videos represented a male subject cutting a piece of material with scissors. In the young group, the pattern of results revealed selective facilitation in the FDI in conditions involving either covert (OBS and IMAG) or overt action execution (IMIT). In the ADM, only overt execution with action imitation was associated with significant MEP facilitation. In the old group, a similar pattern of results was observed, although the modulation was less selective than that seen in the young group. In fact, older individuals often exhibited concomitant facilitation in both the FDI and ADM during either covert (OBS and IMAG conditions) or overt action execution (IMIT condition). Taken together, these results further corroborate the notion that the corticomotor system is selectively active when actions are covertly executed through internal simulation triggered by observation or by motor imagery, as proposed by Jeannerod (Neuroimage 14:S103–S109, 2001). With aging, the ability to produce corticomotor facilitation in association with covert action execution appears to be largely preserved, although there seems to be a loss in selectivity. This lack of selectivity may, in turn, reflect age-related alterations in the function of the corticospinal system, which may impair the ability to individuate finger movements either in the covert or overt stage of action execution.     

Biomechanical analysis of cervical spine sagittal stiffness characteristics

The orientation of the loading, along which the minimum and maximum displacements occur, can be described as the principal axis. This work presents a model to determine extremums of the compliance of the cervical spine and corresponding principal axis, given the pose and flexibility of each functional cervical unit. As the cervical model of C(2)-C(7) section is flexed, it becomes tensionally stiffer and as the structure is extended, it becomes compressively stiffer. The opposite is true for the model including the atlanto-occipito-axial complex suggesting a compressively stiffer column as it is flexed and a tensionally stiffer structure as it is extended.     

A predictive model of anxiety and depression symptoms after a lower limb amputation

Background

Patients with Diabetic Foot Ulcer (DFU) show high levels of depression and anxiety symptoms. The loss of a limb is undoubtedly a devastating experience and several studies have shown that anxiety and depression symptoms are a common reaction after a lower limb amputation (LLA). However, no study has focused on the immediate emotional reactions to LLA as a personal factor based on the ICF Model.

Poor outcomes among elderly patients hospitalized for influenza-like illness

Background and objective: Global Influenza Hospital Surveillance Network is a worldwide initiative that aims to document the burden of influenza infections among acute admissions and vaccine effectiveness in particular countries. As a partner of this platform, we aimed to determine the frequency of influenza infections among acute admissions with influenza-like illness and the outcomes of enrolled patients during the 2015–2016 influenza season in selected hospitals in Turkey.

Patients and methods: The investigators screened the hospital admission registries, chart review or available records, and screened all patients hospitalized in the previous 24–48?hours or overnight in the predefined wards or emergency room. A total of 1351 patients were screened for enrollment in five tertiary care referral hospitals in Ankara and 774 patients (57.3% of the initial screened population) were eligible for swabbing. All of the eligible patients who consented were swabbed and tested for influenza with real-time polymerase chain reaction (PCR) based methods.

Results: Overall, influenza positivity was detected in 142 patients (18.4%). The predominant influenza strain was A H1N1pdm09. Outcomes were worse among elderly patients, regardless of the presence of the influenza virus. Half of the patients over 65 years of age were admitted to the intensive care unit, while one third required any mode of mechanical ventilation and one fourth died in the hospital in that particular episode.

Conclusion: These findings can guide hospitals to plan and prepare for the influenza season. Effective influenza vaccination strategies, particularly aimed at the elderly and adults with chronic diseases, can provide an opportunity for prevention of deaths due to influenza-like illness.     

Respiratory Muscle Strength as a Discriminator of Sarcopenia in Community-Dwelling Elderly: A Cross-Sectional Study

Objectives

To compare the values obtained from maximum respiratory pressures (MRP) between sarcopenic and non-sarcopenic elderly; to verify the association of maximum respiratory pressures with sarcopenia and its indicators; and to establish cut-off points for MRP as a discriminator of sarcopenia.

Design

Cross-sectional study.

Location

Macapá, Brazil.

Participants

Community-dwelling elderly ≥ 60 years old, both sexes.

Measures

Evaluation of respiratory muscle strength (maximal inspiratory pressure - MIP and maximal expiratory pressure - MEP) and sarcopenia, according to the European Working Group on Sarcopenia in Older People (EWGSOP), in which the diagnosis of this condition considered the reduction of muscle mass (muscle mass index - MMI) associated with muscle strength reduction (hand grip strength - HGS) and / or impairment in physical performance (gait speed - GS).

Results

The sample consisted of 383 elderly individuals, with a mean age of 70.02 ± 7.3 years and a prevalence of sarcopenia of 12.53% (n = 48). Sarcopenic individuals presented significantly lower (obtained, obtained versus predicted) mean values for the maximal respiratory pressures compared to the non-sarcopenic elderly, and these were inversely associated with sarcopenia (an increase by 1 cmH2O in MIP and MEP reduced by 5% and 3%, respectively, the probability of sarcopenia). In relation to the association with the sarcopenia indicators, the increase by 1 cmH2O in MIP and MEP decreased, respectively, the probability of decreasing muscle strength (3% and 2%), GS (3% and 4%) and MMI (3 % - MIP). Cut-off points ≤60 cmH2O and ≤50 cmH2O for MEP and ≤55 cmH2O and ≤45 cmH2O for MEP, respectively for elderly men and women, served as a discriminant criterion for the presence of sarcopenia (area under the ROC curve superior to 0.70).

Conclusions

Elderly patients with sarcopenia had lower MIP and MEP values when compared to non-sarcopenic individuals, and respiratory muscle strength was inversely associated with the diagnosis of sarcopenia and its indicators (HGS, gait speed and MMI). Furthermore, cut-off points for MIP and MEP can be used in clinical practice as discriminators of sarcopenia in community-dwelling elderly.

     

Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity

Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles. Mechanisms that link dietary fat, gut microbiota and obesity are mediated by increased intestinal permeability, systemic endotoxemia, and the activity of the endocannabinoid system. Although the probiotic therapy could be a complementary strategy to improve gut microbiota composition, it did not show permanent effects to treat fat-induced dysbiosis. Based upon evidence to date, we believe that high-fat diets and SFA consumption should be avoided, and MUFA and omega-3 PUFA intake should be encouraged in order to regulate gut microbiota and inflammation, promoting body weight/fat control.