Background and Aims Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult ...women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Methods Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Results Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP₄ receptors, but not at E₁, EP₁₋₃ receptors, partially suppressed stimulation of Isc by lubiprostone. Conclusions Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels.
Injection of an adenoviral (Ad) vector encoding human glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic (DA) neurons in the substantia nigra (SN) of young rats. As Parkinson's ...disease occurs primarily in aged populations, we examined whether chronic biosynthesis of GDNF, achieved by adenovirus-mediated delivery of a GDNF gene (AdGDNF), can protect DA neurons and improve DA-dependent behavioral function in aged (20 months) rats with progressive 6-OHDA lesions of the nigrostriatal projection. Furthermore, the differential effects of injecting AdGDNF either near DA cell bodies in the SN or at DA terminals in the striatum were compared. AdGDNF or control vector was injected unilaterally into either the striatum or SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the same side as the vector injection. AdGDNF injection into either the striatum or SN significantly reduced the loss of FG labelled DA neurons 5 weeks after lesion (P </= 0.05). However, only striatal injections of AdGDNF protected against the development of behavioral deficits characteristic of unilateral DA depletion. Striatal AdGDNF injections also reduced tyrosine hydroxylase fiber loss and increased amphetamine-induced striatal Fos expression. These results demonstrate that increased levels of striatal, but not nigral, GDNF biosynthesis prevents DA neuronal loss and protects DA terminals from 6-OHDA-induced damage, thereby maintaining DA function in the aged rat.
Purpose
The purpose of this paper is to explore the relationship between peer support and sense of belonging on the mental health and overall well-being, with a specific focus on comparing the ...perceptions of students in a work-integrated learning (WIL) program to those in a traditional non-WIL program.
Design/methodology/approach
Semi-structured group interviews were conducted with 25 participants, selected from a university with a WIL program. Interview data captured perceptions of peer support, sense of belonging, and how these influenced mental health, overall well-being, and confidence in making school-to-work transitions. Analysis followed the grounded theory approach of Glaser.
Findings
The analysis revealed that peer support and sense of belonging were essential protective factors for university student’s mental health and well-being, particularly during off-campus work terms or when transitioning to the labor market after graduation. Data suggested that participating in a WIL program can exacerbate students’ perceived barriers to accessing peer support resources and, in turn, lead to poor mental health.
Originality/value
The findings provide evidence for the importance of peer support and sense of belonging on mental health and help-seeking behaviors. Findings are important for the development of health programs, initiatives, and policies, particularly in light of the increase in mental illness amongst university students during their studies and as they prepare for the competitive labor market after graduation.
Previous studies on hospital-acquired influenza (HAI) have not systematically evaluated the possible impact of different influenza subtypes. HAI has historically been associated with high mortality, ...but clinical consequences may be less severe in a modern hospital setting.
To identify and quantify HAI for each season, investigate possible associations with varying influenza subtypes, and to determine HAI-associated mortality.
All influenza-PCR-positive adult patients (>18 years old) hospitalized in Skåne County during 2013–2019, were prospectively included in the study. Positive influenza samples were subtyped. Medical records of patients with suspected HAI were examined to confirm a nosocomial origin and to determine 30-day mortality.
Of 4110 hospitalized patients with a positive influenza PCR, 430 (10.5%) were HAI. Influenza A(H3N2) infections were more often HAI (15.1%) than influenza A(H1N1)pdm09, and influenza B (6.3% and 6.8% respectively, P<0.001). The majority of HAI caused by H3N2 were clustered (73.3 %) and were the cause of all 20 hospital outbreaks consisting of ≥4 affected patients. In contrast, the majority of HAI caused by influenza A(H1N1)pdm09 and influenza B were solitary cases (60% and 63.2%, respectively, P<0.001). Mortality associated with HAI was 9.3% and similar between subtypes.
HAI caused by influenza A(H3N2) was associated with an increased risk of hospital dissemination. Our study is relevant for future seasonal influenza infection control preparedness and shows that subtyping of influenza may help to define relevant infection control measures. Mortality in HAI remains substantial in a modern hospital setting.
Yersinia enterocolitica (Ye) evades the immune system of the host by injection of Yersinia outer proteins (Yops) via a type three secretion system into host cells. In this study, a reporter system ...comprising a YopE-beta-lactamase hybrid protein and a fluorescent staining sensitive to beta-lactamase cleavage was used to track Yop injection in cell culture and in an experimental Ye mouse infection model. Experiments with GD25, GD25-beta1A, and HeLa cells demonstrated that beta1-integrins and RhoGTPases play a role for Yop injection. As demonstrated by infection of splenocyte suspensions in vitro, injection of Yops appears to occur randomly into all types of leukocytes. In contrast, upon infection of mice, Yop injection was detected in 13% of F4/80(+), 11% of CD11c(+), 7% of CD49b(+), 5% of Gr1(+) cells, 2.3% of CD19(+), and 2.6% of CD3(+) cells. Taking the different abundance of these cell types in the spleen into account, the highest total number of Yop-injected cells represents B cells, particularly CD19(+)CD21(+)CD23(+) follicular B cells, followed by neutrophils, dendritic cells, and macrophages, suggesting a distinct cellular tropism of Ye. Yop-injected B cells displayed a significantly increased expression of CD69 compared to non-Yop-injected B cells, indicating activation of these cells by Ye. Infection of IFN-gammaR (receptor)- and TNFRp55-deficient mice resulted in increased numbers of Yop-injected spleen cells for yet unknown reasons. The YopE-beta-lactamase hybrid protein reporter system provides new insights into the modulation of host cell and immune responses by Ye Yops.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose:
The burden of upper extremity (UE) osteochondromas on function and self-perception among pediatric patients is unclear. The purpose of our study was to study the impact of osteochondromas in ...comparison to population norms and to evaluate solitary versus multiple osteochondromas on subjective UE function as measured by patient rated outcomes.
Methods:
We utilized the CoULD (Congenital Upper Limb Differences) Registry to review all pediatric patients presenting with osteochondromas between January 2014 and February 2021. Demographic information was collected and patients were classified as having either single or multiple osteochondromas. Patient-Reported Outcome Measurement Information System (PROMIS) and Pediatric Outcomes Data Collection Instrument (PODCI) tools were utilized for assessment. Scores for PODCI subscales of UE function, Pain/comfort, and Happiness and PROMIS domains of UE Function, Pain, Depression, Anxiety, and Peer Relations were reviewed. Differences between groups were analyzed using the Student
t
test.
Results:
Ninety-nine patients met inclusion criteria for the study with an average age of presentation of 9.3 years and 61 patients (62%) were male. Overall, patients demonstrated worse UE Function as well as greater Anxiety and Depression in comparison to the population normals on PROMIS assessment. Patients also demonstrated worse patient and parent reported PODCI UE, Sports and Physical Functioning, Pain/Comfort and Global Functioning scores compared with population norms but demonstrated better than average happiness scores. Patients with multiple osteochondromas demonstrated greater PROMIS pain interference and more disability in PODCI Sports and Physical Functioning, Pain/Comfort and Global Functioning compared with those with solitary osteochondromas.
Conclusion:
Patients with UE osteochondromas have worse overall function in comparison to population norms, exceeding established minimally clinically important difference values. In addition, patients with multiple osteochondromas reported more pain and poorer physical function than those with solitary osteochondromas. Physicians should be alert to the physical and psychosocial burden of this disease.
Level of Evidence:
Level II—prognostic.
Purpose To measure and compare hand function for children with normal hand development, congenital hand differences (CHD), and neuromuscular disease (NMD) using a function test with touch screen ...technology designed as an iPhone application. Methods We measured touch screen hand function in 201 children including 113 with normal hand formation, 43 with CHD, and 45 with NMD. The touch screen test was developed on the iOS platform using an Apple iPhone 4. We measured 4 tasks: touching dots on a 3 × 4 grid, dragging shapes, use of the touch screen camera, and typing a line of text. The test takes 60 to 120 seconds and includes a pretest to familiarize the subject with the format. Each task is timed independently and the overall time is recorded. Results Children with normal hand development took less time to complete all 4 subtests with increasing age. When comparing children with normal hand development with those with CHD or NMD, in children aged less than 5 years we saw minimal differences; those aged 5 to 6 years with CHD took significantly longer total time; those aged 7 to 8 years with NMD took significantly longer total time; those aged 9 to 11 years with CHD took significantly longer total time; and those aged 12 years and older with NMD took significantly longer total time. Conclusions Touch screen technology has becoming increasingly relevant to hand function in modern society. This study provides standardized age norms and shows that our test discriminates between normal hand development and that in children with CHD or NMD. Type of study/level of evidence Diagnostic III.
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