Risks, Benefits, and Therapeutic Potential of Hematopoietic Stem Cell Transplantation for Autoimmune Diabetes

Type 1 diabetes mellitus is a chronic disease that results from the autoimmune response against pancreatic insulin producing β cells. Apart of several insulin regimens, since the decade of 80s various immunomodulatory regimens were tested aiming at blocking some steps of the autoimmune process against β cell mass and at promoting β cell preservation. In the last years, some independent research groups tried to cure type 1 diabetes with an "immunologic reset" provided by autologous hematopoietic stem cell transplantation in newly diagnosed patients, and the majority of patients became free form insulin with increasing levels of C-peptide along the time. In this review, we discuss the biology of hematopoietic stem cells and the possible advantages and disadvantages related to the high dose immunosuppression followed by autologous hematopoietic stem cell transplantation.     

Transmission Dynamics of Extended-Spectrum β-lactamase-Producing Enterobacteriaceae in the Tertiary Care Hospital and the Household Setting

Background.?Studies about transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in hospitals and households are scarce. Methods.?Eighty-two index patients with new carriage of ESBL-producing Escherichia coli (ESBL-Ec; n?=?72) or ESBL-producing Klebsiella pneumoniae (ESBL-Kp; n?=?10) and their hospital (n?=?112) and household (n?=?96) contacts were studied prospectively from May 2008 through September 2010. Isolates were phenotypically and molecularly characterized (sequencing of bla genes, repetitive extragenic palindromic polymerase chain reaction, pulse-field gel electrophoresis, and multilocus sequence typing). Transmission was defined as carriage of a clonally-related ESBL producer with identical bla(ESBL) gene(s) in the index patient and his or her contact(s). Results.?CTX-M-15 was the most prevalent ESBL in ESBL-Ec (58%) and ESBL-Kp (70%) in the index patients. Twenty (28%) ESBL-Ec isolates were of the hyperepidemic clone ST131. In the hospital, transmission rates were 4.5% (ESBL-Ec) and 8.3% (ESBL-Kp) and the incidences of transmissions were 5.6 (Ec) and 13.9 (Kp) per 1000 exposure days, respectively. Incidence of ESBL-Kp hospital transmission was significantly higher than that of ESBL-Ec (P?相似文献   

Paired associate learning in children with neurofibromatosis type 1: implications for clinical trials

Studies investigating behavior in mice with a heterozygous null mutation of the NF1 gene (Nf1 ^+/?) have provided critical insights into the molecular and cellular mechanisms underlying cognitive impairments associated with neurofibromatosis type 1 (NF1). Hyperactivation of the Ras-MAPK signaling cascade, which results in increased GABA-mediated inhibition and significantly reduced long-term potentiation, has been proposed as a core mechanism underlying Nf1 ^+/? mice deficits in visuospatial learning and attention. This assertion has been reinforced by preclinical trials that reveal that these impairments can be rescued both at a cognitive and cellular level. We attempted to demonstrate a phenotypic parallel between Nf1 ^+/? mice and children with NF1 using a well-validated measure of visuospatial learning. Children with NF1 (n = 71) and healthy controls (n = 29) were assessed on a computerized paired associate learning task. Interrelationships between visuospatial learning and other cognitive abilities that may influence performance, such as intelligence, attention and visuospatial function, were explored. Children with NF1 displayed significant impairments in visuospatial learning, with reduced initial retention and poorer learning across repeated trials. Importantly, we demonstrated that visuospatial learning was inferior in NF1 even after accounting for group differences in intelligence, sustained attention and visuospatial abilities. We have thus identified impaired visuospatial learning as a core phenotypic feature in children with NF1. These findings imply that hippocampal-based learning networks are dysfunctional in children with NF1 and provide validation for a primary outcome measure for clinical trials aiming to correct aberrant Ras signaling.     

Systematic Literature Review of Spinal Cord Stimulation in Patients With Chronic Back Pain Without Prior Spine Surgery

ObjectiveLow back pain is the leading cause of disability worldwide and one of the most common reasons for seeking health care. Despite numerous care strategies, patients with low back pain continue to exhibit poor outcomes. Spinal cord stimulation (SCS) is an evidence-based therapeutic modality for patients with failed back surgery syndrome. For patients without a surgical lesion or history, minimally invasive interventions that provide long-term reduction of chronic back pain are needed. Therefore, we conducted a systematic review of the evidence on SCS therapy in patients with chronic back pain who have not undergone spinal surgery.Materials and MethodsA systematic literature search was performed to identify studies reporting outcomes for SCS in chronic back pain patients (with or without secondary radicular leg pain) without prior surgery using date limits from database inception to February 2021. Study results were analyzed and described qualitatively.ResultsA total of ten primary studies (16 publications) were included. The included studies consistently demonstrated favorable outcomes in terms of pain reduction and functional improvement following SCS therapy. Improvements also occurred in quality of life scores; however, not all studies reported statistically significant findings. Additionally, the studies reported that SCS resulted in high patient satisfaction, reductions in opioid use, and an acceptable safety profile, although these data were more limited.ConclusionFindings suggest that SCS is a promising, safe, minimally invasive, and reversible alternative option for managing chronic back pain in patients who have not undergone spinal surgery.     

Using transprofessional care in the emergency department to reduce patient admissions: A retrospective audit of medical histories

The demand for emergency department (ED) services has increased significantly, due to our increasingly ageing population and limited access to primary care. This article reports outcomes from a transprofessional model of care in an ED in Victoria, Australia. Nurses, physiotherapists, social workers, and occupational therapists undertook additional education to increase the range of services they could provide and thereby expedite patient flow through the ED. One hundred patients who received this service were matched against 50 patients who did not. The most common reasons for patient admission were limb injury/limb pain (n = 47, 23.5%) and falls (n = 46, 23.0%). Transprofessional interventions included applying supportive bandages, slings, zimmer splints and controlled ankle motion (CAM) boots, and referral to new services such as case management and mental health teams. The rate of hospital admissions was significantly lower in the transprofessional group (n = 27, 18.0%) than in the reference group (n = 19, 38%, p = 0.005). This group also had a slightly lower re-presentation rate (n = 4, 2.7%) than patients in the reference group (n = 2, 4.0%). There are many benefits that support this model of care that in turn reduces ED overcrowding and work stress. A transprofessional model may offer a creative solution to meeting the varied needs of patients presenting for emergency care.     

Spermatozoa protein alterations in infertile men with bilateral varicocele

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.