A potential reservoir of immature dopaminergic replacement neurons in the adult mammalian olfactory bulb

A significant fraction of the interneurons added in adulthood to the glomerular layer (GL) of the olfactory bulb (OB) are dopaminergic (DA). In the OB, DA neurons are restricted to the GL, but using transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter, we also detected the presence of TH-GFP+ cells in the mitral and external plexiform layers. We hypothesized that these could be adult-generated neurons committed to become DA but not yet entirely differentiated. Accordingly, TH-GFP+ cells outside the GL exhibit functional properties (appearance of pacemaker currents, synaptic connection with the olfactory nerve, intracellular chloride concentration, and other) marking a gradient of maturity toward the dopaminergic phenotype along the mitral–glomerular axis. Finally, we propose that the establishment of a synaptic contact with the olfactory nerve is the key event allowing these cells to complete their differentiation toward the DA phenotype and to reach their final destination.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort

OBJECTIVES: Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. METHODS: From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. RESULTS: The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. CONCLUSION: In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.     

Primary infertility associated with schitosoma mansoni: a case report from the Jos plateau,north central Nigeria

Testicular schistosomiasis caused by Schistosoma mansoni is very rare and more so when associated with primary infertility. A 40 years old man from the Jos Plateau, North Central Nigeria presented with primary infertility after ten years of marriage. Sperm count revealed oligospermia and he also complained of inability to sustain erection. Testicular biopsy revealed several ova of Schistosoma mansoni in the connective tissue of the testes. Cases of infertility in endemic areas especially when there is no supply of potable water should raise suspicion of schistosomiasis among other pathologies and possible hormonal disturbances when the testes are involved.     

Acute exercise-induced glycocalyx shedding does not differ between exercise modalities,but is associated with total antioxidative capacity

ObjectivesRegular physical exercise is known to protect endothelial integrity. It has been proposed that acute exercise-induced changes of the (anti-)oxidative system influence early (glycocalyx shedding) and sustained endothelial activation (shedding of endothelial cells, ECs) as well as endothelial-cell repair by circulating hematopoietic stem and progenitor cells (HPCs). However, results are not conclusive and data in trained participants performing different exercise modalities is lacking.DesignEighteen healthy, well-trained participants (9 runners, 9 cyclists; age: 29.7 ± 4.2 yrs) performed a strenuous acute exercise session consisting of 4 bouts of 4-min high-intensity with decreasing power profile and 3-min low-intensity in-between.MethodsAverage power/speed of intense phases was 85% of the peak achieved in a previous incremental test. Before and shortly after exercise, total oxidative and antioxidative capacities (TAC), shedding of syndecan-1, heparan sulfate, hyaluronan, ECs, and circulating HPCs were investigated.ResultsTAC decreased from 1.81 ± 0.42 nmol/L to 1.47 ± 0.23 nmol/L post-exercise (p = 0.010) only in runners. Exercise-induced early and sustained endothelial activation were enhanced post-exercise- syndecan-1: 103.2 ± 63.3 ng/mL to 111.3 ± 71.3 ng/mL, heparan sulfate: from 2637.9 ± 800.1 ng/mL to 3197.1 ± 1416.3 ng/mL, both p < 0.05; hyaluronan: 84.3 ± 21.8 ng/mL to 121.4 ± 29.4 ng/mL, ECs: from 6.6 ± 4.5 cells/μL to 9.5 ± 6.2 cells/μL, both p < 0.01; results were not different between exercise modalities and negatively related to TAC concentrations post-exercise. HPC proportions and self-renewal ability were negatively, while EC concentrations were positively associated with circulating hyaluronan concentrations.ConclusionsThese results highlight the importance of the antioxidative system to prevent the endothelium from acute exercise-induced vascular injury – independent of exercise modality – in well-trained participants. Endothelial-cell repair is associated with hyluronan signaling, possibly a similar mechanism as in wound repair.     

Antimicrobial technology in orthopedic and spinal implants

Infections can hinder orthopedic implant function and retention.Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion.Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems,material science,immunology,and polymer chemistry are in development and early clinical use.This review outlines orthopedic implant antimicrobial technology,its current applications and supporting evidence,and clinically promising future directions.     

Primary lymphoma of the epididymis: case report and review of the literature.

OBJECTIVE: To report an extremely rare clinical pathological observation of a case of primary lymphoma of the epididymis, without testicular or systemic involvement, and to update the relevant literature. MATERIALS AND METHODS: A 25-year-old white male patient complaining of right scrotal pain was referred to our department. Clinical examination detected a hard painful mass at the right epididymal head. Epididymitis was diagnosed and conservative therapy with antibiotics and anti-inflammatory drugs was given. After 2 months of therapy the patient was admitted to our department because a tumor was suspected. Tumor markers were normal. Right scrotal exploration was performed through a standard inguinal incision. The epididymal head was completely replaced by a hard white mass. Fresh frozen sections indicated a malignant tumor. Right radical orchiectomy was performed. RESULTS: High-grade primary epididymal non-Hodgkin's lymphoma with diffuse large cells (group G according to the Working Formulation) was diagnosed. Clinical pathological staging detected stage IE (extranodal) primary epididymal lymphoma. The patient was referred to the Hematologic Unit for combined chemotherapy, according to the VACOP-B protocol. After an 18-month follow-up the patient is well and disease free. CONCLUSIONS: When an epididymal mass does not benefit from medical treatment, scrotal exploration and fresh frozen sections of the lesion should be done. The possible bilateral involvement by primary epididymal lymphoma has to be kept in mind. Radical orchiectomy is the treatment of choice for primary lymphoma of the epididymis. Adjuvant chemotherapy is indicated in high-grade malignant lymphoma. Prognostic parameters of the disease may be the grade of malignancy and the size of the tumor.