Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease.

The purpose of this study was to determine the effects of unilateral versus bilateral subthalamic nucleus (STN) stimulation on quantitative measures of walking and reaching in Parkinson's disease (PD). We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 6 people with PD who had bilateral STN stimulators implanted for at least 6 months and withheld their anti-parkinson medication for at least 8 hours. Subjects were studied with both stimulators off, one on, and both on. Kinematic data were collected as subjects walked, reached to a target, and were rated using the UPDRS motor subscale. STN stimulation improved walking speed and stride length, with the greatest benefit from bilateral stimulation. Reaching speed was improved by unilateral STN stimulation alone, with no additive effect of bilateral stimulation. UPDRS motor subscale ratings paralleled the kinematic findings. STN stimulation did not restore PD subjects' movements to the level of age-matched controls. Overall, these results provide further evidence that the basal ganglia pathways involved in control of walking and reaching may be distinct. We speculate that basal ganglia may influence walking through bilateral pedunculopontine projections and reaching through ipsilateral thalamocortical projections. Our findings also suggest that maximal improvement of walking requires bilateral rather than unilateral STN stimulation.     

Treatment with anti-LFA-1 alpha monoclonal antibody selectively interferes with the maturation of CD4- 8+ thymocytes.

Maturation of T lymphocytes in the thymus is driven by signals provided by soluble factors and by the direct interaction between thymocytes and stromal cells. Although the interaction between T-cell receptor (TCR) and major histocompalibility complex (MHC) molecules on stromal cells is crucial for T-cell development, other accessory molecules seem to play a role in this process. In order to better understand the role of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) molecules in thymocyte maturation, mice were treated from birth with saturating doses of non-cytolytic-specific monoclonal antibodies. The effect of this treatment on thymocyte subpopulations and the expression of CD3 and TCR-alpha beta by these cells was investigated by flow cytometry. Our data demonstrated that the effective saturation of LFA-1 alpha chain in the thymus, but not ICAM-I or LFA-I beta chain, selectively interfered with the maturation of CD8+ T cells, as manifested by a marked reduction in the frequency of CD4-8+ thymocytes expressing high levels of CD3 and TCR-alpha beta. This selective reduction was also observed in peripheral blood mononuclear cells and spleen cells. The analysis of the frequencies of various V beta TCR showed that CD4-8+ thymocytes were globally affected by the treatment. These results underline the importance of the interaction between LFA-1 and its ligands in the maturation of CD8+ T cells and document the existence of different molecular requirements for the differentiation of CD4+ and CD8+ T cells.     

Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice

Autoimmune diabetes is characterized by an early mononuclear infiltration of pancreatic islets and later selective autoimmune destruction of insulin-producing beta cells. Lymphocyte homing receptors have been considered candidate targets to prevent autoimmune diabetes. L-selectin (CD62L) is an adhesion molecule highly expressed in naive T and B cells. It has been reported that blocking L-selectin in vivo with a specific antibody (Mel-14) partially impairs insulitis and diabetes in autoimmune diabetes-prone non-obese diabetic (NOD) mice. In the present study we aimed to elucidate whether genetic blockade of leukocyte homing into peripheral lymph nodes would prevent the development of diabetes. We backcrossed L-selectin-deficient mice onto the NOD genetic background. Surprisingly NOD/L-selectin-deficient mice exhibited unaltered islet mononuclear infiltration, timing of diabetes onset and cumulative incidence of spontaneous diabetes when compared to L-selectin-sufficient animals. CD4, CD8 T cells and B cells were present in islet infiltrates from 9-week-old L-selectin-sufficient and -deficient littermates. Moreover, total splenocytes from wild-type, heterozygous or NOD/L-selectin-deficient donor mice showed similar capability to adoptively transfer diabetes into NOD/SCID recipients. On the other hand, homing of activated, cloned insulin-specific autoaggressive CD8 T cells (TGNFC8 clone) is not affected in NOD/L-selectin-deficient recipients. We conclude that L-selectin plays a small role in the homing of autoreactive lymphocytes to regional (pancreatic) lymph nodes in NOD mice.     

Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy

BACKGROUND: Some patients develop proteinuria and progressive renal failure after unilateral nephrectomy, although the majority of patients maintain normal renal function. Reasons to explain this different evolution are not known. METHODS: A cross-sectional study was performed in 73 patients who had undergone unilateral nephrectomy 13.6 +/- 8.6 years before. Patients with morphologic abnormalities in the remaining kidney, systemic disorders, or abnormal renal function at the time of nephrectomy were excluded. All of the 73 included patients showed normal renal function and negative proteinuria at nephrectomy. The patient's medical records were reviewed, and clinical and analytical data throughout follow-up were obtained. RESULTS: Fifty-three out of the 73 patients (group I) showed a normal renal function and negative proteinuria at the cross-sectional study. The remaining 20 patients (group II) showed proteinuria (3.4 +/- 3.1 g/day). The time elapsed between nephrectomy and proteinuria appearance was 10.1 +/- 6.1 years. Thirteen patients of group II had developed renal insufficiency (serum creatinine at the cross-sectional study of 3.9 + 3.2 mg/dL) in addition to proteinuria. The time elapsed between proteinuria appearance and the onset of renal insufficiency was 4.1 +/- 4.3 years. Renal insufficiency showed a slowly progressive course in most of these patients. There were no significant differences between group I and group II patients in age, gender, renal function, or blood pressure at the time of nephrectomy. In contrast, group II patients showed a body mass index (BMI) that was significantly higher than group I at nephrectomy (31.6 +/- 5.6 vs. 24.3 +/- 3.7 kg/m(2), P < 0.001), at cross-sectional study (33.3 +/- 6.6 vs. 25.1 +/- 3.5 kg/m(2), P < 0.001), and throughout follow-up. Among the 14 obese (BMI > 30 kg/m(2)) patients at the time of nephrectomy, 13 (92%) developed proteinuria/renal insufficiency. In contrast, among the 59 patients with BMI < 30 kg/m(2), only 7 (12%) developed these complications (P < 0.001). Kaplan-Meier estimated probability of negative proteinuria and normal renal function 10 years after nephrectomy was 40 and 70%, respectively, in obese patients at nephrectomy. At 20 years after nephrectomy, these percentages were 8 and 35%, respectively. In contrast, in nonobese patients, the probability of negative proteinuria and normal renal function was 93 and 98%, respectively, at 10 years (P < 0.001) and 77 and 91%, respectively, at 20 years (P < 0.001). Multiple logistic regression analysis showed that the risk of developing renal disease was only statistically correlated with BMI at the time of unilateral nephrectomy (odds ratio 1.34, 1.03 to 1.76 CI). CONCLUSIONS: Obese patients are at risk for developing proteinuria and chronic renal failure after unilateral nephrectomy. Regular and long-term follow-up are recommended in these patients.     

Systemic Besnoitiosis in a Juvenile Roe Deer (Capreolus capreolus)

Herein, we report the first incidence of systemic besnoitiosis in a male juvenile roe deer Capreolus capreolus. The animal was found dead in an area where bovine besnoitiosis is endemic and showed cachexia and multiple skin erosions in the metacarpal and metatarsal areas. Moreover, round and elevated white structures suggestive of Besnoitia spp. tissue cysts were also present. Twenty‐eight tissue samples from different anatomical locations were collected for microscopic lesion and parasite detection through histopathology and PCR. Immunohistochemistry was performed to confirm Besnoitia‐positive reaction in the tissue cysts. In addition, the identity of Besnoitia spp. in PCR‐positive tissue samples was also investigated using microsatellite (MS) markers, and the comparison of protein disulphide isomerase gene sequences (BbPDI) of B. besnoiti and B. tarandi isolated from cattle and reindeer, respectively. Besnoitia cysts were detected in the skin (several parts), respiratory and upper digestive tracts, eyes, kidney, liver, testicle, cardiac muscle and lymphoid tissue. Remarkably, the presence of tissue cysts in the brain confirmed the capacity of Besnoitia spp. to form tissue cysts in the central nervous system (CNS). Finally, the Besnoitia species detected showed the same MS genotype as B. besnoiti, and BbPDI sequences from roe deer and two B. besnoiti isolates were genetically identical throughout multiple sequence alignment. Thus, for the first time, there is evidence that roe deer might act as an intermediate host of B. besnoiti. Further molecular analyses and parasite isolations are needed to corroborate these findings.     

The value of bone scintigraphy in the follow-up of vertebral osteoporosis

Summary In an open study, we have assessed the bone/soft tissue uptake index in recent osteoporotic vertebral collapse using scintigraphy. The evolution of these cases was followed-up at 6 months in 22 patients treated with 100 IU of salmon calcitonin plus 500 mg of elemental calcium/10 days per month and in 18 patients treated with 500 mg of elemental calcium only on a daily basis. There were no index differences between groups prior to treatment. At six months, the group treated with calcitonin plus calcium showed a significant decrease from 10.2±6.4 to 3.2±1.1 (p<0.001), while the calcium only group did not show any significant changes (12.1±6.6 vs 9.2±4.6), considering that there were significant differences between groups (p<0.001). On a mid-term basis, these results have shown the values of the bone soft tissue index in the follow-up of osteoporotic vertebral collapse.     

Hallazgos iniciales en la radiografía de tórax como predictores de empeoramiento en la infección pulmonar por SARS-CoV-2. Correlación en 265 pacientes

Background and aimsWe aimed to analyze the relationship between the initial chest X-ray findings in patients with severe acute respiratory syndrome due to infection with SARS-CoV-2 and eventual clinical worsening and to compare three systems of quantifying these findings.Material and methodsThis retrospective study reviewed the clinical and radiological evolution of 265 adult patients with COVID-19 attended at our center between March 2020 and April 2020. We recorded data related to patients’ comorbidities, hospital stay, and clinical worsening (admission to the ICU, intubation, and death). We used three scoring systems taking into consideration 6 or 8 lung fields (designated 6 A, 6 B, and 8) to quantify lung involvement in each patient's initial abnormal chest X-ray and to classify its severity as mild, moderate, or severe, and we compared these three systems. We also recorded the presence of alveolar opacities and linear opacities (fundamentally linear atelectasis) in the first chest X-ray with pathologic findings.ResultsIn the χ2 analysis, moderate or severe involvement in the three classification systems correlated with hospital admission (p = 0.009 in 6 A, p = 0.001 in 6 B, and p = 0.001 in 8) and with death (p = 0.02 in 6 A, p = 0.01 in 6 B, and p = 0.006 in 8). In the regression analysis, the most significant associations were 6 B with alveolar involvement (OR 2.3; 95%CI 1.1.–4.7; p = 0.025;) and 8 with alveolar involvement (OR 2.07; 95% CI 1.01.–4.25; p = 0.046). No differences were observed in the ability of the three systems to predict clinical worsening by classifications of involvement in chest X-rays as moderate or severe.ConclusionModerate/severe extension in the three chest X-ray scoring systems evaluating the extent of involvement over 6 or 8 lung fields and the finding of alveolar opacities in the first abnormal X-ray correlated with mortality and the rate of hospitalization in the patients studied. No significant difference was found in the predictive ability of the three classification systems proposed.