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Cryptococcus neoformans var. grubii ( Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MAT a allele were observed in both clinical and environmental isolates; however, the mating-type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MAT a and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans. [ABSTRACT FROM AUTHOR]

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The article describes Healthy Babies Need Healthy Moms (HBNHM), an innovative postpartum screening and education program for women who have gestational diabetes mellitus. It mentions that the HBNHM combines the recom¬mended 2-hour postpartum oral glucose tolerance test (OGTT) with diabetes prevention education. For women who test positive, the educational strategies encourage follow-up care and for those with normal results, it helps in preventing the future development of type 2 dia¬betes.

It has been hypothesized that freezing of gait (FOG) in parkinsonian patients (PD) might be triggered by a breakdown in the normal symmetry of gait. In this study, we evaluated the relationship between asymmetry of gait and FOG and the effects of intensive treadmill treatment on asymmetry. We studied 30 patients with (FOG+) and 30 without (FOG−) freezing in 'on' stage. Patients underwent a 4-week rehabilitation treatment using a treadmill with auditory and visual cues and were evaluated at enrolment and at the end of rehabilitation. Outcome measures were gait speed, stride length, asymmetry of gait, Six-minute walking test (6MWT), Unified Parkinson's Disease Rating Scale (UPDRS) II-III, Berg Balance Scale, Timed Up and Go Test, comfortable-fast gait speeds, freezing of gait questionnaire (FOGQ). At enrolment, no differences in gait parameters were observed between the two groups, which differed only in UPDRS_II and BBS. Both FOG+ and FOG− patients spent more time on the left foot (time on left/time on right foot 1.37, p = 0.002, 1.18, p = 0.016, respectively). Rehabilitation determined a homogeneous improvement in both groups of patients for all variables except UPDRS_II and balance, for which a better improvement was observed in FOG+ patients. The improvement in FOGQ in FOG+ patients was significantly correlated to the improvement in asymmetry of gait (Spearman R = 0.46, p = 0.013). Our data support a direct involvement of the asymmetry of gait in the development of FOG in PD. Treadmill training is effective in improving gait and balance in PD FOG+ patients and this might be related to a reduction of asymmetric gait. [ABSTRACT FROM AUTHOR]

Background: A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis. Methodology/Principal Findings: Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the "Trojan horse" model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA. Conclusions/Significance: This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry. [ABSTRACT FROM AUTHOR]

Background. Rehabilitation treatments have acute beneficial effects in Parkinson’s disease (PD) patients, but whether the effects persist over time is unclear. Objective. To assess whether an intensive rehabilitation treatment (IRT) is effective in improving motor performance compared with a control group in a 12-month follow-up, to investigate whether a second cycle administered after 1 year has the same efficacy as the first treatment, and to determine whether IRT reduces the need for increasing levodopa dosage. Methods. A total of 50 PD patients were randomly assigned to 2 groups; 25 participants had 4 weeks of inpatient physical therapy that included treadmill and stabilometric platform training. At discharge, these patients were invited to continue doing the learned exercises. After 12 months, the same treatment was repeated. The control group of 25 patients received only pharmacological treatment and was invited to practice generic physical exercise at home. The rating scales used for the clinical evaluation were the Unified Parkinson’s Disease Rating Scale Sections II and III (UPDRS II and III) and total (UPDRS tot). Results. The authors found that the beneficial effects of IRT persisted over time. A second rehabilitation cycle administered after 1 year was as effective as the first treatment. At the end of the study, daily medication dosage was reduced in treated patients, whereas it was significantly increased in control patients. Conclusion. These findings suggest that the natural worsening of symptoms associated with PD can be effectively counteracted by a properly designed IRT. [ABSTRACT FROM PUBLISHER]

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms. [ABSTRACT FROM AUTHOR]

Objective measurements to assess the efficacy of rehabilitation treatment in Parkinson's disease, suitable to be carried out routinely in the clinical setting, are lacking. Metabolic parameters, reflecting the recruitment and co-ordination of muscle fibers, might be simple instrumental measurements suitable for use as outcome markers. Twenty parkinsonian patients underwent a 4-week rehabilitation treatment. Functional evaluation was based on Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III), Berg's scale, 6-minute walking test (6MWT), and the metabolic data recorded during the 6MWT namely the active energy expenditure (AEE), the kinetics of the energy consumption curve, and the peak value of energy consumption. Both rating scales and gait improved significantly (UPDRS III decreased by 32%, Berg increased by 21% and the 6MWT increased by 17%). We observed significant improvements also in metabolic measurements (35, 18, and 15 improvement in the kinetics of the energy consumption, AEE, and peak value of energy consumption, respectively). Hence, the rehabilitation protocol improved functional characteristics of the patients and these improvements were clearly reflected also by the metabolic measurements. The improvement in clinical scores corresponded with an increase in energy consumption during the 6MWT, indicating greater speed in the recruitment of motor units and of a capacity to maintain this recruitment over time. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Freezing is a disabling symptom in patients with Parkinson's disease. We investigated the effectiveness of a new rehabilitation strategy based on treadmill training associated with auditory and visual cues. Forty Parkinsonian patients with freezing were randomly assigned to two groups: Group 1 underwent a rehabilitation program based on treadmill training associated with auditory and visual cues, while Group 2 followed a rehabilitation protocol using cues and not associated with treadmill. Functional evaluation was based on the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III), Freezing of Gait Questionnaire (FOGQ), 6-minute walking test (6MWT), gait speed, and stride cycle. Patients in both the groups had significant improvements in all variables considered by the end of the rehabilitation program (all P = 0.0001). Patients treated with the protocol including treadmill, had more improvement than patients in Group 2 in most functional indicators (P = 0.007, P = 0.0004, P = 0.0126, and P = 0.0263 for FOGQ, 6MWT, gait speed, stride cycle, respectively). The most striking result was obtained for 6MWT, with a mean increase of 130 m in Group 1 compared with 57 m in Group 2. Our results suggest that treadmill training associated with auditory and visual cues might give better results than more conventional treatments. Treadmill training probably acts as a supplementary external cue. [ABSTRACT FROM AUTHOR]

NSAIDs have an important central antinociceptive activity, parallel and concomitant with their peripheral anti-inflammatory effects. The nociceptive flexion reflex is an experimental model for neurophysiological studies of pain, providing a sensitive evaluation of the nociceptive threshold during various pharmacological treatments in humans. In this research, the analgesic, antinociceptive effects of rofecoxib and nimesulide were compared in a group of normal subjects, using the inhibition of the nociceptive flexion reflex threshold as marker of analgesic activity. Twelve normal male subjects (37.2± 8.05 years old) were enrolled in a double-blind, threetreatment, three-period crossover design, comparing 50 mg rofecoxib and 100 mg nimesulide vs. placebo. To prevent carryover effects between treatments, a 72-hour wash-out interval was allowed between drug administrations. Nociceptive flexion reflex threshold from the caput brevis of biceps femoris caput brevis elicited by sural nerve electrical stimulation was studied before drug administration and during a 60 min observation. Nociceptive flexion reflex threshold, expressed in mAmp needed to elicit the response, was recorded every 5 min for the first 30 min and then every 10 min. Nociceptive flexion reflex rate of changes in mA/min was also calculated to define the speed of inhibition during the first 5 min and 10 min after drug administration. Rofecoxib has a better inhibitory effect on the nociceptive flexion reflex than does nimesulide with faster onset of action, a maximal inhibitory effect between 20 min and 30 min. Both drugs provided durable inhibition throughout the 60 min of recording, although nociceptive flexion reflex inhibition brought about by rofecoxib was on average 33% higher than that obtained after nimesulide. [ABSTRACT FROM AUTHOR]

Objective: To investigate trigeminal-nerve, brain-stem, and brain function, in order to disclose a possible nervous system involvement in neurologically asymptomatic systemic sclerosis (SSc) patients.Methods: Using a standard electromyographic (EMG) technique, we recorded the early (R1) and late (R2) components of the blink reflex in 35 SSc patients with no history or signs of cranial-nerve impairment and 20 control subjects. SSc patients were classified as limited or diffuse SSc and also evaluated for disease duration, autoantibody pattern (ANA, ACA, Scl70) and skin score (by Rodnan modified method).Results: Whereas no SSc patients had an abnormal R1, six (18%) had delayed R2 responses. We found no correlation between R2 latency and clinical or laboratory data.Conclusions: Whereas previous studies reported both R1 and R2 abnormalities (reasonably due to trigeminal neuropathy) in symptomatic SSc patients, we found selective abnormalities of the R2 components in asymptomatic patients. The selective R2 abnormality is secondary to a central dysfunction, either because of a direct impairment of the polysynaptic circuits in the medulla, or because of a decreased cortico-reticular drive on these circuits. The lack of overt trigeminal symptoms in our patients favours a suprasegmental dysfunction, possibly due to microvascular lesions disseminated in the subcortical white matter. [Copyright &y& Elsevier]

Opuntia ficus indica METHANOLIC FRUIT EXTRACT COUNTERACTS OXIDIZED LDL-MEDIATED HUMAN ENDOTHELIAL CELL DYSFUNCTION THROUGH THE INHIBITION OF NF- B ACTIVATION. [Extracted from the article]

Manna is produced from the spontaneous solidification of the sap of some Fraxinus species, and, owing its content in mannitol, is used in medicine as a mild laxative. Manna is also a rich source of characteristic bio-phenols with reducing, antioxidant and anti-inflammatory properties. This study assesses the activity of a hydrophilic extract of manna (HME) on cellular and molecular events in human colon-rectal cancer cells. HME showed a time- and concentration-dependent anti-proliferative activity, measured by MTT assay, in all the cell lines examined, namely Caco-2, HCT-116 and HT-29. The amounts of HME that caused 50% of cell death after a 24 h treatment were 8.51 ± 0.77, 10.73 ± 1.22 and 28.92 ± 1.99 mg manna equivalents/mL, respectively; no toxicity was observed in normally differentiated Caco-2 intestinal cells. Hydroxytyrosol, a component of HME known for its cytotoxic effects on colon cancer cells, was ineffective, at least at the concentration occurring in the extract. Through flow-cytometric techniques and Western blot analysis, we show that HME treatment causes apoptosis, assessed by phosphatidylserine exposure, as well as a loss of mitochondrial membrane potential, an intracellular formation of reactive oxygen species (ROS), increases in the levels of cleaved PARP-1, caspase 3 and Bax, and a decrease in Bcl-2 expression. Moreover, HME interferes with cell cycle progression, with a block at the G1/S transition. In conclusion, the phytocomplex extracted from manna exerts an anti-proliferative activity on human colon cancer cells through the activation of mitochondrial pathway-mediated apoptosis and cell cycle arrest. Our data may suggest that manna could have the potential to exert chemo-preventive effects for the intestine. [ABSTRACT FROM AUTHOR]

Recently, the statistical analysis of muscle activation patterns highlighted that not only one, but several activation patterns can be identified in the gait of healthy adults, with different occurrence. Although its potential, the application of this approach in pathological populations is still limited and specific implementation issues need to be addressed. This study aims at applying a statistical approach to analyze muscle activation patterns of gait in Parkinson's Disease, integrating gait symmetry and co-activation. Surface electromyographic signal of tibialis anterior and gastrocnemius medialis were recorded during a 6-min walking test in 20 patients. Symmetry between right and left stride time series was verified, different activation patterns identified, and their occurrence (number and timing) quantified, as well as the co-activation of antagonist muscles. Gastrocnemius medialis presented five activation patterns (mean occurrence ranging from 2% to 43%) showing, with respect to healthy adults, the presence of a first shorted and delayed activation (between flat foot contact and push off, and in the final swing) and highlighting a new second region of anticipated activation (during early/mid swing). Tibialis anterior presented five activation patterns (mean occurrence ranging from 3% to 40%) highlighting absent or delayed activity at the beginning of the gait cycle, and generally shorter and anticipated activations during the swing phase with respect to healthy adults. Three regions of co-contraction were identified: from heel strike to mid-stance, from the pre- to initial swing, and during late swing. This study provided a novel insight in the analysis of muscle activation patterns in Parkinson's Disease patients with respect to the literature, where unique, at times conflicting, average patterns were reported. The proposed integrated methodology is meant to be generalized for the analysis of muscle activation patterns in pathologic subjects. [ABSTRACT FROM AUTHOR]

Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay; cell morphology via fluorescence microscopy; apoptosis, cell cycle, mitochondrial membrane potential (MMP) and cell redox balance via flow-cytometry; expression levels of apoptosis-related proteins via western blot. Cell viability assays and Chou-Talalay plot demonstrated that the combination of CDDP and Ind had synergistic cytotoxic effects. Combined treatment had significant effects (p < 0.05) on phosphatidylserine externalization, cell morphological changes, cell cycle arrest, fall in MMP, ROS production and GSH decay compared with the individual treatment groups. Bax, cytochrome c, p53 and p21waf1 were over-expressed, while Bcl-2 was downregulated. Pre-treatment with N-acetyl-l-cysteine abolished the observed synergistic effects. We also demonstrated potentiation of CDDP anticancer activity by nutritionally relevant concentrations of Ind. Oxidative stress-dependent mitochondrial cell death is the basis of the chemosensitizing effect of Ind combined with CDDP against HeLa cancer cells. ROS act as upstream signaling molecules to initiate apoptosis via p53/p21waf1 axis. Ind can be a phytochemical of interest in combo-therapy. [ABSTRACT FROM AUTHOR]