Skill-building through Task-Oriented Motor Practice (STOMP) intervention for activities of daily living: study protocol for a randomized, single blinded clinical trial.

BACKGROUND: Progressive disability in activities of daily living (ADL) is inevitable for people with Alzheimer's disease and related dementias (ADRD). Attempts to slow or prevent ADL disability have been unsuccessful despite making progress in behavioral training methods. Missing from this research is an emphasis on how we maximize a patient's engagement during training and the rigorous examination of implementation protocols (dosing and training methods) which may advantage learning in people with ADRD. Our team addressed this gap with the development of the STOMP (Skill-building through Task-Oriented Motor Practice) intervention which creates methods for obtaining ADL goals that support "personhood" and tests high-intensity protocols that appear to advantage learning and sustained learning over time. Through this study, we aim to evaluate differential outcomes by dose levels as well as assess the moderating effects of attention to task during training. METHODS/DESIGN: Randomized-controlled trial with 32 participants with dementia assigned to either the original, intensive STOMP protocol (3 hours/day, 5 days/week for 2 weeks) or a less-intensive STOMP protocol (1 hour/day, 2 days/week for 2 weeks) delivered by an occupational therapy assistant in the home. ADL training is delivered using motor learning theory techniques of blocked practice, continuous verbal praise, errorless learning and intense dosing schedules. Inclusion criteria: English speaking, adults 50-80 years old that live with a legally-authorized representative that can provide consent, who can follow a one-step command, have three ADL goals they want to address and can participate in an intense therapy protocol. Exclusions include diagnoses of Creutzfeldt-Jakob Dementia, delirium or receptive/global aphasia. Recruitment will occur through direct mailing, physician referral and media/support group presentations. Blinded occupational therapists will complete baseline, post-intervention and 3-month follow-up assessments in the home. Repeated measures ANOVA and graphs will be used to interpret and display results. DISCUSSION: Through this protocol, we will examine differential outcomes by dose for the STOMP ADL intervention. Our results will inform dosing parameters for future intervention studies for people with ADRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02356055. ETHICAL APPROVAL: This study protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#4648) and will be performed in accordance with the Declaration of Helsinki.

Acute hemorrhagic complications are associated with lower coated-platelet levels in non-lacunar brain infarction.

BACKGROUND: Coated platelets are procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. OBJECTIVE: To investigate whether acute hemorrhagic complications occurring during the initial hospital admission for non-lacunar ischemic stroke are associated with lower coated-platelet levels. PATIENTS/METHODS: Coated-platelet levels were determined in 385 consecutive patients with non-lacunar stroke. Hemorrhagic complications were defined as either intracranial hemorrhage or significant extracranial bleeding (drop in hemoglobin of ≥ 2 g dL(-1) ). The rate of acute hemorrhagic complication was compared among subjects categorized into tertiles of coated-platelet levels using an exact Cochrane-Armitage trend test. Logistic regression was used to estimate the adjusted odds of hemorrhagic complication associated with coated-platelet levels. RESULTS: Hemorrhagic complications were present in 15 (3.9%) cases. Of these, four had intracranial hemorrhage and 11 had extracranial hemorrhage. The occurrence of hemorrhagic complications differed among the coated-platelet tertiles: 10.2% for the first tertile (coated-platelet levels < 35.5%), 1.5% for the second tertile and 0% for the third tertile (coated-platelet levels ≥ 47.5%, trend test). Logistic regression showed that the odds of hemorrhagic complication in those with levels < 35.5% were 14.59 times the odds for patients with levels ≥ 35.5% (95% CI: 3.24-65.7). CONCLUSIONS: Lower levels of procoagulant platelets are associated with acute hemorrhagic complications following non-lacunar ischemic stroke. These results suggest a role for coated-platelets in risk/benefit assessment in the early stages of stroke.

Extracellular fluid conductivity analysis by dielectric spectroscopy for in vitro determination of cortical tissue vitality.

Brain tissue is extremely metabolically active in part due to its need to constantly maintain a precise extracellular ionic environment. Under pathological conditions, unhealthy cortical tissue loses its ability to maintain this precise environment and there is a net efflux of charged particles from the cells. Typically, this ionic efflux is measured using ion-selective microelectrodes, which measure a single ionic species at a time. In this paper, we have used a bio-sensing method, dielectric spectroscopy (DS), which allows for the simultaneous measurement of the net efflux of all charged particles from cells by measuring extracellular conductivity. We exposed cortical brain slices from the mouse to different solutions that mimic various pathological states such as hypokalemia, hyperkalemia and ischemia (via oxygen-glucose deprivation). We have found that the changes in conductivity of the extracellular solutions were proportional to the severity of the pathological insult experienced by the brain tissue. Thus, DS allows for the measurement of changes in extracellular conductivity with enough sensitivity to monitor the health of brain tissue in vitro.

Abnormal intestinal function related to hypocupremia in a rodent model.

BACKGROUND: Copper deficiency affects the peripheral (PNS) and central (CNS) nervous systems and can lead to neurological deficits in humans. No studies have addressed whether copper deficiency affects the enteric nervous system (ENS). We hypothesized that ENS abnormalities impair intestinal function in copper deficiency. METHODS: We induced copper deficiency in rats by nutritional deprivation. Once hypocupremia was achieved, we euthanized the animals and harvested the small and large intestine. The longitudinal smooth muscle from the jejunum and colon was suspended in organ baths and contractility in response to electrical field stimulation (EFS) was assessed. Mucosa was also isolated from each region and placed into modified Ussing chambers to determine whether the copper deficiency leads to alterations in epithelial transport measured as a change in short circuit current across the mucosa in response to EFS. KEY RESULTS: A copper deficient diet (CDD) in normal rats for 9 weeks was sufficient to produce hypocupremia. Colonic smooth muscle contractility was significantly decreased in response to EFS in rats fed a CDD compared with controls, however, jejunal smooth muscle contractility in response to EFS in rats fed a CDD rats resembled that observed in controls. No significant changes in secretory function were observed in either region in response to CDD. CONCLUSIONS & INFERENCES: Dietary copper deficiency produces significant changes in the neural regulation of colonic smooth muscle contractility in a rodent model. Thus, along with CNS and PNS effects in humans, copper deficiency results in abnormal ENS regulation of intestinal function in rats.

Coated-platelet levels and progression from mild cognitive impairment to Alzheimer disease.

OBJECTIVES: Coated-platelets are a subset of platelets produced by dual-agonist activation with collagen and thrombin. These platelets retain full-length amyloid precursor protein on their surface, are elevated in patients with amnestic as compared to nonamnestic mild cognitive impairment (MCI), and correlate with disease progression in Alzheimer disease (AD). Prompted by these findings, we investigated the association between coated-platelet production in amnestic MCI and rate of progression to AD. METHODS: Coated-platelet levels were assayed in 74 patients with amnestic MCI who were subsequently followed longitudinally for up to 36 months in an outpatient dementia clinic. Levels are reported as percent of cells converted into coated-platelets. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time to progression to AD were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: The 24-month cumulative incidence of progression to AD was different among tertiles: 4% for the first tertile (lowest coated-platelet levels), 13% for the second tertile, and 37% for the third tertile (overall log-rank test, p = 0.02). The hazard rate of progression to AD for patients in the highest coated-platelet tertile was 5.1 times that for patients in the lowest tertile (p = 0.04), whereas the hazard rate for the middle tertile was similar to that for the lowest tertile (hazard rate ratio = 1.5, p = 0.7). CONCLUSIONS: Elevated coated-platelet levels in patients with amnestic MCI are associated with increased risk for progression to AD.

Design and implementation of a novel superfusion system for ex vivo characterization of neural tissue by dielectric spectroscopy (DS).

Dielectric spectroscopy is a widely utilized electrophysiological characterization method. The obtained dielectric spectra and derived properties have the potential of providing significant information regarding changes in the physiological state of a biological system. However, since many of the dielectric properties are obtained in vitro from excised tissue far removed from physiological conditions, the value of the information obtained may be diminished. In this paper, we introduce a superfusion system that is designed to produce ex vivo dielectric spectroscopy measurements by providing the living tissue with a continuous and ample supply of nutrients and oxygen while removing metabolites and other waste. This superfusion system provides the convenience of in vitro measurement while concurrently producing results that can be more closely correlated with actual physiological changes in the biological system.

Lower coated-platelet levels are associated with early hemorrhagic transformation in patients with non-lacunar brain infarction.

BACKGROUND: Coated-platelets, representing a subset of platelets with procoagulant potential, are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage. However, within the non-lacunar patient population there are individuals with lower levels of coated-platelets, which raises the possibility that these individuals would be susceptible to early hemorrhagic transformation (HT) of ischemic stroke. OBJECTIVE: Because extremes in coated-platelet potential may be associated with either thrombotic or hemorrhagic events, we undertook a pilot study to investigate whether there is an association between coated-platelet production and the presence of early HT in patients with non-lacunar ischemic stroke. PATIENTS AND METHODS: Coated-platelet levels were determined in 115 consecutive eligible patients with a diagnosis of non-lacunar ischemic stroke. Early HT was determined on CT scan examination and confirmed by MRI studies. The distribution of coated-platelet levels was summarized using the median and interquartile range (25th-75th percentiles) and compared statistically between patients with and without early HT using the non-parametric Wilcoxon rank sum test. RESULTS: The median coated-platelet level in all non-lacunar stroke patients was 38.0% (interquartile range 30.5-48.3%). Early HT was detected in 11 patients (9.6%), and these patients had significantly lower coated-platelet levels compared with those without early HT [median 25.1% (interquartile range 20.4-35.5%) vs. 39.2% (31.6-49.5%), P = 0.003]. CONCLUSIONS: Lower levels of coated-platelets are associated with the presence of early HT in patients with non-lacunar ischemic stroke.

Probing the membrane potential of living cells by dielectric spectroscopy.

In this paper we demonstrate a quantitative way to measure the membrane potential of live cells by dielectric spectroscopy. We also show that the values of the membrane potential obtained using our technique are in good agreement with those obtained using traditional methods-voltage-sensitive dyes. The membrane potential is determined by fitting the experimental dielectric dispersion curves with the dispersion curves obtained from a theoretical model. Variations in the membrane potential were induced by modifying the concentration of potassium chloride in the solution of the cell suspension in the presence of valinomycin. For exemplification of the method, E. coli was chosen for our experiments.

Cumulative incidence of vitamin B12 deficiency in patients with Alzheimer disease.

BACKGROUND: Although vitamin B12 is routinely measured in patients with Alzheimer disease (AD) at the time of the initial diagnosis, it is not known if repeat vitamin B12 measurements are indicated to detect new deficiency cases. We aimed to determine the incidence of de-novo vitamin B12 deficiency over a period of 3 years in a cohort of AD patients without a prior diagnosis of vitamin B12 deficiency and with initial vitamin B12 levels greater than 350 ng/L. METHODS: Vitamin B12 levels were measured at the time of AD diagnosis and repeated 3 years later in 102 consecutive patients, unless a diagnosis of B12 deficiency was made in the interim. RESULTS: Vitamin B12 deficiency was diagnosed in 7 patients, corresponding to a cumulative incidence in the cohort studied of 7.6% after 3 years of follow-up. Statistical comparison of initial and repeat vitamin B12 measurements in patients that completed follow-up showed a significant reduction in levels (p=0.003). Among the 79 subjects with follow-up, 17 patients (22%, 95% CI, 13%-32%) had a repeat level less than 350 ng/L. No significant correlates of deficiency incidence were identified. CONCLUSION: Our pilot data indicate that vitamin B12 levels decreased in this cohort of AD patients putting a substantial percentage at risk of deficiency and reaching deficiency state in a meaningful number of patients. Repeat screening for B12 deficiency after approximately 2 years of follow-up seems warranted in order to prevent hematological and neurological manifestations that may significantly alter their quality of life.

Coated-platelets in ischemic stroke: differences between lacunar and cortical stroke.

BACKGROUND: Coated-platelets are a subset of platelets with procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. OBJECTIVE: The goal was to investigate if coated-platelet production differs between patients with lacunar ischemic stroke and non-lacunar (cortical) ischemic stroke as compared with controls. PATIENTS AND METHODS: Blood samples from 60 patients with ischemic stroke (20 lacunar and 40 cortical) and 70 controls were analyzed for coated-platelet production. RESULTS: Coated-platelet production was significantly lower in patients with lacunar stroke (21.8 +/- 11.4%, mean +/- 1 SD) as compared with either controls (31.6 +/- 13.2%, P = 0.008) or patients with cortical stroke (39.4 +/- 12.7%, P < 0.001). The increase in coated-platelets for patients with cortical stroke as compared with controls was also significant (P = 0.008). CONCLUSIONS: Our results indicate a marked difference in coated-platelet synthesis in lacunar vs. non-lacunar stroke, thereby providing additional support for the existence of distinct pathological processes underlying these two subtypes of ischemic stroke. Further investigation of the role of coated-platelets in stroke, taking into account these preliminary findings, is warranted.

Relapsing hypocupraemic myelopathy requiring high-dose oral copper replacement.

Adult-onset copper deficiency with neurological manifestations is a newly recognised syndrome. Long-term oral copper replacement therapy has been the mainstay of treatment in the literature. A case of relapsing hypocupraemic myelopathy responsive to increased doses of copper replacement is reported. Standard doses of copper may not be sufficient for all patients.

Foliculitis en penacho / Tufted hair folliculitis

Presentamos tres pacientes, dos mujeres y un varón, con diagnóstico de foliculitis en penacho, caracterizada por áreas de alopecia cicatrizal dentro de las cuales emergen conglomerados pilosos de un único orificio folicular. Una de las pacientes fue tratada con infiltraciones con corticoides y nadifloxacina tópica; la otra, con corticoides tópicos y queratolíticos, y el paciente varón, con isotretinoína oral. En los tres se obtuvo una mejoría parcial. La FEP sería una variante de la foliculitis decalvante, caracterizada por la formación del penacho piloso como fenómeno principal, evolución tórpida y tratamiento dificultoso

Foliculitis en penacho / Tufted hair folliculitis

Presentamos tres pacientes, dos mujeres y un varón, con diagnóstico de foliculitis en penacho, caracterizada por áreas de alopecia cicatrizal dentro de las cuales emergen conglomerados pilosos de un único orificio folicular. Una de las pacientes fue tratada con infiltraciones con corticoides y nadifloxacina tópica; la otra, con corticoides tópicos y queratolíticos, y el paciente varón, con isotretinoína oral. En los tres se obtuvo una mejoría parcial. La FEP sería una variante de la foliculitis decalvante, caracterizada por la formación del penacho piloso como fenómeno principal, evolución tórpida y tratamiento dificultoso (AU)

[Medical and social implication of cervical cancer screening]. / Implicatiile medico-sociale ale screening-ului cancerului de col uterin.

Invasive cervical cancer represents a major health problem in Romania. When there is a functioning screening network, the incidence of invasive lesions has a marked reduction, this program being the most successful cancer prevention program of all times. 80% of the actual incidence and mortality from this disease occurs in countries without an organized screening. A good infrastructure of the cytopathologist--practitioner relation must be achieved in order to reach the standard of early detection of the preinvasive cervical lesions.

CNS demyelination associated with copper deficiency and hyperzincemia.

CNS demyelination is not a previously reported feature of acquired copper deficiency. The authors report two patients with idiopathic hypocupremia and hyperzincemia, hematologic changes of copper deficiency, and extensive CNS demyelination. Hematologic recovery followed copper supplementation, both initially and after relapse off copper therapy, while serum zinc levels remained high and the neurologic abnormalities only stabilized.

Hemispheric differences in recognizing upper and lower facial displays of emotion.

OBJECTIVE: To determine if there are hemispheric differences in processing upper versus lower facial displays of emotion. BACKGROUND: Recent evidence suggests that there are two broad classes of emotions with differential hemispheric lateralization. Primary emotions (e.g. anger, fear) and associated displays are innate, are recognized across all cultures, and are thought to be modulated by the right hemisphere. Social emotions (e.g., guilt, jealousy) and associated "display rules" are learned during early child development, vary across cultures, and are thought to be modulated by the left hemisphere. Display rules are used by persons to alter, suppress or enhance primary emotional displays for social purposes. During deceitful behaviors, a subject's true emotional state is often leaked through upper rather than lower facial displays, giving rise to facial blends of emotion. We hypothesized that upper facial displays are processed preferentially by the right hemisphere, as part of the primary emotional system, while lower facial displays are processed preferentially by the left hemisphere, as part of the social emotional system. METHOD: 30 strongly right-handed adult volunteers were tested tachistoscopically by randomly flashing facial displays of emotion to the right and left visual fields. The stimuli were line drawings of facial blends with different emotions displayed on the upper versus lower face. The subjects were tested under two conditions: 1) without instructions and 2) with instructions to attend to the upper face. RESULTS: Without instructions, the subjects robustly identified the emotion displayed on the lower face, regardless of visual field presentation. With instructions to attend to the upper face, for the left visual field they robustly identified the emotion displayed on the upper face. For the right visual field, they continued to identify the emotion displayed on the lower face, but to a lesser degree. CONCLUSIONS: Our results support the hypothesis that hemispheric differences exist in the ability to process upper versus lower facial displays of emotion. Attention appears to enhance the ability to explore these hemispheric differences under experimental conditions. Our data also support the recent observation that the right hemisphere has a greater ability to recognize deceitful behaviors compared with the left hemisphere. This may be attributable to the different roles the hemispheres play in modulating social versus primary emotions and related behaviors.

Micosis fungoide folicular / Follicular mycosis fungoides

La micosis fungoide folicular (MFF) es una variante clínica infrecuente de MF. Presentamos el caso de un paciente de 51 años de edad con localización en cuero cabelludo y buena respuesta al tratamiento. Realizamos además una revisión de la literatura