Assessing the Relationship between Vitamin D Status and Impairments in Cognitive and Physical Performance in Older Adults Using a Dual Task Physical Performance Test.

BACKGROUND: Vitamin D deficiency has been associated with an increased risk of falls in older adults. Several studies have demonstrated an association between vitamin D deficiency and gait and cognitive impairments, which are two risk factors for falls in the elderly. There is lack of research about the role of vitamin D in cognitive function in the context of mobility. OBJECTIVE: The purpose of this study was to evaluate the association between vitamin D status with the age-related changes in mobility through higher order cognitive function using a dual task physical performance test. DESIGN: Cross-sectional. SETTING: Community-dwelling older adult population located in Miami, Fl. PARTICIPANTS: Healthy participants over the age of 55 (n=97) who participated in the parent interventional study. MEASUREMENTS: Participants completed assessments that included serum levels of vitamin D, surveys, and dual task physical performance tests. Spearman's correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml) and sufficiency (≥30 ng/ml) and dual task physical performance variables. The significance level was set at α=0.05. RESULTS: There were no significant associations between vitamin D insufficiency and gait velocity during either task. Using Spearman correlations, slower single (P=0.011) and dual task counting rates (P=0.006) were significantly associated with vitamin D insufficiency. Independent t-tests showed dual and single task counting rates were significantly lower in the vitamin D insufficient group compared to the sufficient group (P=0.018 and P=0.028, respectively). The results for the ANOVAs indicated that velocities and counting rates were not significantly different by vitamin D status (Wilk's Lambda =0.999; F (1, 95) =.11, P=.740) (Wilk's Lambda =.999, F(1,95)=.13, P=.718). Vitamin D status was not significantly associated with dual task physical performance (defined as the difference in dual and single task) in gait velocity (OR=1.00, 95% CI: 0.98; 1.02, P=0.772) and counting rate (OR=1.684, 95% CI: 0.15; 19.57, P=0.677), when controlling for confounders. CONCLUSIONS: Since counting backward is a mental tracking task, which is a component of executive function, our results suggest a relationship between vitamin D insufficiency and executive dysfunction. Executive dysfunction has been previously associated with fall risks in the elderly, and it could be a possible mediator between vitamin D and falls. Our data suggest that cognition may play a significant role in vitamin D's influence on falls, while motor function may play a lesser role.

Bradykinin, insulin, and glycemia responses to exercise performed above and below lactate threshold in individuals with type 2 diabetes.

The aim of this study was to analyze the acute responses of bradykinin, insulin, and glycemia to exercise performed above and below lactate threshold (LT) in individuals with type 2 diabetes mellitus (T2D). Eleven participants with a diagnosis of T2D randomly underwent three experimental sessions 72 h apart: 1) 20 min of exercise performed at 120% of LT (120%LT), 2) 20 min of exercise performed at 80% of LT (80%LT), and 3) 20 min of control session. Blood glucose was analyzed before, during, and at 45 min post-exercise. Bradykinin and insulin were analyzed before and at 45 min post-exercise. Both exercise sessions elicited a parallel decrease in glucose level during exercise (P≤0.002), with a greater decrease being observed for 120%LT (P=0.005). Glucose decreased 22.7 mg/dL (95%CI=10.3 to 35, P=0.001) at the 45 min post-exercise recovery period for 80%LT and decreased 31.2 mg/dL (95%CI=18.1 to 44.4, P<0.001) for 120%LT (P=0.004). Insulin decreased at post-exercise for 80%LT (P=0.001) and control (P≤0.035). Bradykinin increased at 45 min post-exercise only for 80%LT (P=0.013), but was unrelated to the decrease in glucose (r=-0.16, P=0.642). In conclusion, exercise performed above and below LT reduced glycemia independently of insulin, but exercise above LT was more effective in individuals with T2D. However, these changes were unrelated to the increase in circulating bradykinin.

Porphyrinoid rotaxanes: building a mechanical picket fence.

Building on recent progress in the synthesis of functional porphyrins for a range of applications using the Cu-mediated azide-alkyne cycloaddition (CuAAC) reaction, we describe the active template CuAAC synthesis of interlocked triazole functionalised porphyrinoids in excellent yield. By synthesising interlocked analogues of previously studied porphyrin-corrole conjugates, we demonstrate that this approach gives access to rotaxanes in which the detailed electronic properties of the axle component are unchanged but whose steric properties are transformed by the mechanical "picket fence" provided by the threaded rings. Our results suggest that interlocked functionalised porphyrins, readily available using the AT-CuAAC approach, are sterically hindered scaffolds for the development of new catalysts and materials.

Short-term synaptic plasticity across topographic maps in the electrosensory system.

The early pathways underlying the active electric sense of the weakly electric fish Apteronotus leptorhynchus involve three parallel processing streams. An array of tuberous electroreceptors distributed over the skin provides inputs to the electrosensory lateral line lobe (ELL), forming the basis for three topographic maps: LS (lateral segment), CLS (centrolateral segment), and CMS (centromedial segment). In addition, each map receives topographically preserved inputs from a direct feedback pathway. How this feedback contributes to the distinct spatiotemporal filtering properties of ELL pyramidal neurons across maps is not clear. We used an in vitro approach to characterize short-term plasticity (STP) in the direct feedback synapses onto pyramidal neurons in each map. Our findings indicated that the dynamics of STP varied across maps in a manner that was consistent with the temporal filtering properties of pyramidal neurons in vivo. Using a modeling approach, we found that the STP of direct feedback synapses in CMS was best described by a simple facilitation-depression model. On the other hand, STP in LS was best described by synaptic facilitation with a use-dependent recovery rate. These results suggest that differential regulation of overlapping STP processes in feedback pathways can contribute to the functional specialization of topographic sensory maps.

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

BACKGROUND: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. METHODS: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. RESULTS: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. CONCLUSIONS: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas.

High yielding synthesis of 2,2'-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes.

We present an operationally simple approach to 2,2'-bipyridine macrocycles. Our method uses simple starting materials to produce these previously hard to access rotaxane precursors in remarkable yields (typically >65%) across a range of scales (0.1-5 mmol). All of the macrocycles reported are efficiently converted (>90%) to rotaxanes under AT-CuAAC conditions. With the requisite macrocycles finally available in sufficient quantities, we further demonstrate their long term utility through the first gram-scale synthesis of an AT-CuAAC [2]rotaxane and extend this powerful methodology to produce novel Sauvage-type molecular shuttles.

Correction: High yielding synthesis of 2,2'-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes.

[This corrects the article DOI: 10.1039/C6SC00011H.].

Aerobic training does not alter CRP in apparently healthy, untrained men.

AIM: Regular aerobic exercise may reduce cardiovascular disease (CVD) risk by lowering the concentration of inflammatory markers, such as C-reactive protein (CRP). While studies in diseased populations have shown significant decreases in CRP concentrations with regular aerobic training, little has been conclusively determined regarding the effects of aerobic training on CRP concentrations in apparently healthy, untrained populations. Aim of the study was to examine the effects of a 17-wk half marathon training program (TP) on CRP concentrations, aerobic fitness, and body composition in apparently healthy, untrained men. METHODS: Twenty men (29.3±1.0 y) enrolled as training subjects (TRN) in a 17-wk half marathon TP. An additional 22 men (27.8±1.4 y) served as controls (CON). Fasting blood samples were taken at four time points over the TP and were analyzed for CRP and interleukin-6 (IL-6) concentrations. Aerobic capacity (VO2max) and body fat percent (BF%) were measured before and after the TP. RESULTS: No significant post-training changes in CRP (P=0.70) or IL-6 concentrations (P=0.67) were seen in TRN as a result of the TP, despite significant improvements in VO2max (42.2±1.9 ml∙kg-1∙min⁻¹, P<0.0001) and significant reductions in resting heart rate (P=0.004), BF% (P=0.03), and body mass index (BMI, P=0.05). No significant changes in CRP, VO2max, BMI, or BF% were detected in CON over time. CONCLUSION: Regular aerobic training does not appear to affect CRP concentrations in apparently healthy, untrained men despite significant improvements in bodyweight, BF%, BMI, and VO2max.

Patient predictor variables for six forms of suicidality.

OBJECTIVES: There has been a significant amount of research performed on the relationship between the presence of chronic pain and all forms of suicidality. This study explored which rehabilitation acute pain patient (APP) and rehabilitation chronic pain patient (CPP) variables are predictive of six suicidality items: wanting to die because of pain; wanting to die because life is hard; history of wanting to die; history of suicide attempts; recent frequent suicide ideation; and having a suicidal plan. METHODS: The six suicide items were contained within the Battery for Health Improvement-Research Version (BHI-R) and were administered to a healthy community sample (n = 1478), community patients (n = 158), rehabilitation APPs (n = 326), rehabilitation CPPs (n = 341) and rehabilitation patients without pain (n = 110). RESULTS: Affirmation of the six items in APPs/CPPs ranged from 6.13% to 34.90%. Logistic regression predictor models for each item for APPs/CPPs were developed utilizing available variables from the BHI-R. Predictor variables differed between APPs and CPPs and between items. Most predictor variables had previously been delineated in non-pain behaviour studies (e.g., substance abuse). Some novel variables such as perseverance were also identified. Contrary to the behaviour suicide literature, no demographic variables (except employment) were predictive. Correct patient classification ranged from 87% to 95%, in most cases being better than the base rate prediction. DISCUSSION: Suicidality predictor variables were differentially distributed between APPs and CPPs and between different forms of suicidality. Some suicidality predictor variables appeared to be specific to pain patients.

Evaluation of a flow cytometry-based assay for natural killer cell activity in clinical settings.

Natural killer (NK) cells are not only important in first line defence against viral and bacterial infections, but also in immune surveillance of malignant cells and thus NK cell cytotoxicity is primary indicator of immune function. Although chromium release assay is recognized as 'gold standard' for measuring NK cell activity, it has disadvantages like use of radioactive compounds, poor loading and high spontaneous release. It is difficult to perform this assay in clinical laboratory because of difficulties with disposal of radioactive waste and standardization problems. We describe a flow cytometry-based assay for the measurement of NK cell activity by incorporating fluorescent dye, DiO, into membranes of target cells. NK cell activity was measured at baseline, 1 and 4 weeks follow-up in 20 normal healthy individuals on a dietary supplement immunomodulator to enhance NK cell function. Mean baseline NK cell activity percentage (21.5; SD = 9.3) increased significantly to a maximum level at 1 week (31.3%; SD = 7.9; P = 0.007) and then returned to baseline level at 4 weeks (21.5; SD = 8.3). An important feature of flow cytometry-based assays is its ability to discriminate effector cells from target cells, and potential for explaining molecular interactions underlying target cell lysis. Under clinical settings, this assay will be of interest for frequently monitoring immunological status of patients on treatment for various diseases that affect their immune status. The assay is easy to perform without using radioactive material and thus could become a tool for monitoring pathogenesis and immune reconstitution.

Reply to Comment on 'Unconventional gap state of trapped exciton in lead sulphide quantum dots'.

This is a reply to a comment on our previously published paper.

Unconventional gap state of trapped exciton in lead sulfide quantum dots.

Exciton states in lead selenide (PbSe) and lead sulfide (PbS) quantum dots have been studied extensively. However, relatively less attention has been paid to the states within the quantum dot bandgap. Our experimental results have revealed a single in-gap state which bears confinement dependence yet cannot be explained by dark exciton theory, nor is it a trap state related to quantum dot surface defects as previously observed. A detailed analysis of the temperature dependence of photoluminescence, Stokes shift, absorption and photoinduced absorption indicates the unconventional GS is a new state of a trapped exciton in a QD film. With appropriate design engineering, these trapped excitons might be harvested in solar cells and other optoelectronic devices.

Zebrafish (Danio rerio) gill neuroepithelial cells are sensitive chemoreceptors for environmental CO2.

Adult zebrafish exhibit hyperventilatory responses to absolute environmental CO(2) levels as low as 0.13% ( mmHg), more than an order of magnitude lower than the typical arterial levels (40 mmHg) monitored by the mammalian carotid body. The sensory basis underlying the ability of fish to detect and respond to low ambient CO(2) levels is not clear. Here, we show that the neuroepithelial cells (NECs) of the zebrafish gill, known to sense O(2) levels, also respond to low levels of CO(2). An electrophysiological characterization of this response using both current and voltage clamp protocols revealed that for increasing CO(2) levels, a background K(+) channel was inhibited, resulting in a partial pressure-dependent depolarization of the NEC. To elucidate the signalling pathway underlying K(+) channel inhibition, we used immunocytochemistry to show that these NECs express carbonic anhydrase (CA), an enzyme involved in CO(2) sensing in the mammalian carotid body. Further, the NEC response to CO(2) (magnitude of membrane depolarization and time required to achieve maximal response), under conditions of constant pH, was reduced by 50% by the CA-inhibitor acetazolamide. This suggests that the CO(2) detection mechanism involves an intracellular sensor that is responsive to the rate of acidification associated with the hydration of CO(2) and which does not require a change of extracellular pH. Because some cells that were responsive to increasing also responded to hypoxia with membrane depolarization, the present results demonstrate that a subset of the NECs in the zebrafish gill are bimodal sensors of CO(2) and O(2).

Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location.

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands. METHODS AND RESULTS: Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20-30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an 'Indian-file' array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for alpha-smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour. CONCLUSIONS: PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.

Hormone replacement therapy after treatment for breast cancer: physicians' attitudes towards randomized trials.

PURPOSE: Physician support is required for successful patient recruitment to a large randomized controlled trial (RCT) designed to determine the safety and benefits of short-term hormone replacement therapy (HRT) after breast cancer (BC). METHODS: A survey was mailed to 1899 Canadian gynaecologists, family physicians, medical, radiation and surgical oncologists to assess willingness to refer patients to an RCT of HRT after BC. RESULTS: Of 538 physicians, 420 (78%) reported that they would be willing to refer a woman after BC to an RCT of HRT versus placebo. Variables predicting willingness to refer included: support for HRT in well women (p = 0.04) and after BC (p = 0.0001); support for clinical trials (p = 0.0001); ongoing BC trials at the physicians' institution (p = 0.003); currently prescribing HRT to women after BC (p = 0.03); and beneficial results in ongoing RCTs of HRT in well women (p = 0.02). CONCLUSIONS: An RCT of short-term HRT after BC may be feasible among Canadian physicians.

Autoantibodies and glomerulonephritis in systemic lupus erythematosus.

Autoantibody diversification to a variety of autoantigens is a hallmark for systemic autoimmunity. SLE represents a prototype. In this article the roots of the important questions probed by the Kunkel laboratory in SLE research are traced. Data from the recent animal work by the laboratory of Shu Man Fu are summarized to emphasize the importance of further exploration of autoantibody specificities in lupus with a special emphasis on nephritis and to suggest a broader perspective regarding lupus autoantibody reactivities in addition to those against nuclear components.

Blurring of the senses: common cues for distance perception in diverse sensory systems.

Distance perception is an essential task of sensory systems. Our visual systems effectively use binocular visual cues to determine an object's distance. Other visual, but monocular, cues are also available for distance perception. Visual contrast and image blur are two such cues [O'Shea et al., 1994. Vis. Res. 34, 1595-1604; O'Shea et al., 1997. Perception 26, 599-612; Mather, 1997. Perception 26, 1147-1158]. We show the effects of combining these cues using a simple psychophysical test. The novelty in our approach is that our exact choice of visual stimuli allows us to show a direct parallel between visual distance perception and distance perception using an entirely different sense, the electric sense of weakly electric fish. We discuss previous work on electrosensory psychophysics [von der Emde et al., 1998. Nature 395, 890-894] and show that cues used for electrosensory distance perception are analogous to visual contrast and blur. We also suggest that analogous cues are involved in auditory distance perception. The utilization of analogous cues implies that these diverse sensory systems perform similar computations for distance perception.

A comparison of Hispanic and African-American sexually abused girls and their families.

OBJECTIVE: To study the differential effects of sexual abuse on Hispanic (HN) and African-American (AA) girls. METHOD: Sexually abused girls and their caretakers (N = 159), of which 52% (n = 82) were AA (mean age 9.8 years, SD = 3.4, R = 6-17) and 48% (n = 77) were HN (mean age 10.1 years, SD = 3.8, R = 6-18), were included in the study. The mother/caretaker was administered a demographic form, the Achenbach's Child Behavior Checklist (CBCL), and the Family Assessment Measure (FAM-P). The child completed the FAM-C and the Trauma Symptom Checklist for Children (TSCC). The clinician completed the Parental Reaction to Incest Disclosure Scale (PRIDS). RESULTS: HN girls were found to have a greater number of sexually abusive episodes and waited longer to disclose their abuse while AA girls were more likely to have experienced vaginal penetration. The perpetrators of HN girls were older and more likely to be fathers or stepfathers. The mothers/ caretakers of HN girls perceived their children as having significantly more aggressive behavior, anxiety/depression, somatic complaints, internalizing and externalizing behaviors, and had a higher total score on the CBCL than did AA girls. The HN girls were more likely to see their family as dysfunctional with confusion regarding family values and rules. HN mothers/caretakers perceived their families as more conflicted regarding adaptability and family controls. CONCLUSIONS: HN girls experienced more emotional and behavioral problems, and both HN girls and their mothers/caretakers perceived their families as more disturbed and dysfunctional.