Effects of gait intervention using the draw-in maneuver on knee joint function and the thoracic kyphosis angle in knee osteoarthritis.

BACKGROUND: To evaluate whether the knee adduction moment (KAM) could be reduced by a short instruction in the Draw-in (DI) maneuver in healthy adults, and whether knee joint function would improve with a longer DI gait intervention in patients with knee osteoarthritis (OA). METHOD: In Study 1, healthy adults received 10 minutes supervised instruction in DI gait in and then practiced the gait independently for 10 minutes. Three-dimensional motion analysis measurement was performed in each phase. In Study 2, patients with OA performed a 20-minute DI gait intervention daily for 6 weeks. At baseline and after 6 weeks, knee pain, the Knee injury and Osteoarthritis Outcome Score, the MOS 8 item Short-Form Health Survey, thoracic kyphosis angle, knee joint range of motion, knee extension muscle strength, hip abduction muscle strength, and activity level were evaluated. RESULTS: In Study 1, the DI gait to decrease KAM could be learning following only 10 minutes of instruction and 10 minutes of self-practice in healthy adults. In Study 2, knee pain was reduced by 19 % and the thoracic kyphosis angle was reduced by 2.6° after 6 weeks. No significant changes in other parameters were detected, and the implementation rate was 86 ±â€¯14 %. SIGNIFICANCE: In healthy adults, DI gait instruction for 10 minutes of instruction and 10 minutes of self-practice reduced the KAM. In patients with knee OA, 20 minutes of DI gait per day for 6 weeks may reduce knee pain and thoracic kyphosis.

Lack of association between angiotensin-converting enzyme genotype and muscle strength in Peruvian older people.

Aging can be associated with decreasing muscle strength, and related factors are comorbidities, sex, physical activity, and possibly genetic factors. Among genetic factors the renin-angiotensin system is of interest, but data on the Peruvian population is lacking. The objective of our study was to evaluate the association of grip strength and angiotensin convertase enzyme (ACE) polymorphism in Peruvian older people. A cross-sectional study in a convenience sample of 104 participants over 60 years in Lima, Perú, with analysis of the ACE polymorphism, was performed. We studied 104 participants, 46 men (44,2%) and 58 women (55,8%), with a mean age and standard deviation (SD) of 73,7 (7,4) years, range between 60-90 years. The frequency of D/D, I/D and I/I genotypes was 12,7; 43,7 and 43,7% respectively. The genotype distribution of ACE polymorphism agreed with the Hardy-Weinberg equilibrium (p=0,746). The mean (SD) of grip strength in the D/D, I/D and I/I polymorphisms were 24,8 (7,2); 22,8 (7,2) and 23,4 (7,6) kg respectively; no significant difference was observed (p=0,41) between genetic groups. In this small convenience sample of older Peruvians, no association was found between grip strength and ACE genotype.

Kimura's disease: effects of age on clinical presentation.

BACKGROUND: Kimura's disease (KD) is known to be dominant among young Asian men, but it can also occur in middle- and advanced-aged people. The clinical characteristics of KD, especially by age, are not well known. AIM: This study was performed to investigate the effects of age on the clinical characteristics of KD. DESIGN: We conducted a case series study. METHODS: All case studies of patients diagnosed with KD were collected via a PubMed search of studies published until August 2018. The data were analyzed by age group. RESULTS: In total, 215 studies were reviewed (238 patients; mean age of 36 years). The male:female ratio was 4:1 overall, 17:1 in patients aged <20 years, 4:1 in patients aged 20-39 years and 2:1 in patients aged ≥40 years (P = 0.01). The percentage of patients with pruritus was 15.4% overall, 3.8% in patients aged <20 years, 15.5% in patients aged 20-39 years and 21.7% in patients aged ≥40 years (P = 0.02). The time to diagnosis was 5.3 years overall, 3.2 years in patients aged <20 years, 4.7 years in patients aged 20-39 years and 7.1 years in patients aged ≥40 years (P < 0.01). CONCLUSIONS: The proportion of female patients affected the incidence of pruritus, and the time to diagnosis increased as the patients' age increased. There were no significant age-related differences in region/race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, immunoglobulin E level, initial treatment, recurrence or outcomes. This may be useful information for the diagnosis of KD.

Cr2Te3 Thin Films for Integration in Magnetic Topological Insulator Heterostructures.

Chromium telluride compounds are promising ferromagnets for proximity coupling to magnetic topological insulators (MTIs) of the Cr-doped (Bi,Sb)2(Se,Te)3 class of materials as they share the same elements, thus simplifying thin film growth, as well as due to their compatible crystal structure. Recently, it has been demonstrated that high quality (001)-oriented Cr2Te3 thin films with perpendicular magnetic anisotropy can be grown on c-plane sapphire substrate. Here, we present a magnetic and soft x-ray absorption spectroscopy study of the chemical and magnetic properties of Cr2Te3 thin films. X-ray magnetic circular dichroism (XMCD) measured at the Cr L2,3 edges gives information about the local electronic and magnetic structure of the Cr ions. We further demonstrate the overgrowth of Cr2Te3 (001) thin films by high-quality Cr-doped Sb2Te3 films. The magnetic properties of the layers have been characterized and our results provide a starting point for refining the physical models of the complex magnetic ordering in Cr2Te3 thin films, and their integration into advanced MTI heterostructures for quantum device applications.

Deep-learning-based, computer-aided classifier developed with a small dataset of clinical images surpasses board-certified dermatologists in skin tumour diagnosis.

BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant or benign classification by the board-certified dermatologists was statistically higher than that of the dermatology trainees (85·3% ± 3·7% and 74·4% ± 6·8%, P < 0·01), the DCNN achieved even greater accuracy, as high as 92·4% ± 2·1% (P < 0·001). CONCLUSIONS: We have developed an efficient skin tumour classifier using a DCNN trained on a relatively small dataset. The DCNN classified images of skin tumours more accurately than board-certified dermatologists. Collectively, the current system may have capabilities for screening purposes in general medical practice, particularly because it requires only a single clinical image for classification.

Comparison of hemodynamic parameters that can predict an aneurysmal rupture: 20 patient-specific models experiment.

Hemodynamic analysis of cerebral aneurysms is widely performed to understand the mechanism of aneurysmal rupture. Computational fluid dynamics (CFD) studies have suggested that several hemodynamic parameters are associated with such ruptures. However, a number of factors remain to be addressed to correlate these parameters with aneurysmal ruptures, especially under analytical conditions. Specifically, CFD analysis is often performed with rigid wall models due to computational cost limitations. Here, to evaluate the effects of the deformation of the aneurysmal wall, experimental flow measurement with elastic models under pulsating conditions was conducted using three-dimensional particle image velocimetry (3D PIV). By analyzing 20 patient-specific, elastic, silicone aneurysm models, the hemodynamic parameters of ruptured and unruptured aneurysms were statistically compared to identify the variables that can effectively predict an aneurysmal rupture. Our analyses yielded three parameters (average wall shear stress ratio, in-phase deviation ratio, and pressure difference) which could effectively predict an aneurysmal rupture. These results suggested that measurement of wall shear stress (WSS) at both the aneurysm dome and parent artery is important and that pressure difference can also be a potential indicator of aneurysmal rupture.

Co-expression of POU4F2/Brn-3b with p53 may be important for controlling expression of pro-apoptotic genes in cardiomyocytes following ischaemic/hypoxic insults.

Cardiomyocyte death following ischaemic/hypoxic injury causes irreversible damage to cardiac function and contributes to chronic diseases such as heart failure. Understanding the mechanisms associated with myocyte loss under these conditions can help to identify strategies to minimise/abrogate such detrimental effects. The p53 protein can induce apoptosis or cell cycle arrest, but effects on cell fate depend on interactions with other regulators such as POU4F2/Brn-3b (Brn-3b), which co-operates with p53 to increase the expression of pro-apoptotic genes. In contrast, the related POU4F1/Brn-3a (Brn-3a) blocks p53-mediated apoptosis but co-operates with p53 to enhance cell cycle arrest. In this study, we showed that permanent coronary artery ligation in mouse hearts, which induced apoptotic markers, activated caspase-3 and -8 and necroptosis markers; RIP-1 and -3 also increased Brn-3b and Brn-3a expression. However, Brn-3a was only detected in uninjured myocardium but not at the site of injury, whereas Brn-3b showed generalised increase, including within the infarct zone. Conversely, p53 was detected in the infarct zone and in some cells adjacent to the site of injury but not in uninjured myocardium. Co-localisation studies showed Brn-3a co-expression with p53 in cardiomyocytes adjacent to the infarct zone, whereas Brn-3b was co-localised with p53 in the infarct zone only. Increased Brn-3b and p53 correlated with elevated expression of pro-apoptotic target genes, Bax, Noxa and PUMA, whereas cleaved caspase-3 confirmed the presence of apoptotic cells within this region of the injured heart. Similarly, simulated ischaemia/reoxygenation (sI/R) injury in neonatal rat ventricular cardiomyocytes (NRVM) and heart derived H9c2 myoblasts increased Brn-3b, p53 as well as apoptotic genes, and this was associated with enhanced apoptosis. Furthermore, targeted reduction of Brn-3b using shRNA caused reduction in pro-apoptotic Bax and Noxa proteins, even though p53 expression remained intact, suggesting that Brn-3b is important for controlling the fate of the myocardium in the injured heart.

A New Grip Strength Measuring Device for Detailed Evaluation of Muscle Contraction among the Elderly.

BACKGROUND: We developed a new grip strength measuring device, which considers the time axis, for evaluating muscle contraction in detail in elderly people. OBJECTIVES: To present the novel device and preliminary results concerning agility in gripping. DESIGN: Cross-sectional analysis. PARTICIPANTS: One hundred and twenty-one older persons (48 men and 73 women, mean age 74.4 years) referring for memory disorders to the outpatient clinic of our institute. MEASUREMENTS: A novel device taking advantage of an industrial force-gauge was developed for measuring gripping performance. The instrument graphically described participants' strength production. Nine indices were derived from four points identified by the graph: 1) starting point ("Go signal"), 2) time when gripping starts, 3) turning point (TP) when the inclination of the curve depicting strength production changes, and 4) peak of strength production. Results obtained from the study sample of older persons were compared (as ratios) to a control group of 30 healthy young adults in their thirties in order to calculate age-related decline rates. Differences between right and left side were compared. RESULTS: A significant difference was observed between right and left hands concerning the time to reach peak of strength, and time from TP to strength peak in both men and women. For women, the following indices were also significantly different: time to reach TP, strength at TP, time from TP to strength peak, curve inclination from TP to strength peak, and ratio of TP strength divided by peak strength. CONCLUSION: Declines in several indices of gripping agility were measured. The parameters which were more closely related to time than strength itself showed significant differences between right and left hands, especially in women.

Prothymosin-alpha plays a defensive role in retinal ischemia through necrosis and apoptosis inhibition.

Prothymosin-alpha (ProTalpha) causes a switch in cell death mode from necrosis to neurotrophin-reversible apoptosis in primary cultured cortical neurons. In the present study, post-ischemic administration (3 or 24 h, intravenously) of recombinant mouse ProTalpha without neurotrophins completely prevented ischemia-induced retinal damage accompanying necrosis and apoptosis, as well as dysfunction assessed by electroretinogram. Treatments with anti-erythropoietin (EPO) or brain-derived neurotrophic factor (BDNF) immunoglobulin G (IgG) reversed ProTalpha-induced inhibition of apoptosis. ProTalpha upregulated retinal EPO and BDNF levels in the presence of ischemia. Moreover, intravitreous administration of anti-ProTalpha IgG or an antisense oligodeoxynucleotide for ProTalpha accelerated ischemia-induced retinal damage. We also observed that ischemia treatment caused a depletion of ProTalpha from retinal cells. Altogether, these results suggest that the systemic administration of ProTalpha switches ischemia-induced necrosis to apoptosis, which in turn is inhibited by neurotrophic factors upregulated by ProTalpha and ischemia. ProTalpha released upon ischemic stress was found to have a defensive role in retinal ischemia.

Estudio fitoquímico y farmacológico de 4 Plantas con efecto hipoglicemiante / Phytochemical and pharmacological studies in four plants with hypoglycemic effect

Se realizó el estudio de la acción hipoglicemiante de Ocimum sanctus (Albahaca morada), Notholaena nivea (Cuti-Cuti), Geranuim lechleri (Pasuchaca) y Smallantus sonchifolius (Yacón), frente a la hiperglicemia aloxánica, tanto de los extractos atomizados, como del pool de alcaloides, de cada una de las plantas. Igualmente, se determinó la DL50 del extracto atomizado y de los alcaloides de las cuatro plantas evaluadas. La toxicidad aguda se determinó en ratones albinos, cepa nihs, cuyos pesos oscilaron entre 25 y 30 g. La acción hipoglicemiante, fue evaluada en ratas albinas cepa holtzman, de 200 a 250 g de peso. Tanto los extractos atomizados, como los alcaloides de Cuti-Cuti, Pasuchaca y hojas de Yacón, mostraron un excelente efecto hipoglicemiante, frente a la hiperglicemia inducida por aloxano. Las tres plantas poseen escasa toxicidad aguda, y según los criterios de Williams podrían considerarse como plantas prácticamente atóxicas. Sin embargo, solamente el pool de alcaloides de Albahaca a la dosis de 250 mg/ kg de peso, mostró una escasa acción hipoglicemiante, no mostrando eficacia la dosis de 500mg/kg, del pool de alcaloides, ni el atomizado de la planta, a la dosis de 1000 mg/kg de peso.

The study of the hypoglicemic action of Ocimum sanctum (Albahaca morada), Notholaena nivea (Cuti-Cuti), Geranuim lechleri (Pasuchaca) and Smallantus sonchifolius (Yacón), was performed on alloxan-induced hyperglicemic rats. In addition, atomized extracts and the pool of alkaloids, of the different plants were studied. To evaluate acute toxicity, DL50 of the atomized extract and of the alkaloids on the four plants were determined using albino mice, whose weights oscillated between 25 and 30 g. The hypoglycemic action, was evaluated in Holtzman albino rats, of 200 to 250 g of weight. The atomized extracts, as well as the alkaloids of Cuti-Cuti, Pasuchaca and leaves of Yacón, showed an excellent hypoglicemic effect in the hyperglicemic alloxaninduced rats. These three plants have little acute toxicity and according to the Williams` criteria they could be considered as practically non toxic. On the other hand only the pool of alkaloids of Albahaca, at the dose of 250 mg/kg showed little hypoglicemic action. No hypoglicemic effect was observed with the albahaca alkaloids at the dose of 500mg/kg nor with the atomized extract of the plant at the dose of 1000 mg/kg.

Mannose-binding lectin and its genetic variants.

Mannose-binding lectin (MBL) is a collagen-like serum protein that mediates activation of the complement system and is of importance for host defence. Common variant alleles situated both in the promoter and structural region of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variation in MBL serum concentration influences the susceptibility to and the course of different types of infections, autoimmune, metabolic and cardiovascular diseases, but this is still a subject of debate. The fact that these genetic variations are very frequent indicates a dual role for MBL in host defence. In this survey, we summarize the current molecular understanding of human MBL genetics.

Protein kinase C-mediated cell death mode switch induced by high glucose.

Cortical neurons rapidly die in necrosis due to poor glucose uptake in the low-density (LD) culture under serum-free condition without any supplements. The scanning and transmission electron microscopical analyses characterized the necrosis by membrane disruption, mitochondrial swelling and loss of cytoplasmic electron density. High-glucose treatment delayed the neuronal death by suppressing necrosis, but induced apoptosis through increase in Bax levels, cytochrome c release, caspase-3 activation and DNA ladder formation. Although pyruvate as well as high glucose inhibited necrotic cell death and rapid decrease in cellular ATP levels, possibly related to decreased [(3)H]-2-deoxy glucose uptake under the serum-free condition, it did not induce apoptosis. Protein kinase C inhibitors blocked these changes related to the cell death mode switch. Several neurotrophic factors did not affect the necrosis, but potentiated high-glucose-induced survival activity, while inhibiting cytochrome c release. All these results suggest that high-glucose treatment causes neuronal cell death mode switch by inhibiting necrosis, while inducing apoptosis, which is prevented by neurotrophic factors.

Protein kinase C-mediated necrosis-apoptosis switch of cortical neurons by conditioned medium factors secreted under the serum-free stress.

Cortical neurons die in necrosis in the low-density (LD) culture, and in apoptosis in the high-density (HD) culture under the serum-free condition without any supplements. The neuronal death in LD culture was delayed by conditioned medium (CM) factors prepared from the HD culture. The CM switched the cell death mode from necrosis to apoptosis, characterized by various cell death markers and transmission electron microscopy. The CM inhibited the rapid decrease in cellular ATP levels and [3H]-2-deoxy glucose ([3H]-2-DG) uptake in the LD culture. Inhibitors of phospholipase C and protein kinase C effectively abolished the CM-induced elevation of survival activity, [3H]-2-DG uptake and ATP levels, and necrosis-apoptosis switch. All these results suggest that CM caused the cell death mode switch from necrosis to apoptosis through phospholipase C- and protein kinase C-mediated mechanisms.

Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide.

We studied the effect of oxatomide, an antiallergic drug, on the resistance of K562 cells to doxorubicin. Oxatomide synergistically potentiated the cytotoxicity of doxorubicin in doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 1-10 microM, but had hardly any synergistic effect on the parental cell line (K562) at the same concentration. Oxatomide inhibit P-glycoprotein pump-efflux activity and the binding of [3H]-azidopine to the cell-surface protein P-glycoprotein, in a dose-related manner. These results indicate that oxatomide reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.

ATP suppresses the K(+) current responses to FSH and adenosine in the follicular cells of Xenopus oocyte.

The application of either follicle-stimulating hormone (FSH) or adenosine (Ade) induces a K(+)-current response in the follicular cells surrounding a Xenopus oocyte under a voltage clamp. These K(+)-current responses are reported to be produced by an increase in intracellular cAMP. A previous application of ATP to the same cells markedly depressed the K(+)-current responses to FSH and Ade. Furthermore, a 2 min application of phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), significantly depressed the K(+)-current responses to FSH and Ade, but it had no significant effect on the Cl(-)-current response to ATP. An application of either ATP or PDBu also depressed the K(+)-current response induced by intracellularly applied cAMP. In contrast to the effect of PDBu, the application of 1-octanol, an inhibitor of gap junction channel, significantly depressed both the Ade- and ATP-induced responses, indicating that the acting site of 1-octanol is different from that of PKC. The results suggest that the depressing effect of ATP on the FSH- and Ade-induced K(+)-current responses might be mediated by PKC activation and that the site of PKC action might be downstream of the cAMP production involved in the K(+) channel opening.