Breaking up prolonged sitting reduces resting blood pressure in overweight/obese adults.

AIM: To compare the effect of 7 h of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity. METHODS AND RESULTS: Overweight/obese adults (n = 19; aged 45-65 years) were recruited for a randomized three-treatment crossover trial with a one-week washout between treatments: 1) uninterrupted sitting; 2) sitting with 2 min bouts of light-intensity walking at 3.2 km/h every 20 min; and, 3) sitting with 2 min bouts of moderate-intensity walking at between 5.8 and 6.4 km/h every 20 min. After an initial 2 h period seated, participants consumed a test meal (75 g carbohydrate, 50 g fat) and completed each condition over the next 5 h. Resting blood pressure was assessed oscillometrically every hour as a single measurement, 5 min prior to each activity bout. GEE models were adjusted for sex, age, BMI, fasting blood pressure and treatment order. After adjustment for potential confounding variables, breaking up prolonged sitting with light and moderate-intensity activity breaks was associated with lower systolic blood pressure [light: 120 ± 1 mmHg (estimated marginal mean ± SEM), P = 0.002; moderate: 121 ± 1 mmHg, P = 0.02], compared to uninterrupted sitting (123 ± 1 mmHg). Diastolic blood pressure was also significantly lower during both of the activity conditions (light: 76 ± 1 mmHg, P = 0.006; moderate: 77 ± 1 mmHg, P = 0.03) compared to uninterrupted sitting (79 ± 1 mmHg). No significant between-condition differences were observed in mean arterial pressure or heart rate. CONCLUSION: Regularly breaking up prolonged sitting may reduce systolic and diastolic blood pressure. TRIAL REGISTRATION NUMBER: ACTRN12609000656235 (http://www.anzctr.org.au) TRIAL REGISTRATION DATE: August 4th 2009.

Comparison of the diagnostic yield of transbronchial lung biopsies by forceps and cryoprobe in diffuse parenchymal lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) in the diagnosis of diffuse parenchymal lung disease (DPLD) has shown a promising yield in recent times, with low post-procedural mortality and morbidity. Objectives: To compare the yield of TBLC and conventional transbronchial forceps lung biopsy (TBLB). Methods: A prospective study was carried out in patients with DPLD over a period of 1 year in a tertiary respiratory care institute in New Delhi, India. All 87 patients enrolled underwent both TBLB and TBLC. The procedures were performed in the bronchoscopy suite under conscious sedation and local anaesthesia, with an attempt to take a minimum of three biopsy specimens by conventional TBLB followed by TBLC. A 1.9 mm cryoprobe with a freezing time of 4 - 5 seconds was used. An Arndt endobronchial blocker was used to control bleeding along with locally administered medications. Results: TBLB and TBLC led to a definitive diagnosis in 27 (31.0%) and 69 (79.3%) cases, respectively. The commonest diagnoses were hypersensitivity pneumonitis, sarcoidosis and pulmonary tuberculosis. TBLC led to additional diagnoses in 42 cases (48.3%). Pneumothorax was observed in 12 cases (13.8%), and moderate bleeding occurred in 63 (72.4%). There were no procedure-related deaths. Conclusion: TBLC had a better diagnostic yield than conventional TBLB in DPLD. It has the potential to become a safe day-care procedure in a resource-limited setting, if certain precautions are taken. Study synopsis: What the study adds. Compared with transbronchial forceps lung biopsy, transbronchial lung cryobiopsy (TBLC) led to additional diagnoses in 42 (48.3%) of 87 patients with clinicoradiological features of diffuse parenchymal lung disease. Pneumothorax was observed in 12 cases (13.8%) and moderate bleeding in 63 (72.4%). TBLC without rigid bronchoscopy or advanced airway devices under conscious sedation had a good diagnostic yield with an acceptable adverse events profile.Implications of the findings. TBLC under conscious sedation is not resource intensive and can be carried out in settings with limited resources.

Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room.

BACKGROUND AND OBJECTIVES: Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. METHODS: This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). RESULTS: Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. CONCLUSIONS: The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation.

High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer.

The gene for E3 ubiquitin ligase WWP1 is located at 8q21, a region frequently amplified in human cancers, including prostate cancer. Recent studies have shown that WWP1 negatively regulates the TGFbeta tumor suppressor pathway by inactivating its molecular components, including Smad2, Smad4 and TbetaR1. These findings suggest an oncogenic role of WWP1 in carcinogenesis, but direct supporting evidence has been lacking. In this study, we examined WWP1 for gene dosage, mRNA expression, mutation and functions in a number of human prostate cancer samples. We found that the WWP1 gene had copy number gain in 15 of 34 (44%) xenografts and cell lines from prostate cancer and 15 of 49 (31%) clinical prostate cancer samples. Consistently, WWP1 was overexpressed in 60% of xenografts and cell lines from prostate cancer. Mutation of WWP1 occurred infrequently in prostate cancer. Functionally, WWP1 overexpression promoted colony formation in the 22Rv1 prostate cancer cell line. In PC-3 prostate cancer cells, WWP1 knockdown significantly suppressed cell proliferation and enhanced TGFbeta-mediated growth inhibition. These findings suggest that WWP1 is an oncogene that undergoes genomic amplification at 8q21 in human prostate cancer, and WWP1 overexpression is a common mechanism involved in the inactivation of TGFbeta function in human cancer.

EMG artifact in brain death electroencephalogram, is it a cry of "medullary death"?

The Uniform Determination of Death Act (UDDA) defines death as irreversible cessation of the functions of the entire brain including the brainstem. Many individuals meeting the clinical criteria of brain death can be documented to have some residual sub-cortical and brainstem function on careful testing. Determination of brain death still remains a persistently unresolved issue in health law and bioethics. The determination of brain death is clinical and involves testing for the integrity of brainstem functions. Documentation of irreversible cessation of brainstem functions when the cause of coma is established is usually sufficient to make a diagnosis of brain death. Confirmatory tests like four-vessel angiogram and electroencephalogram (EEG) are required in cases where the clinical testing is inconclusive or unreliable. EEG criteria for electrocerebral silence (ECS) is absence of any detectable cortical activity above 2 microV in a study performed as per the guidelines developed by the American Electroencephalographic Society. EEG studies carried out for ECS are at times contaminated by electromyographic (EMG) artifacts reflecting scalp motor unit activity. A secure EEG diagnosis of ECS cannot be made in such cases. What exactly is the relevance of scalp EMG activity in these clinically brain dead patients? What is the mechanism of generation of this spontaneous scalp EMG activity and how can the diagnosis of brain death be secured in these patients? These issues are explored in this article by highlighting a case.

Ipsilateral hemispheric ischaemic hypoxic changes during central line placement: a video-electroencephalogram correlate.

When venous access is needed for intravenous fluids or antibiotics and a peripheral site is unavailable or not suitable, a central line is placed either in the neck or the groin. Complications have been reported during central line placement including (but not limited to) pneumothorax, haemothorax, arrhythmias, air embolism and introduction of infection. The case history is reported of a patient who developed ipsilateral hemispheric ischaemic hypoxic changes during central line placement. This was represented on the surface electroencephalogram by ipsilateral hemispheric voltage attenuation.

Physiological responses to divergent selection for phytate phosphorus bioavailability in a randombred chicken population.

An investigation was conducted to study insulin-like growth factor (IGF)-I, IGF-II, insulin, glucagon, leptin, triiodothyronine (T(3)), and thyroxine (T(4)) levels in a chicken population divergently selected for P bioavailability (PBA). There were differences in growth and feed efficiency between the 2 lines. Concentrations of IGF-I, IGF-II, and T(3) were significantly greater in the high PBA line compared with the low PBA line, whereas the reverse was true for glucagon. There were no correlations between IGF-I and II and PBA in either line, suggesting that the line differences may be the result of factors other than PBA. Glucagon and IGF-I have different relationships with feed conversion ratio in the high PBA line compared with the low PBA line. There was a significant correlation between PBA and T(3) in the low line and between PBA and T(4) in the high PBA line. Thyroid hormone levels may be an indirect indicator of PBA in growing chickens. The genes in the thyroid hormone pathway may be key in the identification of genes associated with PBA.

Bi-directional high speed domain wall motion in perpendicular magnetic anisotropy Co/Pt double stack structures.

We report bi-directional domain wall (DW) motion along and against current flow direction in Co/Pt double stack wires with Ta capping. The bi-directionality is achieved by application of hard-axis magnetic field favoring and opposing the Dzyloshinskii-Moriya interaction (DMI), respectively. The speed obtained is enhanced when the hard-axis field favors the DMI and is along the current flow direction. Co/Pt double stack is a modification proposed for the high spin-orbit torque strength Pt/Co/Ta stack, to improve its thermal stability and perpendicular magnetic anisotropy (PMA). The velocity obtained reduces with increase in Pt spacer thickness due to reduction in DMI and enhances on increasing the Ta capping thickness due to higher SOT strength. The velocity obtained is as high as 530 m/s at a reasonable current density of 1 × 1012 A/m2 for device applications. The low anisotropy of the device coupled with the application of hard-axis field aids the velocity enhancement by preventing Walker breakdown.

Role of RKKY torque on domain wall motion in synthetic antiferromagnetic nanowires with opposite spin Hall angles.

We experimentally show the effect of enhanced spin-orbit and RKKY induced torques on the current-induced motion of a pair of domain walls (DWs), which are coupled antiferromagnetically in synthetic antiferromagnetic (SAF) nanowires. The torque from the spin Hall effect (SHE) rotates the Néel DWs pair into the transverse direction, which is due to the fact that heavy metals of opposite spin Hall angles are deposited at the top and the bottom ferromagnetic interfaces. The rotation of both DWs in non-collinear fashion largely perturbs the antiferromagnetic coupling, which in turn stimulates an enhanced interlayer RKKY exchange torque that improved the DW velocity. The interplay between the SHE-induced torque and the RKKY exchange torque is validated via micromagnetic simulations. In addition, the DW velocity can be further improved by increasing the RKKY exchange strength.

Multiple pterygium syndrome: Challenge for anesthesiologist.

Multiple pterygium syndrome (MPS) is a very rare autosomal recessive disorder characterized by flexion of joint and digit contractures, skin webbing, cleft palate, deformity of the spine, and cervical spine fusion. Difficult airway is associated mainly due to micrognathia, retrognathia, webbing of the neck, and limitation of the mouth opening and neck extension. We are reporting a case of a 5-year-old female diagnosed with MPS and exhibiting a bilateral club foot and congenital vertical talus. The patient was posted for manipulation and above the knee casting under general anesthesia.

Inadvertent intrathecal injection of labetalol.

Labetalol is a combined α and ß adrenergic receptor blocker. It is used to treat hypertension, especially in pregnant patients. We report a case of a female patient who was given labetalol intrathecally in place of bupivacaine due to a similar appearance of ampoules which resulted in a drop in blood pressure and pulse rate. The patient responded to fluid resuscitation and there occurred no neurological sequelae.

Reconfigurable logic via gate controlled domain wall trajectory in magnetic network structure.

An all-magnetic logic scheme has the advantages of being non-volatile and energy efficient over the conventional transistor based logic devices. In this work, we present a reconfigurable magnetic logic device which is capable of performing all basic logic operations in a single device. The device exploits the deterministic trajectory of domain wall (DW) in ferromagnetic asymmetric branch structure for obtaining different output combinations. The programmability of the device is achieved by using a current-controlled magnetic gate, which generates a local Oersted field. The field generated at the magnetic gate influences the trajectory of the DW within the structure by exploiting its inherent transverse charge distribution. DW transformation from vortex to transverse configuration close to the output branch plays a pivotal role in governing the DW chirality and hence the output. By simply switching the current direction through the magnetic gate, two universal logic gate functionalities can be obtained in this device. Using magnetic force microscopy imaging and magnetoresistance measurements, all basic logic functionalities are demonstrated.

Direct observation of deterministic domain wall trajectory in magnetic network structures.

Controlling the domain wall (DW) trajectory in magnetic network structures is crucial for spin-based device related applications. The understanding of DW dynamics in network structures is also important for study of fundamental properties like observation of magnetic monopoles at room temperature in artificial spin ice lattice. The trajectory of DW in magnetic network structures has been shown to be chirality dependent. However, the DW chirality periodically oscillates as it propagates a distance longer than its fidelity length due to Walker breakdown phenomenon. This leads to a stochastic behavior in the DW propagation through the network structure. In this study, we show that the DW trajectory can be deterministically controlled in the magnetic network structures irrespective of its chirality by introducing a potential barrier. The DW propagation in the network structure is governed by the geometrically induced potential barrier and pinning strength against the propagation. This technique can be extended for controlling the trajectory of magnetic charge carriers in an artificial spin ice lattice.

Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure.

Zolpidem is a non-benzodiazepine hypnotic drug, acts selectively through omega 1 receptors of GABAA. It is thought to be safer than benzodiazepines but we report a case of zolpidem drug abuse, dependence and withdrawal seizure.

The growth of four human and animal enteroviruses in the central nervous systems of mice.

The pattern of CNS infection of our enteroviruses, Coxsackievirus A14, encephalomyocarditis (EMC) virus, GDVII virus, and Vilyuisk virus, was investigated. The regional sites of virus replication were correlated with pathological changes. These viruses were found to replicate and produce similar lesions in selected sites in the mouse CNS during acute infection. Virus antigen and histological lesions were essentially confined to the gray matter, with additional but less direct support for this being provided by virus assay of CNS regions. Virus antigen only could be confidently identified in neurons, and, histologically, neurons were observed in various stages of degeneration. The distribution of the involvement varied in the different infections. For example, EMC virus infection primarily affected the cerebral hemispheres and thalamus, while Coxsackievirus a14 infection predominantly involved the brainstem and spinal cord. GDVII and Vilyuisk virus infections more uniformly involved the entire neuraxis. There was no evidence of virus replication in the olfactory bulbs, leptomeninges, ependyma, choroid plexus, and vascular endothelium. The cerebellum was generally spared, with the cerebellar hemispheres affected only in Coxsackievirus A14 infection. It therefore appears that enteroviruses selectively infect different populations of nerve cells.

Theiler's virus antigen detected in mouse spinal cord 2 1/2 years after infection.

Spinal cord sections from mice injected with Theiler's murine encephalomyelitis virus (TMEV) and surviving for 1 year and longer after infection were stained for virus antigen by two immunohistochemical techniques. Virus antigen was detected from 1 to 2 1/2 years after infection, a time when no virus was recovered at an assay sensitivity of 50 plaque-forming units per gram of tissue. The implication this has regarding the detection of a virus in MS is discussed.

A new familial syndrome characterized by pigmentary retinopathy, hypogonadism, mental retardation, nerve deafness and glucose intolerance.

Three siblings with retinitis pigmentosa, deafness and mental retardation were studied. Physical abnormalities included nystagmus, acanthosis nigricans and multiple keloids. The two male siblings had gynecomastia, small testes and mild subvirilization whereas the only indication of hypogonadism in the female sibling was oligomenorrhea. Testosterone levels in the males, which were in the low to low normal range, were increased by the administration of large doses of chorionic gonadotropin. The two affected males had elevated plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels which were decreased by the administration of testosterone and increased by the administration of clomiphene. One sibling had mild obesity and diabetes mellitus, one had moderate obesity, normal glucose tolerance and hyperinsulinism and the third had abnormal glucose tolerance and hyperinsulinism. This familial syndrome is distinct from either the Laurence-Moon, Bardet-Biedl or Alström disorders and provides further evidence of genetic heterogeneity in this group of autosomal recessive traits.