Clinical and neurophysiological findings in patients with hereditary neuropathy with liability to pressure palsy and chromosome 17p11.2 deletion.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. METHODS: We retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. RESULTS: In addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). CONCLUSION: Our results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.

Stationary EEG pattern relates to large-scale resting state networks - An EEG-fMRI study connecting brain networks across time-scales.

Relating brain dynamics acting on time scales that differ by at least an order of magnitude is a fundamental issue in brain research. The same is true for the observation of stable dynamical structures in otherwise highly non-stationary signals. The present study addresses both problems by the analysis of simultaneous resting state EEG-fMRI recordings of 53 patients with epilepsy. Confirming previous findings, we observe a generic and temporally stable average correlation pattern in EEG recordings. We design a predictor for the General Linear Model describing fluctuations around the stationary EEG correlation pattern and detect resting state networks in fMRI data. The acquired statistical maps are contrasted to several surrogate tests and compared with maps derived by spatial Independent Component Analysis of the fMRI data. By means of the proposed EEG-predictor we observe core nodes of known fMRI resting state networks with high specificity in the default mode, the executive control and the salience network. Our results suggest that both, the stationary EEG pattern as well as resting state fMRI networks are different expressions of the same brain activity. This activity is interpreted as the dynamics on (or close to) a stable attractor in phase space that is necessary to maintain the brain in an efficient operational mode. We discuss that this interpretation is congruent with the theoretical framework of complex systems as well as with the brain's energy balance.

Frequencies and patterns of microbiology test requests from primary care in Oxfordshire, UK, 2008-2018: a retrospective cohort study of electronic health records to inform point-of-care testing.

OBJECTIVES: To inform point-of-care test (POCT) development, we quantified the primary care demand for laboratory microbiology tests by describing their frequencies overall, frequencies of positives, most common organisms identified, temporal trends in testing and patterns of cotesting on the same and subsequent dates. DESIGN: Retrospective cohort study. SETTING: Primary care practices in Oxfordshire. PARTICIPANTS: 393 905 patients (65% female; 49% aged 18-49). PRIMARY AND SECONDARY OUTCOME MEASURES: The frequencies of all microbiology tests requested between 2008 and 2018 were quantified. Patterns of cotesting were investigated with heat maps. All analyses were done overall, by sex and age categories. RESULTS: 1 596 752 microbiology tests were requested. Urine culture±microscopy was the most common of all tests (n=673 612, 42%), was mainly requested without other tests and was the most common test requested in follow-up within 7 and 14 days. Of all urine cultures, 180 047 (27%) were positive and 172 651 (26%) showed mixed growth, and Escherichia coli was the most prevalent organism (132 277, 73% of positive urine cultures). Antenatal urine cultures and blood tests in pregnancy (hepatitis B, HIV and syphilis) formed a common test combination, consistent with their use in antenatal screening. CONCLUSIONS: The greatest burden of microbiology testing in primary care is attributable to urine culture ± microscopy; genital and routine antenatal urine and blood testing are also significant contributors. Further research should focus on the feasibility and impact of POCTs for these specimen types.

First report of porcine respirovirus 1 in South America.

Porcine respirovirus 1 (PRV1) is an emerging virus in pigs that has been previously described in the USA and China. There are no reports of its presence in the rest of the world. The objective of this study was to determine the occurrence of PRV1 in Chile and to determine its phylogeny. Thus, we collected samples (oral fluids, nasal swabs, and lungs) from a swine influenza A virus (IAV) surveillance program, most of which belonged to pigs with respiratory disease. The samples were analyzed by RT-PCR, and the viral sequencing was obtained using RNA whole-genome sequencing approach. Maximum likelihood phylogeny was constructed with the available references. Thirty-one of 164 samples (18.9 %) were RT-PCR positive for PRV1: 62.5 % oral fluids, 19.0 % nasal swabs, and 8.6 % lungs. All 6 farms in this study had at least one positive sample, with 6-40 % of positive results per farm, which suggests that PRV1 is disseminated in Chilean swine farms. Twenty-one of 31 (677%) PRV1-positive samples were also positive for IAV, so the role of PRV1 as secondary pathogen in respiratory disease needs to be further evaluated. Near to complete genome of two PRV1s were obtained from two farms. The phylogenies, in general, showed low bootstrap support, except the concatenated genome and the L gene trees which showed clustering of the Chilean PRV1 with Asian sequences, suggesting a close genetic relationship. This is the first report of PRV1 in the Southern Hemisphere. Further studies are necessary to determine the genetic diversity of this virus in Chile.

The Influence of EEG References on the Analysis of Spatio-Temporal Interrelation Patterns.

The characterization of the functional network of the brain dynamics has become a prominent tool to illuminate novel aspects of brain functioning. Due to its excellent time resolution, such research is oftentimes based on electroencephalographic recordings (EEG). However, a particular EEG-reference might cause crucial distortions of the spatiotemporal interrelation pattern and may induce spurious correlations as well as diminish genuine interrelations originally present in the dataset. Here we investigate in which manner correlation patterns are affected by a chosen EEG reference. To this end we evaluate the influence of 7 popular reference schemes on artificial recordings derived from well controlled numerical test frameworks. In this respect we are not only interested in the deformation of spatial interrelations, but we test additionally in which way the time evolution of the functional network, estimated via some bi-variate interrelation measures, gets distorted. It turns out that the median reference as well as the global average show the best performance in most situations considered in the present study. However, if a collective brain dynamics is present, where most of the signals get correlated, these schemes may also cause crucial deformations of the functional network, such that the parallel use of different reference schemes seems advisable.

Inpatient hospital fatality related to coding (ICD-9-CM) of the influenza diagnosis in Spain (2009-2015).

BACKGROUND: To analyze hospitalization episodes with an ICD-9 diagnosis code of influenza (codes 487 and 488) in any diagnostic position from 2009 to 2015 in the Spanish hospital surveillance system. METHODS: Information about age, length of stay in hospital, mortality, comorbidity with an influenza diagnosis code between 1 October 2009 and 30 September 2015 was obtained from the National Surveillance System for Hospital Data (Conjunto Mínimo Básico de Datos, CMBD). RESULTS: 52,884 hospital admissions were obtained. A total of 24,527 admissions corresponded to diagnoses ICD-9 code 487 (46.4%), and 28,357 (53.6%) corresponded to ICD-9 code 488. The global hospitalization rates were 8.7 and 10.6 per 100,000 people, respectively. Differences between the two diagnostic groups were found for each of the six analyzed seasons. The diagnostic ICD-9-CM 488, male gender, and high-risk patients classified by risk vaccination groups showed direct relationship with inpatient hospital death. CONCLUSIONS: Influenza diagnosis was present in a significant number of hospital admissions. The code used for diagnosis (ICD-9-CM 488), male sex, age groups and associated risk clinical conditions showed a direct relationship with inpatient hospital fatality.

Clinical and neurophysiological findings in patients with hereditary neuropathy with liability to pressure palsy and chromosome 17p11.2 deletion. / Hallazgos clínico-neurofisiológicos en neuropatías hereditarias sensibles a la presión con deleción del cromosoma 17p11.2.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. METHODS: We retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. RESULTS: In addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). CONCLUSION: Our results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.

Electrokinetics of metal cylinders.

We study theoretically the rotation induced on an uncharged metal nanocylinder immersed in an electrolyte by AC electric fields. We consider the rotation of the cylinder when subjected to a rotating electric field (electrorotation) and the orientation of the cylinder in an AC field with constant direction (electro-orientation). The cylinder rotation is due to two mechanisms: the electric field interaction with the induced dipole on the particle and the hydrodynamic stress on the particle originated by the induced-charge electro-osmotic (ICEO) flow around the particle. The cylinder rotation induced by the ICEO mechanism can be calculated by using the Lorentz reciprocal theorem, while the rotation due to the induced dipole is calculated from the cylinder polarizability. We employ 3D numerical computations using finite elements for the general case as well as analytical methods for slender cylinders. Both calculations use the thin-double-layer approximation. We compare the results for slender cylinders of both methods showing good agreement. The electro-orientation (EOr) due to dipole torque aligns the axis of slender cylinders with the applied field, but aligns the axis of short cylinders perpendicularly to the field. The EOr due to ICEO torque always aligns the axis of cylinders with the field. The rotation induced by ICEO torque tends to disappear for frequencies of the applied field much greater than the characteristic frequency for charging the double-layer capacitance of the metal-electrolyte interface.

Transmuscular quadratus lumborum versus lumbar plexus block for total hip arthroplasty: A retrospective propensity score matched cohort study.

BACKGROUND AND AIMS: Cadaveric studies have shown that injectate from transmuscular quadratus lumborum block (QLB) can spread to the lumbar plexus. Our aim was to compare analgesic efficacy of transmuscular QLB with lumbar plexus block (LPB) for patients undergoing total hip arthroplasty (THA). MATERIAL AND METHODS: Thirty patients receiving transmuscular QLB were propensity score matched with 30 patients receiving LPB for age, sex, ASA score, BMI, operative time, preoperative oxycodone, and intraoperative opioid use. The primary outcome was postoperative opioid consumption during the first 24 postoperative hours. Secondary outcomes included static pain scores at 0-12, 12-24, and 24-48 h intervals, opioid consumption at 0-12, 12-24, and 24-48 h intervals and the length of hospital stay. The incidence of severe adverse events was also compared. RESULTS: Opioid consumption (median [IQR]) in the first 24 h was similar between the transmuscular QLB and LPB patient groups-33.6 mg (22.9-48.5) versus 32.8 mg (24.8-58.3) intravenous morphine equivalents. There was no difference between groups in static pain scores or opioid consumption during any time interval up to 48 h postoperatively. Length of hospital stay (median [IQR]) was similar between the transmuscular QLB and LPB groups-55.6 h (53.7-60.3) versus 57.9 h (54.3-79.1). CONCLUSIONS: This study suggests that transmuscular QLB provides similar analgesia to LPB following THA. Prospective studies are needed to confirm this.

Characteristic Fluctuations Around Stable Attractor Dynamics Extracted from Highly Nonstationary Electroencephalographic Recordings.

Since the discovery of electrical activity of the brain, electroencephalographic (EEG) recordings constitute one of the most popular techniques of brain research. However, EEG signals are highly nonstationary and one should expect that averages of the cross-correlation coefficient, which may take positive and negative values with equal probability, (almost) vanish when estimated over long data segments. Instead, we found that the average zero-lag cross-correlation matrix estimated with a running window over the whole night of sleep EEGs, or of resting state during eyes-open and eyes-closed conditions of healthy subjects shows a characteristic correlation pattern containing pronounced nonzero values. A similar correlation structure has already been encountered in scalp EEG signals containing focal onset seizures. Therefore, we conclude that this structure is independent of the physiological state. Because of its pronounced similarity across subjects, we believe that it depicts a generic feature of the brain dynamics. Namely, we interpret this pattern as a manifestation of a dynamical ground state of the brain activity, necessary to preserve an efficient operational mode, or, expressed in terms of dynamical system theory, we interpret it as a "shadow" of the evolution on (or close to) an attractor in phase space. Nonstationary dynamical aspects of higher cerebral processes should manifest in deviations from this stable pattern. We confirm this hypothesis through a correlation analysis of EEG recordings of 10 healthy subjects during night sleep, 20 recordings of 9 epilepsy patients, and 42 recordings of 21 healthy subjects in resting state during eyes-open and eyes-closed conditions. In particular, we show that the estimation of deviations from the stationary correlation structures provides a more significant differentiation of physiological states and more homogeneous results across subjects.

Resveratrol decreases Rad51 expression and sensitizes cisplatin­resistant MCF­7 breast cancer cells.

Resveratrol (RES), a polyphenol compound with anti­proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the anti­proliferative effects of cisplatin (CIS) on MCF­7 cells, focusing on the inhibitory effects on DNA repair of double­strand breaks (DSBs). Chemoresistant MCF­7 cells (MCF­7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS­IC40) during 5 passages, with the IC50 value increasing ~3­fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF­7, T47­D, MDA­MB­231 and MCF­7R cells in the presence of RES. The relative transcript level of Nbs­1, Mre­11 and Rad­50 genes was assessed using RT­qPCR analysis. Rad51 and H2AX [pSer139] protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the anti­proliferative effects of CIS in both MCF­7 and MCF­7R cells, decreasing the IC50 values for CIS to one­tenth and one­sixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF­7 and MCF­7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damage­based therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue.

BACKGROUND: Eccrine sweat glands (ESGs) are critical for thermoregulation and are involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that the PSU and ESG are more interconnected than previously thought. OBJECTIVES: To re-evaluate the morphology of human skin adnexa with an integrated three-dimensional (3D) perspective in order to explore the possible interconnections that the PSU and the ESG may form. METHODS: A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis. RESULTS: We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, hair follicle-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be visualized intravitally. CONCLUSIONS: We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term 'adnexal skin unit'. The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration and repair and in selected skin diseases.

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

Identification of a divergent genotype of equine arteritis virus from South American donkeys.

A novel equine arteritis virus (EAV) was isolated and sequenced from feral donkeys in Chile. Phylogenetic analysis indicates that the new virus and South African asinine strains diverged at least 100 years from equine EAV strains. The results indicate that asinine strains belonged to a different EAV genotype.