Blood pressure and heart rate variability response to noninvasive ventilation in patients with exacerbations of chronic obstructive pulmonary disease.
Sympathetic activation and parasympathetic withdrawal are commonly observed during acute exacerbations of chronic obstructive pulmonary disease (COPD). We have demonstrated previously that noninvasive positive-pressure ventilation (NPPV) improves parasympathetic neural control of heart rate in patients with obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial effects in COPD as well. Therefore, we assessed the acute effects of NPPV on systemic blood pressure and indexes of heart rate variability (HRV) in 23 patients with acute exacerbations of COPD. The measurements of HRV in the frequency domain were computed by an autoregressive spectral technique. The use of NPPV resulted in significant increases of oxygen saturation (from 89.2+/-1.0 to 92.4+/-0.9 %, p<0.001) in association with reductions in systolic and diastolic blood pressures and heart rate (from 147+/-3 to 138+/-3 mm Hg, from 86+/-2 to 81+/-2 mm Hg, from 85+/-3 to 75+/-2 bpm, p<0.001 for all variables), and increases in ln-transformed high frequency band of HRV (from 6.4+/-0.5 to 7.4+/-0.6 ms(2)/Hz, p<0.01). Reductions in heart rate and increases in ln-transformed HF band persisted after NPPV withdrawal. In conclusion, these findings suggest that NPPV may cause improvements in the neural control of heart rate in patients with acute exacerbations of COPD.


Aeromedical waiver status in U.S. Naval aviators involved in Class A mishaps.
U.S. Naval aviators are subject to stringent aeromedical standards. Aeromedic waivers are considered when a naval aviator develops a medical condition that is deemed safe for flight, allowing that aviator to continue in a flying status. No Class A (serious) mishap to date has been directly attributable to an aviator's waivered condition. However, to date no study has been conducted to review the overall mishap rate among aviators who are flying with a waiver. This study evaluated the aeromedical waiver status of naval aviators involved in Class A mishaps from 1992-1999. Aviation mishaps in the U.S. Navy are investigated by trained personnel, who report their detailed findings to the U.S. Naval Safety Center (NSC). The Navy Operational Medicine Institute (NOMI) maintains a database of all aviation physicals, including the waiver status of individual aviators. A collaborative NSC/NOMI study was done to investigate the prevalence of waivers in mishap and non-mishap aviators. Records were retrieved on 234 naval aviators who were the "pilot at the controls" of Class A mishaps occurring from 1992-1999. This mishap waiver rate was compared with the baseline waiver rate for all pilots in 1994 (midpoint). Odds Ratios were calculated of having a Class A mishap if the aviator had a waiver. Analysis failed to find a statistical difference in waiver rates between mishap aviators and the general naval aviator population indicating that the U.S. Naval Aeromedical Service is providing aeromedically safe naval aviators to the fleet.


On-chip screening for prostate cancer: an EIS microfluidic platform for contemporary detection of free and total PSA.
Prostate cancer affects a large part of the western male population. The need for an early and accurate detection is thus a great challenge in common clinical practice, but the lack of specificity of the serum marker PSA (Prostate Specific Antigen) is a serious problem since its increased concentration can be related to several abnormalities. PSA, however, is found in serum in both a free and a complexed form with other proteins and the percentage amount of unbound PSA (the free-to-total PSA ratio) can be employed to distinguish prostate cancer from benign prostatic conditions, and also to predict the future risk of prostate cancer. To improve the operating characteristics of current PSA tests and to provide a clinical tool able to run label-free and sensitive analysis, we thus developed a biosensing platform based on Electrochemical Impedance Spectroscopy (EIS), which allows the contemporary detection of free and total PSA on a single biochip, enabling a quick screening for the risk of prostate cancer thanks to the presence of two different immobilized antibodies specific for the different antigens researched.


Personalized Machine Learning using Passive Sensing and Ecological Momentary Assessments for Meth Users in Hawaii: A Research Protocol.
Artificial intelligence (AI)-powered digital therapies which detect meth cravings delivered on consumer devices have the potential to reduce these disparities by providing remote and accessible care solutions to Native Hawaiians, Filipinos, and Pacific Islanders (NHFPI) communities with limited care solutions. However, NHFPI are fully understudied with respect to digital therapeutics and AI health sensing despite using technology at the same rates as other races. We seek to fulfill two research aims: (1) Understand the feasibility of continuous remote digital monitoring and ecological momentary assessments (EMAs) in NHFPI in Hawaii by curating a novel dataset of longitudinal FitBit biosignals with corresponding craving and substance use labels. (2) Develop personalized AI models which predict meth craving events in real time using wearable sensor data. We will develop personalized AI/ML (artificial intelligence/machine learning) models for meth use and craving prediction in 40 NHFPI individuals by curating a novel dataset of real-time FitBit biosensor readings and corresponding participant annotations (i.e., raw self-reported substance use data) of their meth use and cravings. In the process of collecting this dataset, we will glean insights about cultural and other human factors which can challenge the proper acquisition of precise annotations. With the resulting dataset, we will employ self-supervised learning (SSL) AI approaches, which are a new family of ML methods that allow a neural network to be trained without labels by being optimized to make predictions about the data itself. The inputs to the proposed AI models are FitBit biosensor readings and the outputs are predictions of meth use or craving. This paradigm is gaining increased attention in AI for healthcare. We expect to develop models which significantly outperform traditional supervised methods by fine-tuning to an individual subject's data. Such methods will enable AI solutions which work with the limited data available from NHFPI populations and which are inherently unbiased due to their personalized nature. Such models can support future AI-powered digital therapeutics for substance abuse.


Maturation of human auditory cortex: implications for speech perception.
This project traced the maturation of the human auditory cortex from midgestation to young adulthood, using immunostaining of axonal neurofilaments to determine the time of onset of rapid conduction. The study identified 3 developmental periods, each characterized by maturation of a different axonal system. During the perinatal period (3rd trimester to 4th postnatal month), neurofilament expression occurs only in axons of the marginal layer. These axons drive the structural and functional development of cells in the deeper cortical layers, but do not relay external stimuli. In early childhood (6 months to 5 years), maturing thalamocortical afferents to the deeper cortical layers are the first source of input to the auditory cortex from lower levels of the auditory system. During later childhood (5 to 12 years), maturation of commissural and association axons in the superficial cortical layers allows communication between different subdivisions of the auditory cortex, thus forming a basis for more complex cortical processing of auditory stimuli.


Therapeutic effects of lactosyl derivative Gu-4 in a collagen-induced arthritis rat model.
Rheumatoid arthritis (RA) is an inflammatory disorder that is characterized by persistent recurrence of joint inflammation leading to cartilage and bone destruction. The present anti-arthritis therapies failed to achieve satisfactory remission in all patients; therefore, it is still necessary to develop novel approaches to fulfill the demand in clinic. Here, we reported the therapeutic effects of lactosyl derivative Gu-4, a synthetic compound that was previously identified as a selective inhibitor against leukocyte integrin CD11b, in a bovine type II collagen induced arthritis (CIA) rat model. First, prophylactic administration of Gu-4 (1.2728 mg/kg) to rats by intraperitoneal injection every 2 days from the first day of collagen immunization significantly decreased the incidence of CIA, diminished the mean paw volume increase, and reduced the number of swollen paws. Second, administration of Gu-4 (1.2728 mg/kg) to rats at early-onset stage of CIA prevented the progression of the pathological process of RA, accelerated the remission of paw edema, and declined the arthritis score; after 5 weeks treatment, X-ray and histological examinations were carried out, the ankle joint of hind limb of Gu-4 treated CIA rats exhibited slighter bone erosion and much less inflammatory cell infiltration compared to those of saline treated animals; furthermore, Gu-4 remarkably attenuated the production of rheumatoid factor (RF) in the serum of CIA rats as determined by ELISA. Moreover, we performed in vitro lymphocyte proliferation assay and found that Gu-4 significantly inhibited the proliferation of splenic lymphocytes isolated from CIA rats in a dose-dependent manner. Our results suggest that Gu-4 can effectively ameliorate CIA and might be an alternative option for the treatment of RA.


[A retrospective study of 10 cases of post-transplant bronchiolitis obliterans].
Objective: To analyze the clinical features of bronchiolitis obliterans syndrome (BOS) in patients with allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This retrospective study included patients who underwent allogeneic HSCT from January 1998 to December 2016. The clinical features, radiological manifestations and treatment of clinically proven BOS were reviewed. Results: Of 681 patients who experienced HSCT, 10(1.47%) met the diagnostic criteria. The duration of BOS onset after transplantation was 5-48 months, averaging (18±15) months. Cough and worsening dyspnea were present in most cases, and 9 (90%) of the cases had manifestations of chronic graft versus host disease. Hyperinflation with areas of decreased attenuation and bronchiectasis were present in 7 (70%) cases and air trapping was present during the expiratory phase of imaging. The management of BOS consisted of high dose systemic corticosteroids and immunosuppressive therapy. Patients were treated with bronchodilators if they were symptomatic and during acute exacerbations of respiratory symptoms. In 5 (50%) patients the condition deteriorated and caused death, while in 3 patients the condition was improved. Two patients were lost to follow up. Conclusion: BOS is the most common late noninfectious pulmonary complication following allogeneic HSCT and has a poor prognosis.


CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease.
To date, only five drugs have been approved for the treatment of Alzheimer's disease (AD); however, these agents impact the symptoms rather than the progression of the disease. It is well established that nerve growth factor (NGF) enhances the function and survival of basal forebrain cholinergic neurons that are vulnerable in AD. However, NGF does not cross the blood-brain barrier, and intraventricular NGF injections in animals and humans were associated with significant side effects. Adeno-associated virus (AAV)-based gene delivery is a novel technology being developed for administration of NGF to the brain to treat AD symptoms and progression. Indeed, the efficacy of ex vivo gene delivery was demonstrated in patients with AD who experienced improvements in cerebral metabolism and cognition compared with pre-operative function without adverse events. CERE-110 (AAV2-NGF), under development by Ceregene Inc, is an AAV serotype 2-based vector expressing human NGF delivered to the nucleus basalis of Meynert by stereotactic injection for the treatment of AD. Animal studies have established the preclinical efficacy of CERE-110, revealing an excellent safety profile. CERE-110 has passed phase I clinical testing and a multicenter phase II clinical trial has commenced. CERE-110 is a promising candidate for the treatment of AD.


Distally based sural fasciomyocutaneous flap: anatomic study and modified technique for complicated wounds of the lower third leg and weight bearing heel.
The reconstruction of the distal third leg and weight-bearing heel, especially when complicated with infection and/or dead space, remains a challenge in reconstructive surgery. The distally based sural neurofasciomyocutaneous flap has been proved a valuable tool in repair of the soft tissue defects of those areas. In this report, we present the results of the anatomical study on vascular communication between the suprafascial sural neurovascular axis and the deep gastrocnemius muscle and a modified technique in clinical applications for reconstruction of the soft tissue defects in the distal lower leg and heel. Six lower limbs of fresh cadavers were injected with red gelatin and dissected. A constant vascular connection with average four musculo-fasciocutaneous perforators with diameter 0.2-0.5 mm was identified in the overlapping area between the suprafascial sural neurovascular axis and the deep gastrocnemius muscle. Based on these findings, a modified distally based sural neurofasciomyocutaneous flap including the distal gastrocnemius muscle component was designed and used for repairs of the soft tissue defects in the distal lower limb and plantar heel pad in six patients. The blood supplies of flaps comprised either the peroneal perforator and adipofascial pedicle or the peroneal perforator only. The average size of the fasciocutaneous flap was 51 cm(2), and the muscle component 17.7 cm(2). All flaps survived uneventfully. Our results suggest that this technical modification could provide wider range for applications of the distally based sural neurofasciomyocutaneous flap in repair of the soft tissue defects of the lower extremity and heel.


Management of toddler's fractures.
Question A 2-year-old boy presented to my office 2 days after he started limping. The history, physical examination, and radiology assessment revealed a toddler's fracture (TF). I understand that there is considerable variation in practice regarding management of TF. What is the best method to confirm the diagnosis? What method should be used to immobilize the affected limb and for how long? Is follow-up with a pediatric orthopedic surgeon needed?Answer Toddler's fracture, also called childhood accidental spiral tibial fracture or CAST fracture, is a fracture unique to ambulatory infants and young children. It is caused by a twisting injury while tripping, stumbling, or falling. Children usually present limping or refusing to walk. Tenderness at the fracture site is common but is at times hard to elicit in young children. Toddler's fracture is diagnosed clinically and frequently can be documented with radiographs. Treatment of both confirmed TF and presumed TF is conservative with immobilization. A controlled ankle motion boot or a short leg back slab are preferred because they are associated with fewer complications and can be removed by the family or the family physician. For most children, no orthopedic follow-up is needed.


[Comparative study of the immunogenicity of neurotoxin preparations and their separate fractions obtained from Shigella sonnei, phases I and II].
The immunogenicity of the preparations of phase I S. sonnei neurotoxin, determined by the keratoconjunctival test on guinea pigs, is linked mainly with the presence of a high-molecular component other than endotoxin in these preparations. The preparations of phase II S. sonnei neurotoxin do not contain the endotoxin and high-molecular antigens of S. sonnei, phase I, which protect guinea pigs from the development of experimental keratoconjunctivitis; these preparations are toxic for mice and possess low immunogenicity.


Interferon-beta treatment alters peripheral blood monocytes chemokine production in MS patients.
Chemokines direct the recruitment of leukocytes to inflammatory sites and may also participate in the regulation of cytokine production by naive T helper cells. Chemokine production by blood monocytes was investigated by intracytoplasmic staining in interferon-beta (IFN-beta)-treated multiple sclerosis (MS) patients, untreated MS patients, and healthy controls. Under unstimulated conditions, no differences in the production of interleukin-8 (IL-8), IFN-inducible protein 10 (IP-10), monokine induced by interferon-gamma (Mig), monocyte chemoattractant protein-1 (MCP-1), and monocyte chemoattractant protein-3 (MCP-3) were seen between untreated MS patients and controls. Chemokine production by monocytes following T cell activation was decreased in MS patients taking IFN-beta compared to controls and untreated MS patients. Unlike other chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha) production by monocytes was significantly decreased in untreated MS patients compared to controls, and IFN-beta treatment increased MIP-1alpha expression to the level seen in controls. In vitro addition of IFN-beta1b to peripheral blood mononuclear cells (PBMC) cultures tended to decrease the production of IL-8, IP-10, Mig, MCP-1, and MCP-3, but not of MIP-1alpha. These findings suggest that IFN-beta treatment may have a differential affect on chemokine production by monocytes. Longitudinal studies must be done to confirm these observations.


Issues in patient-focused care for the respiratory care practitioner.
Patient-focused care is the redesign of patient care so that personnel and resources are organized around the patient instead of departments. The reasons are many but usually involve cost reductions and improvement in the customer's perception of quality. Goals for this process include grouping patients by diagnosis, decentralizing services, and cross-training staff. The respiratory care practitioner is well prepared to fit into the patient-focused care model. Recent surveys show the impact of hospital restructuring on respiratory care to be rather positive.


Maximal bite forces in healthy young adults as predicted by surface electromyography.
To assess the repeatability of maximal bite force estimates as obtained by submaximal electromyographic-force relationships performed simultaneously and symmetrically in both sides of the mouth. The protocol could be used in a clinical context to obtain indicative values for the occlusal loads to be resisted by the prosthetic reconstructions. Ten young healthy subjects performed; (1) a maximum voluntary clench (MVC) directly on their occlusal surfaces; (2) four simultaneous recording of submaximal bite forces (98, 196, 304 and 392 N on two transducers positioned on the left and right first mandibular molars) and surface EMG potentials of the masseter and temporalis anterior muscles. The actual force peak value was recorded. For each subject, a linear regression was run between the simultaneous bite force and EMG submaximal values recorded in the four tests. Using the EMG potentials obtained during the MVC tests, the best fitting line was used to estimate a maximum bite force. Two independent recordings were made by each subject (2 week interval) and analyzed by correlation analysis, paired Student's t-test, and Dahlberg statistic. Significant linear relationships were found between bite force and EMG potentials (p<0.01). The two series of indirect estimates of maximal bite force were correlated (r=0.626) without systematic differences (Student's t, p>0.01). Dahlberg statistic was 115.37 N (approximately 36% of the total variance of the group). Simultaneously recorded submaximal bite forces and surface EMG potentials of mandibular elevator muscles had a linear relationship. The estimates of maximum bite force were repeatable on a short-term basis (2 weeks). The method limited the disadvantages of bite force recordings, and it could be used to obtain indicative values for the occlusal loads to be resisted by the prosthetic reconstructions.


Facile preparation of ultralong dendritic PtIrTe nanotubes and their high electrocatalytic activity on methanol oxidation.
A facile wet chemical approach was developed to prepare ultralong PtIrTe nanotubes (NTs) using Te nanowires (NWs) as template. These PtIrTe NTs were made up of Pt nanodendrites uniformly arrayed on the surface of IrTe NTs and interweaved with each other to nanopores. Their morphology, structure, and composition were investigated by transition electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy. As expected, these PtIrTe NTs catalysts show a larger surface area, a stronger CO tolerance, and a higher catalytic activity toward electrochemical oxidation of methanol relative to the commercial Pt catalysts due to the 1D porous core-shell structure and the modification of the electronic effect by Ir.


Septic arthritis of a lumbar facet joint: detection with bone SPECT imaging.
We present a rare case of septic arthritis of a lumbar facet joint with an associated epidural abscess resulting from Staphylococcus aureus. The infection was initially detected with planar bone scintigraphy and precisely localized with single photon emission computed tomography bone scintigraphy, despite an initially negative radiologic evaluation that included radiographs of the lumbar spine, lumbar myelography, and a postmyelography x-ray computed tomography scan. In the appropriate clinical setting, a bone scan demonstrating unilateral increased activity within the spine should raise the suspicion of inflammatory involvement of the posterior elements.


Guideline compliance improves stroke outcome: a preliminary study in 4 districts in the Italian region of Lombardia.
Guidelines for medical practice in stroke have been proposed in different countries, but their impact on stroke outcome has not been verified to date. The aim of this study was to evaluate the impact of the American Heart Association guidelines for acute stroke and for transient ischemic attack on first-ever stroke patients. Three hundred eighty-six first-ever ischemic stroke patients were admitted to the study. Those observed within 6 hours from stroke onset were eligible for the acute clinical phase of the study, while all were admitted to the early clinical phase. The follow-up lasted 6 months. Primary end points were survival and the effectiveness of treatment on disability, measured as the proportion of potential improvement in the Barthel Index score achieved during treatment. A rating of noncompliance with the guideline recommendations was calculated for each patient, and its association with the end points was investigated. The Kaplan-Meier method and log-rank test were used to estimate and compare survival curves between groups; Cox proportional hazards model and logistic regression were used to identify risk factors for mortality; and correlation tests and regression analysis were used to evaluate the influence of guideline compliance on disability. Both univariate and multivariate statistical analyses were performed. Survival and treatment effectiveness were directly correlated with guideline compliance. The relative risk of death for patients with a noncompliance rating > or =5 was 2.26 with respect to patients with a noncompliance rating <5 (95% CI, 1.51 to 4.67; P<0.0007). In this latter group, at 6 months we detected a 15% decrease in mortality (95% CI, 9.1% to 17.5%). Treatment effectiveness showed a Spearman's rank correlation with the noncompliance rating of -0.3 (P<0.001). At discharge we observed a 13% increase in treatment effectiveness, while no significant differences were detectable at 3 and 6 months. These associations were confirmed by the multivariate analysis, in which we included, together with the noncompliance rating, all the variables previously identified as independent predictors of mortality and disability. This study demonstrates an association between adherence to guidelines and stroke outcome, and it can be viewed as a study that prepares the way for a randomized controlled trial in this area. It also emphasizes the need to develop personnel and structures devoted to stroke care because an evidence-based clinical approach could significantly reduce the risk of death.


A paradigm shift for ethics committees and case consultation: a modest proposal.
In conclusion, the expert-consultation model of ethics consultation is deeply imbedded in modern health care. The paradigm of consultant as expert rather than as community-enabler shapes the expectations and behaviors of healthcare personnel and institutions. This paradigm has also shaped the early stages of HEC development and ethics case consultation. It is time to shift paradigms and adopt one that derives more from the nature of ethics than from the nature of scientific medicine: the role of HECs should be to enable key professionals to carry out the ethical dimensions of patient care. When the HEC does review cases, it should be with the purpose of improving the institution, not of resolving individual cases. One consequence of this is that there will be more individual case reviews than before, but the function, emphasis, agents and locations will shift substantially. A second consequence is that the HEC will function more as an agent of social change by helping to harness the institution's resources. We judge both of these to be a welcome evolution in healthcare ethics.


Development of a wearable global positioning system for place and health research.
An increasing number of studies suggest that characteristics of context, or the attributes of the places within which we live, work and socialize, are associated with variations in health-related behaviours and outcomes. The challenge for health research is to ensure that these places are accurately represented spatially, and to identify those aspects of context that are related to variations in health and amenable to modification. This study focuses on the design of a wearable global positioning system (GPS) data logger for the purpose of objectively measuring the temporal and spatial features of human activities. Person-specific GPS data provides a useful source of information to operationalize the concept of place. We designed and tested a lightweight, wearable GPS receiver, capable of logging location information for up to 70 hours continuously before recharging. The device is accurate to within 7 m in typical urban environments and performs well across a range of static and dynamic conditions. Rather than rely on static areal units as proxies for places, wearable GPS devices can be used to derive a more complete picture of the different places that influence an individual's wellbeing. The measures are objective and are less subject to biases associated with recall of location or misclassification of contextual attributes. This is important for two reasons. First, it brings a dynamic perspective to place and health research. The influence of place on health is dynamic in that certain places are more or less relevant to wellbeing as determined by the length of time in any location and by the frequency of activity in the location. Second, GPS data can be used to assess whether the characteristics of places at specific times are useful to explaining variations in health and wellbeing.


Update on the Virologic and Immunologic Response to Highly Active Antiretroviral Therapy.
Highly active antiretroviral therapy (HAART) delays clinical progression by suppressing viral replication, measured by a substantial reduction in HIV RNA, allowing the immune system to reconstitute, measured in most studies by an increase in CD4 cells. These virologic and immunologic consequences do not occur uniformly among HAART users. Markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while receiving HAART. In this report, we review studies describing the heterogeneous virologic and immunologic progression after the initiation of HAART, discuss methodologic concerns in the study of the response of biomarkers, and update findings obtained in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of antiretroviral therapy, and age at the time of initiation are independent determinants of response.


Paraphenylenediamine (Kala Pathar) Poisoning at the National Poison Control Center in Karachi: A Prospective Study.
Introduction Suicide by self-poisoning is a common cause of death, especially in the younger population. More specifically, hair-dye poisoning is being increasingly used for suicide. Paraphenylenediamine (PPD), also known as "Kala pathar", is a highly toxic ingredient present in hair-dye that can cause death. Therefore, this study is designed to assess the demographics, clinical features, laboratory findings, and outcomes of PPD poisoning in patients admitted to the National Poison Control Center in Karachi, Pakistan. Materials and methods We conducted a prospective study for a period of six months at the National Poison Control Center, Karachi, Pakistan. A total of eight patients with PPD poisoning with no cardiac, liver, or renal co-morbidities were included in this study. The demographic characteristics, clinical features, laboratory findings, mode of intoxication, and route of intoxication were noted in a proforma. Furthermore, hospitalization time, tracheostomy status, mechanical ventilation status, and mortality rates were also recorded. For continuous variables, the means and SDs were calculated. Whereas for categorical data, percentages were calculated. Results In our study, the mean age of the patients was estimated at 25.38 ± 3.77 years. It was deemed that the majority of poisoning cases were intentional in nature (75%). These suicide cases were more commonly observed in young females (75%) who belonged to a low socioeconomic class (87.5%). The preferred route of administration was oral (87.5%). In 87.5% of the patients, the characteristic clinical features such as cervicofacial edema, dysphagia, dysphonia, and stridor were noted. During the later clinical stages of poisoning, clinical features such as rhabdomyolysis (62.5%), chocolate-colored urine (87.5%), hepatitis (75%), and acute renal failure (12.5%) were noteworthy. The mean ± SD of total leukocyte count (TLC), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine and serum potassium were, respectively, noted at 10,500 ± 3,854.4 cells/mm3, 32.87 ± 11.36 IU/L, 1,239.1 ± 1,106.2 IU/L, 776.8 ± 1,149.8 IU/L, 2.125 ± 2.275 mg/dL, and 4.9 ± 1.094 mmol/L. In our patients, the mean intensive care unit stay was 8.25 ± 3.99 days. Emergency tracheostomy was performed in 25% of patients. Mechanical ventilation was required for 50% of our patients. Overall, the mortality rate observed in our study stands at 25%. Conclusion PPD poisoning is associated with a high rate of morbidity and mortality. Therefore, it is imperative for physicians to be mindful of the clinical characteristics and treatment options in order to optimally manage such cases of poisoning. In addition, the use of hair-dyes composed of highly lethal PPD should also be banned.


Neural Correlates of Mild Behavioral Impairment: A Functional Brain Connectivity Study Using Resting-State Functional Magnetic Resonance Imaging.
Mild behavioral impairment (MBI) is associated with accelerated cognitive decline and greater risk of dementia. However, the neural correlates of MBI have not been completely elucidated. The study aimed to investigate the correlation between cognitively normal participants and participants with amnestic mild cognitive impairment (aMCI) using resting-state functional magnetic resonance imaging. The study included 30 cognitively normal participants and 13 participants with aMCI (20 men and 23 women; mean age, 76.9 years). The MBI was assessed using the MBI checklist (MBI-C). Region of interest (ROI)-to-ROI analysis was performed to examine the correlation between MBI-C scores and functional connectivity (FC) of the default mode network, salience network, and frontoparietal control network (FPCN). Age, Mini-Mental State Examination score, sex, and education were used as covariates. A p-value of 0.05, with false discovery rate correction, was considered significant. A negative correlation was observed between the MBI-C total score and FC of the left posterior parietal cortex with the right middle frontal gyrus. A similar result was obtained for the MBI-C affective dysregulation domain score. FPCN dysfunction was detected as a neural correlate of MBI, especially in the affective dysregulation domain. This dysfunction may be associated with cognitive impairment in MBI and conversion of MBI to dementia; however, further longitudinal data are needed to examine this relationship.


Description of a new species of the genus Agamura Blanford, 1874 (Squamata: Gekkonidae) from southern Iran.
Herein, we describe a new species of spider gecko, Agamura kermanensis sp. nov., from south Kerman, Iran. The new species is distinguished from other species by having long forelimbs and hindlimbs and a high interorbital distance. Agamura kermanensis sp. nov. was discovered in the Faryab region of southern Kerman Province, which has a xeric climate and low vegetation density. The habitat of the species is similar to that of A. cruralis in southeast Iran. It can be assumed that the distribution of the species is more extensive than currently known. More investigation is required in Jazmourian and the surrounding areas. This is the third species of the genus Agamura discovered on the Iranian Plateau.


In situ active control of noise in a 4 T MRI scanner.
To evaluate the effectiveness of the proposed active noise control (ANC) system for the reduction of the acoustic noise emission generated by a 4 T MRI scanner during operation and to assess the feasibility of developing an ANC device that can be deployed in situ. Three typical scanning sequences, EPI (echo planar imaging), GEMS (gradient echo multislice), and MDEFT (modified driven equilibrium Fourier transform), were used for evaluating the performance of the ANC system, which was composed of a magnetic compatible headset and a multiple reference feedforward filtered-x least mean square controller. The greatest reduction, about 55 dB, was achieved at the harmonic at a frequency of 1.3 kHz in the GEMS case. Approximately 21 dB and 30 dBA overall reduction was achieved for GEMS noise across the entire audible frequency range. For the MDEFT sequence, the control system achieved 14 dB and 14 dBA overall reduction in the audible frequency range, while 13 dB and 14 dBA reduction was obtained for the EPI case. The result is highly encouraging because it shows great potential for treating magnetic resonance imaging noise with an ANC application during real-time scanning.


Type of infectious disease affects glucose metabolism and liver glycogen content in Surinamese children: malaria vs. pneumonia.
Fasting is an important risk factor for hypoglycemia in children with malaria or pneumonia. Young children are more at risk because of impaired endogenous glucose production presumably due to smaller liver glycogen stores. The aim of this study was to measure the effect of a bolus of glucagon on glucose kinetics, as an indicator of glycogen content, in fasted children with malaria and pneumonia. After a 16-h controlled fast, plasma glucose concentration and endogenous glucose production were measured using [6,6-2H2]glucose in six children with severe malaria and 12 children with severe pneumonia who were 1-5 years of age before and after a bolus glucagon. Basal glucose concentration and endogenous glucose production were higher in children with malaria, p=0.034 and p=0.010, respectively. After glucagon, the increase in the plasma glucose concentration was higher in children with malaria (52±26% vs. 31±23%, p=0.029). Also, the increase in glucose production was higher in children with malaria (106±42% vs. 70±52%, p=0.023). There were no differences in the fasting duration or duration of illness. This is the first study to show infectious disease-related differences in the adaptation of glucose metabolism to fasting in young children. It was found that basal glucose concentration and endogenous glucose production were higher in children with malaria. The increase in plasma glucose concentration and endogenous glucose production in response to glucagon was higher in children with malaria, indicating smaller glycogen stores in children with pneumonia.


Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.
The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.


Biodegradability of Amniotic Membrane as Potential Scaffold for Periodontal Regeneration.
Background In the periodontal regenerative procedure, the membrane used should possess good mechanical stability with suitable resorption time to allow restoration of the lost periodontium. Amniotic membrane (AM) has regenerative potential as a scaffold or barrier membrane due to its various beneficial properties. However, its degradation rate is not clearly reported. Methodology This study aimed to evaluate the resorption capacity of AM and its surface architecture after being subjected to hydrolytic degradation analysis in phosphate buffer solution (PBS). AM was cut into sizes of 10 × 10 mm2 for three replicates. The membranes were weighed before and at different time intervals (days 7, 14, 21, and 28) after immersion in PBS. The degradation rate was determined by the percentage of mean weight loss from the initial weight at different time intervals. The AM surface profile was observed under scanning electron microscopy (SEM) before and after 28 days of immersion. Results The result shows a 92% loss of weight over 28 days with the highest attained in the first seven days (67%), followed by 7%, 17%, and 1% after days 14, 21, and 28, respectively. SEM of the AM surface before the degradation test showed a polygonal shape forming a well-arranged mosaic pattern covered with microvilli. At day 28, the remaining AM appears as porous surface architecture, irregularly arranged fibers, and no microvilli seen. Conclusions This study demonstrated that over four weeks of degradation analysis, AM was not entirely degraded but had lost some of the microstructure. The biodegradability of AM should be further evaluated to elucidate its stability within adequate time parallel with the tissue healing process in periodontal tissue regeneration.


Evaluation of protein metabolism in clinical practice.
The application of stable isotopes creates further possibilities for our understanding of the metabolism. New concepts especially for non-invasive diagnostic procedures could be developed. An important step in our research program was the performing of a 1-year experiment on a volunteer. On the basis of a 10-pool model we received a lot of informations. Based on this knowledge we developed 2 simplified methods for calculating whole body protein turnover. Knowing the problems with whole body protein calculations we intensified our intentions for determining the protein enrichment in organs and isolated cells (hepatocytes), estimating at the same time the precursor pool in the cells. Of special importance was an extensive study, wherein all those 15N-estimations were performed we are able to do up to now. We calculated whole body protein, but especially we studied the enrichment of the cellular protein fractions in hepatocytes, of plasmaproteins, and of the intracellular precursor pool. This study is the base for further tracer investigations.


Angiotensin-(1-7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage.
Aneurysmal subarachnoid hemorrhage (SAH) is a substantial cause of mortality and morbidity worldwide. Moreover, survivors after the initial bleeding are often subject to secondary brain injuries and delayed cerebral ischemia, further increasing the risk of a poor outcome. In recent years, the renin-angiotensin system (RAS) has been proposed as a target pathway for therapeutic interventions after brain injury. The RAS is a complex system of biochemical reactions critical for several systemic functions, namely, inflammation, vascular tone, endothelial activation, water balance, fibrosis, and apoptosis. The RAS system is classically divided into a pro-inflammatory axis, mediated by angiotensin (Ang)-II and its specific receptor AT1R, and a counterbalancing system, presented in humans as Ang-(1-7) and its receptor, MasR. Experimental data suggest that upregulation of the Ang-(1-7)/MasR axis might be neuroprotective in numerous pathological conditions, namely, ischemic stroke, cognitive disorders, Parkinson's disease, and depression. In the presence of SAH, Ang-(1-7)/MasR neuroprotective and modulating properties could help reduce brain damage by acting on neuroinflammation, and through direct vascular and anti-thrombotic effects. Here we review the role of RAS in brain ischemia, with specific focus on SAH and the therapeutic potential of Ang-(1-7).


Adjoint image warping using multivariate splines with application to four-dimensional computed tomography.
Adjoint image warping is an important tool to solve image reconstruction problems that warp the unknown image in the forward model. This includes four-dimensional computed tomography (4D-CT) models in which images are compared against recorded projection images of various time frames using image warping as a model of the motion. The inversion of these models requires the adjoint of image warping, which up to now has been substituted by approximations. We introduce an efficient implementation of the exact adjoints of multivariate spline based image warping, and compare it against previously used alternatives. Using symbolic computer algebra, we computed a list of 64 polynomials that allow us to compute a matrix representation of trivariate cubic image warping. By combining an on-the-fly computation of this matrix with a parallelized implementation of columnwise matrix multiplication, we obtained an efficient, low memory implementation of the adjoint action of 3D cubic image warping. We used this operator in the solution of a previously proposed 4D-CT reconstruction model in which the image of a single subscan was compared against projection data of multiple subscans by warping and then projecting the image. We compared the properties of our exact adjoint with those of approximate adjoints by warping along inverted motion. Our method requires halve the memory to store motion between subscans, compared to methods that need to compute and store an approximate inverse of the motion. It also avoids the computation time to invert the motion and the tunable parameter of the number of iterations used to perform this inversion. Yet, a similar and often better reconstruction quality was obtained in comparison with these more expensive methods, especially when the motion is large. When compared against a simpler method that is similar to ours in computational demands, our method achieves a higher reconstruction quality in general. Our implementation of the exact adjoint of cubic image warping improves efficiency and provides accurate reconstructions.


Message Passing Neural Networks Improve Prediction of Metabolite Authenticity.
Cytochrome P450 enzymes aid in the elimination of a preponderance of small molecule drugs, but can generate reactive metabolites that may adversely react with protein and DNA and prompt drug candidate attrition or market withdrawal. Previously developed models help understand how these enzymes modify molecule structure by predicting sites of metabolism or characterizing formation of metabolite-biomolecule adducts. However, the majority of reactive metabolites are formed by multiple metabolic steps, and understanding the progenitor molecule's network-level behavior necessitates an integrative approach that blends multiple site of metabolism and structure inference models. Our previously developed tool, XenoNet 1.0, generates metabolic networks, where nodes are molecules and weighted edges are metabolic transformations. We extend XenoNet with a bidirectional message passing neural network that integrates edge feature information and local network structure using edge-conditioned graph convolutions and jumping knowledge to predict the authenticity of inferred Phase I metabolite structures. Our model significantly outperformed prior work and algorithmic baselines on a data set of 311 networks and 6606 intermediates annotated using a chemically diverse set of 20 736 individual in vitro and in vivo reaction records accounting for 92.3% of all human Phase I metabolism in the Accelrys Metabolite Database. Cross-validated predictions resulted in area under the receiver operating characteristic curves of 88.5% and 87.6% for separating experimentally observed and unobserved metabolites at global and network levels, respectively. Further analysis verified robustness to networks of varying depth and breadth, accurate detection of metabolites, such as d,l-methamphetamine, that are experimentally observed or unobserved in different network contexts, extraction of important metabolic subnetworks, and identification of known bioactivation pathways, such as for nimesulide and terbinafine. By exploiting network structures, our approach accurately suggests unreported metabolites for experimental study and may rationalize modifications for avoiding deleterious pathways antecedent to reactive metabolite formation.


Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species.
Conditions of stress, such as myocardial infarction, stimulate up-regulation of heme oxygenase (HO-1) to provide cardioprotection. Here, we show that CO, a product of heme catabolism by HO-1, directly inhibits native rat cardiomyocyte L-type Ca2+ currents and the recombinant alpha1C subunit of the human cardiac L-type Ca2+ channel. CO (applied via a recognized CO donor molecule or as the dissolved gas) caused reversible, voltage-independent channel inhibition, which was dependent on the presence of a spliced insert in the cytoplasmic C-terminal region of the channel. Sequential molecular dissection and point mutagenesis identified three key cysteine residues within the proximal 31 amino acids of the splice insert required for CO sensitivity. CO-mediated inhibition was independent of nitric oxide and protein kinase G but was prevented by antioxidants and the reducing agent, dithiothreitol. Inhibition of NADPH oxidase and xanthine oxidase did not affect the inhibitory actions of CO. Instead, inhibitors of complex III (but not complex I) of the mitochondrial electron transport chain and a mitochondrially targeted antioxidant (Mito Q) fully prevented the effects of CO. Our data indicate that the cardioprotective effects of HO-1 activity may be attributable to an inhibitory action of CO on cardiac L-type Ca2+ channels. Inhibition arises from the ability of CO to promote generation of reactive oxygen species from complex III of mitochondria. This in turn leads to redox modulation of any or all of three critical cysteine residues in the channel's cytoplasmic C-terminal tail, resulting in channel inhibition.


Enhanced resistance of mice to Escherichia coli infection induced by administration of peptidoglycan derived from Bifidobacterium thermophilum.
Peptidoglycan (PG) of Bifidobacterium thermophilum (B. thermophilum) from swine were orally administered to SPF-ICR mice in order to confirm the enhancement of the defence activity of the mice against Escherichia coli (E. coli) infection. It was found that the survival rates of the PG-administered group were significantly higher than those of the non-treated control group after the single oral administration of PG. And the proper concentration at which PG enhanced defence activity most effectively was found to be 500 micrograms per mouse. The number of E. coli in the peripheral blood, liver and spleen of the PG-administered group at 24 hr after the inoculation was significantly smaller than that in the control group. Liver weight per body weight in the PG treated group significantly increased in comparison with that of the non-treated group. The number of blastoid plasmacytes in the spleen of the PG-administered mice was found to be greater than that in the control group. These results indicate that the defence activity of mice against E. coli infection was accelerated by PG treatment.


Synthesis and triplex-forming properties of cyclic oligonucleotides with (G,A)-antiparallel strands.
Cyclic oligonucleotides carrying an oligopurine Watson-Crick sequence linked to the corresponding (G,A)- and (G,T)-antiparallel strands were prepared by nonenzymatic template-assisted cyclization of phosphorylated precursors. Cyclization was attempted using 3'-phosphate and 5'-phosphate linear precursors with carbodiimide or BrCN activation. The best results were obtained with the 5'-phosphorylated precursors and carbodiimide activation. Cyclic oligonucleotides bind polypyrimidine target sequence by formation of antiparallel triplexes. We have used UV and circular dichroism (CD) spectroscopy to analyze triplexes formed by cyclic oligonucleotides carrying G and A in the reverse-Hoogsteen strand. The relative stability of the triplexes formed by cyclic and linear oligonucleotides with a common polypyrimidine target was determined by melting experiments. The most-stable triplexes were formed by the cyclic oligonucleotide, followed by the unphosphorylated and phosphorylated oligonucleotide precursors, and, finally, the corresponding hairpin. Although the differences in binding affinity between cyclic oligonucleotides and their corresponding linear precursors are small, the use of cyclic oligonucleotides offers a clear advantage over conventional duplex recognition.


An angiographic technique for three-dimensional determination of arterial supply patterns in cadaver soft tissue.
A method for arterial tree mapping that can be used in cadaver soft tissue is presented. In situ angiograms and photographs are supplemented with profile angiograms of relatively narrow bands of tissue from the removed specimen. The described method was better suited for mapping the course and supply patterns of a soft-tissue arterial network than either in situ angiograms or dissection. While practical problems were encountered with most of the solutions used for providing radiopacity or structural support to the vessels, pure barium sulfate was found to be suitable because it filled the vascular tree to the capillary level without leakage during excision of the specimen.


Nonsurgical management of small and intracanalicular acoustic tumors.
It is generally accepted that the proper treatment for acoustic tumors is surgical removal. In fact, there is little, if any, reference to nonsurgical treatment of these tumors in the recent medical literature. We would like to report on the nonsurgical management of six patients with cerebellopontine angle tumors based upon CT examination. The diagnostic findings, follow-up data, and the rationale upon which the decision was made to treat the patients nonsurgically will be presented, as will a review of the pertinent literature.


Embryo transfer in swine.
Embryo transfer is used to propagate genetically superior swine while minimizing disease risks. Embryos are harvested through a ventral midline incision in the anesthetized sow 4-6 days after estrus, using a glass tube or Foley catheter. Embryos are transferred to similarly prepared sows by injection directly into the uterus through a tomcat catheter or glass pipette. Embryos typically are transferred within a few hours of collection but may be stored in culture medium at 37 C for up to 30 hours.


Thermodynamic and kinetic supercooling of liquid in a wedge pore.
Cyclohexane allowed to capillary condense from vapor in an annular wedge pore of mica in a surface force apparatus (SFA) remains liquid down to at least 14 K below the bulk melting-point T(m). This is an example of supercooling of a liquid due to confinement, like melting-point depression in porous media. In the wedge pore, however, the supercooled liquid is in equilibrium with vapor, and the amount of liquid (and thereby the radius of curvature r of the liquid-vapor interface) depends on the surface tension gamma(LV) of the liquid, not the interfacial tension between the solid and liquid. At coexistence r is inversely proportional to the temperature depression DeltaT below T(m), in accordance with a recently proposed model [P. Barber, T. Asakawa, and H. K. Christenson, J. Phys. Chem. C 111, 2141 (2007)]. We have now extended this model to include effects due to the temperature dependence of both the surface tension and the enthalpy of melting. The predictions of the improved model have been quantitatively verified in experiments using both a Mark IV SFA and an extended surface force apparatus (eSFA). The three-layer interferometer formed by the two opposing, backsilvered mica surfaces in a SFA was analyzed by conventional means (Mark IV) and by fast spectral correlation of up to 40 fringes (eSFA). We discuss the absence of freezing in the outermost region of the wedge pore down to 14 K below T(m) and attribute it to nonequilibrium (kinetic) supercooling, whereas the inner region of the condensate is thermodynamically supercooled.


[Bone marrow microenvironment in chronic myeloid leukemia: implications for disease physiopathology and response to treatment].
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm related to the presence of the BCR-ABL1 fusion gene, linked to t (9;22) (q34;q11). It is originated from an abnormal hematopoietic stem cell, which is characterized as its normal counterparts by long-term self-renewal and multi-lineage differentiation. Both leukemic and quiescent normal hematopoietic stem cells preferentially reside in the osteoblastic niche. Mesenchymal stromal cells (MSC) are located near them, playing a critical role in their regulation. Currently, with tyrosine kinase inhibitor (TKI) therapy, long term clinical responses are achieved in most CML cases. However, late treatment failures may be observed related to the persistence of leukemic stem cells. The interactions between the leukemic stem cell and the microenvironment may be responsible in part for these events. We review the interactions between the leukemic stem cell and BM stroma and its potential clinical and therapeutic implications.


Opioid neuronal denervation in Gilles de la Tourette syndrome.
Increased striatal dopaminergic functions with heightened postsynaptic receptor sensitivity has been proposed to underlie the major clinical symptoms of Tourette's syndrome (TS). The beneficial response of the majority of TS patients to haloperidol supports the hyperdopaminergic pathophysiological concept of TS. However, in 5 recently encountered TS patients, haloperidol failed to ameliorate self-injurious behavior (SIB) while the opiate antagonist, naloxone, attenuated SIB, implicating deranged endorphinergic mechanisms in the pathophysiology of this disorder. Brain damage is commonly associated with partial neuronal denervation, denervation supersensitivity and neuronal habituation (Cannon's Law). While the motor tics of TS possibly reflect neuronal denervation of striatal dopaminergic neurons. SIB may represent opioid denervation with alterations in opioid receptor sensitivity possibly involving striato-limbic-hypothalamic circuits. The effect of naloxone on SIB in TS could thus be explained on the basis of a modulatory effect of this drug on opioid receptor sensitivity.


The phenomenology of comfort.
From patient narratives, the phenomenological literature and reflection of patients' autobiographical accounts of illness, nine themes reflecting the phenomenological concept of corporeality were used to identify the ways patients achieve comfort. The themes were: the dis-eased body, the disobedient body, the vulnerable body, the violated body, the resigned body, the enduring body, the betraying body and the betraying (neurotic) mind. The process of achieving comfort is based on the patients' needs to live with illness or injury without being dominated by their bodies. The authors argue that while the role of nursing is to provide comfort to the sick, the goal of total comfort is unattainable in patient care. However, if the goal is to enhance comfort, to ease and to relieve distress, comfort remains central to the role of nursing.


Workers' compensation law: an overview.
1. The workers' compensation system provides benefits to workers who are injured or made ill in the course of employment or their dependents regardless of fault. 2. The current workers' compensation laws benefit both the employer and the employee; however, workers' compensation is an exclusive remedy which bars recovery through a negligence lawsuit. 3. Workers' compensation regulations interact with other federal statutes such as the Americans With Disabilities Act and the Family Medical Leave Act. 4. Workers' compensation covers occupational injuries and occupational diseases, which may include cumulative trauma and mental stress claims. Nurses may be instrumental in evaluating and planning for an injured employee's return to work and occasionally in detecting fraudulent claims.


Critical Care Considerations for Damage Control in a Trauma Patient.
Traumatic injury remains the leading cause of death among individuals younger than age 45 years. Hemorrhage is the primary preventable cause of death in trauma patients. Management of hemorrhage focuses on rapidly controlling bleeding and addressing the lethal triad of hypothermia, acidosis, and coagulopathy. The principles of damage control surgery are rapid control of hemorrhage, temporary control of contamination, resuscitation in the intensive care unit to restore normal physiology, and a planned, delayed definitive operative procedure. Damage control resuscitation focuses on 3 key components: fluid restriction, permissive hypotension, and fixed-ratio transfusion. Rapid recognition and control of hemorrhage and implementation of resuscitation strategies to control damage have significantly improved mortality and morbidity rates. In addition to describing the basic principles of damage control surgery and damage control resuscitation, this article explains specific management considerations for and potential complications in patients undergoing damage control interventions in an intensive care unit.


In vivo glucose utilization by individual tissues during nonlethal hypermetabolic sepsis.
Febrile sepsis was induced in rats by repeated s.c. injections of live Escherichia coli bacteria. Glucose utilization of different tissues was investigated in vivo by using the 2-deoxyglucose tracer technique. In septic rats the rate of glucose utilization was increased in macrophage-rich tissues, including the liver (2.7-fold), spleen (2.4-fold), and ileum (1.6-fold), compared with tissues from time-matched nonseptic animals. A smaller increase in glucose utilization was evident in the abdominal muscle (1.3-fold) and in the white portion of the quadriceps muscle (1.3-fold). Changes were not significant in nine other tissues, including the brain. We postulate that in sepsis the mononuclear phagocyte system may be responsible for most of the increment of glucose utilization, and the latter provides metabolic support for the increased antibacterial activity of these cells.


Substituent Correlations Characterized by Hammett Constants in the Spiropyran-Merocyanine Transition.
The modification of molecular properties by the use of substituents is a versatile route for molecular design. Here we show for the example of multiresponsive spiropyrans that substituent effects and their correlations can be accurately described by Hammett constants, which in turn can be obtained directly from density functional theory calculations. The internal energetic difference ΔU between the noncolored and the colored form is determined for 63 spiropyran derivatives with substituents at the spiropyran N- and C6-positions, and can be described by only five parameters with an accuracy better than 0.1 eV (9.75 kJ/mol) using Hammett constants. This enables the prediction of ΔU values for other substituents without the need for further calculations nor experiments.


A phyco-nanobionics biohybrid system for increased carotenoid accumulation in C. sorokiniana UUIND6.
Recent advancements in "phyco-nanobionics" have sparked considerable interest in the ability of microalgae to synthesize high-value natural bioactive compounds such as carotenoid pigments, which have been highlighted as an emergent and vital bioactive compound from both industrial and scientific perspectives. Such bioactive compounds are often synthesized by either altering the biogenetic processes existing in living microorganisms or using synthetic techniques derived from petroleum-based chemical sources. A bio-hybrid light-driven cell factory system was established herein by using harmful macroalgal bloom extract (HMBE) and efficient light-harvesting silver nanoparticles (AgNPs) to synthesize HMBE-AgNPs and integrating the synthesized HMBE-AgNPs in various concentrations (1, 2.5, 5 and 10 ppm) into the microalgae C. sorokiniana UUIND6 to improve the overall solar-to-chemical conversion efficiency in carotenoid pigment synthesis in microalgae. The current study findings found high biocompatibility of 5 ppm HMBE-AgNP concentration that can serve as a built-in photo-sensitizer and significantly improve ROS levels in microalgae (6.75 ± 0.25 μmol H2O2 g-1), thus elevating total photosynthesis resulting in a two-fold increase in carotenoids (457.5 ± 2.5 μg mL-1) over the native microalgae without compromising biomass yield. NMR spectroscopy was additionally applied to acquire a better understanding of pure carotenoids derived from microalgae, which indicated similar peaks in both spectra when compared to β-carotene. Thus, this well-planned bio-hybrid system offers a potential option for the cost-effective and long-term supply of these natural carotenoid bio-products.


Adjusting the Reduction Potential of Electrons by Quantum Confinement for Selective Photoreduction of CO2 to Methanol.
The production of CH3 OH from the photocatalytic CO2 reduction reaction (PCRR) presents a promising route for the clean utilization of renewable resources, but charge recombination, an unsatisfying stability and a poor selectivity limit its practical application. In this paper, we present the design and fabrication of 0D/2D materials with polymeric C3 N4 nanosheets and CdSe quantum dots (QDs) to enhance the separation and reduce the diffusion length of charge carriers. The rapid outflow of carriers also restrains self-corrosion and consequently enhances the stability. Furthermore, based on quantum confinement effects of the QDs, the energy of the electrons could be adjusted to a level that inhibits the hydrogen evolution reaction (HER, the main competitive reaction to PCRR) and improves the selectivity and activity for CH3 OH production from the PCRR. The band structures of photocatalysts with various CdSe particle sizes were also investigated quantitatively to establish the relationship between the band energy and the photocatalytic performance.


Ethyl N-phenyloxamate.
The oxamate group in the title compound, C(10)H(11)NO(3), is almost coplanar with the phenyl ring because of intramolecular hydrogen-bonding interactions, and the structure can be described as an anilide single bonded to an ethyl carboxylate group. The supramolecular structure is achieved through intermolecular hard N-H...O and soft C-H...X (X = O and phenyl) hydrogen-bonding interactions.


Renal effects of local infusion of adenosine in man.
1. The effects of local intra-arterial infusion of adenosine on renal blood flow, glomerular filtration and renin release in eight healthy awake subjects have been examined. 2. Renal blood flow and glomerular filtration rate were measured as the clearances of p-aminohippurate and inulin, respectively. After basal samplings, adenosine was infused intra-arterially at successive rates of 2 and 10 micrograms min-1 kg-1 for 40 min at each rate. 3. Apart from a small increase in heart rate (65 +/- 4 to 71 +/- 4 beats/min), there were no signs of sympathetic activation (unchanged blood pressure and catecholamine levels) during the infusion. Clearance of p-aminohippurate tended to increase, but not significantly, during adenosine infusion (518 +/- 48 ml/min basal, 563 +/- 52 ml/min during the highest dose of adenosine). The arterial plasma concentration of p-aminohippurate decreased by 9 +/- 3% (P < 0.05), consistent with a small increase in renal blood flow in the infused kidney. Inulin clearance was reduced from 115 +/- 3 to 97 +/- 2 ml/min (P < 0.001). The extraction of inulin, reflecting the filtration fraction, was 18% in both kidneys in the basal state. During infusion of adenosine the extraction in the infused kidney decreased to 12 +/- 3% (P < 0.01 compared with the control kidney, 23 +/- 3%). 4. The total excretion of Na+ was unchanged, but there was a minor decrease in K+ clearance. Thus, the K+/Na+ excretion ratio decreased from a basal value of 13 +/- 2 to 10 +/- 2 (P < 0.01) at the highest dose of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)


Disruption of the distylous syndrome in Primula veris.
Distyly is a floral polymorphism characterized by the presence of two discrete morphs with reciprocal positioning of anthers and stigmas in flowers on different plants within the same population. Although reciprocal herkogamy and associated floral traits are generally thought to be discrete and strict polymorphisms, little is known about variation in floral traits related to the distylous syndrome within and among populations of a single species. In this study, variation in floral morphology and reciprocal positioning of the sexual organs in the distylous Primula veris (cowslip) is quantified. Data were collected in ten populations occurring in two contrasting habitat types (grasslands and forests), and for each population the average level of reciprocity was assessed, the strength of the self-incompatibility system was determined, and seed production under natural conditions was quantified. In grassland populations, flowers showed clear distyly with low and symmetric reciprocity indices at both the lower and upper level. In forests, P. veris produced larger flowers that showed strong deviations in stigma-anther separation, especially in the L-morph. This deviation was mainly driven by variation in stigma height, resulting in high and asymmetric reciprocity indices and the occurrence of several short-styled homostylous plants. Self-incompatibility was, however, strict in both habitats, and morph ratios did not differ significantly from isoplethy. The observed shift in reciprocity in forest populations was associated with a significant reduction in seed production in the L-morph. The results indicate that populations of P. veris show habitat-specific variation in flower morphology. Deviations from perfect reciprocal positioning of stigmas and anthers also translate into reduced seed production, suggesting that small changes in sexual organ reciprocity can have far-reaching ecological and evolutionary implications.


Clinical zinc deficiency during long-term total enteral nutrition.
Zinc deficiency during long-term total parenteral nutrition has been well reported in the literature. However, there is limited information available on zinc deficiency occurring during total enteral nutrition. Two cases of clinical zinc deficiency in patients on long-term enteral feedings are presented. Nutritional assessment of these two patients on admission revealed hypoalbuminemic malnutrition. Nutritional support in the form of nasogastric tube feedings were initiated in both patients due to altered mental status. The formula used was Ensure (Ross Labs, Columbus, OH), which provided greater than 150% of the RDA for zinc. However, four months and seven months after initiation of adequate nutritional support, both patients developed skin rashes around the groin and under the breasts and axilla. Serum zinc levels were depressed in both patients, to 42 and 54 mg/dL, respectively (normal for the authors' laboratory, 66 to 120 mg/dL). Supplementation with zinc sulfate 220 mg per day via nasogastric tube resulted in disappearance of the rash with return of serum zinc to normal levels. The authors suggest close observation of patients on long-term enteral nutrition for clinical manifestation of zinc deficiency, especially an unexplained skin rash. Further studies are needed to establish minimum daily zinc requirements in patients on long-term enteral feedings.


An intraindividual comparison of standard and mini-Wright scores.
The relationship between peak expiratory flow rate scores recorded with the standard Wright meter and those recorded with the mini-Wright meter was determined by correlating these scores on an intraindividual basis. These correlations were compared with correlations between pairs of standard scores. The latter were computed so as to provide an estimate of peak expiratory flow rate variability unrelated to recording apparatus. The results showed that pairs of standard Wright scores were more highly related to one another than were pairs of standard and mini-Wright scores. From these observations it was concluded that standard and mini-Wright scores are not equivalent and therefore may not confidently be interchanged.


Progress of cereal transformation technology mediated by Agrobacterium tumefaciens.
Monocotyledonous plants were believed to be not transformable by the soil bacterium Agrobacterium tumefaciens until two decades ago, although convenient protocols for infection of leaf disks and subsequent regeneration of transgenic plants had been well established in a number of dicotyledonous species by then. This belief was reinforced by the fact that monocotyledons are mostly outside the host range of crown gall disease caused by the bacterium and by the failures in trials in monocotyledons to mimic the transformation protocols for dicotyledons. However, a key reason for the failure could have been the lack of active cell divisions at the wound sites in monocotyledons. The complexity and narrow optimal windows of critical factors, such as genotypes of plants, conditions of the plants from which explants are prepared, tissue culture methods and culture media, pre-treatments of explants, strains of A. tumefaciens, inducers of virulence genes, transformation vectors, selection marker genes and selective agents, kept technical hurdles high. Eventually it was demonstrated that rice and maize could be transformed by co-cultivating cells of callus cultures or immature embryos, which are actively dividing or about to divide, with A. tumefaciens. Subsequently, these initial difficulties were resolved one by one by many research groups, and the major cereals are now transformed quite efficiently. As many as 15 independent transgenic events may be regenerated from a single piece of immature embryo of rice. Maize transformation protocols are well established, and almost all transgenic events deregulated for commercialization after 2003 were generated by Agrobacterium-mediated transformation. Wheat, barley, and sorghum are also among those plants that can be efficiently transformed by A. tumefaciens.


Late onset acute occlusion of the subclavian artery after clavicle fracture.
Vascular injuries after a clavicle fracture are rare. The treatment remains, if possible, conservative. In case of life-threatening bleeding or limb ischemia, endovascular treatment is the treatment of choice. In this case report, we describe a patient who suffered a clavicle fracture five years before and now presented with acute invalidating claudication caused by an acute occlusion superimposed on a brachial artery stenosis. After unsuccessful thrombolytic therapy a surgical exploration of the brachial artery was performed.


Plasma Symmetric Dimethylarginine Concentration in Dogs with Acute Kidney Injury and Chronic Kidney Disease.
Symmetric dimethylarginine (SDMA) is considered a biomarker for early detection of renal dysfunction in human patients with acute kidney injury (AKI). At present, no studies exist analyzing the relevance of SDMA in dogs with AKI. SDMA would correctly identify dogs with renal disease but would not be able to differentiate between AKI and CKD. Eighteen healthy control dogs, 48 dogs with AKI, and 29 dogs with CKD. Prospective study. Dogs with kidney disease were categorized as having AKI or CKD according to the history, clinical signs, laboratory findings, and results of diagnostic imaging. Plasma SDMA concentration was measured by IDEXX Laboratories. SDMA/creatinine ratio was calculated in dogs with AKI or CKD. Median SDMA concentrations were 8.5 μg/dL (6-12 μg/dL), 39.5 μg/dL (8->100 μg/dL), and 35 μg/dL (12->100 μg/dL), in healthy, AKI, and CKD, respectively. SDMA concentrations were significantly higher in dogs with AKI (P < .0001) or CKD (P < .0001) in comparison with healthy dogs. Median SDMA/creatinine ratio in dogs with AKI and CKD was 6.5 (1.7-20.9) and 10 (2.4-33.9) (P = .0004), respectively. Although there was overlap of the SDMA/creatinine ratio in dogs with AKI or CKD, it was significantly higher in dogs with CKD compared to dogs with AKI (P = .0004). In this population, SDMA was suitable for identifying dogs affected by AKI or CKD, but could not differentiate between them.


A validated UHPLC-QTOF-MS method for quantification of metformin and teneligliptin in rat plasma: Application to pharmacokinetic interaction study.
In this study a sensitive UHPLC-QTOF-MS method was developed and validated for the quantitation of the metformin (MET) and teneligliptin (TEN) in rat plasma using dapagliflozin as an internal standard (IS). Chromatographic separation were carried out on a Acquity UPLC HSS Cyano column (100mm x 2.1mm, 1.8μm) using gradient mobile phase system consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4mL/min, within a run time of 6min. Protein precipitation method was used as sample preparation approach. Detection of target ions [M+H]+ at m/z 130.1085 for MET, m/z 427.2277 for TEN and m/z 409.1623 for IS was performed at positive ion electrospray ionization mode. Linearity was assessed in the range of 0.98-1000ng/mL for both MET and TEN. The developed assay was validated as per US-FDA and EMA bioanalytical guidelines and successfully applied to pharmacokinetic interaction study in SD rats. A 1.1 fold increment in the AUC levels of MET and TEN was observed when co-administered together in rats.


Longitudinal rupture of the peroneal tendons.
To determine more precisely the injury mechanism of the peroneal tendon longitudinal tear, we studied 15 cadaveric lower extremities. Our study was motivated by our observation from a retrospective study of athletes treated by one surgeon (FHB) over a 17-year period. Eight patients who sustained lateral ankle sprains by plantar flexion and inversion of the foot on the leg also had longitudinal tears (1 to 3 cm) of the peroneal tendon--five in the peroneus longus and three in the peroneus brevis. All of the lateral ankle sprains were successfully managed nonoperatively. However, even after a period of rehabilitation, when their ankles should have been asymptomatic, the patients continued to complain of persistent lateral ankle swelling, popping, and retrofibular pain. On physical examination, all ankles were clinically stable. Palpable retrofibular popping occurred with active foot rotation. There was no evidence of peroneal tendon instability. Radiographs were normal and tenograms were suggestive of peroneal tendon injury but did not have the specificity to reveal the rupture. Primary suture repair of this peroneal tendon split was performed and gave excellent long-term results. The cadaveric studies revealed that the tear of the tendon could occur in the 25 degrees to 15 degrees range of plantar flexion as the peroneus longus impinged against the tip of the fibula and as the peroneus brevis impinged against the lateral wall of the peroneal groove or against the longus tendon.


Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.
Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of all meningiomas, but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers in an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets.


[Complete genomic sequence of rapidly replicating strain MB-7 of hepatitis a virus and its characterization in comparison with nucleotide sequences of other hepatitis A virus strains].
Complete nucleotide sequence of genomic RNA of hepatitis A virus (HAV) rapidly replicating strain MB-7 was determined. Comparison of nucleotide and deduced amino-acid sequences demonstrated the highest level of identity of MB-7 with strain HAS-15 (above 99%) and high homology with other HAV strains (HM 175/7, CR326, and GBM/HFS) used in production of anti-hepatitis A vaccines. MB-7 was classified as subgenotype IA. Phylogenetic analysis showed that MB-7 is most closely related to the strain HAS-15 and the HAV variants circulating in Russia. Comparative analysis of genomic differences between MB-7 and HAS-15 with other HAV strains revealed among changes characteristic of MB-7 those typical of the described earlier rapidly replicating HAV strains (nt. 149-162 in 5'-untranslated region and changes in the VP3 and 2C genes). These results suggest the functional importance of changes in above-mentioned regions of HAV genome for the increased replication level of MB-7 in vitro.


Tobacco quitlines: Opportunities for innovation to increase reach and effectiveness.
The largest tobacco treatment network in North America, Tobacco Quitlines are an effective population-based approach to increase tobacco cessation; however, overall reach has decreased significantly in the past decade. A new generation of innovations responsive to evolving shifts in communication preferences, supported by research, and focused on increasing the impact of services have the potential to reinvigorate this network. The goal of this narrative review was to identify opportunities for innovation in Quitline service delivery, synthesize evidence for these opportunities, and identify gaps in the research. Innovation was defined as significant shift in current practice by utilizing novel theoretical concepts, approaches, methodologies, or interventions. The Experimental Medicine Approach informed the identification of gaps in the research. The specific domains were selected by reviewing previous reviews, commentaries, calls for action, and a recent report on promising practices. Evidence was garnered primarily from systematic reviews. Opportunities included automated and interactive digital therapeutics, novel health communications for stigma-free media campaigns, methods to increase access to nicotine replacement therapies, novel treatment options and combinations, and methods to promote engagement with digital therapeutics. Research topics that cross multiple domains include the consideration of theoretical frameworks, the identification of therapeutic targets and mechanisms of action, and the development of adapted approaches to address specific challenges and cultural responsivity. Finally, an examination is needed to understand how to improve the speed with which innovations are developed and implemented in this network.


Pigeons breeders' disease. I. Serum immunoglobulin concentrations; IgG, IgM, IgA and IgE antibodies against pigeon serum.
The clinical course of a patient with severe acute and chronic hypersensitivity pneumonitis of the pigeon breeders' disease (PBD) type was evaluated. A significant remission of symptomatic, roentgenographic and pulmonary function abnormalities occurred after cessation of exposure to antigen. Immunoglobulin G (IgG), A (IgA) and M (IgM) antibody activity against pigeon serum was demonstrated in the patient's serum by a solid phase radioimmunoassay (RIA) technic. The levels of these antibodies fell subsequent to elimination of antigen inhalation. The RIA technic was used to demonstrate IgG, IgA and IgM antibody activity in single serum samples of four other patients with PBD, and this technic may have diagnostic value. Although no immunoglobulin E (IgE) antibody was demonstrable by RIA, a heat-liable, reaginic antibody was also detectable in the serum of the primary case. In addition, Arthus type cutaneous reactivity was passively transferred to the skin of a volunteer subject using heated serum from a patient with PBD.


Medical expulsive therapy for ureteral stones: where do we go from here?
Despite two decades of clinical use, the effectiveness of medical expulsive therapy (MET) for the noninvasive management of patients with ureteral stones has, in the past year, been called into in question. The primary aim of MET is to expedite stone passage, although it has also shown effectiveness in reducing time to stone passage, thus reducing the incidence of colic episodes, improving stone clearance and improving patients' quality of life. At least 11 systematic reviews and meta-analyses have been published showing clinical benefits of MET; however, the results of these analyses have been challenged by data from two randomized controlled, multicentre trials with large patient cohorts, thus providing higher quality evidence that MET is ineffective in patients with ureteral stones. Results of the various systematic reviews and meta-analyses have suggested that MET is effective, however, such analyses incorporate the biases and limitations of smaller cohort studies, resulting in their conclusions being based upon lower-quality evidence. Evidence for the use of MET for small (<5 mm) distal ureteral stones has weakened based on clinical trial data published in 2015. However, MET might remain effective in the management of larger ureteral stones (>5 mm).


Association between the expression of microRNAs and the response of patients with locally advanced rectal cancer to preoperative chemoradiotherapy.
Preoperative chemoradiotherapy (CRT) followed by mesorectal excision is the standard treatment for patients with locally advanced rectal cancer (LARC). The balance between treatment efficacy and toxicity is a major issue in the clinical management of these patients. There is a requirement for the identification of predictive molecular biomarkers for the response of patients to CRT. The present study aimed to analyze the association between microRNA (miRNA/miR) expression and treatment efficacy in patients with LARC who were treated with preoperative CRT. From previous clinical trials, 55 patients for the test cohort and 130 patients for the validation cohort met the criteria for the present investigation. Through reverse transcription-quantitative polymerase chain reaction analysis, the expression of miR-21, -31, -125b, -145 and -630 in the diagnostic biopsies was analyzed. The primary endpoint of tumor regression was evaluated according to Mandard's Tumor Regression Grade (TRG) system. In the test cohort, a significant association was identified between low miRNA-145 expression and TRG1+2 (P=0.0003). Similarly, this association was identified in the validation cohort, although it did not reach statistical significance. Furthermore, a significant association between high miRNA-21 expression and TRG1+2 (P=0.035) was observed in the validation cohort. The remaining miRNAs analyzed were not associated with TRG. The results of the present study highlight the clinical importance of miRNAs in LARC and underline the necessity for validation studies in this setting.


Linking mitochondrial and chloroplast retrograde signalling in plants.
Retrograde signalling refers to the regulation of nuclear gene expression in response to functional changes in organelles. In plants, the two energy-converting organelles, mitochondria and chloroplasts, are tightly coordinated to balance their activities. Although our understanding of components involved in retrograde signalling has greatly increased in the last decade, studies on the regulation of the two organelle signalling pathways have been largely independent. Thus, the mechanism of how mitochondrial and chloroplastic retrograde signals are integrated is largely unknown. Here, we summarize recent findings on the function of mitochondrial signalling components and their links to chloroplast retrograde responses. From this, a picture emerges showing that the major regulators are integrators of both organellar retrograde signalling pathways. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.


A case of AMMoL with 8/21 translocation and loss of the Y as probably secondary events.
The clinical, hematological, and cytogenetic characteristics of a male patient with AMMoL are described. Before treatment a clone with the complex karyotype 45,X,del(7)(q32), t(8;21)(q22;q22) was present in the bone marrow. During partial remission induced by cytostatics, the percentage of normal cells increased, and a cell line having a 46,XY,del(7)(q32) karyotype was found. After four therapy courses, when remission was complete, only chromosomally normal cells were seen. The cytogenetic data suggest that in this case the 8/21 translocation and loss of the Y chromosome were only secondary events.


The hearing aid effect in 2013.
The hearing aid effect is the term used to describe the assignment of negative attributes to individuals using hearing aids. The effect was first empirically identified in 1977 when it was reported that adults rating young children with and without hearing aids assigned negative attributes to the children depicted with hearing aids. Investigations in the 1980s and 1990s reported mixed results related to the extent of the hearing aid effect but continued to identify, on average, some negative attributes assigned to individuals wearing hearing aids. The specific aim of this research was to investigate whether the hearing aid effect has diminished in the past several decades by replicating the methods of previous studies for testing the hearing aid effect while using updated devices. Five device configurations were rated across eight attributes. RESULTS for each attribute were considered separately. A total of 24 adults judged pictures of young men wearing various ear level technologies across 8 attributes on a 7-point Likert scale. Five young men between ages 15 and 17 yr were photographed wearing each of five device configurations including (1) a standard-sized behind-the-ear (BTE) hearing aid coupled to an earmold with #13 tubing, (2) a mini-BTE hearing aid with a slim tube open-fit configuration, (3) a completely-in-the-canal hearing aid that could not be seen because of its location in the ear canal, (4) an earbud, and (5) a Bluetooth receiver. The 24 raters saw pictures of each of the 5 young men with each wearing one of the 5 devices so that devices and young men were never judged twice by the same observer. All judgments of each device, regardless of the young man modeling the device, were combined in the data analysis. The effect of device types on judgments was tested using a one-way between-participant analysis of variance. There was a significant difference on the judgment of age and trustworthiness level among the five devices. However, our post hoc analysis revealed that only two significant effects were present. People wearing a completely-in-the-canal aid (nothing visible in the ear) were rated significantly older than people wearing an earbud, and people wearing the standard-size BTE with earmold were rated significantly more trustworthy than people who wore the Bluetooth device. It was hypothesized that the hearing aid effect would be diminished in 2013 compared with data reported in the past. This proved to be the case, as no hearing aid condition was rated as more negative than any of the non-hearing aid device conditions. In fact, models wearing the standard-size BTE with earmold were rated as more trustworthy than models wearing the Bluetooth device. The standard-sized BTE with earmold condition is the configuration that can be directly compared with previous research because similar devices were used in those studies. These results indicate that the hearing aid effect has diminished, if not completely disappeared, in the 21st century.


Rare NOTCH3 Variants in a Chinese Population-Based Cohort and Its Relationship With Cerebral Small Vessel Disease.
Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.


Mediastinal extension of pancreatic pseudocyst--a case with review of topic and management guidelines.
Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. Extension of a pancreatic pseudocyst into the mediastinum is rare. We present a case of a 43-year-old male with a history of pancreatitis, who presented with dysphagia and was found to have a pancreatic pseudocyst. The pseudocyst was extending to the mediastinum and compressing the esophagus. It was successfully drained externally by computed tomography-guided catheter intervention. Depending on the location and size, patients may present with dyspnea, chest pain, palpitations, or dysphagia; sometimes with hemoptysis, acute respiratory compromise, or cardiogenic shock. There are no recommended guidelines for management. Watchful waiting for spontaneous regression, medical therapy, or drainage internally or externally with endoscopic, percutaneous, or open surgical approach are available options. Based on our own experience and literature review of such cases, we present a management strategy that can limit both complications and recurrence rate. This case emphasizes the importance of the possibility of mediastinal extension of a pancreatic pseudocyst and provides reference guidelines to approach the same.


Caregivers burden of older adults with chronic illnesses in the community: a cross-sectional study.
A chronic physical/mental disease not only has direct consequences for the chronically-ill older adults but can also alter the caregiver's life. The objectives of this study were to identify burdens of community-dwelling older adults, characteristics of caregivers, severity of caregiver burden, and to develop supportive strategies. Caregivers of community-dwelling older adults were randomly interviewed between February and March 2012. Information on baseline characteristics and caregiver burden using Zarit Burden Inventory (ZBI) was collected. One hundred-fifty caregivers were interviewed. The mean ZBI was 20.8 + 11.3 [95% CI 19.0, 22.7]. The majority of caregiver burden was classified as no burden (52%). The age of caregivers, self-reported health status and duration of care had a positive relationship with ZBI scores while self-reported income had a negative one. Caregiver burden among Thai community-dwelling elder persons was small as most of those cared for had uncomplicated illness but this might be underestimated. Caregiver-dependent factors were more strongly associated with high burden than patient characteristics. Healthcare providers should consider these factors for interventions to alleviate burden.


Postnatal changes in corneal curvature.
Corneal curvature was measured in 10 kittens from three litters and found to change significantly during postnatal development. From our data analysis, corneal curvature can be predicted from an animal's age and weight. To facilitate this prediciton for use in fitting contact lenses as occluders or diffusers in developmental studies, prediction equations are given as are expected weights of kittens as a function of age.


How do we apply video-assisted retroperitoneal necrosectomy with minimal access?
The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units. Nevertheless, infected necrosis or persistent multi-organ dysfunction are predictors of poor outcome. In these patients, there is still a need to perform necrosectomy. Open surgery results in extensive operative trauma and is associated with high morbidity and mortality. Therefore, several minimally invasive techniques have been developed recently. Retroperitoneal necrosectomy has been shown to be safe and to reduce morbidity and mortality compared to the open procedure. In an instructive video, we show the technique of video-assisted retroperitoneal necrosectomy with minimal access, including the preoperative percutaneous drainage and several accesses to the necrosis. We discuss the indication for retroperitoneal necrosectomy as well as the optimal time point of the intervention. In the management of acute necrotizing pancreatitis, the multidisciplinary approach is crucial. The initial treatment by the intensive care units should be extended to intervention or surgery in case of infected necrosis or persistent multi-organ dysfunction. We show here a minimal access solution with the placement of a percutaneous drain followed by video-assisted retroperitoneal necrosectomy.