Stereotactic Radiosurgery Results for Patients With Brain Metastases From Gastrointestinal Cancer: A Retrospective Cohort Study of 802 Patients With GI-GPA Validity Test.
The role of stereotactic radiosurgery (SRS) alone for patients with gastrointestinal (GI) cancer has yet to be established based on a large patient series. We analyzed post-SRS treatment results and reappraised whether either the GI graded prognostic assessment (GPA) system or modified-recursive partitioning assessment (M-RPA) system was applicable to our 802 SRS-treated patients with GI cancer with brain metastases. This was an institutional review board approved retrospective cohort study 2 database comprising 802 patients with GI cancer treated with gamma-knife SRS by 2 experienced neurosurgeons during the 1998 to 2018 period. The Kaplan-Meier method was applied to determine post-SRS survival times, and competing risk analyses were used to estimate cumulative incidences of the secondary endpoints. The median survival time (MST; months) after SRS was 5.7. With the GI GPA system, MSTs were 3.5/6.1/7.7/11.0 in the 4 subgroups, that is, 0 to 1.0/1.5 to 2.0/2.5 to 3.0/3.5 to 4.0, respectively (stratified P < .0001). However, there was no significant MST difference between 2 of the subgroups, GI-GPA 1.5 to 2.0 and 2.5 to 3.0 (P = .073). In contrast, using the M-RPA system, 3 plot lines corresponding to the 3 subgroups showed no overlap and the MST differences between the subgroups with M-RPA were 1 + 2a versus 2b (P < .0001) and 2b versus 2c + 3 (P < .0001). Better Karnofsky performance status score, solitary tumor, well-controlled primary cancer, and the absence of extracerebral metastases were shown by multivariable analysis to be significant predictors of longer survival. The crude and cumulative incidences of neurologic death, neurologic deterioration, local recurrence, salvage whole brain radiation therapy, and SRS-related complications did not differ significantly between the 2 patient groups, with upper and lower GI cancers. This study clearly demonstrated the usefulness of the GI GPA. Patients with GI GPA 1.5 to 2.0 or better or M-RPA 2b or better are considered to be favorable candidates for treatment with SRS alone.


Absent and anomalous superior oblique and superior rectus muscles.
Anomalous or absent superior oblique or superior rectus muscles have usually been reported in the context of craniofacial disorders. We report a case of absent superior oblique and superior rectus muscles in the right eye and anomalous superior oblique and superior rectus muscles in the left eye in an otherwise healthy 4-year-old boy. The possibility of anomalous or absent extraocular muscles should be considered in unusual and complex presentations of strabismus, and alternative surgical strategies should be considered preoperatively. The clinical triad of levator palpebrae superioris, superior rectus and superior oblique dysfunction should suggest embryologic abnormalities of these muscles.


Nutritional correlates of the "lean season": effects of seasonality and frugivory on the nutritional ecology of diademed sifakas.
Primate field studies often identify "lean seasons," when preferred foods are scarce, and lower-quality, abundant foods (fallback foods) are consumed. Here, we quantify the nutritional implications of these terms for two diademed sifaka groups (Propithecus diadema) in Madagascar, using detailed feeding observations and chemical analyses of foods. In particular, we sought to understand 1) how macronutrient and energy intakes vary seasonally, including whether these intakes respond in similar or divergent ways; 2) how the amount of food ingested varies seasonally (including whether changes in amount eaten may compensate for altered food quality); and 3) correlations between these variables and the degree of frugivory. In the lean season, sifakas shifted to non-fruit foods (leaves and flowers), which tended to be high in protein while low in other macronutrients and energy, but the average composition of the most used foods in each season was similar. They also showed dramatic decreases in feeding time, food ingested, and consequently, daily intake of macronutrients and energy. The degree of frugivory in the daily diet was a strong positive predictor of feeding time, amount ingested and all macronutrient and energy intakes, though season had an independent effect. These results suggest that factors restricting how much food can be eaten (e.g., handling time, availability, or intrinsic characteristics like fiber and plant secondary metabolites) can be more important than the nutritional composition of foods themselves in determining nutritional outcomes-a finding with relevance for understanding seasonal changes in behavior, life history strategies, competitive regimes, and conservation planning.


Rehabilitation outcomes in persons with spina bifida: A randomised controlled trial.
To assess the effectiveness of an interdisciplinary ambulatory rehabilitation programme for persons with spina bifida in an Australian community cohort. Fifty-four participants randomized to a treatment group (n = 27) for a high-intensity rehabilitation programme (with cognitive behavioural therapy) or a control group (n = 27) comprising usual care. Outcome measures include: Disability: Urogenital Distress Inventory (UDI6), Incontinence Impact Questionnaire-7 (IIQ7), American Urological Association Symptom Index (AUA), Wexner-Faecal Incontinence Score (WFIS), Neurological Disability Scale (NDS); Depression, Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), Brief COPE Scale, Genera-lized Self-efficacy Scale (GSE). Assessments were made at baseline and 3-months post-intervention. Adjusted for baseline disease and demographic covariates, the intervention group improved significantly at 3-month follow-up for primary and secondary outcomes, with moderate to large effect sizes (r): urinary/bowel dysfunction (AUA, UDI6, IIQ7, WFIS) (p < 0.001 for all, r = 0.4-0.7); and cognitive function: NDS "cognitive" and "mood" (p < 0.01, r = 0.6 for both); DASS "depression", "anxiety" and "stress" (p < 0.001 for all, r = 0.5-0.7); MQOL total (p = 0.013, r = 0.5), "psychological symptoms" (p < 0.001, r = 0.8); "active coping" (p = 0.035) and "self-efficacy" scores (GSE p < 0.001). No difference between groups was noted in other subscales. Targeted rehabilitation can improve clinical outcomes in persons with spina bifida. Further research is needed for longer-term outcomes related to "ageing" and participation restriction.


Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.
Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.


Exploring toxicological interactions in a changing sea: The case of the alkaloids caffeine and caulerpin.
The bisindolic alkaloid caulerpin (CAU) is a bioactive compound isolated from green algae of the genus Caulerpa that are highly invasive in the Mediterranean Sea. On the other side, the purine alkaloid caffeine (CAF) is one of the most globally consumed psychoactive substances and a widespread anthropogenic water pollutant. Both compounds display a large panel of biological properties and are well known to accumulate in the tissues of aquatic organisms and, in certain circumstances, co-occur in the human diet. On this premise, the present study aimed to investigate possible synergistic interactions between CAU and CAF by using the bivalve Mytilus galloprovincialis as a model organism. Mussels were exposed to CAF via medium while they were fed food enriched with CAU. After treatments, biochemical analysis confirmed the toxic potential of CAF, with increased AChE activity and lipid peroxidation. Also, histopathological alterations were observed in the gills and digestive tubules. The NMR-based metabolomic analysis detected higher levels of free amino acids under CAF treatments. Conversely, the food administration of CAU did not affect the above toxicological biomarkers. In addition, we did not observe any cumulative effect between CAF and CAU toward increased cellular damage and neurotoxicity. On the other hand, a possible action of CAU in decreasing CAF toxicity could be hypothesized based on our results. This hypothesis is supported by the activity of CAU as an agonist of peroxisome proliferator-activated receptors (PPARs). PPARs mediate xenobiotic detoxification via cytochromes P450, which is involved in CAF metabolism. Overall, the results obtained not only rule out any cumulative adverse effects of CAF and CAU but also encourage further research to evaluate the possible use of CAU, a compound easily obtained through the valorization of biomass from invasive species, as a food additive to improve the clearance of xenobiotics.


Genomic Assays in Ductal Carcinoma In Situ: Implications for Management Decisions.
Breast cancer is the most common cancer in women and a leading cause of cancer death worldwide. The management of breast cancer depends on clinical and pathologic prognostic factors that help guide patient treatment. Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer with an unpredictable risk of either progression to invasive disease or recurrence. To evaluate the utilization of the DCIS score in a large single-institution population and understand reasons for avoidance in eligible patients. A retrospective chart review of eligible patients with pure DCIS treated by lumpectomy (January 2011-May 2015) was performed. Patients were considered eligible for the assay if they met the Eastern Cooperative Oncology Group E5194 pathology criteria. All of the patients underwent breast-conserving surgery and were estrogen receptor positive. Of 182 estrogen receptor-positive patients with DCIS who underwent breast-conserving surgery, 31 (17%) had a DCIS assay performed; however, most of the patients did not have a DCIS score assay performed, yet 47.9% of this cohort would have met the pathologic eligibility criteria. Conversely, 82.5% of the patients having the DCIS score evaluated actually met these criteria. Tumor size, grade, ER status, and calcifications were drivers of patient selection for 12-gene assay use. E5194 eligibility criteria selected for low risk population. Although a large proportion of patients met eligibility criteria, DCIS Score was infrequently considered for recurrence risk estimation. When performed, assay scores supported omission of radiation for over 75% of cases.


Comparison of EHR-based diagnosis documentation locations to a gold standard for risk stratification in patients with multiple chronic conditions.
To measure variation among four different Electronic Health Record (EHR) system documentation locations versus 'gold standard' manual chart review for risk stratification in patients with multiple chronic illnesses. Adults seen in primary care with EHR evidence of at least one of 13 conditions were included. EHRs were manually reviewed to determine presence of active diagnoses, and risk scores were calculated using three different methodologies and five EHR documentation locations. Claims data were used to assess cost and utilization for the following year. Descriptive and diagnostic statistics were calculated for each EHR location. Criterion validity testing compared the gold standard verified diagnoses versus other EHR locations and risk scores in predicting future cost and utilization. Nine hundred patients had 2,179 probable diagnoses. About 70% of the diagnoses from the EHR were verified by gold standard. For a subset of patients having baseline and prediction year data (n=750), modeling showed that the gold standard was the best predictor of outcomes on average for a subset of patients that had these data. However, combining all data sources together had nearly equivalent performance for prediction as the gold standard. EHR data locations were inaccurate 30% of the time, leading to improvement in overall modeling from a gold standard from chart review for individual diagnoses. However, the impact on identification of the highest risk patients was minor, and combining data from different EHR locations was equivalent to gold standard performance. The reviewer's ability to identify a diagnosis as correct was influenced by a variety of factors, including completeness, temporality, and perceived accuracy of chart data.


Optimizing Protein Fiber Spinning to Develop Plant-Based Meat Analogs via Rheological and Physicochemical Analyses.
The substitution of meat products in the human diet with plant-based analogs is growing due to environmental, ethical, and health reasons. In this study, the potential of fiber-spinning technology was explored to spin protein fiber mimicking the structural element of meat muscle for the purpose of developing plant-based meat analogs. Overall, this approach involved extruding fine fibers and then assembling them into hierarchical fibrous structures resembling those found in whole muscle meat products. Considering the nutritional facts and to help build muscle fiber, soy protein, polysaccharide (pectin, xanthan gum, or carrageenan), plasticizer (glycerol), and water were used in the formulations to spin into fibers using an extruder with circular orifice dies. Extrudability and thermal and rheological properties were assessed to characterize the properties of the spun fiber. The extrusion trials showed that the presence of the polysaccharides increased the cohesiveness of the fibers. The properties of the fibers produced also depended on the temperature used during extrusion, varying from pasty gels to elastic strands. The extrudability of the fibers was related to the rheological properties (tan δ) of the formulations. This study demonstrated that fiber-spinning technology can be used to produce fibrous materials from plant-derived ingredients. However, the formulation and operating conditions must be optimized to obtain desirable physicochemical and functional attributes in the fibers produced.


[Mechanisms of development of cardiac insufficiency in old age].
Tests conducted with adult (8--10 months) and old (26--28 months) rats brought evidence that in ageing the cardiac ejection, dp/dt max, contractility index, the ATP concentration, that of creatinophosphate, glycogen, pyruvate decline, the phosphorylation coefficient, the lactate content increase, while the level of water-soluble proteins and collagen diminishes and that of water-insoluble ones decreases. In adult rats hemodynamics and myocardial contractility change but unsignificantly on the 4--6th day after coarctation of the aorta, whereas in the old ones there occur functional and metabolic alterations in the heart that are indicative of a developing cardiac insufficiency. The age-specific differences persist also on the 14--16th day following coarctation of the aorta. During these periods the weight of the heart, the content of the myofribrillary proteins and collagen are on the rise, whereas in the old ones the weight of the heart remains unchanged and the level of water-soluble protein drops. Changes in the properties of the actomyosin complex, disruption of the calcium pump, shifts in the system of the energy generation, limitation of potential possibilities incident to the systems of protein biosynthesis in the myocardial cell, all this leads to the development of cardiac incompetence following loading in old age.


Correlation of clinical and MRI staging in cervical carcinoma treated with radiation therapy: a single-center experience.
To correlate clinical and MRI findings in patients with cervical carcinoma treated with radiation therapy (RT). Forty-two patients with pretreatment IB-IVA cervical carcinoma were included in this retrospective study. Pre- and post-treatment MRI findings of the patients were reevaluated and compared with clinical staging. Six-month, one-year, and two-year follow-up imaging by MR was performed for 36, 20, and 7 patients, respectively. The correlation between clinical and MRI findings was assessed by a Spearman's rho (rank correlation) test. Univariate analyses were performed to identify the prognostic significance of the tumor volume and lymph node status. Pre-treatment correlations between MRI and clinical findings for diagnoses without parametrial invasion, with parametrial invasion, and with pelvic sidewall invasion were 71.0%, 64.7%, and 15.8%, respectively. According to the Spearman's rho (rank correlation) test, the parametrial invasion correlation was poor (r = 0.410, P < 0.01). The correlation of clinical and MRI findings at 6 months was 88.9% (r = 0.674, P < 0.0001). In advanced cervical cancer, the correlation of clinical and MRI staging prior to neoadjuvant RT was low despite a high correspondence in the assessment of local response after RT.


Infected total knee arthroplasty treated with arthrodesis using a modular nail.
Failed treatment of infected total knee replacement presents few attractive surgical options. Knee arthrodesis is challenging surgically and can be complicated by nonunion, malunion, or recurrent infection. Recently, a modular titanium intramedullary nail has been used in an attempt to reduce the incidence of nonunion and the rate of complications. In the present study, a review of the results of knee arthrodesis after infected total knee arthroplasty in 21 patients at three large academic institutions was performed. All patients were followed up for a mean of 2.4 years (range, 2-7.5 years). The mean age of the patients was 64 years. The mean number of previous operations was four (range, 2-9 operations). A solid arthrodesis was achieved without additional surgical treatment in 20 of 21 patients (95%). The mean time to fusion was 6.3 months. The one patient who suffered a nonunion achieved fusion after a subsequent bone grafting procedure. Based on the present study, intramedullary arthrodesis with a coupled titanium nail, is a reliable, effective method of achieving fusion after infection of a total knee arthroplasty. This procedure resulted in a high rate of fusion and a lower rate of complications when compared with traditional methods of arthrodesis.


Experience with more than 500 minimally invasive hepatic procedures.
To evaluate our experience with more than 500 minimally invasive hepatic procedures. Recent data have confirmed the safety and efficacy of minimally invasive liver surgery. Despite these reports, no programmatic approach to minimally invasive liver surgery has been proposed. We retrospectively reviewed all patients who underwent a minimally invasive procedure for the management of hepatic tumors between January 2001 and April 2008. Patients were divided into 3 groups: laparoscopy with intraoperative ultrasound and biopsy only, laparoscopic radiofrequency ablation (RFA), and minimally invasive resection. To compare the various forms of surgery, we analyzed the incidence of complications, tumor recurrence, mortality, and cost. Statistical analysis was performed using chi(2) analysis, Student t test, Kaplan-Meier survival analysis with the log-rank test, and multivariable Cox models. A total of 590 minimally invasive hepatic procedures were performed during 489 operative interventions. The representative tumor histologies were: hepatocellular carcinoma (HCC; N = 210), colorectal carcinoma (N = 40), miscellaneous liver metastases (N = 42), biliary cancer (N = 20), and benign tumors (N = 176). Thirty-five patients underwent laparoscopic ultrasound and confirmatory biopsy alone; 201 patients underwent 240 laparoscopic RFAs, and 253 patients underwent 306 minimally invasive resections. Conversion rates to open surgery for the RFA and resection group were 2% overall. One hundred ninety-nine (40.6%) patients were cirrhotic; 31 resections were performed in cirrhotic patients. Complication and mortality rates for RFA and resection were comparable (11% vs. 16%, and 1.5% vs. 1.6%). However, complication rates (14% vs. 29%; P = 0.02) and mortality (0.3% vs. 9.7%; P = 0.006) rates were higher in the cirrhotic versus noncirrhotic resection group. Overall recurrence rates for RFA and resection groups were 24% and 23%, respectively. Local recurrence rates were higher in the RFA group (6.3% versus 1.5%; P < 0.06). Overall patient survival differed between HCC patients receiving RFA alone and those receiving RFA and OLT (P < 0.0001). Overall survival for cancer patients receiving RFA versus resection differed significantly when unadjusted for other covariates (P = 0.01), and remained marginally significant in a multivariable model (P = 0.056). Minimally invasive hepatic surgery has become a viable alternative to open hepatic surgery. Our present data are equivalent or superior to those encountered in any large open series. Our experience with RFA confirms a low local recurrence rate and an excellent technique for bridging patients to transplantation. Morbidity and mortality rates for minimally invasive hepatic resections in cirrhotics, is similar to other reported open resection series. This series confirmed excellent interim survival rates after laparoscopic HR and superiority over RFA in the treatment of cancer, with significantly lower local tumor recurrence rate.


A metal-binding member of the late embryogenesis abundant protein family transports iron in the phloem of Ricinus communis L.
The transport of metal micronutrients to developing organs in a plant is mediated primarily by the sieve elements. Ligands are thought to form complexes with the free ions in order to prevent cellular damage, but no binding partners have been unequivocally identified from plants so far. This study has used the phloem-mediated transport of micronutrients during the germination of the castor bean seedling to identify an iron transport protein (ITP). It is demonstrated that essentially all (55)Fe fed to seedlings is associated with the protein fraction of phloem exudate. It is shown that ITP carries iron in vivo and binds additional iron in vitro. ITP was purified to homogeneity from minute amounts of phloem exudate using immobilized metal ion affinity chromatography. It preferentially binds to Fe(3+) but not to Fe(2+) and also complexes Cu(2+), Zn(2+), and Mn(2+) in vitro. The corresponding cDNA of ITP was cloned using internal peptide fragments. The deduced protein of 96 amino acids shows high similarity to the stress-related family of late embryogenesis abundant proteins. Its predicted characteristics and its RNA expression pattern are consistent with a function in metal ion binding. The ITP from Ricinus provides the first identified micronutrient binding partner for phloem-mediated long distance transport in plants and is the first member of the late embryogenesis abundant protein family shown to have such a function.


A phylogenomic study of birds reveals their evolutionary history.
Deep avian evolutionary relationships have been difficult to resolve as a result of a putative explosive radiation. Our study examined approximately 32 kilobases of aligned nuclear DNA sequences from 19 independent loci for 169 species, representing all major extant groups, and recovered a robust phylogeny from a genome-wide signal supported by multiple analytical methods. We documented well-supported, previously unrecognized interordinal relationships (such as a sister relationship between passerines and parrots) and corroborated previously contentious groupings (such as flamingos and grebes). Our conclusions challenge current classifications and alter our understanding of trait evolution; for example, some diurnal birds evolved from nocturnal ancestors. Our results provide a valuable resource for phylogenetic and comparative studies in birds.


[The sphincter-related biliodigestive anastomoses in anomalies of bile ducts].
The authors made an analysis of anomalies of the bile ducts with special reference to anatomical peculiarities and iatrogenic lesions of the bile ducts. The anomalies of bile ducts were found in 2.07% of 676 patients operated on for complicated cholelithiasis. Primary operative interventions and reoperations in the patients were completed with the formation of the constriction-biliodigestive anastomoses of different levels having antireflux functions. The authors describe the operation technique and results of the treatment of bile duct obstruction.


Dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium analogs in cultured neurons: relationship to the dopamine uptake system and inhibition of mitochondrial respiration.
Several analogs of 1-methyl-4-phenylpyridinium (MPP+) were evaluated for their affinity for the dopamine uptake system and their ability to inhibit NADH dehydrogenase (complex I) of the mitochondrial electron-transport chain. Moreover, these compounds were tested for their ability to cause selective dopaminergic neurotoxicity in cultured mesencephalic neurons. Simultaneous [3H]dopamine and gamma-amino-[14C]butyric acid uptake and immunocytochemical techniques were used as indices of neuronal damage in cultured cells. The compounds that were potent and selective dopaminergic neurotoxins had high affinity for the dopamine transport system, as measured by their ability to cause dopamine release, and were similar to MPP+ in inhibiting mitochondrial respiration. One compound (1-methyl-4-phenylpyrimidinium) had high affinity for the dopamine uptake system but was a weak inhibitor of mitochondrial respiration and, accordingly, was not neurotoxic. The 4'-alkylated analogs of MPP+, which were poor substrates for the dopamine uptake system and extremely potent inhibitors of mitochondrial respiration, caused a nonselective damage of neurons in culture. Analogs that were not substrates for the dopamine carrier and not inhibitors of mitochondrial respiration were not neurotoxic. This study describes the neurotoxicity of a number of analogs of MPP+ and highlights the importance of the dopamine uptake system and the ability to inhibit mitochondrial respiration as critical processes in conferring selectivity and neurotoxicity, respectively, to MPP+ and analogs, for dopaminergic neurons in culture.


Distribution of actin-binding protein and myosin in macrophages during spreading and phagocytosis.
Actin-binding protein (ABP) and myosin are proteins that influence the rigidity and movement, respectively, of actin filaments in vitro. We examined the distribution of ABP and myosin molecules in acetone-fixed rabbit lung macrophages by means of immunofluorescence. The staining for both of these proteins in unspread cells was quite uniform, but was reduced in the nucleus and concentrated slightly in the periphery. The peripheral accumulation of staining attenuated in uniformly spread cells, although filopodia and hyaline veils definitely stained. In cells fixed during ingestion of yeast particles, the brightest staining correlated with the disposition of organelle-excluding pseudopodia initially surrounding the yeast. After phagocytosis was complete and the yeasts resided in intracellular vacuoles, no concentration of staining around the ingested yeasts was detectable. We conclude that ABP and myosin molecules are components of the structural unit of the cell responsible for spreading and phagocytosis, the hyaline cortex, a region known to be rich in actin filaments. The findings are consistent with the theory that these molecules control the rigidity and movement of filaments in the periphery of the living macrophage.


Pulmonary interstitial emphysema is a risk factor for poor prognosis and a cause of air leaks.
Pulmonary interstitial emphysema is a rare, abnormal condition in which air pressure from the alveolar airspace tears the adjacent interstitial tissues of the lung and causes the formation of cystic spaces. Pulmonary interstitial emphysema is a known indication for mechanical ventilation in premature infants with neonatal respiratory distress syndrome, and it can be observed in various types of interstitial lung disease. Nevertheless, its pathogenesis and clinical impact remain unknown. We reviewed data from 433 cases of interstitial lung disease from an external consultation archive. Multidisciplinary diagnosis along with clinical and follow-up data, including events of air leaks such as pneumothorax and mediastinal emphysema, were obtained and compared to those of 150 control cases of interstitial lung disease without pulmonary interstitial emphysema. We found 22 (5.1%) cases of interstitial lung disease with pulmonary interstitial emphysema. The diagnoses included idiopathic pulmonary fibrosis (5/22 [22.7%]), pleuroparenchymal fibroelastosis (4/22 [18.2%]), chronic hypersensitivity pneumonia (4/22 [18.2%]), and others (9/22 [40.9%]). Cases involving pulmonary interstitial emphysema demonstrated a significantly higher frequency of air leaks than did those without pulmonary interstitial emphysema (12/22 [54.5%] versus 23/150 [15.3%]; P < 0.001; odds ratio, 6.63) and were associated with worse prognosis (P = 0.009 [log-rank]) and a lower median percent forced vital capacity (73.2% versus 84.0%; P < 0.001). We found that pulmonary interstitial emphysema is an independent factor for poor prognosis, which also shows a trend to cause air leaks, including pneumothorax and mediastinal emphysema.


Fresh meat and further processing characteristics of ham muscles from finishing pigs fed ractopamine hydrochloride.
Ractopamine hydrochloride (RAC) has consistently led to an advantage in carcass cutting yields of finishing pigs and remains a common feed additive in US finishing pig diets. Less is known about the effect of RAC on further processing characteristics. Some researchers have reported advantages in ultimate pH of the LM in pigs fed RAC. If a greater ultimate pH was also observed in hams, the increased pH could affect further processing characteristics and lead to better protein interaction and improved textural properties. The objective of this experiment was to determine if RAC-fed pigs yielded hams with a greater ultimate pH, and if so, whether or not that advantage improves textural properties and water retention of further processed hams. Two hundred hams from barrows and gilts fed RAC or control diets were selected based on HCW. Hams were fabricated into 5 separate pieces to determine cutting yields, and 6 muscles were evaluated for ultimate pH. Hams were processed to make cured and smoked hams. Ractopamine increased cutting yields of the whole ham (P < 0.0001), inside (P < 0.01), outside (P < 0.01), and knuckle (P < 0.01) when expressed as a percentage of chilled side weight. Ultimate pH of the rectus femoris, vastus lateralis, and semitendinosus were all 0.06 pH units greater (P < 0.05), the biceps femoris was 0.04 pH units greater (P = 0.02), and the semimembranosus and adductor muscles were 0.03 pH units greater in pigs fed 7.4 mg/kg of RAC when compared with control pigs. Cured hams from RAC-fed pigs were heavier at all stages of production. No differences were detected in binding strengths (P = 0.88) or protein fat-free values (P = 0.13) between RAC (9.06 kg and 20.37) and control hams (9.01 kg and 20.13). Ractopamine increased cutting yields, total weight of cured hams, and ultimate muscle pH. Ractopamine can be fed to pigs to achieve the desired growth characteristic advantages and cutting yields without affecting further processed ham characteristics.


Impact of indian public health standards for rural health care facilities on national programme for control of deafness in India: The results of a cohort study.
In National Programme for Prevention and Control of Deafness (NPPCD), the management of ear diseases of rural India is now guided by Revised Indian Public Health Standards (IPHS) for Rural Health Facilities for providing quality ear care. However, despite the IPHS existence, coverage and quality ear care is questionable. Moreover, this issue has not yet been studied till now in the Indian context. The objective of the study was to assess the role of Private Medical College Training Center (Rural Health Training Centre [RHTC]) in augmenting quality of ear care services in NPPCD at district level by adopting IPHS Standards. A combined retrospective and prospective cohort study was done at RHTC of a Medical College in West Uttar Pradesh from January 1, 2013, to December 31, 2017, by retrospective approach of selecting all ear patients (n = 3840) and prospective way of assessing the impact of IPHS for ear care. The semi-structured Pro forma was used in exploring the coverage and quality of ear care. The data were analyzed by Epi Info version 7.2. Out of total 4817 ear, nose, and throat (ENT) patients, the majority of ear patients (n = 3840) were initially dissatisfied with coverage and quality of ear services provided by ENT specialists at RHTC. However, when IPHS exposure was given from July 1, 2015 to December 31, 2017, not only majority of patients were satisfied (n = 3110, 81%) but also ear curative treatment was significantly higher (n = 2120, 68.1% vs. n = 130, 17.8%, odds ratio = 9.8, RR = 1.5, P < 0.00001). Adherence to IPHS in NPPCD is essential for delivering better ear care by RHTC through primary health-care approach.


3D LIDAR imaging using Ge-on-Si single-photon avalanche diode detectors.
We present a scanning light detection and ranging (LIDAR) system incorporating an individual Ge-on-Si single-photon avalanche diode (SPAD) detector for depth and intensity imaging in the short-wavelength infrared region. The time-correlated single-photon counting technique was used to determine the return photon time-of-flight for target depth information. In laboratory demonstrations, depth and intensity reconstructions were made of targets at short range, using advanced image processing algorithms tailored for the analysis of single-photon time-of-flight data. These laboratory measurements were used to predict the performance of the single-photon LIDAR system at longer ranges, providing estimations that sub-milliwatt average power levels would be required for kilometer range depth measurements.


Structure-activity relationships for the selectivity of hepatitis C virus NS3 protease inhibitors.
The selectivity of hepatitis C virus (HCV) non-structural protein 3 (NS3) protease inhibitors was determined by evaluating their inhibitory effect on other serine proteases (human leukocyte elastase (HLE), porcine pancreatic elastase (PPE), bovine pancreatic chymotrypsin (BPC)) and a cysteine protease (cathepsin B). For these peptide inhibitors, the P1-side chain and the C-terminal group were the major determinants of selectivity. Inhibitors with electrophilic C-terminal residues were generally non-selective while compounds with non-electrophilic C-terminal residues were more selective. Furthermore, compounds with P1 aminobutyric acid residues were non-selective, while 1-aminocyclopropane-1-carboxylic acid (ACPC) and norvaline-based inhibitors were generally selective. The most potent and selective inhibitors of NS3 protease tested contained a non-electrophilic phenyl acyl sulfonamide C-terminal residue. HLE was most likely to be inhibited by the HCV protease inhibitors, in agreement with similar substrate specificities for these enzymes. The identified structure-activity relationships for selectivity are of significance for design of selective HCV NS3 protease inhibitors.


Detection of borreliacidal antibodies by flow cytometry.
Lyme disease is a multisystem disorder that usually begins with a skin lesion called erythema migrans and with constitutional symptoms. If the disease is left untreated or treated inappropriately, dissemination of the organism can lead to more severe sequelae, including nervous system disorders or arthritis. Vaccinations with B. burgdorferi or several individual B. burgdorferi proteins induce borreliacidal antibodies that provide protection against infection by inducing a complement cascade that kills the spirochetes without the necessity of scavenging by phagocytic cells. Detection of borreliacidal antibodies is therefore useful for serodiagnosing Lyme disease and monitoring immune status after vaccination. This unit provides a technique for detecting anti-B. burgdorferi antibodies, as well as for preparing and determining the quality of Barbour-Stoenner-Kelly (BSK medium) and complement. In addition, methods are provided for preparation of a B. burgdorferi stock and Mueller-Hinton agar containing Bacillus subtilis spores.


Fluctuation analysis of nonideal shot noise. Application to the neuromuscular junction.
Procedures are described for analyzing shot noise and determining the waveform, w(t), mean amplitude, (h), and mean rate of occurrence, (r), of the shots under a variety of nonideal conditions that include: (a) slow, spurious changes in the mean, (b) nonstationary shot rates, (c) nonuniform distribution of shot amplitudes, and (d) nonlinear summation of the shots. The procedures are based upon Rice's (1944. Bell Telephone System Journal. 23: 282-332) extension of Campbell's theorem to the second (variance), lambda 2, third (skew), lambda 3, and fourth, lambda 4, semi-invariants (cumulants) of the noise. It is shown that the spectra of lambda 2 and lambda 3 of nonstationary shot noise contain a set of components that are proportional to (r) and arise from w(t), and a set of components that are independent of (r) and arise from the temporal variations in r(t). Since the latter components are additive and are limited by the bandwidth of r(t), they can be removed by appropriate filters; then (r) and (h) can be determined from the lambda 2 and lambda 3 of the filtered noise. We also show that a factor related to the ratio (lambda 3)2/(lambda 2)(lambda 4) monitors the spread in the distribution of shot amplitudes and can be used to correct the estimates of (r) and (h) for the effects of that spread, if the shape of the distribution is known and if r(t) is stationary. The accuracy of the measurements of lambda 4 is assessed and corrections for the effects of nonlinear summation of lambda 2, lambda 3, and lambda 4 are derived. The procedures give valid results when they are used to analyze shot noise produced by the (linear) summation of simulated miniature endplate potentials, which are generated either at nonstationary rates or with a distribution of amplitudes.


Goal-setting, self-efficacy, and memory performance in older and younger adults.
Research in field and laboratory settings has shown that goals lead to improved self-efficacy and performance, especially when individuals also receive positive feedback. The present study extended goal-setting theory to examine self-set goals and feedback in relation to younger and older adults' memory performance and self-efficacy. Following a baseline recall trial, participants completed three shopping list recall trials. Half of the participants were instructed to set goals for the three experimental trials, and half in each goal condition received performance feedback after each trial. Young adults' self-efficacy, clustering, and recall exceeded that of older adults. Goal setting increased self-efficacy for younger but not older adults, and it did not affect performance. Younger adults and participants in the feedback condition increased their goals across trials, as did participants for whom feedback indicated success. These data provide a first look at the motivational impact of feedback and self-set recall goals in memory aging. Additional study is needed to understand the interactive effects of type of feedback, memory task difficulty, and type of goal setting at different ages.


Photochemistry of oil in marine systems: developments since the Deepwater Horizon spill.
Oil spills represent a major source of negative environmental impacts in marine systems. Despite many decades of research on oil spill behavior, photochemistry was neglected as a major factor in the fate of oil spilled in marine systems. Subsequent to the Deepwater Horizon oil spill, numerous studies using varied approaches have demonstrated the importance of photochemistry, including short-term impacts (hours to days) that were previously unrecognized. These studies have demonstrated the importance of photochemistry in the overall oil transformation after a spill and more specifically the impacts on emulsification, oxygenation, and microbial interactions. In addition to new perspectives, advances in analytical approaches have allowed an improved understanding of oil photochemistry after maritime spill. Although the literature on the Deepwater Horizon spill is extensive, this review focuses only on studies relevant to the advances in oil photochemistry understanding since the Deepwater Horizon spill.


Activated hepatic stellate cells induce tumor progression of neoplastic hepatocytes in a TGF-beta dependent fashion.
The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-beta signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of beta-catenin. Genetic interference with TGF-beta signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear beta-catenin accumulation, indicating a crosstalk between TGF-beta and beta-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-beta dependent fashion by inducing autocrine TGF-beta signaling and nuclear beta-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-beta signaling is highly promising in liver cancer therapy.


Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel.
Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic β-cell function. Despite the significance of estrogen hormones for regulation of glucose metabolism, little is known about the roles of endogenous estrogen metabolites in modulating pancreatic β-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic β-cells. We show that catechol estrogens, hydroxylated at positions C2 and C4 of the steroid A ring, rapidly potentiated glucose-induced insulin secretion via a nongenomic mechanism. 2-Hydroxyestrone, the most abundant endogenous estrogen metabolite, was more efficacious in stimulating insulin secretion than any other tested catechol estrogens. In insulin-secreting cells, catechol estrogens produced rapid activation of calcium influx and elevation in cytosolic free calcium. Catechol estrogens also generated sustained elevations in cytosolic free calcium and evoked inward ion current in HEK293 cells expressing the transient receptor potential A1 (TRPA1) cation channel. Calcium influx and insulin secretion stimulated by estrogen metabolites were dependent on the TRPA1 activity and inhibited with the channel-specific pharmacological antagonists or the siRNA. Our results suggest the role of estrogen metabolism in a direct regulation of TRPA1 activity with potential implications for metabolic diseases.


Astrocytes in primary culture have chemically activated sodium channels.
The effects of two neurotoxins, veratridine and alpha-scorpion toxin II, on the resting potential (RMP) of identified astrocytes in primary cell culture were studied using standard electophysiological techniques. Veratridine caused either a series of transient depolarizations or a single sustained depolarization. alpha-Scorpion toxin (II), which alone had no effect on the RMP, increased the duration of the veratridine-induced transient depolarizations. The depolarization caused by veratridine, or veratridine plus alpha-scorpion toxin II, was reversibly inhibited by tetrodotoxin and was reversibly reduced in magnitude by reductions of the external sodium concentration. Cells that were depolarized by veratridine were shown to contain glial fibrillary acidic protein, a marker considered specific for astrocytes. The effect of long-term (10 sec) hyperpolarizing and depolarizing current pulses on the RMP were also studied using two microelectrodes, i.e., dual impalement. In the absence of veratridine, the RMP returned to its original value after termination of the hyperpolarizing current, and the current-voltage relationship was found to be linear over a wide range of membrane potentials. In the presence of veratridine, termination of the hyperpolarizing current produced a transient depolarization that was sensitive to tetrodotoxin. Depolarizing current pulses were without effect. These results show that astrocytes in primary culture have a chemically inducible Na+ channel that appears to be voltage-dependent.


The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.
Background Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.


[Colonization of the rat gastrointestinal tract by Staphylococcus aureus biotopes].
Six groups of Wistar rats were fed different diets. Intestinal mural and fecal microflora was analysed. Four types of colonization of trointestinal tract were distinguished after intragastric administration of Staphylococcus aureus depending on a variety of factors affecting composition of microbial communities. Mechanisms of colonization ensuring circulation of S. aureus in the gastrointestinal tract are discussed.


Intellectual evaluation of children exposed to phthalate-tainted products after the 2011 Taiwan phthalate episode.
Phthalate exposure may reduce intellectual development in young children. In 2011, numerous Taiwanese children had been reported to have consumed phthalate-tainted products. We investigated the effects of phthalate exposure on the intellectual development of these children after the 2011 Taiwan di-2-ethylhexyl phthalate (DEHP) episode. We recruited 204 children, aged 3-12 y, from 3 hospitals in Taiwan between 2012 and 2013. First-morning urine samples were collected for analyzing 5 phthalate metabolites. We applied a Bayesian model to estimate the past DEHP exposure (estDEHPADD) of each participant before the 2011 DEHP episode. Demographic information, consumption of phthalate-tainted products, and maternal education, of each participant were obtained using a questionnaire. We used the Wechsler intelligence evaluation tools for assessing the children's and maternal intelligence quotient. The median levels of mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate, and mono-iso-butyl phthalate in the children were 9.97, 45.8, 32.2, 46.2, and 24.3μg/g creatinine, respectively. Using the aforementioned urinary phthalate metabolites, we found that the children's verbal comprehension index (N =98) was significantly negatively associated with urinary log10 MEOHP (β, -11.92; SE, 5.33; 95%CI, -22.52~ -1.33; P=0.028) and log10 ΣDBP metabolites (β, -10.95; SE, 4.93; 95%CI, -20.74~ -1.16; P=0.029) after adjustment for age, gender, maternal IQ and education, passive smoking, estDEHPADD, active and passive smoking during pregnancy. Through a tolerable daily intake-based approach, we only found a significant negative association between past estimate DEHPADD and VIQ≥3-<6 in preschool children whereas no correlation was observed between current DEHP exposure and IQ≥3-<6 score with/ without estimate DEHPADD adjustment. It revealed that the effect of past high-DEHP exposure on verbal-related neurodevelopment of younger child are more sensitive. Our results are consistent with the hypothesis that exposure to DEHP and DnBP affects intellectual development in preschool and school-aged children, particularly their language learning or expression ability.


[Hygienic assessment of students' nutrition and health].
A randomized study of lifestyle, quality of life, and the degree of depression was carried out in 399 Novokuznetsk high-school students (219 young men and 180 young women). Daily dietary pattern and eating behavior were studied in the students experiencing the highest psychoemotional stress caused by their adjustment to a new behavioral stereotype at higher school. Varying depression was observed in 16.5% of the students. The findings suggest the students' poor awareness of healthy lifestyle; however, 70.5% regarded their life as satisfactory. The students' diets characterized by the low levels of essential nutrients may diminish the body's adaptive abilities and provoke the development of various abnormalities. Eating behavioral disorders were observed in 21.5% of the respondents. Correlation analysis showed that the higher level of depression in young males, the more pronounced emotional eating behavioral disorders are (r = 0.31; p < or = 0.05). Such a correlation was not detected in young females. The higher degree of depression was found to affect the students' life quality (r = -0.37; p < or = 0.05). The study has provided a municipal special program "Health and Education" for 2007-2011, which will make it possible to carry out among students a regional policy aimed at popularizing the principles of healthy lifestyle, forming proper dietary habits and mechanisms of optimal behavioral models and their introduction.


Density-range size relationships in French riverine fishes.
We examined the relation between the local density of species and the size of the geographic range for French riverine fishes. As for most other taxonomic groups, a positive interspecific relationship is found for this group. This relationship is robust to the confounding effects of phylogeny and is not a priori a product of other potential mechanistic artefacts. We formally tested two of the principal biological mechanisms already proposed (i.e. the niche breadth hypothesis and the resource availability hypothesis). We found no support for the niche breadth hypothesis. In contrast, we found consistent support for the closely related resource availability hypothesis. Species utilising resources (habitats) that are marginal tend to appear at low density and to have narrow distribution whereas species utilising widespread habitats tend to be more abundant and more widely distributed. Using data on body size and reproductive traits we explored the potential influence of these variables in explaining significant variation around the density-range size relationship. Only body size explains significant variation around the relationship, being negatively correlated with local density and positively correlated with range size.


Early cardiac catheterization laboratory activation by paramedics for patients with ST-segment elevation myocardial infarction on prehospital 12-lead electrocardiograms.
Prompt reperfusion in ST-segment elevation myocardial infarction (STEMI) saves lives. Although studies have shown that paramedics can reliably interpret STEMI on prehospital 12-lead electrocardiograms (p12ECGs), prehospital activation of the cardiac catheterization laboratory by emergency medical services (EMS) has not yet gained widespread acceptance. To quantify the potential reduction in time to percutaneous coronary intervention (PCI) by early prehospital activation of the cardiac catheterization laboratory in STEMI. This prospective, observational study enrolled all patients diagnosed with STEMI by paramedics in a mid-sized regional EMS system. Patients were enrolled if: 1) the paramedic interpreted STEMI on the p12ECG, 2) the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) score was 75% or greater, and 3) the patient was transported to either of two area PCI centers. Data recorded included the time of initial EMS "STEMI alert" from the scene, time of arrival at the emergency department (ED), and time of actual catheterization laboratory activation by the ED physician, all using synchronized clocks. The primary outcome measure was the time difference between the STEMI alert and the actual activation (i.e., potential time savings). The false-positive rate (patients incorrectly diagnosed with STEMI by paramedics) was also calculated and compared with a locally accepted false-positive rate of 10%. Twelve patients were enrolled prior to early termination of the study. The mean and median potential time reductions were 15 and 11 minutes, respectively (range 7-29 minutes). There was one false STEMI alert (8.3% false-positive rate) for a patient with a right bundle branch block who subsequently had a non-ST-segment elevation myocardial infarction. The study was terminated when our cardiologists adopted a prehospital catheterization laboratory activation protocol based on our initial data. Important reductions in time to reperfusion seem possible by activation of the catheterization laboratory by EMS from the scene, with an acceptably low false-positive rate in this small sample. This type of clinical research can inform multidisciplinary policies and bring about meaningful clinical practice changes.


Determination of 2-Methylimidazole, 4-Methylimidazole, and 2-Acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole in Licorice Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry Stable-Isotope Dilution Analysis.
A quick and selective analytical method was developed for the simultaneous quantitation of 2-methylimidazole, 4-methylimidazole, and 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole, which are known to be formed by Maillard reactions. The methodology reported here employs stable-isotope dilution analysis (SIDA) using 4-methylimidazole-d6 and [(13)C6]-2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole as internal standards. It was successfully applied in a model assay to show that the addition of ammonium chloride during the manufacture of licorice promotes imidazole formation depending on the added amount of ammonium chloride without the well-known impact of present caramel food colorings. Furthermore, a monitoring assay of 29 caramel coloring-free licorice products showed that both 4-methylimidazole and 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole are endogenously generated in detectable quantities. None of the samples showed 2-methylimidazole levels above the limit of detection, 50 μg/kg.


Cystic fibrosis: inflammatory response to infection with Burkholderia cepacia and Pseudomonas aeruginosa.
Pulmonary colonization by Burkholderia cepacia in cystic fibrosis (CF) may be associated with enhanced deterioration of pulmonary function. This may be due to a more florid host inflammatory response than in colonization by Pseudomonas aeruginosa, leading to greater lung injury. Circulating markers of inflammation were determined during infective exacerbations and periods of clinical stability in an 18 month prospective study in adults with CF colonized by P. aeruginosa (n=41). B. cepacia (n=13) and in adults who intermittently grew B. cepacia (n=6). There were no differences between the levels of the inflammation markers measured in the three groups (P. aeruginosa, B. cepacia, B. cepacia intermittent) at any of the assessment points. When clinically stable, levels of inflammatory markers in all groups were elevated compared to a matched non-CF population, indicating, continuous inflammation and the potential for lung damage between infective exacerbations. This study does not support the hypothesis that pulmonary colonization with Burkholderia cepacia is associated with a heightened inflammatory response compared with Pseudomonas aeruginosa colonization.


Comparison of axisymmetric and three-dimensional models for gas uptake in a single bifurcation during steady expiration.
Reactive gas uptake is predicted and compared in a single bifurcation at steady expiratory flow in terms of Sherwood number using an axisymmetric single-path model (ASPM) and a three-dimensional computational fluid dynamics model (CFDM). ASPM is validated in a two-generation geometry by comparing the average gas-phase mass transfer coefficients with the experimental values. ASPM predicted mass transfer coefficients within 20% of the experimental values. The flow and concentration variables in the ASPM were solved using Galerkin finite element method and in the CFDM using commercial finite element software FIDAP. The simulations were performed for reactive gas flowing at Reynolds numbers ranging from 60 to 350 in both symmetric bifurcation for three bifurcation angles, 30 deg, 70 deg, and 90 deg, and in an asymmetric bifurcation. The numerical models compared with each other qualitatively but quantitatively they were within 0.4-8% due to nonfully developed flow in the parent branch predicted by the CFDM. The radially averaged concentration variation along the axial location matched qualitatively between the CFDM and ASPM but quantitatively they were within 32% due to differences in the flow field. ASPM predictions compared well with the CFDM predictions for an asymmetric bifurcation. These results validate the simplified ASPM and the complex CFDM. ASPM predicts higher Sherwood number with a flat velocity inlet profile compared to a parabolic inlet velocity profile. Sherwood number increases with the inlet average velocity, wall mass transfer coefficient, and bifurcation angle since the boundary layer grows slower in the parent and daughter branches.


[Does locoregional chemotherapy improve survival in patients with non-resectable pancreatic carcinoma? Results of an open controlled study].
About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.


Towards culturally competent paediatric oncology care. A qualitative study from the perspective of care providers.
In order to gain more insight on the influence of ethnic diversity in paediatric cancer care, the perspectives of care providers were explored. Semi-structured interviews were conducted among 12 paediatric oncologists and 13 nurses of two different paediatric oncology wards and were analysed using a framework method. We found that care providers described the contact with Turkish and Moroccan parents as more difficult. They offered two reasons for this: (1) language barriers between care provider and parents hindered the exchange of information; (2) cultural barriers between care provider and parents about sharing the diagnosis and palliative perspective hindered communication. Care providers reported different solutions to deal with these barriers, such as using an interpreter and improving their cultural knowledge about their patients. They, however, were not using interpreters sufficiently and were unaware of the importance of eliciting parents' perspectives. Communication techniques to overcome dilemmas between parents and care providers were not used and care providers were unaware of stereotypes and prejudice. Care providers should be offered insight in cultural barriers they are unaware of. Training in cultural competence might be a possibility to overcome manifest barriers.


Emergency department mental health presentations by people born in refugee source countries: an epidemiological logistic regression study in a Medicare Local region in Australia.
This study investigated if people born in refugee source countries are disproportionately represented among those receiving a diagnosis of mental illness within emergency departments (EDs). The setting was the Cities of Greater Dandenong and Casey, the resettlement region for one-twelfth of Australia's refugees. An epidemiological, secondary data analysis compared mental illness diagnoses received in EDs by refugee and non-refugee populations. Data was the Victorian Emergency Minimum Dataset in the 2008-09 financial year. Univariate and multivariate logistic regression created predictive models for mental illness using five variables: age, sex, refugee background, interpreter use and preferred language. Collinearity, model fit and model stability were examined. Multivariate analysis showed age and sex to be the only significant risk factors for mental illness diagnosis in EDs. 'Refugee status', 'interpreter use' and 'preferred language' were not associatedwith a mental health diagnosis following risk adjustment forthe effects ofage and sex. The disappearance ofthe univariate association after adjustment for age and sex is a salutary lesson for Medicare Locals and other health planners regarding the importance of adjusting analyses of health service data for demographic characteristics.


Bioinformatics identification of a T-cell-related signature for predicting prognosis and drug sensitivity in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a fatal disease with poor clinical outcomes. T cells play a vital role in the crosstalk between the tumour microenvironment and HCC. Single-cell RNA sequencing data were downloaded from the GSE149614 dataset. The T-cell-related prognostic signature (TRPS) was developed with the integrative procedure including 10 machine learning algorithms. The TRPS was established using 7 T-cell-related markers in the Cancer Genome Atlas cohort with 1-, 2- and 3-year area under curve values of 0.820, 0.725 and 0.678, respectively. TRPS acted as an independent risk factor for HCC patients. HCC patients with a high TRPS-based risk score had a higher Tumour Immune Dysfunction and Exclusion score, lower PD1 and CTLA4 immunophenoscore and lower level of immunoactivated cells, including CD8+ T cells and NK cells. The response rate was significantly higher in patients with low-risk scores in immunotherapy cohorts, including IMigor210 and GSE91061. The TRPS-based nomogram had a relatively good predictive value in evaluating the mortality risk at 1, 3 and 5 years in HCC. Overall, this study develops a TRPS by integrated bioinformatics analysis. This TRPS acted as an independent risk factor for the OS rate of HCC patients. It can screen for HCC patients who might benefit from immunotherapy, chemotherapy and targeted therapy.


Biological aerated filter treated textile washing wastewater for reuse after ozonation pre-treatment.
The combination of chemical and biological treatment processes is a promising technique to reduce refractory organics from wastewater. Ozonation can achieve high color removal, enhance biodegradability, and reduce the chemical oxygen demand (COD). The biological technique can further decrease COD of wastewater after ozonation as a pre-treatment. In this study the ozonizing-biological aerated filter processes were used to treat textile washing wastewater for reuse after conventional treatment. The result showed that when the influent qualities were COD about 80 mg/L, color 16 degree and turbidity about 8 NTU, using the combination processes with the dosages of ozone at 30-45 mg/L with the hydraulic retention time (HRT) of biological aerated filter (BAF) at 3-4 hours respectively, gave effluent qualities of COD less than 30 mg/L, color 2 degree and turbidity less than 1NTU. The cost of treatment was less than one yuan/t wastewater, and these processes could enable high quality washing water reuse in textile industry.


Physicians' experiences of caring for late-stage HIV patients in the post-HAART era: challenges and adaptations.
As medical treatment for AIDS has become more complex, the need for good palliative and end-of-life care has also increased for patients with advanced disease. Such care is often inadequate, especially among low-income, ethnic minority patients. The current study investigated physicians' experiences with caring for dying HIV patients in an underserved, inner city community in the Bronx, NY. The goals of the study included: (1) to investigate the barriers to effective end-of-life care for HIV patients; and (2) to examine physicians' experiences of role hindrance and frustration in caring for dying patients in the era of HAART. Qualitative, open-ended interviews were conducted with 16 physicians. Physicians identified two core, prescriptive myths shaping their care for patients with HIV. The 'Good Doctor Myth' equates good medical care with the delivery of efficacious biomedical care. The role of the physician is defined as technical curer, while the patient's role is limited to consultation and compliance. The 'Good Death Myth' envisions an ideal death which is acknowledged, organized, and pain free: the role of the physician is defined as that of comforter and supporter in the dying process. Role expectations associated with these myths were often disappointed. First, late-stage patients refused to adhere to treatment and were thus dying "unnecessarily." Second, patients often refused to acknowledge, accept, or plan for the end of life and as a result died painful, chaotic deaths. These realities presented intense psychological and practical challenges for providers. Adaptive coping included both behavioral and cognitive strategies. Successful adaptation resulted in "positive engagement," experienced by participants as a continuing sense of fascination, gratification, and joy. Less successful adaptation could result in detachment or anger. Participants believed that engagement had a powerful impact on patient care. Working with dying HIV patients in the post-HAART era of efficacious treatment challenges physician's cherished roles and values. Physicians adapt to the challenge through a variety of cognitive and behavioral strategies. The failure to adapt successfully has psychological consequences for providers that may impact patient care.


Proposed mechanism for neonatal rat tolerance to normobaric hyperoxia.
Induction of two forms of superoxide dismutase, catalase and glutathione peroxidase, occurs very rapidly in neonatal rat lung tissue upon exposure of these animals to 94 + % normobaric oxygen. No such oxygen-mediated enzyme induction occurs in the lungs of adult rats. The aged-dependent pattern of enzyme induction correlates with the well-established age-dependent tolerance of neonatal rats to hyperoxia. Enzyme induction occurs in the lungs of neonates in only those species known to be resistant to oxygen-provoked lung damage. Compromise of oxygen-mediated enzyme induction predisposed the neonatal rats to pulmonary oxygen toxicity. These data have formed the basis of the proposal that oxygen induction of the superoxide dismutases catalase and glutathione peroxidase provides a vital part of the defense mechanism against oxygen toxicity. A biochemical mechanism of oxygen-provoked pulmonary damage has been elaborated to explain the role of each enzyme in the protection against oxygen and free radical toxicity.


Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli.
Bacterial populations produce persisters, cells that neither grow nor die in the presence of bactericidal agents, and thus exhibit multidrug tolerance (MDT). The mechanisms of MDT and the nature of persisters have remained elusive. Our previous research has shown that persisters are largely responsible for the recalcitrance of biofilm infections. A general method for isolating persisters was developed, based on lysis of regular cells by ampicillin. A gene expression profile of persisters contained toxin-antitoxin (TA) modules and other genes that can block important cellular functions such as translation. Bactericidal antibiotics kill cells by corrupting the target function (for example, aminoglycosides interrupt translation, producing toxic peptides). We reasoned that inhibition of translation will lead to a shutdown of cellular functions, preventing antibiotics from corrupting their targets, giving rise to MDT persister cells. Overproduction of the RelE toxin, an inhibitor of translation, caused a sharp increase in persisters. Functional expression of a putative HipA toxin also increased persisters, while deletion of the hipBA module caused a sharp decrease in persisters in both stationary and biofilm populations. HipA is thus the first validated persister-MDT gene. We suggest that random fluctuation in the levels of MDT proteins leads to the formation of rare persister cells. The function of these specialized dormant cells is to ensure the survival of the population in the presence of lethal factors.


Insights from a Thermodynamic Study and Its Implications on the Freeze-Drying of Pharmaceutical Solutions Containing Water and tert-Butyl Alcohol as a Cosolvent.
In the production of several anticancer drugs, tert-butyl alcohol (TBA) is present as a co-solvent in the aqueous drug solution. In order to ascertain if TBA should be removed beforehand or if it could be retained to facilitate the freeze-drying of the drug solution, it is important to acquire both qualitative and quantitative knowledge of the variations occurring with respect to time in heat and mass transfer during the freeze-drying process. In this work, a thermodynamic model employing the UNIFAC (Dortmund) method was developed to determine the values of the currently experimentally unavailable partial vapor pressures of the binary gas mixture of water and TBA in equilibrium with their frozen solid mixtures. The results agree satisfactorily with relevant experimental measurements and indicate that TBA vapor has constantly higher pressures than water vapor and also promotes the vapor pressure of water during sublimation. The responses of the partial pressures of water and TBA vapors are found, through the analysis of their partial and total differentials, to be increasingly more sensitive to temperature change at elevated temperatures and to compositional change when the mole fraction of water in a frozen binary mixture approaches zero. The increased vapor pressures due to TBA lead to higher total pressures at the moving interface separating the dried and frozen layers, resulting in larger total pressure gradients and convective mass transfer rates in the dried layer during primary drying. But the higher total pressures reduce the magnitude of the bulk diffusivity of the gas mixture, and combined with the smaller Knudsen diffusivity of TBA, the pressures could significantly affect the competing mass transfer mechanisms during freeze-drying. The approach presented in this work could provide a general thermodynamic modeling approach for predicting the vapor pressures of multicomponent vapor mixtures in equilibrium with their multicomponent solid frozen mixtures.LAY ABSTRACT: tert-Butyl alcohol (TBA) is present as a cosolvent in a number of anticancer drug solutions. Its presence is known to affect the freeze-drying process of the drug solutions. In order to determine a better operational policy with respect to the freeze-drying process, a thermodynamic approach was developed in this work to provide the needed data of water and TBA vapors that are currently experimentally unavailable. The results agree satisfactorily with experimental measurements. They indicate that TBA vapor has constantly higher pressures than water vapor, promoting faster sublimation and generating higher total pressures at the moving interface to enhance convective mass transfer during primary drying. However, the higher total pressures also reduce the magnitude of the bulk diffusivity of the gas mixture, and combined with the smaller Knudsen diffusivity of TBA, these pressures could significantly affect the competing mass transfer mechanisms during freeze-drying. The thermodynamic method and analysis developed in this work are useful in their own physicochemical importance and also provide a necessary component for a new class of freeze-drying mathematical models. Moreover, they could provide a general modeling approach for predicting the vapor pressures of multicomponent vapor mixtures in equilibrium with their frozen solid mixtures.


BCR-ABL1 doubling times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold rise: implications for monitoring and management.
Rising BCR-ABL1 transcripts indicate potential loss of imatinib response in CML. We determined whether the BCR-ABL1 doubling time could distinguish nonadherence from resistance as the cause of lost response. Distinct groups were examined: (1) acquired clinical resistance because of blast crisis and/or BCR-ABL1 mutations; and (2) documented imatinib discontinuation/interruption. Short doubling times occurred with blast crisis (median, 9.0 days; range, 6.1-17.6 days; n = 12 patients), relapse after imatinib discontinuation in complete molecular response (median, 9.0 days; range, 6.9-26.5 days; n = 17), and imatinib interruption during an entire measurement interval (median, 9.4 days; range, 4.2-17.6 days; n = 12; P = .72). Whereas these doubling times were consistently short and indicated rapid leukemic expansion, fold rises were highly variable: 71-, 9.5-, and 10.5-fold, respectively. The fold rise depended on the measurement interval, whereas the doubling time was independent of the interval. Longer doubling times occurred for patients with mutations who maintained chronic phase (CP: median, 48 days; range, 17.3-143 days; n = 29; P < .0001). Predicted short and long doubling times were validated on an independent cohort monitored elsewhere. The doubling time revealed major differences in kinetics according to clinical context. Long doubling times observed with mutations in CP allow time for intervention. A short doubling time for a patient in CP should raise the suspicion of nonadherence.


[The impact of capsular repair on the dislocation rate after primary total hip arthroplasty: a retrospective analysis of 1972 cases].
Dislocation is the second most frequently encountered complication in primary total hip arthroplasty (THA) and occurs more commonly in the early postoperative rehabilitation phase. Sir Charnley recommended the "avoidance of resection of the capsule" and emphasised its contribution to hip joint stability in THA. Several authors, however, doubted its significance and considered resection of the capsule to be essential. Since 2002, some surgeons increasingly adopted a modified, less invasive technique of THA via Bauer approach, including the preservation and repair of the hip joint capsule with focus on maintaining its acetabular origin. Another group of surgeons applied the traditional technique including the resection of the joint capsule via an anterolateral approach. In this case-control study we investigated whether the dislocation rate can be reduced through joint capsule reconstruction and whether any negative impact on patient satisfaction, functional results or revision rate is observed. All cases of primary THA performed in our institution in a timeframe between 2002 and 2009 were included with the only exceptions of resurfacing arthroplasty, dual mobility and tumour hip replacements. Joint capsule repair cases were gathered in the study group (SG), capsule resection cases in the control group (CG). Additional patient-related data were taken from the anaesthesia records. The WOMAC score and a questionnaire focusing on detection of dislocations and revision surgeries was sent out for each case. Further targeted research was conducted that included requesting records and reports from external hospitals. In the case of non-responding patients, all available data (operating room documentation, electronic files, archive, X-rays) were reviewed for incidents of dislocation and revision surgery. Groupings and classifications were exclusively performed by senior surgeons. SG and CG were compared regarding epidemiologic, implant-associated and surgery-specific data. Statistical evaluations were performed using the Chi-squared test and the Mann-Whitney U test. 1972 cases of primary THA were included: 992 in the SG and 980 in the CG. The follow-up rates were 92.7 % in the SG and 76.4 % in the CG, the mean follow-up times 33.5 months and 73.4 months, respectively, with a follow-up of at least 12 months in all cases. In the SG, the dislocation rate was 0.3 % (n = 3) and thus significantly lower than the 2.55 % in the CG (n = 25, p < 0.001). Both the WOMAC score (SG: 1.46 ± 1.73; CG: 1.53 ± 1.80; p > 0.05) and the revision rate (SG: 5.24 %; CG: 6.84 %; p = 0.139) showed no significant differences. Preservation and repair of the hip joint capsule causes an 88-%-reduction of the dislocation rate in primary THA in this large series including 1972 cases, operated via the Bauer or the anterolateral approach. Several authors reported comparable results after THA using similar techniques of soft tissue and capsular repair through the posterior or posterolateral approach. Sparing and reconstructing the hip joint capsule therefore seems to reduce the dislocation rate after primary THA by one order of magnitude regardless of the surgical approach and, especially, if the acetabular origin is preserved. Capsule-related specific complications such as an increased revision rate, malfunction or pain were neither recorded in our study nor by others. Thus, careful preservation and reconstruction of the hip joint capsule may be expressly recommended in primary THA.


Relevance of two manual tumour volume estimation methods for diffuse low-grade gliomas.
Management of diffuse low-grade glioma (DLGG) relies extensively on tumour volume estimation from MRI datasets. Two methods are currently clinically used to define this volume: the commonly used three-diameters solution and the more rarely used software-based volume reconstruction from the manual segmentations approach. The authors conducted an initial study of inter-practitioners' variability of software-based manual segmentations on DLGGs MRI datasets. A panel of 13 experts from various specialties and years of experience delineated 12 DLGGs' MRI scans. A statistical analysis on the segmented tumour volumes and pixels indicated that the individual practitioner, the years of experience and the specialty seem to have no significant impact on the segmentation of DLGGs. This is an interesting result as it had not yet been demonstrated and as it encourages cross-disciplinary collaboration. Their second study was with the three-diameters method, investigating its impact and that of the software-based volume reconstruction from manual segmentations method on tumour volume. They relied on the same dataset and on a participant from the first study. They compared the average of tumour volumes acquired by software reconstruction from manual segmentations method with tumour volumes obtained with the three-diameters method. The authors found that there is no statistically significant difference between the volumes estimated with the two approaches. These results correspond to non-operated and easily delineable DLGGs and are particularly interesting for time-consuming CUBE MRIs. Nonetheless, the three-diameters method has limitations in estimating tumour volumes for resected DLGGs, for which case the software-based manual segmentation method becomes more appropriate.


18F-FDG PET/CT of Malignant Angiomyolipoma With Tumor Thrombus.
Renal angiomyolipomas are the most common renal mesenchymal tumors. While classic angiomyolipomas are benign, there are a number of other subtypes. Epithelioid variants are potentially malignant and may be indistinguishable from renal cell carcinoma on imaging. We present a 52-year-old woman who underwent left nephrectomy for an aggressive-appearing malignant renal epithelioid angiomyolipoma. At 6 months postoperatively, restaging FDG PET/CT demonstrated a hypermetabolic left adrenal mass extending to the left adrenal vein, left renal vein, inferior vena cava, and right atrium (SUVmax = 12). Multiple hypermetabolic pulmonary metastases were also noted.


An Insight Into the Molecular Mechanism of Berberine Towards Multiple Cancer Types Through Systems Pharmacology.
Over the past several decades, natural products with poly-pharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Berberine (PubChem CID: 2353), a soliloquies quaternary alkaloid, has been validated to exert powerful effects in many cancers. However, the underlying molecular mechanism is not yet fully elucidated. In this study, we summarized the molecular effects of berberine against multiple cancers based on current available literatures. Furthermore, a systems pharmacology infrastructure was developed to discover new cancer indications of berberine and explore their molecular mechanisms. Specifically, we incorporated 289 high-quality protein targets of berberine by integrating experimental drug-target interactions (DTIs) extracted from literatures and computationally predicted DTIs inferred by network-based inference approach. Statistical network models were developed for identification of new cancer indications of berberine through integration of DTIs and curated cancer significantly mutated genes (SMGs). High accuracy was yielded for our statistical models. We further discussed three typical cancer indications (hepatocarcinoma, lung adenocarcinoma, and bladder carcinoma) of berberine with new mechanisms of actions (MOAs) based on our systems pharmacology framework. In summary, this study systematically provides a powerful strategy to identify potential anti-cancer effects of berberine with novel mechanisms from a systems pharmacology perspective.


Childhood tuberculosis.
Childhood tuberculosis will reflect the incidence of cavitating pulmonary tuberculosis in adults and will consequently be encountered most frequently in those areas with a high incidence of tuberculosis. Problem areas include our continuing inability to confirm the diagnosis of tuberculosis in many children, the escalating interaction of the human immunodeficiency virus (HIV) pandemic and tuberculosis, which is now evident with greater frequency in childhood, and the scarcity of data relating to antituberculosis therapy in childhood, which necessitates reliance on adult studies in many cases. This review highlights several options for obtaining material for culture of Mycobacterium tuberculosis in children, aspects of tuberculin testing, which remains one of the cornerstones supporting a diagnosis of tuberculosis in childhood, the potential importance of therapeutic drug monitoring in problem cases, new data giving epidemiologic and clinical details of the interaction of HIV infection and tuberculosis in children, and studies describing the epidemiology of tuberculosis in the developed and developing world.


Modified Primary Closure Method for the Treatment of Pilonidal Sinus.
Pilonidal sinus (PS) is considered to be the acquired disease of especially in the sacrococcygeal region. Various primary or secondary or flap methods, accompanied by one of local curettage, phenol application, electro-cauterization and total sinus excision methods, are used for the treatment of pilonidal sinus. However, currently there is not a single widely accepted treatment method. Ninety-eight patients who had operation for PS in Atatürk University, Department of General Surgery between January 2012 and August 2014 were included in this study. The patients were categorized into two groups: first, the patients undergone total sinus excision with primary closure (Group 1), and second, patients undergone total sinus excision with modified primary closure (MPC) (Group 2). Among all 98 patients participated in this study, age, sex, type of operation, duration of operation, amount of excised skin, duration of postoperative stay at hospital and complications were evaluated. Forty-four patients (44.9%) underwent primary closure method, while 54 patients (55.1%) underwent MPC method. Mean duration of operation was 39.1 (30-60) minutes, mean diameter of excised material was 9.3 (8-11) cm(2) and mean duration of stay at hospital was 1.4 (1-3) days for the patients in the first group. Meanwhile, duration of operation was 52.2 (35-70) minutes, mean diameter of excised material was 2.6 (2-4) cm(2) and mean duration of stay at hospital was 1.6 (1-3) days for the patients in the second group. There was statistically significant difference between the two groups by means of duration of operation, dehiscence of surgical wound, recurrence and development of general complications (p<0.001, p<0.05, p<0.05 and p<0.005, respectively). According to the multivariate analysis, during surgical treatment of pilonidal sinus, primary closure method increases the rate of complication 6.65 times and MPC method increases the duration of operation 1.2 times. We hereby suggest that MPC method could be a good alternative for surgical treatment of PS, because it causes fewer complications and recurrence.


From monkeys to humans: observation-basedEMGbrain-computer interface decoders for humans with paralysis.
Objective. Intracortical brain-computer interfaces (iBCIs) aim to enable individuals with paralysis to control the movement of virtual limbs and robotic arms. Because patients' paralysis prevents training a direct neural activity to limb movement decoder, most iBCIs rely on 'observation-based' decoding in which the patient watches a moving cursor while mentally envisioning making the movement. However, this reliance on observed target motion for decoder development precludes its application to the prediction of unobservable motor output like muscle activity. Here, we ask whether recordings of muscle activity from a surrogate individual performing the same movement as the iBCI patient can be used as target for an iBCI decoder.Approach. We test two possible approaches, each using data from a human iBCI user and a monkey, both performing similar motor actions. In one approach, we trained a decoder to predict the electromyographic (EMG) activity of a monkey from neural signals recorded from a human. We then contrast this to a second approach, based on the hypothesis that the low-dimensional 'latent' neural representations of motor behavior, known to be preserved across time for a given behavior, might also be preserved across individuals. We 'transferred' an EMG decoder trained solely on monkey data to the human iBCI user after using Canonical Correlation Analysis to align the human latent signals to those of the monkey.Main results. We found that both direct and transfer decoding approaches allowed accurate EMG predictions between two monkeys and from a monkey to a human.Significance. Our findings suggest that these latent representations of behavior are consistent across animals and even primate species. These methods are an important initial step in the development of iBCI decoders that generate EMG predictions that could serve as signals for a biomimetic decoder controlling motion and impedance of a prosthetic arm, or even muscle force directly through functional electrical stimulation.


Accessible virtual reality therapy using portable media devices.
Simulated immersive environments displayed on large screens are a valuable therapeutic asset in the treatment of a range of psychological disorders. Permanent environments are expensive to build and maintain, require specialized clinician training and technical support and often have limited accessibility for clients. Ideally, virtual reality exposure therapy (VRET) could be accessible to the broader community if we could use inexpensive hardware with specifically designed software. This study tested whether watching a handheld non-immersive media device causes nausea and other cybersickness responses. Using a repeated measure design we found that nausea, general discomfort, eyestrain, blurred vision and an increase in salivation significantly increased in response to handheld non-immersive media device exposure.


Rehabilitation of pure alexia: a review.
Acquired reading problems caused by brain injury (alexia) are common, either as a part of an aphasic syndrome, or as an isolated symptom. In pure alexia, reading is impaired while other language functions, including writing, are spared. Being in many ways a simple syndrome, one would think that pure alexia was an easy target for rehabilitation efforts. We review the literature on rehabilitation of pure alexia from 1990 to the present, and find that patients differ widely on several dimensions, such as alexia severity and associated deficits. Many patients reported to have pure alexia in the reviewed studies, have associated deficits such as agraphia or aphasia and thus do not strictly conform to the diagnosis. Few studies report clear and generalisable effects of training, none report control data, and in many cases the reported findings are not supported by statistics. We can, however, tentatively conclude that Multiple Oral Re-reading techniques may have some effect in mild pure alexia where diminished reading speed is the main problem, while Tacile-Kinesthetic training may improve letter identification in more severe cases of alexia. There is, however, still a great need for well-designed and controlled studies of rehabilitation of pure alexia.


Endocan levels in children with renal hypodysplasia.
Severe reduction in nephron numbers that are characteristic of renal hypodysplasia (RHD) are one of the cause of childhood chronic kidney disease (CKD). Glomerular hyperfiltration, glomerular hypertrophy, progressive glomerular scarring, and interstitial fibrosis due to reduced nephron number are risk factors for CKD. In recent years, studies on specific markers for early diagnosis of renal failure and mortality have been carried out. The objectives of this study were to identify serum and urinary endocan levels that are expressed in glomerular endothelial cells and tubular epithelial cells in RHD. 29 children with RHD were compared to 26 healthy controls in terms of serum and urinary endocan levels. The mean serum endocan level in the RHD group and the control group was 700.72 ± 323.19 and 426.86 ± 233.14 pg/mL, respectively. The mean serum endocan level was significantly higher (p = 0.003) in the RHD group. The mean urinary endocan level in the RHD group was 63.62 ± 92.46 pg/mL, and in the control group it was 80.26 ± 142.49 pg/mL. The mean urinary endocan level did not change between groups (p = 0.95). There was also a significant correlation between serum endocan level and uric acid level in the study group (r = 0.325, p = 0.028). To our knowledge, this was the first study that evaluated serum and urinary endocan levels in children with RHD. Although serum endocan level was found to be significantly higher in patients with RHD, further studies are needed to validate whether endocan could serve as a marker of poor renal prognosis in RHD.


Onset, timing and risk for depression and anxiety in family caregivers to heart transplant recipients.
Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31.6%, Adjustment disorders, 35.4% (29.4 % with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22.5%, Generalized Anxiety Disorder, 7.3%, and any assessed disorder, 56.3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.


Effects of phorbol esters on pial arteriolar diameter and brain production of prostanoids in piglets.
We determined the effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C, on pial arteriolar diameter and cerebrospinal fluid (CSF) prostanoid levels in newborn pigs. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. In addition, CSF was sampled from under the window, and prostanoid levels (prostaglandin [PG] E2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2) were determined by radioimmunoassay. Diameter and CSF prostanoid levels were determined during application of artificial CSF containing no drugs and during application of 10(-8), 10(-7), and 10(-6) M PDB. We also determined effects of 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a phorbol ester that does not activate protein kinase C, and dimethyl sulfoxide, the vehicle for the phorbol esters, on pial arteriolar diameter and CSF prostanoid levels. Initial diameters were 100-200 microns. At 10(-8)-10(-6) M, PDB progressively constricted pial arterioles and increased CSF levels of prostanoids; the other phorbol ester and dimethyl sulfoxide had no such effects. Baseline arteriolar diameter was 147 +/- 17 microns (mean +/- SEM), and diameter was 140 +/- 17 microns at 10(-8) M PDB, 120 +/- 18 microns at 10(-7) M PDB (p less than 0.05), and 108 +/- 14 microns at 10(-6) M PDB (p less than 0.05) (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)