A method for marker-assisted selection based on QTLs with epistatic effects.
A method for marker-assisted selection (MAS) based on quantitative trait loci (QTLs) with epistatic effects is proposed. The efficiency of such method is investigated by simulations under a wide range of situations. In the presence of epistasis, MAS generally yields longer persistence response than that based exclusively on additive or additive and dominance. Neglecting epistasis could result in considerable loss in response, and more pronounced at later generations. In addition to population size and trait heritability, genetic variance configurations play an important role in determining both the short- and long-term efficiencies of MAS. MAS using breeding values not only achieves higher response, but also tends to have smaller standard error than other methods in most cases. Errors in QTL detection cause distinct reductions in responses to MAS in most cases. It is thus concluded that verifications of putative QTL and its magnitude of effect and accurate map chromosome location are imperative to realize the potentials of MAS.


Fixation choices for closed simple unstable oblique phalangeal and metacarpal fractures.
Percutaneous K-wire fixation is still a useful technique for closed oblique phalangeal and meta-carpal fractures when an adequate closed reduction can be achieved. Lag screw fixation may be the best choice for open fixation of long oblique phalangeal and metacarpal fractures. For short oblique fractures, plating or tension band wiring is recommended. Plating provide rigid fixation to allow early mobilization; however, one may encounter frequent complications such as extensor lag, stiffness, or joint contracture when plating technique is used in phalangeal fractures. Tension band wiring technique at the phalangeal location may reduce such complications. Overall, successful outcomes of treating phalangeal and metacarpal fractures require a clear appreciation of fracture anatomy and pattern. It is mandatory for the treating surgeon to be familiar with all the treatment techniques discussed in order to tailor a specific technique for a particular injury and patient type.


Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition.
Resistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.


Blood coagulation: a review.
Blood coagulation consists of several interrelated reactions involving platelets and blood vessels, the classical cascade, and the fibrinolytic system. There is a complex of inhibiting influences on each of these schemes, and there are interrelationships among these inhibitory influences.


The Correlation between the Inflammatory Effects of Activated Macrophages in Atherosclerosis and Aortic Dissection.
To study the correlation between lipid metabolism index, inflammatory factor index, and M1 macrophage content and aortic dissection. Patients with only basic atherosclerotic diseases were selected as the control group, and patients with only basic atherosclerotic diseases and aortic dissection were set as the experiment group. Blood of patients was collected. Chemiluminescent immunoassay was applied to determine the concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B1 (ApoB1). Enzyme-linked immunosorbent assay was applied to measure the concentration of tumor necrosis factor-α (TNF-α), Interleukin 1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10). The content of M1 macrophages in blood was measured with the flow cytometry (FCM) method. The correlation between the inflammatory effects of activated macrophages in atherosclerosis and aortic dissection was analyzed by a simple linear regression analysis. Concentration of TC, TG, LDL-C, and ApoB and the concentration of TNF-α, IL-1β, and IL-6 in the experiment group were markedly higher compared to those in the control group, whereas the concentration of HDL-C and ApoA1 and IL-10 concentration in the experiment group was markedly lower. The content of M1 macrophage in the control group was significantly lower compared to the experiment group. The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1β, IL-6, and IL-10 were all significantly correlated to the occurrence of aortic dissection. The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1β, IL-6, and IL-10 are significantly correlated with the occurrence of aortic dissection.


Non-specific physical symptoms and electromagnetic field exposure in the general population: can we get more specific? A systematic review.
A systematic review of observational studies was performed to address the strength of evidence for an association between actual and perceived exposure to electromagnetic fields (EMF) and non-specific physical symptoms (NSPS) in the general population. To gain more insight into the magnitude of a possible association, meta-analyses were conducted. Literature databases Medline, Embase, SciSearch, PsychInfo, Psyndex and Biosis and additional bibliographic sources such as reference sections of key publications were searched for the detection of studies published between January 2000 and April 2011. Twenty-two studies met our inclusion criteria. Qualitative assessment of the epidemiological evidence showed either no association between symptoms and higher EMF exposure or contradictory results. To strengthen our conclusions, random effects meta-analyses were performed, which produced the following results for the association with actual EMF; for symptom severity: Headache odds ratio (OR)=1.65; 95% confidence interval (CI)=0.88-3.08, concentration problems OR=1.28; 95% CI=0.56-2.94, fatigue-related problems OR=1.15; 95% CI=0.59-2.27, dizziness-related problems OR=1.38; 95% CI=0.92-2.07. For symptom frequency: headache OR=1.01; 95% CI=0.66-1.53, fatigue OR=1.12; 95% CI=0.60-2.07 and sleep problems OR=1.18; 95% CI=0.80-1.74. Associations between perceived exposure and NSPS were more consistently observed but a meta-analysis was not performed due to considerable heterogeneity between the studies. This systematic review and meta-analysis finds no evidence for a direct association between frequency and severity of NSPS and higher levels of EMF exposure. An association with perceived exposure seems to exist, but evidence is still limited because of differences in conceptualization and assessment methods.


Predictive value of the C-reactive protein-to-prealbumin ratio in medical ICU patients.
This prospective study aimed to evaluate the relationship between the ratio of C-reactive protein-to-prealbumin (CRP/PAB) and clinical outcomes in medical intensive care unit patients. All 240 consecutive adult patients were enrolled in this study with demographic and clinical features collected. Compared with patients belonging to the CRP/PAB ≤0.24 group, hospital mortality and the total length of stay in hospital (TLSH) were significantly increased in patients in the CRP/PAB >0.24 group. CRP/PAB and Acute Physiology and Chronic Health Evaluation II score score were independently correlated with hospital mortality while CRP/PAB and age were independently associated with TLSH. CRP/PAB were independently correlated with hospital mortality and TLSH in medical intensive care unit.


Rudimentary empathy in macaques' social decision-making.
Primates live in highly social environments, where prosocial behaviors promote social bonds and cohesion and contribute to group members' fitness. Despite a growing interest in the biological basis of nonhuman primates' social interactions, their underlying motivations remain a matter of debate. We report that macaque monkeys take into account the welfare of their peers when making behavioral choices bringing about pleasant or unpleasant outcomes to a monkey partner. Two macaques took turns in making decisions that could impact their own welfare or their partner's. Most monkeys were inclined to refrain from delivering a mildly aversive airpuff and to grant juice rewards to their partner. Choice consistency between these two types of outcome suggests that monkeys display coherent motivations in different social interactions. Furthermore, spontaneous affilitative group interactions in the home environment were mostly consistent with the measured social decisions, thus emphasizing the impact of preexisting social bonds on decision-making. Interestingly, unique behavioral markers predicted these decisions: benevolence was associated with enhanced mutual gaze and empathic eye blinking, whereas indifference or malevolence was associated with lower or suppressed such responses. Together our results suggest that prosocial decision-making is sustained by an intrinsic motivation for social affiliation and controlled through positive and negative vicarious reinforcements.


Reporting of weight history: sexually abused versus nonabused males.
In this study we explored among males a possible relationship between recollection of adult body weights and a history of sexual abuse prior to the age of 15. Using a survey format, 34 men hospitalized in an acute care psychiatric facility completed measures. Of the men who acknowledged sexual abuse (n=9), all reported their lowest, highest, and perceived ideal body weight, compared with non-sexually abused men of whom only 80%, 48%, and 52%, respectively, reported the requested weight information. It may be that sexual abuse among men during childhood results in heightened body awareness in adulthood.


Eyeball Test for the Assessment of Frailty in Elderly Patients With Cardiovascular Disease: A Prospective Study.
Frailty has been associated with poor outcomes in patients with cardiovascular diseases (CVDs). We aimed to assess the accuracy of the Eyeball test for frailty assessment in elderly patients with CVD. This is a prospective study including stable patients ≥75 years old who were followed-up in a cardiology clinic. Frailty assessment was performed separately through the Eyeball test and the Fried test in a blinded way. Cardiologists were asked to rate the frailty status of participants based on their routine clinical assessment and grade frailty on a Fried-type scale (1 to 5, with frailty defined as a score ≥3). Each patient then underwent formal frailty assessment using the Fried test. Included were 300 consecutive patients with a mean age of 81 ± 6 years. Frailty was diagnosed in 109 (36%) and 125 patients (41%) according to the Fried and Eyeball tests, respectively. The Eyeball test demonstrated 86% sensitivity and 82% specificity for the diagnosis of frailty. A receiver operating characteristics curve analysis demonstrated an area under the curve of 0.82 for the diagnosis of frailty. The Eyeball test demonstrated a very high negative predictive value of 90% and a modest positive predictive value of 73% for frailty assessment. Similar results were observed after subgroup analysis according to age and gender. In conclusion, the Eyeball test is an accurate method to rule out frailty in elderly patients with CVD. However, when frailty is suspected based on the Eyeball test, a formal tool such as the Fried test should be used to confirm the diagnosis.


Intrathyroid dermoid cyst presenting as a unilateral "Cold" nodule.
A dermoid cyst arising in the left lobe of the thyroid gland in a 5-year-old boy was managed with a left hemi-thyroidectomy. While congenital lesions feature frequently in the differential diagnosis of childhood neck masses, dermoid cysts presenting as a unilateral neck mass are rare. When found within the thyroid, their pathogenesis may be explained by a disruption of normal thyroid development. Excision appears the treatment of choice.


Membrane phospholipid abnormalities of basal ganglia in never-treated schizophrenia: a 31P magnetic resonance spectroscopy study.
Studies in schizophrenia using in vivo (31)P magnetic resonance spectroscopy (MRS) have mostly focused on the association cortices, including the frontal and temporal lobes. Striatum has also been implicated in schizophrenia, although neuroleptic exposure in the patients is a potential confound limiting interpretation of earlier studies. We examined membrane phospholipid abnormality in the basal ganglia using (31)P MRS in neuroleptic-naive schizophrenia patients. Never-treated, DSM-IV schizophrenia patients (n=20) and age- and gender-matched healthy control subjects (n=30) underwent in vivo 1-D 31P MRS of both basal ganglia using an image-selected technique on a 1.5-T magnetic resonance imaging scanner. A neuroradiologist blind to clinical data measured the phosphomonoester (PME) and phosphodiester (PDE) from the spectra. The schizophrenia patients showed significantly and bilaterally elevated levels of PME/PDE ratios in basal ganglia as compared with control subjects. There were no significant differences in the ratios between the two sides in either patient or control groups. Phosphomonoester/phosphodiester ratio did not correlate with illness duration. Lower Positive and Negative Syndrome Scale scores were associated with lower PME/PDE ratio. The basal ganglia of never-treated schizophrenia patients show features suggestive of reduced breakdown and/or increased synthesis of membrane phospholipids. Lack of correlation between illness duration and the membrane phosphorus moiety ratio may be consistent with a nonprogressive, possibly neurodevelopmental etiopathogenesis.


Comparative study of a biphasic culture system (Roche MB Check system) with a conventional egg medium for recovery of mycobacteria. Aichi Mycobacteriosis Research Group.
The clinical utility of a new biphasic culture system (Roche MB Check system) for the recovery of mycobacteria was evaluated in comparison with a conventional egg based medium. A total of 905 clinical specimens (mainly sputum samples) were tested in 9 clinical microbiology laboratories in Aichi Prefecture, Japan. The recovery rate and detection time of mycobacteria from the specimens were compared between the biphasic system and the egg medium. Of the 905 samples, 311 were positive in the culture of mycobacteria. The recovery rate of the biphasic system was superior to that of the egg medium (99.0% versus 74.0%, P < 0.0001). In addition, the biphasic system showed a considerable decrease in the number of days required for isolation compared with the egg medium (18.8 days vs. 23.1 days for Mycobacterium tuberculosis, P < 0.0001; 13.4 days vs. 19.8 days for M. avium complex, P = 0.007). The biphasic system is therefore proposed as a feasible and practical method for the recovery of mycobacteria from clinical specimens.


Girth pressure measurements reveal high peak pressures that can be avoided using an alternative girth design that also results in increased limb protraction and flexion in the swing phase.
Girths are frequently blamed for veterinary and performance problems, but research into girth/horse interaction is sparse. The study objectives were (1) to determine location of peak pressure under a range of girths, and (2) to compare horse gait between the horse's standard girth and a girth designed to avoid detected peak pressure locations. In the first part of the study, and following validation procedures, a calibrated pressure mat placed under the girth of 10 horses was used to determine the location of peak pressures. A girth was designed to avoid peak pressure locations (Girth F). In the second part, 20 elite horses/riders with no lameness or performance problem were ridden in Girth F and their standard girth (Girth S) in a double blind crossover design. Pressure mat data were acquired from under the girths. High speed video was captured and forelimb and hindlimb protraction, maximal carpal and tarsal flexion during flight were determined in trot. In standard girths, peak pressures were located over the musculature behind the elbow. Pressure mat results revealed that the maximum forces with Girth S were 22% (left) and 14% (right) greater than Girth F, and peak pressures were 76% (left) and 98% (right) greater (P<0.01 for all). On gait evaluation, Girth F was associated with 6-11% greater forelimb protraction, 10-20% greater hindlimb protraction, 4% greater carpal flexion, and 3% greater tarsal flexion than Girth S (P<0.01 for all). Peak pressures were located where horses tend to develop pressure sores. Girth F reduced peak pressures under the girth, and improved limb protraction and carpal/ tarsal flexion, which may reflect improved posture and comfort.


P/N-Heteroleptic Cu(I)-Photosensitizer-Catalyzed [3 + 2] Regiospecific Annulation of Aminocyclopropanes and Functionalized Alkynes.
We report here a regiospecific [3 + 2] annulation between aminocyclopropanes and various functionalized alkynes enabled by a P/N-heteroleptic Cu(I) photosensitizer under photoredox catalysis conditions. Thus, a divergent construction of 3-aminocyclopentene derivatives including methylsulfonyl-, arylsulfonyl-, chloro-, ester-, and trifluoromethyl-functionalized aminocyclopentenes could be achieved with advantages of high regioselectivity, broad substrate compatibility, and mild and environmentally benign reaction conditions.


The small bowel enema made easy.
The small bowel enema (barium infusion, enteroclysis) is a valuable radiological procedure that is easy to use and gives consistently good results. The technique is described and important aspects of the examination are discussed.


Flavored Tobacco Product Use in Youth and Adults: Findings From the First Wave of the PATH Study (2013-2014).
The 2009 Family Smoking Prevention and Tobacco Control Act banned characterizing flavors other than menthol in cigarettes but did not restrict their use in other forms of tobacco (e.g., smokeless, cigars, hookah, e-cigarettes). A cross-sectional analysis of Wave 1 data from 45,971 U.S. adults and youth, aged ≥12 years in the Population Assessment of Tobacco and Health (PATH) Study collected in 2013-2014, was conducted in 2016. This study examined (1) the prevalence and reasons for use of flavored tobacco products; (2) the proportion of ever tobacco users reporting that their first product was flavored; and (3) correlates of current flavored tobacco product use. Current flavored (including menthol) tobacco product use was highest in youth (80%, aged 12-17 years); and young adult tobacco users (73%, aged 18-24 years); and lowest in older adult tobacco users aged ≥65 years (29%). Flavor was a primary reason for using a given tobacco product, particularly among youth. Eighty-one percent of youth and 86% of young adult ever tobacco users reported that their first product was flavored versus 54% of adults aged ≥25 years. In multivariable models, reporting that one's first tobacco product was flavored was associated with a 13% higher prevalence of current tobacco use among youth ever tobacco users and a 32% higher prevalence of current tobacco use among adult ever users. These results add to the evidence base that flavored tobacco products may attract young users and serve as starter products to regular tobacco use.


Absorption of a non-ionic contrast agent from cerebrospinal fluid to blood.
Intrathecal injection of a non-ionic contrast agent in the lumbar area of rabbits resulted in: (1) a rapid rise in blood iodine level with a maximum after 23-46 min; (2) low concentrations in cisterna magna during the observation period (24 h); and (3) complete or almost complete disappearance of visible contrast medium on the radiographs within 30 min. This indicates that after injection in the lumbar area of the rabbit most of the contrast medium absorption takes place from the lumbar area. Similar injections in cisterna magna showed the following: (1) a slow rise in blood level with a maximum after 150-275 min; (2) little or no disappeared of visible contrast medium on the radiographs within the first hour. This indicates that in the rabbit the absorption from the subarachnoid space of the spine takes place at different rates dependent on the level at which the injection has been made and the area of deposition of contrast medium.


Single incision transumbilical laparoscopic varicocelectomy versus the conventional laparoscopic technique: A randomized clinical study.
Varicocele is the most common correctable cause of infertility. We analyzed the outcomes of single incision laparoscopic varicocelectomy (SIL-V) in comparison with conventional transperitoneal varicocelectomy (CTL-V). Patients with clinically palpable varicocele treated by laparoscopic varicocelectomy were randomly allocated into two groups: SIL-V and CTL-V group. The primary outcome measures were improvement in semen parameters and resolution of testicular pain. Secondary outcome measures included operating time, postoperative pain scores, time to return to normal activity, patient satisfaction and postoperative complications. Eighty patients completed the study. No vascular or intestinal complications occurred during both procedures. All patients were discharged 24 h postoperatively. The parameters measuring the success of varicocelectomy had improved for the majority of patients with no significant difference between the two groups. There was significantly longer operating time in SIL-V group (44.6 ± 5.4 min) than in CTL-V group (41.3 ± 8.5 min) (P = 0.03). The difference in operating time was lost when bilateral procedures were compared (P = 0.21). The mean VAS scores for pain at 3, 24 and 48 h postoperatively were significantly lower in SIL-V group (P = 0.02, P = 0.03 and P < 0.001 respectively). Time to return to normal activity was significantly shorter in SIL-V (P < 0.001). Patient satisfaction was significantly higher in SIL-V group (P < 0.01). Postoperative complications were comparable in both groups. SIL-V is a safe and effective straightforward alternative to the well-established and accepted CTL-V. The tendency toward decreased postoperative pain, rapid return to normal activity and the high patients' satisfaction rate regarding cosmetic results are potential benefits of SIL-V procedure. (NCT02335385).


The effect of vasopressor agents upon uterine artery blood flow velocity in the gravid guinea pig subjected to ritodrine infusion.
The purpose of the present study was to assess the effects of intravenously administered vasopressors upon uterine artery blood flow velocity (UBFV) in the gravid guinea pig subjected to ritodrine infusion. Fourteen experiments were performed in 14 chronically instrumented pregnant guinea pigs near term. Immediately following a 1-h intravenous infusion of ritodrine (0.05-0.20 mg.kg.min-1), each animal received an intravenous bolus of vasopressor solution: 1) epinephrine, 0.001 mg/kg; 2) phenylephrine, 0.01 mg/kg; 3) mephentermine, 1.0 mg/kg; 4) ephedrine, 1.0 mg/kg; or 5) placebo. The experimental sequence was performed five times, so that each animal received all five solutions. The vasopressor sequence was randomly altered between animals. Infusion of ritodrine increased maternal heart rate 18 +/- 1% (P less than .0001), decreased maternal mean arterial pressure (MMAP) 4 +/- 1% (P less than .01), and decreased UBFV 5 +/- 1% (P less than .001). The four active vasopressor solutions resulted in similar, though not equivalent, increases in MMAP. Further, the MMAP response to each active vasopressor differed from the response to placebo (P less than .0001). Epinephrine and phenylephrine each significantly decreased UBFV (P less than .002). Ephedrine clearly preserved UBFV, whereas mephentermine appeared to result in an intermediate response.


Confused or not Confused?: Disentangling Brain Activity from EEG Data Using Bidirectional LSTM Recurrent Neural Networks.
Brain fog, also known as confusion, is one of the main reasons for low performance in the learning process or any kind of daily task that involves and requires thinking. Detecting confusion in a human's mind in real time is a challenging and important task that can be applied to online education, driver fatigue detection and so on. In this paper, we apply Bidirectional LSTM Recurrent Neural Networks to classify students' confusion in watching online course videos from EEG data. The results show that Bidirectional LSTM model achieves the state-of-the-art performance compared with other machine learning approaches, and shows strong robustness as evaluated by cross-validation. We can predict whether or not a student is confused in the accuracy of 73.3%. Furthermore, we find the most important feature to detecting the brain confusion is the gamma 1 wave of EEG signal. Our results suggest that machine learning is a potentially powerful tool to model and understand brain activity.


Identification of Cyanidin-3-arabinoside Extracted from Blueberry as a Selective Protein Tyrosine Phosphatase 1B Inhibitor.
Protein tyrosine phosphatase 1B (PTP1B) is an important target for type 2 diabetes. PTP1B inhibitors can reduce blood glucose levels by increasing insulin sensitivity. Anthocyanins often play a hypoglycemic effect, but the research about them have mainly focused on glucosidase. At present, the research about protein tyrosine phosphatase 1B (PTP1B) target is less, and the corresponding molecular mechanism is still unclear. Therefore, in this present study, anthocyanins isolated from blueberry were used to study the inhibitory activity on PTP1B. The isolated cyanidin-3-arabinoside (Cya-3-Ara) exhibited a better inhibitory activity with IC50 = 8.91 ± 0.63 μM, which was higher than the positive control (oleanolic acid, IC50 = 13.9 ± 1.01 μM), and the mechanism of PTP1B inhibition was reversible mixed pattern. The structure-activity relationship (SAR) between anthocyanins and PTP1B inhibition was investigated. The enzyme activity inhibition and molecular docking showed that anthocyanins had high selectivity for PTP1B inhibition. Further study showed that Cya-3-Ara could promote glycogen synthesis through ameliorating PTP1B-involved IRS-1/PI3K/Akt/GSK3β pathways. Cya-3-Ara could also be regarded as a synergistic inhibitor (CI ≤ 0.54) of oleanolic acid to obtain a better inhibitory effect on PTP1B. Taken together, our study clearly illustrates the SAR between anthocyanins and PTP1B inhibition and the mechanism of Cya-3-Ara in the insulin signaling pathway.


Recurrent aneurysms of the upper arteries of the lower limb: an atypical manifestation of fibromuscular dysplasia--a case report.
Fibromuscular dysplasia (syn. arterial dysplasia, fibromuscular hyperplasia, medial fibroplasia) is an arteriopathy of unknown etiology, most frequently involving the renal arteries. The string-of-beads appearance of these lesions seems to be a characteristic angiographic finding. We report atypical angiographic findings at an unusual site, which proved to correspond to fibromuscular dysplasia at histological examination.


Efficient derivation of dopaminergic neurons from SOX1⁻ floor plate cells under defined culture conditions.
Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-β signaling pathways (SB431542) for 24 h under defined culture conditions. Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.


Ultrasonography and 32P test in the diagnosis of choroidal melanoma with massive vitreous hemorrhage.
A malignant melanoma of the choroid presented with a massive vitreous hemorrhage which prevented any view of the posterior pole. The diagnosis was confirmed by the results of a radioactive phosphorus test and ultrasonography. In eyes with opaque media, these tests will ofter prevent delays in diagnosis.


LOXL1-AS1 Aggravates Myocardial Ischemia/Reperfusion Injury Through the miR-761/PTEN Axis.
Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.


Rheumatic pain in a Philippine village. A WHO-ILAR COPCORD Study.
In initiating a community oriented programme for the control of rheumatic disease (COPCORD), 1685 people of all ages from a rural area in the Philippines were questioned by primary health care workers (PHW) for limb and spinal rheumatic pain and disability. The total complaint rate was 15.3% for men and 18.5% for women. For those 15 years and older the age adjusted rheumatic pain rates for pain present at the time of survey were 28.4% for the Philippines and 22.6% for Lawrence's UK population. The most common rheumatic pain sites in this community were knee, lumbar spine, neck and the trapezius muscle. The disability rate was 4.5% for those 15 years and older. One quarter of those with pain had received medical attention and the remainder, herbal treatment, massage, various faith and/or self-treatment methods.


The lateral inframalleolar fat pad: a poorly recognized anatomical structure.
The authors carried out an anatomical histological study of the lateral inframalleolar region in order to improve knowledge of a fat pad of the lateral aspect of the ankle which is not mentioned in most anatomical texts. Twenty-four ankles, from 12 cadavers, free of any local pathology or malformation, were studied. Twenty ankles were dissected, of which, five had samples taken for histological examination. Colored latex was injected into the joint cavities of the last four ankles before anatomical cuts were made in three planes. This study allowed the description of the fat pad which we have called the lateral inframalleolar fat pad (LIMFP). It is oval and made up of a classical unilocular fatty tissue which is clearly distinct from the subcutaneous plane. We have defined its relationships and in particular, the neurovascular ones. The sural nerve which supplies cutaneous sensation to part of the 5th toe runs over the surface of the fat pad. It is accompanied on this part of its course by the short saphenous vein which gives off a medial perforator which traverses the LIMFP. Because of these neurovascular relationships, the LIMFP may play a role in the pathophysiology of neuralgias of the lateral aspect of the 5th toe or of the 4th digital interspace. It should be recognized before any operations on the lower limbs, in particular, before any plastic surgical liposuction, in order to optimize the resection volume to prevent inaesthetic over correction or under corrections which are often confused with residual edema.


Thyroid receptor β might be responsible for breast cancer associated with Hashimoto's thyroiditis: a new insight into pathogenesis.
Breast cancer is the most common cancer affecting females worldwide. Often it is observed that women suffering from Hashimoto's thyroiditis exhibit a greater propensity towards development of breast cancer. The exact mechanism for the same is unknown. However, multiple experimental evidences suggest a significant role of thyroid receptor β (TR-β) in regulating cell growth and proliferation and thus play a potent role as a tumor suppressor in several cancers, including breast cancer. Thyroid receptor β shows anti-proliferative action through mediators like β-catenin, RUNX2, PI3K/AKT, and cyclin regulation. The present review explores the link between these pathways and how they may be dysregulated due to Hashimoto's thyroiditis. Further, we propose a new mechanism for cancer prognosis associated with Hashimoto's thyroiditis, which may lead to the development of TR-β targeting as a novel therapeutic approach.


DNA damage induced by KP372-1 hyperactivates PARP1 and enhances lethality of pancreatic cancer cells with PARP inhibition.
The overall prognosis for pancreatic cancer remains dismal and potent chemotherapeutic agents that selectively target this cancer are critically needed. Elevated expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is frequent in pancreatic cancer, and it offers promising tumor-selective targeting. Recently, KP372-1 was identified as a novel NQO1 redox cycling agent that induces cytotoxicity in cancer cells by creating redox imbalance; however, the mechanistic basis of KP372-1-induced cytotoxicity remains elusive. Here, we show that KP372-1 sensitizes NQO1-expressing pancreatic cancer cells and spares immortalized normal pancreatic duct cells, hTERT-HPNE. Notably, we found that KP372-1 is ~ 10- to 20-fold more potent than β-lapachone, another NQO1 substrate, against pancreatic cancer cells. Mechanistically, our data strongly suggest that reactive oxygen species produced by NQO1-dependent redox cycling of KP372-1 cause robust DNA damage, including DNA breaks. Furthermore, we found that KP372-1-induced DNA damage hyperactivates the central DNA damage sensor protein poly(ADP-ribose) polymerase 1 (PARP1) and activates caspase-3 to initiate cell death. Our data also show that the combination of KP372-1 with PARP inhibition creates enhanced cytotoxicity in pancreatic cancer cells. Collectively, our study provides mechanistic insights into the cytotoxicity instigated by KP372-1 and lays an essential foundation to establish it as a promising chemotherapeutic agent against cancer.


The dynamics of the pi 1 colour mechanism: further evidence for two sites of adaptation.
1. The visual pathway that determines Stiles's Pi(1) colour mechanism was isolated by the auxiliary field technique and studied under dynamic conditions of light adaptation and recovery by threshold measurements.2. The time courses of adaptation to Pi(1)-equated short wave-length (mu </= 500 nm) and long wave-length (mu >/= 550 nm) fields are very distinct: a large and relatively long-enduring transient threshold elevation occurs at the onset of the long wave-length, but not of the short wave-length fields.3. Similarly, the time courses of recovery from Pi(1)-equated long and short wave-length fields are quite distinctive: a large and relatively long enduring transient (;transient tritanopia') occurs at the offset of the long wave-length, but not of the short wave-length fields.4. The wave-lengths of the fields which cause the adaptation transients coincide with those shown previously (Pugh, 1976) to combine non-additively with mu = 430 nm fields in effecting Pi(1) adaptation. The failure of the time course of Pi(1) adaptation to be spectrally ;univariant' combines with the failures of field-additivity to demonstrate that signals from the long and/or middle wave-length sensitive cones affect the adaptation state of the Pi(1) pathway.5. The adaptation transients are not observed in the pathways that determine Pi(4) and Pi(5). Thus, instantaneous signals from the middle and/or long wave-length sensitive cones are not the cause of the transients. Rather the cause must lie in the path by which those cones transmit their signals to the Pi(1) pathway or in the Pi(1) pathway itself.6. The off-transient can be diminished by adding an adequately intense short wave-length field to a long wave-length field that would normally cause it. The Pi(1) pathway must receive chromatically opponent signals.


[Intensive care to facilitate organ donation. ONT-SEMICYUC recommendations].
Intensive care to facilitate organ donation (ICOD) is defined as the initiation or continuation of life-sustaining measures, such as mechanical ventilation, in patients with a devastating brain injury with high probability of evolving to brain death and in whom curative treatment has been completely dismissed and considered futile. ICOD incorporates the option to organ donation allowing a holistic approach to end-of-life care, consistent with the patients wills and values. Should the patient not evolve to brain death, life-supportive treatment must be withdrawal and controlled asystolia donation could be evaluated. ICOD is a legitimate practice, within the ethical and legal regulations that contributes increasing the accessibility of patients to transplantation, promoting health by increasing deceased donation by 24%, and with a mean of 2.3 organs transplanted per donor, and collaborating with the sustainability of health-care system. This ONT-SEMICYUC recommendations provide a guide to facilitate an ICOD harmonized practice in spanish ICUs.


Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302).
FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line. Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H0: 55% and H1= 75%. Data were analyzed in intention to treat. Forty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification. Although the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.


ℓ1-gain filter design of discrete-time positive neural networks with mixed delays.
This paper mainly focuses on the filter design with ℓ1-gain disturbance attenuation performance for a class of discrete-time positive neural networks. Discrete and distributed time-varying delays occurring in neuron transmission are taken into account. Especially, the probabilistic distribution of distributed delays is described by a Bernoulli random process in the system model. First, criteria on the positiveness and the unique equilibrium of discrete-time neural networks are presented. Second, through linear Lyapunov method, sufficient conditions for globally asymptotic stability with ℓ1-gain disturbance attenuation performance of positive neural networks are proposed. Third, using the results obtained above, criteria on ℓ1-gain stability of the established filtering error system are presented, based on which a linear programming (LP) approach is put forward to design the desired positive filter. Finally, two examples of applications to water distribution network and genetic regulatory network are given to demonstrate the effectiveness and applicability of the derived results.


A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies. To investigate the tolerability (rate of AEs) and acceptability (rate of dropouts) of tDCS. Systematic review and meta-analysis of tDCS randomized, sham-controlled trials in healthy or neuropsychiatric adult samples from the first date available to March 9, 2016. We only included parallel studies performing at least 5 tDCS sessions. An adapted version of CONSORT guidelines for reporting harms outcomes was used to evaluate AE reporting. Sixty-four studies (2262 participants) were included. They had a low risk of publication bias and methodological bias for the items assessed. Dropout rates in active and sham tDCS groups were, respectively, 6% and 7.2% (OR = 0.82 [0.59-1.14]). However, almost half of studies reported no dropouts and only 23.4% reported its reasons; when reported, the most frequent reasons were AEs and protocol violation. A tolerability meta-analysis was not performed, as most studies did not report AEs. The quality of AEs reporting was also limited, particularly in smaller studies and stroke studies. Although overall dropout rate was low and similar in active and sham groups, studies did not adequately describe AEs. An updated questionnaire and guidelines for assessment of AEs in tDCS trials are proposed in order to standardize the reporting of AE in the field.


Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers.
Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocyte-derived and TAM-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.


Relationship between physical inactivity and health characteristics among participants in an employee-wellness program.
To characterize factors associated with physical inactivity among employees with access to workplace wellness program. We examined data on physical inactivity, defined as exercise less than once a week, from the 2010 health risk assessment completed by employees at a major academic institution (N = 16,976). Among employees, 18% of individuals reported physical activity less than once a week. Individuals who were physically inactive as compared with physically active reported higher prevalence of cardiovascular diseases (adjusted odds ratio [AOR], 1.36 [1.23 to 1.51]), fair or poor health status (AOR, 3.52 [2.97 to 4.17]), and absenteeism from work (AOR, 1.59 [1.41 to 1.79]). Overall, physically inactive employees as compared with physically active employees reported more interest in health education programs. Future research is needed to address barriers to physical inactivity to improve employee wellness and potentially lower health utility costs.


Impact of generic and therapeutic interchange incentives on community pharmacy.
The purpose of this project was to estimate the increase in revenues that the average community pharmacy could expect from generic and therapeutic interchange bonuses provided by PAID Prescriptions, Inc.'s Coordinated Care Network. Data from the published literature and conversations with managed care experts and PAID employees were used to develop estimates for best-guess, worst-case, and best-case scenarios. Estimates were based on data from early 1994. It was estimated that the interchange bonuses would increase the average community pharmacy's revenues by an average $105 per year, a $0.55 increase in the dispensing fee. Best-case and worse-case estimates were $227 and $44 for increases in revenues. These were equivalent to $1.19 and $0.23 increases in the dispensing fee. Even with the most optimistic estimates, the total fee paid by the Coordinated Care Network (the sum of the dispensing fee plus interchange bonuses) is much less than the average pharmacy's cost of dispensing a third party prescription.


Dopamine-induced changes to thalamic GABA concentration in impulsive Parkinson disease patients.
Impulsivity is inherent to behavioral disorders such as substance abuse and binge eating. While the role of dopamine in impulse behavior is well established, γ-aminobutyric acid (GABA) therapies have promise for the treatment of maladaptive behaviors. In Parkinson disease (PD), dopaminergic therapies can result in the development of impulsive and compulsive behaviors, and this clinical syndrome shares similar pathophysiology to that seen in addiction, substance abuse, and binge-eating disorders. We hypothesized that impulsive PD patients have a reduced thalamic GABAergic response to dopamine therapy. To test this hypothesis, we employed GABA magnetic resonance spectroscopy, D2-like receptor PET imaging, and clinical and quantitative measures of impulsivity in PD patients (n = 33), before and after dopamine agonist administration. We find a blunted thalamic GABA response to dopamine agonists in patients with elevated impulsivity (p = 0.027). These results emphasize how dopamine treatment differentially augments thalamic GABA concentrations, which may modify behavioral impulsivity.


Cytogenetics of bilateral renal cell carcinoma.
We analyzed cytogenetically 6 tumors from 4 patients with bilateral renal cell carcinoma. Comparison among findings in these patients with bilateral disease and previously reported cases of unilateral tumor demonstrates that bilaterality is associated with a more frequent loss of a sex chromosome, and gain of chromosomes 7 and 3, whereas unilateral tumors often are associated with loss of chromosome 3 material. It is proposed that bilateral tumors are distinct genetically from unilateral tumors and that most bilateral tumors have a genetic propensity to either enhanced metastatic spread to other renal tissue or spontaneous degeneration.


[Indications for selective lymphadenectomy and systematic axillary, inguinal and iliac lymph node dissection].
Lymphadenectomy is a surgical procedure in which lymph nodes are surgically resected. It is usually carried out for oncological surgical treatment of various malignant diseases. These include carcinomas of the breast, penis, vulva and anus as well as malignant melanomas and the broad field of sarcomas. A distinction is made between the removal of regional lymph nodes, the sentinel lymph node and the radical removal of lymph nodes in a body region. Cervical, axillary, inguinal and iliac lymph nodes are clinically relevant. The strategy of sentinel lymph node dissection, in which the first lymph node in the drainage system is resected and histopathologically examined for malignant tissue, has brought decisive advantages for the patients, as radical lymphadenectomy with its severe morbidities is utilized in fewer cases. This can improve the patient's quality of life by sparing the lymphatic drainage pathways and reducing lymphedema, inflammation and wound healing disorders. In addition, a lymphadenectomy may be indicated as part of palliative interventions. Another form of lymph node removal is the vascularized lymph node transplantation, which is used for reconstructive purposes in lymphedema. Therefore lymph node grafts are transferred to the site where lymph nodes were previously removed. This review presents the current status of lymphadenectomy in accordance with the German guidelines, anatomical knowledge and specific indications for axillary, inguinal and iliac lymphadenectomy. In addition, an overview of vascularized lymph node transfer is given.


Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome.
Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary hyperparathyroidism, which represents the most common clinical feature, followed by pituitary (functional and non-functional) adenomas, and neuroendocrine tumors. MEN4 clinically overlaps MEN type 1 (MEN1) but differs from it for milder clinical features and an older patient's age at onset. The underlying mutated gene, CDKN1B, encodes the cell cycle regulator p27, implicated in cellular proliferation, motility and apoptosis. Given the paucity of MEN4 cases described in the literature, possible genotype-phenotype correlations have not been thoroughly assessed, and specific clinical recommendations are lacking. The present review provides an extensive overview of molecular genetics and clinical features of MEN4, with the aim of contributing to delineate peculiar strategies for clinical management, screening and follow-up of the last and least known MEN syndrome. A literature search was performed through online databases like MEDLINE and Scopus. MEN4 is much less common that MEN1, tend to present later in life with a more indolent course, although involving the same primary organs as MEN1. As a consequence, MEN4 patients might need specific diagnostic and therapeutic approaches and a different strategy for screening and follow-up. Further studies are needed to assess the real oncological risk of MEN4 carriers, and to establish a standardized screening protocol. Furthermore, a deeper understanding of molecular genetics of MEN4 is needed in order to explore p27 as a novel therapeutic target.


Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer.
A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of β-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a-g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013-8.78 μM, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK2.


Assessment of liver stiffness measurement and ultrasound findings change during inotuzumab ozogamicin cycles for relapsed or refractory acute lymphoblastic leukemia.
In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno-occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver-related complications during clinical trials and real-life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow-up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate-severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver-related changes, especially with the severity of portal hypertension (PH)-related complications. Pre-transplant LSM was higher in patients receiving IO when compared with a control cohort. PH-related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.


Methyl gallate and chemicals structurally related to methyl gallate protect human umbilical vein endothelial cells from oxidative stress.
Methyl gallate (meGAL) is known as one of major antioxidants. To investigate whether meGAL protects human cells from oxidative stress, meGAL extracted from Korean medicinal plant, Cercis chinensis leaves, was primarily screened using cell viability assay against oxidative stress. Human umbilical vein endothelial cells (HUVECs) were treated with three different concentrations of meGAL for indicated time. After or during meGAL treatment, H(2)O(2) was added and incubated. meGAL showed free radical scavenging effect at low concentration (0.02 mM) and cell protective effect against H2O2-mediated oxidative stress. meGAL recovered viability of HUVECs damaged by H(2)O(2)-treatment, reduced the lipid peroxidation (LPO) and decreased the internal reactive oxygen species (ROS) level elevated by H(2)O(2)-treatment. Free radical scavenging effect of meGAL was proven to be very high. Differential display reverse transcription-PCR analysis showed that meGAL upregulated the levels of regulator of chromatin condensation 1, type 1 sigma receptor and phosphate carrier protein expressions, respectively. Based on structural similarity compared with meGAL, 14 chemicals were chosen and viability assay was performed. Four chemicals, haematommic acid (56.2% enhancement of viability), gallic acid (35.0%), methylorsellinic acid (23.7%), and syringic acid (20.8%), enhanced more potent cell viability than meGAL, which showed only 18.1% enhancement of cell viability. These results suggest that meGAL and four meGAL-related chemicals protect HUVECs from oxidative stress.


Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome.
Retrospective study of three cases of MEN type 1 and ZES, to compare with one similar case in publication of The Spanish J of Gastroenterol: MEN-1 and ZES for pancreatic gastrinoma.


Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling.
Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell.


Relation between alcohol consumption and the success of Helicobacter pylori eradication therapy using omeprazole, clarithromycin and amoxicillin for 1 week.
To study the relationship between daily alcohol consumption and the result of eradication therapy for Helicobacter pylori using omeprazole, clarithromycin and amoxicillin for 1 week. Clinical trial. Urban health centre, general medicine section. One hundred and fifty-six patients with a diagnosis of peptic ulcus or chronic gastritis. Helicobacter pylori infection was confirmed by the urease test, the 14C-urea breath test, IgG serology or biopsy. A combination of omeprazole, 20 mg twice daily, clarithromycin, 500 mg twice daily, and amoxicillin, 1000 mg twice daily was administered for 1 week. No other drugs were given. Four to 8 weeks later a 14C-urea breath test was carried out to confirm eradication. Logistic regression was used to assess the relationship between eradication and daily alcohol consumption (main covariable), age, sex, smoking, length of illness, pathology studied (ulcus or gastritis) and therapeutic compliance. Eradication (intention to treat analysis) was successful in 118 patients (75.6%; 95% CI, 68.9-82.4). The only variable significantly associated with the result of the therapy was daily alcohol consumption, with a higher probability of failure in non-consumers (29.9%) than in consumers (12.2%), adjusted OR 3.24 (95% CI, 1.12-9.20; P = 0.03). Eradication was dose dependent: 70.1% in abstemious patients (n = 107), rising to 79.3% in users of 4-16 g of pure ethanol a day (n = 29) and to 100% in users of 18-60 g daily (n = 20) with a P value of 0.005 for the trend. Daily alcohol consumption appears to have an additive effect in this eradication therapy.


A simulation-based selection process for trying to identify medical students who will become outstanding general surgery residents.
Selecting the right applicants for general surgery training is critical and difficult. We refined our selection process by using a pre-interview preparation package and simulation-based assessments. Sixty applicants invited for categorical general-surgery residency interview were mailed an educational package which included a link to instructional videos, surgical instruments and low-cost models for suturing, open knot tying, and adrenal anatomy knowledge. During the interview day, applicants participated in a 48-min simulation-based assessment consisting of same tasks included in the package. Performance scores were used to assist in ranking applicants. The matched 2018class was compared to our previous intern classes on several objective assessments (Surgical-Olympics and ABSITE score). Students scored >50tile moved high in our final rank-list. The 2018 class scored significantly higher in 10 of 15 Surgical-Olympic stations compared to our 2015-17class with no significant difference on ABSITE score. By mailing out a pre-interview welcome package and adding a simulation based assessment to our General Surgery categorical interview process, we believe early objective data suggests we positively influenced our 2018 NRMP match.


SNPs in forensic genetics: a review on SNP typing methodologies.
There is an increasing interest in single nucleotide polymorphism (SNP) typing in the forensic field, not only for the usefulness of SNPs for defining Y chromosome or mtDNA haplogroups or for analyzing the geographical origin of samples, but also for the potential applications of autosomal SNPs. The interest of forensic researchers in autosomal SNPs has been attracted due to the potential advantages in paternity testing because of the low mutation rates and specially in the analysis of degraded samples by use of short amplicons. New SNP genotyping methods, chemistries and platforms are continuously being developed and it is often difficult to be keeping up to date and to decide on the best technology options available. This review offers to the reader a state of the art of SNP genotyping technologies with the advantages and disadvantages of the different chemistries and platforms for different forensic requirements.


Sleep Deficiency and Opioid Use Disorder: Trajectory, Mechanisms, and Interventions.
Opioid use disorder (OUD) is a chronic and relapsing brain disease characterized by loss of control over opioid use and impairments in cognitive function, mood, pain perception, and autonomic activity. Sleep deficiency, a term that encompasses insufficient or disrupted sleep due to multiple potential causes, including sleep disorders (eg, insomnia, sleep apnea), circadian disruption (eg, delayed sleep phase and social jet lag), and poor sleep quality (eg, sleep fragmentation, impaired sleep architecture), is present in greater than 75% of patients with OUD. This article focuses on highlighting bidirectional mechanisms between OUD and sleep deficiency and points toward promising therapeutic targets.


Barriers to supervised exercise training in a randomized controlled trial of breast cancer patients receiving chemotherapy.
Exercise adherence is a challenge for breast cancer patients receiving chemotherapy but few studies have identified the key barriers. In this paper, we report the barriers to supervised exercise in breast cancer patients participating in a randomized controlled trial. Breast cancer patients initiating adjuvant chemotherapy (N = 242) were randomly assigned to usual care (n = 82) or supervised resistance (n = 82) or aerobic (n = 78) exercise. Participants randomized to the two exercise groups (n = 160) were asked to provide a reason for each missed exercise session. The two exercise groups attended 70.2% (5,495/7,829) of their supervised exercise sessions and provided a reason for missing 89.5% (2,090/2,334) of their unattended sessions. The 2,090 reasons represented 36 different barriers. Feeling sick (12%), fatigue (11%), loss of interest (9%), vacation (7%), and nausea/vomiting (5%) accounted for the most missed exercise sessions. Disease/treatment-related barriers (19 of the 36 barriers) accounted for 53% (1,102/2,090) of all missed exercise sessions. Demographic and medical variables did not predict the types of exercise barriers reported. Barriers to supervised exercise in breast cancer patients receiving chemotherapy are varied but over half can be directly attributed to the disease and its treatments. Behavioral support programs need to focus on strategies to maintain exercise in the face of difficult treatment side effects.


An item response theory-based pain item bank can enhance measurement precision.
Cancer-related pain is often under-recognized and undertreated. This is partly due to the lack of appropriate assessments, which need to be comprehensive and precise yet easily integrated into clinics. Computerized adaptive testing (CAT) can enable precise-yet-brief assessments by only selecting the most informative items from a calibrated item bank. The purpose of this study was to create such a bank. The sample included 400 cancer patients who were asked to complete 61 pain-related items. Data were analyzed using factor analysis and the Rasch model. The final bank consisted of 43 items which satisfied the measurement requirement of factor analysis and the Rasch model, demonstrated high internal consistency and reasonable item-total correlations, and discriminated patients with differing degrees of pain. We conclude that this bank demonstrates good psychometric properties, is sensitive to pain reported by patients, and can be used as the foundation for a CAT pain-testing platform for use in clinical practice.


Preserved structural integrity of white matter adjacent to low-grade tumors.
Brain tumors may dislocate, infiltrate, or disrupt the adjacent fiber tracts. We examined (1) microstructural changes of white matter (WM) adjacent to supratentorial low grade tumors in children and (2) WM tracts of the affected hemisphere using diffusion tensor imaging (DTI). We hypothesized that the structural integrity of the adjacent WM tracts would be preserved in these slow-growing tumors. DTI was performed in 11 children with low grade tumors diagnosed by magnetic resonance imaging (MRI). Regions of interest were placed in the tumor, in WM adjacent to tumor, and on the normal contralateral side. Fractional anisotropy (FA), trace, and eigenvalues were measured. Color-coded maps and tractography were used to grade the WM tracts: Grade one was normal tract size and color hue; grade two was reduced tract size but preserved color hue; and grade three was loss of color hue or failure to track on tractography. Grades one and two were subcategorized as "a" or "b," depending on the absence or presence of tract displacement. There were no significant differences in FA, trace, and eigenvalues between WM adjacent to tumor and the contralateral side. One patient had grade 1a changes, six grade 1b, and four grade 2b. We found preserved microstructural integrity of WM adjacent to low grade tumors in children. Color vector maps and tractography demonstrated displacement of the WM tracts in all but one patient. Our findings could be useful for neurosurgical planning to minimize injury to the WM tracts and improve preoperative risk analysis.


Measles outbreak investigation in Artuma Fursi Woreda, Oromia Zone, Amhara Region, Ethiopia, 2018: a case control study.
To confirm the existence of Outbreak, describe cases in person, place and time, and identify determinants of the outbreak. Unmatched case control study in the ratio of 1:4 (38 cases and 152 controls) was conducted in Artuma Fursi Woreda from July 13 to August 1/2018. Data were collected with standard questionnaires. Collected data were entered into Epi Info version 7 and exported to Statistical package for social science (SPSS) version 23 for analysis. A total of 38 cases and 1 death with attack rate and case fatality rate 11.8/100,000 and 2.6%, respectively. All study participants had not vaccination history. Females and age group 5-14 were more affected. Being 5-14 years old versus (vs) ≥ 15 years [adjusted odd ratio (AOR) = 3.53; 95% CI 1.52-8.45)], contact with cases vs no contact with cases [AOR = 2.78; 95% CI 1.23-8.67] and travel history 7-18 days prior onset of illness vs no travel history [AOR = 2.53; 95% CI 1.31-7.24] were significantly associated with contracting measles. Routine and supplement immunization should be strengthened to reduce future occurrence of outbreak.


The effect of physical exercise on cerebral blood flow in Alzheimer's disease.
In recent years there has been an increasing focus on the relation between cerebrovascular health, physical exercise and Alzheimer's disease. The aim of the current study was to determine the effect of moderate-to-high-intensity aerobic exercise on cerebral blood flow in patients with mild to moderate Alzheimer's disease. Fifty-one patients were randomized to either usual care or moderate-to-high intensity aerobic exercise for 16 weeks. Exercise had no consistent effect on whole brain or regional cerebral blood flow. Sixteen weeks of exercise are, therefore, not sufficient to produce a consistent increase in cerebral blood flow in a relatively small sample of Alzheimer's patients.


Intramedullary spinal sarcoidosis: clinical improvement reflected in T-lymphocyte subpopulation ratios.
Case report. A case report of spinal sarcoidosis improving clinically and radiographically with treatment which correlated with improvement in cerebrospinal fluid T-lymphocyte subpopulation ratios. Walter Reed Army Medical Center. A 46-year-old man presented with an enhancing spinal cord lesion. Lymph node biopsy confirmed sarcoidosis, and cerebrospinal fluid (CSF) analysis showed elevation in the ratio of two T-lymphocyte subpopulations. Treatment with steroids resulted in clinical resolution and immunocytologic improvement in the CSF.


Rheological study of α- and κ-carrageenan expansion in solution as effects of the position of the sulfate group.
The viscosity of carrageenan solutions in the coil state was greater for α-carrageenan (α-Car) compared with that for κ-carrageenan (κ-Car); thus, the impact of one sulfate group on 3,6-anhydro-D-galactose was compared with the impact of one sulfate group on D-galactose units of the carrabiose residues. The thermal expansion coefficient of the solutions, B2 × Tc, characterizes the way the viscosity decreases because of extension of the physical bonds of the systems to their rupture point (Tc) under increasing temperature. The Tc and B2 × Tc of water were equal to (100 ± 5) °C and (1.57 ± 0.05) × 10-2/°C, respectively. The Tc of the α-Car and κ-Car systems increased after the addition of CaCl2 and KCl, respectively, and with increasing polysaccharide concentration. However, the B2 × Tc of the α-Car and κ-Car systems were rather sensitive to CaCl2 and KCl, respectively. In the overall solutions examined, the expansion of α-Car systems was found to be between 1.5 × 10-2/°C and 1.61 × 10-2/°C, greater than the expansion of κ-Car systems, which was between 1.5 × 10-2/°C and 1.2 × 10-2/°C. Thus, α-Car is a good alternative to κ-Car for reducing syneresis phenomena, and its sensitivity as ι-Car to divalent cations would be due to the anhydro cycle.


Clinical characteristics, evolution, and treatment-related risk factors for mortality among immunosuppressed patients with influenza A (H1N1) virus admitted to the intensive care unit.
Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. A prospective multicenter observational cohort study was based on data from a Spanish registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15-4.38;p = 0.017). In the subgroup of hematological patients (n = 141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32-7.41; p = 0.010). Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.


Automated assessment of foot elevation in adults with hereditary spastic paraplegia using inertial measurements and machine learning.
Hereditary spastic paraplegias (HSPs) cause characteristic gait impairment leading to an increased risk of stumbling or even falling. Biomechanically, gait deficits are characterized by reduced ranges of motion in lower body joints, limiting foot clearance and ankle range of motion. To date, there is no standardized approach to continuously and objectively track the degree of dysfunction in foot elevation since established clinical rating scales require an experienced investigator and are considered to be rather subjective. Therefore, digital disease-specific biomarkers for foot elevation are needed. This study investigated the performance of machine learning classifiers for the automated detection and classification of reduced foot dorsiflexion and clearance using wearable sensors. Wearable inertial sensors were used to record gait patterns of 50 patients during standardized 4 [Formula: see text] 10 m walking tests at the hospital. Three movement disorder specialists independently annotated symptom severity. The majority vote of these annotations and the wearable sensor data were used to train and evaluate machine learning classifiers in a nested cross-validation scheme. The results showed that automated detection of reduced range of motion and foot clearance was possible with an accuracy of 87%. This accuracy is in the range of individual annotators, reaching an average accuracy of 88% compared to the ground truth majority vote. For classifying symptom severity, the algorithm reached an accuracy of 74%. Here, we show that the present wearable gait analysis system is able to objectively assess foot elevation patterns in HSP. Future studies will aim to improve the granularity for continuous tracking of disease severity and monitoring therapy response of HSP patients in a real-world environment.


Building carbon peak scenario prediction in China using system dynamics model.
As the issue of global climate change caused by carbon emissions is of great concern, China has proposed achieving its achieve carbon peak goal by 2030. Building carbon emissions account for approximately 50% of China's total carbon emissions. It is crucial to study the time and values of building carbon peaks. In this paper, based on a system dynamics model, logarithmic mean Divisia index model and Monte Carlo simulation, we predict the building carbon peak in China. The following conclusions are obtained: 1) in the baseline scenario, China's building carbon emissions will peak at 5,427 million tons in 2027. In the high-speed development scenario, China's building carbon emissions will peak at 6,298 million tons in 2032. In the coordinated development scenario, the green development scenario, the low-carbon development scenario, and the low-speed development scenario, the peak occurs in 2030 at 5,972 million tons, 5,991 million tons, 5,657 million tons, and 6,329 million tons, respectively. 2) According to the comprehensive simulation, China's building carbon emissions will reach the peak in 2030, with an 80% probability of reaching 5,729-6,171 million tons.


Family history of coronary heart disease, health care and health behaviors.
Previous studies on health care and health behaviors in individuals with a family history of coronary heart disease (CHD) have produced contradictory results, and there is still no evidence that these individuals are more aware of their risk and have improved health behaviors and heath care. This study aims to evaluate health care and health behaviors according to family history of CHD. Individuals randomly selected from the general population living in Porto, Portugal, aged ≥ 18 years (evaluation period: 1999-2003), and without prior history of chronic diseases (n=764), were evaluated by questionnaires on family and personal disease history, health care and health behaviors. A family history of CHD was defined as the occurrence of acute myocardial infarction or sudden death in at least one first-degree relative. Odds ratios and 95% confidence intervals (OR, 95% CI) were calculated using unconditional logistic regression after stratification for age (18-39 vs. ≥ 40 years) and education (≤ 6 vs. >6 years schooling). Among men, 20% reported a family history of CHD, approximately the same proportion as in women (19.4%) (p=0.900). The proportion of subjects with a family history of CHD was significantly higher in older (≥ 40 vs. 18-39 years: 25.0% vs. 12.0%, p<0.001) and less educated individuals (>6 vs. ≤ 6 years: 27.0% vs. 17.1%, p=0.004). Overall, no significant associations were found between health care and behaviors and CHD family history. Only in younger individuals, after adjustment for education, was a significant positive association found between 1-2 dental visits and CHD family history (OR=2.92; 95% CI: 1.27-6.70). Younger subjects who smoked and consumed alcohol and caffeine also presented a higher probability of having CHD family history, but the associations were not statistically significant. In this population without disease requiring regular medical care, individuals with CHD family history had similar care-seeking patterns and health behaviors to those without. These results suggest a lack of awareness of their increased risk and highlight the importance of developing measures to promote sustained and effective changes in risk factors in individuals with genetic susceptibility to CHD.


Racial and ethnic differences in abdominal soft tissue sarcoma incidence in New Zealand: a retrospective audit.
Soft tissue sarcomas are a rare and heterogenous group of tumours. Anecdotally there seems to be an over representation of patients of Māori ethnicity presented at the Auckland Regional Sarcoma Multidisciplinary Meeting (MDM). To date no study has reported on ethnicity demographics of abdominal and retroperitoneal sarcoma in New Zealand. The aim of this study is to characterize the ethnicity distribution of patients discussed at the regional MDM. A retrospective audit was performed of patients presented at the Auckland Regional Sarcoma MDM between January 2015 and December 2020 with abdominal sarcoma. Ethnicity documentation for these patients was reviewed. One hundred and twenty-four patients with intra-abdominal and retroperitoneal tumours were discussed at MDM with 61 proceeding for resection, of those 43 (70.5%) were primary tumours, 10 (16.4%) were recurrent tumours and 8 (13.1%) had metastatic disease. Liposarcoma made up 56 (45.2%) cases, Leiomyosarcoma 33 (26.6%), Other 35 (28.2%). Ethnicities for this group specifically were European 64 (51.6%), Māori 31 (25.0%), Pacific Peoples 17 (13.7%), Asian 6 (4.8%) and Other/unknown 3(2.4%). This was found to be statistically significantly different to the expected ethnicity distribution based on 2018 census data from North Island DHBs (χ2 = 19.55, p = 0.00), with Māori and Pacific Peoples being over-represented and Asian patients being under-represented. Recommendation for surgery did not appear to be related to ethnicity. Our descriptive data shows a higher proportion of patients of Māori ethnicity discussed through the North Island regional sarcoma MDM than we would expect comparted to ethnicity distribution in the general population. It is unclear whether this represents a true difference in incidence based on ethnicity.


Radiation dose during interventional cardiology procedures: portable C-arm vs. a new generation fluoroscopy system.
Occupational exposure to ionizing radiation poses health risks for veterinary interventionalists. There are limited veterinary studies evaluating radiation dose in the cardiac catheterization laboratory. The purpose of this study was to report direct radiation dose exposure to patients during common interventional cardiology procedures and compare these doses between two fluoroscopy units. One hundred and fifty-four client-owned dogs. Patient dose during procedures using a portable C-arm were retrospectively analyzed and compared to those performed in a contemporary interventional suite. Fluoroscopy equipment, procedure type, operator, patient weight, fluoroscopy time, dose area product, and air kerma were recorded and statistically modeled using univariable and multivariable linear regression to evaluate the effect of each factor. Patient dose population (154 dogs), comprised 61 patent ductus arteriosus occlusions, 60 balloon pulmonary valvuloplasties, and 33 pacemaker implantations. Patient dose was significantly lower in the group utilizing a newer generation fluoroscopy unit vs. the group utilizing an older portable C-arm, positively correlated with patient weight, and highest during balloon pulmonary valvuloplasties compared to patent ductus arteriosus occlusions or pacemaker implantations (all P<0.010). Newer fluoroscopy systems can be equipped with technologies that improve image quality while reducing patient dose and radiation exposure to interventional personnel. We documented a significant reduction in patient radiation dose using a newer fluoroscopy system as compared to an older portable C-arm for interventional cardiology procedures in animals. Improved knowledge of patient radiation dose factors may promote better radiation safety protocols in veterinary interventional cardiology.


STAT1 inhibits human hepatocellular carcinoma cell growth through induction of p53 and Fbxw7.
Aberrant STAT1 signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell proliferation and survival. However, the role of STAT1 signaling in HCC and its underlying mechanism remain elusive. We transiently transfected pcDNA3.1-STAT1 and STAT1 siRNA into SMMC7721 and HepG2 cells. Western blot and qRT-PCR examined the expression of protein and RNA of target genes. Cell viability was assessed using MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. We found that STAT1 overexpression increased protein expression of p53 and Fbxw7, and downregulated the expression of cyclin A, cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Conversely, ablation of STAT1 had the opposite effect on p53, Fbxw7, Hes-1, NF-κB p65, cyclin A, cyclin D1, cyclin E and CDK2, and improved the viability of SMMC7721 and HepG2 cells. Our data indicate that STAT1 exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis, and may provide a basis for the design of new therapies for the intervention of HCC in the clinic.


Detection of portal venous gas on sonography, but not on CT.
We report three cases of portal venous gas detected on sonography without any portal abnormality on CT. In such a situation portal gas could correspond to a tiny amount of intraluminal gas after blunt abdominal trauma or, in contrast, to large or very large quantities of high blood-solubility gases in case of septicemia. Outcome was favorable in all three cases.


Effects of 0.5 and 1.0 MAC isoflurane, sevoflurane and desflurane on intracranial and cerebral perfusion pressures in children.
Isoflurane has been a commonly used agent for neuroanesthesia, but newer agents, sevoflurane and desflurane, have a quicker onset and shorter emergence from anesthesia and are increasingly preferred for general pediatric anesthesia. But their effects on intracranial pressure (ICP) and cerebral perfusion pressure (CPP), especially in pediatric patients with already increased ICP, have not been well documented. We studied 36 children scheduled for elective implantation of an intraparenchymal pressure device for 24 h monitoring for suspected elevated ICP. After a standardized intravenous anesthesia, the patients were moderately hyperventilated with 60% nitrous oxide (N2O) in oxygen. The patients were then randomized to receive 0.5 and 1.0 MAC of isoflurane (Group I, n = 12), sevoflurane (Group S, n = 12) or desflurane (Group D, n = 12) in 60% N2O in oxygen. Respiratory and hemodynamic variables, ICP and CPP were recorded at baseline and after exposure to a target level of test drug for 10 min or until CPP fell below 30 mmHg (recommended lower ICP level is 25 mmHg in neonates, rising to 40 mmHg in toddlers). When comparing baseline values with values at 1.0 MAC, mean arterial pressure (MAP) decreased (P < 0.001) in all groups, with no differences between the groups. ICP increased (P < 0.001) with all agents, mean +2, +5, and +6 mmHg in Group I, S and D, respectively, with no differences between the groups. Regression analyzes found no relationship between baseline ICP and the increases in ICP from baseline to 1.0 MAC for isoflurane or sevoflurane. However, increased baseline ICP tended to cause a higher ICP increase with 1.0 MAC desflurane; regression coefficient +0.759 (P = 0.077). The difference between regression coefficients for Group I and Group D were not significant (P = 0.055). CPP (MAP-ICP) decreased (P < 0.001) in all groups, mean -18, -14 and -17 mmHg in Group I, S and D, respectively, with no significant difference between the groups. 0.5 and 1.0 MAC isoflurane, sevoflurane and desflurane in N2O all increased ICP and reduced MAP and CPP in a dose-dependent and clinically similar manner. There were no baseline dependent increases in ICP from 0 to 1.0 MAC with isoflurane or sevoflurane, but ICP increased somewhat more, although statistically insignificant, with higher baseline values in patients given desflurane. The effect of MAP on CPP is 3-4 times higher than the effect of the increases in ICP on CPP and this makes MAP the most important factor in preserving CPP. In children with known increased ICP, intravenous anesthesia may be safer. However, maintaining MAP remains the most important determinant of a safe CPP.


Usefulness of teledermatology in prisons. The experience in the Penitentiary Center Castellón II.
Teledermatology is the application of new technologies for the care of skin diseases. Its application in prisons allows the diagnosis and treatment of prisoners without the need to transfer them to the hospital, avoiding the problems associated with travel. The objective of this work is to analyze the usefulness of teledermatology in prisons, through a retrospective observational study in the Castellón II-Albocàsser penitentiary. The study sample consisted of 37 patients and 43 interconsultations. All the consultations corresponded to men, with a mean age of 42.43 years. 95.3% of the consultations were asynchronous and in 86% of them a diagnosis and a complete treatment plan were established. Only 18.6% of the consultations required a face-to-face consultation. It is concluded that teledermatology in prisons is effective in the care and resolution of dermatological problems.


Expression of vascular endothelial growth factor in peripheral blood cells of preeclamptic women.
Preeclampsia is associated with platelet and endothelial dysfunction. Vascular endothelial growth factor (VEGF) is found in peripheral blood leukocytes and released from platelets on activation. We analyzed the content of (VEGF) in peripheral blood cells of preeclamptic women. The VEGF content of platelets, mononuclear white blood cells, and granulocytes of peripheral blood were analyzed from 12 women with preeclampsia, 19 healthy pregnant women, and 20 nonpregnant women. Protein released from lysed cells was analyzed by enzyme-linked immunoassay (ELISA). Platelet VEGF content of preeclamptic women (0.081 ng/109 cells, 0.016 to 2.7 ng/109 cells; median, range) was similar to that of healthy pregnant women (0.31 ng/109 cells, 0.013 to 0.92 ng/109 cells) and that of nonpregnant (0.073 ng/109 cells, 0.012 to 0.76 ng/109 cells) women. Likewise, the VEGF content of granulocytes was similar in preeclamptic (18.5 ng/109 cells, 1.2 to 193 ng/109 cells), healthy pregnant (25.3 ng/109 cells, 0.8 to 441 ng/109 cells), and nonpregnant (29 ng/109 cells, 0.25 to 200 ng/109 cells) women. In mononuclear cells, the VEGF content of healthy pregnant women was higher (4.4 ng/109 cells, 0.13 to 13.7 ng/109 cells) than in nonpregnant women (1.7 ng/109 cells, 0.15 to 11.4 ng/109 cells, P < 0.05). Also, the mononuclear cell VEGF content of preeclamptic women (8.2 ng/109 cells, 0.04 to 23 ng/109 cells) tended to be higher than in nonpregnant women (P approximately 0.07). Uncomplicated pregnancy is associated with an elevated VEGF content of mononuclear cells. Preeclampsia does not seem to affect the VEGF content of maternal peripheral blood mononuclear cells, granulocytes, or platelets.


Important aspects of intrapartum care described by first-time mothers giving birth in specialised obstetric units in Norway: A qualitative analysis of two questions from the Babies Born Better study.
To explore aspects of intrapartum care that were importanrt for primiparous women who had given birth in large obstetric units in Norway. We used data from the Babies Born Better (B3) survey, version 1, which is an international, web-based qualitative survey. We performed a reflexive, thematic analysis of the responses to two questions about descriptions of aspects of positive care and areas of care requiring improvement during the intrapartum period. The responders could give up to three responses to each question and there were no word limits. In all, 677 first time mothers who gave birth at the five largest specialised obstetric units in Norway during 2014-2015 were included in the study. The thematic analysis of the 2 205 responses resulted in three final themes: 'Communication and positive interactions with the caregivers', 'Autonomy and active involvement in the labour process', and 'Safety, competence and quality of labour care'. For women who give birth for the first time in specialised obstetric units both relational aspect such as communication and respect, and environmental aspects such as facilities, are of importance. First-time mothers might be particularly vulnerable to absence of positive interactions with caregivers because they lack the resources former birthing experience can give. It is essential to give unexperienced birthing women special attention during childbirth because the first birth may influence decisions in following pregnancies.


Environmental enrichment facilitates foraging behavior.
Mongolian gerbils (Meriones unguiculatus) were tested at 24 months of age after having experienced an outdoor desert environment for one hour each month after weaning, or at 8 months of age after being reared from birth in outsize cages in the laboratory. Both groups of enriched gerbils found food more rapidly than did 24-month-old handled controls, 8-month-old naive gerbils, or 8-month-old gerbils reared in small cages. There were no differences in locomotor activity, in latency to emerge from a small box, or in attention to novel objects or conspecific odors. Efficiency in finding food was not associated with types of food chosen, and the foods selected were not directly related to types of food eaten previously.


Plasmodium falciparum R2TP complex: driver of parasite Hsp90 function.
Heat shock protein 90 (Hsp90) is essential for the development of the main malaria agent, Plasmodium falciparum. Inhibitors that target Hsp90 function are known to not only kill the parasite, but also reverse resistance of the parasite to traditional antimalarials such as chloroquine. For this reason, Hsp90 has been tagged as a promising antimalarial drug target. As a molecular chaperone, Hsp90 facilitates folding of proteins such as steroid hormone receptors and kinases implicated in cell cycle and development. Central to Hsp90 function is its regulation by several co-chaperones. Various co-chaperones interact with Hsp90 to modulate its co-operation with other molecular chaperones such as Hsp70 and to regulate its interaction with substrates. The role of Hsp90 in the development of malaria parasites continues to receive research attention, and several Hsp90 co-chaperones have been mapped out. Recently, focus has shifted to P. falciparum R2TP proteins, which are thought to couple Hsp90 to a diverse set of client proteins. R2TP proteins are generally known to form a complex with Hsp90, and this complex drives multiple cellular processes central to signal transduction and cell division. Given the central role that the R2TP complex may play, the current review highlights the structure-function features of Hsp90 relative to R2TPs of P. falciparum.


Cross-Linking Mass Spectrometry Uncovers Interactions Between High-Density Lipoproteins and the SARS-CoV-2 Spike Glycoprotein.
High-density lipoprotein (HDL) levels are reduced in patients with coronavirus disease 2019 (COVID-19), and the extent of this reduction is associated with poor clinical outcomes. While lipoproteins are known to play a key role during the life cycle of the hepatitis C virus, their influence on coronavirus (CoV) infections is poorly understood. In this study, we utilize cross-linking mass spectrometry (XL-MS) to determine circulating protein interactors of the severe acute respiratory syndrome (SARS)-CoV-2 spike glycoprotein. XL-MS of plasma isolated from patients with COVID-19 uncovered HDL protein interaction networks, dominated by acute-phase serum amyloid proteins, whereby serum amyloid A2 was shown to bind to apolipoprotein (Apo) D. XL-MS on isolated HDL confirmed ApoD to interact with SARS-CoV-2 spike but not SARS-CoV-1 spike. Other direct interactions of SARS-CoV-2 spike upon HDL included ApoA1 and ApoC3. The interaction between ApoD and spike was further validated in cells using immunoprecipitation-MS, which uncovered a novel interaction between both ApoD and spike with membrane-associated progesterone receptor component 1. Mechanistically, XL-MS coupled with data-driven structural modeling determined that ApoD may interact within the receptor-binding domain of the spike. However, ApoD overexpression in multiple cell-based assays had no effect upon viral replication or infectivity. Thus, SARS-CoV-2 spike can bind to apolipoproteins on HDL, but these interactions do not appear to alter infectivity.