A2A adenosine receptor (AR) activation inhibits pro-inflammatory cytokine production by human CD4+ helper T cells and regulates Helicobacter-induced gastritis and bacterial persistence.
Helicobacter pylori causes a lifelong infection and provides a model of bacterial adaptation and persistent colonization. Adenosine is an anti-inflammatory mediator that limits tissue damage during inflammation. We studied the role of adenosine in the T-cell-mediated regulation of gastritis and bacterial persistence. After 4 h of activation, human T helper (Th) cells increased A(2A) adenosine receptor (A(2A)AR) mRNA level (sevenfold). A(2A)AR was the predominant subtype expressed in resting and stimulated gastric or peripheral Th cells. Stimulation with ATL313, an A(2A)AR agonist, increased cyclic AMP (cAMP) accumulation and reduced interleukin-2 (IL-2) production by 20-50%. ATL313 also attenuated tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production, which was inhibited by an A(2A)AR antagonist. Infection of IL-10-deficient mice with H. pylori is cleared spontaneously due to the marked inflammation. Administration of ATL313 during infection reduced gastritis and pro-inflammatory cytokine responses while bacterial load increased. In contrast, infection of A(2A)AR-deficient mice enhanced gastritis. Thus, A(2A)AR limits the pro-inflammatory effects of Th cells and favor chronic Helicobacter infection.


A child with a foreign body in bronchus misdiagnosed as asthma.
Foreign body ingestion should be considered as an important differential in a child with difficult asthma. We report an 11-year-old male child with foreign body aspiration who initially was diagnosed and treated as difficult asthma. Later on, he was diagnosed to have a foreign body in the right bronchus, which was successfully removed by flexible bronchoscopy.


Erratum: Gas-induced friction and diffusion of rigid rotors [Phys. Rev. E 97, 052112 (2018)].
This corrects the article DOI: 10.1103/PhysRevE.97.052112.


Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception.
Delta opioid receptor agonists produce only a moderate degree of antinociception, possibly reflecting the predominantly intracellular location of delta opioid receptor. However, recent studies suggest that short term morphine pretreatment can increase delta opioid receptor-mediated antinociception by promoting the translocation of delta opioid receptor to the cell surface. Even more striking sensitization has been reported after long term morphine pretreatment and withdrawal in locomotor tests. In the present study we therefore examined the effects of longer term morphine pretreatment and withdrawal on delta opioid receptor-mediated antinociception in the formalin test. Male adult rats were pretreated daily with morphine (10 mg/kg s.c.) or saline for 10 days, and were tested acutely with the delta opioid receptor agonist [D-Ala2,Glu4]-deltorphin (intrathecal) at 0, 7 and 14 days of withdrawal. Unexpectedly, chronic morphine pre-exposure resulted in tolerance to [D-Ala2,Glu4]-deltorphin-induced antinociception, and this occurred at 0 and 7 but not 14 days of morphine withdrawal. Morphine challenge at withdrawal day 7 confirmed the presence of tolerance to the antinociceptive effects of this drug. Chronic morphine pretreatment also resulted in tolerance to the locomotor stimulant effect of [D-Ala2,Glu4]-deltorphin (given i.c.v.), contrary to a previous report of sensitization. However, consistent with previous reports, short term (2 day) pretreatment with morphine did result in sensitization to [D-Ala2,Glu4]-deltorphin. Subsequent in vitro analysis, using [125I][D-Ala2,Glu4]-deltorphin or guanosine 5'(gamma-35S-thio) triphosphate autoradiography, did not reveal any changes in delta opioid receptor binding or function resulting from chronic morphine pretreatment. In conclusion, chronic morphine pretreatment caused tolerance to delta opioid receptor-mediated behavioral effects with no clear change at the receptor level.


Microplastics in fish and sediments from the Montenegrin coast (Adriatic Sea): Similarities in accumulation.
The accumulation of microplastics (MPs) in the biotic and abiotic components of the marine environment poses a major threat to marine ecosystems worldwide. The objective of this study was to document, for the first time, differences in MP accumulation in the gastrointestinal tract of two commercially important fish species and to evaluate the possible correlation between MP accumulation in the biotic (fish) and abiotic (sediment) components of the marine environment of the Montenegrin coast (Adriatic Sea). Samples were collected from two areas of the Montenegrin coast, Boka Kotorska Bay and the coastal part of the open sea. The frequency of MP ingestion was 58.6 % for Mullus barbatus and 54 % for Merluccius merluccius, while the average number of ingested MPs was 2.9 ± 0.5 and 3.2 ± 1.0 items/individual, respectively. Average MP abundance in surface sediments from Boka Kotorska Bay and the coastal part of the open sea was 315 ± 45 and 435 ± 258 MPs/kg of dry sediment, respectively. Most MPs identified were filaments, followed by fragments and films, while the most abundant polymers found in fish and sediments samples were polypropylene and polyethylene. The present results indicate that MP pollution in the study area is reflected in the accumulation of MPs in the biotic (fish) and abiotic (sediment) components of the marine environment. Measures need to be taken to reduce the input of plastics/MPs into the marine environment.


Plasmon-waveguide resonance (PWR) spectroscopy for directly viewing rates of GPCR/G-protein interactions and quantifying affinities.
Plasmon-waveguide resonance (PWR) spectroscopy is an optical technique that has been developed in our laboratories and applied to the study of membrane-associated proteins, especially GPCRs. It has high sensitivity and requires no labeling of materials, and it can monitor changes in proteolipid mass density and conformation in real time using plasmon excitation by light polarized both perpendicular and parallel to the resonator surface. Direct measurements will be described of the association of ligands and G-proteins to GPCRs incorporated into a self-assembled lipid bilayer deposited on the silica surface of a PWR resonator. These studies have provided new insights into the functioning of this important class of signaling proteins.


Preliminary assessment of proanthocyanidin isolates of Vitis vinifera seed on the central nervous system of male Albino mice.
This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice. Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents. One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice. Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.


Methodological issues on 'challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review'.
Challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review' is a policy review paper and we published in BMC - Archives of Public Health. Policy research is the process of conducting research, analysis of, a fundamental social problem in order to provide policymakers with pragmatic, action-oriented recommendations for alleviating the problem. The objective of this paper is to illustrate some methodological issues used in that paper.


Volume regulation of spermatozoa by quinine-sensitive channels.
Bovine spermatozoa were shown to exhibit rapid regulatory volume decrease (RVD) when exposed to hypotonic saline media. This quinine- and quinidine-sensitive regulatory volume decrease was coincident with K+ release due to stretch-activation of inhibitor-specific presumptive K+ channels. The regulatory volume decrease response was much faster than a similar phenomenon observed in human peripheral blood lymphocytes. Studies on volume changes in different electrolyte and nonelectrolyte media suggested that: (1) this inhibitor-specific channel could also be a nonspecific pore in the spermatozoal membrane for nonelectrolytes below 150 daltons; (2) subpopulations (of nearly equal size) of the spermatozoa differ in the expression of the pore; (3) capacitation abolishes this distinction between subpopulations of spermatozoa; and (4) the general case of RVD for other mammalian spermatozoa was also established.


Influence of Age, Sex, and Wait Times on Public Online Ratings of Glaucoma Physicians in the United States.
Glaucoma surgeons are highly rated by the general public. Physicians with shorter wait times and who are younger are more likely to have higher ratings. Female glaucoma physicians are less likely to have higher ratings. Find what characteristics of glaucoma physicians are associated with higher online ratings. All American members of the American Glaucoma Society were queried on Healthgrades, Vitals, and Yelp. Ratings, medical school ranking, region of practice, sex, age, and wait times were recorded. One thousand one hundred six (78.2%) of American Glaucoma Society members had at least 1 review across the 3 platforms. The average score among glaucoma surgeons was 4.160 (0.898 SD). Female physicians were associated with lower online ratings [adjusted odds ratio (aOR): 0.536; 95% CI 0.354-0.808]. Physicians with <30 minutes of wait time had higher ratings: 15-30 minutes wait time (aOR: 2.273; 95% CI: 1.430-3.636) and <15 minutes wait time (aOR: 3.102; 95% CI: 1.888-5.146). Older physicians had lower ratings (aOR: 0.384; 95% CI: 0.255-0.572). Public online ratings of glaucoma specialists in the United States seem to favor those of younger age, men, and those with shorter wait times.


Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors.
Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2'-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2'-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2'-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.


Genomic Signature of Shifts in Selection and Alkaline Adaptation in Highland Fish.
Understanding how organisms adapt to aquatic life at high altitude is fundamental in evolutionary biology. This objective has been addressed primarily related to hypoxia adaptation by recent comparative studies, whereas highland fish has also long suffered extreme alkaline environment, insight into the genomic basis of alkaline adaptation has rarely been provided. Here, we compared the genomes or transcriptomes of 15 fish species, including two alkaline tolerant highland fish species and their six alkaline intolerant relatives, three alkaline tolerant lowland fish species, and four alkaline intolerant species. We found putatively consistent patterns of molecular evolution in alkaline tolerant species in a large number of shared orthologs within highland and lowland fish taxa. Remarkably, we identified consistent signatures of accelerated evolution and positive selection in a set of shared genes associated with ion transport, apoptosis, immune response, and energy metabolisms in alkaline tolerant species within both highland and lowland fish taxa. This is one of the first comparative studies that began to elucidate the consistent genomic signature of alkaline adaptation shared by highland and lowland fish. This finding also highlights the adaptive molecular evolution changes that support fish adapting to extreme environments at high altitude.


Loss of Camk2n1 aggravates cardiac remodeling and malignant ventricular arrhythmia after myocardial infarction in mice via NLRP3 inflammasome activation.
Inflammation response and subsequent ventricular remodeling are critically involved in the development of ventricular arrhythmia post myocardial infarction (MI). However, as the vital endogenous inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII), the effects of CaMKII inhibitor 1 (Camk2n1) on the process of arrhythmia substrate generation following MI remains unclear. In this study, we investigated the role of Camk2n1 in ventricular arrhythmia post-MI and the underlying mechanisms. Camk2n1 was mainly expressed in cardiomyocytes and inhibited the phosphorylation of CaMKIIδ in the infarcted border zone. Compared to wild type (WT) littermates mice, Camk2n1 knockout mice (Camk2n1-/-) manifested exacerbated cardiac dysfunction, larger fibrosis area, higher incidence of premature ventricular contractions (PVCs) and higher vulnerability to ventricular tachycardia (VT) or ventricular fibrillation (VF) after MI. The results of RNA sequencing (RNA-seq) identified that excessive activation of NLRP3 inflammasome was responsible for aggravated inflammation response which led to adverse cardiac remodeling in Camk2n1-/- mice subjected to MI. More importantly, both in vivo and in vitro experiments verified that aggravated NLRP3 inflammasome activation occurred via CaMKIIδ-p38/JNK pathway in Camk2n1-/- mice. Collectively, our results highlight the importance of Camk2n1 in alleviating ventricular remodeling and malignant ventricular arrhythmia post-MI by reducing cardiomyocytes inflammation activation via CaMKIIδ-p38/JNK-NLRP3 inflammasome pathway, targeting Camk2n1 might serve as a novel therapeutic strategy after MI.


Recipient obesity as a risk factor in kidney transplantation.
The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.


Potential new artificial sweetener from study of structure-taste relationships.
4-(Methoxymethyl)-1,4-cyclohexadiene-1-carboxaldehyde syn-oxime is a new sweetening agent developed by systematic synthesis and taste evaluation of 80 new oximes analogous to the little-used osime sweetener, perillartine.


Increase in chloride from baseline is independently associated with mortality in intracerebral hemorrhage patients admitted to intensive care unit: A retrospective study.
Hyperchloremia is associated with increased mortality in critically ill patients. The objective of this study was to investigate the association between increased chloride levels and mortality outcomes in intracerebral hemorrhage (ICH) patients admitted to the intensive care unit (ICU). We performed a retrospective study of all patients diagnosed with ICH and included in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ) from 2001 to 2012. Inclusion criteria were the first diagnosis of ICH, ICU length of stay (LOS) over 72 h, and not receiving hypertonic saline treatment. Serum chloride perturbation within 72 h of admission was evaluated as a predictor of outcomes. The increase in chloride from baseline was dichotomized based on an increase in chloride in 72 h (≤5 mmol/L or >5 mmol/L). The primary outcome was 90-day mortality. A total of 376 patients (54.5% male, median age 70 years, interquartile range:58-79 years) were included. The overall 90-day mortality was 32.2% (n=121), in-hospital mortality was 25.8% (n=97), and Day 2 acute kidney injury (AKI) occurred in 29.0% (n=109) of patients. The prevalence of hyperchloremia on admission, during the first 72 h, and an increase in chloride (>5 mmol/L) were 8.8%, 39.4%, and 42.8%, respectively. After adjusting for confounders, the hazard ratio of increase in chloride (>5 mmol/L) was 1.66 (95% confidence interval:1.05-2.64, P=0.031). An increase in chloride (>5 mmol/L) was associated with a higher odds ratio for 90-day mortality in both the AKI and non-AKI groups. An increase in chloride from baseline is common in adult patients with ICH admitted to ICU. The increase is significantly associated with elevated mortality. These results support the significance of diligently monitoring chloride levels in these patients.


The inflammatory response in sepsis.
The pathophysiology of sepsis and its accompanying systemic inflammatory response syndrome (SIRS) and the events that lead to multiorgan failure and death are poorly understood. It is known that, in septic humans and rodents, the development of SIRS is associated with a loss of the redox balance, but SIRS can also develop in noninfectious states. In addition, a hyperinflammatory state develops, together with impaired innate immune functions of phagocytes, immunosuppression, and complement activation, collectively leading to septic shock and lethality. Here, we discuss recent insights into the signaling pathways in immune and phagocytic cells that underlie sepsis and SIRS and consider how these might be targeted for therapeutic interventions to reverse or attenuate pathways that lead to lethality during sepsis.


Effects of transcranial direct current stimulation on brain network connectivity and complexity in motor imagery.
Related experiments have shown that transcranial direct current stimulation (tDCS) anodal stimulation of the brain's primary motor cortex (M1) and supplementary motor area (SMA) can improve the motor control and clinical manifestations of stroke patients with aphasia and dyskinesia. In this study, to explore the different effects of tDCS on the M1 and SMA in motor imagery, 35 healthy volunteers participated in a double-blind randomized controlled experiment. Five subjects underwent sham stimulation (control), 15 subjects underwent tDCS anode stimulation of the M1, and the remaining 15 subjects underwent tDCS anode stimulation of the SMA. The electroencephalogram data of the subjects' left- and right-hand motor imagery under different stimulation paradigms were recorded. We used a functional brain network and sample entropy to examine the different complexities and functional connectivities in subjects undergoing sham-tDCS and the two stimulation paradigms. The results show that tDCS anodal stimulation of the SMA produces less obvious differences in the motor preparation phase, while tDCS anodal stimulation of the M1 produces significant differences during the motor imaging task execution phase. The effect of tDCS on the motor area of the brain is significant, especially in the M1.


ATM c.7570G>C is a high-risk allele for breast cancer.
ATM is generally described as a moderate-risk breast cancer susceptibility gene. However, some of ATM variants might encounter higher risk. ATM c.7570G>C, p.Ala2524Pro, (rs769142993) is a pathogenic Finnish founder variant causative for recessively inherited ataxia-telangiectasia. At cellular level, it has been reported to have a dominant-negative effect. ATM c.7570G>C has recurrently been described in Finnish breast cancer families and unselected case cohorts collected from different parts of the country, but the rarity of the allele (MAF 0.0002772 in Finns) and lack of confirming segregation analyses have prevented any conclusive risk estimates. Here, we describe seven families from genetic counseling units with ATM c.7570G>C variant showing co-segregation with breast cancer. Further analysis of the unselected breast cancer cohort from Northern Finland (n = 1822), a geographical region previously indicated to have enrichment of the variant, demonstrated that c.7570G>C significantly associates with breast cancer, and the risk is estimated as high (odds ratio [OR] = 8.5, 95% confidence interval [CI] = 1.04-62.46, P = .018). Altogether, these results place ATM c.7570G>C variant among the high-risk alleles for breast cancer, which should be taken into consideration in genetic counseling.


Author Correction: Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine.
The original version of this Article contained an error in the spelling of the author Bin Geng, which was incorrectly given as Bing Geng. This has been corrected in both the PDF and HTML versions of the Article.


Psychometric properties of the Swedish translation of the Obsessive-Compulsive Inventory-Revised and the population characteristics of the symptom dimensions of OCD.
EGOS is an epidemiological obsessive-compulsive disorder (OCD) cohort in Sweden. Individuals contributed DNA for genotyping and sequencing and completed a Swedish translation of the Obsessive-Compulsive Inventory-Revised (OCI-R), a self-report questionnaire for assessing the severity of OCD. This study aimed first to evaluate the psychometric properties of the Swedish translation of the OCI-R and then shed light on the frequency, severity, and symptom dimensions of OCD comorbid with other psychiatric disorders. OCI-R data were available for 1010 individuals diagnosed with OCD, and 124 individuals diagnosed with chronic tic disorders without OCD used as a comparison group. We first performed a confirmatory factor analysis to confirm the six-factor structure of OCI-R. Then, we estimated Cronbach's α coefficient and the generalizability coefficient to evaluate the internal consistency of the OCI-R. We linked the data from the Swedish national registries to access and analyze psychiatric comorbidities of OCD. The Swedish translation of OCI-R demonstrated internal consistency and clear agreement with the OCI-R six-factor model. The mean total OCI-R score for females was significantly higher than for males. The most comorbid psychiatric condition to OCD were anxiety disorders (13.6%) and major depression (12%). The Swedish translation of OCI-R was a valid and reliable measure for assessing the severity of OCD. We observed that individuals with OCD frequently had additional comorbid psychiatric disorders and that the severity of OCD was significantly higher in individuals with at least one additional psychiatric comorbidity as compared to individuals with no psychiatric comorbidity.


Are spray drift losses to agricultural roads more important for surface water contamination than direct drift to surface waters?
Spray drift is considered a major pesticide transport pathway to surface waters. Current research and legislation usually only considers direct spray drift. However, also spray drift on roads and subsequent wash-off to surface waters was identified as a possible transport pathway. Hydraulic shortcuts (storm drainage inlets, channel drains, ditches) have been shown to connect roads to surface waters, thus increasing the risk of drift wash-off to surface waters. However, the importance of this pathway has never been assessed on larger scales. To address this knowledge gap, we studied 26 agricultural catchments with a predominance of arable cropping (n = 17) and vineyards (n = 9). In these study sites, we assessed the occurrence of shortcuts by field mapping. Afterwards, we modelled the areas of roads drained to surface waters using a high-resolution digital elevation model (0.5 m resolution) and a multiple flow algorithm. Finally, we modelled drift deposition to drained roads and surface waters using a spatially explicit, georeferenced spray drift model. Our results show that for most sites, the drift to drained roads is much larger than the direct drift to surface waters. In arable land sites, drift to roads exceeds the direct drift by a factor of 4.5 to 18, and in vineyard sites by 35 to 140. In arable land sites, drift to drained roads is rather small (0.0015% to 0.0049% of applied amount) compared to typical total pesticide losses to surface waters. However, substantial drift to drained roads in vineyard sites was found (0.063% to 0.20% of applied amount). Current literature suggests that major fractions of the drift deposited on roads can be washed off during rain events, especially for pesticides with low soil adsorption coefficients. For such pesticides and particularly in vineyards, spray drift wash-off from drained roads is therefore expected to be a major transport pathway to surface waters.


Assessment of escape from X chromosome inactivation and gene expression in single human immune cells.
X-chromosomal genes escaping from X chromosome inactivation (XCI) in immune cells can contribute to sex-specific differences in immune responses. This protocol describes the specific steps to determine escape from XCI and to simultaneously quantify mRNA expression of multiple genes at the single immune cell level using a single-nucleotide polymorphism approach. The protocol furthermore allows the analysis of allele-specific expression of X-chromosomal genes. For complete details on the use and execution of this protocol, please refer to Hagen et al. (2020).


Efficacy and safety of remimazolam besylate versus propofol during hysteroscopy: single-centre randomized controlled trial.
Remimazolam besylate is a newer benzodiazepine with characteristics of quick onset of effects, short maintenance and recovery times without accumulation in tissues. This trial was conducted to confirm the efficacy and safety of remimazolam besylate versus propofol during hysteroscopy. Patients undergoing hysteroscopy were randomly assigned to either the remimazolam (Group R) or the propofol group (Group P). Group R was administered an induction dose of 0.2 mg/kg and a maintenance dosage of 1.0 mg/kg/h. In Group P, propofol was started at 1.5-2.0 mg/kg and then maintained at 3.0-6.0 mg/kg/h. After remimazolam besylate or propofol induction, remifentanil was infused using a target-controlled infusion system with a target concentration of 1.5 ng/ml and titrated during the procedure. The incidence rates of injection pain, low oxygen saturation (SpO2) and adverse effects in both groups were compared. Eighty-two patients were included in this study. The incidence of adverse events in Group R (3.7%) was significantly lower than that in Group P (36.6%) (p < 0.001). The incidence of injection pain in Group P (80.5%) was much higher than that in Group R (2.4%) (p < 0.001). The incidence of other adverse events, such as low SpO2, bradycardia, and hypotension in Group R was lower than that in Group P (p < 0.05). Remimazolam besylate proves to be a safer alternative for anesthesia during hysteroscopy. Moreover, adverse events caused by propofol, such as low SpO2 and injection pain, are largely avoided. This study was approved by the Clinical Research Ethics Committee of Mengcheng County No. 1 People's Hospital (2020MYL20003) and registered at http://www.chictr.org.cn (15/09/2020, ChiCTR-2000038252 ). The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines.


Human immunodeficiency virus and infectious considerations.
In summary, HIV is a retrovirus with devastating consequences for those infected. Primary modes of transmission are through sexual contact and parenteral exposure to infected blood and body fluids. Prevalence of the virus among trauma patients, risk of exposure, and infection of health care workers are variable and to a large extent not known. Existing HIV infection and AIDS have both direct and indirect effects on care and outcome of trauma patients. Caring for these patients presents many challenges. Manifestations and complications of each condition may mask, mimic, or compound the other. Optimal care and outcome depend on knowledge of both diseases, and the specific nuances of their management. As with all trauma patients, a team approach coordinated by an identified team leader is indicated. Finally, to protect both the patient and the care giver, policies that effectively reduce exposure must be formulated, promulgated, and practiced.


Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma.
Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT- patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT- 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT- 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.


Outcomes following Lower Extremity Amputation in Patients with Diabetes Mellitus and Peripheral Arterial Disease.
Lower extremity amputations (LEAs) are projected to increase drastically in the United States. The potential effects of diabetes mellitus (DM) and peripheral arterial disease (PAD) on LEA outcomes have not been well-explored. We sought to investigate the clinical outcomes of LEA in patients with DM alone, PAD alone, and patients with concurrent DM and PAD (DM + PAD) from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. Adult patients (≥18 years) undergoing LEA in 2007-2011 based on ICD-9 procedure codes were selected. Patient morbidity, and mortality were assessed utilizing logistic and linear regression. Multivariable analyses adjusted for additional patient and hospital characteristics. A total of 62,291 LEAs were identified between 2007 and 2011. The mean (SD) age was 66.4 (13.7) years. Patients were predominantly Caucasian (56.4%), male (62.9%), and admitted as an emergency admission (44.1%). A higher incidence of LEA was observed in patients with DM + PAD (47.3%) than those with either DM alone (26.4%) or PAD alone (26.3%). On adjustment for patient characteristics, PAD alone was associated with significantly higher mortality and complications postoperatively (OR 1.71; P < 0.001, and 1.28; P < 0.001, respectively), but concurrent DM + PAD was not associated with these outcomes. Outcomes were significantly affected by presence of PAD as a comorbidity in patients undergoing LEA. It is imperative to understand and enhance preventive measures and screening guidelines for such comorbidities to optimize postoperative outcomes to ensure best-practice care in this patient population.


[Transient Parkinson syndrome and tremor caused by the use of sodium valproate].
From 1986 till 1988, 88 patients received sodium valproate for the first time as a therapy for epilepsy. One of them developed a fine tremor, three a coarse tremor with a cogwheel phenomenon, two developed a full parkinsonian syndrome. All these symptoms in these six patients disappeared completely or nearly completely after changing to another anti-epileptic drug or reducing the dose.


Lignin provides mechanical support to herbaceous peony (Paeonia lactiflora Pall.) stems.
Stem bending caused by mechanical failure is a major constraint for high-quality herbaceous peony (Paeonia lactiflora Pall.) cut flowers, but little is known about the underlying factors. In this study, two P. lactiflora cultivars, Xixia Yingxue (bending) and Hong Feng (upright), were used to investigate differences in stem bending. The results showed that the stem mechanical strength of Hong Feng was significantly higher than that of Xixia Yingxue, and the thickening of the secondary cell wall and the number of thickened secondary cell wall layers in Hong Feng were significantly higher than those in Xixia Yingxue. Moreover, compared with Xixia Yingxue, Hong Feng showed greater lignification of the cell wall and lignin deposition in the cell walls of the sclerenchyma, vascular bundle sheath and duct. All three types of lignin monomers were detected. The S-lignin, G-lignin, and total lignin contents and the activities of several lignin biosynthesis-related enzymes were higher in Hong Feng than in the other cultivar, and the S-lignin content was closely correlated with stem mechanical strength. In addition, 113,974 full-length isoforms with an average read length of 2106 bp were obtained from the full-length transcriptome of P. lactiflora stems, and differential expression analysis was performed based on the comparative transcriptomes of these two cultivars. Ten lignin biosynthesis-related genes, including 26 members that were closely associated with lignin content, were identified, and multiple upregulated and downregulated transcription factors were found to positively or negatively regulate lignin biosynthesis. Consequently, lignin was shown to provide mechanical support to P. lactiflora stems, providing useful information for understanding the formation of P. lactiflora stem strength.


A comparison of methods for alignment of NMR peaks in the context of cluster analysis.
This paper compares the performance of two recently developed algorithms and methods for peak alignment of first-order NMR data of complex biological samples. The NMR spectra of such samples exhibit variations in peak position and peak shape due to variations in the sample matrix and to instrumental instabilities. The first method comprises an alignment of spectral segments with linear interpolation and shift correction to accommodate correspondence between a target and a test spectrum by a beam search or genetic algorithm. The second method is based on peak picking and needle vector representation of the NMR data with subsequent breadth-first search to establish shift corrections between the target and the test spectrum. The two proposed peak alignment methods and their respective merits are discussed for a real metabonomics application. Both alignment methods have been shown to enhance the interpretability of the resulting multivariate models, thereby increasing the prospect of detecting and following the onset of subtle biological changes reflected in the NMR data.


Gender differences in cardiac rehabilitation programs from the Italian survey on cardiac rehabilitation (ISYDE-2008).
In recent years epidemiological and clinical evidence has shown gender disparities in several aspects of cardiovascular disease. Aim of this study was to identify gender differences in the clinical profile and management of patients admitted to cardiac rehabilitation (CR) programs. Patients enrolled in the ISYDE-2008 survey were considered. The ISYDE-2008 survey enrolled 2281 patients; 604 (26.5%) were women. Compared to men, women were older (mean age 70.8 ± 11.5 versus men's 65.6 ± 11.5 years), had less traditional risk factors (low cardiovascular risk profile in 45.3% of women and 38.0% of men, p=0.003), were more frequently admitted after valvular surgery and heart failure, but less for post-acute myocardial infarction and post-by-pass procedure. Women were more frequently admitted to an in-hospital rehabilitation program. Women showed a more complicated acute and rehabilitative course, with 63.2% of them having at least one complication during acute-phase, compared to 52.5% of men, and 48.3% during rehabilitation, compared to 35.0% of men (p<0.0001). During rehabilitation, women underwent exercise tests less frequently, except for the 6-minute walking test. At discharge, women received ACE-inhibitors/ARBs, β-blockers, statins, omega-3 fatty acids, antiplatelet agents less frequently, but more frequently digoxin, amiodarone, diuretics, oral anticoagulants, insulin and anti-depressive drugs. The duration of the rehabilitation program was longer for women. Mortality was very low in the entire population. Women are less frequently admitted to CR than men. They are older and show a greater cardiovascular burden. Women are more likely to be enrolled in CR after valvular surgery and heart failure than men.


Simultaneous expression of early and late histone messenger RNAs in individual cells during development of the sea urchin embryo.
The transition from early (E) to late (L) histone gene expression in developing sea urchin (Strongylocentrotus purpuratus) embryos was examined for H2B, H3, and H4 mRNAs by in situ hybridization of class-specific probes. Hybridization patterns indicate that the shift from E to L mRNAs occurs gradually and simultaneously in all blastomeres. Thus, during the transition the ratio of L to E mRNAs is similar in most cells. This suggests that no sudden changes in histone composition occur in individual cells which might be related to alterations in gene expression associated with differentiation of cell lineages. Around the midpoint of the transition, clusters of cells progressively appear which contain little, if any, E or L histone mRNA. This modulation of expression is coordinated for the three late genes examined because most individual cells contain either high or low levels of all three mRNAs. At blastula stage these clusters of unlabeled cells appear to be randomly distributed throughout the embryo. Subsequently the unlabeled regions expand and are found predominantly in aboral ectoderm as these cells cease to divide. Thus, the L/E histone mRNA ratio is not differentially regulated in diverse cell lineages, and the major differences in total histone mRNA content among individual cells may be related to cell cycle and/or the cessation of division.


[Predictive molecular diagnostics in breast cancer : What are the requirements for pathology today and in the future?]
With an increasing number of targeted therapy options for the treatment of solid tumors, the demands on predictive molecular diagnostics for pathology are growing. In breast cancer the need to determine genomic predictive markers for available targeted therapies has so far been manageable (detection of PIK3CA mutations in endocrine pretreated luminal tumors and the search for NTRK fusions indicated only in secretory breast cancer). At the latest in cases of nonresponse to first-line or second-line standard treatment, more comprehensive diagnostics using next generation sequencing (NGS) panel diagnostics makes sense. This should be suitable for clarifying resistance mechanisms, e.g. against endocrine therapy or cyclin-dependent kinase 4/cyclin-dependent kinase 6 (CDK4/6) inhibitors and to identify indications for therapies currently in development. The interpretation should be carried out in a quality assured manner in accordance with international standards and the interdisciplinary tumor board should make a transparent and standardized report available in a timely manner.


A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants.
We have compared results obtained with an uncalibrated respiratory inductance plethysmograph (RIP) with those of a face mask and pneumotachograph (PNT) for the computerized measurement of the time to reach peak tidal expiratory flow as a ratio of total expiratory time (tPTEF:tE). Simultaneous measurements were made in 32 healthy neonates aged 0-3 weeks, 35 healthy infants aged 5-82 weeks, and 28 infants aged 15-94 weeks with physician diagnosed recurrent wheeze. The group mean (+/- SD) values of tPTEF:TE determined using a PNT were 0.455 (+/- 0.129), 0.263 (+/- 0.077), and 0.232 (+/- 0.089) for the neonates, healthy infants and infants with recurrent wheeze respectively. RIP gave mean (+/- SD) values that were 0.055 (+/- 0.044) and 0.025 (+/- 0.104) lower than the PNT in healthy neonates and infants with recurrent wheeze respectively; RIP values were 0.002 (+/- 0.073) higher in the healthy infants over 4 weeks of age than measurements by PNT. Although the difference between the two measurements was not related to the thoracoabdominal phase angle, as measured from Lissajous figures, examination of the RIP ribcage and abdominal signals revealed that many healthy subjects, while appearing clinically in phase, had ribcage and abdominal signals that differed markedly from each other in terms of convexity/concavity during early expiration. This may explain the lack of agreement between the two methods. We conclude that uncalibrated RIP should be used with caution for the determination of tPTEF:tE, even in subjects whose ribcage and abdomen appear to move synchronously. The measurement of tPTEF:tE did not differentiate between the healthy infants and infants with recurrent wheezing.


Sphingomyelin synthase overexpression increases cholesterol accumulation and decreases cholesterol secretion in liver cells.
Studies have shown that plasma high density lipoprotein cholesterol levels are negatively correlated with the development of atherosclerosis, whereas epidemiological studies have also shown that plasma sphingomyelin level is an independent risk factor for atherosclerosis. To evaluate the relationship between cellular sphingomyelin level and cholesterol metabolism, we created two cell lines that overexpressed sphingomyelin synthase 1 or 2 (SMS1 or SMS2), using the Tet-off expression system. We found that SMS1 or SMS2 overexpression in Huh7 cells, a human hepatoma cell line, significantly increased the levels of intracellular sphingomyelin, cholesterol, and apolipoprotein A-I and decreased levels of apolipoprotein A-I and cholesterol in the cell culture medium, implying a defect in both processes. Our findings indicate that the manipulation of sphingomyelin synthase activity could influence the metabolism of sphingomyelin, cholesterol and apolipoprotein A-I.


Hormonal reactivity during martial arts practice among high-risk youths.
Martial arts have become a popular afterschool activity for youths across the globe. Accumulating data suggest that these activities may confer substantial cognitive and psychological benefits, and recent efforts have been made to introduce martial arts training into educational and rehabilitation settings. However, few studies have examined the potential mechanisms that may underlie these benefits. The current study evaluated the reactivity of two hormones, oxytocin (OT) and cortisol (CT), thought to be respectively involved in regulating mammalian social behaviors and responsivity to stress, to a session of intensive martial arts training in samples of at high-risk and low-risk (in regular educational establishments) youths. OT and CT were measured at baseline, during peak training, and following a cool down period. Analyses revealed that high-risk youths had lower OT but similar CT baseline levels, compared to low-risk youths, prior to the martial arts session. A significant group by time interaction indicated that whereas the OT levels among low-risk youths returned to baseline levels following training, OT levels among high-risk youths remained elevated. Finally, unlike low-risk youths for whom CT levels continued to increase throughout the training session, high-risk youths showed no significant CT reactivity. This study suggests that some of the beneficial effects of martial arts may be related to hormonal processes, especially increases in OT levels, and highlights the differing effects that training may have in different populations.


Folic acid rescue of ATRA-induced cleft palate by restoring the TGF-β signal and inhibiting apoptosis.
Cleft palate is a frequent congenital malformation with a heterogeneous etiology, for which folic acid (FA) supplementation has a protective effect. To gain more insight into the molecular pathways affected by FA, TGF-β signaling and apoptosis in mouse embryonic palatal mesenchymal (MEPM) cells of all-trans retinoic acid (ATRA)-induced cleft palate in organ culture were tested. C57BL/6J mice embryonic palates were explanted on embryonic day 14 and cultured in DMEM/F12 medium with or without ATRA or FA for 72 h. The palatal fusion was examined by light microscopy. Immunohistochemistry was used to detect TGFβ3/TGF receptor II and caspase 9 in MEPM cells. TUNEL was used to detect apoptosis. Similar to development in vivo, palatal development and fusion were normal in control medium. ATRA inhibited palatal development and induced cleft palate, which can be rescued by FA. A higher apoptosis rate and caspase-9 in MEPM cells were detected in the ATRA group than in the control or the ATRA+FA group. Compared with the control or the ATRA+FA group, ATRA had little effect on TGF-β3 in MEPM cells but significantly inhibited TGF-β receptor II. Folic acid can rescue the cultured palates to continue developing and fusing that were inhibited and resulted in cleft palate by ATRA. Apoptosis and TGFβ signaling in MEPM cells were involved in folic acid rescued ATRA-induced cleft palate.


Artificial intelligence (AI) can be described as an advanced technology in which machines display a certain form of intelligence. The primary objective was to perform a narrative review of studies evaluating the feasibility and impact of AI in pharmacy. The secondary objective was to create a mind map of AI in health care. Four databases were consulted: PubMed, Medline, Embase, and CINAHL. Four search strategies were developed. Initial selection of articles was based on their titles and abstracts; the full texts were then evaluated by a research assistant, with review by a pharmacist. Articles were included if they described or evaluated the feasibility or impact of AI in pharmacy. A total of 362 articles were identified by the literature review, of which 18 met the inclusion criteria. The studies were mainly conducted in the United States (72%, 13/18). The article topics were, in decreasing order, prediction of response to treatments and adverse effects (33%, 6/18), patient prioritization (28%, 5/18), treatment adherence (22%, 4/18), validation of prescriptions and electronic prescription (17%, 3/18), and other themes (e.g., diagnosis, costs, insurance, and verification of syringe volume). This narrative review highlighted 18 studies evaluating the feasibility and impact of AI in pharmacy. The studies used various methodologies in different settings, both retail pharmacies and hospital pharmacies. It is still too soon to predict the implications of AI for pharmacy, but these studies emphasize the importance of attention in this area.


Integration of phosphate functionalized Pt/TiO2 and Ru(bpy)32+ sensitization for ultrasensitive assay of adenosine deaminase activity on a novel split-typed PEC aptasensor.
To date, it is still a challenge for high-performance photoelectrochemical (PEC) assay of low-abundance adenosine deaminase (ADA) in fundamental research and clinical diagnosis. Herein, phosphate-functionalized Pt/TiO2 (termed PO43-/Pt/TiO2) was prepared as ideal photoactive material to develop a split-typed PEC aptasensor for detection of ADA activity, coupled by a Ru(bpy)32+ sensitization strategy. We critically studied the effects of the PO43- and Ru(bpy)32+ on the detection signals, and discussed the signal-amplified mechanism. Specifically, hairpin-structured adenosine (AD) aptamer was splited into single chain via ADA-induced catalytic reaction, and subsequently hybridized with complementary DNA (cDNA, initially coating on magnetic beads). The in-situ formed double-stranded DNA (dsDNA) was further intercalated by more Ru(bpy)32+ to amplify the photocurrents. The resultant PEC biosensor showed a broader linear range of 0.05-100 U L-1 and a lower limit of detection (0.019 U L-1), which can fill the blank for analysis of ADA activity. This research would provide some valuable insights for building advanced PEC aptasensors in ADA-related research and clinical diagnosis.


Are recist criteria adequate in assessing the response to therapy in metastatic NEN?
Response to therapy criteria, known as RECIST (Response Evaluation Criteria in Solid Tumours), are widely used to evaluate neuroendocrine tumours (NET) metastatic to the liver, under treatment. RECIST criteria does not take in account many various distinct features such as tumour growth, secretory capacity and anatomical localisation with wide variation in clinical and biological presentation of different NETs. Key features of RECIST includes definitions of the minimal size of measurable lesions, instructions on how many lesions to measure and follow, and the use of unidimensional, rather than bidimensional, measures for overall evaluation of tumour burden. These measures are currently done with computed tomography (CT) or Magnetic Resonance Imaging (MRI). RECIST criteria are accurate in assessing tumour progression but sometimes inaccurate in assessing tumour response after locoregional therapy or under molecular targeted therapy, tumour vessels being part of the target of such treatments. There is poor correlation between a so called tumour necrosis and conventional methods of response assessment, which poses questions of how best to quantify efficacy of these targeted therapies. Variations in tumour density with computed tomography (CT) could theoretically be associated with tumour necrosis. This hypothesis has been studied proposing alternative CT criteria of response evaluation in metastatic digestive NET treated with targeted therapy. If preliminary results upon the poor relationship between density measured with CT (derived from CHOI criteria) evolution curves at CT and PFS are confirmed by further studies, showing that the correlation between density changing and response to non-targeted treatment is weak, the use of contrast injection, will probably be not mandatory to enable appropriate evaluation.


Birth intentions among US fathers with disabilities.
Men's birth intention is an indicator of their sexual health and plays an important role for their child's health and development; however, birth intendedness in fathers with disabilities has been unknown. This study examines disparities in birth intendedness among fathers with and without disabilities and explores whether the differences vary by marital status or race/ethnicity. Data from the 2011-2017 National Survey of Family Growth (NSFG) were used to examine pregnancy intendedness for fathers with (n = 380) and without disabilities (n = 1,324) about their last birth in the five years preceding the interview. Multinomial regression models estimated the odds ratios of fathers' disability status on birth intention controlling for covariates. Interaction effects of disability status by marital status or race/ethnicity were also tested. Fathers with disabilities were 1.89 (95% CI = 1.21, 2.95) times as likely to report their last birth as unwanted versus intended compared to those without disabilities after adjusting for covariates. Although married fathers without disabilities were less likely to report unintended birth than their unmarried counterparts, the protective effect of marriage was not evident among fathers with disabilities. Disabled fathers are at a higher risk of unintended birth compared to nondisabled fathers. These findings highlight the need to increase access to family planning services for disabled men. Further research is needed to better understand the risk factors that contribute to disabled fathers' unintended birth and how these are linked to their child and family well-being.


Experimental studies of mitochondrial and lysosomal function in in vitro and in vivo models relevant to Parkinson's disease genetic risk.
Several studies have identified the involvement of mitochondrial and lysosomal dysfunction in Parkinson's disease (PD) pathology. In this review we discuss recent work that has identified deficits in mitophagy, mitochondrial network formation, increased sensitivity to mitochondrial stressors and alterations in proteins regulating mitochondrial fission and fusion associated with patient-derived fibroblasts harboring mutations in LRRK2 gene and from sporadic PD patient cells. We further focus on alterations of lysosomal enzymes, in particular glucocerebrosidase activity, and resultant lipid dyshomeostasis in PD and aging, in human tissue and in vivo rodent models. Future studies aimed at understanding the convergence of mitochondrial and lysosomal pathways will be of essence for the identification of unique cellular defects in PD and for the development of new treatments.


Pathology for Thoracic Conditions in Low- and Middle-Income Countries.
Pulmonary disease in low- and middle-income countries is highly diverse and dependent on the population, background epidemiology, environmental exposures, and smoking status. Credible evaluation of lung diseases requires skilled clinicians, imaging infrastructure, microbiology, and pathologic diagnostics, including imaging-guided cytology and biopsy. When these tools are available, improvement in patient outcomes is feasible. Pathologic diagnostics of lung lesions, including histology, immunohistochemistry, and molecular testing, are critical to properly stratify patient risk and determine exact therapies for each patient. A critical focus on research and directed interventions in lung cancer treatment specifically is needed to downstage this disease and improve patient outcome.


Single molecule localization microscopy coupled with touch preparation for the quantification of trastuzumab-bound HER2.
All breast cancers are assessed for levels of human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization (FISH) and immunohistochemistry are currently used to determine if a patient is eligible for anti-HER2 therapy. Limitations of both tests include variability and relatively long processing times. Additionally, neither test determines whether HER2 contains the extracellular domain. While truncated in some tumors, this domain is required for binding of the therapeutic antibody trastuzumab. Here, trastuzumab was used to directly detect HER2 with quantitative single molecule localization microscopy (qSMLM). In proof of concept studies, our new method rapidly quantified both HER2 density and features of nano-organization. In cultured cells, the method was sensitive to subtle variations in HER2 expression. To assess patient samples, we combined qSMLM with tissue touch preparation (touch prep-qSMLM) and examined large areas of intact membranes. For cell lines and patient samples, HER2 copy numbers from FISH showed a significant positive correlation with detected densities from qSMLM and trended with HER2 cluster occupancy.


New epidemiological aspects of patients with severe hyperhidrosis presenting for sympathetic surgery.
Epidemiological data on individuals suffering from severe primary hyperhidrosis are scarce. This study aims to prospectively assess disease-specific characteristics of patients with severe, mostly therapy-resistant hyperhidrosis presenting for sympathetic surgery. We evaluated a total of 227 patients (69.6% women) with a mean age of 30 years (standard deviation, 9.5 years) using a standardized questionnaire. Severity of disease was rated on a visual analogue scale (VAS) graded between 0 (no symptoms) and 10 (worst symptom). Age, sex, previous therapies, hormonal therapies and body mass index were analysed for their possible influence on severity of the disease and on hyperhidrosis sites. In addition, allergies were investigated for the first time in this patient population. There was a positive correlation between age of onset and sites of hyperhidrosis. The most commonly affected areas were palmar-axillary-plantar (51.1%) and palmar-plantar (15.0%), with sex-specific differences. Two hundred and twelve patients (93.4%) had previous conservative therapies; 219 patients (96.5%) reported VAS scores between 8 and 10. Female patients stated higher VAS scores for palmar (P = 0.009) and axillary (P = 0.012) sites. Type IV allergies were found to be much higher than in the general Austrian female population. Hormonal therapies and the body mass index had no influence on severity of hyperhidrosis after analysis of VAS scores. Sex-dependent aspects can be found in patients strongly affected by primary upper limb hyperhidrosis.


Performance optimization of biomimetic ant-nest silver nanoparticle coatings for antibacterial and osseointegration of implant surfaces.
Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.


Complications of the Nissen fundoplication.
A more astute selection of patients and greater attention to technical details will preclude most complications. The first step is standardizing the technique, with avoidance of unnecessary ancillary maneuvers. Equally important is a thorough preoperative evaluation. With these considerations in mind, the authors believe that Nissen fundoplication is the preferred method of treatment for patients with uncomplicated gastroesophageal reflux refractory to medical therapy.


Experimental and theoretical investigation of aortic wall tissue in tensile tests.
Understanding the mechanical properties of aortic tissue is essential for developing numerical computation tools and assessing the risk of aortic aneurysm fractures. Tensile tests using aortic wall specimens allow for the determination of stress and strain depending on the location and direction of the sample. The aim of this study was to perform a mechanical tensile test using canine aorta samples and create a numerical model of aortic tissue tension from the processed data. Dogbone-shaped samples were dissected from canine aortic segments. The initial measurements were made at zero tension and the tensile tests were conducted at 10 mm/min until rupture. Force and stretch data were used to obtain engineering and true stress-strain curves. The true stress-strain curves were taken until the maximum strength was obtained, after which they were smoothed and fitted using a logistic function with three coefficients. These curves were then used as material mechanical properties for a numerical model of the aortic tissue tension. A simplified rectangle form was used to mimic the middle of the dogbone-shaped portion of the tissue specimen. Experimental displacement data were collected for the boundary conditions of the finite element 3D model. The experimental data processing revealed that the logistic function described the nonlinear behaviour of the aorta soft tissue with an accuracy of 95% from the start of the tension to the media layer rupture. By applying numerical simulations, we obtained a correspondence of the load curve with an RMSE = 0.069 for the theoretical and experimental external tension data. The numerical investigation confirmed that the non-linear soft tissue was validated by applying a logistic function approach to the mechanical properties of the aortic wall.


Introduction of the snake antenna array: Geometry optimization of a sinusoidal dipole antenna for 10.5T body imaging with lower peak SAR.
To improve imaging performance for body MRI with a local transmit array at 10.5T, the geometry of a dipole antenna was optimized to achieve lower peak specific absorption rate (SAR) levels and a more uniform transmit profile. Electromagnetic simulations on a phantom were used to evaluate the SAR and B 1 + -performance of different dipole antenna geometries. The best performing antenna (the snake antenna) was simulated on human models in a 12-channel array configuration for safety assessment and for comparison to a previous antenna design. This 12-channel array was constructed after which electromagnetic simulations were validated by B 1 + -maps and temperature measurements. After obtaining approval by the Food and Drug Administration to scan with the snake antenna array, in vivo imaging was performed on 2 volunteers. Simulation results on a phantom indicate a lower SAR and a higher transmit efficiency for the snake antenna compared to the fractionated dipole array. Similar results are found on a human body model: when comparing the trade-off between uniformity and peak SAR, the snake antenna performs better for all imaging targets. Simulations and measurements are in good agreement. Preliminary imaging result were acquired in 2 volunteers with the 12-channel snake antenna array. By optimizing the geometry of a dipole antenna, peak SAR levels were lowered while achieving a more uniform transmit field as demonstrated in simulations on a phantom and a human body model. The array was constructed, validated, and successfully used to image 2 individuals at 10.5T.


Paeoniflorin inhibition of 6-hydroxydopamine-induced apoptosis in PC12 cells via suppressing reactive oxygen species-mediated PKCδ/NF-κB pathway.
Parkinson's disease (PD) is second only to Alzheimer's disease as the most common devastating human neurodegenerative disorder. Despite intense investigation, no curative therapy is available for PD. Paeoniflorin, a monoterpene glucoside isolated from the Paeonia lactiflora Pall., possesses wide pharmacological effects in the nervous system. This study aims at evaluating the effect of paeoniflorin on 6-hydroxydopamine (6-OHDA)-induced apoptosis and to characterize involved signal transduction pathways in PC12 cells. Our results showed that paeoniflorin suppresses mitochondria-mediated apoptosis of PC12 cells induced by 6-OHDA, and anti-apoptotic effects of paeoniflorin on PC12 cells might mainly result from its antioxidant capability by increasing glutathione (GSH). Moreover, we also found that paeoniflorin can dramatically attenuate the 6-OHDA-induced nuclear factor κB (NF-κB) translocation without affecting phosphorylation of Akt, JNK, p38, and ERK1/2. 6-OHDA-induced protein kinase Cδ (PKCδ) upregulation was blocked by paeoniflorin treatment in PC12 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium or NF-κB inhibitor BAY 11-7082 could partially attenuate 6-OHDA-induced cell death. Together, our results indicate that the inhibition of PC12 cell apoptosis by paeoniflorin might be mediated, at least in part, by inhibiting reactive oxygen species (ROS)/PKCδ/NF-κB signaling pathway. This evidence supports the pharmacological potential of paeoniflorin in the management of neurodegenerative disorders associated with oxidative stress, including PD.


Diastereoselective Synthesis of 2'-Dihalopyrimidine Ribonucleoside Inhibitors of Hepatitis C Virus Replication.
We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro ribolactone synthesis. Stereoselective fluorination is key to controlling the 2-diastereoselectivity. We also report a substantially improved glycosylation reaction with both the 2-bromo-2-fluoro and 2-chloro-2-fluoro sugars. These improvements allowed us to prepare 2'-dihalo nucleosides 13 and 14 in an overall 15-20% yield.


Stereoselective high-performance liquid chromatographic assay for the determination of sotalol enantiomers in biological fluids.
A high-performance liquid chromatographic (HPLC) assay for determination of sotalol enantiomers in biological fluids was developed to assess the stereoselective disposition of the drug in man. Following extraction at pH 9.0 with a mixture of chloroform-isopropanol (3:1, v/v), the organic phase was evaporated to dryness and the residue derivatized with (-)-methyl chloroformate. Diastereoisomeric derivatives were resolved by HPLC (C8 column) with fluorescence detection (lambda ex = 235 nm and lambda em = 300 nm). Retention times of l- and d-sotalol derivatives were 13 and 15 min while that of the internal standard, S-(-)-atenolol, was 12.3 min. The detection limit of each enantiomer was 12.5 ng/ml using 1 ml of plasma or urine. Intra-day and inter-day coefficients of variation were less than 10% for each enantiomer in the range 0.125-2.5 micrograms/ml in plasma and 0.25-2.5 micrograms/ml in urine.


Role of lateral parabrachial nucleus in the inhibition of water intake produced by right atrial stretch.
Rats with either bilateral electrolytic or sham lesions of the ventrolateral portion of the lateral parabrachial nucleus (VLLPBN) were implanted with latex balloons that lay at the right superior vena cava/atrial junction (RSVC/AJ). Water intake in response to isoproterenol was measured both with and without inflation of the balloon. Water intake of the sham-lesioned rats was significantly depressed by balloon inflation during the first hour of the experiment. In contrast, water intake in the VLLPBN-lesioned rats was unaffected by balloon inflation. These results suggest that the VLLPBN is involved in the processing of afferent input from stretch-activated RSVC/AJ receptors.


Does the implementation of a national oral health policy reduce inequalities in oral health services utilization? The Brazilian experience.
This study aimed to assess the trend in income-related inequalities in oral health services utilization by the Brazilian population from 1998 to 2013. This period represents a timeline that includes different stages of implementation of the National Oral Health Policy. The design was based on repeated cross-sectional surveys using secondary data from household-based studies carried out in Brazil in 1998, 2003, 2008, and 2013. The dependent variable was "having access to a dentist appointment at least once in a lifetime (yes/no)." Monthly household per capita income, based on Brazil's minimum wage, was included as the main independent variable. To measure the inequalities in oral health access related to economic position, the following complex indexes based on regression were used: (a) the slope index of inequality (SII) and (b) the relative index of inequality (RII). There was a reduction in the percentage of individuals who never had a dentist appointment for all age groups and income classifications. In general, there was a reduction trend in absolute inequality for all age groups (p < 0.001). The relative inequality and reduction trend were different between the age groups studied. The National Oral Health Policy was very important for expanding free of charge, public access to dental appointment. However, despite policy implementation, there continues to be high levels of inequality in access to dental consultation. Assessing which strategies are necessary to overcome this challenge is discussed.


The role of Dnmt1 in oocyte development.
The whitefly Bemisia tabaci is a globally important crop pest that is difficult to manage through current commercially available methods. While RNA interference (RNAi) is a promising strategy for managing this pest, effective target genes remain unclear. We suggest DNA methyltransferase 1 (Dnmt1) as a potential target gene due to its effect on fecundity in females in other taxa of insects. We investigated the role of Dnmt1 in B. tabaci using RNAi and immunohistochemistry to confirm its potential conserved function in insect reproduction, which will define its usefulness as a target gene. Using RNAi to downregulate Dnmt1 in female B. tabaci, we show that Dnmt1 indeed has a conserved role in reproduction, as knockdown interfered with oocyte development. Females in which Dnmt1 was knocked down had greatly reduced fecundity and fertility; this supports Dnmt1 as a suitable target gene for RNAi-mediated pest management of B. tabaci.


Bacterial coaggregation in aquatic systems.
The establishment of a sessile community is believed to occur in a sequence of steps where genetically distinct bacteria can become attached to partner cells via specific molecules, in a process known as coaggregation. The presence of bacteria with the ability to autoaggregate and coaggregate has been described for diverse aquatic systems, particularly freshwater, drinking water, wastewater, and marine water. In these aquatic systems, coaggregation already demonstrated a role in the development of complex multispecies sessile communities, including biofilms. While specific molecular aspects on coaggregation in aquatic systems remain to be understood, clear evidence exist on the impact of this mechanism in multispecies biofilm resilience and homeostasis. The identification of bridging bacteria among coaggregating consortia has potential to improve the performance of wastewater treatment plants and/or to contribute for the development of strategies to control undesirable biofilms. This study provides a comprehensive analysis on the occurrence and role of bacterial coaggregation in diverse aquatic systems. The potential of this mechanism in water-related biotechnology is further described, with particular emphasis on the role of bridging bacteria.


The hepatic transport of taurocholic acid in the rat: development of a mathematical model.
1. The transport of taurocholic acid from portal blood to bile was studied in the anaesthetized rat by injecting a radiolabelled pulse of bile acid. 2. The transport process was very rapid, 50% of the dose being secreted within 5 min, and the total dose within 15 min. 3. The transport process had a large capacity. The secretory profile was little modified by a 500-fold increase in the injected dose. 4. The transport process was modelled with both analogue and digital computers. The simplest model which fitted the data comprised rapid uptake from portal blood, slow transport across the cell and rapid secretion into bile. The digital computer simulation suggested that this model is not unique, but will require further testing.


Replication timing maintains the global epigenetic state in human cells.
The temporal order of DNA replication [replication timing (RT)] is correlated with chromatin modifications and three-dimensional genome architecture; however, causal links have not been established, largely because of an inability to manipulate the global RT program. We show that loss of RIF1 causes near-complete elimination of the RT program by increasing heterogeneity between individual cells. RT changes are coupled with widespread alterations in chromatin modifications and genome compartmentalization. Conditional depletion of RIF1 causes replication-dependent disruption of histone modifications and alterations in genome architecture. These effects were magnified with successive cycles of altered RT. These results support models in which the timing of chromatin replication and thus assembly plays a key role in maintaining the global epigenetic state.


16p11.2 deletion in patients with paroxysmal kinesigenic dyskinesia but without intellectual disability.
Mutations of the PRRT2 gene are the most common cause for paroxysmal kinesigenic dyskinesia. However, patients with negative PRRT2 mutations are not rare. The aim of this study is to determine whether copy number variant of PRRT2 gene is another potential pathogenic mechanism in the patients with paroxysmal kinesigenic dyskinesia with negative PRRT2 point and frameshift mutations. We screened PRRT2 copy number variants using the AccuCopy™ method in 29 patients with paroxysmal kinesigenic dyskinesia with negative PRRT2 point and frameshift mutations. Next-generation sequencing was used to determine the chromosomal deletion sites in patients with PRRT2 copy number variants, and to exclude mutations in other known causative genes for paroxysmal kinesigenic dyskinesia. Two sporadic patients with negative PRRT2 point and frameshift mutations (6.9%) were identified to have de novo PRRT2 copy number deletions (591 and 832 Kb deletions located in 16p11.2). The two patients presented with pure paroxysmal kinesigenic dyskinesia and paroxysmal kinesigenic dyskinesia and benign infantile convulsions, respectively. They had normal intelligence and neuropsychiatric development, in contrast to those previously reported with 16p11.2 deletions complicated with neuropsychiatric disorders. No correlation between the deletion ranges and phenotypic variations was found. 16p11.2 deletions play causative roles in paroxysmal kinesigenic dyskinesia, especially for sporadic cases. Our findings extend the phenotype of 16p11.2 deletions to pure paroxysmal kinesigenic dyskinesia. Screening for 16p11.2 deletions should thus be included in genetic evaluations for patients with paroxysmal kinesigenic dyskinesia.


Immuno-PET imaging of 68Ga-labeled nanobody Nb109 for dynamic monitoring the PD-L1 expression in cancers.
The checkpoint blockade immunotherapy has become a potent treatment strategy for cancers, and programmed death ligand-1 (PD-L1) is a prominent checkpoint ligand that is highly expressed in some cancers. The identification of immune checkpoint marker PD-L1 is critical for improving the success of immunotherapy. Accordingly, the binding specificity and dynamic monitoring property of a non-blocking nanobody tracer 68Ga-NOTA-Nb109 to PD-L1 were assessed in this study. The endogenous expression level of PD-L1 in several cancer cells was measured by flow cytometry, Western blot, and cellular uptake assay. Sensitivity and specificity of 68Ga-NOTA-Nb109 in monitoring the expression of PD-L1 in vivo were evaluated by PET imaging of different tumor-bearing models (U87, high PD-L1 expression; HCT 116, medium PD-L1 expression; and NCI-H1299, low PD-L1 expression). In vivo PET imaging results agreed well with those detected in vitro. In addition, PET imaging of PD-L1 expression in U87 and NCI-H1299 xenografts using 18F-FDG was also performed for comparison. The maximum tumor-to-muscle uptake ratio of 68Ga-NOTA-Nb109 was more than twofold that of 18F-FDG in U87 xenograft. The change of PD-L1 expression in NCI-H1299 cells and xenografts induced by cisplatin (CDDP) was sensitively monitored by 68Ga-NOTA-Nb109. This study demonstrated the feasibility of tracer 68Ga-NOTA-Nb109 for specifically targeting endogenous PD-L1 and dynamic monitoring the change of PD-L1 expression, and could guide the immunotherapy and immunochemotherapy for refractory cancers.


Encrypted antimicrobial peptides from proteins present in the plasma of the millipede Rhinocricus sp.
Millipedes are among the most diverse and abundant arthropods in terrestrial environments. However, little is known about their innate immune response against invading pathogenic microorganisms, which is very intriguing considering that the evolutionary success of millipedes is largely due to this complex and primitive defense system, since it allowed them to colonize a wide variety of microhabitats characterized by their high microbial proliferation. Accordingly, the aim of the present work was to determine the presence of antimicrobial peptides in the hemolymph of the millipede Rhinocricus sp. In total, four native peptides with potent antimicrobial activity against different microorganisms, lack of cytotoxicity against Vero cells and lack of hemolytic effects against human erythrocytes were isolated and named RP40-16, RP40-19, RP40-20/1 and RP40-20/2. The analysis with bioinformatics tools suggested that these peptides may be encrypted in large proteins present in the plasma: Hemocyanin and thioester-containing protein. Considering these results, it can be said that millipede hemolymph represents a promising source of molecules with potential for the development of non-conventional antibiotics. Therefore, in order to have a clearer notion of the biotechnological potential and the role of these peptides in the innate immune response of Rhinocricus sp., future studies should focus on elucidating their mechanisms of action, as well as additional biological properties.


Reviewing the reliability of Land Use and Land Cover data in studies relating human health to the environment.
In recent years, research has been increasingly devoted to understanding the complex human health-environment relationship. Nevertheless, many different measurements have been applied to characterize the environment. Among them, the application of Land Use and Land Cover (LULC) data is becoming more noticeable over time. This research aims to analyse the reliability of Land Use and Land Cover data (LULC) data as a suitable describer of the environment in studies relating human health to the environment. With a specific focus on the methodologies using LULC data, we also examine the study designs and analytical methods that have been commonly performed so far. We gathered studies relating human health outcomes to Land Use and Land Cover (LULC) data. A Boolean search limited to reviews was conducted in February 2019 using Web of Science Core Collection search engines. Five reviews were selected as our preliminary starting set of literature and from those, two backward snowballing searches were conducted. The first backward snowballing search used the reference lists of the first 5 reviews and revealed 17 articles. From these, the second search gathered 24 new articles also fulfilling the inclusion criteria established. In total, 41 articles were examined. Our main results reported that Land Use and Land Cover (LULC) data national level data was preferred over LULC international level data. However, this tendency seems to be strongly related to the specific aims of the articles. They essentially defined the living environment either through buffer zones, using the administrative boundaries wherein the individuals reside, or using the specific location of the individuals assessed. As for the characterization of the environment, authors performed 4 principal methodologies: extracting the percentage of green space, computing the "Land Use mix", recording the type of land cover, and using the percentage of tree canopy. Besides, all the articles included measurements in urban contexts and most of them evaluated the accessibility of individuals to their surroundings. Furthermore, it was clearly stated that the complexity of the topic and the challenging data leads authors to carry out advanced statistical methods and mostly cross-sectional designs with no causal relations. Land Use and Land Cover (LULC) data has been demonstrated to be a versatile tool supporting both local-focused studies with few individuals involved and broad territorial-scoped studies with huge populations. Promising synergy has been highlighted between Electronic Health Records (EHR) and LULC data in studies dealing with massive information and broader scopes with regards to the assessment of territorial realities. As this emerging topic matures, investigators should (1) elucidate subjects of ongoing debate such as the measurement of the living environment and its characterization; (2) explore the whole potential of LULC data, using methodologies that encompass both their biophysical and socioeconomic information; (3) perform innovative designs that are able to establish causal relationships among the studied variables (for example, Cellular Automata models), and (4) expand the current set of studied health outcomes leveraging comprehensive and trustworthy health data sources such as EHR.


Semantic processing in children and adults: incongruity and the N400.
Semantic processing in 10-year-old children and adults was examined using event related potentials (ERPs). The N400 component, an index of semantic processing, was studied in relation to sentences that ended with congruent, moderately incongruent, or strongly incongruent words. N400 amplitude in adults corresponded to levels of semantic incongruity with the greatest amplitude occurring to strongly incongruent sentences at all midline electrodes. In contrast, children's N400s were greater for both moderately and strongly incongruent sentences but did not differ between these levels of incongruity. This finding suggests that semantic processing may differ in adults and children.


Development of high protein, high fiber smoothie as a grab-and-go breakfast option using response surface methodology.
The current work aimed to formulate smoothie by optimizing varying levels of soy protein isolate (1.5-2.5% w/w), sucralose (150-190 ppm) and pectin (0.3-0.5% w/w) along with milk, legume (chickpea), vegetable (carrot), fruit (mango), honey and trisodium citrate by response surface methodology on the basis of sensory (color and appearance, flavor, consistency, sweetness and overall acceptability) and physical (expressible serum and viscosity) responses. Soy protein isolate and pectin levels influenced color and appearance, flavor, consistency and overall acceptability significantly. Soy protein isolate and pectin showed a positive correlation with viscosity of smoothie with reduced expressible serum. Smoothie was optimized with 1.8% (w/w) soy protein isolate, 166.8 ppm sucralose, and 0.5% (w/w) pectin with acceptable quality. One serving (325 ml) of optimized smoothie provides approximately 23% protein, 27% dietary fiber of the recommended daily values and provides approximately 74 kcal per 100 ml of smoothie, which renders smoothie as a high protein, high fiber, grab-and-go breakfast option.


An investigation of simulated umbilical artery Doppler waveforms. I. The effect of three physical parameters on the maximum frequency envelope and on pulsatility index.
The effect of three physical parameters on the accuracy of estimation of the maximum frequency envelope and pulsatility index (PI) of simulated umbilical artery Doppler waveforms was investigated. The physical parameters were beam-vessel angle, the offset between the beam axis and vessel axis, and the thickness of overlying attenuating material. Waveforms were acquired using a physiological flow phantom. The maximum frequency envelope was calculated using a threshold maximum frequency follower which was adaptive to the level of background noise. A gold standard maximum frequency envelope was obtained from the ensemble averaged waveform when there was alignment of beam and vessel axis, a 50 degrees beam-vessel angle and 2 cm of attenuating material. Indices of bias, variability and accuracy of estimation of the maximum frequency envelope and PI were calculated by comparing subsequent maximum frequency envelopes with the gold standard maximum frequency envelope. Both the maximum frequency envelope and PI were estimated to a similar degree of accuracy over a wide range of physical conditions. In this study, the error in PI was less than 0.15 for beam-vessel angles less than 80 degrees, for beam-vessel axis offset distances less than 7.5 mm, at a transducer-vessel distance of 5 cm, and for attenuator thicknesses less than 4.5 cm. The percentage root-mean square error for estimation of the maximum frequency envelope was approximately 10% or less for beam-vessel angles less than 75 degrees, for beam-vessel axis offset distances less than 7.5 mm, and for attenuator thicknesses less than 4 cm.


Total parietal peritonectomy in primary debulking surgery for advanced ovarian cancer.
The object of this study is to evaluate the clinical safety and efficacy of total parietal peritonectomy (TPP) in primary debulking surgery (PDS) for advanced ovarian cancer. This retrospective single-center study analyzed 16 patients with FIGO stages IIIC-IVB epithelial ovarian cancer who underwent TPP in PDS and achieved macroscopically complete resection between April 2015 and June 2016. The median age of 16 patients was 52.5 years old. 12 were in stage IIIC and 4 were in stage IV. Regarding intraoperative complications, unintended diaphragm perforation was observed in two patients. Regarding postoperative complications (Clavien-Dindo classification grade 3-5) before the adjuvant chemotherapy, lymph cysts occured in 3 patients, intra-abdominal abscess in 3, ileus in 2, pancreatic fistula in 1 and temporary kidney failure in 1. Regarding postoperative complications (grade 3-5) after the initiation of adjuvant chemotherapy, diaphragmatic hernia occured in 1 patient, ileus in 2 and intra-abdominal abscess in 2. Except 1 patient who relapsed approximately one month from surgery and died, the other 15 patients overcamed complications and recovered without problems in daily life. This analysis was conducted 3 years after all patients underwent PDS, with the 3-year progression-free and overall survival of 62.5% (95% confidence interval [CI], 34.9-81.1) and 87.5% (95 %CI, 58.6-96.7), respectively. Based on the above results, TPP in PDS may improve the prognosis compared to previous reports such as LION trial. On the other hand, complications may increase. Therefore, further studies are necessary on its safety and efficacy.


The prevalence of cervicogenic headache in a random population sample of 20-59 year olds.
From a random population sample, those experiencing frequent headaches were identified. They were examined to determine how many fulfilled the 1990 International Headache Society classification criteria for cervicogenic headache. To estimate the prevalence of cervicogenic headache in the general population and in the group experiencing frequent headaches. Only with the publication of the 1990 headache classification criteria did a generally accepted clinical definition of cervicogenic headache emerge. The prevalence of this form of headache has been estimated only in two highly selected in-clinic patient populations. No data exist regarding the prevalence in representative unselected populations. A short questionnaire on headaches was mailed to 826 randomly selected residents of a midsized Danish town. A group of 57 individuals in the age range 20-59 years who reported having headache episodes on 5 or more days in the previous month were identified. Forty-five of the 57 were eventually interviewed and examined with respect to the IHS criteria for cervicogenic headache (the radiological criteria were omitted on ethical grounds). Of the 45 persons examined, eight fulfilled the diagnostic criteria for cervicogenic headache, equivalent to a prevalence in the headache group of 17.8% (95% confidence interval = 8%-32%). Cervicogenic headache appears to be a relatively common form of headache, similar to migraine in prevalence.


Cardiopulmonary resuscitation of children.
Cardiopulmonary arrest in children frequently has a respiratory cause. Bradycardia and asystole result from the hypoxia and acidosis of inadequate ventilation. Fortunately, respiratory failure presents warning signs which make early intervention and prevention of arrest a major focus for the nurse. When cardiopulmonary arrest does occur, the nurse must be able to provide the A-B-C's of basic life support, to participate actively in definitive treatment of the arrest, and to assess the child carefully during the post-resuscitation recovery stabilization period.


The relationship between oxygen extraction and extravascular mean transit time in the canine heart.
A significant relationship was observed between myocardial oxygen extraction and the extravascular mean time transit time. This relationship implies that oxygen extraction by the myocardium is a time-dependent process, and emphasizes the critical link between blood flow and myocardial oxygen consumption.


Renal post-mortem findings in myeloproliferative and myelodysplastic/myeloproliferative neoplasms.
Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematological disorders presenting with an increased proliferation in one or several hematological cell lines. Renal manifestations of MPN have not been fully characterized so far. To morphologically assess the potential renal involvement in MPN patients, we analyzed histomorphological findings of a post-mortem cohort (n = 57) with a disease history of Philadelphia-negative MPN including polycythaemia vera, primary myelofibrosis, essential thrombocythemia, or chronic myelomonocytic leukemia (CMML). Seven (12.2%) patients presented with a pattern of diffuse glomerulosclerosis not attributable to diabetic or hypertensive nephropathy. Weak C4d staining suggestive for chronic thrombotic microangiopathy (TMA) was observed in 4/7 cases. Glomerulonephritis was excluded by light microscopy and immunohistochemistry. Patients with a pattern of diffuse glomerulosclerosis did not differ from the rest of the cohort regarding MPN subtype, disease duration, age, or sex. No significant proteinuria had been observed before death. Further findings attributed to MPNs were extramedullary hematopoiesis (n = 5; 8.8%) and tumor involvement in advanced disease (n = 4; 7.0%). Other common findings included arteriolosclerosis (n = 18; 31.6%) and signs of shock (n = 8; 14.0%). To our knowledge, this study is so far the largest investigating renal findings in MPN patients. There may be a causal relationship between idiopathic diffuse glomerular sclerosis and MPN, although its clinical significance and pathophysiology remain uncertain with TMA probably being relevant in a subgroup of cases. Our findings demonstrate the spectrum of renal findings in MPN from early to terminal disease of which hematologists should be aware of in daily clinical practice.


Comparative analysis of contributions of wet deposition and photodegradation to the removal of atmospheric BaP by MFDCCA.
Benzo [a] pyrene (BaP) in the atmosphere possess great carcinogenic potential to human health, and the understanding of its scavenging mechanisms has attracted considerable attention. In this work, a new quantitative method is proposed to make a comparative analysis of the long-term contributions of wet deposition and photodegradation to BaP removal based on multi-fractal detrended cross-correlation analysis (MFDCCA). According to the precipitation and global solar radiation (GSR) observations from 1998 to 2016 for two urban sites (Central/Western District and TsuenWan) in Hong Kong, the wet deposition and photodegradation of BaP are analyzed. Using MFDCCA method, long-term cross-correlation between precipitation/GSR and BaP are investigated. Moreover, the differences of multifractal features in cross-correlations of precipitation-BaP and GSR-BaP system are analyzed. Strong long-term persistence is observed in the cross-correlations for precipitation-BaP system in a one-year cycle; while cross-correlations between GSR and BaP show weak persistence over the whole timescale. Based on the meteorology in Hong Kong, this difference has been discussed. Then, contributions of wet deposition and photodegradation to atmospheric BaP removal are quantified based on MFDCCA method, which are further compared between summer and winter. The comparative analysis suggests that wet deposition plays a more significant role in the removal of atmospheric BaP. Specifically, in summer, the contributions of wet deposition are twice as much as that of photodegradation for both two sites; while in winter, the contribution of photodegradation is a little higher than that of wet deposition to BaP removal. Meanwhile, for wet deposition, the contributions in summer are about ten times greater than that in winter; while for photodegradation, the difference in contributions between summer and winter are relatively smaller. Furthermore, based on sliding window technique, the temporal evolutions in the contributions of wet deposition/photodegradation to BaP removal have been presented for both two sites. On this basis, it is discovered that the comprehensive contributions of wet deposition and photodegradation peak in June, and reach their lowest levels in December for both two sites. Quantifying the contribution of meteorological factors to the removal of atmospheric BaP is help for understanding its geochemical cycle.


Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment.
The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p < 0.05). Plasma oestrone was suppressed by a mean of 40.6% (p < 0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p < 0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.