Effects of aerobic dance training on blood pressure in individuals with uncontrolled hypertension on two antihypertensive drugs: a randomized clinical trial.
There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs.


Clinical outcome following stringent discontinuation of dual antiplatelet therapy after 12 months in real-world patients treated with second-generation zotarolimus-eluting resolute and everolimus-eluting Xience V stents: 2-year follow-up of the randomized TWENTE trial.
The aim of this study was to assess the safety and efficacy of the implantation of Resolute zotarolimus-eluting stents (ZES) (Medtronic Inc., Santa Rosa, California) and Xience V everolimus-eluting stents (EES) (Abbott Vascular, Santa Clara, California) following strict discontinuation of dual antiplatelet therapy (DAPT) after 12 months. Only limited long-term follow-up data are available from head-to-head comparisons of second-generation drug-eluting stents. The randomized TWENTE (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated study performed in a population with many complex patients and lesions and only limited exclusion criteria. Patients were randomly assigned 1:1 to ZES (n = 697) or EES (n = 694). Two-year follow-up information was available on all patients. The rate of continuation of DAPT beyond 12 months was very low (5.4%). The primary endpoint of target vessel failure, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization, did not differ between ZES and EES (10.8% vs. 11.6, p = 0.65), despite fewer target lesion revascularizations in patients with EES (2.6% vs. 4.9%, p = 0.03). The patient-oriented composite endpoint was similar (16.4% vs. 17.1%, p = 0.75). Two-year rates of definite or probable stent thrombosis were 1.2% and 1.4%, respectively (p = 0.63). Very late definite or probable stent thrombosis occurred only in 2 patients in each study arm (0.3% vs. 0.3%, p = 1.00). After 2 years of follow-up and stringent discontinuation of DAPT beyond 12 months, Resolute ZES and Xience V EES showed similar results in terms of safety and efficacy for treating patients with a majority of complex lesions and off-label indications for drug-eluting stents. (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente [TWENTE]; NCT01066650).


Evaluation of left main coronary artery stenosis by transthoracic echocardiography.
We sought to demonstrate left main coronary artery (LM) stenosis by transthoracic echocardiography. Evaluation of LM stenosis was done mostly by transesophageal echocardiography in patients with coronary artery disease. A total of 1456 patients with coronary artery disease were studied, of which 801 patients (55%) had adequate coronary flow assessment. The LM and the adjacent segments of left anterior descending coronary artery and left circumflex coronary artery were evaluated by color flow and Doppler. Mosaic flow and/or peak diastolic velocity of greater than or equal to 1.5 m/s was considered abnormal. These findings were correlated with stenoses at coronary angiography. A total of 40 patients who had abnormal diastolic flow in LM by transthoracic echocardiography constituted group 1 and 56 patients with normal LM flow constituted the control group (group 2). The peak diastolic velocities in LM in group 1 ranged between 1.5 and 4.4 m/s (mean 2.11 +/- 0.78 m/s). Of the 40 patients in group 1, 34 had significant LM stenosis by coronary angiography (sensitivity of 85%, positive predictive value 82.5%). The velocities in LM in group 2 ranged between 0.4 and 1.2 m/s (mean 0.66 +/- 0.25 m/s). In all, 49 of 56 patients in this group had normal LM on coronary angiography (88% specificity, negative predictive value 90.7%). The remaining 7 had distal LM stenosis. Mosaic flow in LM indicated significant LM stenosis in 85% of patients, whereas normal flow in LM did not rule out distal LM stenosis in 12% of patients. LM stenosis could be assessed by transthoracic echocardiography with an acceptable degree of sensitivity and specificity.


Resolutions of the Coulomb Operator: V. The Long-Range Ewald Operator.
We show that the long-range Ewald operator can be resolved as erf(ωr12)/r12 = ∑k ϕk*(r1) ϕk(r2), where ϕk is proportional to the product of a spherical Bessel function and a spherical harmonic. We demonstrate the use of this new resolution by calculating the long-range Coulomb energy of the nanodiamond crystallite C84H64 and the long-range exchange energy of the graphene C96H24. The resolution appears particularly effective for long-range exchange calculations.


Probability distribution of copy number alterations along the genome: an algorithm to distinguish different tumour profiles.
Copy number alterations (CNAs) comprise deletions or amplifications of fragments of genomic material that are particularly common in cancer and play a major contribution in its development and progression. High resolution microarray-based genome-wide technologies have been widely used to detect CNAs, generating complex datasets that require further steps to allow for the determination of meaningful results. In this work, we propose a methodology to determine common regions of CNAs from these datasets, that in turn are used to infer the probability distribution of disease profiles in the population. This methodology was validated using simulated data and assessed using real data from Head and Neck Squamous Cell Carcinoma and Lung Adenocarcinoma, from the TCGA platform. Probability distribution profiles were produced allowing for the distinction between different phenotypic groups established within that cohort. This method may be used to distinguish between groups in the diseased population, within well-established degrees of confidence. The application of such methods may be of greater value in the clinical context both as a diagnostic or prognostic tool and, even as a useful way for helping to establish the most adequate treatment and care plans.


An automated injection system (with patient selection) for SPECT imaging in seizure localization.
Ictal single-photon-emission computed tomography (SPECT) provides lateralization but has technical limitations: (a) a "truly ictal" injection must be shortly after seizure onset; (b) therefore, a seizure of brief duration may be missed; (c) more than one patient may need testing at any given time; (d) a trained health professional must stay next to each patient to inject; and (e) because the radionuclide is placed in the syringe in advance of the injection, decay of the radioactive element could result in less than optimal uptake, if the same volume of material were to be used regardless of the time after ligand preparation. We developed an automated method of ligand injection that shortens time and increases efficiency of ictal SPECT ligand injection. By using an experimental setup, we compared manual injection times with times using an automated injection system. We determined relative costs and efficiency in work hours for the manual and automated methods. Injection times were 8-14 s with automated versus 19-26 s with manual injection. Readjusting volume for "ligand" decay was simple and accurate with the automated system. Injection times for clinical SPECT studies in three patients were 13, 13, and 12 s, respectively. The price of one pump equals 120 work hours of a nurse or 24 ictal injection attempts. Much of the nurse's time is "wasted" because no seizure occurs. The method can be more efficient of staff, shorten injection time, and facilitate obtaining "truly ictal" injections. It allows more cost-effective use of personnel.


DNA barcoding in plants: evolution and applications of in silico approaches and resources.
Bioinformatics has played an important role in the analysis of DNA barcoding data. The process of DNA barcoding initially involves the available data collection from the existing databases. Many databases have been developed in recent years, e.g. MMDBD [Medicinal Materials DNA Barcode Database], BioBarcode, etc. In case of non-availability of sequences, sequencing has to be done in vitro for which a recently developed software ecoPrimers can be helpful. This is followed by multiple sequence alignment. Further, basic sequence statistics computation and phylogenetic analysis can be performed by MEGA and PHYLIP/PAUP tools respectively. Some of the recent tools for in silico and statistical analysis specifically designed for barcoding viz. CAOS (Character Based DNA Barcoding), BRONX (DNA Barcode Sequence Identification Incorporating Taxonomic Hierarchy and within Taxon Variability), Spider (Analysis of species identity and evolution, particularly DNA barcoding), jMOTU and Taxonerator (Turning DNA Barcode Sequences into Annotated OTUs), OTUbase (Analysis of OTU data and taxonomic data), SAP (Statistical Assignment Package), etc. have been discussed and analysed in this review. The paper presents a comprehensive overview of the various in silico methods, tools, softwares and databases used for DNA barcoding of plants.


The importance of being supercoiled: how DNA mechanics regulate dynamic processes.
Through dynamic changes in structure resulting from DNA-protein interactions and constraints given by the structural features of the double helix, chromatin accommodates and regulates different DNA-dependent processes. All DNA transactions (such as transcription, DNA replication and chromosomal segregation) are necessarily linked to strong changes in the topological state of the double helix known as torsional stress or supercoiling. As virtually all DNA transactions are in turn affected by the torsional state of DNA, these changes have the potential to serve as regulatory signals detected by protein partners. This two-way relationship indicates that DNA dynamics may contribute to the regulation of many events occurring during cell life. In this review we will focus on the role of DNA supercoiling in the cellular processes, with particular emphasis on transcription. Besides giving an overview on the multiplicity of factors involved in the generation and dissipation of DNA torsional stress, we will discuss recent studies which give new insight into the way cells use DNA dynamics to perform functions otherwise not achievable. This article is part of a Special Issue entitled: Chromatin in time and space.


Hepatoprotective effect of ultrasonicated ginseng berry extract on a rat mild bile duct ligation model.
The Panax ginseng berry extract (GBE) is well known to have an antidiabetic effect. The aim of this study is to evaluate and investigate the protective effect of ultrasonication-processed P. ginseng berry extract (UGBE) compared with GBE on liver fibrosis induced by mild bile duct ligation (MBDL) model in rats. After ultrasonication process, the composition ratio of ginsenoside in GBE was changed. The component ratio of ginsenosides Rh1, Rh4, Rg2, Rg3, Rk1, Rk3, and F4 in the extract was elevated. In this study, the protective effect of the newly developed UGBE was evaluated on hepatotoxicity and neuronal damage in MBDL model. Silymarin (150 mg/kg) was used for positive control. UGBE (100 mg/kg, 250 mg/kg, 500 mg/kg), GBE (250 mg/kg), and silymarin (150 mg/kg) were orally administered for 6 weeks after MBDL surgery. The MBDL surgery induced severe hepatotoxicity that leads to liver inflammation in rats. Also, the serum ammonia level was increased by MBDL surgery. However, the liver dysfunction of MBDL surgery-operated rats was attenuated by UGBE treatment via myeloid differentiation factor 88-dependent Toll-like receptor 4 signaling pathways. UGBE has a protective effect on liver fibrosis induced by MBDL in rats through inhibition of the TLR4 signaling pathway in liver.


Morphine-induced modification of quinine palatability: effects of multiple morphine-quinine trials.
Morphine pretreatment attenuates aversive taste reactions elicited by quinine solution when assessed by the taste reactivity test. To determine whether this effect changes across trials, rats were administered morphine (2 mg/kg, subcutaneously) 30 min before a 5-min intraoral infusion of quinine solution (0.05%) on each of eight trials. Neither tolerance nor sensitization developed to morphine-induced attenuation of quinine aversiveness; morphine suppressed quinine-elicited aversive reactions on each trial. In addition, when tested in the absence of morphine, rats displayed a reduced aversion to quinine, suggesting that quinine became conditionally less aversive following previous pairings with morphine.


Left ventricular function during porcine-resuscitated septic shock with pre-existing atherosclerosis.
Reversible, depressed cardiac function is frequently encountered during septic shock and commonly called septic cardiomyopathy. Previous studies demonstrated reduced ejection fraction and left ventricular dilatation in both humans and animal models. However, the majority of the studies in humans excluded pre-existing cardiac disease and animal studies were performed on healthy specimen and/or without vasopressor support during sepsis. In order to more closely mimic the actual patients' conditions on intensive care units and to assess the influence of both cardiac comorbidity and vasopressor support on septic cardiomyopathy, we evaluated the left ventricular function in a porcine model of resuscitated septic shock with pre-existing atherosclerosis. Hypercholesterolaemic, atherosclerotic pigs due to homozygous low-density lipoprotein receptor mutation and high-fat diet were anaesthetised and surgically instrumented. Faecal peritonitis was induced by inoculation of autologous faeces into the peritoneal cavity in n = 8 animals; n = 5 pigs underwent sham procedure. Sepsis resuscitation included administration of fluids and noradrenaline. Left ventricular function was analysed via pressure-conductance catheters before, 12 and 24 h after the induction of sepsis. The main findings were impaired ventricular dilatation (no significant change in the left ventricular end-diastolic volume) and unchanged ejection fraction in septic pigs with pre-existing atherosclerosis. The relaxation time constant τ decreased while dp/dtmax increased. Cardiac nitrotyrosine formation increased while expression of the endogenous hydrogen sulphide (H2S)-producing enzyme cystathionine γ-lyase (CSE) decreased. The data of the present study are in conflict with previously published data from healthy animal models, most likely as a result of ongoing resuscitation including noradrenaline treatment or intrinsic pathophysiologic processes of the pre-existing atherosclerosis. Moreover, increased nitrotyrosine formation and decreased expression of CSE suggest the implication of augmented oxidative/nitrosative stress and/or reduced bioavailability of nitric oxide as well as diminished endogenous H2S release in the pathophysiology of septic cardiomyopathy.


Phacoemulsification--why?
When a new operation replaces an old, it must be better, not just equally good. The Kelman method of cataract extraction has given impressive results in patients under the age of 30 years. However, for senile cataracts it is not better, the hospital stay is not shortened, and the recovery time is directly proportional to the age of the patient and to the preoperative condition of the eye, not to the type of extraction. Phacoemulsification is a cataract extraction and, therefore, should receive exactly the same monetary reward. No comparative series of cases done by the same surgeon or surgeons of equal skill has demonstrated that the Kelman phacoemulsification procedure is accompanied by fewer retinal detachments, Irvine-Gass syndromes, or other postoperative complications. The Kelman phacoemulsification method should be an adjunct to, and not a replacement for, the current intracapsular cataract extraction.


CXCL10 conditions alveolar macrophages within the premetastatic niche to promote metastasis.
Formation of the premetastatic niche is triggered by primary tumors and contributes to cancer metastasis. Evidence indicating the roles of macrophages in metastatic niche formation and organ-specific metastatic tropism has been steadily accumulating. However, the role of tissue-resident macrophages in the establishment of the premetastatic niche is not clearly defined. Here, we report that alveolar macrophages (AMs), which are lung tissue-resident macrophages, play a critical role in initiating the recruitment of monocytic myeloid-derived suppressor cells (mo-MDSCs) and the subsequent premetastatic niche formation by increasing CCL12 expression. We found that CXCL10 can induce CCL12 expression by activating CXCR3 and TLR4 in AMs. CXCR3/TLR4 deficiency or inhibition of its activity reduces CCL12 expression in AMs and subsequent mo-MDSC recruitment to the premetastatic niche, thereby attenuating lung metastasis. In addition, Ube2o is a negative modulator of CXCL10-induced CCL12 expression. Downregulation of Ube2o in AMs under tumor conditions enhances TAK1-NF-κB/ERK/JNK signaling and CXCL10-induced CCL12 expression by promoting TRAF6 polyubiquitination and inhibiting DDX3X degradation. Targeting mo-MDSC recruitment via the CXCL10-CXCR3/TLR4-CCL12 axis in AMs may have therapeutic potential for suppressing lung metastasis.


FDA Approves First Biosimilar to Treat Cancer.
The FDA approved the VEGF inhibitor bevacizumab-awwb for the treatment of five types of cancer: nonsquamous non-small cell lung cancer, metastatic colorectal cancer, cervical cancer, renal cell carcinoma, and glioblastoma. A biosimilar to bevacizumab, the agent is the first such drug approved for the treatment of cancer.


Survival outcomes of acute normovolemic hemodilution in patients undergoing primary debulking surgery for advanced ovarian cancer: A Memorial Sloan Kettering Cancer Center Team Ovary study.
To describe oncologic outcomes after using acute normovolemic hemodilution (ANH) to reduce requirement for allogenic red blood cell transfusions (ABT) in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. We performed a post-hoc analysis of a recent prospective trial investigating the safety and feasibility of ANH during PDS for advanced ovarian cancer. We report long-term survival outcomes. We compared demographics, clinicopathological characteristics, survival outcomes in this cohort of Stage IIIB-IVB high-grade serous ovarian cancer patients undergoing ANH (ANH group), with a retrospective cohort of all other patients (standard group) undergoing PDS during the same time period (01/2012-04/2017). Standard statistical tests were used. There were no demographic or clinicopathological differences between ANH (n = 33) and standard groups (n = 360), except for higher median age at diagnosis (57 vs. 62 years, respectively; p = 0.044) and shorter operative time (357 vs. 446 min, respectively; p < 0.001) in the standard group. Cytoreductive outcomes (ANH vs. standard): 0 mm, 69.7 vs. 63.9%; gross residual disease (RD) ≤1 cm, 21.2 vs. 26.9%; >1 cm, 9.1 vs. 9.2% (p = 0.78). RD after PDS was the only independent factor associated with worse progression-free survival (PFS) on multivariable analysis (p < 0.001). Patients with BRCA mutations trended towards improved PFS (p = 0.057). Significant factors for overall survival (OS) on multivariable analysis: preoperative CA125 (p = 0.004), ascites (p = 0.018), RD after PDS (p = 0.04), BRCA mutation status (p < 0.001). After adjustment for potential confounders, ANH was not independently associated with PFS or OS [PFS: HR 0.928 (0.618-1.395); p = 0.721; OS: HR 0.588 (95%CI: 0.317-1.092); p = 0.093]. ANH is an innovative approach in intraoperative management. It was previously proven to decrease need for ABT while maintaining the ability to achieve complete gross resection and associated benefits.


A frog in the throat?
A 44-year-old woman, with an unremarkable medical history, presented in the middle of the night with discomfort in her throat. She described being assaulted by an assailant who put his 'fist in her mouth', trying to suffocate her. On examination, she had normal observations and no signs of injury, other than scratch marks around her mouth; she reported no odynophagia and was able to swallow fluids readily. During examination, she complained that lying flat made her increasingly uncomfortable and was causing burgeoning dyspnoea. She had lateral soft tissue radiography of her neck as shown in figure 1.emermed;34/10/676/EMERMED2016205919F1F1EMERMED2016205919F1Figure 1Lateral neck soft tissue radiograph of the 44-year-old woman. What is the diagnosis? Caustic stricture of the oesophagusPharyngeal perforationPharyngeal pouchBoerhaave's syndrome.


Behavioral and emotional problems in a Kuala Lumpur children's home.
There is a dearth of studies on behavioral and emotional problems in residential care children in Malaysia. This study describes the behavioral and emotional problems in a sample of children in a government residential care home and compares them with their classmates living with their birth parents. A comparative cross-sectional study was carried out where carers from both groups were asked to fill in the translated Bahasa Melayu version of the Child Behavior Check List. Forms for 53 residential care children and 61 classmates were completed. The residential care children had significantly higher scores on the rule-breaking (P < 0.001) and Diagnostic and Statistical Manual of Mental Disorders (DSM) conduct problem subscales (P < 0.001). Residential care children's age significantly correlated with DSM somatic problems (P = 0.03) and post-traumatic stress (P = 0.023). Duration of care was significantly positively correlated with rule-breaking (P = 0.008), DSM conduct problems (P = 0.018) and externalizing scores (P = 0.017). Abuse and neglect cases had higher anxiety and depression scores (P = 0.024). Number of reasons in care positively correlated with several subscales, including total behavioral problem score (P = 0.005). Logistic regression revealed the greater number of reasons for placement a child had was significantly associated with having externalizing scores in the clinical range (P = 0.016). However, after Bonferroni correction, only the initial findings regarding rule-breaking and DSM conduct problem scores remained significant. Challenges exist in managing residential care children in Malaysia, especially regarding externalizing behavior. More studies are required to describe the Malaysian scene.


Value of conventional ultrasound, ultrasound elasticity imaging, and acoustic radiation force impulse elastography for prediction of malignancy in breast lesions.
To evaluate the efficacies of conventional ultrasound (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) elastography in breast malignancy diagnosis. We included 315 women (mean age, 44 years; range, 18-81 years) with 336 pathologically proven breast lesions in this retrospective study. All lesions underwent conventional US, EI, and ARFI (including virtual touch tissue imaging [VTI], virtual touch tissue quantification [VTQ], and virtual touch tissue imaging and quantification [VTIQ]) elastography. Multivariate logistic regression analysis was performed to assess 12 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis. Irregular lesion shape was the strongest independent predictor for breast malignancy, followed by poorly defined margins, taller than wide dimensions, posterior echo attention, VTIQ, and VTI boundaries (P < 0.05). Area under the ROC curve (AUC) for VTIQ was higher than other significant independent variables. With the best cut-off value of 3.74 m/s, the AUC, sensitivity, and specificity were 0.93 (95% CI: 0.90, 0.96), 90.1%, and 91.1%, respectively. ARFI elastography is a promising method in breast malignancy prediction, with good diagnostic performance. For patients requiring surgery, the combination of various methods can provide better diagnostic results and may help to reduce unnecessary biopsy or surgery.


Lumbar olisthesis and lower back symptoms in elderly white women. The Study of Osteoporotic Fractures.
A Cross-sectional study. To determine the prevalence of lumbar olisthesis among white women aged 65 years and older and its relation to low back pain and back function. Degenerative changes in the lumbar spine of elderly individuals may affect spinal stability, causing olisthesis (subluxation) of the lumbar spine. Neither the prevalence of this condition in the United States nor its relation to back symptoms has been studied previously. Lateral radiographs of the lumbar spine for 788 women aged 65 years and older who were enrolled in the Study of Osteoporotic Fractures were digitized. Olisthesis (antero- and retro-) was assessed at L3-L4, L4-L5, and L5-S1. Back pain and function also were assessed. When olisthesis was defined as subluxation of 3 mm or more at any of the three levels studied, the overall prevalence of anterolisthesis was 29% and that of retrolisthesis was 14%. In 90% of women with anterolisthesis and 88% of women with retrolisthesis, subluxation occurred at a single vertebral level. The prevalence of anterolisthesis and retrolisthesis did not vary by smoking status, presence of diabetes, or history of oophorectomy. Anterolisthesis was not associated with the presence of back symptoms. Only retrolisthesis at L3-L4 was associated with a statistically significantly increased likelihood of lower back pain, greater severity of back pain, and impairment of back function. Anterolisthesis of 3 mm or more in the lower lumbar spine is relatively common among elderly women but is not correlated with back problems. Retrolisthesis at L3-L4 is associated with increased back pain and impaired back function.


Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis.
Hepatocellular carcinoma (HCC) is the 3rd most deadly malignancy. Activated hepatic stellate cells (aHSC) give rise to cancer-associated fibroblasts in HCC and are considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase-2 (Scd2) in aHSC globally suppresses nuclear CTNNB1 and YAP1 in tumors and tumor microenvironment and prevents liver tumorigenesis in male mice. Tumor suppression is associated with reduced leukotriene B4 receptor 2 (LTB4R2) and its high affinity oxylipin ligand, 12-hydroxyheptadecatrienoic acid (12-HHTrE). Genetic or pharmacological inhibition of LTB4R2 recapitulates CTNNB1 and YAP1 inactivation and tumor suppression in culture and in vivo. Single cell RNA sequencing identifies a subset of tumor-associated aHSC expressing Cyp1b1 but no other 12-HHTrE biosynthetic genes. aHSC release 12-HHTrE in a manner dependent on SCD and CYP1B1 and their conditioned medium reproduces the LTB4R2-mediated tumor-promoting effects of 12-HHTrE in HCC cells. CYP1B1-expressing aHSC are detected in proximity of LTB4R2-positive HCC cells and the growth of patient HCC organoids is blunted by LTB4R2 antagonism or knockdown. Collectively, our findings suggest aHSC-initiated 12-HHTrE-LTB4R2-CTNNB1-YAP1 pathway as a potential HCC therapeutic target.


Pseudomonas sesami sp. nov., a plant growth-promoting Gammaproteobacteria isolated from the rhizosphere of Sesamum indicum L.
A novel Gram-stain negative, aerobic, motile, rod-shaped bacterium was isolated from Sesame (Sesamum indicum L.) rhizosphere soil. Based on the 16S rRNA gene similarity value (99.4-98.6%) obtained with phylogenetically closely related strains and through analyses of their house keeping genes (atpD, infB and rpoB), the strain SI-P133T was delineated among the species of the genus Pseudomonas and was subjected to polyphasic taxonomic analysis. It was a chemoorganotroph which grew at wide range of temperature (4-45 °C), pH (5.5-9.5) and NaCl concentrations (0-7% (w/v). DNA-DNA hybridization values with closely related type strains DSM 9751T, DSM 19095T, DSM 21509T, ICMP 9151T and DSM 6929T ranged from 23.1 to 44.2%. The most abundant fatty acids were C16:0, C10:0 3-OH, summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c), C17:0 cyclo and C12:0 3-OH. The major isoprenoid quinone system was ubiquinone 9 (Q-9) and the G+C content was 61.3 mol%. The major polar lipids of the strain SI-P133T were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. With regard to prospective use in agriculture, plant growth-promoting properties of the strain were tested and plant growth-promotion was demonstrated under in vitro conditions. Based on the various polyphasic taxonomic traits analysed, the strain SI-P-133T was novel and placed within the genus Pseudomonas. Hence we propose a novel species named Pseudomonas sesami sp. nov., for which the type strain is SI-P133T (=NCIMB 14519T = KCTC 22518T).


Effect of Bariatric Surgery on Metabolic Syndrome in Chinese Patients with Low Body Mass Index: a Propensity Score Matching Study.
Bariatric surgery (BS) is known to improve the components of metabolic syndrome (MS) in patients with obesity. However, few studies have evaluated the effect of BS on patients with MS at low BMI levels. The study aims to assess the effect of BS on MS in patients with low BMI by comparing BS with medical therapy (MT). A total of 271 patients with MS who underwent BS and MT at a single institution were reviewed in this retrospective cohort study. A 1:1 propensity score matching was performed for the BS and MT groups with BMI<35 kg/m2. We analyzed the 5 years effect of BS versus MT on the remission of MS, its components, atherosclerotic cardiovascular disease (ASCVD) risk, and medication used. Patients in the MT group showed a decrease in the prevalence of MS to 62% at the 1st year and 10% at the 5th year. In the BS group, MS prevalence in patients with BMI<35 kg/m2 decreased to 30% and 9% at the 1st and 5th year, whereas in patients with BMI≥35 kg/m2 was 26% and 7%, respectively. The 10-year ASCVD risk and the lifetime ASCVD were significantly decreased 5 years after BS in patients with BMI<35 kg/m2. The number and daily drug dose of hypoglycemic drugs, antihypertensive medications, and lipid-lowering drugs were reduced from baseline in both BS and MT groups. Bariatric surgery significantly improves MS remission rates and long-term cardiovascular risk in Chinese patients with metabolic syndrome and a BMI <35 kg/m2.


Frequency and Risk Factors of Subsyndromal Delirium in the Intensive Care Units: A Prospective Cohort Study.
Subsyndromal delirium (SSD) is a common neuropsychiatric disorder among the intensive care units (ICU) patients. SSD is characterized by the presence of delirium symptoms but it does not meet the diagnostic criteria of delirium, resulting in poor patient prognosis. The aim of this study was to explore the prevalence and risk factors for SSD among adult patients admitted to the ICU of XXX hospital in Southwest China. The study participants comprised 309 patients referred to the ICU in XXX hospital between 10th August 2021 and 5th June 2022. Demographic information, medical history, and other patient information were recorded. ICDSC assessment, physical examination and laboratory tests were performed on enrolled patients. Cognitive evaluation was conducted using the MMSE method. The results showed that out the 309 patients, 99 had possible SSD (prevalence of 32.0%), with 55 SSD1 cases (ICDSC score of 1, 17.8% prevalence), 29 SSD2 cases (ICDSC score of 2, 9.4% prevalence) and 15 SSD3 cases (ICDSC score of 3, 4.9% prevalence). Previous history of mental illness (OR, 3.741; 95% CI, 1.136-12.324; P <0.05), auxiliary ventilation (OR, 3.364; 95% CI, 1.448-7.813; P <0.01), hemodialysis (OR, 11.369; 95% CI, 1.245-103.840; P <0.05), MMSE score (OR, 0.845; 95% CI, 0.789-0.904; P <0.001) and a temperature ≥ 37.5 °C (OR, 3.686; 95% CI, 1.404-9.732; P <0.01) were independent risk factors for occurrence of SSD among ICU patients. Approximately one-third of the patients in the intensive care unit had high risk of SSD. Nursing staff should pay attention to management of the high-risk patients to prevent SSD from progressing delirium to improve patient prognosis.


Gender issues in US science and technology policy: equality of what?
Fairness in evaluation processes for women in science and engineering is only one of a set of issues that need to be addressed to reach gender equality. This article uses concepts from Amartya Sen's work on inequality to frame gender issues in science and technology policy. Programs that focus on increasing the number of women in science and engineering careers have not generally addressed a broader set of circumstances that intersect with gender at various economic levels and stages of life. The agendas in research and innovation policies also need to reflect these issues, and fair allocation of resources within both science and technology needs to be on the agenda. Getting women into high-level positions is not enough. Articulating the full research and innovation agendas for women will require broader participatory processes.


Early warning of red tides using bacterial and eukaryotic communities in nearshore waters.
Anthropogenic discharge activities have increased nutrient pollution in coastal areas, leading to algal blooms and microbial community changes. Particularly, microbial communities could easily be affected with variation in nutrient pollution, and thus offered a promising strategy to predict early red tides warning via microbial community-levels variation and their keystone taxa hysteretic responses to nutrient pollution. Herein high-throughput sequencing technology from 52 samples were used to explore the variation of microbial communities and find the significant tipping points with aggravating nutrient conditions in Xiaoping Island coastal area. Results indicated that bacterial and microeukaryote communities were generally spatial and seasonal heterogeneity and were influenced by the different nutrient conditions. Procrustes test results showed that the comprehensive index of organics polluting (OPI), total nitrogen (TN), inorganic nitrogen (DIN), and total phosphorus (TP) were significantly correlated with the composition of bacteria and microeukaryotes. A SEGMENTED analysis revealed that the threshold of TN, DIN, and NH4-N for bacterial community were 0.23 ± 0.091 mg/L, 0.21 ± 0.084 mg/L, 0.09 ± 0.057 mg/L, respectively. Tipping points for TN, DIN, and NH4-N agreed with the concentration during Ceratium tripos and Skeletonema costatum blooms. Co-occurrence network results found that Planktomarina, Acinetobacter, and Verrucomicrobiaceae were keystone and OPI-discriminatory taxa. The abundant changes of Planktomarina at station A1 were significantly correlated with the development of C. tripos blooms (r = 0.55, p < 0.05), and also significantly correlated with TN, DIN, and NO3-N (r≥|0.55|, p < 0.05). The abundant changes of Acinetobacter and Verrucomicrobiaceae at station C1 were significantly correlated with the development of C. tripos blooms (r ≥ 0.77, p < 0.05), and also significantly correlated with PO4-P (r ≥ 0.64, p < 0.05). The dynamic abundance of keystone taxa showed that the trend of rapid changes could be monitored 1.5 months before the occurrence of red tide. Therefore, this study provides an assessment method for early warning of red tide occurrence and factors that trigger red tide.


CX-5461 can destabilize replication forks in PARP inhibitor-resistant models of ovarian cancer.
Acquired drug resistance leads to poor clinical outcome in high grade serous ovarian cancer (HGSOC). We have demonstrated the efficacy of the novel drug CX-5461 in HGSOC is mediated through destabilization of DNA replication forks. The data highlights the potential of CX-5461 in overcoming a general mechanism of chemotherapeutic resistance.


[Effect of ablation of the basolateral and corticomedial portions of the amygdala on the performance of food-getting conditioned reflexes in rats].
In experiments on 66 albino rats an electrolytic coagulation of the basolateral amygdala caused facilitation while that of the corticomedial amygdala caused inhibition of alimentary conditioned reflexes. The corticomedial amygdala forms a part of the excitatory and the basolateral amygdala--of the inhibitory system of the rat's brain. In intact rats the basolateral amygdala function dominates over the corticomedial amygdala activity in feeding behaviour.


RNA in motion.
Although RNA duplex regions are highly structured and inflexible, other elements of an RNA molecule are capable of dynamic motions. These flexible regions are the sites of interactions with small molecules, proteins, and other RNAs, yet there are few descriptions of these regions that include the timescale and amplitude of their motions. No one technique is sufficient to accurately describe these motions, but the combination of in vitro methods, particularly NMR relaxation methods, and more robust in silico methods, is beginning to yield the type of data that can be used to understand RNA function. Very few RNAs have been described by both techniques, and here one such RNA and one RNA:protein complex are reviewed.


Retrospective evaluation of three different joint surgeries for internal derangements of the temporomandibular joint.
To compare the outcomes achieved with eminectomy, discectomy alone, and discectomy with an abdominal dermis fat graft (D + ADFG) in the treatment of internal derangements (IDs) of the temporomandibular joint (TMJ), and to briefly discuss the failed cases in which a second operation was needed. This was a retrospective study of 31 patients (27 females, 4 males) who were unresponsive to conservative therapy and therefore underwent eminectomy (group A, n = 6), discectomy alone (group B, n = 8), or D + ADFG (group C, n = 17). All of the IDs of the TMJ were unilateral. Functional mandibular pain intensity on a visual analog scale (VAS) and maximum interincisal opening (MIO) were recorded preoperatively and at the latest postoperative examination (average, 30 months). The preoperative and postoperative results were compared between and within each group. Overall, patients in groups B and C had better outcomes than those in group A in terms of TMJ symptom relief. Postoperative increases in MIO were statistically significant in groups A, B, and C (P < 0.027, P < 0.017, and P < 0.000, respectively). Patients with discectomized joints (groups B and C) had significantly improved pain scores (P < 0.05) at the latest follow-up. In 6 of the 31 (19.3%) patients (3 eminectomy, 1 discectomy, and 2 D + ADFG), the procedure was deemed unsuccessful because of persistent symptoms and a second operation was performed. Discectomy with or without ADFG was clearly superior to eminectomy in reducing pain and improving joint function. But there were no significant differences in the two-discectomy groups with respect to symptom improvement.


On the importance of hydrodynamic interactions in lipid membrane formation.
Hydrodynamic interactions (HI) give rise to collective motions between molecules, which are known to be important in the dynamics of random coil polymers and colloids. However, their role in the biological self-assembly of many molecule systems has not been investigated. Here, using Brownian dynamics simulations, we evaluate the importance of HI on the kinetics of self-assembly of lipid membranes. One-thousand coarse-grained lipid molecules in periodic simulation boxes were allowed to assemble into stable bilayers in the presence and absence of intermolecular HI. Hydrodynamic interactions reduce the monomer-monomer association rate by 50%. In contrast, the rate of association of lipid clusters is much faster in the presence of intermolecular HI. In fact, with intermolecular HI, the membrane self-assembly rate is 3-10 times faster than that without intermolecular HI. We introduce an analytical model to describe the size dependence of the diffusive encounter rate of particle clusters, which can qualitatively explain our simulation results for the early stage of the membrane self-assembly process. These results clearly suggest that HI greatly affects the kinetics of self-assembly and that simulations without HI will significantly underestimate the kinetic parameters of such processes.


GnRH and the photoperiodic control of seasonal reproduction: Delegating the task to kisspeptin and RFRP-3.
Synchronization of mammalian breeding activity to the annual change of photoperiod and environmental conditions is of the utmost importance for individual survival and species perpetuation. Subsequent to the early 1960s, when the central role of melatonin in this adaptive process was demonstrated, our comprehension of the mechanisms through which light regulates gonadal activity has increased considerably. The current model for the photoperiodic neuroendocrine system points to pivotal roles for the melatonin-sensitive pars tuberalis (PT) and its seasonally-regulated production of thyroid-stimulating hormone (TSH), as well as for TSH-sensitive hypothalamic tanycytes, radial glia-like cells located in the basal part of the third ventricle. Tanycytes respond to TSH through increased expression of thyroid hormone (TH) deiodinase 2 (Dio2), which leads to heightened production of intrahypothalamic triiodothyronine (T3) during longer days of spring and summer. There is strong evidence that this local, long-day driven, increase in T3 links melatonin input at the PT to gonadotropin-releasing hormone (GnRH) output, to align breeding with the seasons. The mechanism(s) through which T3 impinges upon GnRH remain(s) unclear. However, two distinct neuronal populations of the medio-basal hypothalamus, which express the (Arg)(Phe)-amide peptides kisspeptin and RFamide-related peptide-3, appear to be well-positioned to relay this seasonal T3 message towards GnRH neurons. Here, we summarize our current understanding of the cellular, molecular and neuroendocrine players, which keep track of photoperiod and ultimately govern GnRH output and seasonal breeding.


Tbx1 is required for second heart field proliferation in zebrafish.
The mammalian outflow tract (OFT) and primitive right ventricle arise by accretion of newly differentiated cells to the arterial pole of the heart tube from multi-potent progenitor cells of the second heart field (SHF). While mounting evidence suggests that the genetic pathways regulating SHF development are highly conserved in zebrafish, this topic remains an active area of investigation. Here, we extend previous observations demonstrating that zebrafish tbx1 (van gogh, vgo) mutants show ventricular and OFT defects consistent with a conserved role in SHF-mediated cardiogenesis. Surprisingly, we reveal through double in situ analyses that tbx1 transcripts are excluded from cardiac progenitor cells and differentiated cardiomyocytes, suggesting a non-autonomous role in SHF development. Further, we find that the diminutive ventricle in vgo animals results from a 25% decrease in cardiomyocyte number that occurs subsequent to heart tube stages. Lastly, we report that although SHF progenitors are specified in the absence of Tbx1, they fail to be maintained due to compromised SHF progenitor cell proliferation. These studies highlight conservation of Tbx1 function in zebrafish SHF biology.


Arthroscopic Repair of a Glenoid Avulsion of the Glenohumeral Ligament.
Injury to the glenohumeral capsulolabral complex is the critical lesion in anterior shoulder instability. Various injury patterns have been described including the classic Bankart lesion, the bony Bankart lesion, and humeral avulsion of the glenohumeral ligament. A rare injury variant is a glenoid avulsion of the glenohumeral ligament (GAGL lesion). Careful patient setup and surgical technique are required to identify and arthroscopically repair these lesions. We describe a suture anchor-based arthroscopic GAGL repair performed with the patient in the lateral decubitus position through standard anterior and posterior portals and an accessory posterolateral 7-o'clock portal.


Applied proteomics--analyzing protein structure and function for drug discovery. 27-28 January 1999, London, UK.
This two-day meeting, attended by approximately 60 delegates, was aimed at researchers in the proteomics field. The proteome is defined as the entire protein content of the cell. Proteomics is the analysis of the end-product of gene expression and all regulations governing gene expression are taken into account, ie, transcriptional and translational. The three stages involved in proteomic analysis are: a separation phase, ie, two dimensional (2D) gel electrophoresis; a characterization phase, ie, mass spectrometry; and, a data analysis phase, ie, bioinformatics.


Renal dysfunction is common following resuscitation from out-of-hospital cardiac arrest.
Cardiac arrest patients often suffer from dysfunction of multiple organ systems after return of spontaneous circulation (ROSC). The incidence of renal dysfunction in patients with out-of-hospital cardiac arrest (OHCA) is not well described. Renal dysfunction has been associated with worse outcomes in critical illness. Renal dysfunction is common after OHCA, and renal dysfunction is independently associated with survival. We performed a retrospective review of consecutive adult patients admitted to an intensive care unit after successful resuscitation from OHCA between 01/01/2005 and 12/31/2010. Patients were excluded for death or withdrawal of care within 24h, preexisting end-stage renal disease, or OHCA due to hyperkalemia. The RIFLE criteria were used to classify subjects with renal dysfunction into one of three categories - risk, injury, or failure - based on trending of serum creatinine concentration or glomerular filtration rate. Data were analyzed using descriptive statistics. Of 364 patients, 38 were excluded due to death or withdrawal of care within 24h, 11 due to end-stage renal disease, and 4 due to OHCA from hyperkalemia, leaving 311 patients in the final analysis. The mean age was 58 (SD 16) years; 174 (59%) were male, VF/VT was the primary rhythm in 156 (50%), and 236 (80%) were comatose at hospital arrival. Among 311 patients, 32 (10.3%) developed acute renal failure (ARF), 27 (8.7%) developed acute kidney injury (AKI), and 56 (18.0%) developed risk of renal dysfunction. Of the 32 subjects that developed ARF, renal replacement therapy (RRT) was initiated on 13 (40.6%). Development of ARF was not associated with survival (OR 0.73; 95% CI 0.26, 2.05) after adjusting for initial rhythm or illness severity. More than one-third of patients resuscitated from OHCA developed evidence of renal dysfunction, and 19% of patients meeting criteria for AKI or ARF. In this study, development of renal failure was not independently associated with survival.


Tumor embolism and acute arterial occlusion: A systematic review.
To determine common etiologies, presentations, management strategies and outcomes in patients with tumor embolism causing acute arterial occlusion. This is a systematic review of published case reports on tumor embolism. All published cases of tumor embolism in the MEDLINE and EMBASE databases were reviewed. The search terminologies were (Tumor Embolism), (Ischemia), (Occlusion) and (Infarction). All published reports of tumor embolism were included. Studies regarding venous thromboembolism and cancer-associated thromboembolism without tumor embolization were excluded. The cases included numbered 42. These included the frequencies of different primary tumor types, clinical presentations, anatomical sites of embolization, types of intervention and outcomes including number of deaths and successful discharges. Lung cancer and Atrial Myxoma each accounted for 14 out of 42 cases (33%). There were 11 cases (26.9%) of stroke and 9 cases (21.4%) of myocardial infarction and limb ischemia. Femoral thrombo-embolectomy was performed in all 9 cases of limb ischemia and Primary coronary intervention was performed in 7 out of 9 (77.8%) cases of myocardial infarction. There were 14 inpatient deaths (33.3%) and 19 patients were successfully discharged (45.2%). Lung cancer and atrial myxoma were the most common sources for tumor embolism. Acute stroke was the most common presentation. This is treated with antiplatelets or anticoagulation as well as chemotherapy and resection of primary tumor. Early revascularisation can prevent severe complications such as death, paralysis, heart failure and limb loss in selected cases of tumor embolism. Histopathological examination of embolic tissue can demonstrate tumor tissue and alert the clinician to a cancer elsewhere. This is most likely to be lung cancer or atrial myxoma. Early revascularisation in selected cases of acute tumor embolism can prevent severe complications and these patients should not be automatically palliated due to their underlying neoplasm.


Theoretical Calculations for Highly Selective Direct Heteroarylation Polymerization: New Nitrile-Substituted Dithienyl-Diketopyrrolopyrrole-Based Polymers.
Direct Heteroarylation Polymerization (DHAP) is becoming a valuable alternative to classical polymerization methods being used to synthesize π-conjugated polymers for organic electronics applications. In previous work, we showed that theoretical calculations on activation energy (Ea) of the C⁻H bonds were helpful to rationalize and predict the selectivity of the DHAP. For readers' convenience, we have gathered in this work all our previous theoretical calculations on Ea and performed new ones. Those theoretical calculations cover now most of the widely utilized electron-rich and electron-poor moieties studied in organic electronics like dithienyl-diketopyrrolopyrrole (DT-DPP) derivatives. Theoretical calculations reported herein show strong modulation of the Ea of C⁻H bond on DT-DPP when a bromine atom or strong electron withdrawing groups (such as fluorine or nitrile) are added to the thienyl moiety. Based on those theoretical calculations, new cyanated dithienyl-diketopyrrolopyrrole (CNDT-DPP) monomers and copolymers were prepared by DHAP and their electro-optical properties were compared with their non-fluorinated and fluorinated analogues.


Molecular analysis of a pro-T cell clone transformed by Abelson-murine leukemia virus, displaying progressive gamma delta T cell receptor gene rearrangement and surface expression.
We present a molecular analysis of T cell differentiation in a set of clones derived from in vitro Abelson murine leukemia virus (A-MuLV) infection of fetal liver cells. The parental clone had partial rearrangement of the beta and gamma loci and spontaneously displayed progressive rearrangement of V gamma genes during in vitro culture. Further differentiation of these clones leading to delta gene rearrangement and CD4 expression, then CD8, CD3 and T cell receptor gamma delta chain surface expression was obtained after intrathymic transfer followed by in vitro co-culture with thymic tissue. These A-MuLV clones, therefore, appear to represent a powerful model system for studying the early molecular events of T cell development at the clonal level.


Rest and exercise echocardiography for early detection of pulmonary hypertension.
Early detection of pulmonary hypertension (PH) is essential to ensure that patients receive timely and appropriate treatment for this progressive disease. Rest and exercise echocardiography has been used to screen patients in an attempt to identify early stage PH. However, current PH guidelines recommend against exercise tests because of the lack of evidence. We reviewed previous studies to discuss the current standpoint concerning rest and exercise echocardiography in PH. Around 20 exercise echocardiography studies were included to assess the cutoff value for exercise-induced pulmonary hypertension (EIPH). Approximately 40 exercise echocardiography studies were also included to evaluate the pulmonary artery pressure-flow relationship as assessed by the slope of the mean pulmonary artery pressure and cardiac output (ΔmPAP/ΔQ). There were several EIPH and ΔmPAP/ΔQ reference values in individuals with pulmonary vascular disease. We believed that assessing the ΔmPAP/ΔQ makes sense from a physiological standpoint, and the clinical value should be confirmed in future studies. Exercise echocardiography is an appealing alternative in PH. Further studies are needed to assess the prognostic value of the pulmonary artery pressure-flow relationship in high-risk subjects.


Epidemiology of elderly dependency in Tunisia. HSHS study 7.
Measure the functional autonomy of elderly people and identify its components and determinants in the HSHS (Hammam-Sousse Sahloul Heart Study) population (phase 2009, Tunisia). This study was concerned with the quality of life of elderly people aged 65 years or more, living at home from the HSHS cohort divided into two groups: young-old (65-74 years old) and old-old (≥75 years old). The autonomy was assessed using the "Activities of Daily Living" (ADL) scale ranging from 0 to 6, the "Instrumental Activities of Daily Living" (IADL) scale ranging from 0 to 8 and, the combined scale ranging from zero to 14, iso-weighted at one point per activity. Autonomy in daily activities was retained for an ADL score=6, and an IADL score (F=8; H=5). Subjects with an overall score (sum of ADL and IADL) of 10-14 points were considered globally autonomous. The population study was predominantly female (sex-ratio=0,6) with an important proportion of old-old (M=43%, F=37%). Autonomy rates were by ADL (M=57.4%, F=36.1%, p < 10-2), IADL (M=16%, F=23.9%), and by combined score (M=60.6%, F=69%, p=NS). The typology of dependency was dominated by transferring (M=35%, F=61%) and bathing (M=14%, F=19%) for ADL activities, and shopping (M=36%, F=49%) and the use of means of transport (M=22%, F=43%) for IADL activities. After adjustment, autonomy in daily activities was attributed to two independent factors: male sex (ORa=3.98, CI95% [1.328-11.971]) and age group 65-75 (ORa=4.04, CI95% [2.039- 8.025]). Autonomy in instrumental activities was associated with age group (ORa=31.5, CI95% [4.087-233.514]). Finally, overall autonomy (current and instrumental) was associated independently after logistic regression, with four independent factors, two of which were not modifiable: being female (ORa=3.1, CI95% [1.2-8.1]) and 65 to 75 years (ORa=6.2, CI95% [3.1-12.3]) and two modifiable factors: no recent hospitalization (ORa=3.8, CI95% [1.4-10.4]) and a sufficient level of physical activity (ORa=2.6, CI95% [1.3-5.3]). The physical dependency rate of the elderly is very high in Tunisia. The promotion of physical activity, the extension of similar studies and the development of could improve the support of these people.


[Are the UroLift(®) implants an alternative for the treatment of benign prostatic hyperplasia? Short-term results and predictive factors of failure].
To report the results of UroLift(®) implants after a 2-year experience in the technique. The procedure was proposed between February 2012 and April 2014 in patients with symptomatic benign prostatic hyperplasia, as an alternative to standard endoscopic ablation techniques. Evaluation of BPH related symptoms relied on the IPSS and IPSS-QoL self-questionnaires, as well as on maximum uroflow (Qmax). Evaluation of erectile and ejaculatory functions relied on the IIEF5 and MSHQ-EjD self-questionnaires, respectively. A total of 23 patients were treated during this period. Median age was 66 years [53-78]. Median prostate volume was 38mL [20-80]. Preoperative IPSS and IPSS-QoL were 20 [9-29] and 5 [3-6], respectively. No severe adverse event was observed postoperatively. Median follow-up was 14 [5-31] months. At the end of follow-up, 19 (83%) patients reported sustained symptomatic improvement without any additional treatment. Median IPSS and IPSS-QoL were improved significantly (11 [1-27] and 2 [0-6], P<0.0001), with however no significant improvement in Qmax. Four patients needed additional treatment during the first postoperative year. Among them, 3 had a prostate volume>60mL. No patient reported retrograde ejaculation or worsened erectile function. UroLift(®) implants allowed symptomatic improvement in more than 80% of the patients after 1-year follow-up. A high prostate volume may potentially be predictive of symptomatic failure. 5.


Advantages of 99mTc-3PRGD2 SPECT over CT in the preoperative assessment of lymph node metastasis in patients with esophageal cancer.
Our study was designed to compare the diagnostic efficacies of integrated 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon emission computed tomography (SPECT) images and computed tomography (CT) images in lymph node metastasis in the patients with esophageal cancer. From September 2015 and May 2018, 32 patients with histologically proven primary esophageal carcinoma underwent both 99mTc-3PRGD2 SPECT and CT scans followed by esophagectomy with lymph node dissection. The results of reviewing 99mTc-3PRGD2 SPECT and CT images for the lymph node metastasis were compared in relation with pathologic findings. During surgery, a total of 168 lymph nodes were dissected in 32 patients, of which 42 node groups in 18 patients were malignant on histologic examination. Preoperative nodal staging was compared with postoperative histopathological staging, The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 99mTc-3PRGD2 SPECT for lymph nodes were 80.95%, 86.51%, 85.12%, 66.67%, and 93.16% on per-node basis, respectively; compared with 59.52%, 73.02%, 69.64%, 42.37%, and 84.40% for CT (p = 0.034, 0.008, 0.005, 0.011, and 0.038, respectively). 70.59% (12/17) false-negative interpretations and 50% (17/34) false-positive interpretations on CT were corrected by 99mTc-3PRGD2 SPECT. 37.5% false-negative interpretations on 99mTc-3PRGD2 SPECT were corrected by CT. 11.90% (5/42) positive lymph nodes and 13.49% (17/126) negative nodes at pathology were incorrectly diagnosed both by 99mTc-3PRGD2 SPECT and CT. The accuracy of 99mTc-3PRGD2 SPECT (87.50%, 28/32) was significantly higher than that of CT (62.50, 20/32; p = 0.022) on per-patient basis. 99mTc-3PRGD2 SPECT showed significantly higher sensitivity and accuracy in the neck and upper thoracic regions than CT. For nodal staging, 99mTc-3PRGD2 SPECT was correct in 78.12% (25/32) of the patients, whereas CT was correct in 53.12% (17/32), p = 0.037. 99mTc-3PRGD2 SPECT is more accurate than CT for preoperative assessment of lymph node metastasis in esophageal cancer and may be helpful in determining the therapeutic plan.


Raman spectra of carotenoids in natural products.
Resonance Raman spectra of naturally occurring carotenoids have been obtained from nautilus, periwinkle (Littorina littorea) and clam shells under 514.5 nm excitation and these spectra are compared with the resonance Raman spectra obtained in situ from tomatoes, carrots, red peppers and saffron. The tomatoes, carrots and red peppers gave rise to resonance Raman spectra exhibiting a nu1 band at ca. 1520 cm(-1), in keeping with its assignment to carotenoids with ca. nine conjugated carbon-carbon double bonds in their main chains, whereas the resonance Raman spectrum of saffron showed a nu1 band at 1537 cm(-1) which can be assigned to crocetin, having seven conjugated carbon-carbon double bonds. A correlation between nu1 wavenumber location and effective conjugated chain length has been used to interpret the data obtained from the shells, and the wavenumber position (1522 cm(-1)) of the nu1 band of the carotenoid in the orange clam shell suggests that it contains nine conjugated double bonds in the main chain. However, the black periwinkle and nautilus shells exhibit nu1 bands at 1504 and 1496 cm(-1), respectively. On the basis of the correlation between nu1 wavenumber location and effective conjugated chain length, this indicates that they contain carotenoids with longer conjugated chains, the former having ca. 11 double bonds and the latter ca. 13 or even more. Raman spectra of the nautilus, periwinkle and clam shells also exhibited a strong band at 1085 cm(-1) and a doublet with components at 701 and 705 cm(-1), which can be assigned to biogenic calcium carbonate in the aragonite crystallographic form.


Effects of phthalates on the development and expression of allergic disease and asthma.
To review recent evidence relating phthalate exposures to allergies and asthma and to provide an overview for clinicians interested in the relevance of environmental health research to allergy and who may encounter patients with concerns about phthalates from media reports. PubMed, TOXLINE, and Web of Science were searched using the term phthalate(s) combined with the keywords allergy, asthma, atopy, and inflammation. Articles were selected based on relevance to the goals of this review. Studies that involved humans were prioritized, including routes and levels of exposure, developmental and early-life exposures, immunotoxicity, and the development of allergic disease. The general public and those with allergy are exposed to significant levels of phthalates via diet, pharmaceuticals, phthalate-containing products, and ambient indoor environment via air and dust. Intravenous exposures occur through medical equipment. Phthalates are metabolized and excreted quickly in the body with metabolites measured in urine. Phthalates, which are known endocrine disrupting compounds, have been associated with oxidative stress and alterations in cytokine expression. Metabolites in human urine, particularly of the higher-molecular-weight phthalates, have been associated with allergies and asthma in multiple studies. Despite mounting evidence implicating phthalates, causation of allergic disease by these compounds cannot currently be established. In utero and early-life exposures and possible transgenerational effects are not well understood. However, considering the current evidence, reducing exposures to phthalates by avoiding processed and foods packaged and stored in plastics, personal care products with phthalates, polyvinyl chloride materials indoors, and reducing home dust is advised. Further longitudinal, molecular, and intervention studies are needed to understand the association between phthalates and allergic disease.


A putative 12-oxophytodienoate reductase gene CsOPR3 from Camellia sinensis, is involved in wound and herbivore infestation responses.
12-Oxophytodienoate reductase (OPR) is a key enzyme in the biosynthesis of jasmonic acid (JA), which plays an important role in plant defense responses. Although multiple isoforms of OPRs have been identified in various annual herbaceous plants, genes encoding these enzymes in perennial woody plants have yet to be fully investigated. In the tea plant, Camellia sinensis (L.), no OPR genes have been isolated, and their possible roles in tea plant development and defense mechanism remain unknown. In this study, a putative OPR gene, designated as CsOPR3, was isolated from tea plants for the first time through the rapid amplification of cDNA ends. The open reading frame of CsOPR3 is 1197bp in length, and encodes a protein of 398 amino acids. Real-time qPCR analysis revealed that CsOPR3 was expressed in different organs. In particular, CsOPR3 was highly expressed in flowers, leaves and stems but was weakly expressed in roots and seeds. CsOPR3 expression could be rapidly induced by mechanical wounding, and increased JA levels were correlated with the wound-induced CsOPR3 expression. The infestation of the tea geometrid (TG) Ectropis obliqua Prout, regurgitant derived from TG and exogenous JA application could enhance the CsOPR3 expression. Our study is the first to report that CsOPR3 plays an important role in JA biosynthesis and tea plant defense against herbivorous insects.


Airway hyperreactivity follows anaphylactic microshock in anaesthetized guinea-pigs.
Actively sensitized guinea-pigs were challenged with a dose of ovalbumin aerosol (300 micrograms ml-1, 5 s) that caused submaximal bronchoconstriction (anaphylactic microshock). Airway reactivity to i.v. 5-hydroxytryptamine (5-HT), i.v. acetylcholine (ACh) and aerosolised 5-HT was assessed subsequently. In addition, histological studies were carried out to investigate possible pulmonary recruitment of inflammatory cells following anaphylactic microshock. Following antigen challenge, there was a significant (P less than 0.05) increase in airway reactivity. This phenomenon was temporally separated (60-120 min) from the initial anaphylactic bronchoconstriction, but occurred in the absence of detectable lung pathology other than minor epithelial necrosis. Whilst histamine aerosol (100 micrograms ml-1, 5 s) did not induce airway hyperreactivity, pretreatment with the histamine H1 receptor antagonist mepyramine (2 mg kg-1 i.v.) prevented that occurring following antigen challenge. These observations suggest that in the pathogenesis of airway hyperreactivity, mediator release from resident leukocytes is initially more important than pulmonary infiltration of circulating cells. Depletion of a putative epithelium-derived relaxant factor may also play a contributory role. The anaphylactic release of histamine may modulate the release of secondary mediators of airway hyperreactivity.


Limitations in the echocardiographic assessment of aortic root dimensions in the presence of aortic valve disease.
Aortic root M-mode echocardiograms were evaluated in 79 patients who had aortic valve replacement. Echocardiographic measurements of aortic root dimensions correlated poorly with surgical estimates. Inclusion of a portion of the sinuses of Valsalva in the former set of estimates probably accounts for this discrepancy.


Deserve's Got Nothin' to Do With It: A Philosopher Visits the NICU.
After the death of my daughter Zoe in neonatal intensive care unit (NICU), a colleague asked me whether my status as an academic philosopher changed my experience in the NICU. In this short narrative, I outline 5 ways in which philosophical perspective helped me understand and cope with our hospital experience.


Risk factors for carbapenemase-producing Enterobacteriaceae colonization of asymptomatic carriers on admission to an Italian rehabilitation hospital.
The spread of carbapenemase-producing Enterobacteriaceae (CPE) has become a worldwide problem. Early identification and isolation of asymptomatic carriers are important for infection prevention and control measures. All inpatients (N=1427) admitted to 'Fondazione Santa Lucia' Rehabilitation Hospital in 2014 were screened by rectal swab; 10.2% of them were CPE-colonized. The multivariate analysis on anamnestic data showed that both previous admission to an intensive care unit (odds ratio: 4.04; 95% confidence interval: 2.20-7.44; P<0.001) or post-acute care hospitals (2.88; 1.74-4.77; P<0.001) and presence of a central venous catheter (2.19; 1.34-3.59; P<0.001) were significant risk factors.


Biocompatibility of glass ionomer cements.
Glass ionomer cements (GICs) are widely used in the dental field and are increasingly being considered as materials with potentially good osteogenic properties. This paper details a comprehensive biocompatibility evaluation of a number of GICs. These include conventional, commercially available materials, novel formulations and a new light cured material. The experimental programme entailed in vitro cell culture studies using direct contact and extraction tests and an in vitro rat model in which the GICs were in intimate contact with bone for periods up to 8 wk. The results demonstrate clear differences between the materials and in particular highlight the poor cellular response to the light cured material. Methylthiazolyldiphenyl tetrazolium assay demonstrates stimulation of cell growth by some GIC formulations and indicates that cytotoxic leachable agents can be removed from others. The results obtained following implantation into bone are comprehensively presented using photomicrographs. New bone formation with time is demonstrated with a number of formulations.


Kinetics of galactose uptake by perfused rat livers: applicability of a family of models.
Mathematical models for general substrate uptake mechanisms in the liver have been used to describe the kinetics of galactose removal. In this study sets of galactose uptake rates to galactose concentration relations obtained by perfusion of ten livers of 200 g rats were examined. The rate of galactose uptake (v) was related to the galactose concentration in the sinusoids (calculated as the logarithmic mean of in- and outlet concentration, ĉ). In all experiments a saturation pattern emerged, but the resulting 1/v versus 1/ĉ plots were all markedly convex, discarding simple Michaelis-Menten kinetics. Data were therefore examined in the light of a family of kinetic models, including the following modifications: substrate inhibition, porto-systemic shunting, and allosterism. The kinetic constants were assessed by iterative procedures, aiming at linearization of the double reciprocal plots. The two latter models were found to fit the experimental data by entering a shunting of 61% of the hepatic blood flow, or two active sites, respectively. Since this degree of shunting is improbable the results speak in favour of allosterism. The work gives an example of whole-liver kinetic considerations when simple Michaelis-Menten is insufficient.


Adult attachment measures: a 25-year review.
Over the past 25 years, attachment research has extended beyond infant-parent bonds to examine dyadic relationships in children, adolescents, and adults. Attachment has been shown to influence a wide array of biopsychosocial phenomena, including social functioning, coping, stress response, psychological well-being, health behavior, and morbidity, and has thus emerged as an important focus of psychosomatic research. This article reviews the measurement of adult attachment, highlighting instruments of relevance to-or with potential use in-psychosomatic research. Following a literature search of articles that were related to the scales and measurement methods of attachment in adult populations, 29 instruments were examined with respect to their utility for psychosomatic researchers. Validity, reliability, and feasibility were tabulated on 29 instruments. Eleven of the instruments with strong psychometric properties, wide use, or use in psychosomatic research are described. These include the following: Adult Attachment Interview (George, Kaplan, and Main); Adult Attachment Projective (George and West); Adult Attachment Questionnaire (Simpson, Rholes, and Phillips); Adult Attachment Scale (and Revised Adult Attachment Scale) (Collins and Read); Attachment Style Questionnaire (Feeney); Current Relationship Interview (Crowell and Owens); Experiences in Close Relationships (Brennan, Clark, and Shaver) and Revised Experiences in Close Relationships (Fraley, Waller, and Brennan); Parental Bonding Instrument (Parker, Tupling, and Brown); Reciprocal Attachment Questionnaire (West and Sheldon-Keller); Relationship Questionnaire (Bartholomew and Horowitz); and Relationship Scales Questionnaire (Grifiin and Bartholomew). In addition to reliability and validity, investigators need to consider relationship focus, attachment constructs, dimensions or categories of interest, and the time required for training, administration, and scoring. Further considerations regarding attachment measurement in the context of psychosomatic research are discussed.


Cold-related cardiac mortality in King County, Washington, USA 1980-2001.
Studies have shown that cardiac deaths increase during the winter months and that death rates can be tightly predicted from temperature rather than other atmospheric phenomena such as barometric pressure, humidity, or pollution. The object of this study is to examine the possible relationship between temperature and cardiac death rates in King County, Washington, USA and suggest possible public health measures that can decrease the number of cardiac deaths associated with cold exposure. State death records show that 62,125 total out-of-hospital cardiac-related deaths among persons 55 years and older occurred in King County between 1980 and 2001. We use Poisson regression to examine the association between same-day daily average temperature and death rate after adjusting for seasonal effects. We identified a significant negative association between daily average temperature and cardiac mortality among persons over 55 years of age. A 5 degrees C increase in temperature was associated with a decrease in death rate by a factor of 0.971 (95% CI: 0.961, 0.982). Cold temperatures may be an important triggering factor in bringing on the onset of life-threatening cardiac events, even in regions with relatively mild winters. Public health efforts stressing cold exposure while out of doors may play a prominent role in encouraging a reduction in cold stress, especially among seniors and those already at higher risk of cardiac death.


Neuromuscular blockade by IgG antibodies from patients with Guillain-Barré syndrome: a macro-patch-clamp study.
Guillain-Barré syndrome (GBS) is often associated with serum antibodies to glycoconjugates such as GM1 and GQ1b. The pathogenic role of these antibodies and other serum factors has not yet been clarified. We have investigated the effect of serum, plasma filtrate, and highly purified IgG and IgM from 10 patients with typical GBS on motor nerve terminals in the mouse hemidiaphragm. Quantal endplate currents were recorded by means of a perfused macro-patch-clamp electrode. The plasma filtrate of all GBS patients led to a 5- to 20-fold reduction of evoked quantal release within 7 to 15 minutes of continuous superfusion. In 4 patients, the amplitudes of single quanta were clearly reduced (by 10-66% of control values), indicating an additional postsynaptic action. Blocking effects could be reversed to a variable degree within 15 to 18 minutes after washout. Purified IgG was as effective as native serum, whereas a purified GBS IgM fraction did not block transmission. Sera from convalescent patients and IgG from healthy subjects were without blocking effect. The effects were complement independent and there was no link to the presence (in 6 patients) or absence (in 4 patients) of detectable antibodies to GM1 or GQ1b. In GBS, antibodies to an undetermined antigen depress the presynaptic transmitter release and, in some cases, the activation of postsynaptic channels. We suggest that weakness in the acute stage of GBS may be caused in part by circulating antibodies.


Implications for multiple transmitter mediation of amphetamine-induced stereotypies.
Gerbils were pretreated with the dopamine (DA) receptor blocker, pimozide, prior to stereotypy-inducing injections of d-amphetamine. Some of the stereotypies induced with amphetamine were blocked, but some were not, supporting the hypothesis that multiple neurotransmitters are involved in the mediation of amphetamine-induced stereotypy. In addition, when apomorphine hydrochloride was injected, different stereotypic motor behaviors were induced than were induced with amphetamine. The behavioral changes following amphetamine treatment could be classified into four groups: (1) those that are probably DA related, based on the fact that they were induced with either amphetamine or apomorphine, and amphetamine induction was blocked with pimozide; (2) those that are probably not DA related because they were not induced by apomorphine, and amphetamine induction was not blocked by pimozide; (3) those behaviors that may be incompatible with stereotypic behaviors, were reduced with either amphetamine or apomorphine, but were not maintained with pimozide; and (4) circling, which was induced with amphetamine, blocked with pimozide, but not induced with apomorphine.


Effects of valganciclovir on spermatogenesis in renal transplant patients - results of a multicenter prospective nonrandomized study.
Ganciclovir (GCV) inhibits spermatogenesis in preclinical studies but long-term effects on fertility in renal transplant patients are unknown. In a prospective, multicenter, open-label, nonrandomized study, male patients were assigned to Cohort A [valganciclovir (VGCV), a prodrug of GCV] (n = 38) or B (no VGCV) (n = 21) by cytomegalovirus prophylaxis requirement. Changes in semen parameters and DNA fragmentation were assessed via a mixed-effects linear regression model accounting for baseline differences. Sperm concentration increased post-transplant, but between baseline and treatment end (mean 164 days Cohort A, 211 days Cohort B), the model-based change was lower in Cohort A (difference: 43.82 × 106 /ml; P = 0.0038). Post-treatment, sperm concentration increased in Cohort A so that by end of follow-up (6 months post-treatment) changes were comparable between cohorts (difference: 2.09 × 106 /ml; P = 0.92). Most patients' sperm concentration improved by end of follow-up; none with normal baseline concentrations (≥20 × 106 /ml) were abnormal at end of follow-up. Changes in seminal volume, sperm motility/morphology, DNA fragmentation, and hormone levels were comparable between cohorts at end of follow-up. Improvement in semen parameters after renal transplant was delayed in men receiving VCGV, but 6 months post-treatment parameters were comparable between cohorts.


Comparative evaluation of shear bond strength of three different glass ionomer cement (conventional, zirconium-reinforced and advanced glass hybrid) in primary molars: an in vitro study.
The success of restorative materials is largely dependent on their capacity to adhere to the tooth structure and withstand the various forces present in the oral cavity. So, the aim of present study was to evaluate and compare the shear bond strength (SBS) of Type IX Glass Ionomer Cement (GIC), Zirconomer, and Gold Label Hybrid GIC in primary molars. Thirty primary molars were selected based on inclusion and exclusion criteria. The molars were polished to provide a flat dentin surface after being inserted in auto polymerizing acrylic resin. The samples were randomly divided into three groups, equally and were bonded to GIC. On the dentin surface, restoration cylinders were made using a plastic mould that had an internal diameter and height of 5 mm and 3 mm, respectively. The cement was manipulated according to the manufacturer's directions through the plastic mould. Then, the samples were stored at room temperature for 10 days to mimic oral conditions. The Universal Testing Machine was used to test SBS. One-way ANOVA and the post hoc Tukey test were used to statistically assess the collected data. A statistically significant difference was found in all three groups (p < 0.01), with Zirconomer demonstrating highest SBS, followed by Type IX GIC and Gold Label Hybrid GIC. The SBS value of Zirconomer was better when compared to Type IX GIC and Gold Label Hybrid GIC.


Tris-(μ4-azepane-1-carbodi-thio-ato)bis-(μ3-azepane-1-carbodi-thio-ato)-μ9-bromido-tetra-μ2-bromido-octa-copper(I)-copper(II).
The reaction of Cu(Hm-dtc)2 (H2m-dtc is azepane-1-carbodi-thioic acid), CuBr2 and methyl iso-thio-cyanate yielded the title mixed-valence nona-nuclear Cu(I)/Cu(II) compound, [Cu9Br5(C7H12NS2)5] or [Cu(I) 8Cu(II)Br5(Hm-dtc)5], encapsulating a bromide anion in the center of the Cu9Br4S10 cluster cage. The cage consists of a mononuclear Cu(II) unit [Cu(Hm-dtc)2], three μ4-bridging Hm-dtc(-) ligands, eight Cu(I) ions with distorted tetra-hedral or trigonal pyramidal coordination geometries and four μ2-bridging bromide anions. The incorporated central bromide anion inter-acts with nine Cu ions with shorter Cu-Br separations than the sum of the van der Waals radii for Cu and Br.


Quality of Life in Adolescents and Young Adults: The Role of Symptom Burden.
Adolescents and young adults (AYAs) with cancer report worse health-related quality of life (HRQOL) than other age groups. Symptom burden is a modifiable predictor of HRQOL. The objective of this study was to identify which symptoms are most burdensome to AYAs with advanced cancer. In this observational study, English-speaking individuals aged 12-25 years undergoing treatment for advanced cancer completed assessments of symptom burden (Memorial Symptom Assessment Scale) and HRQOL (Pediatric Quality of Life Inventory Generic Form and Cancer Module; minimal clinically important difference 4.4). We dichotomized participants as having low (<7) or high (≥7) symptom prevalence. Mixed regression models estimated HRQOL differences between groups. For individual symptoms, unadjusted mixed models estimated HRQOL reductions. N = 58 AYAs completed baseline surveys. The median age was 17 years (IQR 15-19), 58% were male, 59% identified as white, and 44% were diagnosed with leukemia/lymphoma. High symptom prevalence was associated with a mean generic HRQOL 7 points lower (95% CI: -11, -3; P < 0.01) and cancer-specific HRQOL score 12 points lower (95% CI: -17, -7; P < 0.01) than low symptom prevalence. The most prevalent symptoms were fatigue (71%), pain (58%), and difficulty sleeping (58%). Fatigue (-8), difficulty concentrating (-7), and mouth sores (-6) were associated with the greatest generic HRQOL score reductions. Dysphagia (-12), difficulty concentrating (-12), and sadness (-11) were associated with the greatest cancer-specific HRQOL score reductions. The symptom experience among AYAs with advanced cancer is unique. Separate evaluation of AYA's symptoms may optimize management and improve HRQOL.


The Natural Course of Pancreatic Cysts in Inflammatory Bowel Disease: Results of a Long-term Follow-up.
The natural course of pancreatic cysts in inflammatory bowel disease (IBD) is unknown. We aim to describe the natural course of pancreatic cysts in IBD and evaluate long-term outcomes. A database of patients with abdominal imaging diagnosis of pancreatic cysts (2008-2019) was reviewed. Patients with IBD and pancreatic cysts (study group) and pancreatic cysts without IBD (controls) were selected. Outcomes were measured at 1, 3, 5, and 10 years. Several logistic regression models were used for analysis. Of the 1789 patients evaluated, 1690 had pancreatic cysts without IBD, and 78 had IBD and pancreatic cysts. Majority of cysts were intraductal papillary mucinous neoplasms. Patients with IBD and pancreatic cysts were more likely to be diagnosed with pancreatic cysts at a younger age (P < 0.001) and were more likely to undergo surgical intervention at a younger age (P < 0.001). This is the first study to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in long-term outcomes. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD.


Environmental factors influencing the seasonality of estrus in chimpanzees.
Although the energetics of the estrous cycle in primates is not well understood, evidence suggests that energy and nutrient acquisition influence ovulation and the timing of conception. Energy for estrus has to compete with energy allocated for cellular maintenance, thermoregulation, movement for food, and predation avoidance. While some chimpanzee (Pan troglodytes) populations do not have a seasonal birth period, evidence suggests that there is seasonality in the number of estrous females. Similarly, the onset of postpartum cycles has been reported to be seasonal. We used 33 months of data from the Taï National Park, Côte d'Ivoire, to examine how the number of estrous females in a given month was influenced by the abundance and distribution of food, diet, rainfall and temperature. In a second analysis, we examined if there was a seasonal effect on first estrous swellings in adolescent females and postpartum adult females. Results demonstrated that the number of females in estrous in a given month was positively related to food abundance and percent foraging time spent eating insects, and negatively related to mean rainfall in the two preceding months and the mean high temperature. The timing of first estrous swellings of postpartum females and prepartum young females was positively related to the food abundance, and negatively related to mean high temperature. These results showed that environmental conditions can seasonally limit the energetically demanding estrus cycle. The presence of estrous females increases gregariousness in chimpanzee communities, and this study identified environmental factors that affect estrus directly and hence social grouping indirectly.


Effects of freezing storage on the stability of maternal cellular and humoral immune components in porcine colostrum.
The placental structure of sows is epitheliochorial and prevents maternal serum immunoglobulin transfer to the fetus; therefore, the piglet relies on the ingestion of colostrum to acquire passive immunity. Colostral antibody-mediated and cell-mediated immunity contribute to immunity in piglets. However, little is known about the effects of freezing at -20 °C on colostral immune components during short-term storage, whether this will somehow compromise the acquisition of passive immunity of newborn piglets fed with this colostrum and the humoral immunity in porcine colostrum, and to possible shifts in immunological levels in colostrum collections during the colostral period. Based on the average concentration of immunoglobulin, frozen and fresh colostrum did not differ significantly. Overall, there were no storage differences in total macrophages, granulocytes, and NK cells. However, the frozen colostrum presented T lymphocyte subsets and B lymphocytes significantly lower than the fresh colostrum (p ≤ 0.05). Therefore, to sustain higher piglet survival rates, B cells may be a selective strategy to ensure immune defense to neonatal piglets. According to our findings, colostrum can be stored by freezing at -20 °C for up to 30 days and surplus porcine colostrum can be collected from the sow up to eight hours after the start of farrowing.


A wave function correction-based approach to the identification of resonances for vibrational perturbation theory.
An approach for identifying resonances in vibrational perturbation theory calculations is introduced. This approach makes use of the corrections to the wave functions that are obtained from non-degenerate perturbation theory calculations to identify spaces of states that must be treated with degenerate perturbation theory. Pairs of states are considered to be in resonance if the magnitude of expansion coefficients in the corrections to the wave functions in the non-degenerate perturbation theory calculation is greater than a specified threshold, χmax. This approach is applied to calculations of the vibrational spectra of CH4, H2CO, HNO3, and cc-HOONO. The question of how the identified resonances depend on the value of χmax and how the choice of the resonance spaces affects the calculated vibrational spectrum is further explored for H2CO. The approach is also compared to the Martin test [J. M. L. Martin et al., J. Chem. Phys. 103, 2589-2602 (1995)] for calculations of the vibrational spectra of H2CO and cc-HOONO.


Dichromacy characterized by chrominance planes.
Dichromacy is described in terms of dichromatic opponent colour spaces. By means of the perceptual criteria 'equally bright', 'neither blue nor yellow' and 'neither red nor green' and embedding in a three-dimensional colour space, it is possible for each type of dichromat to quantify a null-chrominance plane and a null-luminance plane, both of which intersect in the missing colour. These two null planes (or the trace of their intersection with the chromaticity chart) are the chromaticities of the dichromatic opponent primaries. Since a null-luminance plane contains only colour ('chrominance'), it is simply a chrominance plane. Under the assumption that the retinal short-wavelength cones do not contribute to luminance, the chrominance planes of the three types of dichromats intersect in a common straight line, the 'blue' fundamental primary vector. This constellation may serve as a general characterisation of dichromacy.


Predicting medical graduates' clinical performance using national competency examination results in Indonesia.
Indonesia has applied a national competency exit-examination for medical graduates since 2014, called The Indonesia Medical Doctor National Competency Examination (IMDNCE). This examination is administered to ensure the competence of medical graduates from at present 83 medical schools in Indonesia. Although many studies reported their evaluation on medical licensing examinations, there are not many studies performed to evaluate the correlation of a national licensing examination to the graduates' clinical practice. This research aimed to evaluate the performance of new medical doctors in Indonesia in their internship period after the IMDNCE completion, and whether it might become a predictive indicator for the new medical doctors' clinical performance. An observational cross-sectional study was performed in November-December 2017 on 209 doctors who were new medical graduates. Thirty-one senior doctors from a range of regions in Indonesia who were recruited and trained previously participated in the observation. The Clinical Performance Instrument (CPI) tool was developed as an evaluation tool of the new doctors' clinical competence to be observed for three weeks. The obtained data were analysed using descriptive statistics and correlated to the IMDNCE scores. The mean (95% CI) of the CPI for all participants was 83.0 (80.8-85.2), with no correlation of CPI score with IMDNCE results in domains of communication, professionalism and patient safety (p > 0.05). However, the mean total of the CPI observation scores from doctors who graduated from public medical schools was higher than those graduating from private medical schools. Also, there were differences in scores related to the institution's accreditation grade (p < 0.05). There is no difference between CPI and national competency examination results. There was no statistical correlation between the clinical performance of new medical doctors during their internship to CBT and OSCE scores in the national competency examination. New doctors' performance during internship is affected by more complex factors, not only their level of competencies.


Current status of thrombolytic therapy.
The optimal role of thrombolytic therapy in clinical practice has not been defined precisely. A review of available information indicates that such therapy may be useful in a small number of carefully selected patients with deep vein thrombosis and/or pulmonary emboli. The superiority of thrombolytic therapy over conventional surgery for arterial thrombi has not been convincingly demonstrated. Available evidence suggests such therapy should be reserved for those conditions in which surgery may be expected to have a poor outcome or be associated with a high incidence of complications. Preliminary information suggests thrombolytic therapy may be of benefit in selected patients with acute myocardial infarction.


An analysis and validation pipeline for large-scale RNAi-based screens.
Large-scale RNAi-based screens are a major technology, but require adequate prioritization and validation of candidate genes from the primary screen. In this work, we performed a large-scale pooled shRNA screen in mouse embryonic stem cells (ESCs) to discover genes associated with oxidative stress resistance and found several candidates. We then developed a bioinformatics pipeline to prioritize these candidates incorporating effect sizes, functional enrichment analysis, interaction networks and gene expression information. To validate candidates, we mixed normal cells with cells expressing the shRNA coupled to a fluorescent protein, which allows control cells to be used as an internal standard, and thus we could detect shRNAs with subtle effects. Although we did not identify genes associated with oxidative stress resistance, as a proof-of-concept of our pipeline we demonstrate a detrimental role of Edd1 silencing in ESC growth. Our methods may be useful for candidate gene prioritization of large-scale RNAi-based screens.


IL-6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy.
Major hepatic resection in cirrhotic patients is associated with impaired liver regeneration and failure, leading to high peri-operative mortality. In this work, the causes of defective regeneration in cirrhotic liver and the utility of IL-6 treatment were investigated in an experimental model combining cirrhosis and partial hepatectomy in the rat. Relative to normal controls, decompensated cirrhotic animals showed decreased survival, while compensated cirrhotic animals showed similar survival but reduced hepatic DNA synthesis and newly regenerated liver mass amount. Defective liver regeneration was associated with a decrease in STAT3 and NF-kB activation, consistent with an increased accumulation of their respective inhibitors PIAS3 and IkBalpha, and with a decreased induction of Bcl-xL. Treatment with recombinant IL-6 enhanced survival of decompensated cirrhotic animals, while it did not affect survival of compensated cirrhotic animals but sustained liver regeneration, by restoring STAT3 and NF-kB activation and Bcl-xL induction to the levels found in normal controls. The pro-growth effects exerted by IL-6 treatment in cirrhotic liver were attained also at low, pharmacologically acceptable doses. In conclusion, our results suggest that IL-6 treatment may be therapeutic in major resection of cirrhotic liver.


Comparative effects of velnacrine, tacrine and physostigmine on the twitch responses in the rat phrenic-hemidiaphragm preparation.
1. Cholinesterase inhibitors potentiated twitch responses induced by nerve stimulation, with physostigmine more potent than tacrine and velnacrine. However, at higher concentrations, tacrine decreased twitch responses in a concentration-dependent manner. 2. Tacrine strongly depressed directly-induced twitch responses, whereas the other drugs had minimal effects. 3. Physostigmine was the most potent drug in reversal of tubocurarine-induced blockade, but its antagonism index was similar to those obtained with tacrine and velnacrine at higher concentrations. When evaluating their ability to reverse neomycin-induced blockade, all drugs exhibited a similar effect. 4. It is concluded that tacrine and velnacrine are less potent than physostigmine in potentiating skeletal neuromuscular transmission. Additionally, the blocking effects of tacrine could limit its therapeutic efficacy.


Portoazygous disconnection for bleeding esophageal varices.
Between 1971 and 1982, 20 portoazygous disconnections (modified Tanner's operation) were performed in patients with bleeding esophagogastric varices who were anatomically portosystemic shunting. Immediate control of variceal hemorrhage was achieved in all patients, although rebleeding occurred after eight operations at intervals from 2 days to 7.5 years postoperatively, requiring additional surgery at a mean interval of 2.5 years. There were eight perioperative deaths. Analysis has suggested increased mortality in patients with more severely impaired liver function according to Child's classification, and in patients who require urgent or emergent operations. There was an 80 percent incidence of major and minor complications. Portoazygous disconnection is not a satisfactory alternative to portosystemic shunting, except in a selected group of patients with intact hepatic function and with anatomic characteristics that preclude usual shunting procedures.


Winchester syndrome: report of a case from Iran.
A child with Winchester syndrome, studied in Iran, is the sixth reported case in the literature. The cutaneous manifestations of this syndrome include leathery thickening of the skin, hyperpigmentation and hypertrichosis. The lips and gingiva are hypertrophic. There are also arthritic changes involving the small joints.