Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats.
Studies on the effects of (-)-hydroxycitric acid (HCA) in humans are controversial. As differences in the HCA preparations may contribute to this apparent discrepancy, the aim of the current study is to compare different HCA-containing preparations in adult Wistar rats. The effects of 3 different HCA-containing preparations (Regulator, Citrin K, Super CitriMax HCA-600-SXS, all used at an effective HCA dose of 150 and 300 mg/kg, administered intragastrically) on food intake and body weight were studied in adult male Wistar rats. The efficacy was tested under 2 different experimental conditions: 1) after a single dose administration and 2) during repeated administration for 4 subsequent days. Regulator and Citrin K significantly reduced food intake in both experimental setups, while Super CitriMax HCA-600-SXS was less effective. When administered for 4 subsequent days Regulator and Citrin K diminished body weight gain. Regulator and Citrin K were shown to be potent inhibitors of food intake in rats, whereas Super CitriMax HCA-600-SXS showed only small and more inconsistent effects. The striking differences in efficacy between these 3 preparations indicate that low doses of a relatively low-effective HCA preparation may have contributed to the lack of efficacy as found in several human studies.


Enhanced phytoextraction of an agricultural Cr- and Pb-contaminated soil by bioaugmentation with siderophore-producing bacteria.
Bioaugmentation-assisted phytoextraction may enhance the phytoextraction efficiency thanks to larger metal mobilization by microbial metabolites. Green fluorescent protein-tagged cells of Pseudomonas aeruginosa, Pseudomonas fluorescens or Ralstonia metallidurans, able to produce siderophores, were inoculated in an agricultural soil containing Cr (488 mg kg(-1)) and Pb (382 mg kg(-1)) and maize was cultivated. Bacteria were inoculated as free or immobilized cells in Ca-alginate beads, with skim milk in the aim at improving both the bacterial survival and the in situ siderophore production. Skim milk addition increased inoculated Pseudomonads concentration in soil. Soil inoculation with free cells of R. metallidurans supplied with skim milk increased Cr accumulation in maize shoots by a factor of 5.2 and inoculation with immobilized P. aeruginosa cells supplied with skim milk increased Cr and Pb uptake by maize shoots by a factor of 5.4 and 3.8, respectively. However total metal taken up by the whole plant decreases almost always with bioaugmentation. Translocation factor also increased with P. aeruginosa or R. metallidurans by a factor of 6 up to 7. Inoculated bacteria concentration in soil was correlated with metals in the exchangeable fraction. Cr and Pb concentrations in the exchangeable fraction were correlated with metal contents in shoots or roots. Our results suggest that bioaugmentation-assisted phytoextraction is a relevant method in the aim at increasing the phytoextraction rate which usually limits the use of phytoremediation technologies.


Augmented osteosynthesis of OTA 44-B fractures in older patients: a technique allowing early weightbearing.
To determine the effectiveness of an augmented technique of osteosynthesis in allowing early weightbearing in older patients with OTA 44-B (Danis-Weber B) fractures. Case series. University Level I trauma center. Thirty-six patients, nonconsecutive, with OTA 44-B fractures. Augmented internal fixation using an intramedullary wire, lateral plate, and screw augmentation with polymethylmethacrylate. Healed fracture with no loss of reduction. American Orthopaedic Foot and Ankle Society score; percentage of patients who returned to prefracture function. All patients began weightbearing as tolerated in a removable brace at a mean of 13.5 days postoperatively. Thirty patients were available for follow-up at a minimum of 12 months (range, 12-14 months). All fractures healed with no loss of reduction. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 84.9 (range, 74-100), and 90% of patients returned to prefracture function. There were two infections, one in a 74-year-old diabetic woman and the other in a 92-year-old woman with pre-existing arterial insufficiency and a small ulcer over the tip of the second toe. Augmented internal fixation consisting of intramedullary wire, lateral plate, and screw augmentation with polymethylmethacrylate may allow for very early weightbearing without risk of secondary loss of reduction or disruption of the ankle mortise in older patients with OTA 44-B (Danis-Weber B) malleolar fractures.


Efficacy of weekly amrubicin for refractory or relapsed non-small cell lung cancer: A protocol of systematic review and meta-analysis.
The aim of this study is to examine the efficacy of weekly amrubicin (WA) for treating refractory or relapsed non-small cell lung cancer (RRNSCLC). The literature search will be performed using the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, Chinese Biomedical Literature Database, WANGFANG, VIP database, and China National Knowledge Infrastructure from inception onwards up to the March 1, 2020. No language limitation will be implemented. Randomized controlled trials that examined the efficacy and safety of WA for the treatment of RRNSCLC will be included. Literature selection, data extraction, and methodological quality assessment will be handled by 2 independent authors. We will invite a third author to disentangle any divergences between 2 authors. We will carry out statistical analysis using RevMan 5.3 software. This study will summarize current evidence to assess the efficacy and safety of WA for the treatment of RRNSCLC. The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as clarify the direction of research on WA for the management of RRNSCLC.Study registration number: INPLASY202040168.


A large collection of compact box C/D snoRNAs and their isoforms in Euglena gracilis: structural, functional and evolutionary insights.
In the domains Eucarya and Archaea, box C/D RNAs guide methylation at the 2'-position of selected ribose residues in ribosomal RNA (rRNA). Those eukaryotic box C/D RNAs that have been identified to date are larger and more variable in size than their archaeal counterparts. Here, we report the first extensive identification and characterization of box C/D small nucleolar (sno) RNAs from the protist Euglena gracilis. Among several unexpected findings, this organism contains a large assortment of methylation-guide RNAs that are smaller and more uniformly sized than those of other eukaryotes, and that consist of surprisingly few double-guide RNAs targeting sites of rRNA modification. Our comprehensive examination of the modification status of E.gracilis rRNA indicates that many of these box C/D snoRNAs target clustered methylation sites requiring extensive, overlapping guide RNA/rRNA pairings. An examination of the structure of the RNAs, in particular the location of the functional guide elements, suggests that the distances between adjacent box elements are an important factor in determining which of the potential guide elements is used to target a site of O(2')-methylation.


Head-to-head efficacy and safety of rivaroxaban, apixaban, and dabigatran in an observational nationwide targeted trial.
The advantages of direct oral anticoagulants (DOACs) over warfarin are well established in atrial fibrillation (AF) patients, however, studies that can guide the selection between different DOACs are limited. The aim was to compare the clinical outcomes of treatment with apixaban, rivaroxaban, and dabigatran in patients with AF. We conducted a retrospective, nationwide, propensity score-matched-based observational study from Clalit Health Services. Data from 141 992 individuals with AF was used to emulate a target trial for head-to-head comparison of DOACs therapy. Three-matched cohorts of patients assigned to DOACs, from January-2014 through January-2020, were created. One-to-one propensity score matching was performed. Efficacy/safety outcomes were compared using KaplanMeier survival estimates and Cox proportional hazards models. The trial included 56 553 patients (apixaban, n = 35 101; rivaroxaban, n = 15 682; dabigatran, n = 5 770). Mortality and ischaemic stroke rates in patients treated with rivaroxaban were lower compared with apixaban (HR,0.88; 95% CI,0.78-0.99; P,0.037 and HR 0.92; 95% CI,0.86-0.99; P,0.024, respectively). No significant differences in the rates of myocardial infarction, systemic embolism, and overall bleeding were noticed between the different DOACs groups. Patients treated with rivaroxaban demonstrated lower rate of intracranial haemorrhage compared with apixaban (HR,0.86; 95% CI,0.74-1.0; P,0.044). The rate of gastrointestinal bleeding in patients treated with rivaroxaban was higher compared with apixaban (HR, 1.22; 95% CI,1.01-1.44; P, 0.016). We demonstrated significant differences in outcomes between the three studied DOACs. The results emphasize the need for randomized controlled trials that will compare rivaroxaban, apixaban, and dabigatran in order to better guide the selection among them.


Rescue of infective virus from a genome-length cDNA clone of the FMDV serotype O (IND-R2/75) vaccine strain and its characterization.
We report here the construction and characterization of an infectious cDNA clone of the Indian vaccine strain of foot and mouth disease virus (FMDV) serotype O, IND-R2/75. Viral genome was amplified by reverse transcription-polymerase chain reaction (RT-PCR) in five fragments and subsequently assembled sequentially in a plasmid vector to generate a complete cDNA clone, flanked by the T7 RNA polymerase promoter and poly (A) tail at 5' and 3' ends, respectively. Transfection of BHK-21 cells with the RNA transcribed from this genome-length cDNA construct allowed the recovery of infectious recombinant FMDV particles as evidenced by cytopathic effect in BHK-21 cells. Characterization of the recombinant virus revealed its similarity to the parental strain. Recombinant virus could be distinguished from the parental virus based on the presence of a unique marker sequence in the former, which was incorporated in the cDNA using a silent mutation. The virus showed no significant amino acid changes in the capsid-coding region when serially passaged up to ten times in BHK-21 cells, while retaining the marker sequence.


ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of Brazilian acute myeloid leukemia patients.
Polymorphisms in the ABCB1 gene may influence P-glycoprotein (Pgp) expression and/or activity. Because the population in Brazil is markedly heterogeneous, we analyzed the relationship between ABCB1 polymorphisms and Pgp expression/activity in Brazilian acute myeloid leukemia (AML) patients. Acute myeloid leukemia samples from 109 patients were studied. ABCB1 gene variants rs1128503 (C1236T) and rs1045643 (C3435T) were analyzed by PCR-RFLP assay. Pgp expression and Pgp activity were analyzed by flow cytometry. There was a similar distribution of Pgp expression and activity on polymorphisms C1236T, C1236C, and T1236T for exon 12, and C3435T, C3435C, and T3435T for exon 26. An exception was observed in the lowest ratio of mean fluorescence intensity (MFI) median for Pgp expression in the TT genotype for both studied exons, and its correspondence to a low MFI median for Pgp activity. Pgp expression did not show impact on the response to remission induction therapy, but the MFI median of Pgp expression in the remission failure group was higher than that of the complete remission (CR) group of patients (p = 0.04). Overall survival (OS) was significantly influenced by CR (p = 0.0001). Better 5-year OS and 5-year event-free survival rates (p = 0.04 and p = 0.007, respectively) were achieved in patients presenting the genetic variant CC in exon 12 followed by those presenting the variant CT in exon 26 (p = 0.001). Polymorphisms in the ABCB1 gene and the levels of Pgp expression could be useful to identify prognostic in AML patients.


Occludin stalls HCV particle dynamics apart from hepatocyte tight junctions, promoting virion internalization.
Numerous HCV entry factors have been identified, and yet information regarding their spatiotemporal dynamics is still limited. Specifically, one of the main entry factors of HCV is occludin (OCLN), a protein clustered at tight junctions (TJs), away from the HCV landing site. Thus, whether HCV particles slide toward TJs or, conversely, OCLN is recruited away from TJs remain debated. Here, we generated CRISPR/CRISPR-associated protein 9 edited Huh7.5.1 cells expressing endogenous levels of enhanced green fluorescent protein/OCLN and showed that incoming HCV particles recruit OCLN outside TJs, independently of claudin 1 (CLDN1) expression, another important HCV entry factor located at TJs. Using ex vivo organotypic culture of hepatic slices obtained from human liver explants, a physiologically relevant model that preserves the overall tissue architecture, we confirmed that HCV associates with OCLN away from TJs. Furthermore, we showed, by live cell imaging, that increased OCLN recruitment beneath HCV particles correlated with lower HCV motility. To decipher the mechanism underlying virus slow-down upon OCLN recruitment, we performed CRISPR knockout (KO) of CLDN1, an HCV entry factor proposed to act upstream of OCLN. Although CLDN1 KO potently inhibits HCV infection, OCLN kept accumulating underneath the particle, indicating that OCLN recruitment is CLDN1 independent. Moreover, inhibition of the phosphorylation of Ezrin, a protein involved in HCV entry that links receptors to the actin cytoskeleton, increased OCLN accumulation and correlated with more efficient HCV internalization. Together, our data provide robust evidence that HCV particles interact with OCLN away from TJs and shed mechanistic insights regarding the manipulation of transmembrane receptor localization by extracellular virus particles.


Automated analysis of prerecorded evoked electromyographic activity from rat muscle.
An automated microprocessor-based data acquisition and analysis system has been developed specifically to quantify electromyographic (EMG) activity induced by the convulsant agent catechol in the anaesthetized rat. The stimulus and EMG response are recorded on magnetic tape. On playback, the stimulus triggers a digital oscilloscope and, via interface circuitry, a BBC B microcomputer. The myoelectric activity is digitized by the oscilloscope before being transferred under computer control via a RS232 link to the microcomputer. This system overcomes the problems of dealing with signals of variable latency and allows quantification of latency, amplitude, area and frequency of occurrence of specific components within the signal. The captured data can be used to generate either signal or superimposed high resolution graphic reproductions of the original waveforms. Although this system has been designed for a specific application, it could easily be modified to allow analysis of any complex waveform.


Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors.
Immune checkpoint inhibitors that block programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved outcomes for many cancer subtypes but do exhibit toxicity, in the form of immune-related adverse events. The aim of this study was to investigate the emerging toxicities of PD-1 and PD-L1 inhibitors including acute or reactivation of tuberculosis (TB) and atypical mycobacterial infection (AMI). This study was completed as a retrospective review using the US Food and Drug Administration Adverse Events Reporting System (FAERS) for incidence of TB and AMI due to PD-1 and PD-L1 inhibitors compared with other FDA (Food and Drug Administration) approved drugs. The statistical methods included disproportionality signal analysis using the reporting OR (ROR) to compare cases. The 95% Wald CI was reported to assess the precision of the ROR. Out of the 10 146 481 adverse events (AEs) reported to FAERS for all drugs between 1 January 2015 and 31 March 2020, 73 886 AEs were due to the five FDA approved PD-1/PD-L1 inhibitors. Seventy-two cases of TB were due to PD-1/PD-L1 inhibitors. Specifically, 45 cases (62.5%) due to nivolumab, 18 (25%) due to pembrolizumab, 5 (7%) due to atezolizumab and 4 (5.5%) due to durvalumab. There were 13 cases of AMI: 9 (69.3%) due to nivolumab, 2 (15.3%) due to pembrolizumab and 1 (7.7%) each due to durvalumab and atezolizumab. Avelumab was not attributed to any AE of TB or AMI. From analysis of the FAERS database, the calculated ROR for TB due to PD-1/PD-L1 inhibitors was 1.79 (95% CI, 1.42 to 2.26) (p<0.0001) and for AMI was 5.49 (95% CI, 3.15 to 9.55) (p<0.0001). PD-1/PD-L1 inhibitors used in the treatment of cancer subtypes is associated with increased TB and AMI risk. Although this complication is rare, clinicians using PD-1/PD-L1 inhibitors should be aware of the risks.


Preferential loss or inactivation of chromosome Z4 APRT allele in CHO cells.
In CHO cells, heterozygotes for the adenine phosphoribosyltransferase (APRT) locus arise spontaneously at high frequencies. However, such heterozygotes always yield APRT- mutants at low spontaneous rates. In an attempt to determine whether differences in the genomic environments of the two CHO APRT alleles might render one gene more susceptible to high-frequency spontaneous inactivation or deletion, we have mapped the functional APRT allele in four different spontaneous APRT heterozygotes. In each case, the functional APRT gene was found to reside on the Z7 chromosome; it was always the Z4 APRT allele that had been lost or inactivated. Two of these heterozygotes were shown to be physically hemizygous while the other two retained two copies of the APRT gene, indicating that the high-frequency event can involve either spontaneous deletion or inactivation.


Balancing one's mood: experiences of physical activity in adults with severe obesity 18 months after lifestyle intervention.
Patients with severe obesity may have special challenges in regard to increasing health and well-being through physical activity (PA). The biggest challenge is maintaining the recommended PA level on a long-term basis. Yet, little focus has been put on the experiences of individuals with severe obesity during PA when physically active in everyday life after intervention has ended. to explore the experiences of being physically active among individuals with severe obesity in everyday life 18 months after the start of a lifestyle intervention. a qualitative longitudinal study of individual follow-up interviews founded in hermeneutic phenomenology and an existential lifeworld theory of suffering and well-being. The study was approved by the Danish Data Protection Agency (J. no. 1-16-02-425-15). Interviews were conducted by the same interviewer in the participants' home environment across three of five regions in Denmark. Ten adults with severe obesity (BMI>40kg/m2) previously recruited from a public lifestyle intervention program. The analysis revealed that females and males emphasised different experiences of being active in everyday life. The females experienced 'Appreciation of process and vitality' and the males experienced 'The challenge of an active and joyful living'. One common main theme emerged: 'Fluctuating mood' was found to influence physical activity level. The study highlights the experiences of well-being in relation to staying physically active after lifestyle intervention. The fluctuations in mood were part of everyday life and it was an on-going challenge to balance mood in order to keep up the efforts. The ability to find settlement and modify PA expectations was part of feeling capable. Healthcare providers are suggested to address well-being in mood to help patients become and stay physically active in everyday life.


Perceptions of excessive alcohol consumption in stressful and nonstressful situations among undergraduates.
We devised and administered the Alcohol Perceptions Questionnaire (APQ) to 56 male and 51 female undergraduates in a small midwestern university. Findings yielded statistically significant results between the level of alcohol consumption reported by the subjects and their perceptions of excessive drinking in interpersonal situations, social group situations, and under conditions of subjective stress. The greater the amount of personal alcohol consumption among the sample, the less likely they viewed excessive drinking as a problem. In addition, subjects from lower income environments viewed excessive drinking in general as a problem, whereas subjects from higher income environments viewed excessive drinking as no problem at all.


Oral Immunotherapy for Food Allergy.
Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut.


What is the evidence for endoscopic thyroidectomy in the management of benign thyroid disease?
Endoscopic thyroidectomy (ET) is a demanding surgical technique in which dissection of the gland is entirely performed with an endoscope, in a closed area maintained by insufflation or mechanical retraction. ET by direct cervical approach (anterior or lateral) is minimally invasive, but ET using an extracervical access (chest wall, breast, or axillary) is not. No technique seems to be universally accepted yet. This review was designed to clarify the existing evidence for performing endoscopic thyroid resections in the management of benign thyroid nodules. A database search was conducted in PubMed and Embase from which summaries and abstracts were screened for relevant data, matching our definition. Publications were further assessed and assigned their respective levels of evidence. Additional data derived from our own unit's experience with endoscopic thyroidectomy were included. Thirty mainly retrospective cohort studies have been published in which morbidity, such as unilateral vocal cord palsy, is poorly evaluated. ET takes from 90 to 280 minutes for lobectomy by cervical access and total thyroidectomy by chest wall approach, respectively. Cosmetic outcome in extracervical approach is less troubled by size of the resected specimen compared with direct cervical approach. Extracervical approach avoids a neck scar but implies invasiveness in terms of dissection and postoperative discomfort. Long-term cosmetic outcome comparisons with conventional thyroidectomy have not been published. Currently it is not possible to recommend the application of ET based on evidence. Reported complications stress the importance of advanced endoscopic skills. ET should only be offered to carefully selected patients and, therefore, a high volume of patients requiring thyroid surgery is needed. Superiority of endoscopic to conventional thyroidectomy has yet to be demonstrated. Possible advantages of endoscopic thyroid techniques and our patient's desire for the highest cosmetic outcome possible justify further development of ET in expert hands of endocrine surgeons.


Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward "precision" cancer therapy.
We present an updated account of breast cancer treatment and of progress toward "precision" cancer therapy; we focus on new developments in diagnostic molecular pathology and breast cancer that have emerged during the past 2 years. Increasing awareness of new prognostic and predictive methodologies, and introduction of next generation sequencing has increased understanding of both tumor biology and clinical behavior, which offers the possibility of more appropriate therapeutic choices. It remains unclear which of these testing methodologies provides the most informative and cost-effective actionable results for predictive and prognostic pathology. It is likely, however, that an integrated "step-wise" approach that uses the traditional clinical-pathologic paradigms coordinated with molecular characterization of breast tumor tissue, will offer the most comprehensive and cost-effective options for individualized, "precision" therapy for patients with breast cancer.


Striatal neurons encoded temporal information in duration discrimination task.
To clarify the roles of the basal ganglia in time perception, single-unit activity was recorded from both sides of the striatum of a monkey performing a duration discrimination task. In the task, two visual cues were presented successively in different durations (0.2 approximately 1.6 s). Each cue presentation was followed by a 1-s delay period. The subject was instructed to choose a longer presented cue after the second delay period. There were two types of trials for sequence of cue duration, the long-short (LS) trials in which the first cue (C1) was longer than the second cue (C2) and the short-long (SL) trials in which the C1 was shorter than the C2. Striatal neurons phasically responded during the first delay (D1) and second delay (D2) periods. Responses during the D1 period changed depending on C1 duration. Activity of populations of D1-response neurons correlated with C1 duration positively or negatively. Responses during the D2 period differed between the LS and SL trials. Activity of population of D2-response neurons also changed depending on C2 duration. But the dependence on C2 duration was affected by the trial type, that is, whether the C2 was longer or shorter compared to the C1. These findings suggest that striatal neurons could encode cue durations with monotonically changing responses in the D1 period and discrimination results between the two cue durations in the D2 period.


Effect of antacid on bioavailability of a sustained-release theophylline preparation.
The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or "high potency" aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments. A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 +/- 3.03 vs. 8.30 +/- 2.90 micrograms/ml, p less than 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 +/- 1.67 h-combination vs. 10.8 +/- 1.1 h-theophylline, p greater than 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 +/- 41.6 micrograms/ml.h--combination vs. 155.13 +/- 46.6 micrograms/h--theophylline, p greater than 0.05). The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.


Schwannoma of the sellar region.
A 25-year-old woman who had experienced brief periods of loss of consciousness and grand mal seizures was found to have a midline mass in the sellar region as evidenced by computer tomography and angiography. Preoperatively, it was thought to be a meningioma but histologically and ultrastructurally it turned out to be a Schwannoma. Since cranial nerves were not involved, clinically or morphologically, this nerve sheath tumour could have originated from Schwann cells of sensory, possibly trigeminal, nerves, vasomotor nerves, or ectopic Schwann cells.


Porcine IFITM1 is a host restriction factor that inhibits pseudorabies virus infection.
Interferon-inducible transmembrane proteins (IFITMs) restrict infection by several viruses, such as influenza A virus, West Nile virus and dengue virus. It has not been determined whether porcine IFITMs (pIFITMs) inhibit infection by pseudorabies virus (PRV), an enveloped, double-stranded DNA virus, which is the etiological agent of Aujeszky's disease in pigs. Here, we report that PRV infection elicited pIFITM1 expression in PK15 porcine kidney epithelial cells and 3D4/21 alveolar macrophages. pIFITM2 and pIFITM3 expression was only elevated in PK15 cells during PRV infection. Depletion of pIFITM1 using RNA interference, either in PK15 or in 3D4/21 cells, enhanced PRV infection while overexpression of pIFITM1 had the opposite effect. Knockdown of pIFITM2 and pIFITM3 did not influence PRV infection, suggesting that pIFITM2 and pIFITM3 are independent of PRV infection. PRV-induced pIFITM1 expression was dependent on the cGAS/STING/TBK1/IRF3 innate immune pathway and interferon-alpha receptor-1, suggesting that pIFITM1 is up-regulated by the type I interferon signaling pathway. The anti-PRV role of pIFITM1 was inhibited upon PRV entry. Our data demonstrate that pIFITM1 is a host restriction factor that inhibits PRV entry that may shed light on a strategy for prevention of PRV infection.


Generation of iPSC line ICGi024-A from human skin fibroblasts of a patient with ring chromosome 18.
Ring chromosome 18 is a rare chromosomal disorders that usually originate de novo and correlate with clinical manifestation: developmental delay as well as microcephaly, brain and ocular malformations, hypotonia and skeletal abnormalities. We generate iPSC clonal cell line ICGi024-A with pluripotency properties which were demonstrated in vitro by three germ layer differentiation capacity. ICGi024-A can be used for disease modeling and fundamental investigation of ring chromosome instability.


Assessment of chicken intestinal hydrolysates as a new protein source to replace fishmeal on the growth performance, antioxidant capacity and intestinal health of common carp (Cyprinus carpio).
Promoting circular economy by transforming food residues into alternative high-value protein sources for aquaculture feed is a new way to develop alternative raw materials for fishmeal. This study systematically evaluated the effects of chicken intestinal hydrolysates (CIH) on the intestinal immune health of common carp through growth performance, antioxidant capacity, and intestinal immunity analysis in order to replace fishmeal. Five iso-nitrogenous and iso-lipidic experimental feeds were formulated to replace 0% (CIH-0), 25% (CIH-25), 50% (CIH-50), 75% (CIH-75) and 100% (CIH-100) of the fishmeal with CIH. Each experimental diet was fed to triplicate groups of 30 carp for 8 weeks. The results revealed that no significant differences in the final body weight, weight gain rate, feed coefficient radio, feed intake and protein efficiency ratio were found among the CIH-0, CIH-25, and CIH-50 groups, while the final body weight and weight gain rate in the CIH-75 and CIH-100 groups were significantly decreased and the feed coefficient radio was significantly increased. The aspartate aminotransferase of all CIH groups were significantly decrease, and the total protein, albumin did not differ among the CIH-0, CIH-25, CIH-50, and CIH-75 groups. The trypsin content was significantly increased in the CIH-75 and CIH-100 groups. No significant differences in the antioxidant index (catalase, glutathione peroxidase and malonaldehyde) were found among all CIH groups compared with the CIH-0 group. The expression levels of pro-inflammatory cytokines IL-1β and TNF-α were significantly down-regulated in the CIH-50 group and anti-inflammatory cytokines IL-10 and TGF-β2 were significantly up-regulated in the CIH-50 and CIH-75 groups. No significant differences in the expression levels of claudin-1, claudin-7 and claudin-11 were observed between the CIH-0 and CIH-50 groups, while the expression levels of ZO-1, occludin and MLCK were significantly up-regulated in the CIH-50 group compared with the CIH-0 group. The expression level of claudin-1 was down-regulated in the CIH-75 and CIH-100 groups. Hence, the study demonstrated the potential of CIH as a novel protein source for replacing fishmeal, and replacing 50% of fishmeal with CIH did not significantly influence the growth performance, immune responses, and intestinal barrier of common carp (Cyprinus carpio).


Impact of Nab-Paclitaxel-based Second-line Chemotherapy in Metastatic Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with median survival of 20% at 1 year. We conducted a retrospective study to assess the efficacy and tolerability of nab-paclitaxel (NP)-based second-line chemotherapy in metastatic PDAC. The Indiana University Simon Cancer Center pancreatic cancer program was used to identify patients with metastatic PDAC who received any second-line chemotherapy. Demographic, clinical and outcomes data were collected by manual chart abstraction. Patients were divided into two groups: a NP-based treatment group and a non- NP-based treatment group. Overall (OS) and progression-free (PFS) survival were estimated using Kaplan-Meier method. Cox proportional hazards regression was used for multivariate analyses. A total of 120 patients received second-line chemotherapy. There were 47 (39%) patients in the NP group and 73 (61%) in the non-NP group. As compared to the non-NP group, the NP group showed improved median PFS [2.8 vs. 2.1 months; hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.38-1.02; p=0.06] and median OS (7.5 vs. 4.7 months; HR=0.67, 95% CI=0.45-1.00; p=0.05). Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR=0.60, 95% CI=0.36-0.98; p=0.04) and a suggestion of improved OS (adjusted HR=0.67, 95% CI=0.44-1.01, p=0.05) in the NP group as compared to non-NP group. Serious adverse events were seen in 13.3% of patients in the non-NP group and 17.1% patients in the NP group. In a single-institution retrospective cohort study, we report a significant improvement in the PFS and suggestion of improvement in the OS with NP-based second-line chemotherapy with an acceptable toxicity rate.


Online education and improvement of caring behaviors of nurses in pediatric wards: a quasi-experimental study.
Nurses working in pediatric wards should communicate with children well and have appropriate caring behaviors according to the age of their patients, so distance education is very suitable for them due to its availability. This study aimed to determine the effect of online education on the principles of pediatric nursing care on the caring behaviors of nurses working in pediatric wards. This interventional (quasi-experimental) study used a simple random method to select 70 nurses working in pediatric wards and pediatric intensive care units in Kerman. The nurses in the intervention group received online training in the sky room three days a week, while nurses in the control group received routine pediatric care. The study instruments were the demographic information questionnaire and the Caring behaviors Questionnaire, which were completed by two groups before and one month after the intervention. Data were analyzed with SPSS 25. The significance level was set at P < 0.05. The independent samples t-test indicated no significant differences in the mean scores of care behaviors between the intervention (256.61 ± 5.16) and control groups (257.52 ± 3.99) before the intervention (P = 0.23) but indicated a significant difference in the mean scores of caring behaviors between the intervention (275.69 ± 6.52) and control groups (254.21 ± 3.15) after the intervention. Therefore, online education increased the score of caring behaviors in the intervention group. Distance education had an impact on the caring behaviors of nurses in pediatric wards and we recommend the use of e-learning to improve the caring behaviors and the quality of care of nurses.


A comparison of the in vitro permeation of 3-O-ethyl-l-ascorbic acid in human skin and in a living skin equivalent (LabSkin™).
The safety assessment of personal care products often entails determining dermal absorption of their ingredients. Such experiments are typically performed in human or animal skin in vitro; however, ethical and safety considerations are associated with obtaining these tissues. Several human skin equivalent models (HSEs) have been developed as alternatives to human tissue. The barrier function of such models however, is normally less developed than human skin. Here, we examine the permeability of the HSE LabSkinTM to a model compound, 3-O-ethyl-l-ascorbic acid (EA) compared with human skin. Skin uptake and permeation of EA was investigated in vitro using heat-separated human epidermis and LabSkinTM . Finite dose (5 μL cm-2 ) Franz-diffusion studies were conducted using 2 % (w/w) EA in a ternary solvent mixture comprising propylene glycol (PG), propylene glycol monolaurate (PGML), and isopropyl myristate (IPM). These excipients are commonly used in cosmetic products and they have been reported to promote permeation of EA in a different model, namely porcine skin. Permeation of EA through LabSkinTM was evident from 2 h; however, EA permeation in human skin was not detected until 5 h. Similar amounts of EA permeated through the two membranes at time points 8, 10, 12 and 24 h (p > 0.05). The cumulative amounts of EA delivered through LabSkinTM at 24 h were 41.3 ± 2.0 µg cm-2 , corresponding to 55.1 ± 1.8 % of the applied dose. Similar amounts permeated across human skin, 49.4 ± 4.1 µg cm-2 , accounting for 58.0 ± 4.2 % of the dose applied (p > 0.05). The permeation of EA in LabSkinTM compared well with results for human epidermis in terms of the permeation profiles and the cumulative amounts of EA that permeated. The data suggest that the skin barrier of the two models was similar with regard to their overall permeability to the hydrophilic active EA. The findings are promising for the use of LabSkinTM as a surrogate for human skin in permeability testing. Future studies will focus on exploring the reproducibility and robustness of LabSkinTM for delivery of other actives that span a range of physicochemical properties.


Towards estimating the carbon footprint of external beam radiotherapy.
The National Health Service (NHS) in the United Kingdom (UK) is aiming to be carbon net zero by 2040 to help limit the dangerous effects of climate change. Radiotherapy contributes to this with potential sources quantified here. Activity data for 42 patients from within the breast IMRT and prostate VMAT pathways were collected. Data for 20 prostate patients was also collected from 3 other centres to enable cross centre comparison. A process-based, bottom-up approach was used to calculate the carbon footprint. Additionally, patients were split into pre-COVID and COVID groups to assess the impact of protocol changes due to the pandemic. The calculated carbon footprint for prostate and breast pre-COVID were 148 kgCO2e and 101 kgCO2e respectively, and 226 kgCO2e and 75 kgCO2e respectively during COVID. The energy usage by the linac during treatment for a total course of radiotherapy for prostate treatments was 2-3 kWh and about 1 kWh for breast treatments. Patient travel made up the largest proportion (70-80%) of the calculated carbon footprint, with linac idle power second with ∼ 10% and PPE and SF6 leakage were both between 2 and 4%. These initial findings highlight that the biggest contributor to the external beam radiotherapy carbon footprint was patient travel, which may motivate increased used of hypofractionation. Many assumptions and boundaries have been set on the data gathered, which limit the wider application of these results. However, they provide a useful foundation for future more comprehensive life cycle assessments.


Subsequent surgery after primary ACLR results in a significantly inferior subjective outcome at a 2-year follow-up.
To analyze minimal important change (MIC), patient-acceptable symptom state (PASS) and treatment failure after reoperation within 2 years of primary ACL reconstruction and compare them with patients without additional surgery. This is a retrospective follow-up study of a cohort from a single-clinic database with all primary ACLRs enrolled between 2005 and 2015. Additional surgery within 2 years of the primary ACLR on the ipsilateral knee was identified using procedural codes and analysis of medical records. Patients who completed the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire preoperatively and at the 2-year follow-up were included in the study. MIC, PASS and treatment failure thresholds were applied using the aggregate KOOS (KOOS4) and the five KOOS subscales. The cohort included 6030 primary ACLR and from this 1112 (18.4%) subsequent surgeries were performed on 1018 (16.9%) primary ACLRs. 24 months follow-up for KOOS was obtained on 523 patients (54%) in the reoperation group and 2084 (44%) in the no-reoperation group. MIC; the no-reoperation group had a significantly higher improvement on all KOOS subscales, Pain 70.3 vs 60.2% (p < 0.01), Symptoms 72.1 vs 57.4% (p < 0.01), ADL 56.3 vs 51.2% (p < 0.01), Sport/Rec 67.3 vs 54.4% (p < 0.01), QoL 73.9 vs 56.3% (p < 0.01). PASS; 62% in the non-reoperation group reported their KOOS4 scores to be satisfactory, while only 35% reported satisfactory results in the reoperated cohort (p < 0.05). Treatment failure; 2% in the non-reoperation group and 6% (p < 0.05) in the reoperation group considered their treatment to have failed. Patients who underwent subsequent surgeries within 2 years of primary ACLR reported significantly inferior outcomes in MIC, PASS and treatment failure compared to the non-reoperated counterpart at the 2-year follow-up. This study provides clinicians with important information and knowledge about the outcomes after an ACLR with subsequent additional surgery. III.


Antimicrobial susceptibility of pathogens isolated from adult patients with uncomplicated community-acquired urinary tract infections in the Russian Federation: two multicentre studies, UTIAP-1 and UTIAP-2.
In two Russian studies (UTIAP-1 and UTIAP-2) susceptibility to commonly used antimicrobial agents for urinary tract infections (UTI) was determined. 456 urinary isolates were obtained from 588 out-patients with uncomplicated UTI in eight Russian centers during 1998-2001. The most common pathogens were Escherichia coli (85.9%) and Klebsiella pneumoniae (6.0%). Over 90% of the E. coli isolates were susceptible to nitrofurantoin (95.7%), cefuroxime (96.4%) and ciprofloxacin (95.5%). Co-amoxiclav, nalidixic acid and pipemidic acid were less active -84.4%, 93.1% and 93.9% susceptibility stains correspondingly. In contrast, 37.1% of the E. coli isolates were resistant to ampicillin, 22.9% to trimethoprim, 21% to co-trimoxazole. Susceptibility patterns of uropathogens vary between geographical regions of Russia.


Post-traumatic seizures.
Acute traumatic brain injury causes a cascade of changes in brain metabolism, blood flow, and homeostasis that are challenges to survival. Seizures, whether focal or convulsive, may be a manifestation of the acute injury response and are liable to complicate management. This article discusses mechanisms and biochemical effects of brain injury, cellular mechanisms of epileptogenesis, genetic factors, prevention and prophylaxis, alteration of brain injury responses, and recommendations for management.


Chemical constituents of Ganoderma applanatum of British Columbia forests.
A new compound, ganoderma aldehyde (1),was isolated from the fruiting body of Ganoderma applanatum. Its structure was elucidated on the basis of one-dimensional and two-dimensional NMR as well as MS spectroscopic analysis.


Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer.
At present, the treatment of esophageal cancer (EC) is mainly surgical and drug treatment. However, due to drug resistance, these therapies can not effectively improve the prognosis of patients with the EC. Therefore, a multigene prognostic risk scoring system was constructed by bioinformatics analysis method to provide a theoretical basis for the prognosis and treatment decision of EC. The gene expression profiles and clinical data of esophageal cancer patients were gathered from the Cancer Genome Atlas TCGA database, and the differentially expressed genes (DEGs) were screened by R software. Genes with prognostic value were screened by Kaplan Meier analysis, followed by functional enrichment analysis. A cox regression model was used to construct the prognostic risk score model of DEGs. ROC curve and survival curve were utilized to evaluate the performance of the model. Univariate and multivariate Cox regression analysis was used to evaluate whether the model has an independent prognostic value. Network tool mirdip was used to find miRNAs that may regulate risk genes, and Cytoscape software was used to construct gene miRNA regulatory network. GSCA platform is used to analyze the relationship between gene expression and drug sensitivity. 41 DEGs related to prognosis were pre-liminarily screened by survival analysis. A prognostic risk scoring model composed of 8 DEGs (APOA2, COX6A2, CLCNKB, BHLHA15, HIST1H1E, FABP3, UBE2C and ERO1B) was built by Cox regression analysis. In this model, the prognosis of the high-risk score group was poor (P < 0.001). The ROC curve showed that (AUC = 0.862) the model had a good performance in predicting prognosis. In Cox regression analysis, the comprehensive risk score can be employed as an independent prognostic factor of the EC. HIST1H1E, UBE2C and ERO1B interacted with differentially expressed miRNAs. High expression of HIST1H1E was resistant to trametinib, selumetinib, RDEA119, docetaxel and 17-AAG, High expression of UBE2C was resistant to masitinib, and Low expression of ERO1B made the EC more sensitive to FK866. We constructed an EC risk score model composed of 8 DEGs and gene resistance analysis, which can provide reference for prognosis prediction, diagnosis and treatment of the EC patients.


The FRIENDS Emotional Health Programme: Initial Findings from a School-Based Project.
Emotional disorders in children are common and although effective interventions are available comparatively few receive specialist help. School nurses were trained to deliver an evidence-based emotional health cognitive behaviour therapy programme, FRIENDS, to 106 non-referred children aged 9-10 attending three schools. Levels of anxiety and self-esteem were stable in the 6-month period before FRIENDS. Three months after completing FRIENDS, anxiety had significantly decreased and self-esteem increased. Children with the most severe emotional problems benefited from the programme. The value of delivering standardised evidence based programmes in schools by school nurses is discussed and the need for further research highlighted.


Progressive deformation-induced degradation of knee articular cartilage and osteoarthritis.
Articular cartilage (AC) is a dense connective tissue in the diarthrodial joints. Osteoarthritis is a disease associated with progressive changes in the tissue structure which affects mechanical properties of the tissue. Experimental studies show that abnormal/excessive mechanical loading or changes in biochemical composition can alter the structure which leads to degradation and loss of stiffness. In this study, deformation-induced degradation of human knee articular cartilage is investigated by conducting excessive deformations and inspecting progressive changes in mechanical properties of the tissue. Evolution of the properties is formulated to predict the amount of damage and consequently to connect the loss of stiffness to the grade of osteoarthritis. It is shown that, for tensile strains up to almost 15%, the tissue may recover its initial properties without permanent damage but for higher deformations degradation is expected. The proposed model is not confined to tension as the evolution laws are expressed in a 3D framework. The model predicts higher thresholds for compression and shear (25-30%) which is in good correlation with experimental investigations. It is concluded that, modelling the alterations of mechanical properties can be an effective method for predicting degradation of the AC under excessive loading and its connection to the associated diseases.


[Kinetic analysis of the action of cetyltrimethylammonium bromide on the membranes of the capsular variant of Escherichia coli CA189 recorded by ethidium bromide fluorescence].
A mathematical model, describing the kinetics of ethidium bromide probe fluorescence in the suspension of E. coli CA 189 capsular antigen after introduction of cetyltrimethylammonium bromide (a detergent), has been developed. Experimental testing of this mathematical model has confirmed that it describes the kinetics of the probe fluorescence augmentation sufficiently accurately. The new model permits the quantitative characterization of the rate of surfactant diffusion through the bacterial capsule.


Anti-inflammatory potential of lactic acid bacteria from southern Brazil by reducing TNF-α and increasing IL-10 synthesis: an in vitro study.
To evaluate the adhesion capacity and anti-inflammatory activity of lactic acid bacteria (LAB) isolated from raw cow milk and artisan cheese in Southern Brazil, investigating their effect on the release of cytokines such as TNF-α and IL-10 and their influence on the activation of the p38/MAPK pathway. Lentilactobacillus parabuchneri ML4, Lacticaseibacillus paracasei ML33, Lactiplantibacillus pentosus ML82, Lactiplantibacillus plantarum CH131, and L. paracasei CH135 demonstrated high adhesion potential in an in vitro model of the intestinal epithelium, as well as anti-inflammatory activity. After a 4-hour treatment, the strains significantly increased TNF-α levels, while a 24-hour treatment led to a significant decrease in TNF-α release. Moreover, IL-10 levels significantly increased after 24-hour and 48-hour treatments with LAB. The inhibition of p38/MAPK phosphorylation was identified as one of the mechanisms by which the L. paracasei ML33 and L. plantarum CH131 strains suppressed the production and release of TNF-α. We identified LAB strains with potential anti-inflammatory properties that could adhere to the intestinal mucosa and alleviate the inflammatory response by reducing the production and release of TNF-α through the inhibition of the p38/MAPK pathway, while promoting the production of IL-10.


Reproducibility in PD-L1 Immunohistochemistry Quantification through the Tumor Proportion Score and the Combined Positive Score: Could Dual Immunostaining Help Pathologists?
We studied the pathologists' agreements in quantifying PD-L1 expression through the tumor proportion score (TPS) and the combined positive score (CPS) using single PD-L1 immunohistochemistry (S-IHC) and double immunohistochemistry (D-IHC) combining PD-L1 staining and tumor cell markers. S-IHC and D-IHC were applied to 15 cancer samples to generate 60 digital IHC slides (30 whole slides images and 30 regions of interest of 1 mm2) for PD-L1 expression quantification using both TPS and CPS, twice by four pathologists. Agreements were estimated calculating intraclass correlation coefficients (ICC). Both S-IHC and D-IHC slides analyses resulted in excellent (for TPS, ICC > 0.9) to good (for CPS, ICC > 0.75) inter- and intra-pathologist agreements with slightly higher ICC with D-IHC than with S-IHC. S-IHC resulted in higher TPS and CPS than D-IHC (+5.6 and +6.1 mean differences, respectively). High reproducibility in the quantification of PD-L1 expression is attainable using S-IHC and D-IHC.


Comparing free-space and fiber-coupled detectors for Fabry-Pérot-based all-optical photoacoustic tomography.
Highly sensitive detection is crucial for all-optical photoacoustic (PA) imaging. However, free-space optical detectors are prone to optical aberrations, which can degrade the pressure sensitivity and result in deteriorated image quality. While spatial mode-filtering has been proposed to alleviate these problems in Fabry-Pérot-based pressure sensors, their real functional advantage has never been properly investigated. We rigorously and quantitatively compare the performance of free-space and fiber-coupled detectors for Fabry-Pérot-based pressure sensors. We develop and characterize a quantitative correlative setup capable of simultaneous PA imaging using a free space and a fiber-coupled detector. We found that fiber-coupled detectors are superior in terms of both signal level and image quality in realistic all-optical PA tomography settings. Our study has important practical implications in the field of PA imaging, as for most applications and implementations fiber-coupled detectors are relatively easy to employ since they do not require modifications to the core of the system but only to the peripherally located detector.


Chromatin immunoprecipitation: a tool for studying histone acetylation and transcription factor binding.
The function of a protein in gene expression can often be explained, in part, by the location of that protein along a specific gene sequence. In recent years, the chromatin immunoprecipitation (ChIP) assay has been developed to study the association of proteins located within 2 A of DNA such as transcription factors and modified histones. Numerous important findings have been published using the ChIP assay and many questions about transcription have been answered. In this article, we present the ChIP assay currently used in our lab and discuss the various ways to optimize this assay for one's own use.


Bilayer Zwitterionic Metal-Organic Framework for Selective All-Solid-State Superionic Conduction in Lithium Metal Batteries.
Solid-state batteries (SSBs) hold immense potential for improved energy density and safety compared to traditional batteries. However, existing solid-state electrolytes (SSEs) face challenges in meeting the complex operational requirements of SSBs. This study introduces a novel approach to address this issue by developing a metal-organic framework (MOF) with customized bilayer zwitterionic nanochannels (MOF-BZN) as high-performance SSEs. The BZN consist of a rigid anionic MOF channel with chemically grafted soft multicationic oligomers (MCOs) on the pore wall. This design enables selective superionic conduction, with MCOs restricting the movement of anions while coulombic interaction between MCOs and anionic framework promoting the dissociation of Li+ . MOF-BZN exhibits remarkable Li+ conductivity (8.76 × 10-4 S cm-1 ), high Li+ transference number (0.75), and a wide electrochemical window of up to 4.9 V at 30 °C. Ultimately, the SSB utilizing flame retarded MOF-BZN achieves an impressive specific energy of 419.6 Wh kganode+cathode+electrolyte -1 under constrained conditions of high cathode loading (20.1 mg cm-2 ) and limited lithium metal source. The constructed bilayer zwitterionic MOFs present a pioneering strategy for developing advanced SSEs for highly efficient SSBs.


Functional differences in the catabolism of branched-chain L-amino acids in cultured normal and maple syrup urine disease fibroblasts.
Possible functional differences in the catabolism of the four branched-chain L-amino acids in maple syrup urine disease were assessed using cultured human skin fibroblast stains. Transamination and oxidative decarboxylation were comparatively studied in 90-min incubations with 1 mmole/liter of 1-14C-labeled substrates. In normal cell strains (n = 5), apparent transamination rates (sum of branched-chain 2-oxo[14C]acid and 14CO2 release; means expressed in nmole/90 min/mg of cell protein) were in the order L-leucine (32) greater than L-valine (17) greater than or equal to L-isoleucine (14) greater than L-allo-isoleucine (8); 14CO2 production was in the order L-valine (9) greater than L-isoleucine (6) greater than or equal to L-leucine (5) greater than L-allo-isoleucine (2). In variant (n = 5) as well as classical (n = 2) MSUD cell lines, branched-chain 2-oxo-[14C]acid release rates were generally comparable to the control values. As compared to the 14CO2 release in controls (= 100%), branched-chain 2-oxo acid dehydrogenase activity in MSUD fibroblasts was individually reduced and varied considerably between strains (residual activity 2-38%). Within individual strains, only small differences in the residual decarboxylation activity were observed in incubations with L-valine, L-leucine, and L-isoleucine. It was remarkably high, however, when L-allo-isoleucine was applied as a substrate. With the exception of L-allo-isoleucine, apparent total transamination rates of branched-chain L-amino acids were therefore distinctly lower in MSUD cells than in normal cells.


Unusual synthesis of new glycine antagonists via sequential aldol condensation-lactonization-elimination reaction.
Compounds 2 and 3 were designed in order to probe the North-East region of the strichnine-insensitive glycine binding site of the NMDA receptor. The two products were obtained readily by a tandem aldol condensation-lactonization-elimination step which affords the desired E isomer with complete regioselection.


An Improved Bibliometric Analysis on Antibiotics in Soil Research.
Antibiotic compounds can enter the environment and eventually into drinking water, when manure containing non-metabolized antibiotic residues is applied to agricultural land. In this study, the publication data was analyzed from the aspects of countries, subject categories and keywords during the period of 1946-2016 from Web of Science. The results indicated that, during the period of 2004-2016, the United States, followed by China, dominated the publication of antibiotics in soil. Three most representative subject categories were "Microbiology", "Environmental science and ecology" and "Chemistry". The most studied antibiotic was tetracycline. Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) with the fate and transport mechanisms such as degradation, adsorption and desorption were the hot research topics in this field. This study suggests that research on ARB, ARGs and antibiotics in soil should be paid more attention in the future research.


Prediction of Early Recurrence of Solitary Hepatocellular Carcinoma after Orthotopic Liver Transplantation.
Hepatocellular carcinomas(HCC) consisted of heterogeneous subtypes with different recurrence probabilities after liver transplantation(LT). Our study aimed to develop an improved model for predicting the recurrence of solitary HCC after LT. In this retrospective study, 151 solitary HCC patients who received orthotopic LT over a period of 10 consecutive years were included. All recipients received graft from deceased donors. The first eligible 50 patients were used as validation cohort and others were utilized to construct the model. A two-tailed P < 0.05 was considered to indicate statistical significance for all analysis. Based on the maximisation of the Youden's index, the optimal cutoff values for alpha-fetoprotein(AFP) and tumor diameter were 261.6 ng/mL and 3.6 cm, respectively. Vascular involvement includes gross and microscopic vascular invasion. Variables potentially affecting recurrence-free survival(RFS) were examined using univariate and multivariate Cox regression analysis. Univariate and multivariate analysis revealed that AFP, tumor diameter, vascular invasion and cytokeratin-19/glypican-3 sub-typing were independent prognostic factors for RFS, thus comprised the risk scoring model. The AUC values of the model in the cohorts were significantly higher than that of the Milan, UCSF, Fudan and Hangzhou criteria. These findings suggest the model has high performance in predicting early recurrence of solitary HCC patients after LT.


The epidemiology of Helicobacter pylori infection in African refugee children resettled in Australia.
To determine the prevalence and associated epidemiological features of Helicobacter pylori infection in child refugees in Western Australia. Cross-sectional study of 193 eligible African refugee children (aged < 16 years) at their initial health assessment after resettlement in Australia between 1 February and 30 November 2006. (i) Prevalence of H. pylori infection determined by monoclonal faecal antigen enzyme immunoassay testing (MFAT); (ii) associations of H. pylori infection with epidemiological factors (age, sex, transit through refugee camps, comorbidities and treatment interventions). MFAT was performed in 182 of the 193 children; 149 of these 182 (82%) had H. pylori infection. Age was an independent predictor of H. pylori infection (odds ratio [OR], 1.18; 95% CI, 1.07-1.31). No sex differences were observed. Premigration antimalarial therapy (with sulfadoxine-pyrimethamine and artesunate) significantly reduced the prevalence of H. pylori infection (age-adjusted OR, 0.33; 95% CI, 0.15-0.75). African refugee children have a high prevalence of H. pylori infection. Increasing age is a strong predictor of infection and antimalarial treatment may have a protective effect.


Health system evaluation in conflict-affected countries: a scoping review of approaches and methods.
Strengthening health systems in conflict-affected settings has become increasingly professionalised. However, evaluation remains challenging and often insufficiently documented in the literature. Many, particularly small-scale health system evaluations, are conducted by government bodies or non-governmental organisations (NGO) with limited capacity to publish their experiences. It is essential to identify the existing literature and main findings as a baseline for future efforts to evaluate the capacity and resilience of conflict-affected health systems. We thus aimed to synthesise the scope of methodological approaches and methods used in the peer-reviewed literature on health system evaluation in conflict-affected settings. We conducted a scoping review using Arksey and O'Malley's method and synthesised findings using the WHO health system 'building blocks' framework. We included 58 eligible sources of 2,355 screened, which included examination of health systems or components in 26 conflict-affected countries, primarily South Sudan and Afghanistan (7 sources each), Democratic Republic of the Congo (6), and Palestine (5). Most sources (86%) were led by foreign academic institutes and international donors and focused on health services delivery (78%), with qualitative designs predominating (53%). Theoretical or conceptual grounding was extremely limited and study designs were not generally complex, as many sources (43%) were NGO project evaluations for international donors and relied on simple and lower-cost methods. Sources were also limited in terms of geography (e.g., limited coverage of the Americas region), by component (e.g., preferences for specific components such as service delivery), gendered (e.g., limited participation of women), and colonised (e.g., limited authorship and research leadership from affected countries). The evaluation literature in conflict-affected settings remains limited in scope and content, favouring simplified study designs and methods, and including those components and projects implemented or funded internationally. Many identified challenges and limitations (e.g., limited innovation/contextualisation, poor engagement with local actors, gender and language biases) could be mitigated with more rigorous and systematic evaluation approaches.


Comparing self-assessment, functional, and anthropometric techniques in predicting osteoporosis.
The osteoporosis self-assessment tool was more accurate than hand grip strength, gait speed, and calf circumference in predicting osteoporosis in women. Hand grip strength was more accurate than the osteoporosis self-assessment tool, gait speed, and calf circumference in predicting osteoporosis in men. The osteoporosis self-assessment tool, functional assessment, and anthropometric measurement are different techniques to identify those at risk of osteoporosis. This study aimed to compare the performance of these techniques in predicting osteoporosis. In this cross-sectional, hospital-based study including 1109 participants, the bone mineral density of the spine and hips was evaluated using the dual-energy X-ray absorptiometry. The Osteoporosis Self-Assessment Tool was used as a simple clinical risk assessment tool to screen for osteoporosis. Gait speed and hand grip strength were used as functional assessments to predict osteoporosis. Calf circumference was used as an anthropometric measurement to predict osteoporosis risk. In women, the Osteoporosis Self-Assessment Tool was better than hand grip strength, gait speed, and calf circumference in predicting osteoporosis. In contrast, in men, hand grip strength was better than the Osteoporosis Self-Assessment Tool, gait speed, and calf circumference. The application of simple, cost-effective techniques for the identification of osteoporosis risk will be beneficial for both screening and patient care when dual-energy X-ray absorptiometry is not available. We suggest that the Osteoporosis Self-Assessment Tool can be used to identify the risk of osteoporosis in women and hand grip strength measurement can be used for men.


Quantification of proteomic profile changes in the hemolymph of crayfish during in vitro coagulation.
Hemolymph is the circulatory fluid that fills the body cavity of crustaceans, analogous to blood in vertebrates. Hemolymph coagulation, similar to blood clotting in vertebrates, plays a crucial role in wound healing and innate immune responses. Despite extensive studies on the clotting process in crustaceans, no comparative quantitative analysis of the protein composition of non-clotted and clotted hemolymph in any decapod has been reported. In this study, we used label-free protein quantification with high-resolution mass spectrometry to identify the proteomic profile of hemolymph in crayfish and quantify significant changes in protein abundances between non-clotted and clotted hemolymph. Our analysis identified a total of two-hundred and nineteen proteins in both hemolymph groups. Furthermore, we discussed the potential functions of the top most high and low-abundant proteins in hemolymph proteomic profile. The quantity of most of the proteins was not significantly changed during coagulation between non-clotted and clotted hemolymph, which may indicate that clotting proteins are likely pre-synthesized, allowing for a swift coagulation response to injury. Four proteins still showed abundance differences (p < 0.05, fold change>2), including C-type lectin domain-containing proteins, Laminin A chain, Tropomyosin, and Reverse transcriptase domain-containing proteins. While the first three proteins were down-regulated, the last one was up-regulated. The down-regulation of structural and cytoskeletal proteins may affect the process of hemocyte degranulation needed for coagulation, while the up-regulation of an immune-related protein might be attributed to the phagocytosis ability of viable hemocytes during coagulation.


Anatomical characteristics and classifications of gastrocolic trunk of Henle in laparoscopic right colectomy: preliminary results of multicenter observational study.
As a key landmark during laparoscopic right colectomy, the classification and variation of the gastrocolic trunk of Henle (GTH) remains to be clarified. The aim of this nationwide multicenter study was to describe the characteristics of the GTH intra-operatively during laparoscopic right colectomies. Three hundred seventy-one patients who underwent laparoscopic right colectomies from January 2018 to March 2019 in 25 hospitals across China were enrolled in the study. The length of the GTH, the classification with a precise description of confluent tributaries, and other variations were analyzed. Of the 371 patients, 363 had a GTH. The proportion of type-0, type-I, type-II, and type-III was 15.2% (n = 55), 54.8% (n = 199), 25.3% (n = 92), and 4.7% (n = 17), respectively. The average length of the GTH was 8.5 mm, ranging from 2 to 30 mm. This is the first multicenter study with a large sample by which the GTH was classified based on laparoscopic intraoperative observation. Variations in the GTH were classified into four types based on the number of colic drainage veins (right colic, superior right colic, middle colic, accessory middle colic, and ileocolic veins), among which the right colic vein was the most common. The length of the GTH was relatively short, and thus might carry a risk of bleeding. Further clinical data should be correlated with the characteristics of the GTH.


Rapid changes in ultrastructure during deafferentation-induced dendritic atrophy.
This study describes qualitative and quantitative changes in dendritic ultrastructure during the rapid atrophy of nucleus laminaris (NL) dendrites following deafferentation. The dendrites of n. laminaris neurons in the chick auditory system are segregated into dorsal and ventral dendritic tufts, which receive spatially separated innervation from the ipsilateral and contralateral nucleus magnocellularis, respectively. We have previously shown that removing the input to the ventral side of NL results in the rapid atrophy of the ventral dendrites, whereas the nondeafferented dorsal dendrites of the same cells do not change in length. The ultrastructure of NL was examined in normal animals and after deafferentation. Changes in dendritic ultrastructure were not qualitatively apparent 4 hours after deafferentation. Between 12 and 48 hours the cytoplasm of the ventral dendrites became progressively more lucent, and a gap formed in the transition between the soma and ventral dendritic cytoplasm. Many of the dendrite tips, however, appeared normal even 2 days after deafferentation. Degeneration of dendrite plasma membrane was not visible until 2 days after deafferentation. On the other hand, quantitative measurements revealed a 30% decrease in microtubule density in the initial portion of the ventral dendrite by 4 hours, and a 50-60% decrease from 12 to 48 hours after deafferentation. Neurofilament density in the initial ventral dendrites decreased 50% by 12 hours, and 70% by 2 days after deafferentation. Many of the terminals of the severed afferents remained attached to the atrophying dendrite until 2 days after surgery, when they were in advanced stages of degeneration. Glia apparently were not involved in dendrite loss. The implications of these results on the role of cytoskeleton in the production and maintenance of dendritic shape are discussed.


Japanese Society of Anxiety and Related Disorders/Japanese Society of Neuropsychopharmacology: Clinical practice guideline for social anxiety disorder (2021).
The development of clinical practice guidelines for social anxiety disorder began in March 2018 when the Joint Clinical Practice Guideline Development Committee for Anxiety and Obsessive-Compulsive Disorders was formed by the Japanese Society of Anxiety and Related Disorders and Japanese Society of Neuropsychopharmacology to jointly develop guidelines for anxiety and obsessive-compulsive disorders. Based on the universal concept of evidence-based medicine, three clinical questions (CQs) about pharmacotherapy and psychotherapy were developed for clinical guidelines for social anxiety disorder, panic disorders, and obsessive-compulsive disorder in accordance with the Minds "Manual for Guidelines Development 2017 by the Japan Council for Quality Health Care: CQ1-"What is the recommended pharmacotherapy for social anxiety disorder in adults?"; CQ2-"What is the recommended psychotherapy (psychological intervention) for social anxiety disorder in adults?"; and CQ3-"What are the recommendations regarding monotherapy and combination therapy for social anxiety disorder in adults in terms of pharmacotherapy and psychotherapy (psychological interventions)?" Summarized recommendations for social anxiety disorder in adults are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitor for CQ1, cognitive behavioral therapy for CQ2, and there are no recommendations regarding monotherapy and combination therapy for CQ3. These were answered by considering the balance between benefits and harms based on systematic reviews of each. The aim of this brief guideline for the standard-of-care (i.e., medical treatment) for social anxiety disorder in adults (18 years and older) was to help "shared decision making," in which medical professionals, including physicians, and patients share scientific evidence to decide on a course of treatment.


Low body temperature affects associative processes in long-trace conditioned flavor aversion.
A series of experiments examined the effect of low body temperature on the associative process in long-trace conditioned flavor aversion. Experiment 1 demonstrated that maintaining a low body temperature between conditioned stimulus (CS) and unconditioned stimulus (US) administration facilitates the associative process and allows a flavor aversion to be conditioned in young rats over an interval that would normally not support conditioning. Experiments 2 and 3 demonstrated that this was due neither to lingering systemic saccharin serving as a CS nor to a cold induced enhancement of US intensity. Experiment 4 demonstrated that inducing hypothermia at various times during a 3-h CS-US interval results in an apparent delay of reinforcement gradient. We propose that a cold induced decrease in metabolic rate slows the internal clock that governs the perception of time and that the CS-US association depends upon perceived contiguity rather than upon an external clock-referenced contiguity.


Effects of Chinese herbal medicines on dementia risk in patients with sleep disorders in Taiwan.
Sleep disorders affect an estimated 150 million people worldwide and result in adverse health, safety, and work performance-related outcomes that have important economic consequences. In Taiwan, Chinese herbal medicine (CHM) is a complementary natural medicine and has been widely used as an adjunctive therapy. This study aimed to investigate the effect of CHM on dementia risk in patients with sleep disorders in Taiwan. We identified 124,605 patients with sleep disorders between the ages of 20 and 60 years. Of these, 5876 CHM users and 5876 non-CHM users were matched according to age and gender. The chi-squared test, Cox proportional hazard model, Kaplan-Meier method, and log-rank test were used for the comparisons. Association rule mining and network analysis were applied to determine a CHM pattern specialized for sleep disorders. More CHM users did not use sleeping pills than non-CHM users. CHM users had a lower risk of dementia than non-CHM users after adjusting for age, gender, and sleeping pill use (hazard ratio (HR): 0.469, 95% CI = 0.289-0.760; p-value = 0.002). The cumulative incidence of dementia was lower among CHM users (long-rank test, p-value < 0.001). Association rule mining and network analysis showed that Ye-Jiao-Teng (YJT; Caulis Polygoni Multiflori; Polygonum multiflorum Thunb), Suan-Zao-Ren-Tang (SZRT), Jia-Wei-Xiao-Yao-San (JWXYS), He-Huan-Pi (HHP; Cortex Albizziae; Albizia julibrissin Durazz.), and Suan-Zao-Ren (SZR; Semen Zizyphi Spinosae; Ziziphus jujuba Mill.) were important CHMs for patients with sleep disorders in Taiwan. A comprehensive list of herbal medicines may be useful for the clinical treatment of patients with sleep disorders, and for future scientific investigations into the prevention of dementia in these patients.


Context-enabled learning in the human visual system.
Training was found to improve the performance of humans on a variety of visual perceptual tasks. However, the ability to detect small changes in the contrast of simple visual stimuli could not be improved by repetition. Here we show that the performance of this basic task could be modified after the discrimination of the stimulus contrast was practised in the presence of similar laterally placed stimuli, suggesting a change in the local neuronal circuit involved in the task. On the basis of a combination of hebbian and anti-hebbian synaptic learning rules compatible with our results, we propose a mechanism of plasticity in the visual cortex that is enabled by a change in the context.


Study of pelvic floor and sphincter muscles in congenital pouch colon with the help of three-dimensional CT scan.
Congenital pouch colon (CPC) is a pouch-like dilatation of shortened colon associated with anorectal malformation (ARM). The disease is prevalent in northern India. Postoperatively, the continence results are not as good as in other ARMs and there is higher incidence of incontinence and perineal soiling in these patients. The present study aimed to evaluate the pelvic floor and sphincter muscle characteristics in patients of CPC with the help of 64-slice computerized tomography with three-dimensional (3D) volumetric reconstructions of images, thus, to know the overall quality of these muscles in the patients. The study was conducted in patients admitted over a period of July 2007 to November 2008 in our department. Totally, eight patients of CPC were subjected to 64-slice CT with three-dimensional reconstructions of images and different parameters such as quality of pelvic floor muscles, configuration of vertical and parasagittal fibres, shape and thickness of sphincter muscle complex, attenuation values of sphincters were studied. The 3D reconstructed images of pelvis in patients of CPC showed a well-developed pelvic floor and sphincter muscle complex. The length of the parasagittal fibres, transverse width of the vertical fibres and CT attenuation values of these structures with overall muscle quality were found to be good in these patients. In cases of CPC, the pelvic floor muscles including striated muscle complex (vertical and parasagittal fibres) are well developed. Higher rates of incontinence and soiling in CPC are not because of poorly developed pelvic floor and sphincter muscles. Three-dimensional CT can also provide important anatomical information that can help the operating surgeon while performing surgery.


High affinity iron(III) scavenging by a novel hexadentate 3-hydroxypyridin-4-one-based dendrimer: synthesis and characterization.
The synthesis of a novel iron(III)-selective hydroxypyridinone hexadentate-terminated dendritic chelator based on a benzene tricarbonyl core polyamine dendrimer is described. The iron-chelating ability of the dendritic chelator was demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and UV-vis spectroscopy. The physicochemical properties of the isolated hexadentate unit were also investigated. The dendrimer was found to possess an extremely high affinity for iron(III), namely logK=34.8, pFe3+=30.6.


Complement as an Immune Barrier in Platelet Transfusion Refractoriness.
Patients with hematological cancers often have low platelet counts because of progressing bone marrow failure or cytostatic therapy. A large fraction of those patients need platelet transfusions, which can be life-saving if bleedings occur and also allow diagnostic and therapeutic interventions. The outcomes of platelet transfusions are not always easy to predict in terms of bleeding control or increase in platelet count. Reasons could be disease-specific factors, fever, or infections leading to platelet consumption, but the immune system may also be involved, in particular, in patients previously immunized against foreign human leukocyte antigens (HLA). Mechanisms underlying immune-mediated platelet destruction in the presence of antibodies again HLA are not well understood in clinical situations. This review discusses the role of complement in platelet refractoriness, with a focus on HLA antibody-mediated platelet refractoriness. We summarize recent work in this area, discuss complement-platelet interactions in general terms, and a suggest a possible role of complement in platelet transfusion in general.


Effects of isoflurane and halothane on coronary vascular resistance and collateral myocardial blood flow: their capacity to induce coronary steal.
Some coronary vasodilators, paradoxically, may endanger patients with coronary artery disease by causing "coronary steal." To determine the capacity of isoflurane and halothane to cause coronary steal, the authors studied their effects on coronary vascular resistance (CVR), diastolic coronary artery pressure, and collateral myocardial blood flow. Using ameroid constrictors, chronic occlusions of the left anterior descending (LAD) coronary artery were created in ten dogs. Six to eight weeks after implantation, the dogs were anesthetized with fentanyl and pentobarbital, and a stenosis was created on the circumflex (Cx) coronary artery. Isoflurane and halothane were each administered in doses of 0.5 and 1.5 MAC. Diastolic aortic pressure was held constant. Using small catheters in the circumflex and LAD coronary arteries, the authors measured diastolic coronary artery pressures. Collateral myocardial blood flow was measured by the microsphere method. In this model, halothane and isoflurane minimally affect CVR. The maximum change in CVR, which was found during 1.5 MAC isoflurane, was -8% (not significant). Diastolic coronary pressures distal to the Cx stenosis (54.5 +/- 11.5 mmHg) and distal to the LAD occlusion (44.5 +/- 5.2 mmHg) did not change significantly with either isoflurane or halothane. Transmural collateral blood flow distal to the LAD occlusion (0.51 +/- 0.11 cc.g-1.min-1) was unaltered by either drug. There was no evidence of coronary steal. Epicardial ECG S-T segments showed no evidence of ischemia. The finding of minimal direct effects of halothane and isoflurane on CVR, diastolic coronary pressure, and collateral myocardial blood flow suggest that, under the conditions of this study, neither agent, when used as an adjuvant to high-dose narcotic anesthesia, is likely to cause myocardial ischemia by a coronary "steal" mechanism.


Neural fold formation at newly created boundaries between neural plate and epidermis in the axolotl.
According to a recent model, the cortical tractor model, neural fold and neural crest formation occurs at the boundary between neural plate and epidermis because random cell movements become organized at this site. If this is correct, then a fold should form at any boundary between epidermis and neural plate. To test that proposition, we created new boundaries in axolotl embryos by juxtaposing pieces of neural plate and epidermis that would not normally participate in fold formation. These boundaries were examined superficially and histologically for the presence of folds, permitting the following observations. Folds form at each newly created boundary, and as many folds form as there are boundaries. When two folds meet they fuse into a hollow "tube" of neural tissue covered by epidermis. Sections reveal that these ectopic folds and "tubes" are morphologically similar to their natural counterparts. Transplanting neural plate into epidermis produces nodules of neural tissue with central lumens and peripheral nerve fibers, and transplanting epidermis into neural plate causes the neural tube and the dorsal fin to bifurcate in the region of the graft. Tissue transplanted homotypically as a control integrates into the host tissue without forming folds. When tissue from a pigmented embryo is transplanted into an albino host, the presence of pigment allows the donor cells to be distinguished from those of the host. Mesenchymal cells and melanocytes originating from neural plate transplants indicate that neural crest cells form at these new boundaries. Thus, any boundary between neural plate and epidermis denotes the site of a neural fold, and the behavior of cells at this boundary appears to help fold the epithelium. Since folds can form in ectopic locations on an embryo, local interactions rather than classical neural induction appear to be responsible for the formation of neural folds and neural crest.


Emergency contraception: what do our patients know?
Unintended pregnancy is a major medical, social, and public health problem. Emergency contraceptive pills can prevent 75% to 85% of unintended pregnancies if administered within 72 hours of intercourse. We perform this study to measure knowledge, attitudes, practices, and perceived needs about emergency contraception in a sample of women seeking emergency department (ED) care. This was a prospective survey of women presenting to an inner-city ED during an 8-week study period. Women who were aged 18 to 45 years, English speaking, and not critically ill and who presented during 56 randomly generated 4-hour time blocks were eligible. Trained research assistants administered a 20-question survey that included questions on current sexual and contraceptive practices and knowledge, acceptance, and preferences about postcoital contraception. Two hundred thirty-two women met eligibility criteria; 158 (68%) women agreed to participate. Participants and nonparticipants were similar in age, race, ethnicity, and insurance status. The participants' mean age was 30 years. Twenty-five percent were married, whereas 49% had never married and 25% were separated or divorced. Fifty-two percent (95% confidence interval [CI] 44% to 60%) reported at least 1 previous unintended pregnancy; 28% (95% CI 21% to 35%) had 1 or more previous elective abortions. Of women who had been sexually active in the past month, half (47%) reported unprotected intercourse during that time. Among all respondents, 122 (77%; 95% CI 71% to 84%) had heard of emergency contraception as a way of preventing pregnancy after unprotected intercourse. Of these respondents, one fourth to one half did not have enough knowledge to use emergency contraceptive pills effectively. Fifty-seven percent of women were willing to use emergency contraceptive pills in the future, and 16 women said they would consider a change in regular contraception to emergency contraceptive pills if widely available. Sexually active women seeking ED care have high rates of unintended pregnancy and abortion. There is broad acceptance of emergency contraceptive pills to prevent pregnancy, but knowledge of availability, timing, and proper use is limited. Emergency contraceptive pills are a safe, effective, and low-cost primary preventive and emergency care intervention, and information about their use should be made available to ED patients. Patients should be advised not to abandon their use of barrier or other traditional contraceptives.


The formation and function of plant volatiles: perfumes for pollinator attraction and defense.
Plants synthesize and emit a large variety of volatile organic compounds with terpenoids and fatty-acid derivatives the dominant classes. Whereas some volatiles are probably common to almost all plants, others are specific to only one or a few related taxa. The rapid progress in elucidating the biosynthetic pathways, enzymes, and genes involved in the formation of plant volatiles allows their physiology and function to be rigorously investigated at the molecular and biochemical levels. Floral volatiles serve as attractants for species-specific pollinators, whereas the volatiles emitted from vegetative parts, especially those released after herbivory, appear to protect plants by deterring herbivores and by attracting the enemies of herbivores.


Decreased intrinsic neural timescales in obsessive compulsive disorder and two distinct subtypes revealed by heterogeneity through discriminative analysis.
OCD is featured as the destruction of information storage and processing. The cognition of neurobiological and clinical heterogeneity is in suspense and poorly studied. Ninety-nine patients and matched HCs(n = 104) were recruited and underwent resting-state functional MRI scans. We applied INT to evaluate altered local neural dynamics representing the ability of information integration. Moreover, considering OCD was a highly heterogeneous disorder, we investigated putative OCD subtypes from INT using a novel semi-supervised machine learning, named HYDRA. Compared with HCs, patients with OCD showed decreased INTs in extensive brain regions, including bilateral cerebellum and precuneus, STG/MTG and PCC, hippocampus in DMN; right IFG/MFG/SFG, SPL and bilateral angular gyrus in CEN and insula, SMA in SN. Moreover, many other regions involved in visual processing also had disrupted dynamics of local neural organization, consisting of bilateral CUN, LING and fusiform gyrus and occipital lobe. HYDRA divided patients into two distinct neuroanatomical subtypes from INT. Subtype 1 showed decreased INTs in distributed networks, while subtype 2 presented increased in several common regions which were also found to be decreased in subtype 1, such as STG, IPL, postcentral gyrus and left insula, supramarginal gyrus. This study showed distinct abnormalities from the perspective of dynamics of local neural organization in OCD. Such alteration and dimensional approach may provide a new insight into the prior traditional cognition of this disorder and to some extent do favor of more precise diagnosis and treatment response in the future.


Binding of novel fullerene inhibitors to HIV-1 protease: insight through molecular dynamics and molecular mechanics Poisson-Boltzmann surface area calculations.
The objectives of this study include the design of a series of novel fullerene-based inhibitors for HIV-1 protease (HIV-1 PR), by employing two strategies that can also be applied to the design of inhibitors for any other target. Additionally, the interactions which contribute to the observed exceptionally high binding free energies were analyzed. In particular, we investigated: (1) hydrogen bonding (H-bond) interactions between specific fullerene derivatives and the protease, (2) the regions of HIV-1 PR that play a significant role in binding, (3) protease changes upon binding and (4) various contributions to the binding free energy, in order to identify the most significant of them. This study has been performed by employing a docking technique, two 3D-QSAR models, molecular dynamics (MD) simulations and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. Our computed binding free energies are in satisfactory agreement with the experimental results. The suitability of specific fullerene derivatives as drug candidates was further enhanced, after ADMET (absorption, distribution, metabolism, excretion and toxicity) properties have been estimated to be promising. The outcomes of this study revealed important protein-ligand interaction patterns that may lead towards the development of novel, potent HIV-1 PR inhibitors.


[Mitral valve repair for degenerative mitral insufficiency: likelihood of success, early and-long term results at 20 years].
The 2014 Guidelines for the Management of Patients with Valvular Heart Disease require to know the probability of success and operative mortality of Mitral Valve Repair (MVR) for Degenerative Mitral Insufficiency (DMI) at a given institution. To assess the probability of success, operative mortality and long-term results of MVR for DMI. The database of the Cardiovascular Surgery Service was reviewed for the period December 1991 to December 2013. Long-term survival information was obtained from death certificate records of the Chilean Identification Service. One hundred forty seven patients with DMI were identified, all operated by one author (RZ). In 28 (19%) the mitral valve was replaced, including three patients in whom a MVR was intended without success. A successful MVR was performed in 119 patients (81%). The probability of a successful MVR was 97.5% (119 of 122). Prolapsed posterior leaflet was present in 81% and annulus dilatation in 60% of cases. The most frequent surgical procedures were quadrilateral resection (83%) and chordal transfer (13%). A mitral annuloplasty was performed in 92% of cases. Operative mortality was 0.8%. At the end of a 9.9 (0 - 22.7) years follow-up, 87 patients (73%) were alive and mean survival was 16.9 years. Survival rates at 5, 10, 15 and 20 years were 91%, 78%, 71% and 50%, respectively. Six patients were re-operated, due to mitral valve dysfunction in three. Mean re-operation free survival was 21.4 years. Echocardiographic follow-up was 75% completed at an average of 64 months; 84% of cases had no or only 1+ mitral regurgitation. In our experience, MVR for DMI had an operative mortality below 1% and a probability of success greater than 95%, with excellent long-term results.


Intestinal parasites of small mammals from Grand Teton National Park.
A study of the prevalence and identity of Giardia spp. in small mammals of Grand Teton National Park was undertaken. All 90 montane voles examined were positive for Giardia, as were 4 pocket gophers, 1 water shrew, 4 water voles, and 2 meadow voles. How and why these findings contrast with the findings of others are discussed.


Use of topical medication in orofacial neuropathic pain: a retrospective study.
The objective of this study was to evaluate the effect of topical medications as a single treatment or in combination with systemic medications in the treatment of orofacial neuropathic pain conditions. A retrospective chart review of 39 patients treated for orofacial neuropathic pain at the Orofacial Pain Clinic in the New Jersey Dental School was performed. In line with the treatment selection, the subjects were divided into 3 groups: topical medications only (n = 12), systemic medications only (n = 10), and a combination of both (n = 17). The starting pain level as expressed in pain Visual Analog Scale for the 3 groups was significantly different. The combined treatment group baseline pain level (7.5 +/- 0.403 SEM; P = .0015) and the systemic treatment only group pain level (8.6 +/- 0.611 SEM; P = .0375) was significantly elevated compared to the topical only group (6.1 +/- 0.716 SEM; P = .1057). Following treatment, pain level was significantly reduced in all 3 groups. The combined group had the highest pain relief (52.0 +/- 6.676 SEM % reduction; P < .0001) followed by the systemic-only group (40.6 +/- 9.727 SEM % reduction; P = .0029) and the topicals-only group (40.9 +/- 10.775 SEM% reduction; P = .0048). The time taken for the topical treatment only to act was significantly shorter (3 weeks +/- 0.479 SEM; P = .0015) when compared with the systemic-only (4 weeks +/- 0.772 SEM; P = .3629) and the combined group (5.5 weeks +/- 0.912 SEM; P = .1738). Topical medication as single treatment or in combination with systemic medications can reduce orofacial neuropathic pain severity. Further prospective research should be performed to validate this treatment option.


Decellularized liver ECM-based 3D scaffolds: Compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological evaluations.
The extracellular matrix (ECM) is involved in many critical cellular interactions through its biological macromolecules. In this study, a macroporous 3D scaffold originating from decellularized bovine liver ECM (dL-ECM), with defined compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological properties was developed. First, protocols were determined that effectively remove cells and DNA while ECM retains biological macromolecules collagen, elastin, sGAGs in tissue. Rheological analysis revealed the elastic properties of pepsin-digested dL-ECM. Then, dL-ECM hydrogel was neutralized, molded, formed into macroporous (~100-200 μm) scaffolds in aqueous medium at 37 °C, and lyophilized. The scaffolds had water retention ability, and were mechanically stable for at least 14 days in the culture medium. The findings also showed that increasing the dL-ECM concentration from 10 mg/mL to 20 mg/mL resulted in a significant increase in the mechanical strength of the scaffolds. The hemolysis test revealed high in vitro hemocompatibility of the dL-ECM scaffolds. Studies investigating the viability and proliferation status of human adipose stem cells seeded over a 2-week culture period have demonstrated the suitability of dL-ECM scaffolds as a cell substrate. Prospective studies may reveal the extent to which 3D dL-ECM sponges have the potential to create a biomimetic environment for cells.


Diagnosis of functional ischemia in a right coronary artery with anomalous aortic origin.
Anomalous aortic origin of coronary artery (AAOCA) is rare but critical for the association with sudden cardiac death. In detecting the origin of AAOCA, coronary CT angiography is more accurate than invasive coronary angiography, but only with anatomical evaluation. A novel technology FFRCT, which is noninvasively computed by coronary CT image, can evaluate functional ischemia of coronary artery even without atherosclerotic plaque and has potential for innovation in AAOCA.