Investigation of the effect of marathon running on leucocyte counts of subjects of different ethnic origins: relevance to the aetiology of ethnic neutropenia.
Healthy subjects of African ancestry, including Afro-Caribbeans, have been observed to have lower total white cell counts and neutrophil counts than healthy Caucasian subjects. The cause of this ethnic neutropenia is unclear. We have previously found no evidence that increased margination of neutrophils is responsible. In this study, we have investigated mobilization of neutrophils from the bone marrow granulocyte reserve by endurance exercise. We investigated subjects of different ethnic origins before and after they had competed in a marathon race. Before the race, the neutrophil counts of Africans/Afro-Caribbeans were significantly lower than those of Caucasians (means 2.49 and 3.21 x 109/l respectively; P = 0.043). After the race, the difference was greater, as was the degree of significance (means 10.21 and 12.33 respectively; P = 0.017). The percentage increment was almost identical whereas the absolute increment was considerably less, although of marginal statistical significance (increment 7.72 and 9. 12 x 109/l respectively; P = 0.10). Similar changes were observed in the monocyte count. Before the race, the difference in the means was of marginal statistical significance (0.35 and 0.41 x 109/l respectively; P = 0.105), whereas after the race the difference was greater and was highly significant (means 0.75 and 1.05 x 109/l respectively; P = 0.001). These observations support the results of our earlier study, both of which suggested that ethnic neutropenia is likely to result from a diminished bone marrow reserve rather than being consequent on altered distribution of neutrophils within the blood stream.


The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.
The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage.


History of lung disease and risk of lung cancer in a population with high household fuel combustion exposures in rural China.
History of chronic lung diseases and household coal use for heating and cooking are established risk factors of lung cancer; however, few studies have been able to explore these risk factors simultaneously. Xuanwei, China, has some of the highest rates of lung cancer in China and most residents experience substantial in-home coal smoke exposures. Using a population-based case-control study of 498 lung cancer cases and 498 age-matched controls, we evaluated the risk of lung cancer in relation to coal smoke exposure and history of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), chronic bronchitis, and emphysema. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression adjusting for potential confounders. We observed an increased risk of lung cancer with history of any chronic lung disease among males (OR = 14.2; 95%CI = 4.3-46.9), females (OR = 2.6; 95%CI = 1.1-6.3), smokers (OR = 12.7; 95%CI = 3.5-45.8), and nonsmokers (OR = 2.6; 95%CI = 1.1-6.4). Specifically, TB (OR = 83.7; 95%CI = 11.0-634.7), COPD (OR = 3.2; 95%CI = 1.7-6.0), and emphysema and chronic bronchitis (OR = 3.3; 95%CI = 1.7-6.4) were associated with increased risks. These findings suggest that history of chronic lung diseases may also increase risk of lung cancer in populations with indoor coal smoke exposures.


The potential of flow modification in the treatment of intracranial aneurysms.
Abstract: To summarize the theoretical background and existing technical achievements of flow modification techniques in the treatment of intracranial aneurysms. The evolution of the concept of flow modification for aneurysm treatment is overviewed within the published literature on application of stents for aneurysms. The newest achievements using dedicated flow modifying devices is discussed. Reconstruction of laminar flow within intracranial arteries harboring aneurysms is feasible. Reorientation of flow using dedicated flow modifying devices is a highly effective technique in the treatment of large, broad neck, otherwise untreatable aneurysms.


COVID-19-Related Health Literacy of School Leaders in Hong Kong: A Cross-Sectional Study.
To date, we know little about COVID-19-related health literacy among school leaders, particularly in East Asia. The present study aimed to assess the level of COVID-19-related health literacy and associated factors (vaccine hesitancy, self-endangering behaviour, and work satisfaction) among school leaders in Hong Kong. A cross-sectional study of 259 school leaders was carried out during the COVID-19 pandemic between April 2021 and February 2022. COVID-19-related health literacy using HLS-COVID-Q22, three subscales of self-endangering work behaviour scales (i.e., "extensification of work", "intensification of work" and "quality reduction"), and two dimensions of Burnout Assessment Tool (BAT) (i.e., psychosomatic complaints and exhaustion) were used. The study employed independent sample t-test, ANOVA, and multilinear regression models. The findings show that more than half (53.7%) of school leaders had insufficient health literacy. Participants with insufficient health literacy scored significantly higher in the following factors: exhaustion related to work situation (p = 0.029), psychosomatic complaints (p < 0.001), attitude about vaccination (i.e., less agree with vaccination) (p < 0.001), level of informing on COVID-19 related information (i.e., felt less informed) (p < 0.001), and level of confusion about COVID-19-related information (i.e., felt more confused) (p < 0.001). In a linear regression model predicting attitude about coronavirus vaccination, age (β, -0.188, 95% CI, -0.024, -0.005, p = 0.002) and health literacy (β, -0.395, 95% CI, -0.716, -0.361, p < 0.001) were the negative predictors, F(5, 214) = 11.859, p < 0.001. For the linear regression model adjusted for sex and age for predicting health literacy, the model was insignificant. Despite being a highly educated group, this study reveals that one in two Hong Kong school leaders have insufficient health literacy. Inadequate health literacy was strongly associated with a negative attitude about vaccination, low information, and confusion about COVID-19-related information. Additionally, insufficient health literacy was associated with the two secondary symptoms of burnouts. The study highlights an urgent need to develop intervention programmes to promote the COVID-19-specific as well as overall health literacy of the school leaders.


Short term outcomes of children with abusive head trauma two years post injury: A retrospective study.
Abusive head trauma (AHT) can have debilitating sequelae for children who survive. A retrospective medical record review was used to describe short-term developmental outcomes of children with AHT and identify predictors of poorer outcomes. Children with AHT who received follow up by the hospital's rehabilitation department for 12 to 24 months post-injury were included in this review. Data for 85 children were collected on hearing, vision, gross motor, fine motor, speech and language, cognition, play, adaptive functioning, behaviour and personal-social skills. Global assessment found 42% of children had a good recovery, 34% had a moderate disability and 24% had a severe disability. For whom there was data, more than half had abnormal cognition, behaviour and personal-social skills, whilst more than a third had abnormal speech and language, neurological signs on last assessment, vision, play skills, and gross and fine motor skills. Factors that predicted poorer prognosis across all developmental domains included paediatric intensive care unit admission, longer length of hospital stay, breathing difficulty and lower Glasgow Coma Scale on presentation. This study highlights the substantial number of children who have abnormal development in the short-term post-AHT and assists in identifying those who require extensive long-term follow up.


Fetal programming by co-twin rivalry in sheep.
Fetal rivalry for space and nutrients compromises intrauterine environment and fetal growth, this leading to further consequences during adult life (i.e., fetal programming). Focusing on sheep, relevant fetal programming effects have been revealed on body composition and growth although little is known about their potential impact on the reproductive performance of adult ewes. This research focused on the analysis of fetal programming-related effects on 41,475 litter size (LS) records from 7,177 purebred Ripollesa ewes. Fetal programming sources of variation accounted for the linear and quadratic effect of absolute birth BW (ABBW), relative birth BW (RBBW) of twin-born ewes (i.e., both magnitude and direction of the birth BW difference between the ewe and its co-twin), and sex of twin ewe's littermate (SLM). More specifically, data were analyzed under a threshold mixed model and the statistical relevance of models accounting for different combinations of ABBW, RBBW, and SLM effects was compared by Bayes factors (BF; i.e., the ratio between the posterior probability of 2 competing models). The model accounting for RBBW and discarding both ABBW and SLM effects was clearly preferred; its posterior probability was 35.2 to 362.3 times higher than from remaining models and provided very strong (31.6 < BF < 100) and decisive evidences (BF > 100) supporting the relevance of RBBW and the negligibility of both ABBW and SLM. Single-born ewes were included as reference group and they reached a predicted LS of 1.189 lambs per lambing. Twin-born ewes being >600 g lighter than their co-twins suffered from an impaired reproductive ability with 1.162 lambs per lambing (95% credible interval [95CI], 1.147 to 1.179), and this estimate increased until ewes were 151 to 300 g lighter than their co-twins (1.226 lambs per lambing; 95CI, 1.208 to 1.244). Remaining categories (i.e., ewes being heavier or equal than their co-twins) did not provide significant differences and showed an enhanced reproductive ability of approximately 1.23 lambs per lambing. These significant differences in LS highlighted the influence of fetal programming in sheep under rangeland conditions, which implies decisive economic consequences worldwide. Moreover, these results could contribute additional information on twin biology, which could be useful in other mammalian species such as humans.


Evolution of UCP1 Transcriptional Regulatory Elements Across the Mammalian Phylogeny.
Uncoupling protein 1 (UCP1) permits non-shivering thermogenesis (NST) when highly expressed in brown adipose tissue (BAT) mitochondria. Exclusive to placental mammals, BAT has commonly been regarded to be advantageous for thermoregulation in hibernators, small-bodied species, and the neonates of larger species. While numerous regulatory control motifs associated with UCP1 transcription have been proposed for murid rodents, it remains unclear whether these are conserved across the eutherian mammal phylogeny and hence essential for UCP1 expression. To address this shortcoming, we conducted a broad comparative survey of putative UCP1 transcriptional regulatory elements in 139 mammals (135 eutherians). We find no evidence for presence of a UCP1 enhancer in monotremes and marsupials, supporting the hypothesis that this control region evolved in a stem eutherian ancestor. We additionally reveal that several putative promoter elements (e.g., CRE-4, CCAAT) identified in murid rodents are not conserved among BAT-expressing eutherians, and together with the putative regulatory region (PRR) and CpG island do not appear to be crucial for UCP1 expression. The specificity and importance of the upTRE, dnTRE, URE1, CRE-2, RARE-2, NBRE, BRE-1, and BRE-2 enhancer elements first described from rats and mice are moreover uncertain as these motifs differ substantially-but generally remain highly conserved-in other BAT-expressing eutherians. Other UCP1 enhancer motifs (CRE-3, PPRE, and RARE-3) as well as the TATA box are also highly conserved in nearly all eutherian lineages with an intact UCP1. While these transcriptional regulatory motifs are generally also maintained in species where this gene is pseudogenized, the loss or degeneration of key basal promoter (e.g., TATA box) and enhancer elements in other UCP1-lacking lineages make it unlikely that the enhancer region is pleiotropic (i.e., co-regulates additional genes). Importantly, differential losses of (or mutations within) putative regulatory elements among the eutherian lineages with an intact UCP1 suggests that the transcriptional control of gene expression is not highly conserved in this mammalian clade.


Involvement of the Gli3 (extra-toes) gene region in body weight in mice.
The mutation extra-toes (Gli3Xt-J) on chromosome (Chr) 13 of the mouse is known to be involved in the development of the skeleton. The only visible manifestation is the presence of an extra digit on each hind foot. Here we report evidence from several experiments that Gli3XtJ/+ mice weigh more than littermate Gli3+/+ mice, suggesting an effect on body weight of Gli3 or of a gene tightly linked to it on Chr 13. Four independent experiments in different environments were conducted on mice with different genetic backgrounds derived from the C3XtEso Gli3Xt-J/+ Eso/+ linkage testing strain and the JE/Le strain at adult age. The analyses have shown an association between the Gli3Xt-J allele and a body weight increase of about 6.5%. This effect is genetically dominant. It would appear that if the gene of interest is not Gli3 itself, it must be very close to this locus. Indeed, the expected size for this fragment is 7.9 +/- 5.3 cM. The manifestation of this gene, observed in two animal facilities and on different genetic backgrounds, is consistent with the idea that the effect of the gene(s) is displayed in a stable manner. It accounts for a variation of 6.5% of body weight.


The 19-amino acid insertion in the tumor-associated splice isoform Rac1b confers specific binding to p120 catenin.
The Rac1b splice isoform contains a 19-amino acid insertion not found in Rac1; this insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in the intracellular predominance of GTP-bound Rac1b. Here, using co-precipitation and proteomic methods, we find that Rac1b does not bind to many common regulators of Rho family GTPases but that it does display enhanced binding to SmgGDS, RACK1, and p120 catenin (p120(ctn)), proteins involved in cell-cell adhesion, motility, and transcriptional regulation. We use molecular modeling and structure analysis approaches to determine that the interaction between Rac1b and p120(ctn) is dependent upon protein regions that are predicted to be unstructured in the absence of molecular complex formation, suggesting that the interaction between these two proteins involves coupled folding and binding. We also find that directed cell movement initiated by Rac1b is dependent upon p120. These results define a distinct binding functionality of Rac1b and provide insight into how the distinct phenotypic program activated by this protein may be implemented through molecular recognition of effectors distinct from those of Rac1.


Probable reverse zoonosis of influenza A(H1N1)pdm 09 in a striped skunk (Mephitis mephitis).
Striped skunks (skunks) are susceptible to respiratory infection by influenza A viruses (IAV). As they are common synanthropes, maintenance of IAV in skunks could provide a source of infection for humans. We previously studied the nasal turbinates, lungs and faeces of 50 free-ranging skunks for the presence of IAV and identified two individuals with influenza A(H1N1)pdm09 infection during the 2009/2010 and 2013/2014 flu seasons. Subsequent to publication of that study, ferrets were shown to preferentially replicate and harbour A(H1N1)pdm09 in the soft palate, a site which had not been investigated in the skunks. From March 2015 to May 2016, we surveyed a convenience sample of 80 free-ranging urban skunks for IAV in soft palate, nasal turbinates and lungs. The newly emergent influenza A(H1N1)pdm09 clade 6B.1 was detected at all three sites in one skunk with acute rhinitis in February 2016. Clade 6B.1 was the dominant clade in circulation during the 2015/2016 flu season. As the skunk was detected at the height of flu season, reverse zoonosis was considered the most probable source of infection.


Polyethylene wear and osteolysis after cementless total hip arthroplasty with alumina-on-highly cross-linked polyethylene bearings in patients younger than thirty years of age.
We asked whether cementless total hip arthroplasties that made use of alumina-on-highly cross-linked polyethylene bearings would improve hip score and functional activity and reduce the prevalence of polyethylene wear, osteolysis, and aseptic loosening. Consecutive primary total hip arthroplasties were performed in fifty patients (a total of sixty hips among thirty-four men and sixteen women) who were younger than thirty years of age. The average age at the time of the index arthroplasty was 28.3 years (range, twenty-one to twenty-nine years). The average follow-up was 10.8 years (range, ten to twelve years). Osteolysis and polyethylene wear rates were evaluated with use of radiography and computed tomography. The mean Harris hip score, which was 38 points (range, 6 to 45 points) preoperatively, had improved to 95 points (range, 85 to 100 points) at a mean follow-up time of 10.8 years. The mean penetration (and standard error of the mean) of the polyethylene liner was 0.031 ± 0.004 mm per year. No hip had osteolysis or aseptic loosening. At a minimum of ten years and an average of 10.8 years postoperatively, the current generation of cementless acetabular and femoral components with alumina-on-highly cross-linked polyethylene bearings was functioning well and was not associated with the development of osteolysis in our group of patients younger than thirty years of age. While the long-term prevalence of polyethylene wear and osteolysis remains unknown, the midterm data are promising.


Predicting anti-cancer activity of quinoline derivatives: CoMFA and CoMSIA approach.
The 3D quantitative structure-activity relationships of 31 quinoline nuclei containing compounds and their biological activity have been investigated to establish various models. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies resulted in reliable and significant computational models. The obtained CoMFA model showed high predictive ability with q(2) = 0.592, r(2) = 0.966 and standard error of estimation (SEE) = 0.167, explaining majority of the variance in the data with two principal components. Predictions obtained with CoMSIA steric, electrostatic, hydrophobic, hydrogen-bond acceptor and donor fields (q(2) = 0.533, r(2) = 0.985) showed high prediction ability with minimum SEE (0.111) and four principal components. The information obtained from the CoMFA and CoMSIA contour maps can be utilized for the design and development of topoisomerase-II inhibitors for synthesis.


Social support in an Internet weight loss community.
To describe social support for weight loss shared by members of a large Internet weight loss community. We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes. Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily or more frequent basis. Major social support themes were encouragement and motivation, mentioned at least once by 87.6% of survey respondents, followed by information (58.5%) and shared experiences (42.5%). Subthemes included testimonies, recognition for success, accountability, friendly competition, and humor. Members valued convenience, anonymity, and the non-judgmental interactions as unique characteristics of Internet-mediated support. This Internet weight loss community plays a prominent role in participants' weight loss efforts. Social support within Internet weight loss communities merits further evaluation as a weight loss resource for clinicians to recommend to patients. Understanding these communities could improve how health professionals evaluate, build, harness, and manipulate social support for weight loss.


Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal.
The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We recently found that neurons express several TLRs, and that the levels of TLR2 and TLR4 are increased in neurons in response to energy deprivation. Here we report that TLR4 expression increases in neurons when exposed to amyloid beta-peptide (Abeta1-42) or the lipid peroxidation product 4-hydroxynonenal (HNE). Neuronal apoptosis triggered by Abeta and HNE was mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibited reduced JNK and caspase-3 activation and were protected against apoptosis induced by Abeta and HNE. Levels of TLR4 were decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched control subjects, possibly as the result of loss of neurons expressing TLR4. Our findings suggest that TLR4 signaling increases the vulnerability of neurons to Abeta and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD.


Postoperative Therapy for Chronic Thumb Carpometacarpal (CMC) Joint Dislocation.
Surgical arthroplasty of thumb carpometacarpal (CMC) joint osteoarthritis is commonly performed. Postoperative therapeutic protocols aim to improve range of motion and function of the revised thumb. We describe a case in which the thumb CMC joint had been chronically dislocated before surgery, with shortening of the soft-tissue dynamic and static stabilizers of the joint. The postoperative protocol addressed the soft tissues using splinting and exercises aimed at lengthening and strengthening these structures, with good results. It may be beneficial to evaluate soft-tissue tension and the pattern of thumb use after surgery for thumb CMC joint osteoarthritis to improve postoperative functional results.


Quantum yield measurements of short-lived photoactivation intermediates in DNA photolyase: toward a detailed understanding of the triple tryptophan electron transfer chain.
The light-dependent DNA repair enzyme photolyase contains a unique evolutionary conserved triple tryptophan electron transfer chain (W382-W359-W306 in photolyase from E. coli) that bridges the approximately 15 A distance between the buried flavin adenine dinucleotide (FAD) cofactor and the surface of the protein. Upon excitation of the semireduced flavin (FADH(o)), electron transfer through the chain leads to formation of fully reduced flavin (FADH(-); required for DNA repair) and oxidation of the most remote tryptophan residue W306, followed by its deprotonation. The thus-formed tryptophanyl radical W306(o)(+) is reduced either by an extrinsic reductant or by reverse electron transfer from FADH(-). Altogether the kinetics of these charge transfer reactions span 10 orders of magnitude, from a few picoseconds to tens of milliseconds. We investigated electron transfer processes in the picosecond-nanosecond time window bridging the time domains covered by ultrafast pump-probe and "classical" continuous probe techniques. Using a recent dedicated setup, we directly show that virtually no absorption change between 300 ps and 10 ns occurs in wild-type photolyase, implying that no charge recombination takes place in this time window. In contrast, W306F mutant photolyase showed a partial absorption recovery with a time constant of 0.85 ns. In wild-type photolyase, the quantum yield of FADH(-) W306(o)(+) was found at 19 +/- 4%, in reference to the established quantum yield of the long-lived excited state of [Ru(bpy)(3)](2+). With this yield, the optical spectrum of the excited state of FADH(o) can be constructed from ultrafast spectroscopic data; this spectrum is dominated by excited state absorption extending from below 450 to 850 nm. The new experimental results, taken together with previous data, allow us to propose a detailed kinetic and energetic scheme of the electron transfer chain.


Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer.
Lung cancer is the leading cause of cancer death in the United States. Surgical resection for stage I or II non-small cell cancer remains the only reliable treatment for cure. Patients who do not undergo surgery have a median survival of less than 1 year. Despite the survival disadvantage, many patients with early-stage disease do not receive surgical care and rates are even lower for black patients. To identify potentially modifiable factors regarding surgery in patients newly diagnosed with early-stage lung cancer and to explore why blacks undergo surgery less often than whites. Prospective cohort study with patients identified by pulmonary, oncology, thoracic surgery, and generalist practices in 5 communities through study referral or computerized tomography review protocol. A total of 437 patients with biopsy-proven or probable early-stage lung cancer were enrolled between December 2005 and December 2008. Before establishment of treatment plans, patients were administered a survey including questions about trust, patient-physician communication, attitudes toward cancer, and functional status. Information about comorbid illnesses was obtained through chart audits. Lung cancer surgery within 4 months of diagnosis. A total of 386 patients met full eligibility criteria for lung resection surgery. The median age was 66 years (range, 26-90 years) and 29% of patients were black. The surgical rate was 66% for white patients (n = 179/273) compared with 55% for black patients (n = 62/113; P = .05). Negative perceptions of patient-physician communication manifested by a 5-point decrement on a 25-point communication scale (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.32-0.74) and negative perception of 1-year prognosis postsurgery (OR, 0.27; 95% CI, 0.14-0.50; absolute risk, 34%) were associated with decisions against surgery. Surgical rates for blacks were particularly low when they had 2 or more comorbid illnesses (13% vs 62% for <2 comorbidities; OR, 0.04 [95% CI, 0.01-0.25]; absolute risk, 49%) and when blacks lacked a regular source of care (42% with no regular care vs 57% with regular care; OR, 0.20 [95% CI, 0.10-0.43]; absolute risk, 15%). A decision not to undergo surgery by patients with newly diagnosed lung cancer was independently associated with perceptions of communication and prognosis, older age, multiple comorbidities, and black race. Interventions to optimize surgery should consider these factors.


Cernox thermometer under hydrostatic pressure for enhanced temperature accuracy.
Sensors that can be used in a pressurized environment are few. Thus, it is generally considered that the accuracy of temperature measurements decreases in experiments carried out under pressure. Based on a commercially available cryogenic temperature sensor, Cernox from Lake Shore Cryotronics, Inc., we developed and tested an enclosure that enables Cernox to be directly used inside a cylindrical pressure cell, next to the specimen under investigation. To isolate the Cernox thermometer from the pressurized medium inside the pressure cell, we combined the principles of an encapsulated Pt sensor and a cylindrical clamped piston cell. The encapsulated Cernox allows for precise measurement and control of the specimen's temperature. It is also beneficial for accurately determining small changes in physical properties, such as temperature, or measuring the amount of hysteresis in the first-order phase transition. It would also be useful for accurately controlling the sample's temperature when the sample approaches the transition temperature from one side.


Reduced Cerebrospinal Fluid Inflow to the Optic Nerve in Glaucoma.
To determine whether cerebrospinal fluid (CSF) entry into the optic nerve is altered in glaucoma. Fluorescent 10-kDa dextran tracer was injected into the CSF of 2-month-old (n = 9) and 10-month-old DBA/2J glaucoma mice (n = 8) and age-matched controls (C57Bl/6; n = 8 each group). Intraocular pressure (IOP) was measured in all mice before tracer injection into CSF. Tracer distribution was assessed using confocal microscopy of optic nerve cross-sections of mice killed 1 hour after injection. Paravascular tracer distribution in the optic nerve was studied in relation to isolectin-stained blood vessels. Tracer intensity and cross-sectional area in the laminar optic nerve were quantitatively assessed in all four groups and statistically compared. Aquaporin 4 (AQP4) and retinal ganglion cell axonal phosphorylated neurofilament (pNF) were evaluated using immunofluorescence and confocal microscopy. IOP was elevated in 10-month-old glaucoma mice compared with age-matched controls. One hour after tracer injection, controls showed abundant CSF tracer in the optic nerve subarachnoid space and within the nerve in paravascular spaces surrounding isolectin-labeled blood vessels. CSF tracer intensity and signal distribution in the optic nerve were significantly decreased in 10-month-old glaucoma mice compared with age-matched controls (P = 0.0008 and P = 0.0033, respectively). AQP4 immunoreactivity was similar in 10-month-old DBA and age-matched control mice. Half of the 10-month-old DBA mice (n = 4/8) showed a decrease in pNF immunoreactivity compared to controls. Altered pNF staining was seen only in DBA mice lacking CSF tracer at the laminar optic nerve (n = 4/5). This study provides the first evidence that CSF entry into the optic nerve is impaired in glaucoma. This finding points to a novel CSF-related mechanism that may help to understand optic nerve damage in glaucoma.


Laparoscopic sleeve gastrectomy for obesity: can it be considered a definitive procedure?
Providing bariatric surgery services to an inner-city population is a challenge. Laparoscopic sleeve gastrectomy (LSG) is an effective operation for morbid obesity with a relatively low complication rate. LSG appears to be a suitable alternative procedure for this group of patients. This is a retrospective review and analysis of the experience with 185 consecutive LSGs that had completed at least 6 months follow-up. Eleven conversions from LSG to laparoscopic Roux-en-Y gastric bypass were excluded, leaving 174 patients for outcome analysis. Data collected were patient demographics, body mass index (BMI), comorbid conditions, operating time, length of hospital stay, and perioperative complications. Weight loss and resolution/improvement of comorbidities were analyzed. Mean patient age was 39.58 years and mean BMI was 48.97 kg/m(2). The percentage of patients with BMI > 50 kg/m(2) was 37.94%. Mean excess weight loss (EWL) was 44.76, 55.52, 59.22, and 58.92% at 6, 12, 24, and 36 months, respectively. Six patients (3.24%) lost less than 25% EWL. Thirteen patients (7.02%) regained an average of 13 lb after reaching a plateau. Resolution/improvement of comorbidities was 84% for diabetes mellitus, 49.99% for hypertension, 90% for asthma, 90.74% for obstructive sleep apnea, and 45.92% for gastroesophageal reflux disease symptoms (GERD). The mortality rate was zero in this series. Perioperative complications occurred in 26 patients (14.05%): four staple-line leaks (2.16%), four bleeds (2.16%), four obstructions (2.16%), five vomiting/dehydration (2.70%), six new onset of GERD symptoms (3.24%), two with pneumonia (1.08%), and one with pulmonary embolism (0.54%). LSG results in stable and adequate weight loss with resolution/improvement in comorbidities in a high percentage of patients. It can be considered a definitive operation for morbid obesity.


Scapular rotation in swimmers with and without impingement syndrome: practice effects.
The purpose of this study was to examine the effects of a normal swim practice on the scapular kinematics of swimmers with impingement syndrome and healthy swimmers. Twenty swimmers with no known shoulder pathology and 20 swimmers with shoulder impingement syndrome participated in this study. Shoulder strength measurements were made with a hand-held dynamometer. Static scapular upward rotation was measured with an inclinometer with the arm at rest, and at 45, 90, and 135 degrees of humeral elevation. Measurements were made pre- and postswim training. There were no differences in baseline measurements of kinematics between the two groups. After swimming, both groups experienced muscle fatigue as indicated by a significant reduction in force generation. Although swimming practice resulted in no significant differences in scapular kinematics for the healthy swimmers, there were significant decreases in scapular upward rotation in subjects with shoulder impingement. Abnormal scapular kinematics in swimmers with impingement syndrome may only be observed after an intense swim practice. The examination of swimmers immediately after swimming may provide more information regarding impingement syndrome than a typical clinical exam.


Dynamic Changes of Functional Pain Connectome in Women with Primary Dysmenorrhea.
Primary dysmenorrhea (PDM) is the most prevalent gynecological problem. Many key brain systems are engaged in pain processing. In light of dynamic communication within and between systems (or networks) in shaping pain experience and behavior, the intra-regional functional connectivity (FC) in the hub regions of the systems may be altered and the functional interactions in terms of inter-regional FCs among the networks may be reorganized to cope with the repeated stress of menstrual pain in PDM. Forty-six otherwise healthy PDM subjects and 49 age-matched, healthy female control subjects were enrolled. Intra- and inter-regional FC were assessed using regional homogeneity (ReHo) and ReHo-seeded FC analyses, respectively. PDM women exhibited a trait-related ReHo reduction in the ventromedial prefrontal cortex, part of the default mode network (DMN), during the periovulatory phase. The trait-related hypoconnectivity of DMN-salience network and hyperconnectivity of DMN-executive control network across the menstrual cycle featured a dynamic transition from affective processing of pain salience to cognitive modulation. The altered DMN-sensorimotor network may be an ongoing representation of cumulative menstrual pain. The findings indicate that women with long-term PDM may develop adaptive neuroplasticity and functional reorganization with a network shift from affective processing of salience to the cognitive modulation of pain.


A survey of phthalates and parabens in personal care products from the United States and its implications for human exposure.
Despite the widespread usage of phthalates and parabens in personal care products (PCPs), little is known about concentrations and profiles as well as human exposure to these compounds through the use of PCPs. In this study, nine phthalates and six parabens were determined in 170 PCPs (41 rinse-off and 109 leave-on), including 20 baby care products collected from Albany, New York. Phthalates were less frequently found in rinse-off PCPs but were more frequently found in perfumes (detection frequency of 100% for diethyl phthalate [DEP], 67% for dibutyl phthalate [DBP]), skin toners (90% for DEP), and nail polishes (90% for DBP). Parabens were found in ∼40% of rinse-off products and ∼60% of leave-on products. The highest concentrations of DEP, DBP, methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl parabens (BuP) were on the order of 1000 μg per gram of the product. On the basis of amount and frequency of use of PCPs and the measured median concentrations of target analytes, the total dermal intake doses (sum of all phthalates or parabens) were calculated to be 0.37 and 31.0 μg/kg-bw/day for phthalates and parabens, respectively, for adult females. The calculated dermal intake of phthalates from PCPs was lower for infants and toddlers than for adult females. In contrast, dermal intake of parabens from PCPs by infants and toddlers was higher than that for adult females. The calculated maximum daily exposure dose of MeP, EtP, and PrP from PCPs ranged between 58.6 and 766 μg/kg-bw/day for infants and toddlers, which was 3 times higher than that calculated for adult females. PCPs are an important source of human exposure to parabens; the contribution of PCPs to phthalate exposure is low, except for DEP.


Production of CD8+ T cell nonlytic suppressive factors by CD28, CD38, and HLA-DR subpopulations.
HIV infection may be modified by CD8(+) T cells by the production of nonlytic antiviral factors. To determine subpopulations that mediate nonlytic, antiviral activity, we examined the production of beta chemokines and of CD8 antiviral factor (CAF) by different subsets, using CD8(+) cells derived from 24 HIV-1-infected and 25 uninfected individuals. Subjects with CD8(+) cell counts greater than 200/microl produced increased levels of MIP-1alpha by CD8(+)CD28(+), CD8(+)CD38(-), and CD8(+)HLA-DR(+) subsets as compared with uninfected controls. CD8(+)CD38(-) cells produced higher levels of MIP-1beta and RANTES. CAF production was increased by CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells of HIV-infected individuals as compared with uninfected controls. Chemokine production was increased by cells that do not express activation markers, whereas CAF activity was increased by cells expressing CD38 or HLA-DR. These findings shed light on CD8(+) T cell noncytotoxic antiviral factor production during HIV infection.


The influence of postoperative acromial and scapular spine fractures on the results of reverse shoulder arthroplasty.
Fractures of the acromion or scapular spine are recognized complications of reverse arthroplasty. This study reviewed the outcome of reverse arthroplasties with such fractures and compared the results to arthroplasties without the fractures. A consecutive series of 125 reverse arthroplasties were reviewed for the development of a postoperative acromial or scapular spine fracture. Nine cases were identified, all treated nonoperatively. Five fractures occurred from falls, and the remainder were fatigue fractures. These results were compared to 67 patients with similar diagnoses in the series without such fractures. No significant differences existed between the 2 groups in terms of age, sex, side of surgery, or diagnosis. Preoperatively, both groups had substantial pain, limitation of motion, and poor American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) outcome scores. No significant differences existed between the 2 groups. At minimum 1-year follow-up, results in the shoulders with fractures were improved. Mean visual analog score (VAS) was 4.0, flexion was 89.3 degrees, ASES score was 47.9, and SST score was 5.6. Nevertheless, these results were inferior to those in shoulders without a fracture, whose mean VAS was 0.7, flexion was 152.1 degrees, ASES score was 87.7, and SST score was 10.2. Nonoperative management was chosen in these cases due to a concern that stable fixation would not be obtained with surgery. Although the final outcome was diminished, these patients improved their preoperative state. A decision for surgical treatment will need to weigh the challenges of internal fixation with the incremental improvement that may occur with improved fracture healing.


Interaction analyses of SARS-CoV-2 spike protein based on fragment molecular orbital calculations.
At the stage of SARS-CoV-2 infection in human cells, the spike protein consisting of three chains, A, B, and C, with a total of 3300 residues plays a key role, and thus its structural properties and the binding nature of receptor proteins to host human cells or neutralizing antibodies has attracted considerable interest. Here, we report on interaction analyses of the spike protein in both closed (PDB-ID: 6VXX) and open (6VYB) structures, based on large-scale fragment molecular orbital (FMO) calculations at the level of up to the fourth-order Møller-Plesset perturbation with singles, doubles, and quadruples (MP4(SDQ)). Inter-chain interaction energies were evaluated for both structures, and a mutual comparison indicated considerable losses of stabilization energies in the open structure, especially in the receptor binding domain (RBD) of chain-B. The role of charged residues in inter-chain interactions was illuminated as well. By two separate calculations for the RBD complexes with angiotensin-converting enzyme 2 (ACE2) (6M0J) and B38 Fab antibody (7BZ5), it was found that the binding with ACE2 or antibody partially compensated for this stabilization loss of RBD.


The Code of the Street Fights Back! Significant Associations with Arrest, Delinquency, and Violence Withstand Psychological Confounds.
Since Anderson's now classic, Code of the Street: Decency, Violence, and the Moral Life of the Inner City, an increasing number of researchers have found a significant association between the code of the street and antisocial behavior. Less researched, however, is the relationship between the code of the street and cognate psychological factors. Building on the hypothesis that the code of the street is simply a reflection of elements of the population who exhibit antisocial traits, our aim in this study is to empirically test whether the observed association between the code of the street and antisocial behavior can withstand psychological confounds among a sample of institutionalized juvenile delinquents. Negative binomial regression models show that the code of the street remained a significant predictor of antisocial behavior despite the specification of psychopathy and temperamental traits and other controls. Moreover, as theorized, differential effects were found for African American delinquents compared to non-African American delinquents. We discuss theoretical and practical implications.


Terpenoid bio-transformations and applications via cell/organ cultures: a systematic review.
Structurally diverse natural products are valued for their targeted biological activity. The challenge of working with such metabolites is their low natural abundance and complex structure, often with multiple stereocenters, precludes large-scale or unsophisticated chemical synthesis. Since select plants contain the enzymatic machinery necessary to produce specialized compounds, tissue cultures can be used to achieve key transformations for large-scale chemical and/or pharmaceutical applications. In this context, plant tissue-culture bio-transformations have demonstrated great promise in the preparation of pharmaceutical products. This review describes the capacity of cultured plant cells to transform terpenoid natural products and the specific application of such transformations over the past three decades (1988-2019).


Ultra-small wavelength splitters in a subwavelength plasmonic waveguide.
Miniaturizing optical devices beyond the diffraction limit is of great importance for high-integration photonic circuits. By directly fabricating a double-slit aperture structure of different sizes in a subwavelength plasmonic waveguide, an ultra-small plasmonic wavelength splitter is realized experimentally. Due to the different slit widths, the surface plasmon polaritons (SPPs) in the opposite directions exhibit anti-phase interferences. As a result, the SPPs excited at different wavelengths can be split to propagate in the opposite directions along the subwavelength plasmonic waveguide. The plasmonic wavelength splitter only occupies a footprint of about 1.4 μm² on the metal surface, and the splitting wavelengths and their separation can be easily varied by adjusting the structural parameters. This provides it with important applications in the areas of the optical modulating, sensing, and computing networks in highly integrated plasmonic circuits.


Does the declining lethality of gunshot injuries mask a rising epidemic of gun violence in the United States?
Recent mass shootings in the U.S. have reignited the important public health debate concerning measures to decrease the epidemic of gun violence. Editorialists and gun lobbyists have criticized the recent focus on gun violence, arguing that gun-related homicide rates have been stable in the last decade. While true, data from the U.S. Centers for Disease Control and Prevention also demonstrate that although gun-related homicide rates were stable between 2002 and 2011, rates of violent gunshot injuries increased. These seemingly paradoxical trends may reflect the declining lethality of gunshot injuries brought about by surgical advances in the care of the patient with penetrating trauma. Focusing on gun-related homicide rates as a summary statistic of gun violence, rather than total violent gunshot injuries, can therefore misrepresent the rising epidemic of gun violence in the U.S.


Ignoring Clustering in Confirmatory Factor Analysis: Some Consequences for Model Fit and Standardized Parameter Estimates.
In many situations, researchers collect multilevel (clustered or nested) data yet analyze the data either ignoring the clustering (disaggregation) or averaging the micro-level units within each cluster and analyzing the aggregated data at the macro level (aggregation). In this study we investigate the effects of ignoring the nested nature of data in confirmatory factor analysis (CFA). The bias incurred by ignoring clustering is examined in terms of model fit and standardized parameter estimates, which are usually of interest to researchers who use CFA. We find that the disaggregation approach increases model misfit, especially when the intraclass correlation (ICC) is high, whereas the aggregation approach results in accurate detection of model misfit in the macro level. Standardized parameter estimates from the disaggregation and aggregation approaches are deviated toward the values of the macro- and micro-level standardized parameter estimates, respectively. The degree of deviation depends on ICC and cluster size, particularly for the aggregation method. The standard errors of standardized parameter estimates from the disaggregation approach depend on the macro-level item communalities. Those from the aggregation approach underestimate the standard errors in multilevel CFA (MCFA), especially when ICC is low. Thus, we conclude that MCFA or an alternative approach should be used if possible.


Potential antibacterial activity of some Saudi Arabia honey.
The aim of this study was to investigate the potential antibacterial activity of some Saudi Arabia honey against selected bacterial strains of medical importance. A total of 10 Saudi Arabia honey used to evaluate their antimicrobial activity against some antibiotic-resistant pathogenic bacterial strains. The bacterial strains were Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. The antibacterial activity of Saudi honey against five bacterial strains showed different levels of inhibition according to the type of honey. The overall results showed that the potential activity was differing according to the pathogen and honey type. It could be concluded that the Saudi honey inhibit the growth of bacterial strains and that honey can be used as complementary antimicrobial agent against selected pathogenic bacteria.


Sentinel lymph node mapping and biopsy for breast cancer: a review of the literature relative to 4791 procedures.
The status of axillary nodes is the most important prognostic factor in breast cancer to select patient subgroups for adjuvant chemotherapy; the current standard of care for surgical management of invasive breast cancer is complete removal of the tumor by either mastectomy or lumpectomy followed by axillary lymph node dissection (ALND). The recent introduction of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLND) represents a major new opportunity for appropriate and less invasive surgical management of many tumors. There is an almost uniformly enthusiasm concerning the potential of this technique in breast carcinoma management, shown by published data. A peculiar attention to the so-called "sentinel node debate" in breast cancer surgery is a constant in the last years issues of the major medical journals. Even patients have become more aware about medical enthusiasm and their request of concise information on the topic and the possibilities of this approach is an increasing reality in medical practice. The aim of this paper is to review recent literature to offer an overview about the main controversial methodological aspects and a wide analysis of reported results. The most significative international literature papers from Medline were retrieved from 1993 to September 1999, and 4782 procedures were analysed. This extensive review of the literature has confirmed accuracy, feasibility and reliability of the SN detecting technique in axillary mapping. Provided a good proficiency in SN localisation and pathological evaluation, human resources and efforts should be mainly focused on its clinical validation as an alternative to ALND instead of on further phase I-lI clinical studies.


Pulmonary hemodynamics and alveolar oxygenation in healthy dogs anesthetized with propofol or isoflurane during one-lung ventilation in a closed-thoracic experimental model.
OBJECTIVE To assess pulmonary hemodynamics and alveolar oxygenation in dogs anesthetized with propofol or isoflurane during one-lung ventilation (OLV) in a closed-thoracic experimental model. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized with each of 3 protocols (constant rate IV infusion of propofol [0.4 to 1.0 mg/kg/min], isoflurane at the minimum alveolar concentration [MAC], and isoflurane 1.5 MAC), with a 7-day washout period between anesthetic sessions. During each session, dogs were intubated with a double-lumen endotracheal tube, positioned in right lateral recumbency, and administered atracurium (0.1 to 0.2 mg/kg, IV, q 30 min) to allow mechanical ventilation throughout a 2-hour observation period. Dogs underwent two-lung ventilation for 30 minutes, OLV of the right lung for 1 hour, and two-lung ventilation for another 30 minutes. Pulmonary hemodynamic and blood gas variables were evaluated at predetermined times and compared among protocols and over time within each protocol. RESULTS Alveolar oxygenation was not impaired, and mean heart rate and pulmonary artery pressure and occlusion pressure were similar among the 3 protocols. One-lung ventilation caused a significant increase in the arteriovenous shunt fraction only when dogs were anesthetized with isoflurane at 1.5 MAC. Dogs developed respiratory acidosis, which was exacerbated by OLV, during all anesthetic sessions. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated pulmonary hemodynamics and alveolar oxygenation during OLV in a closed-thoracic model were similar regardless of whether dogs were anesthetized with propofol or isoflurane. One-lung ventilation can be successfully performed in dogs by use of a double-lumen endotracheal tube and either propofol or isoflurane.


Establishment of a clinically relevant specification for dissolution testing using physiologically based pharmacokinetic (PBPK) modeling approaches.
This paper presented how to establish a clinically relevant specification (CRS) using in silico physiologically based pharmacokinetic (PBPK) modeling. Three different formulations of model drug products were used in the clinical studies in order to distinguish between bioequivalent (BE) batches from non-BE batches. A human PBPK model was constructed by integrating the clinical and non-clinical observations by using GastroPlusTM software. The developed model was verified by the comparison between human PK behavior observed in clinical studies and human PK behavior predicted from the software. The simulation results were obtained by using the dissolution profiles showing clinically relevant discriminatory power as input variables for the developed PBPK model. For three investigated formulations, the simulated PK behavior was comparable to the PK behavior observed in clinical studies. In addition, in silico BE simulation studies confirmed that the verified PBPK model can successfully reproduce the clinical study results. In conclusion, a CRS was established with the BE simulation by using the verified PBPK model, in order to detect and reject non-BE batches of drug products. The establishment of the CRS is useful for a quality control and finding optimal formulation to accomplish target PK behavior, safety, and efficacy.


Loading of the Hip and Knee During Swimming: An in Vivo Load Study.
Swimming is commonly recommended as postoperative rehabilitation following total hip arthroplasty (THA) and total knee arthroplasty (TKA). So far, in vivo hip and knee joint loads during swimming remain undescribed. In vivo hip and knee joint loads were measured in 6 patients who underwent THA and 5 patients who underwent TKA with instrumented joint implants. Joint loads, including the resultant joint contact force (FRes), torsional moment around the femoral shaft axis or the tibial axis (MTors), bending moment at the middle of the femoral neck (MBend), torsional moment around the femoral neck axis (MTne), and medial force ratio (MFR) in the knee, were measured during breaststroke swimming at 0.5, 0.6, and 0.7 m/s and the breaststroke and crawl kicks at 0.5 and 1.0 m/s. The ranges of the median maximal FRes were 157% to 193% of body weight for the hip and 93% to 145% of body weight for the knee during breaststroke swimming. Greater maxima of FRes (hip and knee), MTors (hip and knee), MBend (hip), and MTne (hip) were observed with higher breaststroke swimming velocities, but significance was only identified between 0.5 and 0.6 m/s in FRes (p = 0.028), MTors (p = 0.028), and MBend (p = 0.028) and between 0.5 and 0.7 m/s in FRes (p = 0.045) in hips. No difference was found in maximal MFR between different breaststroke swimming velocities. The maximal FRes was significantly positively correlated with the breaststroke swimming velocity (hip: r = 0.541; p < 0.05; and knee: r = 0.414; p < 0.001). The maximal FRes (hip and knee) and moments (hip) were higher in the crawl kick than in the breaststroke kick, and a significant difference was recognized in FRes Max for the hip: median, 179% versus 118% of body weight (p = 0.028) for 0.5 m/s and 166% versus 133% of body weight (p = 0.028) for 1.0 m/s. Swimming is a safe and low-impact activity, particularly recommended for patients who undergo THA or TKA. Hip and knee joint loads are greater with higher swimming velocities and can be influenced by swimming styles. Nevertheless, concrete suggestions to patients who undergo arthroplasty on swimming should involve individual considerations. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Diagnosis and immunotherapy of mould allergy. IV. Relation between asthma symptoms, spore counts and diagnostic tests.
Twenty-four adult asthmatics with autumnal asthma and positive bronchial provocation test to the mould species Cladosporium were evaluated by daily symptoms scores during 11 weeks in the peak mould spore season. A significant association with fluctuation in Cladosporium spore count was found regarding the relative weekly symptom score (mean of subjective asthma and peak flow scores), relative use of antiasthmatic medication and the combined (total) score (mean of symptom and medication scores). The median weekly symptom, medication, and total scores were positively correlated to Cladosporium spore count, but only significantly so in the medication score. Eighteen patients were allergic to both Cladosporium and Alternaria, but asthma symptoms were not associated to Alternaria spore counts; on the contrary, a negative correlation indicated that Alternaria only played a minor role in eliciting asthma. Neither mugwort nor house dust mites seemed to be of importance. The results of diagnostic tests (bronchial provocation test, quantitative skin prick test, RAST and histamine release) were correlated to the mean absolute symptom score of the spore season. The highest correlation to asthma score, peak flow score, medication score, and the combined score was found with the bronchial provocation test. The data indicate that autumnal asthma, to a high degree, is elicited by Cladosporium spores, and further, that the specific allergic diagnosis can only be established by a combination of positive diagnostic tests and careful recording of symptoms elicited by the causative allergen.


LIVES for families psychological first aid training programme to address COVID-19 psychological distress: a mixed methods acceptability and feasibility protocol.
Best practice approaches for addressing COVID-19-related psychological distress among young people (<25 years) and their families remain unclear. Psychological first aid (PFA) is promoted by public health authorities to provide psychological support in the context of extreme events; however, there is limited evidence for its effectiveness. As a prerequisite to conducting a randomised controlled trial to examine programme effectiveness, this project is evaluating the acceptability and feasibility of implementing and evaluating a PFA training programme ('LIVES for Families') for mental health (MH) practitioners to improve their ability to recognise and respond to COVID-19-related psychological distress among their clients. We are using a triangulation mixed methods research design; complementary strands of quantitative and qualitative data are being collected in parallel and will be merged at the interpretation phase of the project. The quantitative strand uses a repeated measures design; a consecutive sample of MH practitioners (n=80) providing MH support to young people or their families are being recruited to participate in the LIVES for Families PFA training programme and complete quantitative measures at baseline (pretraining), 2-week and 6-month follow-up time points. The qualitative strand uses fundamental description and semistructured interviews with a subset of practitioners (n=30), as well as managers of MH agencies (n=20). A mixed methods joint display and associated narrative will generate a comprehensive understanding regarding acceptability and feasibility. The Hamilton Integrated Research Ethics Board approved the study (project number: 11295). Results will be shared broadly with the policy and practice community through publications, presentations and public webinars. As a brief, evidence-informed intervention, the LIVES for Families PFA training programme is suitable in its mode of delivery across care settings. The outcomes of this study could have international implications for mitigating the MH impacts of viral pandemics.


Setting specifications for potency assays--basic principles.
To develop any biological therapeutic successfully, it is necessary to characterise the product thoroughly, both physicochemically and biologically. To ensure that consistency of production is maintained, some level of control is required to limit the variability of the product from batch to batch. This premise forms the basis of specification setting. The biological activity or potency of the product must be appropriately assessed through a functional assay unless specifically justified otherwise e.g. for binding proteins where binding has been correlated with biological activity. Biological assays are particularly prone to assay variability and therefore it is necessary to design and execute the assay to reduce variability as much as possible while providing a statistically valid measure of the reproducibility of potency estimates. Therefore, specifications for potency should only be derived following establishment of a well validated and controlled bioassay and should include some measure of the variability of the estimate in addition to the actual potency estimate itself. The limits applied to those specifications need to reflect the true batch to batch consistency of the product, its nature and toxicity as well as its intended use.


Caspase cleavage of gasdermin E causes neuronal pyroptosis in HIV-associated neurocognitive disorder.
Despite effective anti-retroviral therapies, 20-30% of persons with treated HIV infection develop a neurodegenerative syndrome termed HIV-associated neurocognitive disorder (HAND). HAND is driven by HIV expression coupled with inflammation in the brain but the mechanisms underlying neuronal damage and death are uncertain. The inflammasome-pyroptosis axis (IPA) coordinates an inflammatory type of regulated lytic cell death that is underpinned by the caspase-activated pore-forming gasdermin proteins. The mechanisms driving neuronal pyroptosis were investigated herein in models of HAND, using multi-platform molecular and morphological approaches that included brain tissues from persons with HAND and simian immunodeficiency virus (SIV)-infected nonhuman primates as well as cultured human neurons. Neurons in the frontal cortices from persons with HAND showed increased cleaved gasdermin E (GSDME), which was associated with βIII-tubulin degradation and increased HIV levels. Exposure of cultured human neurons to the HIV-encoded viral protein R (Vpr) elicited time-dependent cleavage of GSDME and Ninjurin-1 (NINJ1) induction with associated cell lysis that was inhibited by siRNA suppression of both proteins. Upstream of GSDME cleavage, Vpr-exposure resulted in activation of caspases-1 and -3. Pre-treatment of Vpr-exposed neurons with the caspase-1 inhibitor, VX-765, reduced cleavage of both caspase-3 and GSDME, resulting in diminished cell death. To validate these findings, we examined frontal cortical tissues from SIV-infected macaques, disclosing increased expression of GSDME and NINJ1 in cortical neurons, which was co-localized with caspase-3 detection in animals with neurological disease. Thus, HIV infection of the brain triggers the convergent activation of caspases-1 and -3, which results in GSDME-mediated neuronal pyroptosis in persons with HAND. These findings demonstrate a novel mechanism by which a viral infection causes pyroptotic death in neurons while also offering new diagnostic and therapeutic strategies for HAND and other neurodegenerative disorders.


Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15.
The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system that allows the two parental chromosomes to be studied independently. We profiled the paternal and maternal methylation on chromosome 15 using immunoprecipitation of methylated DNA and hybridization to tiling oligonucleotide arrays. Comparison of six individuals with maternal versus paternal UPD15 revealed 12 differentially methylated regions (DMRs). Putative DMRs were validated by bisulfite sequencing, confirming the presence of parent-of-origin-specific methylation marks. We detected DMRs associated with known imprinted genes within the Prader-Willi/Angelman syndrome region, such as SNRPN and MAGEL2, validating this as a method of detecting imprinted loci. Of the 12 DMRs identified, eight were novel, some of which are associated with genes not previously thought to be imprinted. These include a site within intron 2 of IGF1R at 15q26.3, a gene that plays a fundamental role in growth, and an intergenic site upstream of GABRG3 that lies within a previously defined candidate region conferring an increased maternal risk of psychosis. These data provide a map of parent-of-origin-specific epigenetic modifications on chromosome 15, identifying DNA elements that may play a functional role in the imprinting process. Application of this methodology to other chromosomes for which UPD has been reported will allow the systematic identification of imprinted sites throughout the genome.


Procalcitonin as a biomarker in respiratory tract infection.
Serum procalcitonin (PCT) levels rapidly increase in patients with invasive bacterial disease. PCT levels increase faster than do C-reactive protein levels. Furthermore, a rapid decrease in the PCT level is supporting evidence that the source of the bacterial infection is responding to clinical management. In patients with community-acquired bacterial pneumonia, sequential PCT levels are useful as a guide to shorter courses of antimicrobial therapy. With use of emerging multiplex real-time polymerase chain reaction platforms for the detection of viral and bacterial respiratory pathogens, it should be possible to critically assess whether an elevated serum PCT level is a valid biomarker of invasive bacterial infection.


Effects of a combined strengthening, stretching and functional training program versus usual-care on gait biomechanics and foot function for diabetic neuropathy: a randomized controlled trial.
Polyneuropathy is a complication of diabetes mellitus that has been very challenging for clinicians. It results in high public health costs and has a huge impact on patients' quality of life. Preventive interventions are still the most important approach to avoid plantar ulceration and amputation, which is the most devastating endpoint of the disease. Some therapeutic interventions improve gait quality, confidence, and quality of life; however, there is no evidence yet of an effective physical therapy treatment for recovering musculoskeletal function and foot rollover during gait that could potentially redistribute plantar pressure and reduce the risk of ulcer formation. A randomised, controlled trial, with blind assessment, was designed to study the effect of a physiotherapy intervention on foot rollover during gait, range of motion, muscle strength and function of the foot and ankle, and balance confidence. The main outcome is plantar pressure during foot rollover, and the secondary outcomes are kinetic and kinematic parameters of gait, neuropathy signs and symptoms, foot and ankle range of motion and function, muscle strength, and balance confidence. The intervention is carried out for 12 weeks, twice a week, for 40-60 min each session. The follow-up period is 24 weeks from the baseline condition. Herein, we present a more comprehensive and specific physiotherapy approach for foot and ankle function, by choosing simple tasks, focusing on recovering range of motion, strength, and functionality of the joints most impaired by diabetic polyneuropathy. In addition, this intervention aims to transfer these peripheral gains to the functional and more complex task of foot rollover during gait, in order to reduce risk of ulceration. If it shows any benefit, this protocol can be used in clinical practice and can be indicated as complementary treatment for this disease. ClinicalTrials.gov Identifier: NCT01207284.


The PeptideAtlas of a widely cultivated fish Labeo rohita: A resource for the Aquaculture Community.
Labeo rohita (Rohu) is one of the most important fish species produced in world aquaculture. Integrative omics research provides a strong platform to understand the basic biology and translate this knowledge into sustainable solutions in tackling disease outbreak, increasing productivity and ensuring food security. Mass spectrometry-based proteomics has provided insights to understand the biology in a new direction. Very little proteomics work has been done on 'Rohu' limiting such resources for the aquaculture community. Here, we utilised an extensive mass spectrometry based proteomic profiling data of 17 histologically normal tissues, plasma and embryo of Rohu to develop an open source PeptideAtlas. The current build of "Rohu PeptideAtlas" has mass-spectrometric evidence for 6015 high confidence canonical proteins at 1% false discovery rate, 2.9 million PSMs and ~150 thousand peptides. This is the first open-source proteomics repository for an aquaculture species. The 'Rohu PeptideAtlas' would promote basic and applied aquaculture research to address the most critical challenge of ensuring nutritional security for a growing population.


Cognitive and psychiatric comorbidities in neuromyelitis optica.
Our primary objective was to examine the neuropsychological and psychopathological profile of patients with neuromyelitis optica (NMO) and compare these to multiple sclerosis (MS) and healthy control (HC) groups. We also examined for relationships between cognitive and psychiatric variables and clinical factors including accumulated neurological disability and disease duration. A neuropsychological test battery was administered along with a structured psychiatric interview and quantitative measures of mood symptoms. 42 NMO, 42 MS and 42 HC participants were assessed. Cognitive impairments were observed in 67% of NMO patients. The prevalence and profile of cognitive impairments and lifetime prevalence of depression was similar between NMO and MS groups. However, significantly higher rates of recurrent depression and suicidality were observed in NMO patients. Correlational analyses revealed higher levels of anxiety symptoms were associated with shorter disease duration in NMO, while higher depression symptom levels were associated with higher neurological disability and poorer cognition. Our results demonstrate substantial cognitive and psychiatric comorbidities in NMO patients. Similar rates of lifetime and current depression between NMO and MS appear to mask greater underlying psychiatric burden in NMO and further understandings of the course of neurobehavioural comorbidities is required to better comprehend the additional morbidity in NMO. Our data support a role for cognitive and psychiatric assessments in the comprehensive care of NMO patients.


Chinese dumpling scare hits Japan--a case of methamidophos food poisoning.
An outbreak of food poisoning that affected at least ten people in various regions of Japan was traced to exposure to Chinese dumplings contaminated with the organophosphate insecticide Methamidophos. We experienced the most serious case, a five years old girl, who suffered coma. She presented with features of cholinergic overactivity and her serum cholinesterase activity was 9 U/l. We started intravenous treatment with pralidoxime iodide, atropine sulfate, and midazolam. Her symptoms improved gradually and she was discharged on day 25 without any sequelae. Though poisoning attributed to organophosphate insecticides has become less common in recent years, it is even more important to diagnose the problem rapidly based on the characteristic symptoms and to start specific treatment at the earliest possible stage after poisoning.


Does Bt rice pose risks to non-target arthropods? Results of a meta-analysis in China.
Transgenic Bt rice expressing the insecticidal proteins derived from Bacillus thuringiensis Berliner (Bt) has been developed since 1989. Their ecological risks towards non-target organisms have been investigated; however, these studies were conducted individually, yielding uncertainty regarding potential agroecological risks associated with large-scale deployment of Bt rice lines. Here, we developed a meta-analysis of the existing literature to synthesize current knowledge of the impacts of Bt rice on functional arthropod guilds, including herbivores, predators, parasitoids and detritivores in laboratory and field studies. Laboratory results indicate Bt rice did not influence survival rate and developmental duration of herbivores, although exposure to Bt rice led to reduced egg laying, which correctly predicted their reduced abundance in Bt rice agroecosystems. Similarly, consuming prey exposed to Bt protein did not influence survival, development or fecundity of predators, indicating constant abundances of predators in Bt rice fields. Compared to control agroecosystems, parasitoid populations decreased slightly in Bt rice cropping systems, while detritivores increased. We draw two inferences. One, laboratory studies of Bt rice showing effects on ecological functional groups are mainly either consistent with or more conservative than results of field studies, and two, Bt rice will pose negligible risks to the non-target functional guilds in future large-scale Bt rice agroecosystems in China.


"That's not me anymore": Resistance strategies for managing intersectional stigmas for women with substance use and incarceration histories.
Significant previous research has focused on how individuals experience stigma when interacting with the public sphere and service agencies; the purpose of this grounded theory study is to explore how formerly incarcerated mothers with histories of substance use experience stigmas from their intimate relationships with family and romantic partners. Using an intersectionality lens, this study reveals that the women perceived multiple stigmas due to their previous substance use, incarceration, and other addiction-related behaviors that challenged their roles as mothers and romantic partners. Compounding the behavioral-related stigmas were race and class-based stereotypes of black criminality that also challenged women's ability to embody key motherhood and womanhood roles. As a result, the women employed resistance strategies to safeguard against stigma and preserve their recovery. The implications for practice underscore the significance of addressing personal experiences of stigma, complex relational dynamics, and understanding the needs of support systems that are also shaped by the women's cycles of incarceration and illness.


High school youth and suicide risk: exploring protection afforded through physical activity and sport participation.
Suicide ranks as the third leading cause of death for adolescents. Recent data from the Centers for Disease Control and Prevention (CDC) indicate that the adolescent suicide rate increased 18% between 2003 and 2004. Sport may represent a promising protective factor against adolescent suicide. This study examined the relative risk of hopelessness and suicidality associated with physical activity and sport participation. Data from the CDC's 2005 Youth Risk Behavior Survey were analyzed. Logistic regression modeling was used to compare the odds of hopelessness and suicidality in students who engaged in various levels of physical activity to inactive students. Similar analyses were performed comparing risks of athletes to nonathletes, and the risks of highly involved athletes to nonathletes. Findings showed that frequent, vigorous activity reduced the risk of hopelessness and suicidality among male adolescents. However, low levels of activity actually increased the risk of feeling hopeless among young females. Yet, for both males and females, sport participation protected against hopelessness and suicidality. These findings indicate that involvement in sport confers unique psychosocial benefits that protect adolescents against suicidality. Findings suggest that mechanisms other than physical activity contribute to the protective association between sport and reduced suicidality. Social support and integration may account for some of the differences found in suicidality between athletes and nonathletes.


The evolution of robotic thoracic surgery.
Robotic surgery has the features to represent the future of surgery, considering the rapid evolution of its technology and the resulting in the surgical field. In the last years, the robotic technique in thoracic surgery has progressively become widespread in the word, particularly for the treatment of the mediastinal and pulmonary lesions. The development of technology in the robotic system has been associated with the improvement of intraoperative and postoperative results. Due to the satisfying results and increasing experience and confidence with the robotic technique, surgeons are consequently enlarging the surgical indication, moving to increasingly challenging cases. Thoracic robotic surgery is being affirmed as a safe technique also for those complex cases, which in the past were considered a matter solely for open surgery. In fact, robotic surgery is increasingly associated with positive surgical results and guarantees less traumatism and a fast recovery to the patients. These positive results have resulted from the evolution of the technique, which has developed in parallel with the evolution of the technology, exploiting to its best the latest features of the robotic system. These features, such as the fluorescence-detection tool or the robotic stapler, have been aiding the surgeon to maximise the safety and feasibility of the application of the robotic technique to thoracic surgery.


Diagnostic utility of P63 and CD10 in distinguishing cutaneous spindle cell/sarcomatoid squamous cell carcinomas and atypical fibroxanthomas.
The pathologic distinction of atypical fibroxanthomas (AFXs) from cutaneous spindle cell/sarcomatoid squamous cell carcinomas (SCSCCs) may occasionally pose a significant diagnostic challenge, given the substantial clinicopathologic overlap between these lesions. Recent studies indicate that p63 and CD10 are expressed in significant proportions of SCSCC and AFX, respectively. The purpose of this study is to investigate the utility of CD10 and p63 in distinguishing cutaneous SCSCCs and AFXs. The immunohistochemical expression of p63, CD10, cytokeratin AE-1/3, cytokeratin 5/6 and a cytokeratin cocktail (Kermix) was evaluated in an archived group of 23 AFXs and 10 SCSCCs. CD10 was positive in 18/23 AFXs (78%), with most demonstrating strong and/or diffuse staining. Three of 23 AFXs (13%), all negative for cytokeratins, showed focal and weak nuclear staining for p63. Two of 23 AFXs (9%) demonstrated very focal or weak staining for only one cytokeratin; in both cases, p63 and CD10 were negative. One AFX was negative with all immunostains. CD10 was positive in 6/10 SCSCCs (60%), with half demonstrating strong and/or diffuse staining. P63 was positive in 9/10 SCSCCs (90%), with most demonstrating strong and diffuse staining. One SCSCC was negative for p63, but positive with two cytokeratin immunostains. In conclusion, the expression of any of the cytokeratins evaluated herein significantly distinguished AFX from SCSCC. CD10 used in isolation, however, was not useful in making this distinction (positive in 18/23 AFXs versus 6/10 SCSCCs, p=0.4). The addition of CD10 to a panel that includes p63 did not provide any additional information to that obtained from the latter alone. Overall, the most effective combination to distinguish AFX from SCSCC was p63 and cytokeratin AE-1/3. Positivity for both p63 and cytokeratin AE-1/3 was seen in 9/10 SCSCCs (90%) and was not observed in any of the 23 AFXs (p<0.0001). The usefulness of CD10 in this differential diagnosis is limited.


Management of cervicofacial infection: a 7-year retrospective study.
We aimed to describe and analyze the epidemiologic and clinical variables associated with, treatment for, and development of cervicofacial infection (CFI). We retrospectively examined 201 patients older than 14 years who had met the CFI diagnostic criteria and whose treatment required hospitalization and intervention under general anesthesia at our hospital. We performed chi-square tests to compare proportions in categorical variables and either the Student t test or the Wilcoxon signed-rank test to compare quantitative variables. We performed an analysis of variance to compare 3 or more categories and either Pearson or Spearman correlation coefficient analysis to examine the correlations between quantitative variables. The majority (85.07%) of the CFIs were of odontogenic origin. The mean hospitalization length was 4.58 days. Patients with diabetes who used tobacco and/or alcohol had a significantly longer length of hospitalization and several postoperative complications.The most common symptoms were pain, trismus and toothache. Symptoms of fever and nausea were associated with longer hospitalization. The most affected anatomic spaces were submandibular and pterygomandibular. Buccal and infraorbital, temporal, and parotid spaces were associated with longer hospitalization. Most CFIs are of odontogenic origin. Diabetes and tobacco and alcohol use are important risk factors. Treatment should be surgical and target the cause of infection. Timely referrals are important when patients present symptoms compatible with CFI for immediate treatment.


Atherogenic index predicts all-cause and cardiovascular mortality in incident peritoneal dialysis patients.
Atherosclerosis, the main cause of cardiovascular disease (CVD), is prevalent in patients undergoing peritoneal dialysis (PD). Atherogenic index (AI) is a strong predictor of atherosclerosis. However, its prognostic value in CVD outcomes and all-cause mortality among patients undergoing PD remains uncertain. Therefore, we aimed to evaluate the association between AI and all-cause and CVD mortality in PD patients. Calculated based on lipid profiles obtained through standard laboratory procedures, AI was evaluated in 2682 patients who underwent PD therapy between January 2006 and December 2017 and were followed up until December 2018. The study population was divided into four groups according to the quartile distribution of AI (Q1: <2.20, Q2: 2.20 to <2.97, Q3: 2.97 to <4.04, and Q4: ≥4.04). Multivariable Cox models were employed to explore the associations between AI and CVD and all-cause mortality was evaluated. During a median follow-up of 35.5 months (interquartile range, 20.9-57.2 months), 800 patients died, including 416 deaths from CVD. Restricted cubic splines showed non-linear relationship between AI and adverse clinical outcomes. The risks of all-cause and CVD mortality gradually increased across quartiles (log-rank, p < 0.001). After adjusting for potential confounders, the highest quartile (Q4) showed significantly elevated hazard ratio (HR) for both all-cause mortality (HR 1.54 [95% confidence interval (CI), 1.21-1.96]) and CVD mortality risk (HR 1.78 [95% CI, 1.26-2.52]), compared to the lowest quartile (Q1). AI was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that AI might be a useful prognostic marker.


Hormonal protection of gender-related peculiarities of testosterone metabolism in the brain of prenatally stressed rats.
Prenatal stress results in demasculinization and feminization of sexual behavior in adult male rats. Earlier the preventive effect of testosterone replacement of an androgen deficiency in male fetuses during exposure to stress has been demonstrated. Nevertheless the neuroendocrine mechanisms underlying hormonal protection of the brain sexual differentiation are not clear. Time-mated rats were undergone to 1 h strict immobilization during days 15 to 21 of gestation. Another group of stressed dams was injected with testosterone propionate on the 17th, 19th and 21st gestational days subcutaneously (5 mg/kg b.w.) 30 min prior to restraining. Aromatase and 5alpha-reductase activities were determined in the preoptic area and medial basal hypothalamus of 10-day old offspring. Aromatase activity in the preoptic area declined in affected with prenatal stress males and reached the normal female level. It completely restored in prenatally stressed males under influence of prenatal testosterone replacement. 5alpha-reductase activity decreased in the preoptic area of prenatally stressed females. In those pretreated with testosterone propionate, 5alpha-reductase activity was significantly elevated above normal level. The data obtained demonstrate a preservation of aromatase activity in the preoptic area of males resulted from testosterone replacement. Presumably testosterone exerts its protective effect on the male sexual behavior by prevention of neurochemical feminization of the brain preoptic area and, perhaps, due to some other mechanisms.


The continent ileostomy and the isolated ileal bladder.
The histories of 19 patients operated on by Kock's technique are reported. Follow-up extended from 3 years 4 months for the first case to 2 weeks for the last. There was one fatality. Some details of technique, contraindications, and complications and their treatment are discussed. Seventeen patients had a total proctocolectomy for ulcerative colitis and 2 had urinary diversion into an isolated ileal reservoir for inoperable carcinoma of the urinary bladder.


Attractiveness of Host Plants at Different Growth Stage to Kudzu Bug, Megacopta cribraria (Heteroptera: Plataspidae): Behavioral Responses to Whole Plant and Constitutive Volatiles.
The kudzu bug, Megacopta cribraria (Fabricius), is an invasive pest of soybeans, Glycine max (L.) Merr., that has recently been detected in the United States. This study investigated whether there was a differential attraction of adult bugs to soybean growth stages, and whether the attraction was related to soybean constitutive volatiles. Greenhouse choice assays examined the behavioral orientation preference of adult bugs exposed to four growth stages of whole soybean plants: vegetative (V2), flowering (R1), pod (R3), and seed (R5). Results show that significantly more adults landed on plants in the early reproductive stage R1 than in other stages. Laboratory olfactometer assays also demonstrate that significantly more adult bugs were attracted to R1 plants, with females responding more strongly than males. Both greenhouse and olfactometer assays indicate that the differential attraction of adult bugs to soybean growth stages was mediated by plant constitutive volatiles. These results offer an insight into kudzu bug chemical and behavioral ecology and thus are of great significance for optimizing the timing of field scouting and treatment as well as the development of soybean pest management programs.


VIRGO: computational prediction of gene functions.
Dramatic advances in sequencing technology and sophisticated experimental assays that interrogate the cell, combined with the public availability of the resulting data, herald the era of systems biology. However, the biological functions of more than 40% of the genes in sequenced genomes are unknown, posing a fundamental barrier to progress in systems biology. The large scale and diversity of available data requires the development of techniques that can automatically utilize these datasets to make quantified and robust predictions of gene function that can be experimentally verified. We present a service called the VIRtual Gene Ontology (VIRGO) that (i) constructs a functional linkage network (FLN) from gene expression and molecular interaction data, (ii) labels genes in the FLN with their functional annotations in the Gene Ontology and (iii) systematically propagates these labels across the FLN in order to precisely predict the functions of unlabelled genes. VIRGO assigns confidence estimates to predicted functions so that a biologist can prioritize predictions for further experimental study. For each prediction, VIRGO also provides an informative 'propagation diagram' that traces the flow of information in the FLN that led to the prediction. VIRGO is available at http://whipple.cs.vt.edu:8080/virgo.


Chicken food calls are functionally referential.
Male chickens, Gallus gallus domesticus, usually produce characteristic 'food' calls upon discovering edible objects, and are more likely to do so in the presence of a hen. Food calling is thus dependent upon food and modulated by social context, which is consistent with the idea that hens respond because they anticipate a feeding opportunity. An alternative model suggests that female behaviour is not mediated by the predicted presence of food but rather by social information, such as a low probability of male aggression. We conducted two playback experiments to explore the type of information encoded in food-associated vocal signals. Isolated hens were played recorded food calls and we compared their responses with those evoked by ground alarm calls (which have similar acoustic characteristics) and by contact calls (which are produced under similar social circumstances). Hens responded to food call playbacks by fixating downwards with the frontal binocular field. This anticipatory feeding movement was specific to food calls and did not occur in either of the control conditions. Food calls also affected looking downwards selectively. There were no differences between the call types in their effects on social behaviour, such as approach and contact calling, nor were there differences in the nonspecific effects of sound playback, such as orienting towards the loudspeaker or increased locomotor activity. Chicken food calls appear to provide conspecifics with information about the presence of food. This property has not hitherto been demonstrated in any natural system of animal acoustic signals. Copyright 1999 The Association for the Study of Animal Behaviour.


Sex differences in the management and outcome of acute coronary syndrome-Still an issue of equal treatment?
Significant sex-specific differences were described in the presentation, management and outcome of acute coronary syndrom (ACS) patients. Female ACS patients more often presented with noncardiac symptoms, which lead to significant time delays between symptom onset and treatment. Furthermore, multiple studies from various countries described that women with ACS were less likely to receive the medical or reperfusion therapy recommended by the respective guidelines, resulting in higher in-hospital mortality rates.The treating physicians and the patients need to be more aware of the described differences to ensure the best possible medical care for ACS patients, irrespective of sex.


Relation of statin therapy to psychological functioning in patients with an implantable cardioverter defibrillator.
Statin therapy is an important secondary prevention measure in cardiovascular disease. However, the side effects associated with statin use could potentially affect patients' quality of life. Little is known about the influence of statin therapy on the well-being and health status of cardiac patients, in general, and patients with an implantable cardioverter defibrillator (ICD), in particular. We investigated the association between statin therapy and symptoms of anxiety and depression and patients' health status during the 12 months after implantation, reckoning with statin type and dosage. Consecutively implanted ICD patients (n = 409; 78.2% men) completed the Hospital Anxiety and Depression Scale and the Medical Outcomes Study Short Form 36-item Health Survey at baseline and 3, 6, and 12 months after implantation. The data were analyzed using general linear mixed modeling repeated measures multivariate analysis of variance. Of the 409 patients, 60% were prescribed statins. Statin use was independently associated with poorer role limitations-physical (p = 0.001), social functioning (p = 0.007), and role limitations-emotional (p = 0.006) during the 12 months after implantation, independent of statin type, dosage, and other potential confounders. The associations between statin therapy and depression (p = 0.06) and statin therapy and physical functioning (p = 0.05) were borderline significant, and no association was found with anxiety (p >0.05). In conclusion, statin therapy was associated with impaired health status on 3 of the 8 Medical Outcomes Study Short Form 36-item Health Survey health status subdomains. This is the first study of ICD patients to examine the association between statin therapy and patient well-being. Future research is warranted to replicate these findings.


Multimodality approaches to localized gastric cancer.
Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.


Exclusively plant, whole-food diet for polypharmacy due to persistent atrial fibrillation, ischaemic cardiomyopathy, hyperlipidaemia and hypertension in an octogenarian.
Polypharmacy is common and associated with negative health outcomes in the elderly. We report the case of an 82-year-old man with a history of polypharmacy due to coronary artery disease, myocardial infarction, ischaemic cardiomyopathy, hyperlipidaemia, hypertension and persistent atrial fibrillation who presented with memory loss, cognitive impairment, fatigue and weakness. His treatment plan included an exclusively plant, whole-food diet and moderate physical activity which resulted in a rapid reduction of hyperlipidaemia and high blood pressure and the discontinuation of statin, antihypertensive and beta blocker drug therapy. The patient also reported reversal of impaired cognition and symptoms associated with atrial fibrillation and ischaemic cardiomyopathy, including light-headedness, fatigue and weakness. This case demonstrates that dietary and lifestyle modifications have the potential to improve symptoms of cardiovascular disease and reduce polypharmacy along with associated negative consequences in the elderly.


Photoexcitation and relaxation dynamics of catecholato-iron(III) spin-crossover complexes.
The photophysical properties of the ferric catecholate spin-crossover compounds [(TPA)Fe(R-Cat)]X (TPA=tris(2-pyridylmethyl)amine; X=PF(6) (-), BPh(4) (-); R-Cat=catecholate dianion substituted by R=NO(2), Cl, or H) are investigated in the solid state. The catecholate-to-iron(III) charge-transfer bands are sensitive both to the spin state of the metal ion and the charge-transfer interactions associated with the different catecholate substituents. Vibronic progressions are identified in the near-infrared (NIR) absorption of the low-spin species. Evidence for a low-temperature photoexcitation process is provided. The relaxation dynamics between 10 and 100 K indicate a pure tunneling process below approximately 40 K, and a thermally activated region at higher temperatures. The relaxation rate constants in the tunneling regime at low temperature, k(HL)(T-->0), vary in the range from 0.58 to 8.84 s(-1). These values are in qualitative agreement with the inverse energy-gap law and with structural parameters. A comparison with ferrous spin-crossover complexes shows that the high-spin to low-spin relaxation is generally faster for ferric complexes, owing to the smaller bond length changes for the latter. However, in the present case the corresponding rate constants are smaller than expected based on the single configurational coordinate model. This is attributed to the combined influence of the electronic configuration and the molecular geometry.


[Deficiency in alpha 1 antitrypsin in a case of adult Pi M phenotype with hepatocellular overcharge].
The authors point out a case of intrahepatic cells overload of PAS positive, globules and resistant to amylase digestion in a young Tunisian women of 26 years old with an hepatopathy looking like the one encountered in phenotype Pi Z subjects and a recently appeared total bilateral cataract. The patient and also 4 of the 5 members of her family have a lowered alpha 1 antitrypsin rate serum but the whole family is homozygote phenotype Pi M. The association alpha 1 antitrypsin deficiency bilateral cataract has not been described to our knowledge. The literature review pointing out similar globules in phenotype Pi M subjects and our observation remind us of the possibility of more complicated metabolic trouble of liver, the alpha 1 antitrypsin intrahepatic cells overload of which should be one of its clinical mode of expression.