The Natural History of Knee Osteoarthritis Pain Experience and Risk Profiles.
The study aimed to characterize the natural history of the pain experience, concurrently considering intermittent and constant pain over 4 years, and determine baseline factors associated with unfavorable trajectories in individuals with chronic knee pain. The Osteoarthritis Initiative (OAI) is a prospective, observational study of people with or at higher risk for knee osteoarthritis. The Intermittent and Constant Osteoarthritis Pain (ICOAP) was assessed annually at 48-to-96-month OAI visits. Twenty-eight baseline sociodemographic, knee-specific, and health-related characteristics were assessed. Group-based dual-trajectory modeling identified pain experience patterns indicated by ICOAP intermittent and constant pain scores over 4 years. Multivariable multinomial logistic regression models determined baseline factors associated with membership in each dual-trajectory group. Four longitudinal pain experience patterns were identified (n = 3,584, mean age = 64.8 [standard deviation 9.0] years, BMI = 28.6 [5.0] kg/m2; 57.9% women). Group 1 (37.7%) had minimal intermittent and no constant pain; Group 2 (35.1%) had mild intermittent and no constant pain; Group 3 (18.5%) had mild intermittent and low-grade constant pain; and Group 4 (8.7%) had moderate intermittent and constant pain. Baseline widespread pain, knee stiffness, back pain, hip pain, ankle pain, obesity, depressive symptoms, more advanced radiographic disease, and analgesic use were each associated with an increased risk of membership in less favorable Groups 2, 3, and 4. These distinct courses of pain experience may be driven by different underlying pain mechanisms. The benchmarked ICOAP scores could be used to stratify patients and tailor management. Addressing and preventing the development of modifiable risks (eg, widespread pain and knee joint stiffness) may reduce the chance of belonging to unfavorable dual-trajectory groups. PERSPECTIVE: Concurrently tracking intermittent versus constant pain experience, group-based dual-trajectory modeling identified 4 distinct pain experience patterns over 4 years. The benchmarked ICOAP scores in these dual trajectories could aid in stratifying patients for tailored management strategies and intensity of care.


The extracellular matrix composition of the monkey optic nerve head.
The presence and distribution of laminin, heparan sulfate proteoglycan and collagen types I, III and IV were immunohistologically determined in cynomolgus monkey optic nerve heads using the avidin-biotin-peroxidase complex technique. Collagen types I and III were detected within the collagenous plates of the scleral lamina cribrosa, in the septa and pia mater of the postlaminar optic nerve and in blood vessel walls in all regions of the optic nerve head. Collagen type IV, laminin and heparan sulfate proteoglycans were all localized to the margins of the collagenous laminar plates of the scleral lamina cribrosa and along the margins of the optic nerve septa and the pia mater. All three components also appeared beneath the blood vessel endothelium throughout the optic nerve head. Within the lamina cribrosa, collagen types I and III occupy the core of the scleral laminar plates and may provide structural support for optic nerve bundles exiting the eye. The distribution of collagen type IV, laminin and heparan sulfate proteoglycan corresponds to basement membranes from two sources: vascular endothelial cells and glial cells lining the axonal bundles. Abnormalities of these substances may influence optic nerve function and susceptibility to elevated intraocular pressure by altering their mechanical support functions within the nerve head, by interfering with axonal nutrition, or both.


Unraveling the auditory system of Drosophila.
Acoustic communication in flies is based on the production and perception of courtship song. Drosophila males sing to females during the courtship ritual, while females listen for the correct species-specific song parameters before deciding to mate. While we know that song is important for mating, the neural mechanisms involved in song recognition remain mysterious. However, the last few years have seen major advances in our understanding of the auditory system of Drosophila, including delineation of the neurons involved in song production, detailed characterization of the auditory receptor organ, and mapping of auditory projections into the brain. The stage is being set to tackle the auditory system of Drosophila in much the same way as has been done for its olfactory system. This review covers recent work and discusses prospects for future research on Drosophila audition.


Sequence polymorphism in acetylcholinesterase transcripts and genotyping survey of BmAchE1 in laboratory and Mexican strains of Rhipicephalus (Boophilus) microplus.
ABSTRACT Acetylcholinesterase cDNAs, BmAChE1, BmAChE2, and BmAChE3 of Rhipicephalus (Boophilus) microplus (Canestrini) were sequenced and found to exhibit significant polymorphism. A portion of the predicted amino acid substitutions in BmAChE1, BmAChE2, and BmAChE3 were found predominantly in organophosphate-resistant strains, but most did not correlate with resistant status. Multiple transcripts were observed from individual ticks, suggesting possible gene duplication or alternative splicing to produce more than two transcripts per individual. BmAChE1 transcript polymorphisms associating with organophosphate-resistant status in laboratory strains were surveyed in laboratory and Mexican strains of R. microplus by sequencing BmAChE1 genomic DNA. Quantitative real-time polymerase chain reaction was used to determine copy numbers of BmAChE1 (eight copies/haploid genome), BmAChE2 (16 copies/haploid genome), and BmAChE3 (four copies/haploid genome). Presence of at least three highly polymorphic amplified genes expressing AChE in tick synganglion suggested that ticks maintain a large and diverse assortment of AChE alleles available for rapid recombination and selection, which potentially reduces fitness costs associated with individual mutations. Elevated copy numbers for each of the BmAChEs may also explain previous failures to identify mutations resulting in insensitivity to organophosphates. It is clear that development of phenotypic resistance to organophosphates is highly complex and may be multigenic in character.


The history of cerebral PET scanning: from physiology to cutting-edge technology.
To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post-World War II period provided the necessary infrastructure for the first cerebral PET scan. A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders.


mRNA display selection of a high-affinity, modification-specific phospho-IkappaBalpha-binding fibronectin.
The complexity of the human proteome is greatly expanded by post-translational modifications. New tools capable of recognizing these modifications in a sequence-specific fashion provide a route to purify these modified proteins, to alter protein trafficking, and to visualize signal transduction in real time. Here, we have evolved novel, modification-specific ligands that target phosphorylated IkappaBalpha. To do this, we employed mRNA display-based in vitro selection using a 30-trillion-member protein library based on the fibronectin type III domain. The selection yielded one fibronectin molecule, 10C17C25, that binds a phospho-IkappaBalpha peptide with K d = 18 nM and is over 1000-fold specific compared to the nonphosphorylated peptide. 10C17C25 specifically recognizes endogenous phosphorylated IkappaBalpha from mammalian cell extract and stabilizes phospho-IkappaBalpha in vivo. We also incorporated 10C17C25 into a FRET indicator that detects IkappaB kinase (IKK) activity in vitro, demonstrating the utility of selecting designed adaptors for kinase activity sensors.


Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests.
The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report.


[Expression and pathobiological significance of Col I, Col IV and Fn in laryngeal squamous cell carcinomas].
To investigate the expression of collagen type I (Col I), collagen type IV (Col IV) and fibronectin (Fn) in laryngeal squamous cell carcinomas (LSCC) and their pathobiological relationship with invasion and metastasis of tumor. The expression of Col I, Col IV and Fn was detected by immunohistochemistry method in normal tissue of latero-carcinoma and tissue of carcinoma in 60 specimens of LSCC. Integral optical density (iOD) was detected by image analysis of computer and was analyzed by SPSS13.0. The expression of Col I was obvious and integrity. The expression of Col IV and Fn of basal membrane was like intact line-shape appearance and Fn of interstitial substance appeared like a complete network in the normal tissue of latero-carcinoma. Their expression decreased gradually and their integrity was broken and disappeared gradually from well to poorly differentiated LSCC. Their expressions also fell off with the tumor size, clinical stage and cervical lymphatic metastasis gradually and consistently in LSCC. Their variances were statistical significance separately (P<0.05 or P<0.01). The expression of Col I, Col IV and Fn was closely related to tumor invasion, the regional lymph node metastasis and other some pathobiological features in LSCC. A detection of Col I, Col IV and Fn was of definite significance on a better comprehension of the possibility of metastasis, choice of surgery and prognosis.


Substrate specificity of ascorbate oxidase: unexpected similarity to the reduction site of dopamine beta-monooxygenase.
A series of ascorbate derivatives has been used to examine the specificity of the reduction site of ascorbate oxidase. Replacement of the 6-OH group of ascorbic acid with either hydrogen or bromine does not alter the substrate activity significantly. 6-Amino-6-deoxy-L-ascorbic acid is a weak substrate for the enzyme, suggesting that positively charged groups at the 6-position are not well tolerated by the enzyme. The modification of the 5-OH reduces the effective interaction with the enzyme and the replacement of 6-OH with 6-S-phenyl- or 6-O-phenyl groups significantly increases the affinity for the enzyme. Both 2-Amino-6-S-phenyl-L-ascorbic acid and imino-D-glucoascorbic acid are not substrates for the enzyme. The stereoelectronic properties and alternate binding modes of these molecules are being considered to explain these observations. The substrate specificity of the enzyme is compared to the specificity of the reduction site of dopamine beta-monooxygenase.


Impact of dissolved organic matter on copper mobility in aquifer material.
Naturally occurring dissolved organic matter (DOM) and biosolids-derived DOM have been implicated in the mobility of metals in soils and aquifer materials. To investigate the effect of DOM on copper mobility in aquifer material, DOM derived from sewage biosolids was separated into two apparent molecular-weight (MW) fractions, 500 to 3500 Da (LMW) and > 14 000 Da (HMW). In each MW fraction, the DOM was further fractionated into hydrophilic, hydrophobic acid, and hydrophobic neutral compounds by an XAD-8 chromatography technique. The mobility of these DOM components and their influences on copper transport in a sesquioxide-coated, sandy aquifer material were examined with column transport experiments. The LMW DOM was found to be highly mobile, whereas the HMW DOM had a greater tendency to be retained by the aquifer material. Within the same MW fraction, the mobility of DOM followed the order of hydrophilic DOM > hydrophobic acid DOM > hydrophobic neutral DOM. Copper breakthrough curves in the presence of various DOM components showed that, except for the HMW hydrophilic fraction, DOM components enhanced Cu transport through the aquifer columns at early stages of transport (the first 75 pore volumes). In the later stages, however, all the DOM components substantially inhibited Cu mobility. We hypothesize that several mechanisms could account for retardation of Cu movement in the presence of the DOM fractions, including the formation of ternary complexes between the aquifer material, Cu, and DOM; changes in the electrostatic potential at the solid-phase surface; and pH buffering by DOM.


[Effect of tryptase inhibitors on histamine release from human colon mast cells].
To investigate the effect of tryptase inhibitors (TPIs) on histamine release from human colon mast cells. Human mast cells were prepared by digestion of colon tissue and with collagenase and hyaluronidase, cultured with four kinds of TPIs, leupeptin, protamine, TLCK, and lactoferrin for 15 min at 37 degrees Celsius respectively. A glass fibre-based fluorometry assay was used to detect histamine in mast cell suspension. 200 mmol/L leupeptin and 100 mmol/L protamine were able to stimulate histamine release from colon mast cells, while TLCK and lactoferrin did not. All TPIs inhibited anti-IgE-induced histamine release in a concentration dependent manner, and the inhibitory rates were 48.7%, 36.7%, 40.2% and 34.1%, respectively. However preincubation of TPIs with mast cells for 20 min at 37 degrees Celsius before adding anti-IgE had little effect on anti-IgE induced histamine release. All TPIs were able to inhibit calcium ionophore (CI)-induced histamine release, and the maximum inhibition rate was between 25%-32%. Inhibition on histamine release by leupeptin and TLCK obviously enhanced when colon mast cells were preincubated with them for 20 min before adding CI. However, under the same condition, protamine failed to inhibit histamine release. We prove for the first time that TPIs inhibit anti-IgE-and CI-induced histamine release from human colon mast cells, suggesting that it is possible to treat inflammatory bowel disease or other mast cell-related diseases by using TPIs.


Evolution of anti-malaria policies and measures in P.R. China for achieving and sustaining malaria-free.
Malaria is a major public health threat worldwide, and it was also widely prevalent in the history in China, seriously endangering people's health and affecting socioeconomic development. China was certified malaria elimination in 2021 with unremitting efforts since the founding of the People's Republic of China in 1949. This great achievement has been another milestone in the fight against major infectious diseases following the elimination of smallpox, poliomyelitis, leprosy, filariasis, neonatal tetanus and blinding trachoma in China. This paper briefly introduces the malaria burden dynamics and the corresponding malaria transmission risk stratificantions, as well as systematically reviews the evolution of anti-malaria policies and measures from severe epidemic to elimination in China. Meanwhile, five key lessons in malaria control and elimination in China are also briefly summarized. All of the above provide evidences for promoting global malaria eradication and preventing reestablishment of malaria transmission, finally benefit all individuals still suffering from the scourge of malaria.


Poly(ADP-ribose) polymerase 1-sirtuin 1 functional interplay regulates LPS-mediated high mobility group box 1 secretion.
Pathophysiological conditions that lead to the release of the prototypic damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) also result in activation of poly(ADP-ribose) polymerase 1 (PARP1; now known as ADP-ribosyl transferase 1 [ARTD1]). Persistent activation of PARP1 promotes energy failure and cell death. The role of poly(ADP-ribosyl)ation in HMGB1 release has been explored previously; however, PARP1 is a versatile enzyme and performs several other functions including cross-talk with another nicotinamide adenine dinucleotide- (NAD(+)) dependent member of the Class III histone deacetylases (HDACs), sirtuin-1 (SIRT1). Previously, it has been shown that the hyperacetylation of HMGB1 is a seminal event prior to its secretion, a process that also is dependent on HDACs. Therefore, in this study, we seek to determine if PARP1 inhibition alters LPS-mediated HMGB1 hyperacetylation and subsequent secretion due to its effect on SIRT1. We demonstrate in an in vitro model that LPS treatment leads to hyperacetylated HMGB1 with concomitant reduction in nuclear HDAC activity. Treatment with PARP1 inhibitors mitigates the LPS-mediated reduction in nuclear HDAC activity and decreases HMGB1 acetylation. By utilizing an NAD(+)-based mechanism, PARP1 inhibition increases the activity of SIRT1. Consequently, there is an increased nuclear retention and decreased extracellular secretion of HMGB1. We also demonstrate that PARP1 physically interacts with SIRT1. Further confirmation of this data was obtained in a murine model of sepsis, that is, administration of PJ-34, a specific PARP1 inhibitor, led to decreased serum HMGB1 concentrations in mice subjected to cecal ligation and puncture (CLP) as compared with untreated mice. In conclusion, our study provides new insights in understanding the molecular mechanisms of HMGB1 secretion in sepsis.


Evaluation of microRNA-205 expression as a potential triage marker for patients with low-grade squamous intraepithelial lesions.
High-risk human papillomavirus (HPV) testing is a recommended triage approach for females with atypical squamous cells of undetermined significance (ASCUS), but due to its poor specificity this approach is not recommended for patients with low-grade squamous intraepithelial lesions (LSIL). The objective of the current study was to determine microRNA (miR)-205 expression levels in liquid-based cytology (LBC) samples, and evaluate their ability to predict cervical intraepithelial neoplasia grade 2/3 or worse (CIN2/3+) in females with minor cytological abnormalities. LBC samples were obtained from patients attending the Swedish Cervical Cancer Screening Program. The Mann-Whitney U test, one-way analysis of variance, Kruskal-Wallis test, Spearman rank order correlation analysis, and Pearson's χ2 test were used to assess the results. Accuracy analyses indicated that high miR-205 expression had a significantly higher specificity to high-risk HPV testing, and a sensitivity similar to that of high-risk HPV testing to predict CIN2+ and CIN3+ in women with LSIL, but not those with high-grade squamous intraepithelial lesions. Although further research is required for females with LSIL, miR-205 expression in LBC samples may be a novel triage marker for, or a beneficial supplement to high-risk-HPV testing in these patients.


Clinical assessment of uterine contractions.
The assessment of uterine contractions is important in clinical decision-making, but the precise role for appraising contractions remains controversial. Four clinical approaches to assessing contractions are available: manual palpation; intrauterine pressure determination; external tocodynamometry; and electrohysterography. Palpation is inexpensive and harmless but requires the constant bedside presence of a trained observer. Intrauterine pressure measurement is considered the most sensitive and specific technique, and has become the standard by which other methods are judged; however, its quantitative measurements are not always precise or reproducible. Moreover, the availability of intrauterine pressure measurements does not seem to improve maternal or neonatal outcomes in most situations. External tocodynamometry is the most widely used technique. It is easy to apply and provides reasonably accurate information about the frequency and duration of contractions, but not their amplitude. It can require frequent adjustment during labor and might not work well in patients who are obese. Electrohysterography is a recently available noninvasive technology that detects uterine electrical activity using electrodes placed on the mother's abdominal wall. This approach is at least as reliable and accurate as tocodynamometry.


The strategy of cardiopulmonary bypass for total aortic arch replacement and the frozen elephant trunk technique with aortic balloon occlusion.
To investigate the use of the aortic balloon occlusion technique to assist total aortic arch replacement (TAR) with frozen elephant trunk (FET) to shorten the lower body circulatory arrest (CA) time and raise the nadir temperature during cardiopulmonary bypass. This retrospective study reviewed consecutive patients that underwent aortic balloon occlusion to assist TAR with FET and patients that received conventional TAR with FET procedures. Preoperative characteristics, perioperative characteristics and postoperative outcomes were compared between the two groups. The study included130 patients treated with aortic balloon occlusion and 230 patients treated with conventional TAR with FET. The 30-day mortality rate was similar between the aortic balloon occlusion and conventional groups (4.62% versus 7.83%, respectively). Multivariate analysis showed that aortic balloon occlusion reduced the incidence of acute kidney injury, hepatic injury and red blood cell transfusion. The application of aortic balloon occlusion reduced the mean ± SD CA time from 17.24 ± 4.36 min to 6.33 ± 5.74 min, with the target nadir nasal temperature being increased from 25°C to 28°C. The aortic balloon occlusion technique achieved significant improvements in reducing complications, but this did not translate into lower 30-day mortality.


Effects of pelleting diets without or with distillers' dried grains with solubles on growth performance, carcass characteristics, and gastrointestinal weights of growing-finishing barrows and gilts.
Pigs (192 total) were blocked by age and stratified by initial BW (25.75 ± 2.29 kg) into pens (2 barrows and 2 gilts per pen). Within blocks, pens were randomly allotted to treatments in a 2 × 2 factorial arrangement, with 2 diet forms (meal vs. pellet) and 2 distillers' dried grains with solubles (DDGS) inclusion levels (0 vs. 30%). Pigs were weighed at the beginning of the experiment and at the end of each feeding phase (d 35, 70, and 91) and daily feed allotments were recorded. Pigs were slaughtered at the end of the 91-d experiment, and full gastrointestinal (GI) tract and GI tract component weights were recorded immediately following evisceration. Carcass characteristics and meat quality were determined after a 24-h chill. Overall ADG was increased ( < 0.01) 3.2% when pigs were fed pelleted diets rather than meal diets, but there was no effect ( = 0.46) of DDGS inclusion on overall ADG. Overall ADFI of meal-fed pigs fed 30% DDGS was 4.7% greater ( < 0.01) than that of pigs fed 0% DDGS in meal form, but overall ADFI did not differ ( ≥ 0.19) between DDGS inclusion level in pellet-fed pigs (diet form × DDGS inclusion, < 0.01). When fed meal diets, pigs fed 0% DDGS had 2.7% greater ( = 0.02) overall G:F than pigs fed 30% DDGS; however, there was no difference ( = 0.42) in overall G:F between DDGS inclusion levels in pigs fed pelleted diets (diet form × DDGS inclusion, < 0.03). Pigs fed pelleted diets had 2.9% heavier HCW ( = 0.01), 10.4% greater 10th-rib back fat ( = 0.01), and 1.8 percentage units less estimated lean percentage ( = 0.04) than meal-fed pigs. Full GI tracts of pigs fed pelleted diets were 0.33 percentage units less ( = 0.03) of the ending live weight than that of meal-fed pigs due to decreased ( < 0.01) GI tract contents. Inclusion of DDGS increased ( = 0.03) full GI tract weight, large intestine weight ( < 0.01), and GI tract contents ( = 0.02). Severity of parakeratosis of the pars esophagea was greater ( < 0.01) in pellet-fed pigs than in meal-fed pigs, but the magnitude of the difference was likely not great enough to negatively affect drop credit of stomachs. In conclusion, feeding pelleted diets improved growth performance and increased carcass weight and fatness without causing the development of gastric lesions that would reduce the value of the stomach to packers. Furthermore, inclusion of DDGS in diets reduced HCW and dressing percent and increased GI tract and GI tract contents weight but had no effect on gastric lesion development or LM quality.


Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies.
Interferon-alpha induces durable cytogenetic remissions in about one-quarter of newly diagnosed patients with chronic myelogenous leukemia (CML). Even so, after short-term follow-up, previous studies have shown that residual leukemic cells can be detected by the polymerase chain reaction (PCR) in all of these individuals. The objectives of our study were therefore to obtain long-term follow-up data on residual disease in a cohort of complete responders and to determine if leukemic cells with clonogenic potential are present in patients despite the absence of relapse. We performed (a) serial analysis of blood and/or bone marrow for a reverse transcriptase PCR amplified BCR-ABL transcript at times well beyond the point that cytogenetic remission was first attained and (b) reverse transcriptase PCR of individually plucked myeloid and erythroid colonies for the presence of the same transcript. Seven CML patients who had previously attained complete cytogenetic remission while on interferon-alpha were investigated. Six of the seven patients were in complete cytogenetic remission at the time of analysis, whereas one patient had early evidence of cytogenetic relapse. With ongoing therapy, five patients with the longest follow-up eventually achieved PCR negativity at time periods of 27, 32, 36, 49, and 67 mo after a complete cytogenetic remission was first noted. Even so, residual disease was detected in progenitor cells derived from two patients, each of whom had been in continuous cytogenetic remission for approximately 2.5 and 3.5 yr, respectively. Progenitors expressing BCR-ABL transcripts were also detected in the patient with early cytogenetic relapse. These observations demonstrate that residual disease resides in colony-forming cells that should have the potential to repopulate the bone marrow. However, the presence of a minority of Ph-positive CML progenitor cells for a very long period of time is still compatible with durable remission, confirming that a situation of tumor dormancy may be induced in CML by interferon therapy.


The effects of the integration of an economic strengthening and HIV prevention education programme on the prevalence of sexually transmitted infections and savings behaviours among adolescents: a full-factorial randomised controlled trial in South Africa.
Multisectoral approaches are thought necessary to prevent HIV among adolescents. We examined whether an economic strengthening (ES) and an HIV-prevention education intervention improved outcomes when combined versus separately. We conducted a full-factorial randomised controlled study to randomise participants into all possible intervention groups based on the two interventions: economic strengthening only (ES-only), HIV-prevention only (HIV-only), both interventions combined (ES+HIV) and no intervention (control). We measured sexually transmitted infections (STIs), self-reported economic and sexual behaviours/knowledge, and pregnancy at a pre-intervention and two post-intervention assessments. Eligible participants were adolescents 14 to 17 years old from a programme supporting vulnerable families in Gauteng Province, South Africa. We estimated intervention effects using repeated measures, generalised linear mixed models. A total of 1773 adolescents participated (57% female). ES+HIV adolescents had the lowest STI prevalence at first endline; however, the comparison with the control was not significant (OR 0.62, 95% CI 0.27 to 1.41). ES-only or HIV-only groups were not significantly better than the control on STI prevalence (OR 1.53, 95% CI 0.73 to 3.20 and OR 1.47, 95% CI 0.69 to 3.12, respectively). STI prevalence became more similar among the groups at second endline.ES-only adolescents were more likely to participate in savings groups (p=0.004) and plan to save for education (p=0.001) versus the control. ES+HIV adolescents were more likely to plan to save for education versus the control (p=0.001) and HIV-only groups (p=0.002) but did not differ significantly from the ES-only group (p=0.803). The ES+HIV intervention's effect on HIV knowledge was significant compared with the control (p=0.03) and ES-only groups (p<0.001), but not when compared with the HIV-only group (p=0.091). Effects on pregnancy, sexual behaviours or other economic behaviours were not significant. We could not confirm the ES and HIV interventions, separately or combined, were effective to reduce STI prevalence. Evaluations of multicomponent interventions should use full-factorial designs to fully assess effects. NCT02888678.


Time to wait: a systematic review of strategies that affect out-patient waiting times.
Objective Out-patient waiting times pose a significant challenge for public patients in need of specialist evaluation and intervention. The aim of the present study was to identify and categorise effective strategies to reduce waiting times for specialist out-patient services with a focus on the Australian healthcare system. Methods A systematic review of major health databases was conducted using the key terms 'outpatient*' AND 'waiting time', 'process*' AND 'improvement in outpatient clinics'. Identified articles were assessed for their relevance by sequential review of the title, abstract and full text. References of the selected manuscripts were scanned for additional relevant articles. Selected articles were evaluated for consistent and emerging themes. Results In all, 152 articles were screened, of which 38 were included in the present review. Numerous strategies identified in the articles were consolidated into 26 consistent approaches. Three overarching themes were identified as significantly affecting waiting times: resource realignment, operational efficiency and process improvement. Conclusions Strategies to align resources, increase operational efficiency and improve processes provide a comprehensive approach that may reduce out-patient waiting times. What is known about the topic? Out-patient waiting times are a challenge in most countries that seek to provide universal access to health care for all citizens. Although there has been extensive research in this area, many patients still experience extensive delays accessing specialist care, particularly in the public health sector. The multiple factors that contribute to bottlenecks and inefficiencies in the referral process and affect patient waiting times are often poorly understood. What does this paper add? This paper reviews the published healthcare literature to identify strategies that affect specialist out-patient waiting times for patients. The findings suggest that there are numerous operational strategies that affect waiting times. These strategies may be categorised into three overarching themes (resource alignment, operational efficiencies and out-patient processes) that, when actioned in a coordinated approach, have the potential to significantly reduce out-patient waiting times. What are the implications for practitioners? This paper identifies evidence-based strategies for aligning resources, improving operational efficiency and streamlining processes, which may provide improvements to specialist out-patient waiting times for patients. Addressing the identified organisational, person-related, cultural and attitudinal factors will assist health system managers and health practitioners target the most appropriate improvement activities to reduce waiting times.


Peer review: empirical data base and practical implications.
Psychiatrists in the U.S. have raised a host of issues related to their experience with peer review including a concern for the patient's confidentiality, the need to correlate normative standards with local customary practice, the significance of the reviewer's theoretical orientation and training, the optimal documentation required and the impact of peer review on the reimbursement of claims for services rendered. The empirical and experimental evidence relevant to these issues is reviewed. The resulting implications for our clinical freedom and developing quality assurance network are discussed.


Immune Evasion by Epstein-Barr Virus.
Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.


Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of some 6-nitrobenzothiazole-derived semicarbazones.
Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders. A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme. Most of the compounds were found to be potent inhibitors of MAO-B, with IC(50) values in the nanomolar to micromolar range. Molecular docking studies were performed with AutoDock 4.2 to deduce the affinity and binding mode of these inhibitors toward the MAO-B active site. The free energies of binding (ΔG) and inhibition constants (K(i)) of the docked compounds were calculated by the Lamarckian genetic algorithm (LGA) of AutoDock 4.2. Good correlations between the calculated and experimental results were obtained. 1-[(4-Chlorophenyl)(phenyl)methylene]-4-(6-nitrobenzothiazol-2-yl)semicarbazide emerged as the lead MAO-B inhibitor, with top ranking in both the experimental MAO-B assay (IC(50): 0.004±0.001 μM) and in computational docking studies (K(i): 1.08 μM). Binding mode analysis of potent inhibitors suggests that these compounds are well accommodated by the MAO-B active site through stable hydrophobic and hydrogen bonding interactions. Interestingly, the 6-nitrobenzothiazole moiety is stabilized in the substrate cavity with the aryl or diaryl residues extending up into the entrance cavity of the active site. According to our results, docking experiments could be an interesting approach for predicting the activity and binding interactions of this class of semicarbazones against MAO-B. Thus, a binding site model consisting of three essential pharmacophoric features is proposed, and this can be used for the design of future MAO-B inhibitors.


The generating function approach for Peptide identification in spectral networks.
Tandem mass (MS/MS) spectrometry has become the method of choice for protein identification and has launched a quest for the identification of every translated protein and peptide. However, computational developments have lagged behind the pace of modern data acquisition protocols and have become a major bottleneck in proteomics analysis of complex samples. As it stands today, attempts to identify MS/MS spectra against large databases (e.g., the human microbiome or 6-frame translation of the human genome) face a search space that is 10-100 times larger than the human proteome, where it becomes increasingly challenging to separate between true and false peptide matches. As a result, the sensitivity of current state-of-the-art database search methods drops by nearly 38% to such low identification rates that almost 90% of all MS/MS spectra are left as unidentified. We address this problem by extending the generating function approach to rigorously compute the joint spectral probability of multiple spectra being matched to peptides with overlapping sequences, thus enabling the confident assignment of higher significance to overlapping peptide-spectrum matches (PSMs). We find that these joint spectral probabilities can be several orders of magnitude more significant than individual PSMs, even in the ideal case when perfect separation between signal and noise peaks could be achieved per individual MS/MS spectrum. After benchmarking this approach on a typical lysate MS/MS dataset, we show that the proposed intersecting spectral probabilities for spectra from overlapping peptides improve peptide identification by 30-62%.


Hepatitis C virus infection in children: How do we prevent it and how do we treat it?
Hepatitis C virus (HCV) infection is an important contributor to the worldwide burden of liver-related morbidity and mortality. Mother-to-child transmission of HCV ranges from 6 to 11% in different populations globally, but accurate estimates on the burden of pediatric HCV infection are limited because screening approaches are not consistent. Areas covered: The advent of new direct-acting antiviral agents that achieve very high rates of sustained virologic response (representing virologic cure) with short (i.e. 8-12 weeks) regimens has revolutionized the field of HCV treatment and led to the development of global elimination goals for HCV transmission and mortality. However, information on their safety during pregnancy and efficacy in preventing mother-to-child transmission is lacking. Currently, there are no approved treatment regimens with these antiviral agents for children younger than 12 years of age. Expert commentary: If these agents are shown to be safe during pregnancy and effective in preventing transmission to the infant, screening of pregnant women and antenatal treatment of those infected, could pave the way for eliminating pediatric HCV infection- particularly as these drugs become less costly and more accessible. Treatment of infected children when indicated, along with universal safe health care practices, can further pediatric HCV elimination.


[Taurine induces apoptosis in pulmonary artery smooth muscle cells].
To study the effect of taurine on apoptosis in PASMCs, and whether the death-receptor pathway act in the mechanism. Culture the PASMCs, and divided the cells into control, SD. Acridine orange(AO) assay and western-blot analysis on the expression of Bax, Bcl-2, Procaspase-3 and Fas were used to study the mechanism. A major finding of this study is that the Tau effects many apoptosis index, such as increasing the expression of Bax and Fas, decreasing the expression of Procaspase-3, and Bcl-2, accrescencing the mitochondrial depolarization, causing the nuclear shrinkage, all these datas demonstrated that Tau induced the apoptosis in pulmonary artery smooth muscle cells through mitochondrial-dependent pathway. Tau induces the apoptosis in pulmonary artery smooth muscle cells through death-receptor.


Low dose-ethanol modulates toxic effect of iron-overloading in the liver.
The oxidant properties of iron-overload and simultaneous ethanol consumption have received much interest, due to evidence reporting from hereditary hemochromatosis (HC). The full form of this disease is often associated with chronic alcoholism. An additive effect of toxicity of iron and ethanol was assumed. In this study, we examined nutritively iron-loaded Wistar rats (n = 59) (TMH-Ferrocene) additionally fed with ethanol up to 8% in drinking water for 36 wk. By reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole and retinol in serum and liver homogenates as well as transaminases in the serum. Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron concentration in the liver was measured with the Bathophenanthrolin-method. Liver histology was performed to investigate the iron deposits and the organ damage (H.E., Azan and Berlin-blue-stainings). 1. Vitamin C: A linear decrease of the concentration of vitamin C in serum and liver was found independent of alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin A: Elevated levels in serum but strongly decreasing levels in liver could be measured. 4. All iron-fed animals showed massive deposits of iron in the liver. Iron diet caused liver cirrhosis, while an additional administration of ethanol could prevent this. 5. Lipid peroxidation increased in animals fed ethanol and iron, but was significantly lower in animals only receiving an iron diet. Evidence indicates that the additional exposition to ethanol in iron-loaded animals could modulate the organ damage and oxidative stress. The biochemical findings are positively correlated to the histology.


Worldwide burden of cancer attributable to HPV by site, country and HPV type.
HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV-attributable cancer burden can boost programs of HPV vaccination and HPV-based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age-standardized incidence rates of HPV-attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from <3% in Australia/New Zealand and the USA to >20% in India and sub-Saharan Africa. Cervix accounts for 83% of HPV-attributable cancer, two-thirds of which occur in less developed countries. Other HPV-attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV-attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV-attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross-protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.


Bone matrix proteins: isolation and characterization of a novel cell-binding keratan sulfate proteoglycan (osteoadherin) from bovine bone.
A small cell-binding proteoglycan for which we propose the name osteoadherin was extracted from bovine bone with guanidine hydrochloride-containing EDTA. It was purified to homogeneity using a combination of ion-exchange chromatography, hydroxyapatite chromatography, and gel filtration. The Mof the proteoglycan was 85, 000 as determined by SDS-PAGE. The protein is rich in aspartic acid, glutamic acid, and leucine. Two internal octapeptides from the proteoglycan contained the sequences Glu-Ile-Asn-Leu-Ser-His-Asn-Lys and Arg-Asp-Leu-Tyr-Phe-Asn-Lys-Ile. These sequences are not previously described, and support the notion that osteoadherin belongs to the family of leucine-rich repeat proteins. A monospecific antiserum was raised in rabbits. An enzyme-linked immunosorbent assay was developed, and showed the osteoadherin content of bone extracts to be 0.4 mg/g of tissue wet weight, whereas none was found in extracts of various other bovine tissues. Metabolic labeling of primary bovine osteoblasts followed by immunoprecipitation showed the cells to synthesize and secrete the proteoglycan. Digesting the immunoprecipitated osteoadherin with N-glycosidase reduced its apparent size to 47 kD, thus showing the presence of several N-linked oligosaccharides. Digestion with keratanase indicated some of the oligosaccharides to be extended to keratan sulfate chains. In immunohistochemical studies of the bovine fetal rib growth plate, osteoadherin was exclusively identified in the primary bone spongiosa. Osteoadherin binds to hydroxyapatite. A potential function of this proteoglycan is to bind cells, since we showed it to be as efficient as fibronectin in promoting osteoblast attachment in vitro. The binding appears to be mediated by the integrin alphavbeta3, since this was the only integrin isolated by osteoadherin affinity chromatography of surface-iodinated osteoblast extracts.


Primary Hodgkin's disease of the sigmoid colon: a case report and review of the literature.
We report the case of an 81-year-old man who underwent a segmental resection of the sigmoid colon for severe diverticular disease. Histopathologic diagnosis revealed extranodal Hodgkin's disease, and the diagnosis was confirmed by immunohistochemistry. The incidence of extranodal Hodgkin's disease is rare and represents an infrequent occurrence as a gastrointestinal neoplasm and primary gastrointestinal lymphoma. A review of the literature for gastrointestinal lymphomas with emphasis on the occurrence of Hodgkin's disease, the diagnostic features, and the site of gastrointestinal tract involvement is reported.


Leprosy of the upper respiratory tract. A clinical bacteriological, histopathological and histochemical study of twenty cases.
Twenty cases clinically diagnosed as leprosy were thoroughly examined for E.N.T. lesions. These lesions were subjected to bacteriological, histopathological and histochemical studies. The results have been tabulated and discussed with special stress on some findings which are of help in diagnosing the disease.


Does toxic defence in Nycticebus spp. relate to ectoparasites? The lethal effects of slow loris venom on arthropods.
The venom produced by slow lorises (Nycticebus spp.) is toxic both intra- and inter-specifically. In this study we assessed the ecoparasite repellent properties of their venom. We tested venom from two Indonesian slow loris species: Nycticebus javanicus and Nycticebus coucang. Arthropods directly exposed to brachial gland secretions mixed with saliva from both species were immediately impaired or exhibited reduced activity (76%), and often died as a result (61%). We found no significant difference in the result of 60-min trials between N. coucang and N. javanicus [X(2)(1, n = 140) = 2.110, p = 0.3482]. We found evidence that the degree of lethality of the venom varies according to the arthropod taxa to which it is exposed. While most maggots (84%) were initially impaired from the venom after 10 min, maggots died after a 1 h trial 42% of the time. In contrast, at the end of 1 h trial, spiders died 78% of the time. For all arthropods, the average time to death from exposure was less than 25 min (M = 24.40, SD = 22.60). Ectoparasites including ticks, members of the arachnid order, are known to transmit pathogens to hosts and may be an intended target of the toxic secretions. Our results suggest that one function of slow loris venom is to repel parasites that affect their fitness, and that their topical anointing behaviour may be an adaptive response to ectoparasites.


Seroepidemiological aspects of human Strongyloides stercoralis infections in Chile.
To determine the frequency of Strongyloides stercoralis antibodies by means of the enzyme linked immunosorbent assay (ELISA) in Chile, in 2001-2003, 675 blood samples of patients of two psychiatric hospitals and 172 of healthy individuals (doctors, nurses and paramedicals) of these institutions, and 1,200 serum samples of blood donors of Northern region (Arica and Antofagasta), Central region (Valparaiso and Santiago) and Southern region (La Union) were collected. ELISA showed positivity of 12.1% in psychiatric hospitalized patients, none (0%) in the health personnel and 0.25% in blood donors (p < 0.05). Only in blood donors of Arica (1%) and La Union (0.5%) the ELISA test was positive suggesting that strongyloidiasis is focalized in determinate zones of the country. In Chile, human infections by S. stercoralis are endemic with very low frequency in apparently healthy individuals and high prevalence in risk groups such as the mentally ill hospitalized patients.


Sputter sample preparation for ion beam delivery of radium-223 at ATLAS.
A radium-223 ion beam was delivered to an experiment from the electron cyclotron resonance ion source, ECR2, at the Argonne Tandem Linac Accelerator System (ATLAS). The radium-223 material was in a nitrate salt form within a vial, prior to being converted to a usable sputter sample. The sputter sample was produced using a new sample preparation method, where the radium nitrate was dissolved into a solution and pipetted onto pressed aluminum powder. This sample was then allowed to dry, distributing the radium-223 material throughout the sputter sample. Ion source operation using the radium sputter sample is described with the operating parameters listed. The intensity and energy requirements for this ion beam were 1 × 106 particles/s and 1.07 GeV, respectively. Because the intensity is relatively low compared to most experiments at ATLAS, previously developed accelerator mass spectrometry methods were used Scott et al. [Rev. Sci. Instrum. 87, 02A732 (2016)] to avoid the need for tuning of the low-intensity beam of interest. Handling of the radium material, as well as loading and unloading of the sputter sample from ECR2, required collaboration with Health Physics. Procedures were used and dry runs were carried out before, during, and after the experiment to ensure the safety of the workers. The processes used and lessons learned are described within.


Novel porcelain laminate preparation approach driven by a diagnostic mock-up.
One critical step in the porcelain laminate technique is the achievement of sufficient ceramic thickness. At least two different strategies for tooth preparation can be found in the literature: (1) earlier simplified techniques included the use of depth cutters guided by the existing tooth surface-however, that approach did not take into consideration alterations of the tooth owing to aging, wear, or loss of enamel and thus led to greater risks for dentin exposures; (2) more recent and sophisticated methods have integrated an additive diagnostic procedure (ie, wax-up or mock-up) to compensate for tooth aging or severe existing loss of tooth substance. This approach allows for more enamel preservation and, as a consequence, more predictable bonding, biomechanics, and esthetics. The present article illustrates in detail the latest development in tooth preparation for porcelain laminates. This technique combines the time efficiency of earliest methods with the rationale and diagnostic foundations of the more recent techniques. Using this new laminate porcelain preparation approach, clinicians should be able to produce not only more accurate preparations, but also higher-quality tooth preparations in a time-efficient fashion.


Bonding durability of single-step adhesives to previously acid-etched dentin.
This study investigated the effect of phosphoric acid etching on the dentin bond strength of five single-step self-etch adhesive systems; Absolute, Clearfil tri-S Bond, Fluoro Bond Shake One, G-Bond and One-Up Bond F Plus. Bovine mandibular incisors were mounted in self-curing resin and the facial surfaces were wet ground with #600 SiC paper. Adhesives were applied on the prepared dentin surfaces with and without prior phosphoric acid etching and light irradiated. Resin composite was condensed into a mold (ø4x2 mm), light irradiated and stored in water at 37 degrees C. Four groups (n=10) were made per adhesive system: with and without prior acid etching and with and without thermal cycling between 5 degrees C and 55 degrees C for 10,000 cycles. The specimens were tested in a shear mode at a crosshead speed of 1.0 mm/minute. Two-way ANOVA, Student t-test and Tukey HSD test at a level of 0.05 were done. For specimens without prior acid etching, the mean bond strengths to bovine dentin ranged from 12.8 to 17.1 MPa and ranged from 6.7 to 13.3 MPa for specimens with prior acid etching after 24 hours storage in water. When the specimens were subjected to thermal cycling, the mean bond strengths ranged from 10.7 to 24.8 MPa for the specimens without prior acid etching and 4.6 to 13.9 MPa for the specimens with prior acid etching. The changes in dentin bond strength were different among the adhesive systems tested. Failure modes were commonly adhesive failure associated with mixed failure for specimens with prior acid etching. For specimens without prior acid etching, failures in composite and dentin were increased. From the results of this in vitro study, prior acid etching might be not acceptable for increasing the dentin bond strengths of single-step self-etch adhesive systems.


The uncanny return of the race concept.
The aim of this Hypothesis and Theory is to question the recently increasing use of the "race" concept in contemporary genetic, psychiatric, neuroscience as well as social studies. We discuss "race" and related terms used to assign individuals to distinct groups and caution that also concepts such as "ethnicity" or "culture" unduly neglect diversity. We suggest that one factor contributing to the dangerous nature of the "race" concept is that it is based on a mixture of traditional stereotypes about "physiognomy", which are deeply imbued by colonial traditions. Furthermore, the social impact of "race classifications" will be critically reflected. We then examine current ways to apply the term "culture" and caution that while originally derived from a fundamentally different background, "culture" is all too often used as a proxy for "race", particularly when referring to the population of a certain national state or wider region. When used in such contexts, suggesting that all inhabitants of a geographical or political unit belong to a certain "culture" tends to ignore diversity and to suggest a homogeneity, which consciously or unconsciously appears to extend into the realm of biological similarities and differences. Finally, we discuss alternative approaches and their respective relevance to biological and cultural studies.


Evolution and Interspecies Transmission of Canine Distemper Virus-An Outlook of the Diverse Evolutionary Landscapes of a Multi-Host Virus.
Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus Morbillivirus within the Paramyxoviridae family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections.


[Effect of cardiac embolism sources on origin of territorial cerebral infarcts].
To test the association of cardiac sources of embolism with territorial type brain infarcts. From a prospective cerebral ischemia data base the 106 consecutive patients with territorial type cerebral infarcts on computerized tomography were analyzed. The 85 consecutive patients with lacunar lesions served as a comparison group. The association of cardiac sources of embolism with territorial types infarcts was assessed using univariate Chi Square tests and logistic regression models. Cardiac sources of embolism were defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall motion and valvular abnormalities, left atrial enlargement, open foramen ovale, septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all findings--except for atrial fibrillation--assessed by echocardiography). Atrial fibrillation was significantly associated with territorial type infarcts (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent of additional cardiac diseases, other cardiac abnormalities, carotid artery stenosis, and patient age. Most likely due to the small sample size, left cardiac thrombi only showed a non-significant trend towards an association with territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate of all other cardiac findings did not differ significantly between the comparison groups. Atrial fibrillation and cardiac thrombi showed an association with territorial type infarcts. Other so-called cardiac sources of embolism--except for mechanical valves and bacterial endocarditis which were not represented in our sample--revealed no clinically relevant association with embolic brain infarct pattern.


Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells.
Photodynamic therapy is useful for the treatment of cancer because it is minimally invasive for patients. Certain porphyrin compounds and their derivatives have been used as the photosensitizer because they accumulate specifically in cancerous tissues. However, the detailed mechanism of this phenomenon has not been clarified. We previously reported that a proton-coupled folate transporter, HCP1, transported porphyrins and that regulation of the protein was associated with cancer-specific reactive oxygen species from mitochondria (mitROS). Therefore, over-generation of mitROS could increase HCP1 expression and the effect of photodynamic therapy. We investigated whether pretreatment with indomethacin influenced photodynamic therapy by using a rat normal gastric mucosal cell line, RGM1, its cancer-like mutated cell line, RGK1, and a manganese superoxide dismutase (MnSOD)-overexpressing RGK cell line, RGK-MnSOD. Indomethacin promotes the generation of cellular mitROS by inhibiting the electron transport chain, and MnSOD scavenges the mitROS. We elucidated that indomethacin enhanced cancer-specific mitROS generation and increased HCP1 expression. Furthermore, RGK1 cells showed higher cellular incorporation of hematoporphyrin and better therapeutic effect with indomethacin treatment whereas RGK-MnSOD cells did not show a difference. Thus, we concluded that indomethacin improved the effect of photodynamic therapy by inducing increased mitROS generation in cancer cells.


Health-Related Quality of Life among American Indian and Alaska Native People: Exploring Associations with Adversities and Psychosocial Strengths.
Identifying psychosocial strengths that support physical health can lead to better pathways to prevention and intervention. Relying on the resilience portfolio model as a conceptual framework, this study explores strengths in three domains (regulation, meaning making, and interpersonal) to identify promising protective factors to support physical health-related quality of life (P-HRQOL), controlling for prior exposure to adversity, age, and gender. This study uses data from four resilience portfolio model studies collected in the southern United States, combined to increase the number of people who identified as American Indian/Alaska Native. The sample included 147 people (M age = 28.5 years; SD = 16.26), of which 57 percent are female. The surveys collected data on adversities (polyvictimization, other adversities, county poverty), psychosocial strengths (psychological endurance, sense of purpose, religious meaning making, compassion, and community support), and P-HRQOL. The full model accounted for 24 percent of the variance in P-HRQOL, with strengths explaining more than twice as much variance as adversities (13 percent versus 6 percent). A sense of purpose showed the most promise for supporting P-HRQOL. Regarding implications, authors recommend exploring a wider range of protective factors that might improve resilience in Native communities. Several evidence-based pathways to meaning making, such as narrative and mindfulness, may improve health outcomes for Native people.


Evolution of coloration patterns.
There is an amazing amount of diversity in coloration patterns in nature. The ease of observing this diversity and the recent application of genetic and molecular techniques to model and nonmodel animals are allowing us to investigate the genetic basis and evolution of coloration in an ever-increasing variety of animals. It is now possible to ask questions about how many genes are responsible for any given pattern, what types of genetic changes have occurred to generate the diversity, and if the same underlying genetic changes occur repeatedly when coloration phenotypes arise through convergent evolution or parallel evolution.


Using HIV Risk Self-Assessment Tools to Increase HIV Testing in Men Who Have Sex With Men in Beijing, China: App-Based Randomized Controlled Trial.
Men who have sex with men (MSM) in China hold a low-risk perception of acquiring HIV. This has resulted in an inadequate HIV testing rate. This study aims to investigate whether administering HIV risk self-assessments with tailored feedback on a gay geosocial networking (GSN) app could improve HIV testing rates and reduce sexual risk behaviors in Chinese MSM. We recruited MSM from Beijing, China, who used the GSN platform Blued in October 2017 in this 12-month double-blinded randomized controlled trial. From October 2017 to September 2018, eligible participants were randomly assigned to use a self-reported HIV risk assessment tool that provided tailored feedback according to transmission risk (group 1), access to the same HIV risk assessment without feedback (group 2), or government-recommended HIV education materials (control). All interventions were remotely delivered through the mobile phone-based app Blued, and participants were followed up at 1, 3, 6, and 12 months from baseline. The number of HIV tests over the 12-month study was the primary outcome and was assessed using an intention-to-treat analysis with an incident rate ratio (IRR). Unprotected anal intercourse (UAI) over 6 months was assessed by a modified intention-to-treat analysis and was the secondary outcome. All statistical analyses were conducted in SAS 9.3 (SAS Institute, Inc.), and a P value <.05 was considered statistically significant. In total, 9280 MSM were recruited from baseline and were randomly assigned to group 1 (n=3028), group 2 (n=3065), or controls (n=3187). After follow-up, 1034 (34.1%), 993 (32.4%), and 1103 (34.6%) remained in each group, respectively. Over 12 months, group 1 took 391 tests (mean of 2.51 tests per person), group 2 took 352 tests (mean of 2.01 tests per person), and controls took 295 tests (mean of 1.72 tests per person). Group 1 had significantly more HIV testing than the control group (IRR 1.32, 95% CI 1.09-4.58; P=.01), while group 2 did not differ significantly from the controls (IRR 1.06, 95% CI 0.86-1.30; P=.60). The proportion of UAI was not statistically different among different groups, but all 3 groups had UAI, which declined from baseline. Repeated HIV risk assessments coupled with tailored feedback through GSN apps improved HIV testing. Such interventions should be considered a simple way of improving HIV testing among MSM in China and increasing awareness of HIV status. ClinicalTrials.gov NCT03320239; https://clinicaltrials.gov/study/NCT03320239.


LTUA--a new and more reproducible method of estimating intrauterine size.
A system of estimating intrauterine size by adding the maximal longitudinal and transverse uterine areas (LTUA) is described. In our hands this measurement is less prone to observer variability and more sensitive in diagnosing intrauterine growth retardation (IUGR) than the total intrauterine volume (TIUV) measurement. Intraobserver variability for the LTUA was 3.7 per cent, whereas that for the TIUV was 10.0 per cent. Interobserver variability was 6.5 per cent for the LTUA and 12.9 per cent for the TIUV. Sensitivity for the LTUA and the TIUV was 70 per cent and 40 per cent, respectively, and the respective specificities were 94 per cent and 96 per cent. These results suggest that the LTUA may be a more accurate and reliable method of predicting IUGR than is the TIUV.


Impact of PCV7/PCV13 introduction on invasive pneumococcal disease (IPD) in young children: Comparison between meningitis and non-meningitis IPD.
The worldwide introduction of pneumococcal conjugate vaccines (PCV) into National Immunization Programs resulted in rapid and substantial reduction of invasive pneumococcal disease (IPD) rates in children. However, the reduction of meningitis vs. non-meningitis IPD (nm-IPD) was not yet fully elucidated. We compared 7-valent and 13-valent PCV (PCV7 and PCV13) impact on pneumococcal-meningitis vs. nm-IPD in Israeli children <5years. We conducted an ongoing nationwide, prospective, population-based, active surveillance. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All pneumococcal isolates (blood and/or CSF) from IPD episodes in children <5years from July 2000 through June 2015 were included. Extrapolation for missing serotypes (34.7% of all isolates) was conducted. 4163 IPD cases were identified; 3739nm-IPD (89.8%) and 424 meningitis (10.2%). During the pre-PCV period (2000-2008), children <12months constituted 52.1% and 33.7% of meningitis and nm-IPD, respectively (p<0.001). The respective proportions of non-PCV13 serotypes (non-VT) were 18.2% vs. 10.1%, (p<0.001). Comparing the last study year (2014-2015) to the mean of pre-PCV period, meningitis incidence in children <5years decreased non-significantly by 27%, while nm-IPD decreased significantly by 69%. Dynamic rates of meningitis and nm-IPD caused by PCV13 serotypes were similar, with 93% and 95% overall reductions, respectively. However, non-VT increased in meningitis relatively to nm-IPD, mainly in children <24months. Serotype 12F rose sharply and significantly since 2009-2010 through 2014-2015 (28.6% of all non-VT meningitis in children <24m). The overall impact of PCV7/PCV13 in children <5years in Israel was less prominent in meningitis than in nm-IPD. This could be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar. Continuous monitoring of meningitis and nm-IPD is warranted.


Enantioselective N-Heterocyclic Carbene Catalyzed Diene Regenerative (4 + 2) Annulation.
An enantioselective N-heterocyclic carbene (NHC)-catalyzed diene regenerative (4 + 2) annulation has been achieved through the use of highly nucleophilic morpholinone-derived catalysts. The reaction proceeds with good to excellent yields, high enantioselectivity (most >92% ee), and good diastereoselectivity (most >7:1). The generality of the reaction is high, with 19 examples reported. The utility of the products has been examined with subsequent derivatization in Diels-Alder reactions using electron-poor dienophiles. Furthermore, interception of the proposed β-lactone intermediate has been achieved, allowing the synthesis of compounds bearing four contiguous stereocenters with high levels of enantio- and diastereoselectivity.


Cervical biomarkers as predictors of successful induction of labour by Foley catheter.
The prediction of successful labour induction is difficult, indicating a need for a biomarker test. Little is known about the effect of Foley catheter (FC) induction on biochemical mediators in the cervix, such as the insulin-like growth factor binding protein-1 (IGFBP-1), matrix metalloproteinases (MMP) and their inhibitors (TIMP). We enrolled 35 nulliparous women with singleton pregnancies, intact amniotic membranes and cephalic presentation ≥40 gestational weeks scheduled for labour induction by FC. Serial cervical swab samples were collected at FC insertion and expulsion. The concentrations of IGFBP-1, PhIGFBP-1, MMP-8, MMP-2, MMP-9, TIMP-1 and TIMP-2 were analysed. The IGFBP-1 and phIGFBP-1 concentrations increased during the FC-induced cervical ripening. In contrast, MMP-8 and MMP-9 concentrations decreased. However, these changes did not predict the outcome of the labour induction, thus appearing not suitable for clinical use. Impact statement What is already known on this subject? During cervical ripening, various constituents interact in a complex network. Insulin-like growth factor binding protein-1 (IGFBP-1), matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) appear to play a role in cervical ripening. The mechanism of Foley catheter on cervical ripening consists of direct mechanical stretching of the cervix and lower uterine segment, and the stimulation of local secretion of endogenous prostaglandins. What do the results of this study add? This study investigated the role of cervical biochemical mediators during Foley catheter-induced cervical ripening, and their predictive value in a successful labour induction and vaginal delivery. The IGFBP-1 and phosphorylated IGFBP-1 concentrations increased, whereas MMP-8 and MMP-9 concentrations decreased during the Foley catheter-induced cervical ripening in nulliparous women. However, these changes did not predict the outcome of labour induction, thus appearing not suitable for clinical use. What are the implications of these findings for clinical practice and/or further research? Prediction of a successful labour induction is difficult, indicating a need for a biomarker test. Future studies with larger data are needed for investigating the role of these cervical biomarkers in successful labour induction, and in developing a future bedside a screening tool for clinical use.


Diet-Induced Obesity and the Mechanism of Leptin Resistance.
Leptin signaling blockade by chronic overstimulation of the leptin receptor or hypothalamic pro-inflammatory responses due to elevated levels of saturated fatty acid can induce leptin resistance by activating negative feedback pathways. Although, long form leptin receptor (Ob-Rb) initiates leptin signaling through more than seven different signal transduction pathways, excessive suppressor of cytokine signaling-3 (SOCS-3) activity is a potential mechanism for the leptin resistance that characterizes human obesity. Because the leptin-responsive metabolic pathways broadly integrate with other neurons to control energy balance, the methods used to counteract the leptin resistance has extremely limited effect. In this chapter, besides the impairment of central and peripheral leptin signaling pathways, limited access of leptin to central nervous system (CNS) through blood-brain barrier, mismatch between high leptin and the amount of leptin receptor expression, contradictory effects of cellular and circulating molecules on leptin signaling, the connection between leptin signaling and endoplasmic reticulum (ER) stress and self-regulation of leptin signaling has been discussed in terms of leptin resistance.


Functional Latissimus Dorsi Transfer for Upper-Extremity Reconstruction: A Case Report and Review of the Literature.
Objective: The latissimus dorsi flap is a workhorse for plastic surgeons, being used for many years for soft-tissue coverage of the upper extremity as well as for functional reconstruction to restore motion to the elbow and shoulder. The authors present a case of functional latissimus dorsi transfer for restoration of elbow flexion and review the literature on technique and outcomes. Methods: A literature review was performed using MEDLINE and the Cochrane Collaboration Library for primary research articles on functional latissimus dorsi flap transfer. Data related to surgical techniques and outcomes were extracted. Results: The literature search yielded 13 relevant studies, with a total of 52 patients who received pedicled, functional latissimus dorsi flaps for upper-extremity reconstruction. The most common etiology requiring reconstruction was closed brachial plexus injury (n = 13). After flap transfer, 98% of patients were able to flex the elbow against gravity and 82.3% were able to flex against resistance. In the presented case, a 77-year-old man underwent resection of myxofibrosarcoma of the upper arm with elbow prosthesis placement and functional latissimus dorsi transfer. The patient was able to actively flex against gravity at 3-month follow-up. Conclusions: A review of the literature shows that nearly all patients undergoing functional latissimus dorsi transfer for upper-extremity reconstruction regain at least motion against gravity whereas a large proportion regain motion against resistance. Considerations when planning for functional latissimus dorsi transfer include patient positioning, appropriate tensioning of the muscle, safe inset, polarity, management of other affected upper-extremity joints, and educating patients on the expected outcomes.


Gender and magnetic resonance imaging classification-related differences in clinical and biochemical characteristics of Cushing's disease: a single-centre study.
Cushing's disease (CD) presents a remarkable preponderance in female gender, and a significant minority of patients with CD presented with negative magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate gender-related and MRI classification-related differences in clinical and biochemical characteristics of CD. We retrospectively studied 169 patients with CD, comprising 132 females and 37 males, and 33 patients had no visible adenoma on MRI. We observed that male and MRI-positive patients presented with high adrenocorticotropic hormone (ACTH) values (P < 0.05). Female patients presented with higher prevalence of hirsutism and hyperpigmentation and lower prevalence of purple striae (P < 0.05). The prevalence of buffalo-hump and hypertension was greater in MRI-negative patients (P < 0.05). In addition, male patients with CD presented at a younger age compared with females (P < 0.05). Patients with fatigue and hypokalaemia presented significantly higher urinary-free cortisol, ACTH and cortisol levels compared with patients without these symptoms (P < 0.05). The prevalence of LH reduction, hyper total cholesterol (TC) and hyper low-density lipoprotein was more frequent in MRI-positive patients (P < 0.05). Hyper-TC levels and PRL reduction were more frequent in males (P < 0.05). T3, T4 and FT3 levels negatively correlated with age at diagnosis (r = -0.310, P < 0.01; r = -0.191, P < 0.05; r = -0.216, P < 0.05). T3, T4, FT3 and FT4 levels significantly negatively correlated with 8-am plasma cortisol levels (r = -0.328, P < 0.01; r = -0.195, P < 0.05; r = -0.333, P < 0.01; r = -0.180, P < 0.05). Females presented higher total protein level (P < 0.01) and lower blood urea nitrogen and serum creatinine levels (P < 0.01), compared with male patients. Carefulness and caution are required in all patients with CD, because of the complexity of clinical and biochemical characteristics in CD patients of different gender and MRI classification, particularly male patients and MRI-negative patients.


Status quo of exercise participation among gastric cancer patients after radical gastrectomy and analysis of the influencing factors.
To investigate the status quo of participation in exercise among gastric cancer patients after radical gastrectomy and analyze the influencing factors. Convenient sampling was used to conduct a questionnaire survey of 163 patients after radical gastric cancer surgery from January to December 2020. The survey content included general information, exercise participation, exercise knowledge, attitude, and social support. Descriptive statistics, single factor analysis, and multiple linear regression analysis were performed using Statistical Product and Service Solutions 24.0 (SPSS24.0, IBM, USA). After radical gastrectomy, the form of exercise that patients participated in was relatively simple. The average amount of exercise involved was 8.10 Mets-h/week, which was at the level of almost no exercise. Univariate analysis showed that differences in age, gender, education level, work status, main caregivers and sports knowledge, attitudes, and social support levels all led to different levels of exercise participation. Multiple linear regression analysis showed that the factors affecting the patient's level of participation in exercise included age, degree of self-care in life, attitude towards exercise after surgery, and level of social support. The status quo of exercise participation among gastric cancer patients after radical gastrectomy is not ideal. In this study, we found that age, level of self-care in life, sports attitude, and level of social support were the main factors affecting the exercise participation of patients. Therefore, improving patients' self-care ability, exercise attitude, and increasing social support may play an important role in improving the status quo of patients' exercise participation after radical gastric cancer surgery.


Significance of Thyroglobulin Autoantibodies in Patients With Thyroid Cancer Treated With Lenvatinib.
Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with multitarget kinase inhibitors as lenvatinib, expressed according to the Response Evaluation Criteria in Solid Tumors (RECIST), is also associated with a drastic reduction of Tg levels. However, interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg. To evaluate if in RAIR-DTC TgAb could be considered a surrogate marker of Tg in monitoring response to treatment with lenvatinib. We retrospectively evaluated patients who had started lenvatinib and correlated serum Tg and TgAb with the radiological response across visits. University of Pisa, Italy. We selected 9/97 RAIR-DTC patients with detectable TgAb. None. None. Tg values correlated neither with TgAb title nor with radiological response across visits. Greater decreases in TgAb titer correlated with favorable radiological response to lenvatinib after 1 month (Spearman's correlation = 0.74, P = .021) and 6 months (correlation = 0.61, P = .079). According to RECIST, patients with partial response showed a ∼10-fold greater decrease in TgAb compared to those with stable disease at 1 month (median TgAb decrease: -142 vs -14 IU/mL, P = .01) and those with progressive disease at 6 months (median TgAb decrease: -264 vs-24 IU/mL, P = .04). TgAb evaluation may represent a reliable surrogate marker for Tg trend in evaluating response of RAIR-DTC to treatment with lenvatinib. A multicentric study would be useful to confirm our results.


Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway.
Currently, the effect and molecular mechanism of calycosin, the main active ingredient of Qinshi Simiao San, which can alleviate chronic prostatitis (CP), on CP remain unclear. This study aimed to elucidate the potential mechanism of action of calycosin in CP in a rat CP model. The prostate tissue morphology was evaluated based on hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was conducted to evaluate inflammatory cytokine and immune factor levels (secretory immunoglobulin A [SIgA]; immunoglobulin G [IgG]) in prostate tissues and serum. Additionally, representative biomarkers of oxidative stress, including malondialdehyde, superoxide dismutase, and catalase were detected using detection kits, and reactive oxygen species release was evaluated using immunofluorescence staining. Furthermore, the p38 mitogen-activated protein kinase (p38MAPK)/NF-kappaB (NF-κB) signaling pathway was analyzed by western blotting. The results showed that calycosin substantially ameliorated the pathological damage to prostate tissues of the CP rats. Moreover, calycosin significantly downregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha, IgG, and SIgA levels. Furthermore, we found that calycosin considerably suppressed oxidative stress and inhibited the activation of the p38MAPK/NF-κB signaling pathway in rats with CP. In summary, our findings revealed that calycosin protects against CP in rats by inhibiting the p38MAPK/NF-κB pathway.


Application of physiological genomics to the study of hearing disorders.
Although the biophysical principles of how the ear operates are reasonably well understood, little is known about the specific genes that confer normal function to the inner ear. Nevertheless, the recent implementation of genomic tools has led to extraordinary progress in the identification of mutated genes that cause non-syndromic and syndromic forms of deafness. Part of this success is directly related to the sequencing of the human and mouse genomes and improved gene annotation methods. This review discusses how physiological genomic tools, such as genomic databases, expressed sequence tag databases and DNA arrays have been applied to find candidate genes for important molecular processes in the inner ear. It also illustrates, using the discovery of genes encoding essential components of cochlear K+ homeostasis as an example, how the combination of physiological genomic tools with physiological and morphological information has led to an in-depth understanding of cochlear ion homeostasis. Finally, it discusses how the use of applied genomic tools, such as gene arrays, will further advance our knowledge of how the inner ear works, develops, ages and regenerates.


Risk factors for posttraumatic stress disorder in Australian Vietnam veterans.
The aims of this paper are to determine the risk factors for combat-related posttraumatic stress disorder (PTSD) and to examine the relative contribution of pre-military factors, pre-trauma psychiatric diagnoses, military factors such as combat posting, and combat and casualty stress exposure. An epidemiological cohort study using standardised psychiatric, social and health interviews was undertaken with a national random sample of male Australian Army Vietnam veterans. Multivariate logistic regression was used to examine the relative contribution of factors derived from interview and from military records in four categories: pre-enlistment circumstances including home life, education, major life stress; pre-Vietnam psychiatric diagnoses; military experiences before and during Vietnam; and combat and stress experiences. Of the 128 data items examined, significant associations were found for 39, in addition to combat stress. Pre-enlistment items accounted for about 3% of the deviance towards PTSD diagnosis, pre-enlistment psychiatric diagnosis about 13%, military variables about 7% and combat stress about 18%; all factors together accounted for 42%. The results confirm that pre-military and military variables make only a small but significant contribution to PTSD either alone or after controlling for combat stress; that psychiatric diagnoses of depression, dysthymia and agoraphobia make strong contributions to PTSD; but that combat stress makes the largest contribution even after controlling for the effects of other variables. Psychiatric diagnoses and combat stress appear to be independent in their effects on PTSD.


Design and implementation of a prototype head and neck phantom for the performance evaluation of gamma imaging systems.
A prototype anthropomorphic head and neck phantom has been designed to simulate the adult head and neck anatomy including some internal organs and tissues of interest, such as thyroid gland and sentinel lymph nodes (SLNs). The design of the head and neck phantom includes an inner jig holding the simulated SLNs and thyroid gland. The thyroid gland structure was manufactured using three-dimensional (3D) printing taking into consideration the morphology and shape of a healthy adult thyroid gland. The head and neck phantom was employed to simulate a situation where there are four SLNs distributed at two different vertical levels and at two depths within the neck. Contrast to noise ratio (CNR) calculations were performed for the detected SLNs at an 80 mm distance between both pinhole collimators (0.5 and 1.0 mm diameters) and the surface of the head and neck phantom with a 100 s acquisition time. The recorded CNR values for the simulated SLNs are higher when the hybrid gamma camera (HGC) was fitted with the 1.0 mm diameter pinhole collimator. For instance, the recorded CNR values for the superficially simulated SLN (15 mm depth) containing 0.1 MBq of 99mTc using 0.5 and 1.0 mm diameter pinhole collimators are 6.48 and 16.42, respectively (~87% difference). Gamma and hybrid optical images were acquired using the HGC for the simulated thyroid gland. The count profiles through the middle of the simulated thyroid gland images provided by both pinhole collimators were obtained. The HGC could clearly differentiate the individual peaks of both thyroid lobes in the gamma image produced by the 0.5-mm pinhole collimator. In contrast, the recorded count profile for the acquired image using the 1.0-mm-diameter pinhole collimator showed broader peaks for both lobes, reflecting the degradation of the spatial resolution with increasing the diameter of the pinhole collimator. This anthropomorphic head and neck phantom provides a valuable tool for assessing the imaging ability of gamma cameras used for imaging the head and neck region. The standardisation of test phantoms for SFOV gamma systems will provide an opportunity to collect data across various medical centres. The phantom described is cost effective, reproducible, flexible and anatomically representative.


Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention.
Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100-200ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72-channel ERPs recorded from 152 individuals (ages 13-68years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212ms peak latency), P3 source (385ms) and a late centroparietal source (630ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSD-PCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli.


[Liver monooxygenase system inducers in the treatment of respiratory distress syndrome in newborn].
Physical and biochemical parameters of pulmonary surfactant (PS) were studied in 6-day-old rabbits with the respiratory distress syndrome (RDS) treated by benzonal and zixorin inductors. Surface-active characteristics of PS were impaired under conditions of RDS at the expense of deficiency of total phospholipids, specifically phosphatidylcholine (PC) and phosphatidylethanolamine (PEA). Treatment with benzonal and zixorin improved the surface-active characteristics of PS and increased the content of total phospholipids mainly at the expense of PC and PEA.


A critical analysis of secondary overtriage to a Level I trauma center.
Trauma centers often receive transfers from lower-level trauma centers or nontrauma hospitals. The aim of this study was to analyze the incidence and pattern of secondary overtriage to our Level I trauma center. We performed a 2-year retrospective analysis of all trauma patients transferred to our Level I trauma center and discharged within 24 hours of admission. Reason for referral, referring specialty, mode of transport, and intervention details were collected. Outcomes measures were incidence of secondary overtriage as well as requirement of major or minor procedure. Major procedure was defined as surgical intervention in the operating room. Minor procedures were defined as procedures performed in the emergency department. A total of 1,846 patients were transferred to our Level I trauma center, of whom 440 (24%) were discharged within 24 hours of admission. The mean (SD) age was 35 (21) years, 72% were male, and mean (SD) Injury Severity Score (ISS) 4 (4). The most common reasons for referral were extremity fractures (31%), followed by head injury (23%) and soft tissue injuries (13%).Of the 440 patients discharged within 24 hours, 380 (86%) required only observation (268 of 380) or minor procedure (112 of 380). Minor procedures were entirely consisted of fracture management (n = 47, 42%) and wound care (n = 65, 58%). The mean (SD) interfacility transfer distance was 45 (46) miles. Mean (SD) hospital charges per transfer were $12,549 ($5,863). A significant number of patients transferred to our trauma center were discharged within 24 hours; most of them required observation and/or minor procedures. Appropriately increasing primary hospital resources, in addition to interhospital outreach in the form of education or telemedicine, should be considered to decrease the number of avoidable transfers. Epidemiologic study, level III.


Proliferative responses of lymphocytes to food antigens are useful for detection of allergens in nonimmediate types of food allergy.
Food allergy is clinically classified into two types, immediate and nonimmediate. Radioallergosorbent test (RAST) is a sensitive procedure for the diagnosis of IgE-mediated hypersensitivity but not for other types of hypersensitivity. There is not yet a sensitive blood examination for detection of allergens in nonimmediate types of food allergy. Of the total number of subjects in our study, twenty-two children had nonimmediate types of food allergy (hen's egg, cow's milk, soybean, or buckwheat flour), atopic dermatitis, allergic tension fatigue syndrome or pulmonary hemosiderosis. For these children, manifestations of the allergy did not appear earlier than 2 hours after ingestion of the offending food. Eighteen children in the study developed acute urticaria, angioedema, or bronchial asthma appearing within 2 hours of the challenge. Fifteen nonatopic healthy children were selected as controls. Proliferative responses of peripheral blood mononuclear cells (PBMCs) to food antigens were measured in nonimmediate types of food allergy. The proliferative responses of PBMCs to each offending food antigen in patients with nonimmediate types of food allergy were significantly higher than those of healthy controls and patients with immediate types of food allergy, respectively. Moreover, in each case with nonimmediate type, the proliferative responses to food antigens other than the offending food were not detected. When PBMCs were twice stimulated with the offending food antigen, the same results were obtained. These results indicate that the proliferative response of PBMCs to food antigens is specific to each offending food antigen in nonimmediate types of food allergy. Taken together, proliferative responses of PBMCs to each food antigen are useful for detection of allergens in nonimmediate types of food allergy.