Quantitative evaluation of HIV and SIV co-receptor use with GHOST(3) cell assay.
An assay has been established for quantitative evaluation of lentivirus coreceptor use with the help of GHOST(3) cells. GHOST(3) cells were derived from the human osteosarcoma cell line, HOS, and have been engineered to stably express CD4 and one or another of the chemokine receptors CCR3, CCR5, CXCR4, CXCR6/STRL33/Bonzo, or the orphan receptor GPR15/BOB. The indicator cell line carries the HIV-2 long terminal repeat-driven green fluorescence protein (GFP) gene, which becomes activated upon infection with HIV or SIV. Viral entry is followed by Tat activation of transcription and GFP becomes expressed. Infected cells can be detected as early as 2 or 3 d after infection by simple fluorescence microscopic observation. The simplicity of the GHOST(3) cell system makes it particularly suitable for screening of a large number of isolates. In addition, the efficiency of co-receptor use can be accurately quantitated with flow cytometric analysis. Thus, the most efficiently used co-receptor of multitropic isolates can be determined. It is also possible to sensitively determine co-receptor switch of sequential isolates from the same individual.


Changes in vascular function and structure in juvenile idiopathic arthritis.
Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).


Factors that influence exhaled nitric oxide in Italian schoolchildren.
Conflicting results exist about the meaning of exhaled nitric oxide (eNO) in epidemiologic studies, mainly because of the numerous factors that may affect the measurement. To evaluate the role of the factors that influence eNO levels in a sample of schoolchildren with or without respiratory diseases. We studied 335 schoolchildren, ages 10 to 16 years, from 8 schools in Palermo, Italy. After a respiratory questionnaire was completed, spirometry, skin tests, and eNO measurements were performed. Among 335 children, 13.7% reported symptoms of bronchial asthma, 46.9% reported symptoms of rhinitis, and 39.4% were asymptomatic. The ratio of forced expiratory volume in 1 second to forced vital capacity was 87.6% (SD, 6.4%) in the bronchial asthma group, 90.6% (SD, 5.0%) in the rhinitis group, and 90.4% (SD, 5.1%) in the asymptomatic group (P < .002). Atopic children constituted 52.2% of the bronchial asthma group, 40.1% of the rhinitis group, and 28.8% of the asymptomatic group. Among atopic children, 102 (82%) had a positive skin test result for Dermatophagoides. Median eNO was 12.6 ppb in nonatopic children and 21.2 ppb in atopic children (P < .001, by Mann-Whitney U test). Among asymptomatic children, atopic children had significantly higher eNO levels than did nonatopic children (P < .001). In nonatopic children, no difference was found in log transformation eNO among healthy, rhinitic, or asthmatic children. Log transformation eNO increased with the number of positive skin test results (P < .001). Atopy, asthma, male sex, and indoor allergens were predictors of increased eNO in a logistic model. Atopy (in particular, sensitization to indoor and perennial allergens) is strongly associated with higher eNO levels. Such association is enhanced by asthma.


The prospective isolation of viable, high ploidy megakaryocytes from adult murine bone marrow by fluorescence activated cell sorting.
Mature megakaryocytes (MM) can be up to 65 μM in diameter and due to their size, viable and pure MM populations have been difficult to isolate in large numbers. Here in, we report a fluorescence activated cell sorting (FACS) method by which viable and pure populations of 8 N, 16 N, 32 N, and 64 N MM can be isolated from murine bone marrow (BM).


Behavioral and Psychological Factors in Buffering Diabetes-related Disability Development.
Diabetes is associated with disability development. Healthy behaviors and psychosocial support can help patients manage their disease. To examine the role of various behavioral and psychological factors in buffering the effect of diabetes on disability development over time in Taiwanese adults. Data on 5,131 adults aged ≥50 years were obtained from the Taiwan Longitudinal Study on Aging. A cohort sequential multilevel design was employed to analyze the association between behavioral and psychosocial factors and the risk of disability over a 11-year period. In patients with diabetes, having social support and exercising more than six times a week were associated with 4% and 49% reductions in the risk of disability, respectively (βdiabetes*socialsupport = -0.285, p = .006; βdiabetes*exercise3 = -2.612, p = .007). Exercising more than six times a week had an additional significant protective effect against disability development per year (βdiabetes*exercises3*age = -0.241, p = .038). Depression did not significantly interact with diabetes. However, a trajectory analysis revealed that individuals who had both diabetes and depression had the highest disability score from middle age among all participants. Engaging in frequent exercise is the most influential factor for reducing the risk of disability in patients with diabetes. Social support provides an additional benefit for disability prevention in individuals with diabetes.


[Physiotherapy treatments for the care of patients with chronic pain].
In recent years, numerous studies have highlighted the advances made possible by kinesitherapy treatments. These can be used to reduce the frequency, intensity and duration of pain, as well as the functional repercussions of chronic pain. The neurophysiological mechanism involved in primary chronic pain and the pathology producing secondary chronic pain must be taken into account in determining the nature of the treatments to be implemented. This article presents the main physiotherapy interventions recommended for the management of patients with chronic pain, according to the type of pain experienced (nociceptive, neuropathic or nociplastic).


Cooperating mutations of receptor tyrosine kinases and Ras genes in childhood core-binding factor acute myeloid leukemia and a comparative analysis on paired diagnosis and relapse samples.
c-KIT mutations have been described in core-binding factor (CBF) acute myeloid leukemia (AML) at diagnosis. The role of c-KIT mutations in the relapse of CBF-AML is not clear. The role of CSF1R mutation in the pathogenesis of AML remains to be determined. We analyzed receptor tyrosine kinases (RTKs) and Ras mutations on 154 children with AML. Also, we examined the paired diagnosis and relapse samples in CBF-AML. CBF-AML accounted for 27% (41/154). c-KIT mutations were detected in 41.5% of CBF-AML at diagnosis (6 in exon 8, 10 in exon 17 and 1 in both exons 8 and 17) , FLT3-TKD 2.7%, N-Ras mutations 7.3% and K-Ras mutations 4.9%. FLT3-LM and CSF1R mutations were not found in CBF-AML. The mutations of RTKs and Ras were mutually exclusive except for one patient who had both c-KIT and N-Ras mutations. Eight of the 41 CBF-AML patients relapsed; four patients retained the identical c-KIT mutation patterns as those at diagnosis, the remaining four without c-KIT mutations at diagnosis did not acquire c-KIT mutations at relapse. Our study showed that 54% of childhood CBF-AML had RTKs and/or Ras mutations; c-KIT but not CSF1R mutations play a role in the leukemogenesis of childhood CBF-AML.


Comparison of three files to prepare curved root canals.
Flex-R, Ultra-Flex (Ni-Ti construction), and K-type files were compared using a circumferential filing technique on 96 extracted human maxillary molars. Buccal canals with minimal initial curvature of 24 degrees were used. The maximal initial curvature was 52 degrees. Canal curvature was measured before and after filling, and changes were analyzed statistically. The angle of curvature was better maintained with the Flex-R and Ultra-Flex files.


Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins.
This randomized controlled trial assessed the safety and effects of twice-weekly weight training among recent breast cancer survivors. Outcomes included body size and biomarkers hypothesized to link exercise and breast cancer risk. A convenience sample of 85 recent survivors was randomized into immediate and delayed treatment groups. The immediate group trained from months 0 to 12; the delayed treatment group served as a no exercise parallel comparison group from months 0 to 6 and trained from months 7 to 12. Measures at baseline, 6 and 12 months included body weight, height, body fat, lean mass, body fat %, and waist circumference, as well as fasting glucose, insulin, insulin resistance, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding protein-1, IGFBP-2, and IGFBP-3. Injury reporting was standardized. The intervention resulted in significant increases in lean mass (0.88 versus 0.02 kg, P < 0.01), as well as significant decreases in body fat % (-1.15% versus 0.23%, P = 0.03) and IGF-II (-6.23 versus 28.28 ng/mL, P = 0.02) comparing immediate with delayed treatment from baseline to 6 months. Within-person changes experienced by delayed treatment group participants during training versus no training were similar. Only one participant experienced a study related injury that prevented continued participation. Twice-weekly weight training is a safe exercise program for recent breast cancer survivors that may result in increased muscle mass, as well as decreased body fat % and IGF-II. The implications of these results on cancer recurrence or survival may become more evident with longer exercise intervention trials among breast cancer survivors.


Endoscopic re-establishment of urethral continuity after traumatic disruption of the membranous urethra.
We report 3 cases of complete traumatic disruption of the membranous urethra treated by transurethral section of the scar tissue with transvesical endoscopic guidance and digital rectal control. Postoperatively, the patients required an average of 3 subsequent urethrotomies. They remain well, continent and free of voiding symptoms for 28, 11 and 14 months after re-establishment of urethral continuity. We suggest that this treatment be considered as an alternative to conventional surgical repair, particularly in elderly and other high risk patients.


Impact of unilateral stroke on right hemisphere superiority in executive control.
In our previous study, we have demonstrated a right hemisphere superiority in executive control of attention, with the right hemisphere being more efficient in dealing with conflict for stimuli presented in the left visual field. However, the unique and synergetic contribution of the two hemispheres to this superiority effect is still elusive. Here, using the lateralized attention network test, we compared the flanker conflict effect for stimuli presented in the left and right visual fields in patients with an ischemic stroke in the right or left hemisphere as the unilateral lesion groups and in patients with a transient ischemic attack without an acute infarction as the control group. In contrast to the transient ischemic attack group, which demonstrated a right hemisphere superiority in conflict processing, there was no evidence for such an effect in both unilateral stroke groups. These results can be explained by our model proposing that there is bilateral hemispheric involvement for conflict processing for information received from the left visual field and unilateral hemispheric involvement for conflict processing for information received from the right visual field, resulting in more efficient processing for the left visual field, i.e., the right hemisphere superiority effect. When there is damage to either hemisphere, the responsibility of conflict processing will largely fall on the intact hemisphere, eliminating the right hemisphere superiority effect.


Three-Dimensional Peri-Implant Tissue Changes in Immediately vs. Early Placed Tapered Implants Restored with Two Different Ceramic Materials-1 Year Results.
A prospective multi-center randomized controlled clinical trial was performed to digitally analyze tissue volume changes in immediately and early placed implants with simultaneous bone augmentation restored with two different all-ceramic materials. A total of 60 patients received 60 bone-level tapered implants (BLT, Straumann AG) immediately (n = 30) or early placed, 8-10 weeks after tooth extraction, (n = 30). Implants were restored with all-ceramic single crowns fabricated out of zirconia (Lava Plus, 3M), or lithium disilicate (E.max CAD, Ivoclar Vivadent AG) bonded to titanium base abutments (Variobase for Cerec, Straumann AG). Impressions were taken at baseline (BL), 6 and 12 months, and STL data were used to define an area of interest (AOI) to analyze peri-implant volume changes and midfacial recessions. For immediate placement, a mean volume loss of -5.56 mm3 (±5.83 mm3) was found at 6 months, and of -6.62 mm3 (±6.56 mm3) at 12 months. For early placement, a mean volume loss of -1.99 mm3 (±5.82 mm3) at 6 months, and of -3.7 mm3 (±5.62 mm3) at 12 months was found. The differences in volume loss at 12 months between the two implant placement protocols were significant (p = 0.005). In both groups, mean midfacial recessions of 0.48 mm (±0.52) occurred. A more pronounced peri-implant volume loss can be expected 12 months after immediate implant placement compared with early placement.


Mechanism of phage P22 tailspike protein folding mutations.
Temperature-sensitive folding (tsf) and global-tsf-suppressor (su) point mutations affect the folding yields of the trimeric, thermostable phage P22 tailspike endorhamnosidase at elevated temperature, both in vivo and in vitro, but they have little effect on function and stability of the native folded protein. To delineate the mechanism by which these mutations modify the partitioning between productive folding and off-pathway aggregation, the kinetics of refolding after dilution from acid-urea solutions and the thermal stability of folding intermediates were analyzed. The study included five tsf mutations of varying severity, the two known su mutations, and four tsf/su double mutants. At low temperature (10 degrees C), subunit-folding rates, measured as an increase in fluorescence, were similar for wild-type and mutants. At 25 degrees C, however, tsf mutations reduced the rate of subunit folding. The su mutations increased this rate, when present in the tsf-mutant background, but had no effect in the wild-type background. Conversely, tsf mutations accelerated, and su mutations retarded the irreversible off-pathway reaction, as revealed by temperature down-shifts after varied times during refolding at high temperature (40 degrees C). The kinetic results are consistent with tsf mutations destabilizing and su mutations stabilizing an essential subunit folding intermediate. In accordance with this interpretation, tsf mutations decreased, and su mutations increased the temperature resistance of folding intermediates, as disclosed by temperature up-shifts during refolding at 25 degrees C. The stabilizing and destabilizing effects were most pronounced early during refolding. However, they were not limited to subunit-folding intermediates and were also observable during thermal unfolding of the native protein.


Silicosis and tuberculosis: A systematic review and meta-analysis.
Silicosis mostly happens in workers with high silica exposure and may accompany the development of various diseases like tuberculosis, cancer, or autoimmune diseases. The term silico-tuberculosis describes a condition in which an individual is affected by both silicosis and tuberculosis at the same time. This systematic review and meta-analysis study was conducted to evaluate the risk of tuberculosis in silicosis patients and individuals exposed to silica dust. We performed a systematic search for relevant studies up to 6 September 2022 using PubMed/ Medline, and Embase with the following keywords in titles or abstracts: "silicosis" OR "silicoses" OR "pneumoconiosis" OR "pneumoconioses" AND "tuberculosis". Cohort and case-control studies containing relevant and original information about tuberculosis infection in silicosis patients were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the relative risk of tuberculosis in individuals with silicosis compared to those without; these were evaluated using the random effects model due to the estimated heterogeneity of the true effect sizes. Out of 5352 potentially relevant articles, 7 studies were eligible for systematic review, of which 4 cohort studies were included for meta-analysis. The total population of all studies was 5884, and 90.63% were male. The mean age of participants was 47.7 years. Our meta-analysis revealed a pooled risk ratio of 1.35 (95%CI 1.18-1.53, I 2: 94.30%) which means an increased risk of silicosis patients and silica-exposed individuals to tuberculosis infection. Silicosis and silica dust exposure increase the risk of tuberculosis. Therefore, we suggest that individuals with long-time silica exposure, like mine workers, be routinely considered for both silicosis and tuberculosis screening programs.


[Amputation injuries of the upper extremity--early complications after replantation and revascularization].
Within a time of ten years 144 patients with difficult injuries on their hands were operated. These were 95 replantations and 102 revascularizations. 26 patients had to be operated again because of arterial and venous thrombosis. 46% of our patients had early vascular complications already within 24 hours. The frequency of thrombosis was increasing with the accompanying soft tissue injury and therefore with the gravity of the trauma. Avulsion injuries had of course the worst prognosis. After diagnosis of vascular occlusion within the replanted finger there should be a quick surgical revision of the anastomosis. With the help of application of urokinase into the artery we could create the circulation without any new production of the anastomosis in two cases. With a subtile technique of the disposition of the anastomosis and two venous connections to one artery with the replanted fingers we could reduce the rate of thrombosis and improve the results.


Does Lichen Planus Cause Increased Carotid Intima-Media Thickness and Impaired Endothelial Function?
Lichen planus (LP) has been associated with cardiovascular disease (CVD) risk factors, but there are no studies on the association between LP and subclinical atherosclerosis. We investigated the presence of subclinical atherosclerosis in patients with LP not known to have CVD using carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD). The study included 30 patients with LP and 30 controls. High-resolution ultrasonography was used to assess CIMT and FMD. Participants' biochemical parameters, body mass index (BMI), and waist circumference were recorded in both groups. FMD was significantly lower (7.45% ± 3.63% vs 11.01% ± 5.34%; P = 0.004) and CIMT was higher (0.8 mm [range, 0.7-0.9 mm] vs 0.6 mm [0.4-0.6 mm]; P < 0.001) in the LP group compared with the control group. After adjustment for age, sex, BMI, high-density lipoprotein cholesterol levels, and C-reactive protein levels, the presence of LP was associated with impairment of FMD (β = -0.441; 95% CI, -9.336 to -0.321; P = 0.037) and an increase in CIMT (β = 0.459; 95% CI, 0.057 to -0.351; P = 0.008). Reduced FMD and increased CIMT levels are sensitive indicators of target-organ damage and display increased risk for cardiovascular morbidity and mortality. Our study found that patients with LP showed a tendency toward impaired levels of FMD and increased CIMT. LP may be a novel predictor of early vascular dysfunction and structural changes.


Association of DNA adducts and genotypes with birth weight.
The relationships between DNA adducts and birth weight and between birth weight and genetic polymorphisms of metabolic genotypes were studied using DNA from the children part of placental samples. The samples were collected in the districts of Teplice and Prachatice and in the city of Prague. DNA adducts were analyzed by (32)P-postlabeling in a total of 199 subjects, genetic polymorphisms in 1013 subjects. GSTM1, GSTP1, GSTT1, CYP1A1*2A, and CYP1A1*2C genotypes were determined for each subject. The level of DNA adducts was not correlated with birth weight in any group (N=199), including that from the polluted district of Teplice (N=90). Birth weight was significantly decreased by smoking, ETS and alleles of CYP1A1*2C. The risk of low birth weight and prematurity was significantly increased by genotypes of GSTM1 and CYP1A1*2C and the combination GSTM1+CYP1A1*2A. Genotypes are primarily effect modifiers, whose effect incorporates the effect of environmental factors. This means that in the future, the impact of air pollution on children's health should be studied together with their genetic polymorphisms.


The effect of verapamil, lanthanum and local anesthetics of serotonin release from rabbit platelets.
The effect of calcium blockers (verapamil, local anesthetics and lanthanum chloride) on serotonin release from rabbit platelets was studied. The following results were obtained: (1) Verapamil and tetracaine (but not lanthanum) caused a time- and dose-dependent release of serotonin. The curves describing the time-course and those describing the concentration dependence of the release were sigmoid, suggesting cooperativity. (2) Thrombin-induced release from the platelets was dependent upon extracellular sodium ions, while no dependence was observed for the drug-induced release. (3) The release by verapamil was partially inhibited by prostaglandin E1 and theophylline which are known to raise intracellular cAMP levels, but was unaffected by the prostaglandin-synthesis inhibitor, indomethacin. (4) Verapamil, tetracaine and lanthanum inhibited thrombin-induced release of serotonin. The curve of dose dependence of the inhibition by verapamil and tetracaine was not sigmoid. The inhibition by verapamil and tetracaine was reversed by extracellular calcium ions, but no effect of this ion on the drug-induced release reaction was observed. It is concluded that the serotonin release induced by some calcium blockers and the inhibition of the thrombin-induced release by the same drugs are two separate phenomena. It is suggested that verapamil and tetracaine-induced release are mediated by exocytotic processes brought about by the interference of the drugs with calcium distribution between the cytosol and storage compartments within the platelet.


Levels and composition of microplastics and microfibers in the South Saskatchewan River and stormwater retention ponds in the City of Saskatoon, Canada.
In recent decades, contamination of the environment with microplastics and microfibers has been recognized as a pervasive and ubiquitous issue of global concern. While much research in this field has been undertaken in marine environments, more recent studies have identified rivers as major conveyors of plastic pollution from terrestrial into marine systems. However, reports on the levels and composition of microplastic and microfiber contamination in rivers of the Canadian prairie region, specifically the South Saskatchewan River (SSR), are scarce, which leaves this vital source of water for societies and ecosystems in a vulnerable state. To fill this gap, we obtained samples from seven sites along the Saskatchewan portion of the SSR, as well as three stormwater retention ponds (SRP) in the city of Saskatoon during the spring, summer, and fall of 2020. We used optical and Raman microscopy to enumerate and characterize particles in these samples. Total levels of particles and fibers in all samples ranged from 32 to 116 particles m-3. Most particles (approximately 77%) were natural fibers, while polymers accounted for the remaining 33%. Average microplastic levels were lower (3.18 ± 3 particles m-3) downstream of Lake Diefenbaker, a large reservoir on the SSR, compared to upstream (12.0 ± 9 particles m-3). Retention of microplastics in the reservoir could explain the lower mean microplastic concentration of 4.43 ± 3 particles m-3 recorded in the SSR compared to mean concentrations of 26.2 ± 18 particles m-3 reported in the North Saskatchewan River, which is not dammed. This study is among the first to describe microplastic and microfiber levels in the SSR and thereby helps improve our understanding of this pervasive environmental contaminant on the Canadian prairies.


The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism.
This study aimed to determine whether postnatal treatment with recombinant human IGF-1 (rhIGF-1)/binding peptide 3 (BP3) ameliorates lung injury and prevents pulmonary hypertension (PH) in bronchopulmonary dysplasia (BPD) models. We used two models of BPD in this study: one model that was associated with chorioamnionitis (CA), stimulated by intra-amniotic fluid and exposure to lipopolysaccharide (LPS), whereas the other was exposed to postnatal hyperoxia. Newborn rats were treated with rhIGF-1/BP3 (0.2 mg/Kg/d) or saline via intraperitoneal injection. The study endpoints included the wet/dry weight (W/D) ratio of lung tissues, radial alveolar counts (RACs), vessel density, right ventricular hypertrophy (RVH), lung resistance, and lung compliance. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the degree of lung injury and pulmonary fibrosis. IGF-1 and eNOS expression were detected using western blotting or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The levels of SP-C, E-cadherin, N-cadherin, FSP1, and Vimentin in the lung tissues were detected by immunofluorescence. LPS and hyperoxia treatment increased lung injury and pulmonary fibrosis, enhanced RVH and total respiratory resistance, and decreased RAC, pulmonary vascular density and pulmonary compliance in young mice (all p < 0.01). Simultaneously, LPS and hyperoxia induced an increase in epithelial-mesenchymal transition (EMT) in airway epithelial cells. However, rhIGF-1/BP3 treatment reduced lung injury and pulmonary fibrosis, decreased RVH and total respiratory resistance, and enhanced RAC, pulmonary vascular density and pulmonary compliance, as well as inhibited EMT in airway epithelial cells in LPS and hyperoxia treated mice. Postnatal rhIGF-1/BP3 treatment relieved the effects of LPS or hyperoxia on lung injury and prevented RVH, providing a promising strategy for the treatment of BPD.


Identity-related experiences of Asian American trainees in gynecologic oncology.
Anti-Asian violence increased during the COVID-19 pandemic. Asian American/Pacific Islanders (AAPI) represent a diverse population experiencing a long history of stereotyping and exclusionism; however, this group is often left out of diversity/inclusion conversations. In academic medicine, AAPI are under-represented in leadership. We characterized the personal/professional experiences of AAPI gynecologic oncology trainees and assessed the impact of a virtual panel discussion with leaders in the field. An anonymous survey was disseminated online to trainees in/interested in gynecologic oncology fellowship who identified as AAPI, using modified snowball sampling. A virtual session with AAPI leaders in gynecologic oncology discussed themes emerging from survey responses. Session attendees completed an anonymous follow-up survey. Results were assessed quantitatively and qualitatively. 44/59 (75%) respondents participated in the pre-survey; 23 (39%) participated in the virtual session. All session participants (23/23, 100%) completed the post-session survey. Participants reported increased identity-related thoughts with the COVID-19 pandemic (88% during, 61% prior). Sixty-eight percent reported that identity-related thoughts/awareness changed during the pandemic. Presence of AAPI colleagues was associated with higher perceived identity-related support from their department. Of those without AAPI coworkers, none (0%) felt 'moderately' or 'extremely well supported.' Qualitative analysis demonstrated that the panel discussion created a sense of community and encouragement, combating previously reported isolation and self-consciousness. Participants reported more connection with their heritage and identified more personal/professional topics that might be related to their cultural backgrounds. This intervention demonstrates the opportunity to provide a supportive network for mentorship and professional development in a culturally inclusive way.


Monitoring photosynthetic activity of crustose lichens using a PAM-2000 fluorescence system.
CO2 exchange and fluorescence yield of the crustose lichen Buellia frigida were measured in situ by means of a CO2 porometer and a PAM-2000, a newly developed portable fluorescence system. The pulse amplitude modulation system of the PAM-2000 allows measurements in the field under ambient light, temperature and moisture conditions without dark adaptation of the sample. CO2 exchange and fluorescence measurements were well correlated when measured under natural conditions in continental Antarctica during a drying cycle of melt-water-soaked lichen thalli. It was shown that the fluorescence parameter ΔF/Fm' is a measure of the photosynthetic activity of the lichen. It proved possible, using the PAM-2000, to differentiate the physiological performance of the thallus centre and the marginal lobes. The distribution of water in the thallus during a drying cycle was shown to be inhomogeneous. The photosynthetic rates of B. frigida calculated on an area basis are comparatively high and indicate that this lichen is well adapted to its habitat conditions in this part of continental Antarctica.


Salter-Harris type III fracture of the proximal humeral physis.
Salter-Harris type III, IV and V injuries of the proximal humeral physis are rare. We report an undisplaced Salter-Harris type III injury of the humeral head physis in a 10-year-old girl. The fracture united with non-operative treatment.


An audit of external trigeminal nerve stimulation (eTNS) in epilepsy.
External trigeminal nerve stimulation (eTNS) is a non-invasive neurostimulation treatment for drug refractory epilepsy. There is limited published data on the efficacy of eTNS and none relating to quality of life, mood or effect on sleep quality. We audited its use in 42 patients with drug refractory epilepsy at a tertiary centre, between 02/04/2013 and 14/08/2015. Data was collected on seizure frequency, quality of life, mood and sleep quality before and after initiating treatment. 45% of patients continued to use eTNS at the end of the audit period. We observed a significant improvement in both quality of life and mood in those without intellectual disabilities. A decrease in seizures (-11.0%, min -60, max +65) was observed though this did not reach statistical significance with the relatively small numbers available for analysis. Further controlled studies are required to confirm the efficacy of eTNS. However, as it is non-invasive, flexible and safe eTNS can be considered as an option in patients with drug refractory epilepsy.


Identification of a TuMV isolate (TuMV-ZR) from Pseudostellaria heterophylla and its development into a viral expression vector.
Pseudostellaria heterophylla (P. heterophylla) is a popular Chinese medicinal herb that is cultivated widely in China. Viral infection is commonly encountered during the production of P. heterophylla. To identify viruses causing P. heterophylla disease, sRNA and mRNA libraries were built for 2 sets of P. heterophylla plants, one set that was planted only once (FGP) and one that was planted three consecutive three times (TGP) in a field, using virus-free tuberous roots as reproductive materials. A comprehensive procedure, including assembling virus-derived sRNA (vsRNA), assessing and cloning the full-length viral genome, building an infectious cloning vector and constructing a virus-based expression vector, was performed to identify viruses infecting P. heterophylla. Ultimately, 48 contig-related viruses were mined from 6 sRNA and 6 mRNA P. heterophylla libraries. A 9762-bp fragment was predicted to be the complete genome of TuMV virus. This sequence was cloned from P. heterophylla, and its infectivity was evaluated using the virus-infection model plant Nicotiana benthamiana (N. benthamiana) and host plant P. heterophylla. The resulting 9839-bp viral genome was successfully obtained from P. heterophylla and identified as a new P. heterophylla TuMV-ZR isolate. Simultaneously, TuMV-ZR infectious clones were shown to effectively infect P. heterophylla. Furthermore, TuMV-ZR expression vectors were developed, and the ability of a TuMV-ZR-based vector to express foreign genes was determined by analysis with the reporter gene EGFP. TuMV-ZR-based vectors were found to continuously express foreign genes in different organs of P. heterophylla throughout the whole vegetative period. In addition, TuMV-ZR vectors carrying EGFP accumulated in the tuberous roots of P. heterophylla, confirming that tuberous roots are key targets for viral infection and transmission. This study revealed the core pathogenicity of P. heterophylla mosaic virus and developed a new TuMV-ZR-based expression tool that led to long-term protein expression in P. heterophylla, laying the foundation for the identification of the mechanisms of P. heterophylla infection with mosaic viruses and developing tools to express value proteins in the tuberous roots of the medicinal plant P. heterophylla.


Peripheral inflammation facilitates Abeta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord.
Whole-cell patch-clamp recordings were made from substantia gelatinosa (SG) neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in fast synaptic transmission induced by peripheral inflammation. In slices from naive rats, primary afferent stimulation at Abeta fiber intensity elicited polysynaptic EPSCs in only 14 of 57 (25%) SG neurons. In contrast, Abeta fiber stimulation evoked polysynaptic EPSCs in 39 of 62 (63%) SG neurons recorded in slices from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48 hr earlier (p < 0.001). Although the peripheral inflammation had no significant effect on the threshold and conduction velocities of Abeta, Adelta, and C fibers recorded in dorsal roots, the mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive: 33.2 +/- 15.1 microA, n = 57; inflamed: 22.8 +/- 11.3 microA, n = 62, p < 0.001), and the mean latency of EPSCs elicited by Abeta fiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3 +/- 1.8 msec, n = 36 vs 6.0 +/- 3.5 msec, n = 12; p = 0.010). Abeta fiber stimulation evoked polysynaptic IPSCs in 4 of 25 (16%) cells recorded from naive rat preparations and 14 of 26 (54%) SG neurons from CFA-treated rats (p < 0.001). The mean threshold intensity for IPSCs was also significantly lower in CFA-treated rats (naive: 32.5 +/- 15.7 microA, n = 25; inflamed: 21. 9 +/- 9.9 microA, n = 26, p = 0.013). The facilitation of Abeta fiber-mediated input into the substantia gelatinosa after peripheral inflammation may contribute to altered sensory processing.


[Electron-microscopic autoradiography of RNA synthesis in the myocardium after damage to it].
Thermic burn of the wall of the left cardiac ventricle was inflicted to new born rats. Twenty-four hours after the injury the RNA synthesis of the myocardial cells remote from the site of burn were investigated by electron-microscopic autoradiography. Tissue samples were fixed 2 and 6 hours after the 3H-uridine injections. As compared with the control, experimental animals displayed a reduction of silver grains density over the nucleus and the cytoplasm of cardiomyocytes.


Studies of cholesterol and bile acid metabolism, and early atherogenesis in hamsters fed GT16-239, a novel bile acid sequestrant (BAS).
The purpose of this study was to compare the efficacy of GT16-239, an alkylated, cross-linked poly(allylamine) bile acid sequestrant with cholestyramine on cholesterol and bile acid metabolism, and early aortic atherosclerosis in hypercholesterolemic male F1B Golden Syrian hamsters. In this controlled study, 42 hamsters were divided into six groups and were fed a chow-based hypercholesterolemic diet supplemented with a 10% oil blend (55% coconut/45% corn), 0.1% cholesterol (w/w) (control) and either 0.9 or 1.2% cholestyramine or 0.2, 0.4 or 0.6% GT16-239 for 13 weeks. Laboratory analyses included evaluating plasma lipoprotein cholesterol and triglyceride concentrations, hepatic HMG-CoA reductase and 7 alpha-hydroxylase activities, fecal excretion of bile acids and neutral sterols, hepatic cholesterol concentrations, and early atherosclerosis (aortic fatty streak area). Relative to the control diet, the 0.6% GT16-239 versus the 1.2% cholestyramine significantly inhibited the elevation of plasma lipoprotein total cholesterol (TC) (-69% vs -40%), high density lipoprotein-cholesterol (HDL-C) (-49% vs -30%), and non-HDL-C (-81 vs -48%) concentrations; increased the activities of both HMG-CoA reductase (1492% vs 62%) and 7 alpha-hydroxylase (175% vs 86%); lowered the concentration of hepatic cholesteryl ester (-94% vs -59%); increased fecal cholesterol concentration (+28% vs -10%); and decreased aortic fatty streak area (-100% vs -86%). Unexpected findings of this comparison were increased fecal concentrations of cholic acid (533%) and chenodeoxycholic acid (400%) and the reduction in lithocholic acid (-50%) in the 0.6% GT16-239 compared to the 1.2% cholestyramine group. In summary, GT16-239 had a greater impact on cholesterol metabolism and early atherosclerosis in hypercholesterolemic hamsters than cholestyramine.


The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer.
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway.


Future treatment options with capecitabine in solid tumours.
The oral fluoropyrimidine, capecitabine is attracting great interest in the context of tumour-selective therapy and rationally designed combination regimens. Agents such as taxanes upregulate thymidine phosphorylase (TP), and there is therefore a clear rationale for their combination with capecitabine. Preclinical studies of capecitabine/taxane combination therapy demonstrated synergistic antitumour activity and phase I studies showed encouraging efficacy. Therefore, a randomised, phase III trial (docetaxel versus docetaxel/capecitabine) has been initiated in anthracycline-refractory metastatic breast cancer patients. Recruitment is complete. In colorectal cancer, capecitabine/oxaliplatin combination therapy is promising and a phase I, dose-finding trial has been conducted in patients with refractory metastatic solid tumours. A similar trial has evaluated capecitabine/irinotecan combination treatment. Capecitabine is also being investigated as adjuvant therapy for colorectal and breast cancers. The primary objective of the ongoing X-ACT trial in almost 2000 Dukes' C colon cancer patients is to demonstrate at least equivalent disease-free survival between capecitabine and the Mayo Clinic regimen. In addition, the CALGB is planning a randomised, phase III trial of capecitabine versus doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil (CMF) as adjuvant treatment in high-risk, node-negative breast cancer patients aged >65 years.


Effect of scraping therapy on interleukin-1 in serum of rats with lumbar disc herniation.
To explore the effect of scraping therapy on the Interleukin-1 (IL-1) levels of rats with lumbar disc herniation (LDH). Fifty male rats were devided into a blank group (A), a sham operation group (B), a model group (C), a scraping group (D), and a drug group (E). The rats in the group B were treated with sham operation, and groups C, D and E were made into the LDH model by operation. After operation, group C were treated with no interventions, D were given scraping and E were fed with azathioprine. Then the IL-1 levels of different groups were detected by enzyme-linked immuno sorbent assay method. And the transplanted coccygeal vertebra discs were observed by pathological section. The IL-1 levels in the groups C, D, and E were significantly higher than those in the groups A and B (all P < 0.01), which proved the operation was successful. The IL-1 levels in the groups D and E at different periods had statistical significance (F = 414.158, P < 0.01). The treatment periods and interventions have interation (F = 46.613, P < 0.01). Multiple comparison results showed that the IL-1 levels in the groups D and E was significantly lower than that in the group C (P < 0.01), while the IL-1 levels between the groups D and E had no statistical significance (P > 0.05). Moreover, pathological section indicated that immuno-inflammatory response was hardly found in coccygeal vertebra discs in the groups A and B, while local immuno-inflammatory responses of the groups D and E were much lighter than that of the group C. Scraping therapy could inhibit the immuno-inflammatory responses in the rats with LDH caused by transplantation of autologous nucleus pulposus.


Factors predicting caregivers' readiness for vaccination of 5-11 years old children against SARS-CoV-2 - Saudi Arabia, 2022.
A significant proportion of parents are still reluctant to have their children vaccinated against COVID-19. This study aimed to determine what factors influence parents' decision to get COVID-19 vaccine for the children of age group 5-11 years. A cross-sectional study was conducted in the region Qassim of Saudi Arabia, by using a self-administered, pre-tested questionnaire to assess the predicting factors of caregivers' readiness to get their children vaccinated against COVID-19. Two-thirds of the caregivers surveyed were unwilling to get their children vaccinated against COVID-19. The factors that influence the parents' decision to get their young children (5-11 years old) vaccinated against COVID-19 were: having secondary school education (p = 0.019), family members infected with SARS-CoV-2 (p = 0.016), caregivers completed the three doses of vaccination (p = 0.003) and those who received additional flu vaccine (p = 0.014), and not experiencing the side effects of COVID-19 vaccine (p = 0.0001). Additionally, no history of COVID-19 vaccine adverse events in older 12-18 year old children (p = 0.011) and no chronic diseases in the 5-11 year old children (p = 0.001) were predictors. Caregivers' preferences about the children's vaccination were influenced by multiple factors, including educational level, having family members infected with SARS-CoV-2, caregivers completing three doses of COVID-19 vaccine, receiving additional flu vaccine with no or mild adverse events, and history of chronic diseases in the child. Understanding these factors can help determine the likelihood of the caregivers getting their child vaccinated.


Prevalence of imported malaria in Parma during 2005-2006.
Malaria is a protozoan infection caused by parasites of the genus Plasmodium (P. falciparum, P. ovale, P. vivax, P. malariae) that is transmitted from one human to another by female Anopheles mosquitoes. It can be considered a reemerging imported disease in our area because of increasing of movements from endemic countries, and nowadays it is the most common imported infection in Italy. This study describes the occurrence of imported malaria in our area between January 2005 and May 2006. During 17 months we analysed 170 blood samples belonging to 139 patients (95 foreigners and 44 Italians) with the clinical suspect of malaria. Samples were used to prepare orange acridine and Giemsa stained thin blood films for microscopic observation and to perform an immunochromatographic assay for the detection of specific plasmodia antigens. Molecular assays (nested-PCR and Real-time PCR) were also performed in order to confirm the diagnosis. Thirty-six cases of malaria were diagnosed: 35 in foreigners coming from Africa and only one in an Italian who lived in Chad. Thirty-three patients were infected by P. falciparum, 1 by P. ovale, 1 by P. vivax, and a mixed infection by P. falciparum, P. ovale and P. malariae was also found. Malaria is usually associated with travels within areas where the infection is endemic and our data demonstrated that imported malaria in our area has a prevalence of 25.89%.


Kainic acid-induced seizures: changes in brain extracellular ions as assessed by intracranial microdialysis.
The effect of kainic acid on extracellular [K+], [Ca2+], and [Na+] in the rat piriform cortex and hippocampus was studied by means of intracranial microdialysis. Either a dialysis fiber loop or horizontal Vita fiber were stereotaxically implanted within the piriform cortex or hippocampus, respectively. About 24 h later, fibers were perfused (1 ml/min) with Krebs-Ringer bicarbonate solution. Effluent samples were collected before (four at 30 min intervals), and after (six at 30 min intervals) administration of kainic acid (16 mg/kg, i.p.) or kainic acid vehicle. Kainic acid induced sequential signs of lethargy, staring, "wet-dog shakes," forepaw clonus, and tonic-clonic convulsions. In these awake free-moving rats, kainic acid induced a rapid and prolonged increase in extracellular [K+] and an apparent, but not statistically significant, decrease in extracellular [Ca2+] within the hippocampus. In the piriform cortex, kainic acid induced increases in extracellular [K+] and [Na+], which were associated with early pre-convulsive signs. In contrast to the pronounced ion changes commonly seen when the brain is activated by factors such as local application of excitatory substances or when the brain is made ischemic or hypoxic, extracellular ion concentrations are relatively well maintained during parenteral kainic acid-induced seizures.


Spring-like fibers for cardiac tissue engineering.
Recapitulation of the cellular microenvironment of the heart, which promotes cell contraction, remains a key challenge in cardiac tissue engineering. We report here on our work, where for the first time, a 3-dimensional (3D) spring-like fiber scaffold was fabricated, successfully mimicking the coiled perimysial fibers of the heart. We hypothesized that since in vivo straightening and re-coiling of these fibers allow stretching and contraction of the myocardium in the direction of the cardiomyocytes, such a scaffold can support the assembly of a functional cardiac tissue capable of generating a strong contraction force. In this study, the mechanical properties of both spring-like single fibers and 3D scaffolds composed of them were investigated. The measurements showed that they have increased elasticity and extensibility compared to corresponding straight fibers and straight fiber scaffolds. We have also shown that cardiac cells cultivated on single spring-like fibers formed cell-fiber interactions that induced fiber stretching in the direction of contraction. Moreover, cardiac cells engineered within 3D thick spring-like fiber scaffolds formed a functional tissue exhibiting significantly improved function, including stronger contraction force (p = 0.002), higher beating rate (p < 0.0001) and lower excitation threshold (p = 0.02), compared to straight fiber scaffolds. Collectively, our results suggest that spring-like fibers can play a key role in contributing to the ex vivo formation of a contracting cardiac muscle tissue. We envision that cardiac tissues engineered within these spring-like fiber scaffolds can be used to improve heart function after infarction.


Scopolamine interacts with reactions to cat and genotypic emotional reactivity in rat.
In the presence or absence of a cat the effects of scopolamine hydrobromide were investigated on approach, freezing and defecation behaviors of the bidirectionally selectively bred rat strains for emotional reactivity. Compared to the baseline behavior (absence of cat and scopolamine), both the genetic lines showed decrease in approach and increase in freezing in the presence of cat. Scopolamine in the absence of cat did not affect any of the behaviors of the nonreactive strain but increased approach and decreased freezing in the reactive strain. The presence of both cat and scopolamine affected both the strains but differently, i.e., showing no significantly change in the nonreactive, but increase in freezing and decrease in approach in the reactive strain, as compared to the respective baselines.


Inhibition of cholinergic neurotransmission in isolated guinea-pig main bronchi by SR 48968.
SR 48968 (10(-6) to 10(-5) M) inhibited the cholinergic response of the isolated guinea-pig main bronchus to electrical field stimulation. Since this effect was reversed by naloxone 10(-5) M and since SR 48968 had no effect on the contractile response to exogenous acetylcholine, we conclude that SR 48968 acts at a prejunctional level and that opioid receptors are involved. This effect was observed at concentrations approximately 75,000 times higher than those needed for blockade of tachykinin NK2 receptors.


The role of the phosphatidylinositol cycle in mitosis in sea urchin zygotes. Lithium inhibition is overcome by myo-inositol but not by other cyclitols or sugars.
We have investigated the role of the phosphatidylinositol (PI) cycle in cellular events between fertilization and first cleavage in zygotes of the sea urchin Lytechinus pictus. The effects of lithium were studied: The lithium-induced changes due to effects on the PI cycle were reversed by myo-inositol, the next step in the cycle after the lithium block, but were not reversed by scyllo-inositol or other cyclitols or sugars. In this way we implicated the PI cycle in the formation of streak birefringence, in nuclear membrane breakdown, in onset of anaphase, and in cytokinesis. With respect to karyokinesis, mitotic apparatus (MA) structure often was altered when the PI cycle was blocked, and anaphase was blocked when the PI cycle was blocked. For all stages, the effects of 400 mM lithium were overcome by 10-100 microM myo-inositol. Excess myo-inositol potentiated the effect of lithium on MA structure (and on cytokinesis), suggesting that there is a negative feedback loop in the control of the PI cycle.


HER2 Genetic Intratumor Heterogeneity Is Associated With Resistance to Trastuzumab and Trastuzumab Emtansine Therapy in Recurrent High-Grade Endometrial Cancer.
Anti-HER2 targeted therapies have recently demonstrated clinical activity in the treatment of high-grade endometrial carcinomas (ECs), particularly serous carcinomas with HER2 amplification and/or overexpression. Intratumor heterogeneity of HER2 amplification or HER2 genetic intratumor heterogeneity (G-ITH) has been associated with resistance to anti-HER2 therapies in breast and gastroesophageal cancers; however, its clinical relevance in EC is unknown. To characterize HER2 G-ITH in EC, archival specimens from a clinically annotated cohort of 57 ECs treated with trastuzumab or trasutuzmab emtansine in the recurrent (n = 38) or adjuvant (n = 19) setting were subjected to central pathology review, HER2 assessment by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and next-generation sequencing. HER2 G-ITH, defined as HER2 amplification in 5% to 50% of tumor cells examined by FISH, was identified in 36% (19/53) of ECs and was associated with lower HER2 copy number and levels of protein expression. HER2 IHC revealed spatially distinct areas of strong expression juxtaposed with areas of low/absent expression in tumors with the "cluster" pattern of G-ITH, whereas the "mosaic" pattern was typically associated with a diffuse admixture of cells with variable levels of HER2 expression. HER2 G-ITH was frequently observed in cases with IHC/FISH or FISH/next-generation sequencing discrepancies and/or with an equivocal/negative FISH result (9/13, 69%). Although the objective response rate to anti-HER2 therapy in recurrent ECs was 52% (13/25) for tumors lacking HER2 G-ITH, none (0%, 0/10) of the patients with HER2 G-ITH achieved a complete or partial response (P = .005). HER2 G-ITH was significantly associated with worse progression-free survival (hazard ratio, 2.88; 95% CI, 1.33-6.27; P = .005) but not overall survival. HER2 IHC score, HER2/CEP17 ratio, HER2 copy number, histologic subtype, and other genetic alterations, including PIK3CA hotspot mutations, were not significantly associated with therapeutic response or survival outcomes. Treatment responses were not restricted to serous carcinomas, supporting consideration of anti-HER2 therapy in patients with HER2-positive high-grade ECs of non-serous histology. Our results demonstrate that HER2 G-ITH is an important determinant of response to trastuzumab and trastuzumab emtansine in EC, providing a rationale for the development of novel therapeutic strategies to target HER2-nonamplified resistant tumor subpopulations, such as HER2 antibody-drug conjugates with bystander effects.


Is extracorporeal shock wave lithotripsy safe in patients with calcific arterial disease?
In an experimental model using calcified aortic and iliac vessels ex vivo it has been shown that extracorporeal shock wave lithotripsy (ESWL) does not produce radiologically detectable damage to the vessel wall using the treatment regimen required to destroy renal calculi in vivo. The wall of aneurysmal vessels differ in being both calcified and expanded, and whilst anecdotal evidence suggests that lithotripsy of these too may be safe, experimental evidence is not yet available.


Anticoagulation instability with life-threatening complication after dietary modification.
Anticoagulation instability due to a change in intake of vitamin K after dietary modification was observed in 2 patients on long-term oral anticoagulants. One patient developed diffuse bruises treated conservatively with fresh frozen plasma transfusion and the other had a thrombosed aortic prosthesis which required emergency operation. To prevent such complications, dietary modification especially with food rich in vitamin K should be undertaken with care in patients on long-term oral anticoagulants.


Fabrication of hybrid chitosan encapsulated magnetic-kaolin beads for adsorption of phosphate and nitrate ions from aqueous solutions.
Phosphate and nitrate are commonly used industrial and agricultural nutrients that are of great anxiety because of their ubiquitous existence in water and wastewater sources and association with harmful health effects. Herein, we aimed to fabricate a novel and environmental-friendly chitosan encapsulated magnetic kaolin beads for the first time and applied for the adsorption of phosphate and nitrate ions from water. The physico-chemical properties of MK-chitosan beads were established by XRD, FTIR, and TGA-DSC techniques. Surface area (BET) analysis shows that MK-chitosan beads have a specific surface area of 2.12 m2/g. Surface morphology and elemental studies (SEM and EDAX) revealed the porous nature of MK-chitosan beads. The synthesized bead material employed as selective and effective adsorbent material for the remediation of phosphate and nitrate from water/ wastewater. The impact of external adsorption influencing effects likes, adsorbent dose, contact time, co-anions, pH of the solution, and temperature experiments have been performed. Adsorption isotherm and kinetic experiments have been studied and the data have been well tailored by the Freundlich isotherm and pseudo-second-order kinetic models. Thermodynamic parametric studies revealed endothermic and spontaneous nature of the overall sorption system. Besides, MK-chitosan beads were found to regeneration performance up to eight consecutive cycles. Furthermore, the adsorbent-adsorbate system implying that MK-chitosan beads could be a promising candidate for the removal of phosphate and nitrate ions from aqueous solutions.


Treating stage I nonseminomatous germ cell tumours with a single cycle of chemotherapy.
To estimate the rate of relapse in men with stage I nonseminomatous germ cell tumours (NSGCT) of the testis treated with one cycle of chemotherapy instead of the usual two cycles. Between 1992 and 1996, 22 men with stage I NSGCT who had normalized tumour markers after orchidectomy and negative findings on computed tomography, and who were at moderate risk of relapse, were treated with one cycle of platinum-containing chemotherapy (bleomycin and etoposide with either cisplatin or carboplatin). At a median follow-up of 10.2 years, none of the patients have relapsed with malignant GCTs. The results after one cycle of chemotherapy are no worse than after two cycles. The present study needs to be replicated in a larger cohort of patients to define the relapse risk more accurately. This approach is soon to be tested in a large multicentre trial randomizing patients between one and two cycles.


Do green supply chain management practices improve organizational resilience during the COVID-19 crisis? A survival analysis of global firms.
This study investigates whether green supply chain management (GSCM) practices help companies to be resilient against the buffer effect in the context of COVID-19. Building on the instrumental version of stakeholder theory, companies implementing GSCM practices should build environmental skills and competitive advantage to cope with a crisis caused by supply chain disruptions. Our survival analysis, conducted on 5,696 firms headquartered in 35 countries, shows clear evidence that GSCM companies' market prices recover quickly from the shock. Considering mounting pressure on environmental issues, this study documents the new benefits of GSCM for companies confronted with a global financial shock. By applying a large sample, the study has originality and implications for stakeholders, including investors, governments, and policymakers, to push firms to become more eco-friendly and resilient.


Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.
The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin improves cognitive functions in HFD-induced obese mice.


COVID-19 seroprevalence in Pakistan: a cross-sectional study.
This study adapted WHO's 'Unity Study' protocol to estimate the population prevalence of antibodies to SARS CoV-2 and risk factors for developing SARS-CoV-2 infection. This population-based, age-stratified cross-sectional study was conducted at the level of households (HH). All ages and genders were eligible for the study (exclusion criteria: contraindications to venipuncture- however, no such case was encountered). 4998 HH out of 6599 consented (1 individual per HH). The proportion of male and female study participants was similar. Following were the measured outcome measures- these were different from the planned indicators (i.e. two out of the three planned indicators were measured) due to operational reasons and time constraints: -Primary indicators: Seroprevalence (population and age specific).Secondary indicators: Population groups most at risk for SARS-CoV-2-infection. Overall seroprevalence of SARS-CoV-2 antibodies was 7.1%. 6.3% of individuals were IgG positive while IgM positivity was 1.9%. Seroprevalence in districts ranged from 0% (Ghotki) to 17% (Gilgit). The seroprevalence among different age groups ranged from 3.9% (0-9 years) to 10.1% (40-59 years). There were no significant differences in the overall seroprevalence for males and females. A history of contact with a confirmed COVID-19 case, urban residence and mask use were key risk factors for developing SARS-CoV-2 infection. This survey provides useful estimates for seroprevalence in the general population and information on risk factors for developing SARS-CoV-2 infection in the country. It is premised that similar studies need to be replicated at the population level on a regular basis to monitor the disease and immunity patterns related to COVID-19.


A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide.
Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. A S315T katG mutation conferred resistance to TCH while katG expression from a plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible involvement of KatG in TCH activation. Whole genome sequencing of mutants from this second group revealed a single mutation in the alkylhydroperoxide reductase ahpC promoter locus in half of the mutants, while the remaining contained mutations in dispensable genes. This is the first report of the genetics underlying the action of TCH and of the involvement of ahpC as the sole basis for resistance to an anti-tubercular compound.


Detection and treatment of Fiebig stage I HIV-1 infection in young at-risk women in South Africa: a prospective cohort study.
HIV incidence among young women in sub-Saharan Africa remains high and their inclusion in vaccine and cure efforts is crucial. We aimed to establish a cohort of young women detected during Fiebig stage I acute HIV infection in whom treatment was initiated immediately after diagnosis to advance research in this high-risk group. 945 women aged 18-23 years in KwaZulu-Natal, South Africa, who were HIV uninfected and sexually active consented to HIV-1 RNA testing twice a week and biological sampling and risk assessment every 3 months during participation in a 48-96 week life-skills and job-readiness programme. We analysed the effect of immediate combination antiretroviral therapy (ART) on viraemia and immune responses, sexual risk behaviour, and the effect of the socioeconomic intervention. 42 women were diagnosed with acute HIV infection between Dec 1, 2012, and June 30, 2016, (incidence 8·2 per 100 person-years, 95% CI 5·9-11·1), of whom 36 (86%) were diagnosed in Fiebig stage I infection with a median initial viral load of 2·97 log10 copies per mL (IQR 2·42-3·85). 23 of these 36 women started ART at a median of 1 day (1-1) after detection, which limited the median peak viral load to 4·22 log10 copies per mL (3·27-4·83) and the CD4 nadir to 685 cells per μL (561-802). ART also suppressed viral load (to <20 copies per mL) within a median of 16 days (12-26) and, in 20 (87%) of 23 women, prevented seroconversion, as shown with western blotting. 385 women completed the 48 week socioeconomic intervention, of whom 231 were followed up for 1 year. 202 (87%) of these 231 women were placed in jobs, returned to school, or started a business. Frequent HIV screening combined with a socioeconomic intervention facilitated sampling and risk assessment before and after infection. In addition to detection of acute infection and immediate treatment, we established a cohort optimised for prevention and cure research. Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases, International AIDS Vaccine Initiative, Wellcome Trust, Howard Hughes Medical Institute.


On the late invention of the stereoscope.
It was not until 1838, when Wheatstone published his account of the stereoscope, that stereoscopic depth perception entered into the body of binocular phenomena. It is argued that the stereoscope was not invented earlier because the phenomenon of stereopsis based on disparity had not been adequately described. This was the case despite the fact that there had been earlier descriptions of tasks that could be performed better with two eyes than with one; the perceptual deficits attendant upon the loss of one eye had been remarked upon; analyses of the projections to each eye were commonplace, and binocular disparities were accurately illustrated; moreover, binocular microscopes and telescopes had been made over a century earlier. Theories of binocular vision were generally confined to accounting for singleness of vision with two eyes, and the concepts employed to account for this were visible direction, corresponding retinal points, and union in the brain. The application of these concepts inhibited any consideration of disparities, other than for yielding diplopia. When perception of the third dimension was addressed by Berkeley at the beginning of the eighteenth century, it was in the context of monocular vision and binocular convergence. Thereafter visual direction became the province for binocular vision and it was analysed in terms of geometrical optics, whereas visual distance was examined in the context of learned associations between vision and touch. This artificial division was challenged initially with respect to visual direction and later with respect to stereopsis. An additional factor delaying the invention of the stereoscope was that experiments on binocular vision generally involved abnormal convergence on extended objects. Wheatstone's accidental observation of stereopsis was under artificial conditions in which disparity alone defined the binocular depth perceived. Once invented the stereoscope was enthusiastically embraced by students of vision. It is suggested that the ease with which retinal disparity could be manipulated in stereopairs has led to an exaggeration of its importance in space perception. "The appearances, which are by this simple instrument rendered so obvious, may be easily inferred from the established laws of perspective; for the same object in relief is, when viewed by a different eye, seen from the two points of sight at a distance from each other equal to the line joining the two eyes. Yet they seem to have escaped the attention of every philosopher and artist who has treated of the subjects of vision and perspective." (Wheatstone 1838, page 371).


Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity via inhibiting lipid peroxidation associated ferroptosis.
Ferroptosis has been suggested to involve in doxorubicin (DOX)-induced cardiotoxicity. However, the underlying mechanisms and regulatory targets of cardiomyocyte ferroptosis remains to be understood. This study demonstrated that the up-regulation of ferroptosis associated proteins genes were accompanied with the down-regulation of AMPKα2 phosphorylation in DOX treated mouse heart or neonatal rat cardiomyocytes (NRCMs). AMPKα2 knockout (AMPKα2-/-) significantly exacerbated mouse cardiac dysfunction, increased mortality, promoting ferroptosis associated mitochondrial injuries, enhanced ferroptosis associated proteins and genes expression, and lead to accumulation of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in mouse serum and hearts respectively. Ferrostatin-1 administration markedly improved cardiac function, decreased mortality, inhibited mitochondrial injuries and ferroptosis associated proteins and genes expression, and depressed accumulation of LDH and MDA in DOX treated AMPKα2-/- mouse. Moreover, Adeno-associated virus serotype 9 AMPKα2 (AAV9-AMPKα2) or AICAR treatment mediated AMPKα2 activation could significantly improve cardiac function and depress ferroptosis in mouse. AMPKα2 activation or silence could also inhibit or promote ferroptosis associated injuries in DOX treated NRCMs respecitively. Mechanistically, AMPKα2/ACC mediated lipid metabolism has been suggested to involve in regulating DOX-treatment induced ferroptosis other than mTORC1 or autophagy dependent pathway. The metabolomics analysis exhibited that AMPKα2-/- significantly enhanced accumulation of polyunsaturated fatty acids (PFAs), oxidized lipid, and phosphatidylethanolamine (PE). Finally, this study also demonstrated that metformin (MET) treatment could inhibit ferroptosis and improve cardiac function via activating AMPKα2 phosphorylation. The metabolomics analysis exhibited that MET treatment significantly depressed PFAs accumulation in DOX treated mouse hearts. Collectively, this study suggested that AMPKα2 activation might protect against anthracycline chemotherapeutic drugs mediated cardiotoxicity via inhibiting ferroptosis.


Inhibition of HIV-1 replication by RNA interference of p53 expression.
p53 expression and activation have been associated to faster human immunodeficiency virus (HIV) disease progression, most probably by inducing CD4+ T cell death but also through its cooperative effect in the control of viral gene transcription by viral regulatory proteins. Here, we show that RNA interference of p53 in HIV-1 reporter (HeLa P4-R5 MAGI) and lymphoid (SupT1) cell lines blocked HIV-1 and Tat-induced transcription from the HIV-1 promoter and HIV-1 replication in acutely infected cells, suggesting a cooperative role of p53 in HIV-1 transcription. Contrary to SupT1 cells, which encode several mutations on the p53 DNA binding domain, death of HIV-1-induced syncytia was reduced in cocultures of HeLa P4-R5 MAGI with persistently infected HIV-1 cells. To our knowledge, this is the first demonstration of the effect of the loss of function of p53 in HIV-1 replication, which is independent on its classical DNA binding activity. Our results suggest two independent roles for p53 in HIV-1 infection: cooperation in HIV long-terminal repeat transcription and virus-induced cell death.


Supramalleolar osteotomy: indications and technique.
The distal tibial (supramalleolar) osteotomy for the treatment of pathologic entities of the adult distal tibia and foot and ankle has received limited attention in the literature. It is technically demanding and requires an extensive and careful preoperative planning. In our experience, it has been a useful tool in the surgical armamentarium to reconstruct the normal mechanical environment in malunion preventing any long-term deleterious effects, and to shift and redistribute loads in the ankle joint to protect the articular cartilage from further degeneration.


The Admission Checklist: The key steps and responsibilities for the admitting resident.
The process of admitting patients from the emergency department to the general medicine floor is foundational to the medical training process and medical practice more generally. Yet this process is rife with potential error if not approached systematically, and residents rarely receive explicit teaching in this area. The creation of an "Admission Checklist" proposed by the authors could serve the function of reducing error and enhancing inter-provider communication throughout this process. Such a checklist could improve trainee experience and education, and ultimately allow for improved outcomes for patients during transitions of care.


Sex and cell-specific gene expression in corticolimbic brain regions associated with psychiatric disorders revealed by bulk and single-nuclei RNA sequencing.
There are sex-specific differences in the prevalence, symptomology and course of psychiatric disorders. However, preclinical models have primarily used males, such that the molecular mechanisms underlying sex-specific differences in psychiatric disorders are not well established. In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala (n = 22-24 per group/region). We found over 3000 differentially expressed genes (DEGs) in the NAcS between males and females. Of these DEGs in the NAcS, 303 showed sex-dependent conservation DEGs in humans and were significantly enriched for gene ontology terms related to blood vessel morphogenesis and regulation of cell migration. Single nuclei RNA sequencing in the NAcS of male and female rats identified widespread sex-dependent expression, with genes upregulated in females showing a notable enrichment for synaptic function. Female upregulated genes in astrocytes, Drd3+MSNs and oligodendrocyte were also enriched in several psychiatric genome-wide association studies (GWAS). Our data provide comprehensive evidence of sex- and cell-specific molecular profiles in the NAcS. Importantly these differences associate with anxiety, bipolar disorder, schizophrenia, and cross-disorder, suggesting an intrinsic molecular basis for sex-based differences in psychiatric disorders that strongly implicates the NAcS. This work was supported by funding from the Hope for Depression Research Foundation (MJM).


EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation.
Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (χ(2) <0.001). Most cases showed an activated phenotype (95% non-germinal center (Hans algorithm); 78% activated B cell (Choi algorithm)). Clonality testing demonstrated IgH and/or K/Kde/L monoclonal rearrangements in 64% of cases and clonal T-cell populations in 24% of cases. C-MYC (1 case), BCL6 (2 cases) or IgH (3 cases) translocations were detected by FISH in 18% cases. These tumors had a poor overall survival and progression-free survival (the estimated 2-year overall survival was 40 ± 10% and the estimated 2-year progression-free survival was 36 ± 9%). Thus, alternative therapies, based on the tumor biology, need to be tested in patients with EBV-positive diffuse large B-cell lymphoma of the elderly.


Self-co-attention neural network for anatomy segmentation in whole breast ultrasound.
The automated whole breast ultrasound (AWBUS) is a new breast imaging technique that can depict the whole breast anatomy. To facilitate the reading of AWBUS images and support the breast density estimation, an automatic breast anatomy segmentation method for AWBUS images is proposed in this study. The problem at hand is quite challenging as it needs to address issues of low image quality, ill-defined boundary, large anatomical variation, etc. To address these issues, a new deep learning encoder-decoder segmentation method based on a self-co-attention mechanism is developed. The self-attention mechanism is comprised of spatial and channel attention module (SC) and embedded in the ResNeXt (i.e., Res-SC) block in the encoder path. A non-local context block (NCB) is further incorporated to augment the learning of high-level contextual cues. The decoder path of the proposed method is equipped with the weighted up-sampling block (WUB) to attain class-specific better up-sampling effect. Meanwhile, the co-attention mechanism is also developed to improve the segmentation coherence among two consecutive slices. Extensive experiments are conducted with comparison to several the state-of-the-art deep learning segmentation methods. The experimental results corroborate the effectiveness of the proposed method on the difficult breast anatomy segmentation problem on AWBUS images.


Discovery of substituted-2,4-dimethyl-(naphthalene-4-carbonyl)amino-benzoic acid as potent and selective EP4 antagonists.
A novel series of EP4 antagonists, based on a quinoline scaffold, has been discovered. Medicinal chemistry efforts to optimize the potency of the initial hit are described. A highly potent compound in a clinically relevant human whole blood assay was identified. Selectivity and pharmacokinetic profiles of this compound are discussed.


Relationships between body dimensions and resting and working oxygen consumption in boys aged 11 to 18 years.
The relationships between VO2 at rest, VO2max and VO2 during submaximal work on a treadmill with body weight, height and lean body mass assessed by densitometry were analyzed annually in 39 boys aged 11 to 18 years. Interindividual differences in VO2 at rest and VO2max during growth depended in the first place on interindividual differences in lean body mass, to a lesser extent on differences in body weight and least on differences in height. Intersubject differences in VO2 during submaximal work were primarily conditioned by differences in body weight, due to the fact that, at a given running speed, energy output depends on body weight. The differences in submaximal VO2 depended to a lesser extent on differences in lean body mass and least on differences in height. The relationships between VO2 increments and increases in body dimensions were somewhat different in 90 boys between the ages of 11 and 15 years: VO2max increments were determined primarily by changes in body weight and height, changes in lean body mass being of secondary importance. Increases in submaximal VO2 were influenced decisively by increments in body weight, followed by increments in lean body mass and least by increments in height. In the equation y = a.xb expressing the relationship of VO2max to body weight and height, the values of b at the ages of 14 and 15 years were 0.87 and 0.88 in relation to body weight, 2.63 and 2.72 in relation to height. These values are significantly higher than the theoretical values of 0.67 for body weight and 2.00 for height. Similar significant differences from these theoretical values were found for all values between the ages of 11 and 15 years.


Lack of a pharmacological distinction between alpha-1 adrenoceptors mediating intracellular calcium-dependent and independent contractions to sympathetic nerve stimulation in the perfused rat caudal artery.
The contractile response of the rat caudal artery to field stimulation occurred in two phases; an initial rapidly developing contraction (phasic) and a subsequent more slowly developing contraction (tonic). Phenoxybenzamine, an irreversible antagonist, and prazosin, a competitive antagonist at the alpha-1 adrenoceptor, nonselectively inhibited both contractile phases. Ryanodine, an inhibitor of intracellular calcium release, selectively inhibited the phasic component, whereas nifedipine, a membrane calcium channel blocker, selectively inhibited the tonic component. These data demonstrate that both contractile phases are mediated by alpha-1 adrenoceptors and the phases are distinguished by the calcium source mobilized; intracellular stores of calcium are mobilized during the phasic component and extracellular calcium is mobilized during the tonic component. Inasmuch as alpha-1 adrenoceptors on nonvascular smooth muscle may be divided into alpha-1A and alpha-1B subtypes based on ability to open membrane calcium channels or ability to stimulate intracellular calcium release, respectively, we characterized the alpha-1 adrenoceptor mediating the contraction to determine whether a specific subtype was coupled to each phase. WB4101, a marginally alpha-1A adrenoceptor selective antagonist, 5-methyl-urapidil, a highly alpha-1A adrenoceptor selective antagonist and chloroethylclonidine, a highly alpha-1B adrenoceptor selective antagonist, all inhibited both contractile phases. These findings indicate that endogenous norepinephrine contracts the rat caudal artery via alpha-1 adrenoceptors that mobilize both the release of intracellular calcium and the influx of calcium through membrane channels.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute effects of Benzo[a]pyrene, anthracene and a fuel oil on biomarkers of the common goby Pomatoschistus microps (Teleostei, Gobiidae).
The objective of this study was to investigate the effects of two different PAHs and a complex petrochemical mixture on the common goby, Pomatoschistus microps, using selected biomarkers as effect criteria. Benzo[a]pyrene (BaP) and anthracene were used as reference substances, while the water accommodated fraction of #4 fuel-oil (#4 WAF) was used as an example of a petrochemical mixture. P. microps was used since it is both a suitable bioindicator and a good test organism. Groups of fish were exposed to different concentrations of each of the test substances for 96 h and the activities of several enzymes commonly used as biomarkers were determined at the end of the bioassays. All the substances inhibited P. microps acetylcholinesterase (AChE) indicating that they have at least one mechanism of neurotoxicity in common: the disruption of cholinergic transmission by inhibition of AChE. An induction of lactate dehydrogenase (LDH) activity was found in fish exposed to BaP or to anthracene, suggesting an increase of the anaerobic pathway of energy production. On the contrary, inhibition of LDH was found in fish exposed to #4 WAF, suggesting a distinct effect of the mixture. An induction of P. microps glutathione S-transferase (GST) activity was found in fish exposed to BaP or to #4 WAF, while an inhibition was observed after exposure to anthracene. These results suggest that GST is involved in the detoxification of BaP and #4 WAF, but not of anthracene. All the substances increased catalase activity and isolated PAHs also increased superoxide dismutase, glutathione reductase and glutathione peroxidase activities, while #4 WAF did not cause significant alterations on these enzymes. These results suggest that all the substances may induce oxidative stress on P. microps, with BaP and anthracene apparently having more oxidative stress potential than #4 WAF.


Health status of Medicare-enrolled autistic older adults with and without co-occurring intellectual disability: An analysis of inpatient and institutional outpatient medical claims.
Little is known about the extent to which the healthcare needs of autistic older adults with intellectual disability differ from autistic older adults without intellectual disability. Our study is the first, to our knowledge, to use US national data to compare physical and mental health conditions among autistic older adults with and without intellectual disability. The data analyzed in this study consisted of records from inpatient hospitalizations as well as "institutional outpatient" healthcare visits, which include visits to hospital outpatient departments, rural health clinics, renal dialysis facilities, outpatient rehabilitation facilities, Federally Qualified Health Centers, and community mental health centers. Autistic older adults with intellectual disability were significantly more likely to have thyroid disorders, epilepsy, respiratory infections, gastrointestinal conditions, osteoporosis, cognitive disorders, and schizophrenia/psychotic disorders. In contrast, autistic older adults without intellectual disability were significantly more likely to have obesity, diabetes, high blood pressure, cerebrovascular disease, chronic obstructive pulmonary disease, arthritis, back conditions, attention deficit disorders, substance use disorders, and suicidal ideation or intentional self-injury. These findings highlight the importance of developing distinct, tailored health management strategies for the autistic older adults with and without intellectual disability.


Selenium and mercury concentrations in some fish species of the Madeira River, Amazon Basin, Brazil.
Samples of 7 species of piscivorous, omnivorous, and herbivorous fish caught at 12 different sites on the Madeira River, Amazon Basin, were analyzed for selenium and mercury. Selenium was determined by anodic stripping voltammetry and mercury by cold vapor atomic absorption spectrophotometry. The means for selenium concentrations ranged from 0.49 to 3.11 nmol/g and for mercury from 0.41 to 6.66 nmol/g depending on the fish species. The molar ratios of Hg:Se increased according to the fish trophic level. Piscivorous species had the highest mean ratio (4.0) and herbivorous species the lowest (0.9). There was a positive and statistically significant correlation between selenium and mercury concentrations for the herbivorous species (r = 0.716; p = 0.0088) not seen for omnivororus and piscivorous species (r = -0.2032; p = 0.3407). These findings are significant for the fish-eating population of the Madeira River because the ingestion of mercury would always be in excess of selenium.


The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats.
The purpose of this study was to investigate the effect of Sulforaphane on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. Fourty Wistar rats were assigned into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and Sulforaphane application, Group III hepatic IR; and Group IV as hepatic IR and Sulforaphane application group. Animals were subjected to liver ischemia for 30 min and then reperfusion is started. 5 mg/kg Sulforaphane was applied via oral lavage 15 minutes before initiating the experimental study. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. The administration of sulforaphane significantly reduced the serum TOA and liver TOA levels, increased the serum TAC and liver TAC levels and also decreased The OSI and liver OSI levels. In the histopathologic examination, the injury was reduced by the administration of sulforaphane. Administration of sulforaphane did not lead to any significant changes in any parameter including histopathological parameters in both the kidney and the lung. Sulforaphane reduced the liver oxidative stress from I/R injury. A histological injury in liver was reduced by sulforaphane administration. However, there were no significant effects of sulforaphane on the remote organ injuries induced by IR.


DON calibrant: Towards the production of certified B-trichothecene calibrants.
Within an EC-funded project calibrants with certified concentrations of Deoxynivalenol (DON), 3-Acetyl-Deoxynivalenol (3-Ac-DON), 15-Acetyl-Deoxynivalenol (15-Ac-DON) and Nivalenol (NIV) in acetonitrile have been produced. So far the project has led to improved isolation and purification of the solid toxins fromFusarium cultures. In addition, conditions for the production, ampouling and transport of the toxin solutions have been optimised. Further investigations should lead to knowledge about storage conditions and internationally accepted molar absorption coefficients for DON, 3-Ac-DON, 15-Ac-DON and NIV in acetonitrile. The intercomparison study which is currently carried out will also help to support knowledge and experience exchange between laboratories in the field ofFusarium mycotoxin analysis.


Acute toxicity, bioaccumulation and effects of dietary transfer of silver from brine shrimp exposed to PVP/PEI-coated silver nanoparticles to zebrafish.
The extensive use and release to the aquatic environment of silver nanoparticles (NPs) could lead to their incorporation into the food web. Brine shrimp larvae of 24h showed low sensitivity to the exposure to PVP/PEI-coated Ag NPs (5nm), with EC50 values at 24h of 19.63mgAgL-1, but they significantly accumulated silver after 24h of exposure to 100μgL-1 of Ag NPs. Thus, to assess bioaccumulation and effects of silver transferred by the diet in zebrafish, brine shrimp larvae were exposed to 100ngL-1 of Ag NPs as an environmentally relevant concentration or to 100μgL-1 as a potentially effective concentration and used to feed zebrafish for 21days. Autometallography revealed a dose- and time-dependent metal accumulation in the intestine and in the liver of zebrafish. Three-day feeding with brine shrimps exposed to 100ngL-1 of Ag NPs was enough to impair fish health as reflected by the significant reduction of lysosomal membrane stability and the presence of vacuolization and necrosis in the liver. However, dietary exposure to 100μgL-1 of Ag NPs for 3days did not significantly alter gene transcription levels, neither in the liver nor in the intestine. After 21days, biological processes such as lipid transport and localization, cellular response to chemical stimulus and response to xenobiotic stimulus were significantly altered in the liver. Overall, these results indicate an effective dietary transfer of silver and point out to liver as the main target organ for Ag NP toxicity in zebrafish after dietary exposure.


Clinical index to quantify the 1-year risk for common postpartum mental disorders at the time of delivery (PMH CAREPLAN): development and internal validation.
Common postpartum mental health (PMH) disorders such as depression and anxiety are preventable, but determining individual-level risk is difficult. To create and internally validate a clinical risk index for common PMH disorders. Using population-based health administrative data in Ontario, Canada, comprising sociodemographic, clinical and health service variables easily collectible from hospital birth records, we developed and internally validated a predictive model for common PMH disorders and converted the final model into a risk index. We developed the model in 75% of the cohort (n = 152 362), validating it in the remaining 25% (n = 75 772). The 1-year prevalence of common PMH disorders was 6.0%. Independently associated variables (forming the mnemonic PMH CAREPLAN) that made up the risk index were: (P) prenatal care provider; (M) mental health diagnosis history and medications during pregnancy; (H) psychiatric hospital admissions or emergency department visits; (C) conception type and complications; (A) apprehension of newborn by child services (newborn taken into care); (R) region of maternal origin; (E) extremes of gestational age at birth; (P) primary maternal language; (L) lactation intention; (A) maternal age; (N) number of prenatal visits. In the index (scored 0-39), 1-year common PMH disorder risk ranged from 1.5 to 40.5%. Discrimination (C-statistic) was 0.69 in development and validation samples; the 95% confidence interval of expected risk encompassed observed risk for all scores in development and validation samples, indicating adequate risk index calibration. Individual-level risk of developing a common postpartum mental health disorder can be estimated with data feasibly collectable from birth records. Next steps are external validation and evaluation of various cut-off scores for their utility in guiding postpartum individuals to interventions that reduce their risk of illness.


Retinoid-induced haemorrhagic bullae in Darier's disease.
Haemorrhagic epidermal bullae developed in a patient with Darier's disease undergoing long term treatment with the retinoid, etretinate. We suggest that these lesions result from cumulative toxic effects of long term retinoid therapy upon the abnormal keratinocyte found in Darier's disease.


Animal models of Parkinson's disease.
Animal models of Parkinson's disease (PD) have been widely used in the past four decades to investigate the pathogenesis and pathophysiology of this neurodegenerative disorder. These models have been classically based on the systemic or local (intracerebral) administration of neutoxins that are able to replicate most of the pathological and phenotypic features of PD in mammals (i.e. rodents or primates). In the last decade, the advent of the 'genetic era' of PD has provided a phenomenal enrichment of the research possibilities in this field, with the development of various mammalian (mice and, more recently, rats) and non-mammalian transgenic models that replicate most of the disease-causing mutations identified for monogenic forms of familial PD. Both toxic and transgenic classes of animal PD models have their own specificities and limitations, which must be carefully taken into consideration when choosing the model to be used. If a substantial and reproducible nigrostriatal lesion is required (e.g. for testing therapeutic interventions aimed at counteracting PD-related cell death), a classic toxic model such as one based on the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 6-hydroxydopamine will adequately serve the purpose. On the other hand, if selected molecular mechanisms of PD pathogenesis must be investigated, transgenic models will offer invaluable insights. Therefore, until the 'perfect' model is developed, indications to use one model or another will depend on the specific objectives that are being pursued.


Nanometer-micrometer sized depleted uranium (DU) particles in the environment.
Depleted uranium (DU) is a waste product from uranium enrichment that has several civilian and military applications. Significant amounts of DU in the form of particles or as fragments have been released into the environment as a consequence of military use of DU munitions, of industrial releases and of aircraft accidents. Thus, the present paper summarizes present knowledge on nanometer-micrometer sized depleted uranium (DU) particles collected in areas contaminated with such particles. Analysis of DU particles released to the environment has shown that uranium can be present in different crystalline structures and in different oxidation states. The weathering rates of DU particles and the subsequent remobilization of uranium species are also strongly connected to the oxidation state and crystalline phases of uranium, influencing the mobility and potential ecosystem transfer. Therefore, as has been observed for radioactive particles released from most nuclear events, the characteristics of DU particles can be linked to the source term and the release scenario as well as to environmental transformation processes. Although the radiation dose and radiotoxicity of DU is less than from natural occurring uranium, the mobility of U from oxidized DU and the associated chemical toxicity could be significantly higher than from natural UO2. The present paper summarizes present knowledge on depleted uranium particles identified in the environment.