Shortened-Duration Immunosuppressive Therapy after Nonmyeloablative, Related HLA-Haploidentical or Unrelated Peripheral Blood Grafts and Post-Transplantation Cyclophosphamide.
With post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative (NMA) HLA-haploidentical (haplo) and HLA-matched blood or marrow transplantation (BMT) have comparable outcomes. Previous reports have shown that discontinuation of immunosuppression (IS) as early as day 60 after infusion of a bone marrow (BM) haplo allograft with PTCy is feasible. There are certain diseases in which peripheral blood (PB) may be favored over BM, but given the higher rates of GVHD with PB, excessive GVHD is of increased concern. We report a completed, prospective single-center trial of stopping IS at days 90 and 60 after NMA PB stem cell transplantation (PBSCT). Between 12/2015-7/2018, 117 consecutive patients with hematologic malignancies associated with higher rates of graft failure after NMA conditioned BMT and PTCy, received NMA PB allografts on trial. The primary objective of this study was to evaluate the safety and feasibility of reduced-duration IS (from day 5 through day 90 in the D90 cohort and through day 60 in the D60 cohort). Of the 117 patients (median age, 64 years; range, 22 to 78 years), the most common diagnoses were myelodysplastic syndrome (33%), acute myelogenous leukemia (with minimal residual disease or arising from an antecedent disorder) (32%), myeloproliferative neoplasms (19%), myeloma (9%), and chronic lymphoblastic leukemia (7%). Shortened IS was feasible in 75 patients (64%) overall. Ineligibility for shortened IS resulted most commonly from GVHD (17 patients), followed by early relapse (11 patients), nonrelapse mortality (NRM) (7 patients), patient/ physician preference (4 patients) or graft failure (3 patients). Of the 57 patients in the D90 cohort, 33 (58%) stopped IS early as planned, and among the 60 patients in the D60 cohort, 42 (70%) stopped IS early as planned. The graft failure rate was 2.6%. After IS cessation, the median time to diagnosis of grade II-IV acute GVHD was 21 days in the D90 cohort and 32 days in the D60 cohort, with almost all cases developing within 40 days. Approximately one-third of these patients resumed IS. All outcome measures were similar in the 2 cohorts and our historical outcomes with 180 days of IS. The cumulative incidence of grade III-IV acute GVHD was low, 2% in the D90 cohort and 7% in the D60 cohort. The incidence of severe chronic GVHD at 2 years was 9% in the D90 cohort and 5% in the D60 cohort. The 2-year overall survival was 67% for both the D90 and D60 cohorts. The 2-year progression-free survival was 47% for the D90 cohort and 52% for the D60 cohort, and the GVHD-free, relapse-free survival was <35% for both cohorts. These data suggest that reduced-duration IS in patients undergoing NMA PBSCT with PTCy is feasible and has an acceptable safety profile. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.


Fibrin glue for refractory hemorrhagic cystitis after unrelated marrow, cord blood, and haploidentical hematopoietic stem cell transplantation.
Patients undergoing hematopoietic stem cell transplant (HSCT) are particularly exposed to the risk of developing hemorrhagic cystitis (HC), which is characterized by symptoms ranging from macroscopic hematuria to renal failure. Although HC significantly affects the quality of life and in a few cases becomes intractable leading to patient death, its therapeutic management has not been established. Fibrin glue (FG), a hemostatic agent derived from human plasma, has been largely employed in different surgical settings including urologic procedures. In this pilot study we used FG to treat refractory HC. During cystoscopy, bladder distension was maintained at a constant pressure of 12 mmHg by a carbon dioxide insufflator. An endoscopic applicator allowed spraying FG on the bleeding and raw surfaces of bladder mucosa. Five of 221 patients undergoing an HSCT developed a very severe, refractory HC and have been treated with endoscopic FG. The treatment was successful in 3 patients; the response was partial in 1 patient and transient in the last one, whose clinical course was severely complicated by acute graft-versus-host disease and multiple organ failure. FG therapy is a feasible procedure and this pilot study suggests that it may be an effective treatment for refractory HC. Its application could be considered also in Grade 1 or 2 HC to prevent progression of damaged mucosa. The use of FG for HC should be prospectively investigated in terms of therapeutic efficacy, transfusion support, length of hospitalization, quality of life, and costs.


60Co and 45Ca autoradiography in cerebral ischemia in the rat.
Radioisotopes of divalent Co (57Co in single photon emission tomography (SPECT)and 55Co in positron emission tomography (PET) have clinically been applied to visualize Ca related brain damage. The cerebral uptake of 45Ca and 60Co in a unilateral stroke model in the rat was compared; 100 microCi 45CaCl2 or 60 microCi 60CoCl2 was intravenously given at day 2 or 9 and the rats were killed 24 h later for autoradiography. Similarly increased uptake of 45Ca and 60Co was observed at both time points in unilaterally affected areas such as the cerebral cortex, dentate gyrus, caudate putamen of the striatum, substantia nigra pars reticulatum and corpus geniculatum. More Ca-uptake was found in the hippocampus CA1 region (at day 10) and the thalamus (ventral part at both time points). Radioactive Co but not Ca accumulated in the choroid plexus. Although the present investigation supports the idea that divalent Co-isotopes are useful to visualize stroke induced damage and choroid plexus function, these radionuclides do, however, not allow to detect excessive Ca-influx in degenerating neurones.


Overcoming bread quality decay concerns: main issues for bread shelf life as a function of biological leavening agents and different extra ingredients used in formulation. A review.
As is widely accepted, the quality decay of freshly baked bread that affects product shelf life is the result of a complex multifactorial process that involves physical staling, together with microbiological, chemical and sensorial spoilage. In this context, this paper provides a critical review of the recent literature about the main factors affecting shelf life of bread during post-baking. An overview of the recent findings about the mechanism of bread staling is firstly provided. Afterwards, the effect on staling induced by baker's yeasts and sourdough as well as by the extra ingredients commonly utilized for bread fortification is also addressed and discussed. As inclusion/exclusion criteria, only papers dealing with wheat bread and not with long-life bread or gluten-free bakery products are taken into consideration. Despite recent developments in international scientific literature, the whole mechanism that induces bread staling is far from being completely understood and the best analytical methods to be adopted to measure and/or describe in depth this process appear still debated. In this topic, the effects induced on bread shelf life by the use of biological leavening agents (baker's yeasts and sourdough) as well as by some extra ingredients included in the bread recipe have been individuated as two key issues to be addressed and discussed in terms of their influence on the kinetics of bread staling. © 2020 Society of Chemical Industry.


Impact of pre-appointment contact and short message service alerts in reducing 'Did Not Attend' (DNA) rate on rapid access new patient breast clinics: a DGH perspective.
Failure to attend the clinic without prior intimation, known as "Did Not Attend" (DNA) is a significant global issue. There have been no published studies attempting to reduce DNA rates in breast clinics. We aimed to assess the impact of contacting patients prior to clinic attendance and Short Message Service (SMS) reminder on DNA rates in rapid access new patient breast clinics, evaluate 'Could Not Attend' (CNA) rate, and explore any correlation between age, sex, clinic days and sessions. Initially, DNAs at the rapid access new patient breast clinic between 01/04/2018 and 31/03/2019 at a district general hospital in the North-West of England was assessed (Cycle 1). Changes were introduced in terms of contacting patients prior to offering appointments, followed by SMS reminders nearer the clinic dates. Subsequently, DNA was reassessed between 01/10/2019 and 31/03/2020 (Cycle 2). Following implementation of changes, DNA rate reduced from 8.2 to 4.1% (p < 0.00001). CNA rates were 0.9% (Cycle 1) and 1.1% (Cycle 2) [p = 0.36]. Evening clinics had the lowest DNA rates throughout. DNA patients in cycle 2 were significantly older than those in cycle 1 (p = 0.002). Contacting patients prior to clinic appointments and sending SMS reminders helped reduce DNA rates significantly in rapid access new patient breast clinics. Scheduling clinic sessions with least DNA rates, such as evening clinics, should be contemplated. One should be cautious of mobile phone technology that conveys SMS, which can potentially disadvantage the older age group. This model could be considered across the board to improve DNA rates.


Chronic corticosterone exposure induces liver inflammation and fibrosis in association with m6A-linked post-transcriptional suppression of heat shock proteins in chicken.
Our previous study had shown that chronic corticosterone (CORT) exposure causes excessive fat deposition in chicken liver, yet it remains unknown whether it is associated with inflammation and fibrosis. In general, heat shock proteins (HSPs) are activated in response to acute stress to play a cytoprotective role, and this activation is associated with m6A-mediated post-transcriptional regulation. However, changes of HSPs and the m6A methylation on their mRNAs in response to chronic CORT treatment in chicken liver have not been reported. In this study, chronic CORT exposure induced inflammation and fibrosis in chicken liver, associated with significantly modulated expression of HSPs that was significantly upregulated at mRNA level yet downregulated at protein level. Concurrently, m6A methyltransferases METTL3 content was upregulated together with the level of m6A methylation on HSPs transcripts. The m6A-seq analysis revealed 2-6 significantly (P < 0.05) hypermethylated m6A peaks in the mRNA of 4 different species of HSPs in CORT-treated chicken liver. HSP90B1 transcript had 6 differentially methylated m6A peaks among which peaks on exon 16 and exon 17 showed 3.14- and 4.72-fold of increase, respectively. Mutation of the 8 predicted m6A sites on exon 16 and exon 17 resulted in a significant (P < 0.05) increase in eGFP-fused content of HSP90B1 exon 16 and exon 17 fragment in 293 T cells, indicating a possible role of m6A in post-transcriptional regulation of HSPs. In conclusion, chronic CORT exposure induces inflammation and fibrosis in chicken liver along with an increase in the levels and m6A methylation of several HSPs mRNAs; HSPs levels were however reduced under the indicated conditions. Results presented suggest that the reduction in HSPs levels may be associated with m6A methylation in CORT-exposed chickens.


Selecting Optimal Proton Pencil Beam Scanning Plan Parameters to Reduce Dose Discrepancy between Discrete Spot Plan and Continuous Scanning: A Proof-of-Concept Study.
Pencil beam scanning delivered with continuous scanning has several advantages over conventional discrete spot scanning. Such advantages include improved beam delivery efficiency and reduced beam delivery time. However, a move dose is delivered between consecutive spots with continuous scanning, and current treatment planning systems do not take this into account. Therefore, continuous scanning and discrete spot plans have an inherent dose discrepancy. Using the operating parameters of the state-of-the-art particle therapy system, we conducted a proof-of-concept study in which we systematically generated 28 plans for cubic targets with different combinations of plan parameters and simulated the dose discrepancies between continuous scanning and a planned one. A nomograph to guide the selection of plan parameters was developed to reduce the dose discrepancy. The effectiveness of the nomograph was evaluated with two clinical cases (one prostate and one liver). Plans with parameters guided by the nomograph decreased dose discrepancy than those used standard plan parameters. Specifically, the 2%/2 mm gamma passing rate increased from 96.3% to 100% for the prostate case and from 97.8% to 99.7% for the liver case. The CTV DVH root mean square error decreased from 2.2% to 0.2% for the prostate case and from 1.8% to 0.9% for the liver case. The decreased dose discrepancy may allow the relaxing of the delivery constraint for some cases, leading to greater benefits in continuous scanning. Further investigation is warranted.


Eosinophilia associated with chronic pancreatitis.
Eosinophilia (>0.5 x 10/L eosinophils [EOSs] in the peripheral blood) has been overlooked in the study of chronic pancreatitis (CP). The purpose of this study was to investigate the clinical significance and causes of eosinophilia by analyzing the features of CP cases with eosinophilia. We retrospectively analyzed the clinical features of CP patients with eosinophilia and compared them with CP patients without eosinophilia. There were 28 cases (15.6%) of CP with eosinophilia among 180 CP patients. The ratio of male to female patients was 8.3:1. The mean patient age at the time of diagnosis was 49.0 (+/- 16.2) years. The peak value of EOSs in the patients' peripheral blood was 0.935 (+/- 0.600) x 10/L. The incidence of eosinophilia in autoimmune pancreatitis was significantly higher than in non-autoimmune pancreatitis CP cases. The incidence of pancreatic ascites, pancreatic enlargement, or jaundice in CP cases with eosinophilia was significantly higher than in those without eosinophilia. There was no obvious infiltration of EOSs in the pancreatic tissues of 16 pathology or cytology specimens. The occurrence of eosinophilia during the course of CP is not unusual. This may be related to autoimmune mechanisms, serous membrane response, or the progression of pancreatic inflammation and fibrosis.


Randomized Controlled Trial of Preoperative Topical Decolonization to Reduce Surgical Site Infection for Staphylococcus aureus Nasal Swab-Negative Mohs Micrographic Surgery Patients.
Surgical site infection (SSI) is mainly due to endogenous bacteria. Topical decolonization is a preoperative intervention currently advised for proven nasal carriers of Staphylococcus aureus (S. aureus). The authors assessed whether topical decolonization could be of benefit for patients who are not nasal carriers of S. aureus. The authors performed a randomized controlled trial of S. aureus nasal swab-negative patients. Five days before Mohs surgery topical decolonization with nasal mupirocin and chlorhexidine, body wash was started. The control group had no intervention. In the week after Mohs surgery, the infection rate in the intervention group was 2% (n = 661, 14) and that of the control group was 4% (n = 689, 29). Topical decolonization reduces SSI in nasal swab-negative Mohs surgery patients.


PREventing Maternal And Neonatal Deaths (PREMAND): a study protocol for examining social and cultural factors contributing to infant and maternal deaths and near-misses in rural northern Ghana.
While Ghana is a leader in some health indicators among West African nations, it still struggles with high maternal and neonatal morbidity and mortality rates, especially in the northern areas. The clinical causes of mortality and morbidity are relatively well understood in Ghana, but little is known about the impact of social and cultural factors on maternal and neonatal outcomes. Less still is understood about how such factors may vary by geographic location, and how such variability may inform locally-tailored solutions. Preventing Maternal And Neonatal Deaths (PREMAND) is a three-year, three-phase project that takes place in four districts in the Upper East, Upper West, and Northern Regions of Ghana. PREMAND will prospectively identify all maternal and neonatal deaths and 'near-misses', or those mothers and babies who survive a life threatening complication, in the project districts. Each event will be followed by either a social autopsy (in the case of deaths) or a sociocultural audit (in the case of near-misses). Geospatial technology will be used to visualize the variability in outcomes as well as the social, cultural, and clinical predictors of those outcomes. Data from PREMAND will be used to generate maps for local leaders, community members and Government of Ghana to identify priority areas for intervention. PREMAND is an effort of the Navrongo Health Research Centre and the University of Michigan Medical School. PREMAND uses an innovative, multifaceted approach to better understand and address neonatal and maternal morbidity and mortality in northern Ghana. It will provide unprecedented access to information on the social and cultural factors that contribute to deaths and near-misses in the project regions, and will allow such causal factors to be situated geographically. PREMAND will create the opportunity for local, regional, and national stakeholders to see how these events cluster, and place them relative to traditional healer compounds, health facilities, and other important geographic markers. Finally, PREMAND will enable local communities to generate their own solutions to maternal and neonatal morbidity and mortality, an effort that has great potential for long-term impact.


Genetic polymorphism in normal human fibroblasts as analyzed by two-dimensional polyacrylamide gel electrophoresis.
Two dimensional gel electrophoresis has been used to measure the degree of genetic polymorphism among the proteins of normal human fibroblasts. Autoradiographic analysis of the gel protein profiles from radioactively labeled cells allowed comparison of as many as 300 discrete polypeptides at a time. In addition, a newly developed technique for double label autoradiography was used to increase the sensitivity of the system for detection of small differences in the protein profiles of different cell lines. Only about 1.2% of the proteins of different cell lines were found to differ in their electrophoretic mobility. This corresponds to an average heterozygosity of approximately 0.6%. Previous studies of genetic polymorphism using different methods of one-dimensional electrophoretic analysis have estimated the average heterozygosity of the human population at about 6.7%. Detailed mathematical analysis shows the variation of the observed from the expected number of differences to be statistically highly significant. While the reasons for this difference are not clear, the observation of low levels of genetic polymorphism on two-dimensional gels should enhance the usefulness of this technique for detection of altered proteins in inherited disease.


Modelling the regional potential for reaching carbon neutrality in Finland: Sustainable forestry, energy use and biodiversity protection.
The EU aims at reaching carbon neutrality by 2050 and Finland by 2035. We integrated results of three spatially distributed model systems (FRES, PREBAS, Zonation) to evaluate the potential to reach this goal at both national and regional scale in Finland, by simultaneously considering protection targets of the EU biodiversity (BD) strategy. Modelling of both anthropogenic emissions and forestry measures were carried out, and forested areas important for BD protection were identified based on spatial prioritization. We used scenarios until 2050 based on mitigation measures of the national climate and energy strategy, forestry policies and predicted climate change, and evaluated how implementation of these scenarios would affect greenhouse gas fluxes, carbon storages, and the possibility to reach the carbon neutrality target. Potential new forested areas for BD protection according to the EU 10% protection target provided a significant carbon storage (426-452 TgC) and sequestration potential (- 12 to - 17.5 TgCO2eq a-1) by 2050, indicating complementarity of emission mitigation and conservation measures. The results of the study can be utilized for integrating climate and BD policies, accounting of ecosystem services for climate regulation, and delimitation of areas for conservation.


Effects of urine alkalinization with sodium bicarbonate orally on lower urinary tract symptoms in female patients: a pilot study.
In this study, we planned to explore the effects of sodium bicarbonate orally (NaHCO3) treatment on female patients with lower urinary tract symptoms (LUTS) who have acidic urine pH values (<6). NaHCO3 was given orally to 33 female patients for 4 weeks at a dose of 2 × 4 g/day. Laboratory values, bladder diary, the Patient Perception of Bladder Condition Score (PPBC), Patient Perception of Intensity of Urgency Scale (PPIUS), Overactive Bladder-Validated 8-question Awareness tool (OAB-V8), Pelvic Pain and Urgency & Frequency Patient Symptom Scale tests (PUFSS), and the King's Health Questionnaire (KHQ) scores before and after treatment were compared. A significant increase was detected in urine pH values measured after treatment (5.31 ± 0.52 to 7.2 ± 0.66, p < 0.001), but not in blood pH values (7.369 ± 0.33 to 7.384 ± 0.28, p = 0.14). After treatment, a significant decrease was detected in daily frequency, nocturia, urgency, and urge incontinence prevalence (p < 0.001,p = 0.003, p < 0.001, p = 0.002, respectively) and PPBC, PPIUS, PUFSS, and OAB-V8 symptom scores (p = 0.004, p = 0.002, p < 0.001, p < 0.001, respectively). A significant decrease was detected in all KHQ subunit scores. Urine alkalinization with NaHCO3 orally in female patients with LUTS and acidic urine pH has a significant level of positive effects on symptoms and symptom scores. Our results show that this new treatment modality-which is inexpensive, easy to use, and has a low side-effect profile is effective in this chronic patient group.


NH vs. CH hydrogen bond formation in metal-organic anion receptors containing pyrrolylpyridine ligands.
Anion complexation studies on a series of platinum(II) tetrakis(pyrrolylpyridine) salts demonstrate the importance of CH-anion hydrogen bonds in coordinating anionic guests in solution and the solid-state.


Control of intermediate filament protein synthesis by cell-cell interaction and cell configuration.
The expression of cytokeratins and vimentin was investigated in epithelial cells under conditions of varied cell spreading and cell-cell contact. When extensive cell-cell contact was achieved in dense monolayer cultures, or in suspension in multicellular aggregates, the cells synthesized high levels of cytokeratins and low levels of vimentin. In contrast, sparse monolayer and suspension cultures, with minimal cell-cell contact, synthesized low levels of cytokeratins and high levels of vimentin. The ratio of cytokeratin to vimentin synthesis was independent of the cell cycle and was also reflected at the level of mRNA translational activity in vitro. Thus control of cytokeratin synthesis involves cell-cell contact, while vimentin synthesis responds to cell shape changes.


Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data.
Dostarlimab (JEMPERLI) is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody (mAb) which is approved by the US Food and Drug Administration for patients with recurrent/advanced mismatch repair-deficient solid tumors, including endometrial cancer, following progression on prior treatment, with approval based on data from the phase I GARNET trial. To support dostarlimab dose regimen recommendations, we estimated and compared the potency of dostarlimab relative to anti-PD-1 mAb pembrolizumab using both data published from the KEYNOTE-001 trial of pembrolizumab and data from the GARNET trial. PD-1 target engagement was assessed ex vivo in blood samples via a super antigen staphylococcal enterotoxin B stimulation assay and interleukin-2 (IL-2) stimulation ratios calculated for dostarlimab. A non-linear mixed-effect sigmoid maximum effect inhibitory model was fitted to dostarlimab IL-2 stimulation ratios using extracted pembrolizumab data as informative priors. The estimated half-maximal effective concentration was 1.95 μg ml-1 (95% credibility interval: 0.21-5.87) for dostarlimab and 1.59 μg ml-1 (95% confidence interval: 0.42-6.12) for pembrolizumab. These findings suggest dostarlimab and pembrolizumab to be equipotent for peripheral PD-1 suppression based on analysis of ex vivo IL-2 stimulation ratios. Accounting for a three-fold dilution between serum and tumor, a target dostarlimab trough concentration of ~54 μg ml-1 would be needed for 90% suppression in the tumor. These data support the use of dostarlimab as a potent PD-1 suppressor and the recommended dostarlimab monotherapy dose regimen of 500 mg Q3W ×4 cycles followed by 1000 mg Q6W thereafter in recurrent/advanced solid tumors.


Age-specific prevalence of intellectual disability in Finland at the beginning of new millennium--multiple register method.
In the national study of multiple registers in 2000, the average prevalence of intellectual disability (ID) was 0.70%, with marked differences by age group (range 0.38-0.96%) - what are these differences in detail, and can they be understood? This study was based on two national health registers and six social benefit registers. Prevalence of ID was calculated by 1-year age cohorts. The multiple register prevalence of ID increased steadily from 0.20% in the first life year to 0.74% (male: 0.90%, female: 0.58%) at 10 years. For boys, the rate fell to 0.71% at 11 years. For both sexes, a steady increase was noted in the distribution up to 40 years (male: 0.84%, female: 0.73%), followed by a sharper increase to the maximum prevalence (male: 1.19% at 48 years, female: 1.05% at 50 years). At the pension age of 66 years, a sudden drop to 0.49% occurred for men and women. Different registers gave very different age distributions. By examining the data by 1-year age cohorts, and by understanding the role of each register, it could be deduced that a proportion of cases in younger age groups is lacking, and a remarkable proportion of elderly ID persons is missing from the pooled data. The findings were more difficult to interpret, if the data were grouped into bigger age groups.


Cross-blocking studies with monoclonal antibodies against I-A molecules of haplotypes b, d and k.
For assessment of the distribution of allodeterminants on I-A molecules, binding inhibition studies were performed with monoclonal anti-I-A antibodies (mAb) in which pairs of labeled and unlabeled mAb were tested for cross-blocking on spleen cells of H-2 haplotypes b, d and k. The data suggest that allodeterminants are randomly distributed on the surface of the I-A molecule. Comparison of mAb with cross-reactivity for b, d or k haplotypes indicates that the allelic forms of determinants are located in analogous positions on different I-A antigens.


Disrupting life events and the sleep-wake cycle in depression.
Social rhythm disruption life events are significant predictors of mood relapse in bipolar patients. However, no research has examined the relationship between these events and their hypothesized mechanism of action: disrupted sleep-wake patterns. The goal of this study was to test whether participants with major depressive disorder have a greater disruption of daily sleep and motor activity following disrupting life events when compared to normal controls. Over the course of 2 weeks, 39 normal controls and 39 individuals with major depressive disorder completed life events interviews and wore actigraphs to obtain estimates of sleep/wake activity. Statistically significant interactions indicated that the presence of at least one disrupting life event in the previous 4 months correlated with elevations in the amount of time spent awake after sleep onset [beta=0.45, deltaF(1,73)=4.80, p<0.05], and decreases in the percentage of time spent asleep [beta=-0.53, deltaF(1,73)=6.57, p<0.05], in depressed individuals but not in normal controls. The results indicated that depressed individuals may be more susceptible to the effects of life events on sleep than normal controls. This is the first study to date to correlate life events with objective measures of sleep. However, prospective longitudinal research is necessary to clarify the temporal relationship among these variables.


Spousal caregiving, widowhood, and cognition: A systematic review and a biopsychosocial framework for understanding the relationship between interpersonal losses and dementia risk in older adulthood.
Accumulating research suggests that stressful life events, especially those that threaten close intimate bonds, are associated with an increased risk of dementia. Grieving the loss of a spouse, whether in the form of caregiving or after the death, ranks among 'life's most significant stressors', evoking intense psychological and physiological distress. Despite numerous studies reporting elevated dementia risk or poorer cognition among spousal caregivers and widow(er)s compared to controls, no review has summarized findings across cognitive outcomes (i.e., dementia incidence, cognitive impairment rates, cognitive performance) or proposed a theoretical model for understanding the links between partner loss and abnormal cognitive decline. The current systematic review summarizes findings across 64 empirical studies. Overall, both cross-sectional and longitudinal studies revealed an adverse association between partner loss and cognitive outcomes. In turn, we propose a biopsychosocial model of cognitive decline that explains how caregiving and bereavement may position some to develop cognitive impairment or Alzheimer's disease and related dementias. More longitudinal studies that focus on the biopsychosocial context of caregivers and widow(er)s are needed.


Elimination of mycoplasma contamination from mammalian cell cultures by the bibenzimidazole derivative Hoechst 33258.
Cell cultures contaminated with mycoplasma or bacterial L-forms were treated with 8 micrograms/ml of Hoechst 33258. No microorganisms could be detected by fluorescence microscopy after two rounds of treatment.


Clinical practice guidelines on newborn hearing screening: A systematic quality appraisal using the AGREE II instrument.
Several guidelines and consensus statements have been produced and disseminated for the detection and management of newborn hearing loss. However, to date, the quality and methodologic rigor of these screening and management protocols have not been appraised. To identify and evaluate existing guidelines and consensus statements for the detection and management of neonatal hearing loss. A comprehensive search of EMBASE, MEDLINE/PubMed, SCOPUS and grey literature sources was conducted until August 2020. The quality of these guidelines was assessed by four independent reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). Domain scores were considered satisfactory quality if they scored >60%, and intraclass correlation coefficients (ICC) were calculated to assess agreement among the appraisers. Twelve guidelines were assessed for critical evaluation. Only two guidelines were classified as 'high quality', and the remaining were 'average' or 'low quality'. The 'Scope and Purpose' domain achieved the highest mean score (91.3% ± 5.8%), and lowest was 'Rigor of Development' (35.8% ± 19.1%). ICC analysis showed good to very good agreement across all domains (0.63-0.95). These findings highlight the variability in methodologic quality of guidelines and consensus statement for the detection and management of neonatal hearing loss. These results may help to improve the reporting of future guidelines and guide the selection and use of these guidelines in clinical practice.


Synthesis and evaluation of aza HUN-7293.
The aza analogue of the cyclic heptadepsipeptide HUN-7293 (1), which is a potent naturally occurring inhibitor of inducible cell adhesion molecule expression, and its C2(3) (MLEU3 C2) epimer were prepared via solution-phase synthesis. Biological evaluations of these two compounds as inhibitors of cell adhesion molecules expression are detailed.


Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection.
Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.


Pulmonary manifestations masquerading a longstanding neglected metallic foreign body in the esophagus of a paediatric patient from Tanzania: Rare case report.
Paediatric foreign body (FB) ingestion remains to be a common encounter in otorhinolaryngology and may manifest with pulmonary manifestations. Pulmonary manifestations masquerading chronic esophageal FBs in children is rare in clinical practice. This is perhaps the first documented case in Tanzania. The patient was a 6-year old boy with a 6-month history of ingesting a metallic object. The child was reported to have presented with sudden onset of drooling of saliva and difficulty in swallowing that lasted for several hours. While preparing to visit a hospital, no more drooling of saliva was noted thus the visit was cancelled. A month later the patient presented with recurrent episodes of dry cough associated with wheezing and unresponsive to medical treatment. Upon attending other health facilities no chest X-ray was ordered but rather prescribed antibiotics, mucolytics, antihistamines and antileukotrienes without relief. Chest x-ray was indicated and revealed an esophageal metallic object. Rigid esophagoscopy under general anaesthesia yielded the rusted metallic object in piece meals. Postoperative antibiotic, analgesic and an oral corticosteroid were prescribed. Postoperative visits were uneventful. The patient underwent esophagoscopy and the rusted` metallic object was extracted in piece meals. Postoperative antibiotic, analgesic and oral corticosteroid were prescribed. Postoperative visits were uneventful. It is always important to suspect FB ingestion in a child with a history of sudden onset of drooling of saliva and difficulty in swallowing. Imaging should be advocated to avoid delayed diagnosis otherwise pulmonary manifestations can masquerade the diagnosis of chronic esophageal FBs.


Basement Membranes in the Worm: A Dynamic Scaffolding that Instructs Cellular Behaviors and Shapes Tissues.
The nematode worm Caenorhabditis elegans has all the major basement membrane proteins found in vertebrates, usually with a smaller gene family encoding each component. With its powerful forward genetics, optical clarity, simple tissue organization, and the capability to functionally tag most basement membrane components with fluorescent proteins, C. elegans has facilitated novel insights into the assembly and function of basement membranes. Although basement membranes are generally thought of as static structures, studies in C. elegans have revealed their active properties and essential functions in tissue formation and maintenance. Here, we review discoveries from C. elegans development that highlight dynamic aspects of basement membrane assembly, function, and regulation during organ growth, tissue polarity, cell migration, cell invasion, and tissue attachment. These studies have helped transform our view of basement membranes from static support structures to dynamic scaffoldings that play broad roles in regulating tissue organization and cellular behavior that are essential for development and have important implications in human diseases.


A high-performance liquid chromatographic method for the enantiomeric analysis of the enzymatically synthesized coenzyme A ester of 2-tetradecylglycidic acid.
The enantiomeric composition of an enzymatically synthesized sample of the coenzyme A ester of 2-tetradecylglycidic acid (TDGA-CoA) was determined by the use of high-performance liquid chromatography with a chiral stationary phase. The stationary phase was commercially available and consisted of (R)-N-(3,5-dinitrobenzoyl)phenylglycine covalently bonded to aminopropyl silica gel. Analysis was performed using the phenacyl derivative of 2-tetradecylglycidic acid (TDGA), obtained by mild hydrolysis of the TDGA-CoA followed by reaction of the extracted TDGA with phenacyl chloride. Chromatography showed the enantiomeric purity of TDGA-CoA, synthesized in a rat liver microsomal enzyme mixture over a 2-h period, to be a 15.6:1 ratio of the R:S enantiomers (88% ee). The result demonstrates the stereoselectivity of the long-chain fatty acid-coenzyme A synthetase for chiral fatty acid epoxide, TDGA.


Cold tolerance, water balance, energetics, gas exchange, and diapause in overwintering brown marmorated stink bugs.
Halyomorpha halys (Hemiptera: Pentatomidae) is an emerging pest which established in Ontario, Canada, in 2012. Halyomporpha halys overwinters in anthropogenic structures as an adult. We investigated seasonal variation in the cold tolerance, water balance, and energetics of H. halys in southwestern Ontario. We also induced diapause in laboratory-reared animals with short daylength at permissive temperatures and compared cold tolerance, water balance, energetics, and metabolism and gas exchange between diapausing and non-diapausing individuals. Halyomorpha halys that overwintered outside in Ontario all died, but most of those that overwintered in sheltered habitats survived. We confirm that overwintering H. halys are chill-susceptible. Over winter, Ontario H. halys depressed their supercooling point to c. -15.4 °C, and 50% survived a 1 h exposure to -17.5 °C. They reduce water loss rates over winter, and do not appear to significantly consume lipid or carbohydrate reserves to a level that might cause starvation. Overall, it appears that H. halys is dependent on built structures and other buffered microhabitats to successfully overwinter in Ontario. Laboratory-reared diapausing H. halys have lower supercooling points than their non-diapausing counterparts, but LT50 is not enhanced by diapause induction. Diapausing H. halys survive desiccating conditions for 3-4 times longer than those not in diapause, through decreases in both respiratory and cuticular water loss. Diapausing H. halys do not appear to accumulate any more lipid or carbohydrate than those not in diapause, but do have lower metabolic rates, and are slightly more likely to exhibit discontinuous gas exchange.


Spatial heterogeneity of the microbiome and metabolome profiles of high-temperature Daqu in the same workshop.
High-temperature Daqu, usually used as a fermentation starter for sauce-flavor Baijiu production, plays an essential role in the yield and flavor quality of Baijiu. The environmental heterogeneity of different locations in the workshop during fermentation led to the final production of Daqu with three different types (i.e., white, yellow, and black Daqu). How to use these three types of Daqu in Baijiu production mainly depends on the workers' experience so far. Here, we aimed to reveal the potential functions of different types of Daqu by comparing enzyme activity, volatile metabolites, and microbiota characteristics. White_Qu exhibited the highest liquefaction and saccharification enzyme activities, while the highest neutral proteinase and cellulase enzyme activities were detected in black_Qu. The total volatile content of yellow_Qu and black_Qu was roughly double that of white_Qu, and multivariate analysis revealed distinct volatile dissimilarities across different types of Daqu. Significant differences in bacterial and fungal community structures, assembly patterns, and potential functional profiles were discovered among different types of Daqu. At the genus level, Oceanobacillus and Thermomyces dominated the white_Qu microbiota, and the abundant microbes in yellow_Qu and black_Qu were scattered in Kroppenstedtia and Thermoascus. Bacterial and fungal communities were dominated by deterministic and stochastic assembly processes, respectively, suggesting that bacteria may be more affected by abiotic environmental factors and species interaction than fungi. Co-occurrence network analysis showed positive correlations characterized Daqu microbial networks, and network topological features indicated stronger interactions between bacterial taxa compared with fungal community. The Spearman correlation analysis revealed that four bacterial genera (Kroppenstedtia, Virgibacillus, Scopulibacillus, and Staphylococcus) and two fungal genera (Thermoascus and Aspergillus) exhibited positive correlations with almost all of the abundant volatiles. This work reveals that spatially varying environments lead to the microbiome and metabolome heterogeneity of high-temperature Daqu in the same workshop.


High-resolution and high-sensitivity PET for quantitative molecular imaging of the monoaminergic nuclei: A GATE simulation study.
Quantitative in vivo molecular imaging of fine brain structures requires high-spatial resolution and high-sensitivity. Positron emission tomography (PET) is an attractive candidate to introduce molecular imaging into standard clinical care due to its highly targeted and versatile imaging capabilities based on the radiotracer being used. However, PET suffers from relatively poor spatial resolution compared to other clinical imaging modalities, which limits its ability to accurately quantify radiotracer uptake in brain regions and nuclei smaller than 3 mm in diameter. Here we introduce a new practical and cost-effective high-resolution and high-sensitivity brain-dedicated PET scanner, using our depth-encoding Prism-PET detector modules arranged in a conformal decagon geometry, to substantially reduce the partial volume effect and enable accurate radiotracer uptake quantification in small subcortical nuclei. Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels using 1.5 × 1.5 × 20 $1.5 \times 1.5 \times 20$ mm3 and 0.987 × 0.987 × 20 $0.987 \times 0.987 \times 20$ mm3 crystal columns, respectively. Monte Carlo simulations of our Prism-PET scanners, Siemens Biograph Vision, and United Imaging EXPLORER were performed using Geant4 application for tomographic emission (GATE). National Electrical Manufacturers Association (NEMA) standard was followed for the evaluation of spatial resolution, sensitivity, and count-rate performance. An ultra-micro hot spot phantom was simulated for assessing image quality. A modified Zubal brain phantom was utilized for radiotracer imaging simulations of 5-HT1A receptors, which are abundant in the raphe nuclei (RN), and norepinephrine transporters, which are highly concentrated in the bilateral locus coeruleus (LC). The Prism-PET brain scanner with 1.5 mm crystals is superior to that with 1 mm crystals as the former offers better depth-of-interaction (DOI) resolution, which is key to realizing compact and conformal PET scanner geometries. We achieved uniform 1.3 mm full-width-at-half-maximum (FWHM) spatial resolutions across the entire transaxial field-of-view (FOV), a NEMA sensitivity of 52.1 kcps/MBq, and a peak noise equivalent count rate (NECR) of 957.8 kcps at 25.2 kBq/mL using 450-650 keV energy window. Hot spot phantom results demonstrate that our scanner can resolve regions as small as 1.35 mm in diameter at both center and 10 cm away from the center of the transaixal FOV. Both 5-HT1A receptor and norepinephrine transporter brain simulations prove that our Prism-PET scanner enables accurate quantification of radiotracer uptake in small brain regions, with a 1.8-fold and 2.6-fold improvement in the dorsal RN as well as a 3.2-fold and 4.4-fold improvement in the bilateral LC compared to the Biograph Vision and EXPLORER, respectively. Based on our simulation results, the proposed high-resolution and high-sensitivity Prism-PET brain scanner is a promising cost-effective candidate to achieve quantitative molecular neuroimaging of small but important brain regions with PET clinically viable.


Impact of Recreational Cannabis Legalization on Opioid Prescribing and Opioid-Related Hospital Visits in Colorado: an Observational Study.
Cannabis may be a substitute for opioids but previous studies have found conflicting results when using data from more recent years. Most studies have examined the relationship using state-level data, missing important sub-state variation in cannabis access. To examine cannabis legalization on opioid use at the county level, using Colorado as a case study. Colorado allowed recreational cannabis stores in January 2014. Local communities could decide whether to allow dispensaries, creating variation in the level of exposure to cannabis outlets. Observational, quasi-experimental design exploiting county-level variation in allowance of recreational dispensaries. Colorado residents MEASURES: We use licensing information from the Colorado Department of Revenue to measure county-level exposure to cannabis outlets. We use the state's Prescription Drug Monitoring Program (2013-2018) to construct opioid-prescribing measures of number of 30-day fills and total morphine equivalents, both per county resident per quarter. We construct outcomes of opioid-related inpatient visits (2011-2018) and emergency department visits (2013-2018) with Colorado Hospital Association data. We use linear models in a differences-in-differences framework that accounts for the varying exposure to medical and recreational cannabis over time. There are 2048 county-quarter observations used in the analysis. We find mixed evidence of cannabis exposure on opioid-related outcomes at the county level. We find increasing exposure to recreational cannabis is associated with a statistically significant decrease in number of 30-day fills (coefficient: -117.6, p-value<0.01) and inpatient visits (coefficient: -0.8, p-value: 0.03), but not total MME nor ED visits. Counties with no medical exposure prior to recreational legalization experience greater reductions in the number of 30-day fills and MME than counties with prior medical exposure (p=0.02 for both). Our mixed findings suggest that further increases in cannabis beyond medical access may not always reduce opioid prescribing or opioid-related hospital visits at a population level.


Evolutional aspects of children and adolescents with surgically corrected aortic coarctation: clinical, echocardiographic, and magnetic resonance image analysis of 113 patients.
The goals of this study were to determine the prevalence of hypertension and recoarctation in operated children and teenagers and to integrate clinical and imaging technique data. One hundred thirteen infants and children (ages 14 years or less) were retrospectively divided into 3 groups according to the age at operation and the surgical technique: 79 underwent resection with end-to-end anastomosis; 14 had patch enlargement; 13 had subclavian flap aortoplasty; and 7 had other techniques performed. The mean age at operation was 3.95 +/- 4.17 years and the mean follow-up period was 4.62 +/- 4.90 years. Each patient was clinically examined and Doppler echocardiography was performed in 112 patients. Sixty-six patients underwent magnetic resonance imaging. Diameters of aortic arch were measured at 4 levels; the ratios between each one and descendent aorta diameters were calculated. Qualitative variables and associations were studied by Fisher exact test or chi-squared test. Comparisons of measurements in different groups were performed using variance analysis, with tests of selective contrasts (nonparametric tests). The level of statistical significance was <.05. The prevalence of hypertension and recoarctation was 38% and 14%, respectively. No statistical difference was found among the age groups. In 65 patients who underwent magnetic resonance imaging, the transverse aortic arch was hypoplastic in 31 (47%) patients; 41 (63%) had stenosis at the site of anastomosis (ratio < 0.9). Hypoplasia of transverse aortic arch was highly prevalent. These data suggest that hypoplastic aortic arch should be corrected concomitantly with coarctation.


Nonpharmacological interventions for osteoporosis treatment: Systematic review of clinical practice guidelines.
The aim of this study was to perform a systematic review of clinical practice guidelines to identify nonpharmacologic recommendations for osteoporosis treatment. A systematic review of literature following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-statement methodology for clinical practice guidelines was conducted; PROSPERO CRD42019138548. Assessment of selected clinical practice guidelines with the AGREE (Appraisal of Guidelines for Research & Evaluation)-II methodological quality instrument was performed, and those graded over 60 points were selected for recommendations extraction and evidence analysis. Only 6 clinical practice guidelines fulfilled criteria, 69 nonpharmacological recommendations were extracted: 13 from American Association of Clinical Endocrinologists and American College of Endocrinology guideline, 16 from Malaysian Osteoporosis Society guideline, 15 from the Ministry of Health in Mexico guideline, 14 from Royal Australian College of General Practitioners guideline, 7 from Sociedad Española de Investigación Ósea y del Metabolismo Mineral guideline, and 7 from National Osteoporosis Guideline Group guideline. Percentage by theme showed that the highest number of recommendations were 12 (17.1%) for vitamin D, 11 (15.7%) for a combination of calcium and vitamin D, and 11 (15.7%) for exercise. These recommendations address integrating interventions to modify lifestyle, mainly calcium and vitamin D intake, and exercise. Other recommendations include maintaining adequate protein intake, identification and treatment of risk factors for falls, and limiting the consumption of coffee, alcohol and tobacco. Considerations on prescription must be taken.


A Systematic Review of Wearable Systems for Cancer Detection: Current State and Challenges.
Rapid growth of sensor and computing platforms have introduced the wearable systems. In recent years, wearable systems have led to new applications across all medical fields. The aim of this review is to present current state-of-the-art approach in the field of wearable system based cancer detection and identify key challenges that resist it from clinical adoption. A total of 472 records were screened and 11 were finally included in this study. Two types of records were studied in this context that includes 45% research articles and 55% manufactured products. The review was performed per PRISMA guidelines where considerations was given to records that were published or reported between 2009 and 2017. The identified records included 4 cancer detecting wearable systems such as breast cancer (36.3%), skin cancer (36.3%), prostate cancer (18.1%), and multi-type cancer (9%). Most works involved sensor based smart systems comprising of microcontroller, Bluetooth module, and smart phone. Few demonstrated Ultra-Wide Band (i.e. UWB) antenna based wearable systems. Skin cancer detecting wearable systems were most comprehensible ones. The current works are gradually progressing with seamless integration of sensory units along with smart networking. However, they lack in cloud computing and long-range communication paradigms. Artificial intelligence and machine learning are key ports that need to be attached with current wearable systems. Further, clinical inertia, lack of awareness, and high cost are altogether pulling back the actual growth of such system. It is well comprehended that upon sincere orientation of all identified challenges, wearable systems would emerge as vital alternative to futuristic cancer detection.


Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways.
Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose‑ and time‑dependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated B‑cell lymphoma 2 (Bcl‑2) expression, and upregulated Bcl‑2‑associated X protein and Bcl‑2 homologous antagonist killer expression in a dose‑dependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signal‑regulated kinase (Erk) and Akt phosphorylation. These results indicated that shikonin may exert its anti‑proliferative effects by inducing apoptosis via activation of the mitochondrial signaling pathway and inactivation of the Akt and Erk pathways in HaCaT cells. Therefore, the present study suggested that shikonin may have potential as a component of therapeutic strategies for the treatment of skin diseases.


Excision repair in ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome, and Bloom's syndrome after treatment with ultraviolet radiation and N-acetoxy-2-acetylaminofluorene.
Excision repair of damage due to ultraviolet radiation, N-acetoxy-2-acetyl-aminofluorene and a combination of both agents was studied in normal human fibroblasts and various cells from cancer prone patients (ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome and Bloom's syndrome). Three methods giving similar results were used: unscheduled DNA synthesis by radioautography, photolysis of bromodeoxyuridine incorporated into parental DNA during repari, and loss of sites sensitive to an ultraviolet endonuclease. All cell lines were proficient in repair of ultraviolet and acetoxy acetylaminofluorene damage and at saturation doses of both agents repair was additive. We interpret these data as indicating that the rate limiting step in excision repair of ultraviolet and acetoxy acetylaminofluorene is different and that there are different enzyme(s) working on incision of both types of damages.


Three- and four-dimensional HDlive rendering image of fetal acrania/exencephaly in early pregnancy.
We present two cases of fetal acrania/exencephaly reconstructed employing the three- (3D) and four-dimensional (4D) HDlive rendering mode in early gestation. Two fetuses with acrania/exencephaly were studied with the 3D/4D HDlive rendering mode at 13 and 15 weeks, respectively. In Case 1, at 13 weeks' gestation, deformed and degenerated brain tissues were clearly shown using the 3D/4D HDlive rendering mode. In Case 2, at 15 weeks and 6 days of gestation, two amniotic bands and acrania/exencephaly were depicted with the 3D/4D HDlive rendering mode. Fragile brain hemispheres with amniotic bands were rocking with fetal movements. The 3D/4D HDlive rendering mode provides physicians, couples, and their families with important and additional information, and has the potential to supplement two-dimensional and conventional 3D ultrasound in diagnosing fetal acrania/exencephaly.


Correlation of electronic and vibrational properties with the chiro-optical activity of polyfluorene copolymers.
The rationale of this paper is to shed some light on the origin of the optical response of two similar chiral fluorene copolymers in correlation with their vibrational modes, to understand how a chiral center placed in a ramification affects the optical properties of the main chain. Various spectroscopic ellipsometric techniques, in the scope of the Stokes theory were used to characterize the optical-vibrational behavior of the polyfluorenes: ellipsometry in emission (EE), transmission (TE), and Raman (ERS). The results showed that the optical activity and the emission of the circularly polarized light depends substantially on the interaction of the chiral carbon in the ramification and the main chain through specific optically active vibrational modes, for each sample. One interesting achievement was to find the absolute dextrorotatory configuration of the studied molecules, that could induce a helicoidal structure to the entire material.


Effects of phorbol ester on mitogen and orthovanadate stimulated responses of cultured human fibroblasts.
Mitogenic stimulation of quiescent human fibroblasts (HSWP) with serum or a mixture of growth factors (consisting of vasopressin, bradykinin, EGF, and insulin) stimulates the release of inositol phosphates, mobilization of intracellular Ca, activation of Na/H exchange and subsequent incorporation of [3H]-thymidine. We have determined previously that pretreatment with the tumor-promoting phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA) inhibits mitogen-stimulated Na influx in HSWP cells. We report herein that TPA pretreatment also substantially inhibits the mitogen-stimulated release of inositol phosphates in HSWP cells. Half maximal inhibition of mitogen-stimulated inositol phosphate release occurs at 1-2 nM TPA. Treatment of cells with TPA alone has no effect on inositol phosphate release. The effect of TPA pretreatment on inositol phosphate release induced by individual growth factors has also been determined. Orthovanadate, reported by Cassel et al. (1984) to increase Na/H exchange in A431 cells, has been demonstrated to stimulate both Na influx and inositol phosphate release in HSWP cells. TPA pretreatment also inhibits both orthovanadate-stimulated inositol phosphate release and Na influx. In addition, orthovanadate was determined to increase intracellular Ca activity by mobilizing intracellular calcium stores, as determined with the fluorescent intracellular calcium probe fura-2. TPA pretreatment blocks orthovanadate stimulated mobilization of intracellular Ca stores. It appears clear that in HSWP cells pretreatment of cells with phorbol ester is capable of artificially desensitizing the early cellular responses to mitogenic stimuli (growth factors, orthovanadate) by blocking the signal transduction mechanism involved at a point prior to the release of inositol phosphates. We hypothesize that in HSWP cells the normal desensitization of both inositol phosphate release and Na/H exchange is mediated via activation of protein kinase C subsequent to the stimulus-mediated activation of phospholipase C and release of protein kinase C activator diacylglycerol. However it is interesting to note that TPA-mediated inhibition of these early responses in HSWP cells does not inhibit their ability to be stimulated to incorporate [3H]-thymidine.(ABSTRACT TRUNCATED AT 400 WORDS)


A month-by-month long-term study on carbamazepine:clinical, EEG and pharmacological evaluation.
Carbamazephine plasma levels were monitored for a twelve-month period in twenty epileptic patients. Seizure frequency decreased remarkably on inclusion of the drug in the therapy and attainment of plasma levels of 7-9 microgram/ml. A faster breakdown rate in children was confirmed, while carbamazepine-10, 11-epoxide was present for carbamazepine levels above 4-5 microgram/ml. EEG tracings did not show substantial modifications; this variable was thus considered to be of little value in assessing the clinical picture. Side-effects were minimal. Carbamazepine is increasingly becoming the drug of first choice in the management of both generalized and partial epilepsy, while better and more rapid results are obtained in monotherapy.


Anatomic and technical considerations in needle electromyography of the lumbar spine.
Interpretation of the paraspinal needle electromyographic examination requires knowledge of complex and specialized anatomy and pathophysiological processes. The purpose of this article is to elucidate the anatomy and physiology of the lumbar paraspinal needle examination and apply this knowledge to accurate needle technique and rational clinical interpretation of the paraspinal examination.


Energetics and food requirements of the female snake Phillodryas chamissonis during the breeding season.
1.The energetic performance and food requirements of female Phillodryas chamissonis was determined during its breeding season at different ambient temperatures. 2. If the long tailed snake is active for 24 weeks, 25 to 32 30-g rodents are required for reproduction and maintenance. This is slightly more than one rodent per week. 3. The energy cost of reproduction (38 to 48% of total metabolism) is close to the values reported for fish (35% of metabolizable energy). 4. Due to their low metabolic rates, the theoretical predation pressure (on a prey biomass basis) exerted by the snakes should be 2 to 2.5% of that expected for endothermic predators of similar body size.


Review: Correlation between bladder obstruction with bladder function and erectile dysfunction in mice.
Bladder obstruction, including due to benign prostate enlargement (BPH), will trigger its anatomy and physiological function changes. Men with BPH have a 6 times higher risk of erectile dysfunction than those without BPH. Morphological and functional changes in subjects with partial bladder outlet obstruction (pBOO) occur differently depending on the duration of pBOO that has been experienced. The underlying pathophysiology of BPH is closely related to erectile dysfunction. Anatomically, functionally, and psychologically changes due to BPH will also have an impact on sexual function. Chronic pBOO causes lower urinary tract symptoms (LUTS) through a complex pathophysiological pathway. LUTS and bladder obstruction can lead to erectile dysfunction. The severity of LUTS and sexual dysfunction is inversely related to the quality of life. The treatment of LUTS symptoms will also enhance sexual function.


Profiles of subjective well-being among people living with HIV during the COVID-19 pandemic.
The aim of our study was to examine subjective well-being (SWB) profiles and their sociodemographic and clinical correlates among people living with HIV (PLWH) during the COVID-19 pandemic. The participants were 663 PLWH undergoing antiretroviral treatment. Their SWB was evaluated using the Satisfaction with Life Scale and the Positive and Negative Affect Schedule. Sociodemographic and clinical covariates, together with COVID-19 distress, were assessed with a self-report survey. Latent profile analysis revealed four SWB profiles: average negative, average positive, flourishing and languishing. The languishing profile was the worse in terms of values of SWB components and had a relative overrepresentation of PLWH who were single, without a university degree, and not employed for money. The pandemic-related distress was positively related to being a member of average negative and languishing profiles. Gender and age had no significant effect on either profile membership or directly on the SWB components. It seems that in the context of chronic illness and socially shared stressful circumstances, which was the COVID-19 pandemic, the components of SWB among PLWH developed rather congruent profiles. Sociodemographic, but not clinical characteristics were found to be significant correlates of belonging to obtained SWB profiles in this sample. The most striking effect with this regards was obtained for the members of the languishing profile, defined by the co-occurrence of low positive affect, low satisfaction with life, and high negative affect.


Association of actin with DNA and nuclear matrix from Guerin ascites tumour cells.
The protein composition of nuclear matrices containing different amount of DNA was examined. It was found that, in matrices containing 2% to 80% of total DNA, the quantity of DNA-bound proteins remains relatively constant varying from 10% to 15% of total nuclear proteins. Electrophoretic patterns do not differ substantially, but autoradiograms with in vitro 125I labelled proteins show quantitative variations in the actin content. Application of radioimmunoassay (RIA) enabled to determine the exact content of actin in GAT nuclei and nuclear matrices - 5 micrograms/ml in nuclei, of which 50% are bound to DNA and 30% being a component of the protein part of the nuclear matrix. These results are supported by electron microscopic data, where immunogold technique was performed on thin sections and spread material. The applied methods suggest that part of the nuclear actin is tightly bound (resistant to 2 M NaCl) to DNA and represents a component of the internal nuclear matrix.


Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.
The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.


Semicarbazide-based fluorescent probe for detection of Cu2+ and formaldehyde in different channels.
Two fluorescent sensors with the receptor semicarbazide respectively at 7- (CAA) and 3-position (CAB) of coumarin were designed and synthesized. CAA exhibits fluorescence turn-on response to Cu2+ by triggering the intramolecular charge transfer (ICT) process via Cu2+-catalyzed hydrolysis, and can detect formaldehyde (FA) at different channel by inhibiting the photo-induced electron transfer (PET). However, CAB displays quite different responses: the photophysical properties hardly changed in the presence of FA; while a three-stage fluorescence response of fast quenching, steady increasing and slowly decreasing was found upon addition of Cu2+. The high selectivity enabled CAA a good candidate for quantification of Cu2+ and formaldehyde as well as bioimaging Cu2+ in living cells. Good linear relationships between the fluorescence intensity and analyte concentration were observed in the range of 0.1-30 μM for Cu2+ and 1.0-50 μM for FA, and their detection limits (LOD) were calculated to be 0.43 μM and 1.92 μM (3δ/k), respectively.


Protective role of tetrahydrocurcumin against erythromycin estolate-induced hepatotoxicity.
Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, was investigated for its possible hepatoprotective effect in Wistar rats against erythromycin estolate-induced toxicity. Oral administration of THC significantly prevented the occurrence of erythromycin estolate-induced liver damage. The increased level of serum enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)), bilirubin, cholesterol, triglycerides, phospholipids, free fatty acids and plasma thiobarbituric acid reactive substances (TBARS) and hydroperoxides observed in rats treated with erythromycin estolate were very much reduced in rats treated with THC and erythromycin estolate. This biochemical observation were supplemented by histopathological examination of liver section. Results of this study revealed that THC could afford a significant protection against erthromycin estolate-induced hepatocellular damage. Tetrahydrocurcumin had a better protective effect when compared with Silymarin, a reference drug.


Stimulatory effect of ascorbate on iron transfer from bleomycin to apotransferrin.
The chemotherapeutic agent, bleomycin, forms a 1:1 complex with both Fe(III) and Fe(II). The rate of ferric ion transfer from bleomycin to apotransferrin is rather slow. However, when ascorbate was added to Fe(III)-bleomycin prior to exposure to apotransferrin, the transfer rate was markedly increased. Ascorbate readily reduces Fe(III)-bleomycin to Fe(II)-bleomycin. A second order rate constant of 2.4 mM-1 min-1 was estimated for this reaction. Fe(II)-bleomycin immediately combines with O2, generating the so-called 'activated bleomycin' complex. The data suggest that a reduced form of iron-bleomycin more readily donates its iron ion to apotransferrin. Reoxidation of ferrous ions, and Fe(III)-transferrin formation occur rapidly.


Single-molecule analysis of cell surface dynamics in Caenorhabditis elegans embryos.
We describe a general, versatile and minimally invasive method to image single molecules near the cell surface that can be applied to any GFP-tagged protein in Caenorhabditis elegans embryos. We exploited tunable expression via RNAi and a dynamically exchanging monomer pool to achieve fast, continuous single-molecule imaging at optimal densities with signal-to-noise ratios adequate for robust single-particle tracking (SPT). We introduce a method called smPReSS, single-molecule photobleaching relaxation to steady state, that infers exchange rates from quantitative analysis of single-molecule photobleaching kinetics without using SPT. Combining SPT and smPReSS allowed for spatially and temporally resolved measurements of protein mobility and exchange kinetics. We used these methods to (i) resolve distinct mobility states and spatial variation in exchange rates of the polarity protein PAR-6 and (ii) measure spatiotemporal modulation of actin filament assembly and disassembly. These methods offer a promising avenue to investigate dynamic mechanisms that pattern the embryonic cell surface.


An insertion mutation of the MECP2 gene in severe neonatal encephalopathy and ocular and oropharyngeal dyskinesia: a case report.
Pathogenic variation of the MECP2 gene presents mostly as Rett syndrome in females and is extremely rare in males. Most male patients with MECP2 gene mutation show MECP2 duplication syndrome. Here we report a rare case in a 10-month-old boy with a hemizygous insertion mutation in MECP2 as NM_001110792, c.799_c.800insAGGAAGC, which results in a frameshift mutation (p.R267fs*6). The patient presented with severe encephalopathy in the neonatal period, accompanied by severe development backwardness, hypotonia, and ocular and oropharyngeal dyskinesia. This is the first report of this mutation, which highlights the phenotype variability associated with MECP2 variants. This case helps to expand the clinical spectrum associated with MECP2 variants. Close attention should be paid to the growth and development of patients carrying a MECP2 variant or Xq28 duplication. Early interventions may help improve symptoms to some certain extent.


Hypomethylation of an exon I estrogen receptor CpG island in spontaneous and carcinogen-induced mammary tumorigenesis in the rat.
Loss of methylation at a CpG island in exon I of the rat ER gene was observed in 48% of the spontaneous mammary tumors in old female Wistar rats and 22% of the contralateral normal mammary tissues. The majority of the methylation losses were total. Similarly, 50% of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in young Sprague-Dawley rats exhibited a partial or total loss of methylation at this site, while all normal mammary tissues in young rats were fully methylated. Loss of ER methylation also increased with age in normal mammary tissues of tumor-free rats approaching 12.5% in middle-aged and 43% in old rats. In addition, 66% of mammary glands obtained from young rats that are subsequently at an increased risk to develop breast cancer due to manipulation of in utero dietary fat intake, exhibited methylation loss while no methylation changes were observed in rats at no increased risk for breast cancer. Therefore, the loss of ER methylation is more extensive in mammary glands of rats at high than low breast cancer risk, in old than young, and in mammary tumors than in normal tissues. The data suggest that hypomethylation of a growth-associated ER gene may be a common event in mammary tumorigenesis in the rat and may be of predictive value as a marker of increased breast cancer risk in aged individuals.


Direct detection of sulfide ions [S2-] in aqueous media based on fluorescence quenching of functionalized CdS QDs at trace levels: analytical applications to environmental analysis.
A novel, simple but highly selective fluorescent probe is developed for the direct detection of sulfide ions [S(2-)] based on the fluorescence quenching of the functionalized CdS QDs in aqueous solution at trace levels and successfully applied for quantitation of S(2-) from water samples in a complex matrix exclusive of pretreatment by standard addition method.


Clinicopathologic characteristics and prognosis for young gastric adenocarcinoma patients after curative resection.
Conflicting results from previous studies on gastric adenocarcinoma (GC) in young patients have led to controversy surrounding the prognosis for young GC patients. The authors studied 6954 patients with GC who received curative resections. They were classified into three groups: those aged 40 years or less ("young," 12.7%); those aged 41-65 years ("middle-aged," 66.7%); and those aged more than 65 years ("elderly," 20.6%). Clinicopathologic characteristics and overall survival rates were analyzed. Young patients were predominately female and had tumors that were histologically undifferentiated. However, in regard to T4 invasion, N3 lymph node metastasis, and TNM stage IV, the characteristics of the tumors of young patients were similar to those of middle-aged and elderly patients. Overall survival rate was significantly better in young patients than middle-aged patients (P = .018) and elderly patients (P < .001). Stratified by TNM stage, young patients showed better overall survival at stage I than middle-aged patients, and at stages I, II, and IIIa than elderly patients. Multivariate analysis indicated that age was an independent prognostic factor (as well as gender, operation type, depth of invasion, and lymph node status). The predominance of female cases and tumors that were histologically undifferentiated were distinctive characteristics in young patients. Young patients could gain a survival benefit after curative resection with stage I disease.


Desensitization protocols for prospective pediatric renal transplant recipients.
Desensitization protocols should be considered for children with positive crossmatches awaiting renal transplantation. Children are sensitized usually due to previous renal (and/or other solid-organ) transplants but can be from administration of blood and/or platelet transfusions, infections, and immunizations (as sensitization from pregnancy is a rare occurrence in pediatric patients). However, the definition of HLA-incompatible (HLAi) renal transplantation in the literature varies and is best considered only when there is a positive cross-match (positive baseline flow cytometric cross-match or positive complement-dependent cytotoxic cross-match). Renal transplantation where the recipient has donor-specific antibodies (DSA) but a negative cross-match should not fall into this category, although they are higher risk.


Isolation and analysis of group 2 innate lymphoid cells in mice.
Recent studies have identified distinct subsets of innate lymphocytes, collectively called innate lymphoid cells (ILCs), which lack antigen receptor expression but produce various effector cytokines. Group 2 ILCs (ILC2s) respond to epithelial cell-derived cytokines such as interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), produce large amounts of type 2 cytokines, and have a key role in anti-helminth innate immunity and in the pathophysiology of allergic inflammation. The reported phenotypic characteristics of mouse ILC2s vary, depending on the tissue source and preparation method. This protocol describes improved methods for tissue-specific isolation and analysis of mouse ILC2s of high purity and yield from fat tissue, lung, bronchoalveolar lavage fluid (BALF) and small intestine. These improved methods are the result of our thorough investigation of enzymes used for tissue digestion, methods for the elimination of undesired cells, and a combination of antibodies for the detection and isolation of ILC2s. In addition, this new protocol now enables the isolation of ILC2s of high yield, even from inflamed tissues. Depending on the tissue being analyzed, it takes ∼2-4 h for isolation and flow cytometric analysis of ILC2s from the various tissues of a single mouse and ∼4-8 h to sort purified ILC2s from pooled tissues of multiple mice.


AIEgen-Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy.
The engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF are reported, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuroinflammation peri-SG microenvironment, which is favorable for inhibiting ischemia-induced VAs. In vivo studies have confirmed that BTDBETA-COF-mediated LHT enhances thermogenesis and browning-related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri-SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA-COF-mediated LHT in ameliorating the neuroinflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. The work on AIE COF-based hyperthermia agent for VAs inhibition provides a new avenue for mitigating cardiac sympathetic nerve hyperactivity.


Clinicopathological features of pure mica pneumoconiosis associated with Sjögren syndrome.
There are few reports on the clinical, radiologic, and pathologic features of pure mica pneumoconiosis. A case of definite pure mica pneumoconiosis in a rubber factory worker is reported with the clinicopathological findings. Chest HRCT demonstrated subpleural and peribronchovascular interstitial thickening. The characteristic histologic features were pulmonary fibrosis accompanied by prominent histiocytic granulomas containing giant cells. Pure mica pneumoconiosis can be identified by specific radiologic and pathologic findings.


Lysine methyltransferase Smyd2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function.
Protein lysine methylation controls gene expression and repair of deoxyribonucleic acid in the nucleus but also occurs in the cytoplasm, where the role of this posttranslational modification is less understood. Members of the Smyd protein family of lysine methyltransferases are particularly abundant in the cytoplasm, with Smyd1 and Smyd2 being most highly expressed in the heart and in skeletal muscles. Smyd1 is a crucial myogenic regulator with histone methyltransferase activity but also associates with myosin, which promotes sarcomere assembly. Smyd2 methylates histones and non-histone proteins, such as the tumor suppressors, p53 and retinoblastoma protein, RB. Smyd2 has an intriguing function in the cytoplasm of skeletal myocytes, where it methylates the chaperone Hsp90, thus promoting the interaction of a Smyd2-methyl-Hsp90 complex with the N2A-domain of titin. This complex protects the sarcomeric I-band region and myocyte organization. We briefly summarize some novel functions of Smyd family members, with a focus on Smyd2, and highlight their role in striated muscles and cytoplasmic actions. We then provide experimental evidence that Smyd2 is also important for cardiac function. In the cytoplasm of cardiomyocytes, Smyd2 was found to associate with the sarcomeric I-band region at the titin N2A-domain. Binding to N2A occurred in vitro and in yeast via N-terminal and extreme C-terminal regions of Smyd2. Smyd2-knockdown in zebrafish using an antisense oligonucleotide morpholino approach strongly impaired cardiac performance. We conclude that Smyd2 and presumably several other Smyd family members are lysine methyltransferases which have, next to their nuclear activity, specific regulatory functions in the cytoplasm of heart and skeletal muscle cells. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.


Protein supplementation increases adaptations to endurance training: A systematic review and meta-analysis.
Trials that assessed the impact of protein supplementation on endurance training adaptations have reported conflicting findings. To determine the impact of protein supplementation during chronic endurance training on aerobic capacity, body composition and exercise performance in healthy and clinical populations. A systematic database search was conducted for randomised controlled trials addressing the effects of protein supplementation during endurance training on aerobic capacity, body composition and exercise performance in PubMed, Embase, Web of Science, and CINAHL. Meta-analyses were performed to outline the overall effects of protein supplementation with all studies containing endurance training components. The effects of endurance training and add-on effects of protein supplementation were evaluated by the meta-analyses with endurance training-focused studies. Nineteen studies and 1162 participants contributed to the analyses. Compared with the control group, the protein supplementation group demonstrated greater improvements in aerobic capacity measured by mixed peak oxygen uptake (V̇O2peak) and peak workload power (Wpeak) (standardised mean difference [SMD] = 0.36, 95% confidence interval [CI]: 0.05 to 0.67), and V̇O2peak (mean difference [MD] = 0.89 mL‧kg-1‧min-1, 95% CI: 0.07 to 1.70); had a greater lean mass gain (MD = 0.32 kg, 95% CI: 0.07 to 0.58); and had a greater improvement in time trial performance (MD = -29.1s, 95% CI:-55.3 to -3.0). Secondary analyses showed that, in addition to the substantial improvement in V̇O2peak (MD = 3.67 mL‧kg-1‧min-1, 95% CI: 2.32 to 5.03) attributed to endurance training, protein supplementation provided an additional 26.4% gain in V̇O2peak (MD = 0.97 mL‧kg-1‧min-1, 95% CI: -0.03 to 1.97). Protein supplementation further increased aerobic capacity, stimulated lean mass gain, and improved time trial performance during chronic endurance training in healthy and clinical populations. PROSPERO REGISTRATION NUMBER: (CRD42020155239).


Characterization of sensory neurons in the dorsal root ganglia of Bax-deficient mice.
During development, the rescue of spinal motoneurons as well as sensory neurons in the dorsal root ganglion (DRG) from programmed cell death (PCD) depends on the integrity of peripheral target innervation. Following deletion of the pro-apoptotic gene Bax, both motoneurons and DRG neurons are rescued from PCD. In the present paper, we asked whether different cell types in the DRG exhibit distinct responses to Bax deletion. In 1-month-old Bax-deficient (Bax-/-) mice, distinct subsets of DRG neurons that were immunopositive for TrkA, CGRP, TRPV1 or TrkC, were all increased in number and exhibited cell atrophy compared to wild type DRG neurons. In addition there was hyperinnervation of the epidermis by CGRP immunopositive processes and a correlated functional hypersensitivity of mechanical nociception in Bax-/- mice. By contrast, the functional properties of populations of rescued thermoreceptor and mechanoreceptor DRG neurons were unchanged. These data indicate that although Bax deletion rescues all of the DRG cell types examined here from PCD, the functional consequences of having excess cells differ between sensory phenotypes.


Opportunistic predator prefers habitat complexity that exposes prey while reducing cannibalism and intraguild encounters.
Structural features of habitat are known to affect the density of predators and prey, and it is generally accepted that complexity provides some protection from the environment and predators but may also reduce foraging success. A next step in understanding these interactions is to decouple the impacts of both spatial and trophic ingredients of complexity to explicitly explore the trade-offs between the habitat, its effects on foraging success, and the competition that ensues as predator densities increase. We quantified the accumulation of spiders and their prey in habitat islands with different habitat complexities created in the field using natural plants, plant debris and plastic plant mimics. Spiders were observed at higher densities in the complex habitat structure composed of both live plants and thatch. However, the numerically dominant predator in the system, the wolf spider Pardosa milvina, was observed at high densities in habitat islands containing plastic mimics of plants and thatch. In a laboratory experiment, we examined the interactive effects of conspecific density and habitat on the prey capture of P. milvina. Thatch, with or without vertical plant structure, reduced prey capture, but the plastic fiber did not. Pairwise interactions among spiders reduced prey capture, but this effect was moderated by thatch. Taken together, these experiments highlight the flexibility of one important predator in the food web, where multiple environmental cues intersect to explain the role of habitat complexity in determining generalist predator accumulation.


Direct evidence of recombination in the recA gene of Aeromonas bestiarum.
Two hundred and twenty-one strains representative of all Aeromonas species were characterized using the recA gene sequence, assessing its potential as a molecular marker for the genus Aeromonas. The inter-species distance values obtained demonstrated that recA has a high discriminatory power. Phylogenetic analysis, based on full-length gene nucleotide sequences, revealed a robust topology with clearly separated clusters for each species. The maximum likelihood tree showed the Aeromonas bestiarum strains in a well-defined cluster, containing a subset of four strains of different geographical origins in a deep internal branch. Data analysis provided strong evidence of recombination at the end of the recA sequences in these four strains. Intergenomic recombination corresponding to partial regions of the two adjacent genes recA and recX (248 bp) was identified between A. bestiarum (major parent) and Aeromonas eucrenophila (minor parent). The low number of recombinant strains detected (1.8%) suggests that horizontal flow between recA sequences is relatively uncommon in this genus. Moreover, only a few nucleotide differences were detected among these fragments, indicating that recombination has occurred recently. Finally, we also determined if the recombinant fragment could have influenced the structure and basic functions of the RecA protein, comparing models reconstructed from the translated amino acid sequences of our A. bestiarum strains with known Escherichia coli RecA structures.


Chromosomal distribution of genes coding for fast twitch skeletal muscle myosin light chains.
The mouse fast twitch skeletal muscle myosin light chains are encoded by a multigene family which comprises the gene coding for the myosin light chain 2 (Myl2f), and the gene coding for both myosin light chains 1 and 3 (Myl1f/Myl3f). In addition, a Myl1f/Myl3f-related pseudogene is present in the domestic mouse Mus musculus. The members of this gene family were assigned to chromosomes by molecular hybridization, using DNA extracted from a panel of cloned mouse-Chinese hamster somatic hybrid cells and specific DNA probes. The genes coding for the light chains of the myosin molecule are dispersed on several chromosomes, while genes coding for the heavy chain of myosin are located on a single, different chromosome.


Effect of yellow filter on visual acuity and contrast sensitivity under glare condition among different age groups.
The aim of this study is to investigate the effect of yellow filter on visual acuity and contrast sensitivity under glare condition for various ages. A total of 60 subjects, aged 5-60 years, with no ocular pathology and no previous surgery were assessed in this cross-sectional study. We divided subjects into six subgroups according to their ages, and the number of subjects in each group was 10: group 1, aged 5-10 years; group 2, aged 11-20 years; group 3, aged 21-30 years; group 4, aged 31-40 years; group 5, aged 41-50 years; and group 6, aged 51-60 years. Snellen visual acuity and Pelli Robson contrast sensitivity with and without glare and with the use of yellow filter under glare condition were determined. Data analysis was carried out using SPSS, version 20. Our results showed a significant reduction in contrast sensitivity under glare condition in all age groups (p = 0.000), which improved significantly with the use of yellow filter (p = 0.000). Although when data in different age groups were analyzed separately, this improvement was only significant in older subjects, aged 51-60 years (p = 0.007). No significant difference was found between Snellen visual acuity with and without glare (p = 0.083), and also we found no yellow filter effect on visual acuity under glare condition. We conclude that yellow filter, which absorbs short wavelength, may provide significant contrast sensitivity benefits for individuals and influences older subjects more than younger ones.


Functional imaging of the visual pathways.
Functional neuroimaging has provided a new view of activity in human visual cortex. There have been a series of interesting developments in understanding the relationship between the functional signals, particularly functional MRI, and basic measurements of action potentials and local field potentials. The new human neuro-imaging measurements have clarified some of the similarities and differences between the general organization of visual areas in human and macaque visual cortex, and there have been some interesting new results concerning cortical visual plasticity and dysfunction. The new fMRI focus on measurements of the human brain will drive new relationships between neurology and visual neuroscience that should help us learn much more about the neural basis of perception.


[Congenital anomalies of the spine].
Congenital anomalies of the spine usually originate in (toxic) disturbances during pregnancy. There are occasional hereditary types. These are characterized by the presence of multiple anomalies. Congenital scolioses are often associated with other anomalies like spinal dysraphy (20-30%) and fusion of the ribs. Furthermore heart defects, Sprengel's deformity, cleft palates, hemimelias, clubfeet or congenital vertical talus are frequently associated with congenital scoliosis. We classify in failures of formation, segmentation and combined types. The type of malformation determines the prognosis. One hemivertebra is associated with a risk of progression of 0-2 degrees/year, 2 ipsilateral hemivertebra with 2-3 degrees/year, a unilateral unsegmented bar with 5 degrees/year and a combination of a unilateral unsegmented bar with a contralateral hemivertebra with approximately 10 degrees/year. Conservative treatment is usually ineffective. The indication for operative treatment should be made before the deformity becomes unacceptable, as a correction is difficult and dangerous. The following operations can be carried out: Anterior and/or posterior fusion with or without instrumentation, epiphyseodesis, (hemi)vertebrectomies (with anterior and/or posterior approach), distraction with a halo, osteotomies, separation of the fused ribs and gradual distraction (Campbell's expansion thoracoplasty). The operations carry significant risks and the indication to the various treatment modalities is difficult. Operations should be made under monitoring of sensory and motor evoked potentials. From 498 patients with congenital anomalies of the spine in our observation we have operated on 143. Hemivertebrectomies were the most frequent interventions (56).


Heterologous supersensitization between serotonin2 and alpha 2-adrenergic receptor-mediated intracellular calcium mobilization in human platelets.
Recent reports suggest that serotonin (5-HT)2 receptor-mediated second messenger systems are enhanced in platelets of affective disorders. To make the mechanism of the enhanced response clear, we investigated 5-HT2 and alpha (alpha) 2-adrenergic receptor-induced intracellular calcium (Ca2+) mobilization in platelets of healthy volunteers, using fura-2. 5-HT2 and alpha 2-adrenergic receptor-mediated Ca2+ mobilization was enhanced by prior exposure to the other type of agonist, so called "heterologous supersensitization." The supersensitization was due to the enhancement of maximal response without change in agonist affinity. Chelating extracellular Ca2+ did not diminish the supersensitization. This enhancement of Ca2+ mobilization was not inhibited by H-7, an inhibitor of protein kinase C. However, this supersensitization was inhibited by pretreatment with sodium fluoride which directly activates guanine nucleotide binding regulatory proteins (G proteins). These results suggest that the supersensitization was caused from intracellular Ca2+ storage sites through a G protein-coupled pathway.


Completely resected recurrent soft tissue sarcoma: primary anatomic site governs outcomes.
We define the natural history and influence of primary anatomic site for completely resected locally recurrent soft tissue sarcoma (STS) without distant metastasis. We selected 290 patients having at least one local recurrence (LR) after complete resection of primary STS (all sites) between 1982 and 1999. Of these, 239 patients had complete resection of their first LR: 161 extremity-trunk and 78 retroperitoneal-head and neck-visceral-thoracic sarcomas. Study end points included second local recurrence-free survival, distant recurrence-free survival, and disease-specific survival, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and Cox's proportional hazards model for extremity-trunk and retroperitoneal (RP; n 39) tumor sites only. Median followup was 82 months. Complete gross resection rates declined with each subsequent recurrence. Primary tumor site (extremity-trunk: relative risk ERR] 0.74, confidence interval [CI] 0.57 to 0.96, p = 0.03) and microscopic resection margin (negative: RR 0.80, CI 0.62 to 0.99, p 0.04) independently predicted subsequent local control. Extremity-trunk sire and high tumor grade were significant independent predictors of distant disease relapse after complete resection of LR. Site also had a notable influence on disease-specific survival: RP recurrence was associated with 1.4 times increased risk of tumor-related mortality (p = 0.02; 5-year disease-specific survival: extremity-trunk 70% versus RP 57%). High tumor grade was the most marked predictor of tumor-related mortality (RR 1.66, CI 1.28 to 2.18, p<0.001. Nine percent of extremity-trunk and 77% of RP STS-related deaths were caused by advanced LR without synchronous metastasis. Site governs local control, distant recurrence-free and disease-specific survival for completely resected locally recurrent sarcoma without metastasis. Distant disease relapse determines outcomes for recurrent extremity-trunk STS, and local recurrence is the determinant of tumor-related death in the RP.