Differential regulation of multiple c-erbA expression by thyrotropin, insulin and insulin-like growth factor I in rat thyroid FRTL-5 cells.
Regulation of multiple c-erbA gene expression was studied in rat thyroid FRTL-5 cells. Two species of erbA alpha (alpha 1 and alpha 2) mRNA and one species of erbA beta (beta 1) mRNA were identified by Northern blot analysis. Withdrawal of thyrotropin (TSH), insulin and serum from the complete medium resulted in an increase in alpha 1 and alpha 2 erbA mRNA levels without altering the level of erbA beta 1 mRNA. Readdition of TSH, N6,2'-O-dibutyryl cAMP or forskolin caused a transient reduction of alpha 1 and alpha 2 mRNA levels (75-90%) at 3-12 h. The alpha 1 and alpha 2 mRNA levels were restored at 24 h. The TSH action was dose-dependent showing the half-maximal effect at around 10(-9) M. Readdition of TSH did not show any effect on beta 1 mRNA level. The action of TSH was not dependent on ongoing protein synthesis but required ongoing transcription. Inhibitors of thyroid hormone biosynthesis, propylthiouracil and methylmercaptoimidazole, did not show any effect on TSH action. Readdition of insulin or insulin-like growth factor I (IGF-I) caused a dose-dependent reduction of alpha 1 and alpha 2 mRNA levels without any effect on beta 1 mRNA level. Their action was slower than TSH and persistent. The actions of insulin and IGF-I were dependent on both ongoing translation and transcription. These results indicate that TSH and insulin/IGF-I reduce levels of c-erbA alpha 1 and alpha 2 mRNA possibly by two distinct mechanisms without altering c-erbA beta 1 mRNA level in FRTL-5 cells.


Cryo-shocked cancer cell microgels for tumor postoperative combination immunotherapy and tissue regeneration.
Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, immunoadjuvant, and immune checkpoint inhibitor is presented by microfluidic electrospray technology and liquid nitrogen treatment. Owing to the encapsulation of cryo-shocked cancer cells and immunoadjuvant, the microgels can recruit dendritic cells and activate them in situ, and evoke a robust immune response. Moreover, with the combination of the immune checkpoint inhibitor, the antitumor immune response is further enhanced by inhibiting the interaction of PD1 and PDL1. With this, the excellent anti-recurrence and anti-metastasis efficacy of the microgels are demonstrated in an orthotopic breast cancer mouse model. Besides, because of the excellent biocompatibility and appropriate degradation performance, the microgels can provide support for normal cell adhesion and growth, which is beneficial to tissue reconstruction. These properties indicate the great value of the cryo-shocked cancer cell microgels for efficient tumor postoperative combination immunotherapy and tissue regeneration.


Antigenic analysis of intraepidemic variants of influenza A (H3N2) viruses by hyperimmune rat antisera.
Hyperimmune rat antisera prepared against 5 recent antigenic variants of influenza A (H3N2) viruses were studied for haemagglutination inhibiting (HI) antibodies to the homologous and the heterologous viruses. The ratios of homologous to heterologous reactions varied from one animal to another in immunizations with each of the immunogens. Some antisera exhibited a ratio high enough to allow differentiation of the epidemic variants and demonstration of an intraepidemic heterogeneity of field strains isolated during the outbreak of 1985/86. The variation of cross-reactions of polyclonal antisera may reflect differences in the range of specificities of anti-haemagglutinin antibodies produced by individual animals. The significance of this finding in the classification of influenza A (H3N2) viruses is discussed. Lack of nonspecific inhibitors interfering with the HI test is an additional advantage of hyperimmune rat antisera in typing influenza A and B virus isolates.


Assessment of Parasite Liver-Stage Burden in Human-Liver Chimeric Mice.
Humanized mice with a chimeric liver are a promising tool to evaluate the "in vivo" efficacy of novel compounds or vaccine-induced antibodies directed against the pre-erythrocytic stages of Plasmodium falciparum. The absence of human red blood cells in these humanized mice precludes the transition from liver to blood stage. The qPCR-based method described below allows for a sensitive and reliable quantification of parasite DNA in the chimeric liver following a challenge via infected mosquito bite or intravenous injection of sporozoites. With this method approximately 25 % of the total chimeric liver is examined and a single infected hepatocyte can be detected in the analyzed tissue. The use of appropriate species-specific probes can also allow for the detection of other Plasmodium species in vivo.


Interaction of lactate dehydrogenase with skeletal muscle troponin.
Rabbit muscle troponin complex covalently bound to CNBr-activated Sepharose 4B was shown to interact with soluble lactate dehydrogenase with a stoichiometry of 2 mol lactate dehydrogenase/mol of troponin. The presence of Ca2+ influenced the strength of association (the KD values of 0.73 and 2.3 microM were determined in the presence of 200 microM EGTA or 100 microM Ca2+, respectively). In the absence of Ca2+, the affinity of lactate dehydrogenase to troponin was strongly pH-dependent, reaching a maximum in the region of pH 6.0-7.0. No change of catalytic activity was observed as a result of interaction between lactate dehydrogenase and troponin, the enzyme appeared capable of functioning in the bound form.


Spatio-temporal analysis of differences in campylobacteriosis incidence between urban and rural areas in the Southern District Health Board, New Zealand.
The objective of this paper is to investigate differences in campylobacteriosis incidence between urban and rural areas in the Southern District Health Board of New Zealand between 2000 and 2015. The data were analysed using a Bayesian change-point model to evaluate how campylobacteriosis incidence changed over time and to see whether the dynamics differed between rural and urban areas. A conditional auto regressive error term was introduced to account for any spatial effects. The results of our analysis showed that campylobacteriosis incidence increased between 2000 and 2005, decreased between 2006 and 2008 then stabilised from 2009 onward. In addition we found that the changes in incidence were greater in urban areas than in rural ones.


Proposal of a new classification: "sealed type" postinfarction left ventricular free wall rupture.
Postinfarction left ventricular free wall rupture (FWR) has been classified into blow-out type and oozing type. However, considering past papers, oozing type included the cases in which the bleeding had spontaneously stopped or sealed, and the distinction between blow-out type and oozing type was not always clear. We classified FWR into the BO type (combination of blow-out type and oozing type) with continuous bleeding and sealed type and clarified the pathophysiology of the sealed type. Thirty-five patients who underwent surgical treatment for FWR during the past 21 years were retrospectively evaluated. Twenty-one patients (60%) were sealed. Comparing the sealed type with the BO type, the incidence of sudden collapse with acute onset was significantly lower (sealed type; 62%, BO type; 100%, P = 0.0118), and there were more cases of transport from outside the hospital (76%, 43%, P = 0.0453). Significantly few cases had electro-mechanical dissociation immediately before surgery (10%, 71%, P = 0.0001). In the sealed type, median sternotomy was performed in 9 patients (43%), and subxiphoid drainage was performed in 12 (57%). Fifteen patients (71%) were supported by IABP postoperatively, and re-rupture occurred in 3 patients without IABP. Long-term outcomes were significantly better in the sealed type than in the BO type. Sixty percent of postinfarction ventricular free wall rupture was the sealed type. Median sternotomy and sutureless repair with postoperative IABP support were reliable treatments. Subxiphoid drainage and strict blood pressure control with IABP may be acceptable surgical strategies in elderly, frail patients.


Extraordinary Claims in the Literature on High-Intensity Interval Training (HIIT): I. Bonafide Scientific Revolution or a Looming Crisis of Replication and Credibility?
The literature on high-intensity interval training (HIIT) contains claims that, if true, could revolutionize the science and practice of exercise. This critical analysis examines two varieties of claims: (i) HIIT is effective in improving various indices of fitness and health, and (ii) HIIT is as effective as more time-consuming moderate-intensity continuous exercise. Using data from two recent systematic reviews as working examples, we show that studies in both categories exhibit considerable weaknesses when judged through the prism of fundamental statistical principles. Predominantly, small-to-medium effects are investigated in severely underpowered studies, thus greatly increasing the risk of both type I and type II errors of statistical inference. Studies in the first category combine the volatility of estimates associated with small samples with numerous dependent variables analyzed without consideration of the inflation of the type I error rate. Studies in the second category inappropriately use the p > 0.05 criterion from small studies to support claims of 'similar' or 'comparable' effects. It is concluded that the situation in the HIIT literature is reminiscent of the research climate that led to the replication crisis in psychology. As in psychology, this could be an opportunity to reform statistical practices in exercise science.


The relationship between sleep quality and emotional modulation of spinal, supraspinal, and perceptual measures of pain.
Poor sleep quality is often comorbid with chronic pain. Research has also shown that poor and disrupted sleep may increase risk for chronic pain by promoting pronociceptive processes. This could occur through disrupted emotional modulation of pain since poor sleep can impact emotional experience and emotional experience modulates pain and nociception. To assess the pain system, nociceptive flexion reflexes (spinal level), pain-evoked potentials (supraspinal level), and perceived pain were recorded during an emotional picture-viewing task in which 37 healthy individuals received painful electric stimulations. The Pittsburgh Sleep Quality Index assessed sleep quality. Individuals with poor sleep quality were unable to inhibit signals at the spinal level in response to positive pictures, whereas emotional modulation of supraspinal nociception and pain perception remained unaffected by sleep quality. This suggests poor sleep quality may promote pronociception by impairing descending, emotional modulation of spinal nociception.


Investigating non-point pollution mitigation strategies in response to changing environments: A cross-regional study in China and Germany.
Climate change and urbanization have altered regional hydro-environments. Yet, the impact of future changes on the pollution risk and associated mitigation strategies requires further exploration. This study proposed a hydraulic and water-quality modeling framework, to investigate the spatiotemporal characteristics of pollution risk mitigation by low impact development (LID) strategies under future Representative Concentration Pathways (RCP) and Shared Socioeconomic Pathways (SSP) scenarios. Results demonstrated that the LID strategies exhibited an effective performance of pollutant removal in the current hydro-environment, with the removal rates ranging from 33% to 56%. In future climate and urbanization scenarios, the LID performance declined and turned to be uncertain as the greenhouse gas (GHG) emissions increased, with the removal rates ranging from 12% to 59%. Scenario analysis suggested that the LID performance was enhanced by a maximum of 73% through the diversified implementation of LID practices, and the performance uncertainty was reduced by a maximum of 67% through the increased LID deployment. In addition, comparative analysis revealed that the LID strategies in a well-developed region (Dresden, Germany) were more resilient in response to changing environments, while the LID strategy in a high-growth region (Chaohu, China) exhibited a better pollutant removal performance under low-GHG scenarios. The methods and findings in this study could provide additional insights into sustainable water quality management in response to climate change and urbanization.


[Infantile arterial hypertension: A diagnostic challenge in paediatrics].
Arterial Hypertension prevalence (HTN) has significantly increased in paediatric patients, mainly in older children and teenagers. In these subjects the most common type is essential or primary HTN. However, in infants HTN prevalence is significantly lower and is almost always due to secondary causes, which can be potentially severe. Hence the importance of its detection, in order to establish an etiological diagnosis and provide an appropriate treatment, which usually requires a specialist physician. In addition to the technical difficulties of blood pressure measurement in infants, the lack of recommendations to perform a systematic screening in this age range and the absence of well-established normal values turns infancy-onset HTN into a diagnostic and therapeutic challenge for the physician. By means of the exposition of three infancy-onset HTN cases, the aim is to increase the paediatrician's awareness of this pathology and also to provide information about its diagnostic and therapeutic approach, dealing also with pharmacological measures of treatment.


Unconscious response inhibition differences between table tennis athletes and non-athletes.
Response inhibition is associated with successful sporting performance. However, research on response inhibition in athletes from open-skill sports has mainly focused on a consciously triggered variety; little is known about open-skill athletes' response inhibition elicited by unconscious stimuli. Here, we explored unconscious response inhibition differences between table tennis athletes (n = 20) and non-athletes (n = 19) using the masked go/no-go task and event-related potentials technique (ERPs). At the behavioral level, table tennis athletes displayed shorter go-response times (RTs) than non-athletes in the conscious condition. Furthermore, table tennis athletes exhibited longer response time-slowing (RT-slowing) than non-athletes in the unconscious condition. At the neural level, table tennis athletes displayed shorter event-related potential N2 component latencies than non-athletes for all conditions. More importantly, athletes displayed larger no-go event-related potential P3 component amplitudes than non-athletes at both the conscious and unconscious levels. The present study results suggested that table tennis athletes have superior conscious and unconscious response inhibition compared to non-athletes.


Facile one-pot green synthesis of Ag-ZnO Nanocomposites using potato peeland their Ag concentration dependent photocatalytic properties.
Herein, a facile green synthesis route was reported for the synthesis of Ag-ZnO nanocomposites using potato residue by simple and cost effective combustion route and investigated the photocatalytic degradation of methylene blue (MB) dye. In the preparation potato extract functioned as a biogenic reducing as well as stabilizing agent for the reduction of Ag + , thus eliminating the need for conventional reducing/stabilizing agents. Ag-ZnO nanocomposites with different Ag mass fractions ranging from 2 to 10% were characterized by using XRD, FT-IR, XPS, SEM, TEM, and UV-Vis spectroscopy. XRD analysis revealed that the as prepared Ag-ZnO nanocomposites possessed high crystallinity with hexagonal wurtzite structure. TEM and SEM images showed that the Ag-ZnO nanocomposites in size ranging from 15 to 25 nm have been obtained, and the particle size was found to increase with the increase in percentage of Ag. FTIR results confirmed the characteristics band of ZnO along with the Ag bands. XPS analysis revealed a pair of doublet with peaks corresponding to Ag and a singlet with peaks corresponding to ZnO. With the increase of concentration of Ag in ZnO, the intensity of NBE emission in the PL spectra was observed to be decrease, resulted to the high photocatalytic activity. Photocatalytic properties of Ag-ZnO nanocomposites evaluated against the MB dye under visible-light irradiation showed superior photodegradation of ~ 96% within 80 min for 2% Ag-ZnO nanocomposites. The apparent reaction rate constant for 2% Ag-ZnO nanocomposites was higher than that of other nanocomposites, which proved to be the best photocatalyst for the maximum degradation of MB. Furthermore, various functional parameters such as dosing, reaction medium, concentration variation were performed on it for better understanding. The enhancement in photocatalytic degradation might be due to the presence of Ag nanoparticles on the surface of ZnO by minimizing the recombination of photo induced charge carriers in the nanocomposites.


Flea species from dogs and cats in north-central Florida.
Fleas were identified after removal from 100 dogs and 60 cats following routine presentation at a Veterinary Hospital in Gainesville, FL. Ctenocephalides felis comprised 92.4% and 99.8% of the fleas taken from dogs and cats respectively. Pulex irritans accounted for 7.5% of the fleas found on dogs and for 0.2% of those found on cats. Echidnophagia gallinacia was found on one dog. Of the 100 dogs, 80 were infested with C. felis alone, one with P. irritans alone, and 18 carried a mixed infestation of the two. One animal was infested with all three species. Ctenocephalides canis was not identified amongst the total of 1887 fleas examined.


The Alvarado Score Is the Most Impactful Diagnostic Tool for Appendicitis: A Bibliometric Analysis.
The objective of this bibliometric analysis was to investigate the citation pattern of studies that have developed a diagnostic tool to diagnose appendicitis. We investigated characteristics of citations, publication frequency, evolution of citations, and fluctuation of previously highly cited studies. We analyzed which studies had been cited in the method section and identified impactful studies in this research field by a network visualization. We analyzed the differences in citations between diagnostic tools requiring a doctor to be present against the diagnostic tools not requiring doctors to be present, English language studies against non-English studies, and identified diagnostic tools targeting children. There was an upward trend in publications in this research field, and between 1999-2021 the Alvarado score has been cited the most. In general, there was a high fluctuation, and 40 studies had been cited in the methods sections. There were significant differences in studies regarding diagnostic tools written in English compared to non-English studies, with more citations in the English-language studies. Furthermore, 22 studies had children as the target population. The Alvarado score was the highest cited study since 1999, with 1086 citations, making it the most impactful study in this research field of diagnostic tools to diagnose appendicitis. Due to the diversity of target populations and settings for which diagnostic tools are developed, there is a need to expand research on diagnostic tools for appendicitis.


Use of cauliflower mosaic virus DNA markers to assess the potential for pathogen transmission from physicians' white coats.
In an observational study, the sleeves and pockets of physicians' white coats often directly or indirectly contacted patients and environmental surfaces. DNA markers on the sleeves or pockets were frequently transferred to surfaces and patients. These findings suggest that contaminated white coats have the potential to contribute to pathogen transmission.


Early Post-stroke Depressive Symptoms are Associated with Low Peripheral Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and Glial Cell-derived Neurotrophic Factor (GDNF).
Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management. The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms. We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers. In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels. This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke.


Reminiscence Therapy as a Potential Method to Improve Psychological Health and Quality of Life in Elderly Hepatocellular Carcinoma Patients: A Randomized, Controlled Trial.
Reminiscence therapy mitigates psychological issues and improves the quality of life of cancer survivors. However, its role in elderly patients with hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to detect the effect of reminiscence therapy on anxiety, depression, and the quality of life of elderly patients with HCC. In total, 106 elderly patients with HCC after resection were randomized in a 1:1 ratio to the reminiscence therapy group (N = 54) and control care group (N = 52) and then received intervention for 12 months. Anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale (HADS) at baseline [Month (M) 0], 3 months (M3), 6 months (M6), 9 months (M9), and 12 months (M12). Meanwhile, quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life Questionnaire-Core 30 (QLQ-C30) at M0, M6, and M12. The HADS for anxiety score at M9 (6.8 ± 2.3 vs. 7.8 ± 2.4, P = 0.039) and M12 (6.6 ± 2.4 vs. 7.8 ± 2.6, P = 0.013) and the anxiety proportion at M12 (27.8% vs. 46.2%, P = 0.050) were reduced in the reminiscence therapy group compared with those in the control care group. Moreover, the HADS for depression score declined at M9 (6.6 ± 2.0 vs. 7.5 ± 2.2, P = 0.025) and M12 (6.3 ± 2.3 vs. 7.7 ± 2.6, P = 0.005), but the proportion of those with depression was not different at each visit (P > 0.05) in the reminiscence therapy group compared with that of the control care group. In addition, the QLQ-C30 global health status score increased at M6 (71.3 ± 12.8 vs. 66.3 ± 12.9, P = 0.048) and M12 (74.5 ± 12.9 vs. 68.2 ± 13.3, P = 0.014) in the reminiscence therapy group compared to that in the control care group. Reminiscence therapy effectively mitigates anxiety and depression and improves the quality of life of elderly patients with HCC.


SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol.
Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular-targeted drugs. Since interleukin-6 (IL-6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL-6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL-6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL-6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator-initiated clinical study using satralizumab, a recycling anti-IL6 receptor monoclonal antibody, for patients with an immune-responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti-IL6 therapy.


Clinicopathologic features, treatment, and prognosis of postirradiation osteosarcoma in patients with nasopharyngeal cancer.
Postirradiation osteosarcoma (PIOS) arising after radiation of nasopharyngeal cancer (NPC) is rare and seldom reported. In this article, we report its clinicopathologic features, outcome, and prognostic factors. Retrospective cohort study. Fifteen patients with NPC were determined to have PIOS after reviewing 426 patients with osteogenic sarcomas. Their clinical records, image and pathologic slides, and follow-up data after treatment were collected to perform analysis. The incidence rate of PIOS in NPC was approximately 0.037% (15/40,719), which occupied approximately 3.5% (15/426) among all kinds of osteogenic sarcomas. The latent time of PIOS after irradiation for NPC ranged from 4 to 27 years, with a mean of 13.3 years. The location where PIOS arose included 33.3% (5/15) from maxilla, 46.7% (7/15) from mandible, and 20% (3/15) from a mixture of nasal cavity and paranasal sinuses. Radiologically, soft tissue mass, bone destruction, and tumor new bone formation were the main characteristics. Pathologic subtypes included 53.3% (8/15) of fibroblastic osteosarcoma, 33.3% (5/15) of chondroblastic osteosarcoma, and 13.3% (2/15) of mixed type osteosarcoma. Of 15 patients with PIOS, 12 patients were treated with curative intent, and the remaining 3 patients with palliative intent. For 12 patients who had undertaken ablative surgery, 1 patient had residual tumor, and 6 patients had tumor recurrence. The survival time after treatment for all patients ranged from 7 to 41 months, with a mean of 18 months. Kaplan-Meier estimates of 1 year and 2 year survival rates were 60% and 24%, respectively. Statistical analysis showed that sex and tumor bone formation are significant prognostic factors. PIOS in NPC is a highly malignant disease with poorer prognosis than in other sites. Surgery combined with pre- and postoperative chemotherapy might be an effective way to improve survival.


Obstructive sleep apnea and hypertrophic cardiomyopathy: a common and potential harmful combination.
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is characterized by large and asymmetric septal and left ventricle hypertrophy. HCM is a cause of disability, including heart failure, atrial fibrillation, and sudden death, with an annual mortality varying from 1% to 6%. Obstructive sleep apnea (OSA) is extremely common among patients with established cardiovascular disease, including hypertension and atrial fibrillation and when present may contribute to worse cardiovascular outcome. Although patients with HCM do not necessarily have typical characteristics of patients with OSA, such as obesity and increasing age, there is recent evidence that OSA is extremely common among patients with HCM, with a prevalence ranging from 32% to 71%. The presence of OSA among patients with HCM is independently associated with worse structural and functional impairment of the heart, including atrial and aorta enlargement, worse New York Heart Association functional class, and worse quality of life. The prevalence of atria fibrillation, an independent marker of mortality among patients with HCM, is significantly higher (∼four times) in the presence of OSA. Therefore, the recognition of OSA is a new area of research that may impact the management of patients with HCM.


Incorporating charged Ag@MOFs to boost the antibacterial and filtration properties of porous electrospinning polylactide films.
Faced with the pollution caused by particulate matter (PM) in the air, the prevalence of infectious diseases, and the environmental burden by use of nondegradable polymers, the existing filter materials such as meltblown cloth of polypropylene cannot satisfactorily meet people's requirements. In this study, Ag nanoparticles were loaded onto ZIF-8 particles by impregnation reduction to prepare the positively charged Ag@ZIF-8. The porous fibrous membranes of Ag@ZIF-8 with polylactide (PLA) were manufactured by electrostatic spinning technology. Due to the inherently charged feature of Ag@ZIF-8 particles and the presence of pores on fibers, the prepared membranes showed a stable good filtration efficiency of over 97 % at different humidity (30-90%RH, relative humidity). Meanwhile, the presence of charge on Ag@ZIF-8 and the synergistic effects of Ag and ZIF-8 particles made the membranes exhibit good antibacterial effects. The width of the inhibition zone of 3 wt%Ag@ZIF-8/PLA membrane reached 1.33 mm for E. coli and 1.35 mm for S. aureus, respectively.


An acute tiny left putamenal lesion presenting with transient global amnesia.
Transient global amnesia (TGA) is one of the most striking syndromes in clinical neurology. Brain lesions producing TGA have been reported in the hippocampus, amygdala, thalamus, caudate nucleus, and neocortex. We report a 63-year-old woman presenting with TGA associated with a localized lesion in the left putamen. This case suggests a potential role of the putamen in human memory processing.


Translational Potential of High-Resistance Inspiratory Muscle Strength Training.
Age-associated cardiovascular (CV) dysfunction increases the risk for CV diseases. Aerobic exercise training can improve CV function, but only a minority of adults meet aerobic exercise guidelines. High-resistance inspiratory muscle strength training is a time-efficient lifestyle intervention that may promote adherence and improve CV function. However, further investigation is needed to translate inspiratory muscle strength training into the public health domain.


Effect of person-centred care on antipsychotic drug use in nursing homes (EPCentCare): a cluster-randomised controlled trial.
antipsychotic drugs are regularly prescribed as first-line treatment for neuropsychiatric symptoms in persons with dementia although guidelines clearly prioritise non-pharmacological interventions. we investigated a person-centred care approach, which has been successfully evaluated in nursing homes in the UK, and adapted it to German conditions. a 2-armed 12-month cluster-randomised controlled trial. nursing homes in East, North and West Germany. all prescribing physicians from both study arms received medication reviews for individual patients and were offered access to 2 h of continuing medical education. Nursing homes in the intervention group received educational interventions on person-centred care and a continuous supervision programme. Primary outcome: proportion of residents receiving at least one antipsychotic prescription after 12 months of follow-up. Secondary outcomes: quality of life, agitated behaviour, falls and fall-related medical attention, a health economics evaluation and a process evaluation. the study was conducted in 37 nursing homes with n = 1,153 residents (intervention group: n = 493; control group: n = 660). The proportion of residents with at least one antipsychotic medication changed after 12 months from 44.6% to 44.8% in the intervention group and from 39.8 to 33.3% in the control group. After 12 months, the difference in the prevalence was 11.4% between the intervention and control groups (95% confidence interval: 0.9-21.9; P = 0.033); odds ratio: 1.621 (95% confidence interval: 1.038-2.532). the implementation of a proven person-centred care approach adapted to national conditions did not reduce antipsychotic prescriptions in German nursing homes. ClinicalTrials.gov NCT02295462.


Acarbose reduces body weight irrespective of glycemic control in patients with diabetes: results of a worldwide, non-interventional, observational study data pool.
The objective of this study is to examine the effect of acarbose, an alpha-glucosidase inhibitor, on body weight in a real-life setting by pooling data from post-marketing surveillance. Data from 10 studies were pooled (n=67,682) and the effect of acarbose on body weight was analysed taking into account baseline body weight, glycemic parameters and other baseline characteristics. The mean relative reduction in body weight was 1.45 ± 3.24% at the 3-month visit (n=43,510; mean baseline 73.4 kg) and 1.40 ± 3.28% at the last visit (n=54,760; mean baseline 73.6 kg) (both p<0.0001). These reductions were dependent on baseline body weight (overweight: -1.33 ± 2.98% [n=13,498; mean baseline 71.6 kg]; obese: -1.98 ± 3.40% [n=20,216; mean baseline 81.3 kg]). When analysed by baseline glycemic parameter quartiles, the reduction was independent of fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c) and postprandial glucose excursion (PPGE). A bivariate analysis of covariance identified female sex, South East Asian and East Asian ethnicity, younger age, higher body mass index, short duration of diabetes, and no previous treatment as factors likely to impact positively on body weight reduction with acarbose. This post-hoc analysis showed that acarbose treatment reduces body weight independent of glycemic control status but dependent on baseline body weight.


Clinical and endocrinological aspects of induced parturition in multiparous sows.
Intramuscular administration of PGF2alpha or its analogue ICI 80996 at 110--112 days of gestation results in grouped parturition. The decrease of progesterone levels is interrupted by a temporary increase. During expulsion rather high values are obtained compared to the control group. Unconjugated oestrogens increase, reaching maximum values just before expulsion.


How stigma impacts on people with psychosis: The mediating effect of self-esteem and hopelessness on subjective recovery and psychotic experiences.
This study aimed to examine how stigma impacts on symptomatic and subjective recovery from psychosis, both concurrently and longitudinally. We also aimed to investigate whether self-esteem and hopelessness mediated the observed associations between stigma and outcomes. 80 service-users with psychosis completed symptom (Positive and Negative Syndrome Scale) and subjective recovery measures (Process of Recovery Questionnaire) at baseline and 6-months later, and also completed the King Stigma Scale, the Self-Esteem Rating Scale and the Beck Hopelessness Scale at baseline. In cross sectional regression and multiple mediation analyses of the baseline data, we found that stigma predicted both symptomatic and subjective recovery, and the effects of stigma on these outcomes were mediated by hopelessness and self-esteem. When the follow-up data were examined, stigma at baseline continued to predict recovery judgements and symptoms. However, self-esteem only mediated the effect of stigma on PANSS passive social withdrawal. Self-esteem and hopelessness should be considered in interventions to reduce the effects of stigma. Interventions that address the current and long-term effects of stigma may positively affect outcome for people being treated for psychosis.


A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer.
The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment. Patients received neratinib 240 mg/d continuously (n=117) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m(2) per day on days 1-14 of each 21-d cycle (n=116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS). The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P=0.067) and clinical benefit rate (44% versus 64%; P=0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P=0.002) and of grade 3/4 (28% versus 10%; P<0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity. The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer.


p38 MAPK inhibitors, IKK2 inhibitors, and TNFα inhibitors in COPD.
COPD represents a major respiratory disorder, causing significant morbidity and mortality throughout the world. While therapies exist for COPD, they are not always effective, and many patients experience exacerbations and morbidity despite current therapies. Study of the molecular mechanisms involved in the underlying physiological manifestations of COPD has yielded multiple new targets for therapeutic intervention. In this review, we discuss signaling pathways involved in COPD pathogenesis and review clinical studies of p38 MAPK inhibitors, TNFα inhibitors, and IKK2 inhibitors as potential COPD therapies.


Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study.
T helper (Th) cells regulate sepsis processes, including primary pathogen clear and secondary pathogen defence. The objectives of this study were to determine the early and dynamic alterations of Th1 and Th2 populations to community-acquired severe sepsis upon onset among previously immunocompetent patients and whether it was related to clinical outcomes. This prospective observational cohort study was conducted at a general intensive care unit (ICU) of a tertiary teaching hospital in China. Immunocompetent patients with community-acquired severe sepsis within 24 h upon onset were included as septic group. Healthy volunteers and critically ill patients without severe sepsis were recruited as controls. Whole blood was collected on D0, 3rd day (D3) and 7th day (D7) for septic group and once upon enrollment for controls. Th1 and Th2 populations were measured by flow cytometry and assessed for associations with 28-day mortality using cox proportional hazard models. Associations of dynamic alterations of Th cell subpopulations with clinical outcomes were investigated. This study demonstrated that community-acquired severe sepsis patients (n = 71) had increased Th2/Th1 and Th2 populations, compared to healthy controls (n = 7) and critically ill patients without severe sepsis (n = 7) at admission. Among the septic cohort, values of Th2/Th1 were significantly higher in non-survivors than survivors on D0 (p = 0.04), D3 (p < 0.001) and D7 (p < 0.001). Patients with persistently increasing Th2/Th1 demonstrated the highest mortality (47.1%) and incidence of ICU-acquired infections (64.7%). Th2/Th1 was markedly up-regulated with Th2 dominance upon community-acquired severe sepsis onset among previously immunocompetent patients and its persistently dynamic increase was associated with ICU-acquired infections and 28-day death. Trial registration Institutional Ethics Committee of Zhongda Hospital, 2014ZDSYLL086, registered in June 2014-prospectively registered; ClinicalTrials.gov, NCT02883218, registered on 25 Aug 2016-retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02883218?cond=NCT02883218&rank=1.


Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance.
Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase-cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects.


Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: early Chinese clinical experience.
The objective of this article is to introduce the early Chinese clinical experience of using extracorporeal focused ultrasound (US) surgery (FUS) for the treatment of solid tumors. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent FUS ablation in 10 Chinese hospitals. The tumors included primary and metastatic liver cancer, malignant bone tumors, breast cancer, soft tissue sarcomas, kidney cancer, pancreatic cancer, abdominal and pelvic malignant tumors, uterine myoma, benign breast tumors, hepatic hemangioma and other solid tumors. In this article, pathologic changes in tumors treated with FUS, real-time diagnostic imaging for targeting, monitoring and assessment of results by follow-up images are presented. Early clinical results and complications of the technique are also reported.


Multiple valve replacement: changing status.
Review of our experience with multiple valve replacement over a 6-year-period revealed a recent marked reduction in operative risk. Operative mortality for 62 patients operated on before 1974 was 34%; for 44 patients operated on since 1974, mortality was only 11%. In both groups, mortality was clearly related to the preoperative cardiac functional status. Several recent technical advances including myocardial protection by topical hypothermia, shortened perfusion time, and the intraaortic balloon pump may all have contributed to the reduced operative risk.


Adaptation mechanisms in spatial vision--I. Bleaches and backgrounds.
To examine how the mechanisms of bleaching and background adaptation affect spatial pattern vision, contrast detection thresholds were measured in the fovea for sinusoidal (increment-Gabor) targets, during long-term dark adaptation following full bleaches, and against steady adapting backgrounds of various intensities. The dark-adaptation curves were found to be invariant in shape over the range of spatial frequencies tested (1-15 c/deg); in other words, the amplitude sensitivity functions were invariant during dark adaptation. These results support the hypothesis that bleaching adaptation is local and multiplicative. On the other hand, the background-adaptation curves measured for different spatial frequencies were found to converge as background intensity increased; the amplitude sensitivity functions became flatter. These results reject the equivalent-background hypothesis.


Metabolomics and proteomics reveal the toxicological mechanisms of florfenicol stress on wheat (Triticum aestivum L.) seedlings.
Although the ecological impacts of antibiotics have received attention worldwide, research on the toxicity of florfenicol is still limited. We conducted a metabolomic and proteomic study on wheat (Triticum aestivum L.) seedlings to reveal the toxicological mechanism of florfenicol. The growth of the wheat seedlings was found to be inhibited by florfenicol. Antioxidant enzyme activities (superoxide dismutase, peroxidase and catalase), malondialdehyde content and membrane permeability increased with increasing florfenicol concentration. The contents of chlorophyll and chlorophyll synthesis precursor substances (Proto IX, Mg-proto IX and Pchlide), photosynthetic and respiration rates, and chlorophyll fluorescence parameters decreased, indicating that photosynthesis was inhibited. The ultrastructure of chloroplasts was destroyed, as evidenced by the blurred membrane surface, irregular grana arrangement, irregular thylakoid lamella structure, and increased plastoglobuli number. Proteome analysis revealed that up-regulated proteins were highly involved in protein refolding, translation, oxidation-reduction, tricarboxylic acid cycle (TCA cycle), reactive oxygen species metabolic process, cellular oxidant detoxification, and response to oxidative stress. The down-regulated proteins were mainly enriched in photosynthesis-related pathways. In the metabolome analysis, the content of most of the metabolites in wheat leaves, such as carbohydrates and amino acids increased significantly (p < 0.05). Combined pathway analysis showed that florfenicol stress stimulated the TCA cycle pathway and downregulated the photosynthesis pathway.


Tidal volume optimization and heart rate response during stabilization of very preterm infants.
To verify the added value of respiratory function monitor (RFM) to assess ventilation and the heart rate (HR) changes during stabilization of preterm infants. Preterm infants <32 weeks' gestation, bradycardic at birth and in need for positive pressure ventilation (PPV) were included. The first 15 min of stabilization was monitored with RFM. Three time points were identified according to HR values (T0 the start of mask PPV; T1 the HR rise >100 bpm; T2 the delivery of the last PPV). For each inflation, PIP, PEEP, MAP, expired tidal volume/kg (Vte/kg), and mean dynamic compliance (Cdyn) were analyzed. PIP and MAP values were significantly higher at T1 (27.09 ± 5.37 and 17.47 ± 3.85 cmH2 O) and at T2 (24.7 ± 3.86 and 15.2 ± 3.78 cmH2 O) compared to T0 (24.05 ± 2.27 and 15.85 ± 2.77 cmH2 O). PEEP at T1 was significantly higher (6.27 ± 2.17 cmH2 O) compared to T2 (5.61 ± 1.50 cmH2 O). Vte/kg showed significantly lower T0 values (3.57 ± 2.14 ml/kg) compared to T1 (6.18 ± 2.51 ml/kg) and T2 (6.89 ± 2.40 ml/kg). There was a significant effect of time on Cdyn. A clear correspondence between HR rise and adequate Vte/kg during stabilization of very preterm infants was highlighted. RFM might be useful to tailor ventilation, following real-time changes of lung compliance.


Deoxyribonucleic acid polymer nanoparticle hydrogels.
Polymer nanoparticle hydrogels made of deoxyribonucleic acid and silica have been prepared and shown to display shear thinning and self-healing properties, sustained release of cargo and enzymatic degradation.


Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: reactivities of acyclic seven-carbon trans dienophiles derived from aldopentoses.
Acyclic trans-2,3-unsaturated aldoheptonate derivatives (1-9) obtained from D-aldopentoses by Wittig chain-extension served as dienophiles for a detailed comparative study of their asymmetric Diels-Alder cycloaddition with cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and the diastereofacial selectivities in the formation of the adducts were determined by NMR spectroscopy and by chemical transformations. The quantitative distribution of adducts as a function of stereochemistry of the dienophile is discussed.


Diagnosis of resectable pancreatic carcinomas by means of ERCP and intraoperative fine-needle biopsy.
In 27 out of 30 resectable carcinomas of the pancreas or the periampullary region we succeeded in recognizing microscopically the malignant nature of the lesion before removing the neoplasm. This was possible 3 times preoperatively during ERCP by means of forceps biopsy taken from the tumorinfiltrated duodenal wall and with 24 patients intraoperatively by means of fine needle biopsy and cytological rapid diagnosis.


Neural mechanisms of acupuncture for peripheral facial nerve palsy: A protocol for systematic review and meta analysis.
Peripheral facial nerve palsy (PFNP) is a cranial neuropathy that occurs when the seventh facial nerve is damaged. PFNP seriously affects patients' quality of life, and approximately 30% of patients suffer from sequelae, such as unrecovered palsy, synkinesis, facial muscle contracture, and facial spasm. Many studies have confirmed the effectiveness of acupuncture for the treatment of PFNP. However, the specific mechanism remains unclear and needs to be further explored. Therefore, the purpose of this systematic review is to investigate the neural mechanisms underlying acupuncture treatment for PFNP using neuroimaging methods. We will search all published studies from inception to March 2023 using the following databases: MEDLINE, Cochrane Library, EMBASE, CNKI, KMBASE, KISS, ScienceON, and OASIS. All clinical studies evaluating the effectiveness of acupuncture for treating PFNP using functional neuroimaging will be selected without language restrictions. Two reviewers will independently conduct the study selection, data extraction, and risk of bias assessment, according to a predetermined protocol. The outcomes, including the types of functional neuroimaging techniques, brain function alterations, and clinical outcomes, such as the House-Brackmann scale and Sunnybrook Facial Grading System, will also be analyzed. Coordinate-based meta-analysis and subgroup analyses will be performed if possible. This study will analyze the effect of acupuncture on brain activity alterations and clinical improvement in patients with PFNP using functional neuroimaging. This study will provide a comprehensive summary and help elucidate the neural mechanisms of acupuncture treatment for PFNP. CRD42022321827.


Idiopathic lactic acidemia with developmental delay and type 1 muscle fiber atrophy: report of two patients.
Two infants with generalized muscle hypotonia with mild muscle weakness and markedly delayed developmental milestones, had high lactate levels in serum and cerebrospinal fluid from early infancy. Biochemical and morphologic studies of biopsied muscles disclosed no abnormality except for type 1 fiber atrophy, which was quite different from patients with central nervous involvement with type 2 fiber atrophy. In both patients, the disease was not progressive and lactate levels gradually decreased. Although no metabolic defect was found, these patients probably shared common pathogenetic mechanism.


Reliability of joint kinematic calculations based on direct kinematic and inverse kinematic models in obese children.
In recent years, the reliability of inverse (IK) and direct kinematic (DK) models in gait analysis have been assessed intensively, but mainly for lean populations. However, obesity is a growing issue. So far, the sparse results available for the reliability of clinical gait analysis in obese populations are limited to direct kinematic models. Reliability error-margins for inverse kinematic models in obese populations have not been reported yet. Is there a difference in the reliability of IK models compared with a DK model in obese children? Are there any differences in the joint kinematic output between IK and DK models? A test-retest study was conducted using three-dimensional gait analysis data from two obese female and eight obese male participants from an earlier study. Data were analyzed using a DK model and two OpenSim-based IK models. Test-retest reliability was compared by calculating the Standard Error of Measurement (SEM) along with similar absolute reliability measures. A Friedman Test was used to assess whether there were any significant differences in the reliability between the models. Kinematic output of the models was compared by using Statistical Parametric Mapping (SPM). No significant differences were found in the reliability between the DK and IK models. The SPM analysis indicated several significant differences between both IK models and the DK approach. Most of these differences were continuous offsets. Reliability values showed clinically acceptable error-margins and were comparable between all models. Therefore, our results support the careful use of IK models in overweight or obese populations, e.g. for musculoskeletal modelling studies. The inconsistent kinematic output can mainly be explained by different model conventions and anatomical segment coordinate frame definitions.


Radial keratotomy to treat myopic refractive error after cataract surgery.
To assess the predictability and effectiveness of radial keratotomy in patients with myopic refractive error and unacceptable anisometropia after cataract surgery. A prospective multicenter study. This study comprised 40 eyes of 40 Japanese patients who had had cataract surgery. Radial keratotomy was performed, and the 6 month postoperative data were analyzed. Mean patient age was 71.0 years +/- 7.4 (SD) (range 51 to 84 years) and mean preoperative anisometropia -3.41 +/- 1.69 D (range -1.25 to -7.75 D). The surgery decreased mean anisometropia to -1.01 +/- 0.94 D (P < .000001, Wilcoxon signed-rank test), a mean reduction of 2.22 +/- 1.23 D (range 0.75 to 5.88 D). Postoperative anisometropia ranged from 0.81 to -3.13 D. The surgical effects were overestimated by the nomograms developed for the correction of naturally occurring myopia in the eyes of white patients. Multiple regression analysis revealed that optical zone size and number of incisions were significantly correlated with the amount of myopic correction, and the regression equation (R2 = 0.77) was expressed as follows: Effects = (-1.45 x optical zone size) + (0.24 x incision number) + 7.60. A new nomogram was derived based on this equation. Radial keratotomy was a safe and efficient procedure to treat myopic refractive error in pseudophakic eyes. Separate nomograms are necessary for white and Asian populations.


Novel type of general protein assay using a chromogenic and fluorogenic amine-reactive probe.
We report on a new and simple one-reagent method for general protein assay. It makes use of one of two new reactive labeling reagents presented here (and referred to as pyrylium [Py] labels). These can be applied for both photometric and fluorometric protein assays at near neutral pHs at room temperature. The Py labels undergo a large spectral change on conjugation to the amino group of proteins and typically change their color from blue to red. Therefore, and unlike in other assays, there is no need to separate the unconjugated (blue) label from the red conjugate, which can be determined by direct photometry with a limit of detection of 1.2 microg/ml for human serum albumin. The assay can be extended to fluorometry because the fluorescence of the free Py label is weak (with a quantum yield of <1%) but increases strongly (to >40%) on conjugation. The strong fluorescence of the red conjugates can be determined directly and without interference by the blue (and weakly fluorescent) free label. The fluorometric assay resulted in a limit of detection of 60 ng/ml for bovine serum albumin (BSA). Validation of the fluorescence assay of blood plasma samples spiked with BSA gave recoveries in the range from 91 to 103%.


[Effects of FPIL6/IL2 on the differentiation and proliferation of lymphoid in the ML-IC assay].
To develop an in vitro assay that allows the culture and identification of a single human bone marrow progenitor closely related to hematopoietic stem cell, which is more primitive than LTC-IC, and to find an efficient culture conditions for NK-IC expansion. Fusion protein IL6/IL2 was reconstructed and expressed in E. coli DH5 alpha. ML-IC was determined by watching if the single cell can give rise to secondary progenitors with both LTC-IC and NK-IC characteristics. LTC-IC frequency was determined by the CFC clonogenic methylcellulose assay. NK-IC frequency was determined by phenotyping CD56 positive NK cells. The effect of FPIL6/IL2 on the expansion of NK-IC was examined by comparing the colony number of NK cells before and after the culture. After the initial 4-week expansion culture, we showed that (25.75 +/- 5.68)% of freshly sorted Lin-/34+/DRdim cells were able to generate functional NK-IC in one or more secondary FPIL6/IL2 cultures, whereas (6.81 +/- 1.97)% in the control. A total of 102 NK-IC cells were present when were cultured for 6-7 weeks in FPIL6/IL2 expansion medium, which was much higher than the 33 NK-IC cells in the control. ML-IC assay will prove useful to assess a very primitive hematopoietic cell with multilineage generative capacity. FPIL6/IL2 is capable of initiating and promoting NK-IC expansion greatly in ex vivo cultures in terms of net-conservation and net proliferation.


(4-Butyl-1-methyl-1,2,4-triazol-5-yl-idene)[(1,2,5,6-η)-cyclo-octa-1,5-diene](tri-phenyl-phosphane)iridium(I) tetra-fluorido-borate.
A new triazole-based N-heterocyclic cationic carbene iridium(I) complex with a tetra-fluorido-borate counter-anion, [Ir(C8H12)(C7H13N3)(C18H15P)]BF4, has been synthesized and structurally characterized. The IrI atom of the cationic complex has an expected square-planar coordination environment with unexceptional bond lengths. There are several close F⋯H contacts between the cations and the anions in the range 2.36-2.58 Å, stabilizing the orientation of the out-sphere [BF4 -] counter-anion. In the crystal, C-H⋯π(ring) inter-actions are observed that orient the phenyl rings of the tri-phenyl-phosphane ligands.


Application of exoantigens of Babesia and Plasmodium in vaccine development.
The University of Illinois malaria vaccine programme uses culture-derived soluble exoantigens of Plasmodium falciparum and the squirrel monkey as an experimental model. Exoantigens are soluble polypeptides naturally released into the blood plasma of animals infected with Babesia or Plasmodium species, or into the supernatant medium of in vitro cultures of these organisms. Immunization with soluble B. bovis and B. bigemina exoantigens prepared from culture supernatant fluids protected cattle against homologous and heterologous challenge. Similarly, vaccination of squirrel monkeys with supernatant fluids from P. falciparum cultures containing exoantigen induced protective immunity against acute clinical malaria. Susceptible monkeys have been vaccinated with an aluminium hydroxide-fortified antigenic fraction partially purified from supernatants of P. falciparum strains Indochina I and Genève/SGE-1; this conferred significant clinical protection against needle challenge with the homologous Indochina I strain, and a moderate degree of immunity to the heterologous strain. Following sequential purification by high performance liquid chromatography, the N-terminal amino acid sequences of P. falciparum 100 kDa, 83 kDa and 70 kDa exoantigens were determined. A 29 amino acid peptide constructed from the N-terminal sequence of the P. falciparum (Genève strain) 83 kDa exoantigen has been synthesized. When coupled to a carrier protein, the peptide was immunogenic in rabbits, mice and squirrel monkeys, inducing antibodies which were trophozoite-specific, reactive to native parasite proteins in a two-site enzyme immunoassay (EIA) and in Western blots, and which inhibited P. falciparum growth in vitro. Using this synthetic peptide, EIAs are being developed for the detection of antibodies to P. falciparum blood-phase parasites in individuals living in malaria-endemic areas of Africa, Asia and South America.


Stroke in diabetic and non-diabetic patients: course and prognostic value of admission serum glucose.
Whether diabetes mellitus affects the prognosis of stroke patients, and whether admission hyperglycemia influences prognosis similarly in diabetic as in non-diabetic patients is assessed controversially. The aims of the study were: 1) to compare the course of diabetic and non-diabetic acute stroke patients, and 2) to assess the influence of admission serum glucose levels on case fatality. In 57 Austrian medical departments the hospital course of consecutive stroke patients was documented prospectively between June 1999 and October 2000. Two hundred and ninety-six (30%) of 992 patients had a history of diabetes mellitus. Intracerebral hemorrhage was more frequent in non-diabetic patients than diabetic (13% versus 5%, P=0.0001). Coronary heart disease was more frequent in diabetic than in non-diabetic patients (35% versus 24%, P=0.0003). The case fatality was 18% among non-diabetic and 16% among diabetic patients (P=0.3559). Among patients who were discharged alive, the Barthel Index increased from 50 to 90 in non-diabetic and from 45 to 75 in diabetic patients (P=0.0403). In non-diabetic patients, admission serum glucose>9.2 mmol/L was associated with a more than 4-fold increase in case fatality, compared with patients with serum glucose<5.7 mmol/L (P<0.0001). Diabetic stroke patients need special care since they tend to have a poorer recovery than non-diabetic patients. Admission hyperglycemia in non-diabetic acute stroke patients predicts a poor prognosis.


A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles.
Recently activated, but not resting, CD4(+) T cells express CD154, providing costimulatory signals to B cells and antigen-presenting cells (APCs). Therefore, de novo CD154 expression after stimulation identifies antigen-specific CD4(+) T cells. Previous assays were limited by the transient nature of surface CD154 expression; we overcame this by including fluorescently conjugated CD154-specific antibody during stimulation. Our assay is fully compatible with intracellular cytokine staining, and can be used for stimulations as long as 24 h. Notably, it is nonlethal, providing a means to purify viable antigen-specific CD4(+) T cells for further analysis. Using this assay, we found that stimulated cells expressing tumor necrosis factor (TNF)-alpha, interleukin (IL)-2 or interferon (IFN)-gamma were predominantly CD154(+). Furthermore, some cells expressing none of these cytokines also expressed CD154, suggesting that CD154 marks cells with other effector functions. For vaccine- or pathogen-specific responses, we found substantial heterogeneity in expression of CD154 and cytokines, suggesting previously unrecognized diversity in abilities of responding cells to stimulate APCs through CD40.


Cellular events in tolerance IX: maintenance of immunological tolerance in the presence of normal b-cell precursors and in the absence of demonstrable suppression.
The cellular events involved in immunological tolerance to fluoresceinated sheep gammaglobulin (FL-SGG) were analyzed at the level of hapten-specific B cells. One single iv injection of FL-SGG induced tolerance as measured by challenge with thymus-dependent (FL-KLH) or thymus-independent (FL-Ficoll) antigens in vivo or thymus-independent (FL-LPS) antigen in vitro. As noted earlier, unresponsiveness was maintained until 6-8 weeks after tolerance induction. Limiting-dilution precursor analysis demonstrated a reduction in B-cell precursors on Day 7 after tolerogen treatment; precursor frequencies returned to control levels by 3-4 weeks. This recovery of precursors in the presence of stable tolerance was not due to suppressor activity. Rather, results show that tolerant hapten-specific B cells are clonally anergic and display a reduced burst size in response to antigen. Hence, unresponsiveness is maintained in the presence of apparently normal precursor levels by an intrinsic defect in antigen-specific B cells.


Extrathermodynamics: Varieties of Compensation Effect.
There are several types of the ΔH compensation. Along with well-known phenomenon of the ΔH - ΔS compensation, two more types of the ΔH - (ΔS + RΔ ln Ω) compensation are observed in some series of systems. The nature of these phenomena is connected with the behavior of phase volume of systems, Ω. The role of other thermodynamic parameters, which describe series in manifestation of this or that types of the ΔH compensation, is shown in light of molecular statistical mechanics.


A vision for eye care: a brief study of the change process.
Eye care is recognised as a basic nursing care procedure required by critically ill patients, to prevent complications such as eye infection or injury (Lloyd 1990). There is scanty literature available on the subject, with little evidence to support the action advised (Smith 1983, Lloyd 1990). Despite this, critically ill patients are given eye care by nurses, but the practical application varies widely (Farrell & Wray 1993). Selection of eye care techniques is based on the individual nurses' beliefs and values, and established largely by tradition. This article describes how this haphazard system of eye care was standardised in a general intensive care unit using the Dynamic Standard Setting System format for standard construction (RCN 1990). This formulation of a standard for eye care was used to explore the process of planned change underpinned by Lewin's theoretical model of change (Lewin 1964).


Isolated lateral rectus muscle large B cell lymphoma: A rare case report and review of the literature.
To report a 65-year-old male patient with primary lateral rectus large B cell lymphoma. The patient had been referred because of progressive proptosis and limitation of ductions, especially abduction (ortho position at primary gaze) and conjunctival injection. Computerized tomography of the orbit and paranasal sinuses depicted a massive lateral rectus muscle enlargement without any other orbital involvement. Lateral orbitotomy and lateral rectus belly incisional biopsy was done, and histopathologic and immunohistochemical staining and systemic evaluations revealed the diagnosis of primary orbital large B-cell lymphoma. This case indicated that, though rare, extraocular muscle enlargement could be the main finding of primary orbital lymphoma. Large B-cell lymphoma could involve only the orbital tissues, although it is more prevalent with systemic involvement.


[Adrenal cortical carcinoma].
To study the diagnosis and treatment of adrenal cortical carcinoma. Fifteen cases of adrenal cortical carcinoma (8 functional and 7 nonfunctional) were treated surgically during the period of 1978 - 1998. They were confirmed operatively and pathologically. The functional carcinoma usually showed typical clinical features such as Cushing's syndrome, primary aldosteronism, and adrenogenital syndrome. The nonfunctional had extra-adrenal symptoms such as acute abdominal pain and hypertension. A definite diagnosis can be made by the measurements of urine 17-ketosteroid, 17-hydrosteroid, cortisol, aldosterone, CT, and B-ultrasonography. Surgical removal of the tumor is the only effective treatment. Early diagnosis of adrenal cortical carcinoma is very difficult, especially in the non-functional.


LC-1000 flow cytometry system complements intraoperative peritoneal cytology for pancreatic and biliary tract cancer.
The exfoliative cell analyzer, LC-1000, is medical device that utilizes the principles of flow cytometry, and might provide digital diagnostic information for cytology using a different approach from conventional cytomorphology. In this study, wae examined the usefulness of the LC-1000 as a diagnostic support system for intraoperative peritoneal lavage cytology and its prognostic impact for pancreatic (PC) and biliary tract cancer (BTC). Patients with PC and BTC who underwent surgical treatment were included. First, we identified useful indicators of LC-1000 and established cutoff values to discriminate positive cytology. Next, we verified the validity of these cutoff values. In the test set (n = 48), of the LC-1000 indicators examined, only MR-CPIx was significantly different between the negative and positive cytology groups, yielding a cutoff value of 0.86. In the validation set (n = 52), the sensitivity, specificity, positive and negative predictive value of the LC-1000 for cytology results was 1.0, 0.49, 0.11 and 1.0, respectively. In patients who had undergone radical resection, recurrence-free survival rate was significantly higher in the LC-1000 negative group than in the positive group in PC, but not in BTC. The LC-1000 was useful as digital support system for peritoneal cytology, and it might have potential as a prognostic factor for PC.


Educational needs and employment status of Scottish dental technicians.
To investigate the educational needs and employment status of dental technicians in Scotland. Two hundred and fifty dental technicians with postal addresses in Scotland. Structured questionnaire. An 83% response rate was achieved following three mailings. The majority of respondents were employed in commercial dental laboratories largely within the 'central belt' of Scotland, with 96% stating they were in full-time employment. Only 33% of these essential health-care workers were voluntarily registered with the Dental Technicians' Association, suggesting that a significant number had not felt it necessary or beneficial to do so. A lack of educational structure was identified, as was poor remuneration and an absence of opportunity for career progression. Although the prospect of continuing professional development was desirable, many respondents reported that they would be penalised financially for undertaking this and, in addition, may not be given the opportunity to pursue education because of lack of co-operation from their employer. Only 47% had attended an educational event within the preceding year, and of those who had not done this, a period of two-32 years had elapsed since any CPD involvement. Of the respondents, only 34% stated that any financial assistance had been available for educational purposes, with access to education being highlighted as problematic by 68%. A total of 64% of subjects felt they were out-of-date with professional education. This study highlights a number of real and potential problems in the field of education in dental technology. It is apparent that change within the structure of education and professional status, although largely welcomed, may be difficult to implement. The profession, as a whole, must realise that these changes in education and employment are not optional, and should be embraced as a positive step which will hopefully raise the profile and status of dental technicians throughout the UK.


Biotransformation kinetics of Pseudomonas putida for cometabolism of phenol and 4-chlorophenol in the presence of sodium glutamate.
A kinetic model to describe the degradation of phenol and cometabolic transformation of 4-chlorophenol (4-cp) in the presence of sodium glutamate (SG) has been developed and validated experimentally. The integrated model accounts for cell growth, toxicity of 4-cp, cross-inhibitions among the three substrates, and the different roles of the specific growth substrate (phenol) and the conventional carbon source (SG) in the cometabolism of 4-cp. In this ternary substrate system, the overall phenol degradation and 4-cp transformation rates are greatly enhanced by the addition of SG since SG is able to attenuate the toxicity of 4-cp and therefore increase the cell growth rate. Model analysis indicates that the maximum specific degradation rate of phenol (0.819 mg (mg.h)(-1)) is lowered by SG by up to 46% whereas the specific transformation rate of 4-cp is not directly affected by the presence of SG. The competitive inhibition coefficient of 4-cp to phenol degradation (Ki,cp) and that of phenol to 4-cp transformation (Ki,ph) were determined to be 6.49 mg l(-1) and 0.193 mg l(-1), respectively, indicating that phenol imposes much larger competitive inhibition to 4-cp transformation than the converse. The model developed can simultaneously predict phenol degradation and 4-cp transformation, and is useful for dealing with cometabolism involving multiple substrates.


Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions.
Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60°C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60°C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants.


An accurate dihydrouracil/uracil determination using improved high performance liquid chromatography method for preventing fluoropyrimidines-related toxicity in clinical practice.
An accurate and improved HPLC method was set up to measure both dihydrouracil (UH2) and uracil (U) in plasma, and to assess their ratio. Analytes retention time, separation and peak purity were greatly optimized with a Hypercarb column and a diode array detector. U and UH2 limits of quantification were 1.25 and 0.625 ng/mL. U and UH2 within-day precisions were 0.9-2.3% and 0.7-5.6%. Between-day precisions were 1.3-5.3% and 1.3-7.1%. Accuracy was 0.1-6.1%. UH2/U ratio between-day variability was low, but ratio decreased from 02:00 p.m. This method is now used in practice to detect patients at risk of fluoropyrimidine toxicity and to individually adapt the dosage.


Neurofibromatosis type 1 tumour suppressor gene expression is deficient in psoriatic skin in vivo and in vitro: a potential link to increased Ras activity.
Neurofibromatosis type 1 (NF1) protein (neurofibromin) accelerates the inactivation of Ras-GTP in various cell types. Somatic mutations of the NF1 gene may lead to malignant transformation and uncontrolled proliferation. We have previously shown that NF1 protein expression is downregulated in psoriasis in vivo. To study the functional expression and distribution of NF1 mRNA and protein in vivo and in psoriatic and normal keratinocyte cultures. Immunohistochemistry and in situ hybridization were used to study NF1 gene and protein expression in psoriasis in vivo. Furthermore, Northern and in situ hybridizations, immunoblot and localization analyses were utilized to study NF1 mRNA and protein in vitro in keratinocyte cultures. NF1 tumour suppressor gene expression was reduced in lesional psoriatic skin compared with perilesional and normal skin in vivo. The in vitro results showed that the levels of NF1 mRNA and protein were reduced in cultured psoriatic keratinocytes during cellular differentiation even after multiple passaging of the cells. Moreover, cultured nonlesional psoriatic keratinocytes were almost equally defective as lesional cells with respect to NF1 expression. Our findings demonstrate that psoriatic keratinocytes maintain an altered phenotype and gene expression profile even when isolated from interaction with lymphocytes and fibroblasts, which are known to increase proliferation of keratinocytes. As NF1 protein is regarded as a Ras proto-oncogene regulator, the aberrant expression and distribution of NF1 protein and mRNA found in the present study may be causative to the previously described increased activation of Ras in psoriatic lesions, and relate to altered cellular behaviour.


BCL-2: found bound and drugged!
The BCL-2 gene was first cloned in 1985 from the t(14;18) chromosomal translocation found in nearly all follicular lymphomas. BCL-2 is understood to have a central role in inhibiting apoptosis. Now, Oltersdorf et al. report the development of a high-affinity, mechanistically validated small-molecule antagonist of BCL-2 that kills cancer in mouse xenograft models and primary human cancer cells in vitro. The two decades spanning these two achievements provide an interesting case study of rational drug development. The investigation of antiapoptotic protein antagonists holds new promise for selectively inducing programmed cell death in cancer cells.


Cardio-respiratory contributions to the magnetoencephalogram.
Modern MEG technology provides whole head helmet systems which extend posterior to the base of the skull. While this provides better visualization of low temporal structures it also allows the intrusion of activity that is of cardiac origin. This consists not only of the QRS complex of the MCG but a late component (LC) during the SP interval. This tends to consist of a series of waves and has a different topographic distribution from the magnetic QRS complex. The LC is usually most prominent in the low occipital and sub-occipital sensors but can occur also in other areas. When the high pass filter is set to 0.1 Hz it can be seen that the LC rides on a slow wave of about 0.3 Hz, which is linked to respiration. Principal component analysis of cardiac cycles averaged from the ECG separates the MCG from the LC. The physiology of the LC is unknown at this time but it may be related to the ballistocardiogram. Algorhythms designed to remove the cardiac contributions to the MEG will have to take the LC and its marked variability into account.


Cell wall lytic enzyme released by mating gametes of Chlamydomonas reinhardtii is a metalloprotease and digests the sodium perchlorate-insoluble component of cell wall.
Chlamydomonas lytic enzyme of the cell wall, which is released during agglutination of gametes of opposite mating types, has been characterized as a metalloprotease. The purified enzyme contains zinc. Removal of zinc with EDTA results in an inactive, metal-free apoenzyme, and Co2+ restores the activity most effectively. Among various protease inhibitors of microbial origin, pepstatin A, chymostatin, antipain, leupeptin, and E-64 do not inactivate the enzyme, whereas phosphoramidon causes a complete loss of lytic activity. Cysteine, histidine, aspartic acid, and glutamic acid also inhibit the activity. The lytic enzyme splits casein and RNase A into several polypeptides of lower molecular masses. To determine which polypeptides of the cell wall are sensitive to the lytic enzyme, we first separated the intact cell walls into sodium perchlorate-soluble and -insoluble components, treated them with enzyme, and then analyzed them by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. We conclude that only 2 of 16 polypeptides are digested by exposure to the enzyme and that the sensitive polypeptides belong to the salt-insoluble component of the cell wall. The mechanism of cell wall digestion with the lytic enzyme is discussed.


Data on clinical significance of GAS2 in colorectal cancer cells.
The growth arrest-specific 2 (GAS2) was cloned and found to be upregulated in the feces of recurrent CRC patients. This overexpressed GAS2 induced different patterns of gene expressions in CRC cells. Briefly, one cell proliferation marker, Ki-67 antigen (Ki-67), was upregulated in the cells with overexpressed GAS2, "Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer" [1]. Whereas, the expression of another cell proliferation marker, proliferating cell nuclear antigen (PCNA), changed insignificantly [1]. In addition, the mRNA level of one cyclin involving in both cell cycle G1/S and G2/M transitions was also not affected by GAS2 overexpression, "Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A" [2]. The experimental design and procedures in this article can be helpful for understanding the molecular significance of GAS2 in SW480 and SW620 CRC cells.


[Post-traumatic bipolar dislocation of the clavicle: is operative treatment reasonable?].
Bipolar dislocation of the clavicle ("floating clavicle") is extremely rare. It exists no standardised treatment for this trauma and the treatment is often conservative. This is mainly an anterior displacement of the sternoclavicular joint (type III according to Allman) and a posterior dislocation of the acromioclavicular joint (type IV according to Rockwood).We report on a 60 year old male who fell onto the right shoulder. He sustained a 'floating clavicle' and had a massive dislocation, impairment of range of motion and pain. Venous congestion was observable. We stabilised the dislocated acromioclavicular joint with a Balser's plate, the sternoclavicular joint was fixed with PDS cord tension band technique around the first rip and the sternum. In addition we resected the anterior part of the distal clavicle to get a better cosmetic result. Post-operatively the patient had an excellent range of motion without any further symptoms after six weeks and one year. Venous congestion was not more observable.In most of the cases dislocations of both ends of the clavicle are treated conservatively. We recommend an operative treatment especially in young and active patients to avoid re-dislocation and to archive better cosmetic results.


Sensitivity of the OLGA and VCM models to erroneous marker placement: effects on 3D-gait kinematics.
Gait data need to be reliable to be valuable for clinical decision-making. To reduce the impact of marker placement errors, the Optimized Lower Limb Gait Analysis (OLGA) model was developed. The purpose of this study was to assess the sensitivity of the kinematic gait data to a standard marker displacement of the OLGA model compared with the standard Vicon Clinical Manager (VCM) model and to determine whether OLGA reduces the errors due to the most critical marker displacements. Healthy adults performed six gait sessions. The first session was a standard gait session. For the following sessions, 10mm marker displacements were applied. Kinematic data were collected for both models. The root mean squares of the differences (RMS) were calculated for the kinematics of the displacement sessions with respect to the first session. The results showed that the RMS values were generally larger than the stride-to-stride variation except for the pelvic kinematics. For the ankle, knee and hip kinematics, OLGA significantly reduced the averaged RMS values for most planes. The shank, knee and thigh anterior-posterior marker displacements resulted in RMS values exceeding 10°. OLGA reduced the errors due to the knee and thigh marker displacements, but not the errors due to the ankle marker displacements. In conclusion, OLGA reduces the effect of erroneous marker placement, but does not fully compensate all effects, indicating that accurate marker placement remains of crucial importance for adequate 3D-gait analysis and subsequent clinical decision-making.


Factors influencing the blood-brain barrier permeability.
The blood-brain barrier (BBB) is a dynamic structure that protects the brain from harmful blood-borne, endogenous and exogenous substances and maintains the homeostatic microenvironment. All constituent cell types play indispensable roles in the BBB's integrity, and other structural BBB components, such as tight junction proteins, adherens junctions, and junctional proteins, can control the barrier permeability. Regarding the need to exchange nutrients and toxic materials, solute carriers, ATP-binding case families, and ion transporter, as well as transcytosis regulate the influx and efflux transport, while the difference in localisation and expression can contribute to functional differences in transport properties. Numerous chemical mediators and other factors such as non-physicochemical factors have been identified to alter BBB permeability by mediating the structural components and barrier function, because of the close relationship with inflammation. In this review, we highlight recently gained mechanistic insights into the maintenance and disruption of the BBB. A better understanding of the factors influencing BBB permeability could contribute to supporting promising potential therapeutic targets for protecting the BBB and the delivery of central nervous system drugs via BBB permeability interventions under pathological conditions.


Pacemaker follow-up and adequacy of Medicare guidelines.
The time of occurrence of cardiac pacemaker problems after implantation was identified to assess the adequacy of published federal guidelines for clinic and transtelephonic follow-up. One hundred eighty-nine pacemaker patients' charts were examined retrospectively to identify pacemaker problems: inadequate sensing, non-capture, battery failure, myoinhibition, muscle stimulation, and inadequate threshold safety margin. Twenty-nine patients (15%) were identified as having pacemaker problems. A total of 41 problems were identified, of which 28 (68%) were corrected by reprogramming. Sixty-one percent of the problems were found during a clinic visit. Problems occurred more frequently during the first year in dual-chamber devices (62%) vs single-chamber devices (35%). During years 1 to 4, when few problems are expected, 30% of all problems of single-chamber devices occurred and 39% of all problems of dual-chamber devices occurred. This is a period of time that Medicare guidelines allow for one clinic visit per year for single- and two visits per year for dual-chamber devices. These data suggest: (1) Many pacemaker problems will be missed with transtelephonic follow-up alone. (2) The majority of problems involving dual-chamber devices occurred in the first year. (3) For both dual- and single-chamber devices, an unexpected significant percentage of problems occurred in 1 to 4 years. (4) Medicare guidelines may be inadequate for follow-up during this time period.


Phenolic compounds of willow bark as deterrents against feeding by mountain hare.
Overwintering mountain hares (Lepus timidus) fed selectively on the shoots of a number of northern willow (Salix spp.) species. The hares preferred certain species over others and mature shoots over juvenile ones. There was a negative correlation between the phenolic glycoside concentration in the twigs and the hares' feeding. This correlation was substantiated by feeding experiments in which oat grains treated with purified phenoglycoside and catechin fractions of willow bark were offered along with untreated control oat grains to free-ranging mountain hares. Both fractions in concentrations normally found in willow twigs inhibited hare feeding. The results suggest that these phenolic compounds play a crucial role in the building up of resistance patterns among the willows. The decline in resistance in mature shoots of tall willows indicates that the juvenile resistance can be, perhaps secondarily, an adaptation against mammals browsing from ground level. Accordingly, low willow species retain a high level of resistance also in maturity.


[Demonstration of Precipitating antibodies in patients with echinococcosis using a counter immunoelectrophoresis (author's transl)].
A counter immunoelectrophoresis was used for the demonstration of antibodies to echinococci. The antigen was prepared from hydatid fluid obtained from liver cysts of sheep. After concentration the antigenic material contained 1800 to 2900 micrograms of nitrogen per milliliter fluid. One or more precipitating lines were regarded as positive. Serum samples of 184 patients with surgically proven echinococcosis gave positive results in 80,4% of the cases. Among them, patients with hydatid disease of the liver were positive in 83,2% of the cases, and patients with hydatid disease of the lung were positive in 78,6 of the cases. The arithmetric mean of the number of lines was 2,4. Sera of 1182 patients with other diseases (among others diseases of the gastro-intestinal and respiratory tract, allergies, neuro-psychiatric, gynecologic and parasitic diseases) reached in 4,6% of the cases with the formation of precipitating lines. The described test is simple to perform, it can be read after a short period of time and it can be used as a screening test for mass case finding.


Wild-type ATTR amyloidosis may be associated with unexpected death among the elderly.
Wild-type ATTR amyloidosis (ATTR-wt) is characterized by the accumulation of amyloid in the heart, leading to fatal heart failure and arrhythmia. In this study, we investigated the amyloid deposits in the heart from 556 forensic autopsy cases over 60 years of age. The prevalence of ATTR-wt was 5.8% (32 of the 556), with the prevalence increasing as a function of age. We identified an ATTR-wt-specific morbidity rate of 12.3% for patients over 80 years of age, while the prevalence among individuals over 90 years of age was 34.9%. In none of these 32 cases had a clinical diagnosis of ATTR-wt been made. In 29 of the 32 cases found to be ATTR-wt positive, an obvious extraneous cause of death was identified and included burning, drowning, hypothermia, suicide, and traffic accident. On the other hand, heart failure due to ATTR-wt was confirmed as the cause of death in 3 of the 32 cases. It is suggested that ATTR-wt may be associated with unexpected death among the elderly.


Secondary breast reconstruction after mastectomy using the DIEP flap.
Breast reconstruction is an important element in the successful therapy of breast cancer [1]. Thereby, autologous microvascular breast reconstruction has been shown to be a reliable technique. The use of a deep inferior epigastric perforator (DIEP) flap or a muscle-sparing (MS) free transverse rectus abdominis musculocutaneous (TRAM) flap is recognized in many centres as gold standard for reconstructive options [2-4]. Based on our experiences with 137 patients over a 5-year period we want to highlight the technical aspects of the free microsurgical autologous breast reconstruction using a DIEP flap. Between 01/2013 and 12/2017 we treated 137 patients (age 32-78 years, mean age 52 years) after mastectomy with autologous microsurgical free flap breast reconstruction. A DIEP flap was used for breast reconstruction in 33 patients. In 104 cases, we performed a muscle sparing TRAM flap. In this video we demonstrate the typical sequence of operative steps of a DIEP flap in a 32 year old patient after mastectomy due to an invasive ductal breast carcinoma. The rate of total flap loss in our department was 2.2% including all patients. In less than 1%, partial flap necrosis could be observed. 61% of the patients had undergone previous irradiation. Within the small number of flap loss, we could not observe a trend towards a correlation between flap loss and previous irradiation. Autologous breast reconstruction using a DIEP or MS-TRAM flap provides a surgically safe technique including a low incidence of flap loss in specialized centres.


Modern intraocular lens implants in children with new age limitations.
Seventy-three children received modern designs of posterior and flexible anterior chamber intraocular lenses. Twenty-eight (38%) had anterior chamber and 45 (62%) had posterior chamber lenses implanted. Postoperative implant complications occurred in 38 (54%) eyes; the most frequent was secondary membrane formation. Six eyes (22%) with anterior chamber lenses and 25 eyes (58%) with posterior chamber lenses required posterior capsulotomies. Seventy percent of the posterior chamber lens recipients less than six years of age developed secondary membranes. All of these eyes had a discission except one Nd:YAG laser patient. Forty-eight percent of the patients with posterior chamber lenses over six years of age required posterior capsulotomies: 55% had Nd:YAG laser capsulotomies and 45% had discissions. Based upon these observations, we now recommend primary implantation of flexible anterior chamber lenses in three- to six-year old children who have tissue-free visual axes and for all secondary implantations. Primary posterior chamber lenses are recommended for children six years of age and older and for younger children who will tolerate a Nd:YAG laser capsulotomy.


Prosecution of women arrested for intimate partner abuse.
Increasing arrests of women for domestic violence (DV) in the wake of mandatory arrest laws have generated significant concern among victim advocates, researchers, and practitioners. It is commonly believed that many, if not most, of the women arrested are victims who were acting in self-defense. Understanding how these cases are handled by prosecutors and judges is important if we wish to minimize the negative consequences of these errant arrests. The present study examines factors prosecutors in a large southern city considered when accepting or rejecting DV cases involving female defendants. The results indicate that almost one half (47%) of the cases involving women arrested for DV against a heterosexual intimate partner were rejected by prosecutors; another 16% were dismissed by a judge. Legal factors like a defendant's prior criminal arrests, use of a weapon, victim injury, and, most important, the type of arrest (i.e., dual vs. single arrest) all affected prosecutors' decisions to take these cases. Female defendants arrested for offending against a male intimate partner were treated more leniently than male defendants and women arrested for domestic offenses involving other types of relationships (i.e., familial, homosexual). The results highlight the need for a further study of officers' arrest decisions in cases involving heterosexual intimate partners.


Associations of methylenetetrahydrofolate reductase gene (MTHFR) rs1801131 and rs1801133 polymorphisms with susceptibility to vitiligo: A meta-analysis.
Vitiligo is a common pigmentary skin disorder, and genetic factors were acknowledged to be greatly associated with the pathogenesis of this disease. Recently, increasing studies investigated the associations of methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms with risks of vitiligo, but the results still remained controversial. The current meta-analysis was conducted to further evaluate the association of MTHFR polymorphisms with risk of vitiligo. Eligible studies were searched in PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Database until October 2020. All analyses were carried out using the Review Manager 5.3 software. A total of 6 studies that involved MTHFR rs1801131 and/or rs1801133 polymorphism were finally included, which enrolled 3599 participants. Our results showed that no correlations were found between MTHFR rs1801131, rs1801133 polymorphisms and vitiligo risks in overall group. However, subgroup analysis revealed that rs1801131 polymorphism was significantly associated with increased vitiligo risk in the allelic (C vs A: OR = 1.15, 95% CI = 1.02-1.29, P = .02) and homozygous models (CC vs AA: OR = 1.48, 95% CI = 1.10-2.01, P = .01) in Asian population and that the rs1801133 polymorphism was significantly associated with decreased vitiligo risk in the allelic model (T vs C: OR = 0.82, 95% CI = 0.74-0.92, P = .0005) also in Asian population. This meta-analysis confirmed the associations of MTHFR rs1801131 and rs1801133 polymorphisms with vitiligo risks and provided comprehensive insight into the pathogenesis of vitiligo.


Influence of food on the absorption of phenytoin in man.
The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.