Dose-response relation between dietary inflammatory index and human cancer risk: evidence from 44 epidemiologic studies involving 1,082,092 participants.
A newly developed dietary inflammatory index (DII) to evaluate the inflammatory potential of diets was published recently. Many studies have investigated the link between diet-related inflammation and human cancer risk, but the results remain controversial. We sought to determine the dose-response relation between DII and human cancer risk based on published epidemiologic literature. To summarize evidence, we performed a dose-response meta-analysis to investigate the association between DII and cancer incidence. We systematically searched PubMed, Embase, Web of Science, and the Cochrane library up to 5 November 2017. After data extraction, pooled RRs were calculated and dose-response analyses were performed using a restricted cubic spline model with 4 knots. Subgroup analyses, sensitivity analyses, and tests for publication bias were also performed. In all, 44 high-quality studies with 1,082,092 participants were included. The results showed that an elevated DII (continuous-RR: 1.13; 95% CI: 1.09, 1.16; category DIIhighest vs lowest-RR: 1.58; 95% CI: 1.45, 1.72) independently indicated higher cancer risk except for lung cancer and Australian studies. A linear dose-response relation between DII and overall cancer risk was found, with an 8.3% increase in the risk of cancer per DII score. The pooled RR of DII and cancer risk was 1.86 (95% CI: 1.63, 2.13) from 30 case-control studies but was lower in 14 prospective cohorts (RR: 1.29; 95% CI: 1.19, 1.40). The sensitivity analysis and Egger's test supported the main results. Our analysis indicated that higher DII is significantly correlated with cancer risk. More prospective studies with large sample sizes, involving more ethnic groups and different cancer types, are required in the future. This review was registered with PROSPERO as CRD42017077075.


Thirty neurological eponyms associated with the nazi era.
In the 1920s, the neurosciences in Germany were world-class. Then came Hitler's regime, and with it 2 distinct changes happened to the research milieus in Berlin and elsewhere. First, the persecution of Jews and others deprived Germany of many of its most outstanding scientists. Second, numerous German and Austrian physicians became active in National Socialist (NS)-euthanasia programs. In recent years, the medical community has become more aware of the ethical burden associated with eponyms derived from scientists of the Third Reich. Yet a list of these eponyms with emphasis on clinical neurology is still missing. This paper therefore reviews 30 neurological eponyms derived from 29 physicians who lived in the Nazi era. Among them are victims who were forced out of the country or murdered in concentration camps, protestors who risked their academic careers and often their lives, beneficiaries who published on brains from 'euthanized' children, and collaborators who were directly involved in the planning and execution of NS-euthanasia programs.


Fetal antigen hypothesis and ovarian cancer: is there an immunogenic explanation for the reduction in risk associated with parity?
The hypothesis that a woman's immunologic response to fetal antigens arising from paternal genes may explain some of the reduction in risk of ovarian cancer associated with parity has not, to our knowledge, been examined. We analyzed data from a case-control study to evaluate the risk of epithelial ovarian cancer among women of similar parity associated with proposed indices of paternally derived fetal antigen exposure. Cases included white women 20-79 years of age diagnosed with epithelial ovarian cancer in three counties in Washington State between January 1, 1986, and December 31, 1988 (N = 322). Controls (N = 426) were selected by random-digit dialing and were broadly similar to cases in age and county of residence. After excluding women who had fewer than two pregnancies (or, in some analyses, fewer than two livebirths) and adjusting for age and number of livebirths, we observed no reduction in risk associated with number of marriages or number of partners with whom a study participant conceived a pregnancy and/or had a child. Nevertheless, these relatively crude indices of exposure to paternally derived fetal antigens do not preclude the possibility that a woman's response to other fetal or pregnancy-related antigens may antagonize the development of ovarian cancer.


Estimation of epistatic variance components and heritability in founder populations and crosses.
Genetic association studies have explained only a small proportion of the estimated heritability of complex traits, leaving the remaining heritability "missing." Genetic interactions have been proposed as an explanation for this, because they lead to overestimates of the heritability and are hard to detect. Whether this explanation is true depends on the proportion of variance attributable to genetic interactions, which is difficult to measure in outbred populations. Founder populations exhibit a greater range of kinship than outbred populations, which helps in fitting the epistatic variance. We extend classic theory to founder populations, giving the covariance between individuals due to epistasis of any order. We recover the classic theory as a limit, and we derive a recently proposed estimator of the narrow sense heritability as a corollary. We extend the variance decomposition to include dominance. We show in simulations that it would be possible to estimate the variance from pairwise interactions with samples of a few thousand from strongly bottlenecked human founder populations, and we provide an analytical approximation of the standard error. Applying these methods to 46 traits measured in a yeast (Saccharomyces cerevisiae) cross, we estimate that pairwise interactions explain 10% of the phenotypic variance on average and that third- and higher-order interactions explain 14% of the phenotypic variance on average. We search for third-order interactions, discovering an interaction that is shared between two traits. Our methods will be relevant to future studies of epistatic variance in founder populations and crosses.


[Clinical picture and therapy of endometriosis].
This paper defines endometriosis disease and summarizes its clinical and pathological features. Definitive diagnosis of endometriosis requires direct visualization of the disease. Laparoscopy is the most commonly employed method to inspect the peritoneal cavity directly. We list the drugs employed for the medical therapy of endometriosis and put evidence on limits and side effects of medical treatment. The surgical treatment is mainly laparoscopic for excision or coagulation of pelvic endometriosis implants but frequently the rate of recurrences or new implants is high. In this paper we stressed the urological aspect of endometriosis in particular bladder and ureteral locations and the secondary ureteral injuries resulting from surgical treatment.


Colonoscopy screening for individuals aged 40-49 years with a family history of stomach cancer in Korea.
For asymptomatic individuals aged 40-49 years, screening for colorectal cancer is recommended only if individuals are at an increased risk. A family history of colon cancer (FHCRC) is considered to increase risk, however, whether family history of stomach cancer (FHSC) increases the risk of adenoma is not well known. We aimed to see whether FHSC increases the risk in asymptomatic individuals aged 40-49 years in Korea. Among asymptomatic individual aged 40-49 years who underwent colonoscopy screening, risk of adenoma was assessed according to FHCRC or FHSC. Of 3,160 individuals, male comprised 1,602 individuals (50.7%). FHCRC and FHSC was noticed in 163 (5.2%) and 227 (7.0%) individuals, respectively. Prevalence of adenoma was 31.9 %, 28.8%, and 22.3% for individuals with FHCRC, individuals with FHSC, and individuals without family history of cancer, respectively. FHSC was an independent risk factor for adenoma (odds ratio, 1.38; 95% confidence interval, 1.02-1.87, P = 0.039) in asymptomatic individuals aged 40-49 years. Compared with individuals with FHCRC, individuals with FHSC showed no difference in risk for adenoma (P = 0.347). As with individuals with FHCRC, individuals with FHSC might need to be considered as an individual with increased risk for adenoma. Therefore, earlier screening might be needed for asymptomatic individuals aged 40-49 years with FHSC in Korea.


Self-Limitations of Heat Release in Coupled Core-Shell Spinel Ferrite Nanoparticles: Frequency, Time, and Temperature Dependencies.
We explored a series of highly uniform magnetic nanoparticles (MNPs) with a core-shell nanoarchitecture prepared by an efficient solvothermal approach. In our study, we focused on the water dispersion of MNPs based on two different CoFe2O4 core sizes and the chemical nature of the shell (MnFe2O4 and spinel iron oxide). We performed an uncommon systematic investigation of the time and temperature evolution of the adiabatic heat release at different frequencies of the alternating magnetic field (AMF). Our systematic study elucidates the nontrivial variations in the heating efficiency of core-shell MNPs concerning their structural, magnetic, and morphological properties. In addition, we identified anomalies in the temperature and frequency dependencies of the specific power absorption (SPA). We conclude that after the initial heating phase, the heat release is governed by the competition of the Brown and Néel mechanism. In addition, we demonstrated that a rational parameter sufficiently mirroring the heating ability is the mean magnetic moment per MNP. Our study, thus, paves the road to fine control of the AMF-induced heating by MNPs with fine-tuned structural, chemical, and magnetic parameters. Importantly, we claim that the nontrivial variations of the SPA with the temperature must be considered, e.g., in the emerging concept of MF-assisted catalysis, where the temperature profile influences the undergoing chemical reactions.


Mediastinal endodermal sinus tumor associated with fatal hemophagocytic syndrome.
The association of endodermal sinus tumor, known also as yolk sac tumor, of the mediastinum with hemophagocytic syndrome is exceedingly rare with only a few cases on record. We report a 24-year-old male who had a large mediastinal germ cell tumor, proven to be an endodermal sinus tumor on biopsy. The patient developed pancytopenia and coagulopathy related to associated hemophagocytic syndrome, with a fatal outcome. A brief review of the relevant literature is presented as well.


Synthesis of long-chain polyunsaturated fatty acids in lactating mammary gland: role of Delta5 and Delta6 desaturases, SREBP-1, PPARalpha, and PGC-1.
The purpose of this work was to study whether rat lactating mammary gland can synthesize PUFAs through the expression of Delta5 and Delta6 desaturases (Delta5D and Delta6D), whether these enzymes are regulated by the transcription factors sterol-regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor alpha (PPARalpha) and the coactivator peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), and whether these desaturases are regulated by the lipid concentration in the diet. The results showed that on day 12 of lactation, approximately 35% of the linoleic acid in the diet, which is the precursor of PUFAs, is transferred to the mammary gland. There was expression of Delta5D and Delta6D in mammary gland, and it was regulated by the corn oil content in the diet. The higher the corn oil content in the diet, the lower the expression of both desaturases. Induction of Delta5D and Delta6D was associated positively with similar changes in SREBP-1 and PGC-1beta. Expression of PPARalpha was barely detected and was not affected by the corn oil content in the diet, whereas PGC-1beta expression increased as the corn oil in the diet increased. These results indicate that the lactating mammary gland has the capacity to synthesize PUFAs and can be regulated by the lipid content in the diet.


Oxidation of formic acid on the Pt(111) surface in the gas phase.
Formic acid (HCOOH) oxidation on Pt(111) under gas-phase conditions is a benchmark heterogeneous catalysis reaction used to probe electro-catalytic HCOOH conversion in fuel cells, itself an important reaction in energy conversion. We used density functional theory (DFT) calculations to elucidate the fundamental oxidation mechanisms of HCOOH in the gas phase, determining the relative strengths of chemical interactions between HCOOH oxidation intermediates and the Pt(111) surface. We focused on investigating how water and adsorption coverage affects reaction intermediate structures and transition states. Our results show that adsorbed HCOO is a reactive intermediate in gas phase, and co-adsorbed water plays a key role in HCOOH oxidation influencing the structure of reaction intermediates and reaction barriers on Pt(111). The simulations show the preferred catalytic pathway is qualitatively dependent on surface coverage. These results provide a conceptual basis to better interpret its complicated experimental reaction kinetics.


Suction drainage fluid culture during septic orthopaedic surgery, a retrospective study.
We evaluated the usefulness of suction drainage fluid culture after septic orthopaedic surgery to predict early surgical reintervention. We conducted a retrospective observational study, at the Groupe Hospitalier Paris Saint-Joseph between 2014 and 2019. All the patients undergoing septic orthopaedic surgery, with perioperative samples and a postoperative suction drainage device, were enrolled. We compared the group with positive or negative postoperative drainage fluid cultures, respectively, on surgical outcome. We included 246 patients. The drainage fluid culture was positive in 42.3% of the cases. Early surgical reintervention concerned 14.6% of the cases (n = 36), including 61.1% of patients with positive drainage fluid culture (n = 22/36). The risk factors associated with positive drainage fluid cultures were the debridement of the infected site (without orthopaedic device removal), an infection located at the spine, perioperative positive cultures to Staphylococcus aureus. The complete change of the orthopaedic device, and coagulase-negative staphylococci on the preoperative samples, was associated with negative drainage fluid cultures. Positive drainage fluid culture was predictive of early surgical reintervention, and coagulase-negative staphylococci in the preoperative samples and knee infection were predictive of surgical success. Postoperative drainage fluid cultures were predictive of early surgical reintervention. Randomized multicentric studies should be further conducted.


Sudden Death and Cardiac Arrythmia With Lamotrigine: A Rapid Systematic Review.
A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or ECG abnormalities. We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions. There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results.


Consequences of getting the head covered during sleep in infancy.
To study the consequences of getting the head covered by bedding (fiber quilt) on carbon dioxide (CO2) accumulation around the face, behavior, and physiologic responses during prone and supine sleep in infants to add understanding to why victims of sudden infant death syndrome are often found under the bedding. METHPDOLOGY: Of 33 healthy term, usually nonprone sleeping infants, behavior and computerized polysomnography were successfully recorded for 30 during prone and supine sleep at 21/2 months and for 23 prone and 25 supine at 5 months. For both ages and body positions, covering the head resulted in significant CO2 accumulation around the face, fewer apneas (3 to 10 seconds), shorter duration of apneas after sighs, higher heart and respiratory rates, and peripheral skin temperature. Differences were generally greater at 21/2 than at 5 months. While covered, the prone position was associated with higher CO2 levels close to the face, slightly higher transcutaneous PCO2, and higher heart rates and peripheral skin temperatures than the supine position. In the supine position 23% were able to remove the cover from the head at 21/2 and 60% at 5 months, whereas only 1 infant of 5 months managed to remove the cover when prone. The observed responses are consistent with a potential for distress when the head is covered, particularly when placed prone. Probably most important with respect to sudden infant death syndrome is the infants' inability to remove the bedding from the head upon awakening from prone sleep.


Clinical significance of the preoperative platelet count and platelet-to-lymphocyte ratio (PLT-PLR) in patients with surgically resected non-small cell lung cancer.
The aim of this study was to assess the prognostic significance of the preoperative platelet count (PLT) and platelet-to-lymphocyte ratio (PLR) in patients with surgically resected non-small-cell lung cancer (NSCLC). We retrospectively reviewed 202 patients treated for NSCLC between January 2002 and December 2007. Preoperative PLT and PLR scores were calculated using data obtained at the time of admission. Patients were assigned a PLT-PLR score of 0, 1, or 2 based upon the presence of thrombocytosis, an elevated PLR, or both. Patients with a PLT-PLR score of 2 had a significantly lower median overall survival (OS) [12.715 mo; 95% confidence interval (CI) 1.215-24.215] when compared with patients with PLT-PLR scores of 1 (52.238 mo; 95% CI 17.062-87.414, p = 0.002) or 0 (not reached, p < 0.001). Relapse-free survival (RFS) was also significantly decreased in patients with a PLT-PLR score of 2 (10.107 mo; 95% CI 3.388-16.826) relative to patients with a PLT-PLR score of 1 (27.214 mo; 95% CI 0-56.253, p = 0.002) or 0 (58.893 mo; 95% CI 32.938-84.848, p < 0.001). In multivariate analysis, a PLT-PLR score of 2 was an independent prognostic factor for poor OS (hazard ratio (HR) 3.473; 95% CI 1.765-6.835, p < 0.001) and RFS (HR 2.286; 95% CI 1.243-4.206, p = 0.008) compared with a PLT-PLR score of 0. Preoperative PLT-PLR scores can be useful for predicting disease prognosis in patients with surgically resected NSCLC. Further large prospective studies will be necessary to validate our findings.


Fructooligosaccharide ameliorates high-fat induced intrauterine inflammation and improves lipid profile in the hamster offspring.
Maternal high-fat diet (HFD) often results in intrauterine and feto-placental inflammation, and increases the risks of fetal programming of metabolic diseases. Intake of prebiotic is reported beneficial. However, its effects on HFD during pregnancy and lactation is not known. We evaluated the maternal intake of fructooligosaccharide (FOS) and its impact on placental inflammation, offspring's adiposity, glucose, and lipid metabolism in their later life. Female Golden Syrian hamsters were fed with a control diet (CD, 26.4 % energy from fat) or HFD (60.7% energy from fat) in the presence or absence of FOS from preconception until lactation. All pups were switched over to CD after lactation and continued until the end. Placental inflammation was upregulated in HFD-fed dam, as measured by a high concentration of hsCRP in the serum and amniotic fluid. Neutrophil infiltration was significantly increased in the decidua through the chorionic layer of the placenta. The expression of pro-inflammatory cytokines such as COX2, NFκβ, IL-8, TGFβ mRNA was increased in the chorioamniotic membrane (P <.05). The HFD/CD hamsters had more adiposity, higher triglyceride, and low HDL at 12 months of age compared to CD/CD (P <.05). However, HFD+FOS/CD-fed hamsters prevented adverse effects such as placental inflammation, neutrophil infiltration, glucose, and lipid profiles in the offspring (P <.05). Anti-inflammatory and lipid-lowering effects of FOS may reduce placental inflammation by lowering neutrophil infiltration and decreasing the production of pro-inflammatory cytokines. Intake of FOS during pregnancy may be beneficial in maintaining lipid metabolism and preventing excess adiposity for mother and their offspring.


Dual-frequency impedance assays for intracellular components in microalgal cells.
Intracellular components (including organelles and biomolecules) at the submicron level are typically analyzed in situ by special preparation or expensive setups. Here, a label-free and cost-effective approach of screening microalgal single-cells at a subcellular resolution is available based on impedance cytometry. To the best of our knowledge, it is the first time that the relationships between impedance signals and submicron intracellular organelles and biomolecules are shown. Experiments were performed on Euglena gracilis (E. gracilis) cells incubated under different incubation conditions (i.e., aerobic and anaerobic) and 15 μm polystyrene beads (reference) at two distinct stimulation frequencies (i.e., 500 kHz and 6 MHz). Based on the impedance detection of tens of thousands of samples at a throughput of about 900 cells per second, three metrics were used to track the changes in biophysical properties of samples. As a result, the electrical diameters of cells showed a clear shrinkage in cell volume and intracellular components, as observed under a microscope. The morphology metric of impedance pulses (i.e., tilt index) successfully characterized the changes in cell shape and intracellular composition distribution. Besides, the electrical opacity showed a stable ratio of the intracellular components to cell volume under the cellular self-regulation. Additionally, simulations were used to support these findings and to elucidate how submicron intracellular components and cell morphology affect impedance signals, providing a basis for future improvements. This work opens up a label-free and high-throughput way to analyze single-cell intracellular components by impedance cytometry.


[Cutaneous manifestations of strongyloidosis].
Strongyloidiasis is a parasitic disease, caused by Strongyloides stercoralis, an intestinal nematode, which is mainly endemic in tropical and subtropical regions. It can be sporadically found in the temperate zone, especially in closed communities and among people living under bad social conditions. Gastrointestinal, pulmonary and cutaneous symptoms may arise during the migration of the larvae. The infections are chronic and poor in symptoms among immunocompetent patients. Sometimes the cutaneous manifestation is the only symptom of the disease besides the distinct eosinophilia. Intense itching, erythematosus papule and petechiae develop at the site of the skin infection. Rapidly progressing linear, serpiginous, urticarial streaks are the pathognomic cutaneous manifestations that are called larva currents. The appearance of erythematosus, linear stripes are due to the migrating larvae in the skin. The most common nonspecific symptoms are urticaria, maculopapular exanthema, localized or generalized pruritus and prurigo. The parasite is uniquely able to carry out its whole life cycle inside the human body, so in immunocompromised patients the disease can lead to a hyperinfection syndrome with high mortality, due to the accelerated endogenous autoinfection. Authors present all possible skin manifestations of the strongyloidiasis, based on the case history of three brothers and sisters and that of a female patient suffering from hyperinfection syndrome.


Facklamia sourekii sp. nov., isolated from human sources.
Two strains of a Gram-positive catalase-negative, facultatively anaerobic coccus originating from human sources were characterized by phenotypic and molecular taxonomic methods. The strains were found to be identical to each other based on 16S rRNA gene sequencing and constitute a new subline within the genus Facklamia. The unknown bacterium was readily distinguished from Facklamis hominis and Facklamia ignava by biochemical tests and electrophoretic analysis of whole-cell proteins. Based on phylogenetic and phenotypic evidence it is proposed that the unknown bacterium be classified as Facklamia sourekii sp. nov., the type strain of which is CCUG 28783AT.


Solvation influences flap collapse in HIV-1 protease.
HIV-1 protease (HIVp) is an important target for the development of therapies to treat AIDS and is one of the classic examples of structure-based drug design. The flap region of HIVp is known to be highly flexible and undergoes a large conformational change upon binding a ligand. Accurately modeling the inherent flexibility of the HIVp system is critical for developing new methods for structure-based drug design. We report several 3-ns molecular dynamics simulations investigating the role of solvation in HIVp flap rearrangement. Using an unliganded crystal structure of HIVp, other groups have observed flap reorganization on the nanosecond timescale. We have also observed rapid, initial flap movement, but we propose that it may be caused by system setup. The initial solvation of the system creates vacuum regions around the protein that may encourage large conformational deformities. By reducing the vacuum space created by the solvation routine, the observed flap collapse is attenuated. Also, a more thorough equilibration procedure preserves a more stable protein conformation over the course of the simulation.


Comprehensive Knowledge of Reservoir Hosts is Key to Mitigating Future Pandemics.
Coronavirus disease 2019 (COVID-19) and other epidemics (such as severe acute respiratory syndrome [SARS], Ebola, and H1N1) are stark reminders that knowledge of animal behavior and ecosystem health are key to controlling the spread of zoonotic diseases early in their onset. However, we have very limited information about the set of behavioral and ecological factors that promote viral spillover and the effects that has on ecosystem health and disease transmission. Thus, expanding our current knowledge of reservoir hosts and pandemics represents an urgent and critical tool in ecological epidemiology. We also propose to create an integrative database that ranks animal species in terms of their likelihood as hosts for specific infectious diseases. We call for a global and cooperative effort of field and laboratory scientists to create, maintain, and update this information in order to reduce the severity of future pandemics.


Why and how antipsychotic drugs are used in 40 Sydney nursing homes.
For decades there has been a high use of antipsychotic medication in nursing homes, though recently the use of typical antipsychotics has reduced while use of atypical antipsychotic medication has increased. The Australian government subsidises use of the latter in management of schizophrenia, and since April 2005 has subsidised use of risperidone (but still not the other atypicals) in cases of dementia with behavioural disturbance. This study was designed to examine the pattern of, and reasons for, antipsychotic use in a range of Sydney nursing homes. Clinical files and medication cards in 40 Sydney nursing homes were examined in late 2003 by a research nurse, who recorded documented diagnoses, blood glucose levels and use of medication in the previous 4 weeks. Antipsychotics were prescribed for 577 (25.1%) of the 2302 residents. Of these, 114 had schizophrenia. Of the 2302, 6.1% and 15.6%, respectively, had documented diagnoses of schizophrenia and/or diabetes. Of those with schizophrenia, 13.6% had diabetes. Two-thirds of those given antipsychotics had dementia or cerebral disease and not schizophrenia. Two-thirds of the antipsychotic prescriptions for residents with schizophrenia, and also for those without, were for atypicals (n = 200 olanzapine, 174 risperidone, 19 quetiapine). Blood glucose measurements had been recorded in less than 45%. In Sydney in 2003, most (80%) of the nursing home residents for whom antipsychotics were prescribed did not have a diagnosis of schizophrenia. The records suggested that insufficient attention had been given to the possibility that use of certain antipsychotics can be associated with impaired glucose metabolism.


Quality benchmarks for brain injury rehabilitation services.
Quality, a leading priority in health care today, must be quantified if a rehabilitation facility is to accurately evaluate its treatment effectiveness and durability. Quality can be seen as including four domains, or dimensions: accountability, professional staffing, value, and proven results. This article offers suggestions to rehabilitation case managers and discharge planners, who are in search of quality, on how to evaluate a brain injury rehabilitation program prior to referring patients to a facility.


Uterine distension media for outpatient hysteroscopy.
Hysteroscopy done in an outpatient setting is the 'gold standard' method for evaluating the uterine cavity. Media used to distend the uterine cavity include gas as carbon dioxide and liquid as saline that can be used at room temperature or warmed to body temperature. Both media offer advantages as well as disadvantages. The objective of this review is to compare the effectiveness, tolerability, and safety of gas (carbon dioxide) and liquid (normal saline) used for uterine distension during outpatient hysteroscopy. We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO on 28 April 2021. We checked references of relevant trials and contacted study authors and experts in the field to identify additional studies. CINAHL records and ongoing trials from the trial registries were included in the CENTRAL search. We included randomised controlled trials (RCTs) comparing saline with carbon dioxide, as well as RCTs comparing saline at different temperatures, for uterine distension in outpatient hysteroscopy done for any indication. We used standard methodological procedures recommended by Cochrane. Primary review outcomes were patient tolerability and adverse events or complications related to the distending medium. Secondary outcomes were quality of the hysteroscopic view and duration of the procedure. We included 12 RCTs (1946 women). The quality of evidence ranged from very low to high: the main limitations were risk of bias due to absence of blinding due to the nature of the procedure, imprecision, and inconsistency. Saline versus carbon dioxide Analysis ruled out a clinically relevant difference in pain scores during the procedure between saline and carbon dioxide, but the quality of evidence was low (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.17 to 0.02; 9 RCTs, N = 1705; I² = 86%). This translates to differences of 0.39 cm (lower) and 0.05 cm (higher) on a 10-cm visual analogue scale (VAS). Evidence was insufficient to show differences between groups in the proportion of procedures abandoned due to intense pain (Peto odds ratio (OR) 0.48, 95% CI 0.09 to 2.42; 1 RCT, N = 189; very low-quality evidence). We are uncertain whether saline decreases the need for analgesia compared to carbon dioxide (Peto OR 0.34, 95% CI 0.12 to 0.99; 1 RCT, N = 189; very low-quality evidence). Saline compared to carbon dioxide is probably associated with fewer vasovagal reaction events (Peto OR 0.53, 95% CI 0.32 to 0.86; 6 RCTs, N = 1076; I² = 0%; moderate-quality evidence) and fewer shoulder-tip pain events (Peto OR 0.28, 95% CI 0.14 to 0.54; 4 RCTs, N = 623; I² = 0%, moderate-quality evidence). Evidence suggests that if 10% of women undergoing outpatient hysteroscopy experience a vasovagal reaction event with the use of carbon dioxide, this rate would be between 3% and 9% with the use of saline. Similarly, if the rate of shoulder-tip pain with carbon dioxide is 9%, it would be between 1% and 5% with saline. We are uncertain whether saline is similar to carbon dioxide in terms of endometrial bleeding (Peto OR 0.83, 95% CI 0.25 to 2.75; 2 RCTs, N = 349; I² = 0%; very low-quality evidence). Infection was not reported by any study in this comparison. Saline may result in fewer procedures with an unsatisfactory hysteroscopic view than carbon dioxide (Peto OR 0.51, 95% CI 0.32 to 0.82; 5 RCTs, N = 1082; I² = 67%; low-quality evidence). The duration of the procedure was shorter with saline in three of the four studies that reported this outcome, and duration was similar in both arms in the fourth study. Warm saline versus room temperature saline Use of warm saline for uterine distension during office hysteroscopy may reduce pain scores when compared with room temperature saline (mean difference (MD) -1.14, 95% CI -1.55 to -0.73; 3 RCTs, N = 241; I² = 77%; low-quality evidence). Evidence is insufficient to show differences between groups in either the proportion of procedures abandoned due to intense pain (Peto OR 0.97, 95% CI 0.06 to 15.87; 1 RCT, N = 77; very low-quality evidence) or the need for analgesia (Peto OR 1.00, 95% CI 0.14 to 7.32; 1 RCT, N = 100; very low-quality evidence). Analysis ruled out a clinically relevant difference in duration of the procedure between warm and room temperature saline, but the quality of evidence is low (MD 13.17 seconds, 95% CI -12.96 to 39.29; 2 RCTs, N = 141; I² = 21%). No cases of infection were reported in either group (1 RCT, N = 100). No other adverse events and no information on quality of the hysteroscopic view were reported by any study in this comparison. Evidence was insufficient to show differences between different distension media used for uterine distension in outpatient hysteroscopy in terms of patient tolerability, operator satisfaction, or duration of the procedure. However, saline was superior to carbon dioxide in producing fewer adverse events (shoulder-tip pain and vasovagal reaction).


Fatty acid synthase - Modern tumor cell biology insights into a classical oncology target.
Decades of preclinical and natural history studies have highlighted the potential of fatty acid synthase (FASN) as a bona fide drug target for oncology. This review will highlight the foundational concepts upon which this perspective is built. Published studies have shown that high levels of FASN in patient tumor tissues are present at later stages of disease and this overexpression predicts poor prognosis. Preclinical studies have shown that experimental overexpression of FASN in previously normal cells leads to changes that are critical for establishing a tumor phenotype. Once the tumor phenotype is established, FASN elicits several changes to the tumor cell and becomes intertwined with its survival. The product of FASN, palmitate, changes the biophysical nature of the tumor cell membrane; membrane microdomains enable the efficient assembly of signaling complexes required for continued tumor cell proliferation and survival. Membranes densely packed with phospholipids containing saturated fatty acids become resistant to the action of other chemotherapeutic agents. Inhibiting FASN leads to tumor cell death while sparing normal cells, which do not have the dependence of this enzyme for normal functions, and restores membrane architecture to more normal properties thereby resensitizing tumors to killing by chemotherapies. One compound has recently reached clinical studies in solid tumor patients and highlights the need for continued evaluation of the role of FASN in tumor cell biology. Significant advances have been made and much remains to be done to optimally apply this class of pharmacological agents for the treatment of specific cancers.


Cerebrospinal fluid and plasma beta-endorphin in combat veterans with post-traumatic stress disorder.
Opioid-mediated analgesia develops in experimental animals following traumatic stress and increased opioid-mediated analgesia has been observed in combat veterans with post-traumatic stress disorder (PTSD). These observations have led to the hypothesis that increased central nervous system (CNS) opioidergic activity exists in patients with PTSD. However, direct CNS data on opioid peptide concentrations and dynamics in patients with PTSD are lacking. We withdrew cerebrospinal fluid (CSF) via a flexible, indwelling subarachnoid catheter over a 6-h period and determined hourly CSF concentrations of immunoreactive beta-endorphin (ir beta END) in 10 well-characterized combat veterans with PTSD and nine matched normal volunteers. Blood was simultaneously withdrawn to obtain plasma for ir beta END. PTSD symptom clusters, as measured by the CAPS, were correlated with neuroendocrine data. Mean CSF ir beta END was significantly greater in patients with PTSD compared with normals and there was a negative correlation between the ir beta END and PTSD intrusive and avoidant symptoms of PTSD. No intergroup difference between plasma ir beta END was found, nor was there a significant correlation between CSF and plasma ir beta END. Immunoreactive beta-lipotropin (ir beta LPH) and pro-opiomelanocortin (irPOMC), both precursors of beta END, were much more plentiful in human CSF than was beta-endorphin itself, as has been previously reported. It remains to be determined whether the increased CNS opioid concentrations predate traumatic stress, thereby conferring a vulnerability to dissociative states and PTSD itself, or result from the trauma. The negative correlation between CSF ir beta END and avoidant and intrusive symptoms suggests that CNS hypersecretion of opioids might constitute an adaptive response to traumatic experience. Poor correlation between CSF and plasma ir beta END limits use of plasma measures to assess CNS opioid activity.


Prolyl 4 hydroxylase: a critical target in the pathophysiology of diseases.
Prolyl 4 hydroxylases (P4H) are iron- and 2-oxoglutamate-dependent dioxygenase enzymes and hypoxia-inducible transcription factor (HIF)-P4Hs play a critical role in the regulating oxygen homeostasis in the local tissues as well in the systemic circulation. Over a period of time, a number of prolyl hydroxylase inhibitors and activators have been developed. By employing the pharmacological tools and transgenic knock out animals, the critical role of these enzymes has been established in the pathophysiology of number of diseases including myocardial infarction, congestive heart failure, stroke, neurodegeneration, inflammatory disease, respiratory diseases, retinopathy and others. The present review discusses the different aspects of these enzymes including their pathophysiological role in disease development.


Silaphenolates and silaphenylthiolates: two unexplored unsaturated silicon compound classes influenced by aromaticity.
Monosilicon analogs of phenolates and phenylthiolates are studied by quantum chemical calculations. Three different silaphenolates and three different silaphenylthiolates are possible; the ortho-, meta-, and para-isomers. For the silaphenolates, the meta-isomer is the thermodynamically most stable, regardless if the substituent R at Si is H, t-Bu or SiMe(3). However, with R = H and SiMe(3) the energy differences between the three isomers are small, whereas with R = t-Bu the meta-isomer is ~5 kcal/mol more stable than the ortho-isomer. For the silaphenylthiolates the ortho-isomer is of lowest energy, although with R = H the ortho- and meta-isomers are isoenergetic. The calculated nucleus independent chemical shifts (NICS) indicate that the silaphenolates and silaphenylthiolates are influenced by aromaticity, but they are less aromatic than the parent silabenzene. The geometries and charge distributions suggest that all silaphenolates and silaphenylthiolates to substantial degrees are described by resonance structures with an exocyclic C=O double bond and a silapentadienyl anionic segment. Indeed, they resemble the all-carbon phenolate and phenylthiolate. Silaphenylthiolates are less bond alternate and have slightly more negative NICS values than analogous silaphenolates, suggesting that this compound class is a bit more aromatic. Dimerization of the silaphenolates and silaphenylthiolates is hampered due to intramolecular Coulomb repulsion in the dimers, and silaphenolates with a moderately bulky SiMe(3) group as substituent at Si should prefer the monomeric form.


The study of the dynamics of the order parameter of coupled oscillators in the Ott-Antonsen scheme for generic frequency distributions.
The Ott-Antonsen ansatz shows that, for certain classes of distribution of the natural frequencies in systems of N globally coupled Kuramoto oscillators, the dynamics of the order parameter, in the limit N → ∞, evolves, under suitable initial conditions, in a manifold of low dimension. This is not possible when the frequency distribution, continued in the complex plane, has an essential singularity at infinity; this is the case, for example, of a Gaussian distribution. In this work, we propose a simple approximation scheme that allows one to extend also to this case the representation of the dynamics of the order parameter in a low dimensional manifold. Using the Gaussian frequency distribution as a working example, we compare the dynamical evolution of the order parameter of the system of oscillators, obtained by the numerical integration of the N equations of motion, with the analogous dynamics in the low dimensional manifold obtained with the application of the approximation scheme. The results confirm the validity of the approximation. The method could be employed for general frequency distributions, allowing the determination of the corresponding phase diagram of the oscillator system.


Systematics of the genus Capra inferred from mitochondrial DNA sequence data.
Traditional classification in the genus Capra is based mainly on horn morphology. However, previous investigations based on allozyme data are not consistent with this classification. We thus reexamined the evolutionary history of the genus by analyzing mitochondrial DNA (mtDNA) sequence variation. We collected bone samples from museums or dead animals found in the field. Thirty-four individuals were successfully sequenced for a portion of the mtDNA cytochrome b gene and control region (500 bp in total). We obtained a star-like phylogeny supporting a rapid radiation of the genus. In accordance with traditional classification, mtDNA data support the presence of two clades in the Caucasus and the hypothesis of a domestication event in the Fertile Crescent. However, in conflict with morphology, we found that C. aegagrus and C. ibex are polyphyletic species, and we propose a new scenario for Capra immigration into Europe.


Syncatalytic inactivation of prolyl 4-hydroxylase by synthetic peptides containing the unphysiologic amino acid 5-oxaproline.
Peptides containing the unphysiological amino acid 5-oxaproline (Opr) in the sequence R1-Xaa-Opr-Gly-OR2 were found to inactivate prolyl 4-hydroxylase from chick and human origins. Of the substances investigated, compounds with aromatic substituents R1 and R2 were particularly effective when compared with those with an aliphatic group or without a C-terminal blocking group. Both affinity of the individual peptides for the enzyme and partition ratio contributed to the differences in efficiency. Benzylcarbonyl-Phe-Opr-Gly-benzyl ester was the most effective substance tested, its concentration giving 50% inactivation in 1 h being 0.8 microM. Inactivation was only observed in the presence of 2-oxoglutarate and Fe2+. The Opr peptides enhanced the decarboxylation of 2-oxoglutarate by prolyl 4-hydroxylase, the Vmax values obtained with the individual peptides being positively correlated with their inactivating efficiency. Inactivation was prevented by high concentrations of peptide substrate and ascorbate. Lineweaver-Burk kinetics experiments suggested noncompetitive inhibition with respect to peptide substrate and ascorbate. Lysyl hydroxylase was not affected by Opr peptides in concentrations of up to 1.5 mM in either the presence or absence of prolyl 4-hydroxylase. The results suggest that the oxaproline compounds are specific syncatalytic inactivators of prolyl 4-hydroxylase.


Short bowel syndrome: epidemiology and etiology.
Pediatric short bowel syndrome (SBS) is most commonly caused by congenital or acquired conditions of the newborn. SBS is associated with an inability of the bowel to adequately absorb water and nutrients in sufficient quantities to meet caloric, fluid, and electrolyte demands, thus necessitating dependence on parenteral nutrition (PN). It is this dependence on PN, that is responsible for the majority of morbidity and mortality associated with SBS, including central venous catheter infections and PN-induced cholestatic liver dysfunction. There are very few estimates of SBS incidence and mortality in the literature. The epidemiology of SBS is reviewed and the limitations of the published literature are discussed.


Arrayed waveguide collimators for integrating free-space optics on polymeric waveguide devices.
Array-type optical devices are important for wavelength-division multiplexing optical communication system to achieve small footprint, mass production, and reliability. For fabricating transmitter module in an array configuration, it is difficult to achieve a passive alignment of isolator, collimating lens, and laser diode. To facilitate array isolator integration, a waveguide collimator is proposed in this work by using a low-contrast, large-core polymer waveguide. The diffraction of a guided mode propagating through a free-space region is suppressed by enlarging the guided mode. The fiber coupling loss due to the enlarged mode was overcome by incorporating an adiabatic taper structure. The excess loss of waveguide collimator including the loss through a 400-μm free-propagation region was less than 1.0 dB.


The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors.
Modern imaging modalities lead to frequent detection of adrenal masses, most of them incidental findings. Although the majority of adrenocortical and adrenomedullary tumors are benign, there are no reliable clinical and laboratory markers to distinguish most of them from malignant neoplasms. The molecular mechanisms underlying the pathogenesis of these tumors have recently begun to be unraveled. A fruitful avenue for the elucidation of tumorigenesis has been the study of adrenal tumors that are manifestations of hereditary or postzygotic genetic syndromes, because one knows the "first hit", i.e. the primary gene defect. In contrast, in sporadic adrenal tumors the first hit, possibly a somatic mutation of a tumor-related gene, is unknown, and therefore the sequence of genetic alterations is difficult to establish. In this article we review in addition to our own work the literature on molecular aspects of adrenocortical and adrenomedullary tumorigenesis.


[Internal coil trapping for a doughnut-shaped giant intracranial aneurysm: a case report].
We present the case of a 65-year-old woman with a doughnut-shaped giant intracranial aneurysm that was treated using endovascular internal coil trapping. She presented with a history of headache. Magnetic resonance imaging and cerebral angiography showed a doughnut-shaped giant intracranial aneurysm in the intracavernous portion of the internal cerebral artery. A microcatheter was placed distal to the internal cerebral artery, along the wall of the aneurysm. The aneurysm was then occluded by internal coil trapping without bypass surgery, because the outcome of the balloon occlusion test was acceptable. The aneurysm was completely obliterated without causing permanent neurological deficits.


Protozoan parasite aquaporins.
Protozoan parasites are a major threat to human health with millions of fatalities worldwide, especially in nonindustrialized countries. Currently, there is no cure for many of these parasitic diseases. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites. Aquaporins, members of membrane proteins discovered and characterized within the past 20 years, are the mechanism through which water is transported through living membranes. The presence of aquaporins explains disease etiology related to water physiology and presents new pharmacogenomic targets. In this article, we review the literature on aquaporins found in Apicomplexan, Kinetoplastida and Microsporidia parasites as potential drug targets. Furthermore, by analyzing protein motion dynamics, we identify impediments that need to be surmounted for developing effective drugs targeting the aquaglyceroporin of Plasmodium falciparum, the causative agent of the most fatal form of human malaria.


Characterization of the pierce two-node model under exercise load by parameter optimization toward construction of a modified thermal model for persons with spinal cord injury.
In this study, we attempted to develop a thermal model for estimating a body temperature in persons with spinal cord injury (SCI) during exercise. To clarify requisites for the SCI thermal model, we compared actual body temperature of SCI subjects with that calculated with a standard thermal model, that is, the Pierce two-node model. Model optimization by the parameter search method was able to fit the model-estimated skin and core temperature with those in able-bodied subjects during repeated exercise and rest. However, there remained a phase shift between actual and model-estimated core temperature trends in SCI subjects even after the optimization. The comparison of the optimized parameter combinations revealed that the Pierce two-node model was able to express loss of sweating in the SCI subjects, but unable to express delay in heat accumulation and dissipation. These results suggest that SCI thermal model requires additional nodes that express the speed and extent of heat transfer in the body of SCI persons.


Static and dynamic balance performance in patients with osteoporotic vertebral compression fracture.
Patients with osteoporotic vertebral compression fracture (OVCF) have postural changes and increased risk of falling. The aim of this study is to compare balance characteristics between patients with OVCF and healthy control subjects. Patients with severe OVCF and control subjects underwent computerised dynamic posturography (CDP) in this case-control study. Forty-seven OVCF patients and 45 controls were recruited. Compared with the control group, the OVCF group had significantly decreased average stability; maximal stability under the `eye open with swayed support surface' (CDP subtest 4) and 'eye closed with swayed support surface' conditions (subtest 5); and decreased ankle strategy during subtests 4 and 5 and under the `swayed vision with swayed support surface' condition (subtest 6). The OVCF group fell more frequently during subtests 5 and 6 and had longer overall reaction time and longer reaction time when moving backward during the directional control test. OVCF patients had poorer static and dynamic balance performance compared with normal control. They had decreased postural stability and ankle strategy with increased fall frequency on a swayed surface; they also had longer reaction times overall and in the backward direction. Therefore, we suggest balance rehabilitation for patients with OVCF to prevent fall.


First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia.
Previous studies report an association between vitamin D deficiency and hypertension, including the pregnancy-specific disorder preeclampsia. Circulating vitamin D is almost entirely bound to vitamin D binding protein, which increases 2-fold during pregnancy and previous studies have not examined vitamin D binding protein or free vitamin D levels. We performed a nested case-control study within the Massachusetts General Hospital Obstetric Maternal Study, measuring first trimester total 25-hydroxyvitamin D (25[OH]D) and vitamin D binding protein and calculating free 25(OH)D levels. We compared these levels from pregnancies complicated by subsequent preeclampsia (cases, n=39) with those from normotensive pregnancies (controls, n=131). First trimester total 25(OH)D levels were similar in cases and controls (27.4±1.9 versus 28.8±0.80 ng/mL; P=0.435). Despite an association between higher first trimester blood pressures and subsequent preeclampsia, first trimester total 25(OH)D was not associated with first trimester systolic (r=0.11; P=0.16) or diastolic blood pressures (r=0.03; P=0.72). Although there was a trend toward increased risk of preeclampsia with 25(OH)D levels <15 ng/mL (odds ratio: 2.5 [95% CI: 0.89 to 6.90]), this was attenuated after adjustment for body mass index and other covariates (odds ratio: 1.35 [95% CI: 0.40 to 4.50]). First trimester vitamin D binding protein and free 25(OH)D levels were similar in cases and controls and were not associated with first trimester blood pressures. These data suggest that first trimester total and free 25(OH)D levels are not independently associated with first trimester blood pressure or subsequent preeclampsia.


Single-stage operation for giant substernal goiter with severe coronary artery disease.
A 76-year-old female, with a history of asthma and tracheal bronchitis, presented with a non-ST elevation, myocardial infarction. Chest x-ray on admission showed a widened mediastinum, which was further evaluated with a computed tomography (CT) scan. It disclosed a giant substernal goiter compressing the trachea and the ascending aorta. Cardiac catheterization showed significant coronary disease unsuitable for percutaneous intervention; thus, the patient was scheduled for coronary artery bypass grafting. Single stage thyroidectomy immediately followed by coronary artery bypass was performed. After surgery, her upper airway symptoms were improved, and no cardiac events were noted. Collaboration between otolaryngology and thoracic surgery teams contributed to good outcomes for this patient with substernal goiter and severe cardiac disease.


Exosomes and immune surveillance of neoplastic lesions: a review.
The immune system has been reported to suppress the development and progression of neoplastic lesions; however, the exact mechanisms by which neoplastic lesions and the immune system interact are not well understood. Within the last decade, tiny membrane bound particles, approximately 30-100 nm in diameter, have been observed in the blood and other body fluids. These particles, currently called exosomes, are released from many types of tissues including tumors, and they contain and carry many proteins, and mRNAs and microRNA species. We review here how tumors suppress the immune system, especially by the formation of exosomes. Exosomes released from tumors are carried in part by the vascular system to distant cells, which phagocytose them. Depending on the proteins, mRNAs or microRNAs in the exosomes and the cell type, phagocytosis of exosomes may provide a modulating signal to the cell. In the case of exosomes from tumors, uptake of the exosomes by cells of the immune system has been reported to have three main effects: 1) suppression of the number and activity of natural killer cells, 2) suppression of the activity of T cells and 3) suppression of the number and maturation of mature dendritic cells.


Refractory plasmonics with titanium nitride: broadband metamaterial absorber.
A high-temperature stable broadband plasmonic absorber is designed, fabricated, and optically characterized. A broadband absorber with an average high absorption of 95% and a total thickness of 240 nm is fabricated, using a refractory plasmonic material, titanium nitride. This absorber integrates both the plasmonic resonances and the dielectric-like loss. It opens a path for the interesting applications such as solar thermophotovoltaics and optical circuits.


Improving Walking Economy With an Ankle Exoskeleton Prior to Human-in-the-Loop Optimization.
Lower limb robotic exoskeletons have shown the capability to enhance human locomotion for healthy individuals or to assist motion rehabilitation and daily activities for patients. Recent advances in human-in-the-loop optimization that allowed for assistance customization have demonstrated great potential for performance improvement of exoskeletons. In the optimization process, subjects need to experience multiple types of assistance patterns, thus, leading to a long evaluation time. Besides, some patterns may be uncomfortable for the wearers, thereby resulting in unpleasant optimization experiences and inaccurate outcomes. In this study, we investigated the effectiveness of a series of ankle exoskeleton assistance patterns on improving walking economy prior to optimization. We conducted experiments to systematically evaluate the wearers' biomechanical and physiological responses to different assistance patterns on a lightweight cable-driven ankle exoskeleton during walking. We designed nine patterns in the optimization parameters range which varied peak torque magnitude and peak torque timing independently. Results showed that metabolic cost of walking was reduced by 17.1 ± 7.6% under one assistance pattern. Meanwhile, soleus (SOL) muscle activity was reduced by 40.9 ± 19.8% with that pattern. Exoskeleton assistance changed maximum ankle dorsiflexion and plantarflexion angle and reduced biological ankle moment. Assistance pattern with 48% peak torque timing and 0.75 N·m·kg -1 peak torque magnitude was effective in improving walking economy and can be selected as an initial pattern in the optimization procedure. Our results provided a preliminary understanding of how humans respond to different assistances and can be used to guide the initial assistance pattern selection in the optimization.


Vitamin D - current stage of knowledge about analysis and supplementation.
Nowadays, topics related to the proper nutrition of the body, which requires a complex of compounds and supplementation of these ingredients have undoubtedly gained popularity, so it should come as no surprise that there is a widespread interest in vitamin D in science, medicine, analytics and nutrition. In the world of developing technologies, new directions of physiological action of this vitamin on the body are being discovered. Issues related to the demand for vitamin D in various populations and its sources in food, the appropriate form of supplementation, safety and toxicity are extremely important. The present manuscript focuses on the concise evaluation of key data in the field of vitamin D. Structure and physicochemical properties, demand and delivery trails, deficiency and its diagnosis, supplementation, interactions of vitamin D with supplements and drugs are discussed. Attention has also been paid to the methods of vitamin D analysis in various matrices, which allow for an accurate and precise quality assessment of dietary supplements, drugs and food products. The presented information allows deeper understanding of the mechanisms responsible for the development of many diseases in the context of vitamin D levels.


4-Methylumbelliferyl glycosides of N-acetyl 4-thiochito-oligosaccharides as fluorogenic substrates for chitodextrinase from Vibrio furnissii.
The degradation of chitin involves a diverse array of enzymes, some with overlapping substrate specificities. In order to distinguish between different types of enzymes, specific substrates are needed. Toward this end, two new fluorogenic substrates containing thio-glycosidic linkages, 4-methylumbelliferyl N,N'-diacetyl-4-thio-beta-chitobioside (Mu-TCB) and N,N',N"-triacetyl-4,4'-dithio-beta-chitotrioside (Mu-TCT) are described. The substitution of the glycosidic oxygens (except the one that links oligosaccharide with the fluorogenic aglycon) with a sulfur atom resulted in resistance of these compounds to N-acetyl-beta-hexosaminidases while they were specific substrates for the newly discovered chitodextrinase from Vibrio furnissii (Keyhani,N.O. and Roseman,S. (1996) J. Biol. Chem., 271, 33414-33424) and some bacterial chitinases. The enzyme kinetics of these 4-S-linked substrates, Mu-TCB and Mu-TCT, as well as the O-linked 4-methylumbelliferyl N,N'-diacetyl-beta-chitobioside (Mu-CB) and N,N',N"-triacetyl-beta-chitotrioside (Mu-CT) with the chitodextrinase were studied and compared. The usefulness of the substrates for screening for chitodextrinase and/or chitinase activity was demonstrated.


Fate and removal of antibiotics and antibiotic resistance genes in hybrid constructed wetlands.
Hybrid design and artificial aeration has been widely applied in wetlands, but little is known about their effectiveness in the removal of antibiotics and antibiotic resistance genes (ARGs). Here we investigated the performance of various mesocosm-scale constructed wetlands (CWs) with artificial aeration and hybrid design in removal of antibiotics and ARGs from antibiotics-spiked domestic sewage. Four hybrid constructed wetland systems with zeolite as substrate and Iris tectorum Maxim as plant were set up to have different artificial aeration designs. The aqueous removal efficiencies of total antibiotics ranged from 87.4% to 95.3%, while those of total ARGs varied from 87.8% to 99.1%. The mass removal of antibiotics by the CWs was attributed mainly to the microbial degradation. The present study imply that sorption of substrates and biological processes could be the two main mechanisms for ARGs elimination. The results from this study showed the hybrid CWs with artificial aeration could enhance treatment efficiencies of antibiotics and ARGs as well as conventional pollutants.


Sirolimus use in patients with subglottic stenosis in the context of granulomatosis with polyangiitis (GPA), suspected GPA, and immunoglobulin G4-related disease.
Objective: Subglottic stenosis (SGS) is a severe, life-threatening disease found in immune-mediated diseases such as granulomatosis with polyangiitis (GPA) and in rare cases of immunoglobulin G4 (IgG4)-related disease. It can result in persistent airway compromise due to the fibrotic response following inflammation. Standard management involves repeated endoscopic interventions to dilate the airway, and tracheostomy is occasionally required. In addition, immunosuppression remains a cornerstone of therapy aimed at controlling the underlying inflammatory disease; however, cumulative dosing leads to significant adverse effects. We present five cases of predominantly anti-neutrophil cytoplasmic antibody-negative GPA and a case of IgG4-related disease with SGS, in whom we evaluated the long-term utility of sirolimus, which has beneficial anti-proliferative and fibrotic effects, in the management of their disease. Method: We conducted a retrospective review of a cohort of patients with SGS at a tertiary vasculitis unit. These patients were treated with sirolimus, in addition to conventional medical and endoscopic treatment. Clinical symptoms, frequency and time to endoscopic intervention pre- and post-treatment, additional rescue therapy, and any adverse effects were recorded and analysed. Results: Six patients were treated with sirolimus and followed for up to 9 years; two discontinued the drug owing to adverse effects, early on. In the remaining four patients, glucocorticoids were withdrawn, and the frequency of endoscopic intervention was reduced. One patient on sirolimus required rituximab therapy for disease flare. Conclusion: Sirolimus may be a therapeutic option for some patients with severe SGS, allowing steroid withdrawal and resulting in a positive adverse effect profile.


Sense of coherence in patients with inflammatory bowel disease.
Background and Aim. Sense of coherence (SOC) is a health-promoting concept reflecting a person's view of life and response to stressful situations and may be of importance in coping with chronic illness. The aim of this study was to explore associations between SOC and sociodemographic, disease-related, and personal characteristics in a sample of patients with inflammatory bowel disease (IBD). Methods. Measures included sociodemographic and disease-related data, the Sense of Coherence Scale, General Self-Efficacy Scale (GSE), and Fatigue Severity Scale (FSS-5). Results. In total, 428 IBD patients had evaluable questionnaires (response rate 93%). The overall mean SOC total score was 66.25 (SD 11.47) and with no statistically significant difference between patients with ulcerative colitis (UC) and patients with Crohn's disease (CD). In the multivariate analyses, higher GSE scores were significantly associated with higher SOC scores and higher FSS-5 scores were significantly associated with lower SOC scores in both UC and CD. Conclusion. GSE and FSS-5 contributed more to the variance in SOC than sociodemographic and disease-related variables. Longitudinal studies are warranted to investigate the value of SOC as a predictor of disability, medication adherence, coping behavior, and health-related quality of life.


Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells.
Insulin exerts a vasodilatory effect through the release of nitric oxide (NO) from the endothelium. We have recently demonstrated that insulin also inhibits the expression of intracellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), 2 major proinflammatory mediators, by human aortic endothelial cells (HAEC) and the proinflammatory mediator, nuclear factor (NF-kappa B), in the nucleus in parallel with an increase in endothelial nitric oxide synthase (e-NOS) expression. The inhibition of ICAM-1 by insulin is NO dependent. Because tumor necrosis factor-alpha (TNF-a ) is proinflammatory and may thus inhibit the action of insulin at the endothelial cell level, we have now investigated whether TNF-a affects (1) insulin receptor content; (2) insulin receptor (IR) autophosphorylation induced by insulin, and (3) e-NOS expression by the endothelial cells. TNF-alpha (1 to 5 ng/mL) caused e-NOS inhibition in a dose-dependent fashion as measured by Western blotting. This inhibition was reduced with insulin addition. TNF-alpha also inhibited tyrosine autophosphorylation of the IR in HAEC induced by insulin and reduced IR beta-subunit protein expression in HAEC. These effects of insulin and TNF-alpha were independent of cell proliferation, as cell counts did not change with insulin or TNF-alpha. Our data demonstrate that TNF-alpha may exert its effect by inhibiting IR autophosphorylation in HAEC and also by reducing IR protein (IRP) expression. Although the inhibition of IR autophosphorylation by TNF-alpha is known to occur at the adipocyte level, the data on the inhibitory effect of TNF-alpha on insulin-induced e-NOS expression and IRP contents are novel.


PGP repository: a plant phenomics and genomics data publication infrastructure.
Plant genomics and phenomics represents the most promising tools for accelerating yield gains and overcoming emerging crop productivity bottlenecks. However, accessing this wealth of plant diversity requires the characterization of this material using state-of-the-art genomic, phenomic and molecular technologies and the release of subsequent research data via a long-term stable, open-access portal. Although several international consortia and public resource centres offer services for plant research data management, valuable digital assets remains unpublished and thus inaccessible to the scientific community. Recently, the Leibniz Institute of Plant Genetics and Crop Plant Research and the German Plant Phenotyping Network have jointly initiated the Plant Genomics and Phenomics Research Data Repository (PGP) as infrastructure to comprehensively publish plant research data. This covers in particular cross-domain datasets that are not being published in central repositories because of its volume or unsupported data scope, like image collections from plant phenotyping and microscopy, unfinished genomes, genotyping data, visualizations of morphological plant models, data from mass spectrometry as well as software and documents.The repository is hosted at Leibniz Institute of Plant Genetics and Crop Plant Research using e!DAL as software infrastructure and a Hierarchical Storage Management System as data archival backend. A novel developed data submission tool was made available for the consortium that features a high level of automation to lower the barriers of data publication. After an internal review process, data are published as citable digital object identifiers and a core set of technical metadata is registered at DataCite. The used e!DAL-embedded Web frontend generates for each dataset a landing page and supports an interactive exploration. PGP is registered as research data repository at BioSharing.org, re3data.org and OpenAIRE as valid EU Horizon 2020 open data archive. Above features, the programmatic interface and the support of standard metadata formats, enable PGP to fulfil the FAIR data principles-findable, accessible, interoperable, reusable.Database URL:http://edal.ipk-gatersleben.de/repos/pgp/.


Fenton-Inspired C-H Functionalization: Peroxide-Directed C-H Thioetherification.
Substoichiometric iron mediates the thioetherification of unactivated aliphatic C-H bonds directed by resident silylperoxides. Upon exposure to a catalytic amount of iron(II) triflate, TIPS-protected peroxides bearing primary, secondary, and tertiary C-H sites undergo chemoselective thioetherification of remote C-H bonds with diaryl disulfides. The reaction demonstrates a broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic experiments suggest that the reaction proceeds through 1,5-H atom abstraction by a hydroxyl radical generated with iron.


Lupus enteritis: from clinical findings to therapeutic management.
Lupus enteritis is a rare and poorly understood cause of abdominal pain in patients with systemic lupus erythematosus (SLE). In this study, we report a series of 7 new patients with this rare condition who were referred to French tertiary care centers and perform a systematic literature review of SLE cases fulfilling the revised ACR criteria, with evidence for small bowel involvement, excluding those with infectious enteritis. We describe the characteristics of 143 previously published and 7 new cases. Clinical symptoms mostly included abdominal pain (97%), vomiting (42%), diarrhea (32%) and fever (20%). Laboratory features mostly reflected lupus activity: low complement levels (88%), anemia (52%), leukocytopenia or lymphocytopenia (40%) and thrombocytopenia (21%). Median CRP level was 2.0 mg/dL (range 0-8.2 mg/dL). Proteinuria was present in 47% of cases. Imaging studies revealed bowel wall edema (95%), ascites (78%), the characteristic target sign (71%), mesenteric abnormalities (71%) and bowel dilatation (24%). Only 9 patients (6%) had histologically confirmed vasculitis. All patients received corticosteroids as a first-line therapy, with additional immunosuppressants administered either from the initial episode or only in case of relapse (recurrence rate: 25%). Seven percent developed intestinal necrosis or perforation, yielding a mortality rate of 2.7%. Altogether, lupus enteritis is a poorly known cause of abdominal pain in SLE patients, with distinct clinical and therapeutic features. The disease may evolve to intestinal necrosis and perforation if untreated. Adding with this an excellent steroid responsiveness, timely diagnosis becomes primordial for the adequate management of this rare entity.


Cluster randomized trial comparing school-based mass drug administration schedules in areas of western Kenya with moderate initial prevalence of Schistosoma mansoni infections.
Mass drug administration (MDA) using praziquantel is the WHO-recommended approach for control of schistosomiasis. However, few studies have compared the impact of different schedules of MDA on the resultant infection levels. We wished to evaluate whether annual MDA was more effective than less frequent treatments for reducing community-level prevalence and intensity of Schistosoma mansoni infections. We performed a cluster randomized trial (ISRCTN 14849830) of 3 different MDA frequencies over a 5 year period in 75 villages with moderate (10%-24%) initial prevalence of S. mansoni in school children in western Kenya. Praziquantel was distributed by school teachers to students either annually, the first 2 years, or every other year over a 4 year period. Prevalence and intensity of infection were measured by stool examination in 9-12 year old students using the Kato-Katz method at baseline, each treatment year, and for the final evaluation at year 5. S. mansoni prevalence and intensity were also measured in first year students at baseline and year 5. Twenty-five schools were randomly assigned to each arm. S. mansoni prevalence and infection intensity in 9-12 year old students significantly decreased within each arm from baseline to year 5 but there were no differences between arms. There were no differences in infection levels in first year students either within or between arms. Strategies employing 2 or 4 rounds of MDA had a similar impact in schools with moderate initial prevalence, suggesting that schistosomiasis control can be sustained by school-based MDA, even if provided only every other year.


Pharmaceutical treatment of obesity.
The prevalence of obesity in America has increased steadily in the past 7 decades, especially in the last decade. Health factors that lead to obesity are discussed. This article focuses on the treatment of obesity and potential results.


Neuroimaging studies of emotional responses in PTSD.
Neuroimaging research offers a powerful and noninvasive means to understand healthy as well as dysregulated emotional processing in healthy subjects and PTSD patients. Functional neuroimaging findings suggest specific roles for subregions of the medial prefrontal (mPFC), orbito frontal (OFC), anterior cingulate (ACC), and insular cortices as well as the sublenticular extended amygdala (SLEA) and hippocampus in various components of emotional processing. Some of the same regions appear to be associated with emotional response to trauma, and with symptom formation in PTSD. Neuroimaging findings of emotional processing in healthy subjects and PTSD patients are discussed, addressing the specific roles of cortical regions like mPFC, ACC, and insula, and their potential contribution to PTSD pathophysiology. Processes of cognitive-emotional interactions and social emotions are discussed in an attempt to synthesize the prefrontal findings in healthy subjects and PTSD patients. Further links between functional neuroanatomy of emotional responses and neuroendocrine stress regulation are proposed.


[Soft tissue necrotizing infection].
Necrotizing fasciitis and gas gangrene represent a rapidly progressive and fatal tissue infection in the absence of early multidisciplinary treatment. There are multiple risk factors, but diabetes remains the main one. The presence of crackles or extensive lesions are an indication for exploration and surgical treatment. Conservative management is associated with zero survival. Iconography, biology or bacteriology can help in the diagnosis, but the latter is only made during surgery. The associated mortality is high, despite appropriate management. We report here the case of a diabetic patient requiring insulin, having presented this pathology, the starting point of which is a traumatic wound, with an extensive acute course, contra-indicating any surgical procedure.


A case of gas gangrene in an immunosuppressed Crohn's patient.
Clostridium septicum (C. septicum) gas gangrene is well documented in the literature, typically in the setting of trauma or immunosuppression. In this paper, we report a unique case of spontaneous clostridial myonecrosis in a patient with Crohn's disease and sulfasalazine-induced neutropenia. The patient presented with left thigh pain, vomiting and diarrhea. Blood tests demonstrated a profound neutropenia, and magnetic resonance imaging of the thigh confirmed extensive myonecrosis. The patient underwent emergency hip disarticulation, followed by hemicolectomy. C. septicum was cultured from the blood. Following completion of antibiotic therapy, the patient developed myonecrosis of the right pectoral muscle necessitating further debridement, and remains on lifelong prophylactic antibiotic therapy.


[Laparoscopic appendicectomy: an 8-year clinical experience].
For more than a century, open appendectomy through a laparotomy has been the golden standard for the surgical removal of the appendix. Nowadays, many surgeons question the utility of laparoscopic surgery to perform appendectomies because it is commonly stated that the appendix can be removed through a small surgical incision carrying a minimal surgical trauma to the patient. Although open appendectomy is really safe, on the other hand it carries a considerable risk of postoperative complications, is associated with postoperative pain and affects patient s normal activity. Laparoscopic appendectomy was first described in 1983 and, in many studies, it is described to be better than open standard technique for the treatment of appendiceal diseases. The aim of the present study is the retrospective analysis of laparoscopic appendectomies performed in a 8-year period. The authors report on 129 patients who underwent laparoscopic appendectomy. Conversion rate was 0.7 %, while the laparoscopic procedure was completed in 96 female and 32 male patients. The position of the appendix was behind the cecum in 37 cases, associate diseases were found in 15 cases. Mean operative time was 51 minutes; kind of laparoscopic instrumentation affected the operation time. Histologically there were 71 (55.5 %) focal appendicitis, 22 (17.1 %) suppurative appendicitis, 11 (8.6 %) gangrenous appendicitis, 18 (14.1 %) chronic appendicitis showing signs of previous suppurative episodes and 6 (4.7 %) normal appendix. There were neither in-hospital morbidity nor mortality. Follow-up showed reduced postoperative pain, short hospital stay, fast return to complete social activity. The authors conclude that laparoscopic technique can be considered a safe and effective procedure for the removal of the appendix as it has the advantage of allowing faster postoperative recovery; moreover the author recommend a wider and routinely use for appendectomy.


[Pharmacokinetics and electrolyte balance following administration of furosemide in pregnant women with E gestosis].
In pregnant women with E-gestosis distribution and elimination of furosemid are significantly different to a non-pregnant control group. Furosemid guarantees a rapid and safe excretion of edemas. The efficiency of furosemid concerning electrolyte excretion is stronger in pregnant women with E-gestosis than in nonpregnant women. Therefore furosemide should be administered to pregnant women under intensive electrolyte control only.


Complementation between nucleotide binding domains in an anion-translocating ATPase.
The catalytic component of the oxyanion-translocating ATPase of the plasmid-encoded ars operon of Escherichia coli is a homodimer of the ArsA protein. This enzyme is an oxyanion-stimulated ATPase with two consensus nucleotide binding sequences in each subunit, one in the N-terminal (A1) half and one in the C-terminal (A2) half of the ArsA protein. The two halves of both the arsA gene and the ArsA protein exhibit similar nucleotide and amino acid sequences, respectively. The two halves of the arsA gene were subcloned into compatible plasmids. Neither alone was sufficient to confer resistance, but cells in which the arsA1 and arsA2 half genes were coexpressed were resistant to arsenicals. Genetic complementation was also observed in cells bearing plasmids with point mutations in the two halves of the arsA gene and between cells with plasmids carrying combinations of the arsA1 or arsA2 subclones and point mutations. In every case, complementation was observed only when one plasmid contained a wild-type arsA1 sequence and the other contained a wild-type arsA2 sequence. These results demonstrate that both sites are required for resistance but that the two nucleotide binding domains need not reside in a single polypeptide. We propose a model in which the ArsA dimer has two catalytic units, each composed of an A1 domain from one monomer and an A2 domain from the other monomer.


Does dialysis modality influence the oxidative stress of uremic patients?
Since peritoneal membrane is more compatible and residual renal function better preserved during peritoneal dialysis, we questioned whether the oxidative burden in chronic kidney disease (CKD) is influenced by dialysis modality. 49 stable CKD patients, 17 on continuous ambulatory peritoneal dialysis (CAPD), 16 on hemodialysis (HD), and 16 non-dialyzed, and 13 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS; nmol/g protein), serum total antioxidant activity (TAA), total plasma-free thiols (Pt-SH; μmol/g protein), albumin and uric acid were measured by spectrophotometry. Serum residual antioxidant activity (RAA) was calculated. TBARS were higher in HD (78.3 ± 20.3) versus both non-dialyzed (53.1 ± 27.9, p = 0.007) and CAPD groups (58.3 ± 19.8, p = 0.008). Pt-SH was reduced in CKD patients, but showed comparable values between dialysis groups. TAA and RAA were similarly increased in HD and CAPD patients than in the other two groups. Oxidative stress occurs in all CKD patients and worsens as renal function declines. Lipid peroxidation seems more augmented during chronic HD as compared to CAPD, but the plasma antioxidant status did not differ between the investigated dialysis methods. Therefore, dialysis modality appears to influence lipid peroxidation without changing the extracellular antioxidant defense of CKD patients.


Appearance of hyperostosis frontalis interna on indium-111 leukocyte scans: potential diagnostic pitfall.
The appearance of hyperostosis frontalis interna on an [111In]leukocyte scan is reported. Recognition of the potential for normal accumulation of 111In-labeled white blood cells within this common process involving the skull is necessary to avoid misdiagnosis.


Generating a multi-mode vortex beam based on spoof surface plasmon polaritons.
The vortex beam provides a promising alternative for next-generation wireless communication, but it is a long-standing challenge to generate a multi-mode and robust vortex beam. In this Letter, a multi-mode vortex beam emitter is introduced and experimentally verified based on spoof surface plasmon polaritons (SSPP). The SSPP on a helical grating carries multi-mode orbital angular momentum and can be converted into a high-purity vortex beam via the diffraction of a ring array. The operation frequency and topological charge are determined by that of the SSPP. This emitter can achieve the function of beam-scanning in each radiation band. The beam-scanning and vortex characteristics are experimentally verified. The designed emitter is compact and robust, and we are confident that this work will have great application prospects in communication systems.


A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes.
Fatty acids play a vital role in glucose homeostasis; however, studies on habitual dietary fat intakes and gestational diabetes mellitus (GDM) risk are limited and provide conflicting findings. We determined whether the total amount and the type and source of prepregnancy dietary fats are related to risk of GDM. A prospective study was conducted in 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses' Health Study II. In these women, 860 incident GDM cases were reported. The adjusted RR of GDM was estimated for quintiles of total fat, specific fat, and the source of fat intakes by pooled logistic regression. Higher animal fat and cholesterol intakes were significantly associated with increased GDM risk. Across increasing quintiles of animal fat, RRs (95% CIs) for GDM were 1.00 (reference), 1.55 (1.20, 1.98), 1.43 (1.09, 1.88), 1.40 (1.04, 1.89), and 1.88 (1.36, 2.60) (P-trend = 0.05). Corresponding RRs (95% CIs) for dietary cholesterol were 1.00 (reference), 1.08 (0.84, 1.32), 1.02 (0.78, 1.29), 1.20 (0.93, 1.55), and 1.45 (1.11, 1.89) (P-trend = 0.04). The substitution of 5% of energy from animal fat for an equal percentage of energy from carbohydrates was associated with significantly increased risk of GDM [RR (95% CI): 1.13 (1.08, 1.18); P < 0.0001]. No significant associations were observed between dietary polyunsaturated fat, monounsaturated fat, or trans fat intakes and GDM risk. Higher prepregnancy intakes of animal fat and cholesterol were associated with elevated GDM risk.


Simplifying screening for osteoporosis in Australian primary care: the Prospective Screening for Osteoporosis; Australian Primary Care Evaluation of Clinical Tests (PROSPECT) study.
Although bone density by dual-energy x-ray absorptiometry (DXA) is the standard measure for the diagnosis of osteoporosis, as a screening tool, it has significant cost and availability of DXA is not universal. Prospective Screening for Osteoporosis; Australian Primary Care Evaluation of Clinical Tests (PROSPECT) was a national study undertaken to establish an effective prescreening protocol to be used in primary care facilitating targeted radiological investigation for osteoporosis in older women. Two hundred sixty-seven primary care physicians recruited 2,466 women 70 years and older who had no previous diagnosis of osteoporosis in a community-based cross-sectional study. The main outcome measures used were lumbar spine and femoral neck T-scores on DXA and presence of a vertebral fracture on thoracolumbar x-ray. Participant characteristics, gap-on-wall occiput test, and rib-to-pelvis distance measurements were provided by each primary care physician. Of the study population, 21.8% (95% CI, 19.9%-23.8%) had osteoporosis of the femoral neck and/or lumbar spine based on DXA, and 24.7% (95% CI, 22.5%-26.9%) had at least one vertebral fracture. Only 7.3% (95% CI, 6.2%-8.3%) had both osteoporosis and radiological vertebral fracture. Univariate and multivariate regression modeling of the demographic and clinical data collected resulted in a three-factor predictive tool for the diagnosis of osteoporosis and/or vertebral fracture that included the following variables: rib-pelvis distance greater than 2 fingerbreadths (yes/no), ever use of estrogen for more than 6 months (yes/no), and body mass index (<25, 25-30, >30 kg/m²). Only screening women classified as moderate to high risk by the tool DXA plus plain x-ray would then result in 14% of women 70 years or older who were not being screened, with 93% of cases being detected. The Prospective Screening for Osteoporosis; Australian Primary Care Evaluation of Clinical Tests tool will contribute to the diagnosis and management of osteoporosis by facilitating targeted screening and hence reducing the need for unnecessary radiology tests at the primary care level.


[Study on the blood concentration and clinical efficacy of ceftazidime, a cephem antibiotic at dose of one gram q.i.d, for adult hospital-acquired pneumonia patients].
Ceftazidime (CAZ), a cephem antibiotic for injection, was administered at dose of one gram q.i.d. to adult hospital-acquired pneimonia patients, and the clinical efficacy and blood concentration of CAZ was studied in five cases. The assessment of clinical efficacy was "efficacy" in all cases, and early improvement of examination value including body temperature, the value of CRP, and white blood cell counts were obtained. Abnormality of hepatic function as adverse effect was noted in two cases. However, the severity was mild and didn't affect the treatment in both cases. The maximum drug concentration immediately after the end of infusion was 72.1-176.5 microg/mL (median, 82.7 microg/mL) and the trough level was 5.1-72.1 microg/mL (median, 26.6 microg/mL), therefore the blood concentration was maintained a higher level than the MIC of bacteria estimated to be causative. From these results, administration method of ceftazidime one gram q.i.d. was considered to be a good way with increase of drug efficacy by maintaining highly blood concentration over prolonged period, and expected to be a good effect for hospital-acquired pneumonia.


Differential and redundant functions of gooseberry and gooseberry neuro in the central nervous system and segmentation of the Drosophila embryo.
The gooseberry locus of Drosophila consists of two homologous Pax genes, gooseberry neuro (gsbn) and gooseberry (gsb). Originally characterized by genetics as a single segment-polarity gene, its role in segmentation has been enigmatic, as only deficiencies uncovering both genes showed a strong segmentation phenotype while mutants of gsb did not. To solve this conundrum and assay for differential roles of gsbn and gsb, we have obtained by homologous recombination for the first time null mutants of either gene as well as a deficiency inactivating only gsbn and gsb. Our analysis shows that (i) gsbn null mutants are subviable while all surviving males and most females are sterile; (ii) gsb and gsbn share overlapping functions in segmentation and the CNS, in which gsbn largely, but not completely depends on the transcriptional activation by the product of gsb; (iii) as a consequence, in the absence of gsbn, gsb becomes haploinsufficient for its function in the CNS, and gsbn(-/-)gsb(-/+) mutants die as larvae. Such mutants display defects in the proper specification of the SNa branch of the segmental nerve, which appears intact in gsbn(-/-) mutants. Lineage analysis in the embryonic CNS showed that gsbn is expressed in the entire lineage derived from NB5-4, which generates 4 or 5 motoneurons whose axons are part of the SNa branch and all of which except one also express BarH1. Analysis of gsbn(-/-)gsb(-/+) clones originating from NB5-4 further suggests that gsb and gsbn specify the SNa fate and concomitantly repress the SNc fate in this lineage and that their products activate BarH1 transcription. Specification of the SNa fate by Gsb and Gsbn occurs mainly at the NB and GMC stage. However, the SNa mutant phenotype can be rescued by providing Gsbn as late as at the postmitotic stage. The hierarchical relationship between gsb and gsbn, the haploinsufficiency of gsb in gsbn mutants, and their redundant roles in the epidermis and CNS are discussed. A model is proposed how selection for both genes occurred after their duplication during evolution.


In vitro and in vivo influence of adjunct clarithromycin on the treatment of mucoid Pseudomonas aeruginosa.
Recent in vitro and in vivo data have substantiated the beneficial effects of macrolides/ azalides for use against Pseudomonas aeruginosa. While macrolides/azalides are not very potent in vitro antimicrobial agents against this pathogen, they appear to have an adjunctive role by either altering the course of infection owing to their inhibition of biofilm production or modulation of the host anti-inflammatory response, or both. To determine the in vitro and in vivo effects of clarithromycin as adjunctive therapy with ceftazidime against a mucoidproducing strain of P. aeruginosa, we performed a standard time-kill experiment and a pneumonia model in mice, respectively. Time-kill studies were performed over a 24 h period with varying concentrations of clarithromycin and ceftazidime alone or in combination. Synergic activity was noted with the use of 0.5 x MIC of ceftazidime combined with either 0.5 or 2 x MIC of clarithromycin. Neutropenic mice were infected with 10(8) cfu of mucoid P. aeruginosa intranasally to produce pneumonia and subsequently treated with oral clarithromycin (100 mg/kg) and/or sc ceftazidime (1500 mg/kg) as monotherapy or in combination. The addition of 5 days of clarithromycin to the ceftazidime regimen significantly improved survival as compared with the beta-lactam alone (48% versus 32%, P = 0.04). While a statistically significant difference was not detected with the addition of 3 days of clarithromycin therapy, a trend towards improved survival was noted with this regimen (38% versus 32%). These data demonstrate the adjunctive potential of clarithromycin when administered in combination with an antipseudomonal agent for the treatment of mucoid-producing Pseudomonas in acute respiratory infection.


Conformationally defined 6-s-trans-retinoic acid analogs. 3. Structure-activity relationships for nuclear receptor binding, transcriptional activity, and cancer chemopreventive activity.
We recently demonstrated that conformationally defined 6-s-trans-retinoic acid (RA) analogs were effective in the prevention of skin papillomas (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) and selective agonists for nuclear receptor binding and activation (Alam et al. J. Med. Chem. 1995, 38, 2302-2310). In order to probe important structure-activity relationships, we evaluated a homologous series of four 6-s-trans-retinoids that are 8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different substituents at 2' (R2) and 3' (R1) positions on the cyclohexene ring. UAB1 (R1 = R2 = H), UAB4 (R1 = R2 = Me), UAB7 (R1 = Me, R2 = iPr), and UAB8 (R1 = Et, R2 = iPr) contain alkyl R groups that mimic, to different extents, portions of the trimethylcyclohexenyl ring of RA. Both 9Z- and all-E-isomers of these retinoids were evaluated in binding assays for cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), a nuclear retinoic acid receptor (RAR alpha), and a nuclear retinoid X receptor (RXR alpha). The all-E-isomers of UAB retinoids bound tightly to CRABPs and RAR alpha, the binding affinity of the all-E-isomer increased systematically from UAB1 to UAB8, and binding for the latter was comparable to that of all-E-RA. In contrast to RA, the (9Z)-UAB retinoids were at least 200-fold less active than the all-E-isomers in binding to RAR alpha. The (9Z)-UAB isomers exhibited increasingly stronger binding to RXR alpha, and (9Z)-UAB8 was nearly as effective as (9Z)-RA in binding affinity. The retinoids were also evaluated in gene expression assays mediated by RAR alpha and RXR alpha homodimers or RAR alpha/RXR alpha heterodimers. Consistent with the binding affinities, the (all-E)-UAB retinoids activated gene transciption mediated by RAR alpha homodimers or RAR alpha/RXR alpha heterodimers, while the (9Z)-UAB isomers activated only the RXR alpha homodimer-mediated transcription. The all-E- and 9Z-isomers of the UAB retinoids were further evaluated for their capacity to prevent the induction of mouse skin papillomas. When compared to RA, only the (all-E)-UAB retinoids containing bulky R1 and R2 groups were effective in this chemoprevention assay. (9Z)-RA displayed equal capacity as RA to prevent papillomas, while the 9Z-isomers of the UAB retinoids were much less effective. Taken together, these studies demonstrate that the cyclohexenyl ring substituents of 6-s-trans-UAB retinoids are important for their biological activities and that the chemopreventive effect of the all-E-isomers of these retinoids correlates well with their capacity to bind to RARs and activate RAR/RXR-mediated transcription.


Lichen planus pemphigoides: its relationship to bullous pemphigoid.
Clinical and immunopathological studies of three patients with lichen planus pemphigoides (LPP) were carried out to investigate the relationship between LPP and bullous pemphigoid (BP) and to determine whether the antigen in LPP is the classical BP antigen. LPP is usually considered to be the coexistence of lichen planus with BP. The bullae in LPP were subepidermal and indistinguishable from BP. Indirect immunofluorescence demonstrated antibody binding to the epidermal surface of 1 M NaCl-split skin and mucosae, as in BP. The tissue distribution of the LPP antigen mirrored the distribution of BP in stratified squamous epithelia but was absent from transitional epithelia (pig bladder). Immunoelectron microscopy, both direct (two cases) and indirect (one case), showed binding to the lamina lucida as with BP antigen. Western blotting of epidermal extracts using the patients' sera showed that instead of reacting with the classical bullous pemphigoid antigen (220 kDa in our series), the antisera reacted with a unique band of 200 kDa in addition to the band of 180 kDa found as a minor antigen in bullous pemphigoid, but more commonly in pemphigoid gestationis. The relationship between these antigens awaits molecular characterization. These findings suggest that the target antigen in LPP may be unique.


Epidural analgesia in an obstetric patient with Klippel-Trenaunay syndrome.
We describe the use of epidural analgesia for vaginal delivery of a parturient with Klippel-Trenaunay syndrome in whom the use of repeated magnetic resonance imaging during her obstetric care allowed us to see deep haemangiomata. This also allowed the safe sitting of an epidural catheter at L1-2 to provide analgesia for labour and delivery. Klippel-Trenaunay syndrome and the anaesthetic implications of the congenital vascular abnormalities and potential coagulopathy are discussed.