Radiological fibrosis score is strongly associated with worse survival in rheumatoid arthritis-related interstitial lung disease.
High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD). We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified. During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score >20% had higher mortality (HR, 9.019; 95% CI, 2.87-28.35; p < .05). This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.


Quickscan assesses risk factors of long-term sickness absence: A cross-sectional (factorial) construct validation study.
The number of sick-listed employees has increased dramatically worldwide. Therefore, many countries aim to stimulate early and sustainable return to work opportunities to obtain better health outcomes and lower costs for disability pensions. To effectively orientate resources to patients with a high risk of not resuming work spontaneously, it is necessary to screen patients early in their sickness absence process. In this study, we validate "Quickscan", a new instrument to assess return-to-work needs and to predict risks of long-term sick leave. As part of the Quickscan validation process, we tested and compared the reliability and construct validity of the questionnaire in two different populations. First, we conducted a cross-sectional study in which the screening instrument was sent to sick-listed individuals in healthcare insurance. In a second cross-sectional study, sick-listed workers who consulted the occupational health physician for return-to-work assessment were asked to fill out the questionnaire. We compared both samples for descriptive statistics: frequencies, means and standard deviations. Reliability of the scales was calculated using Cronbach's alpha. Confirmatory factor analysis was performed to evaluate the construct (factorial) validity of the studied scales using software package AMOS 24. The screening tool was shown to be an instrument with reliable scales (except for the perfectionism and health perception patient scale) in both populations. The construct validity was satisfactory: we found that the hypothesized measurement models with the theoretical factors fitted the data well in both populations. In the first sample, the model improved for scales concerning stressful life events and showed worse fit for person-related factors. Work-related factors and functioning factors both showed similar fit indices across samples. We found small differences in descriptive statistics, which we could explain by the differences in characteristics of both populations. We can conclude that the instrument has considerable potential to function as a screening tool for disability management and follow-up of sick-leave, provided that some adaptations and validation tests are executed.


Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review.
To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.


Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.
We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.


Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol: an observational study.
Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of >300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of >300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (-45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium × phosphorus product remained unchanged. This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150-300 pg/ml) and had minimal impact on serum minerals.


Endogenous social distancing and its underappreciated impact on the epidemic curve.
Social distancing is an effective strategy to mitigate the impact of infectious diseases. If sick or healthy, or both, predominantly socially distance, the epidemic curve flattens. Contact reductions may occur for different reasons during a pandemic including health-related mobility loss (severity of symptoms), duty of care for a member of a high-risk group, and forced quarantine. Other decisions to reduce contacts are of a more voluntary nature. In particular, sick people reduce contacts consciously to avoid infecting others, and healthy individuals reduce contacts in order to stay healthy. We use game theory to formalize the interaction of voluntary social distancing in a partially infected population. This improves the behavioral micro-foundations of epidemiological models, and predicts differential social distancing rates dependent on health status. The model's key predictions in terms of comparative statics are derived, which concern changes and interactions between social distancing behaviors of sick and healthy. We fit the relevant parameters for endogenous social distancing to an epidemiological model with evidence from influenza waves to provide a benchmark for an epidemic curve with endogenous social distancing. Our results suggest that spreading similar in peak and case numbers to what partial immobilization of the population produces, yet quicker to pass, could occur endogenously. Going forward, eventual social distancing orders and lockdown policies should be benchmarked against more realistic epidemic models that take endogenous social distancing into account, rather than be driven by static, and therefore unrealistic, estimates for social mixing that intrinsically overestimate spreading.


Oxidative stress and inflammation in Parkinson's disease: is there a causal link?
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD.


Global optimization of clusters, crystals, and biomolecules.
Finding the optimal solution to a complex optimization problem is of great importance in many fields, ranging from protein structure prediction to the design of microprocessor circuitry. Some recent progress in finding the global minima of potential energy functions is described, focusing on applications of the simple "basin-hopping" approach to atomic and molecular clusters and more complicated hypersurface deformation techniques for crystals and biomolecules. These methods have produced promising results and should enable larger and more complex systems to be treated in the future.


Diverse cytopathologies in mitochondrial disease are caused by AMP-activated protein kinase signaling.
The complex cytopathology of mitochondrial diseases is usually attributed to insufficient ATP. AMP-activated protein kinase (AMPK) is a highly sensitive cellular energy sensor that is stimulated by ATP-depleting stresses. By antisense-inhibiting chaperonin 60 expression, we produced mitochondrially diseased strains with gene dose-dependent defects in phototaxis, growth, and multicellular morphogenesis. Mitochondrial disease was phenocopied in a gene dose-dependent manner by overexpressing a constitutively active AMPK alpha subunit (AMPKalphaT). The aberrant phenotypes in mitochondrially diseased strains were suppressed completely by antisense-inhibiting AMPKalpha expression. Phagocytosis and macropinocytosis, although energy consuming, were unaffected by mitochondrial disease and AMPKalpha expression levels. Consistent with the role of AMPK in energy homeostasis, mitochondrial "mass" and ATP levels were reduced by AMPKalpha antisense inhibition and increased by AMPKalphaT overexpression, but they were near normal in mitochondrially diseased cells. We also found that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, a pharmacological AMPK activator in mammalian cells, mimics mitochondrial disease in impairing Dictyostelium phototaxis and that AMPKalpha antisense-inhibited cells were resistant to this effect. The results show that diverse cytopathologies in Dictyostelium mitochondrial disease are caused by chronic AMPK signaling not by insufficient ATP.


(-)-Bornyl acetate induces autonomic relaxation and reduces arousal level after visual display terminal work without any influences of task performance in low-dose condition.
(-)-Bornyl acetate is the main volatile constituent in numerous conifer oils and has a camphoraceous, pine-needle-like odor. It is frequently used as the conifer needle composition in soap, bath products, room sprays, and pharmaceutical products. However, the psychophysiological effects of (-)-bornyl acetate remained unclear. We investigated the effects of breathing air mixed with (-)-bornyl acetate at different doses (low-dose and high-dose conditions) on the individuals during and after VDT (visual display terminal) work using a visual discrimination task. The amounts of (-)-bornyl acetate through our odorant delivery system for 40 min were 279.4 µg in the low-dose and 716.3 µg in the high-dose (-)-bornyl acetate condition. (-)-Bornyl acetate induced changes of autonomic nervous system for relaxation and reduced arousal level after VDT work without any influences of task performance in low-dose condition, but not in high-dose condition.


Adhesive bonding of arch bars for maxillomandibular fixation.
From a preliminary evaluation, many of the disadvantages of the conventional arch bars appear to be overcome with this new technique. Of particular importance is that no anesthetic is required during placement of the arch bars except when needed for aligning displaced segments or open reductions. The laboratory work can be delegated to a technician, and operating time rarely exceeds an hour. Further evaluation is being done.


Genetic analysis of the GcvA binding site in the gcvA control region.
The GcvA protein both activates and represses the gcv operon and negatively regulates its own transcription. GcvA binds to three sites in the gcv control region and to one site in the gcvA control region; each of these binding sites contains the conserved 5 bp DNA sequence 5'-CTAAT-3'. This report describes the role this DNA sequence plays in autoregulation and expression of gcvA. Through single base-pair mutations, the importance of three of these five basepairs in the autoregulation of gcvA expression is shown. Two of the gcvA control region mutations described cause a gcvA::lacZ fusion to be overexpressed at 9-24 times the wild-type level. The increase in expression is due in part to a complete loss of autoregulation and in part to a GcvA-independent mechanism. One of the mutants was shown by Western blot analysis to increase the intracellular concentration of GcvA. This high level of gcvA expression subsequently causes the loss of purine-mediated repression of a gcvT::lacZ fusion. However, overexpression of gcvR re-established purine-mediated repression of the gcvT::lacZ fusion, supporting the model for gcv regulation that suggests the need for a relatively constant GcvA to GcvR ratio for appropriate regulation of gcv expression in response to glycine and purine availability.


Carboplatin and recurrent childhood brain tumors.
Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.


Theoretical Analysis of Local Search and Simple Evolutionary Algorithms for the Generalized Travelling Salesperson Problem.
The generalized travelling salesperson problem is an important NP-hard combinatorial optimization problem for which metaheuristics, such as local search and evolutionary algorithms, have been used very successfully. Two hierarchical approaches with different neighbourhood structures, namely a cluster-based approach and a node-based approach, have been proposed by Hu and Raidl (2008) for solving this problem. In this article, local search algorithms and simple evolutionary algorithms based on these approaches are investigated from a theoretical perspective. For local search algorithms, we point out the complementary abilities of the two approaches by presenting instances where they mutually outperform each other. Afterwards, we introduce an instance which is hard for both approaches when initialized on a particular point of the search space, but where a variable neighbourhood search combining them finds the optimal solution in polynomial time. Then we turn our attention to analysing the behaviour of simple evolutionary algorithms that use these approaches. We show that the node-based approach solves the hard instance of the cluster-based approach presented in Corus et al. (2016) in polynomial time. Furthermore, we prove an exponential lower bound on the optimization time of the node-based approach for a class of Euclidean instances.


Structure-function studies of Escherichia coli RpoH (sigma32) by in vitro linker insertion mutagenesis.
The sigma factor RpoH (sigma(32)) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2.


Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in transurethral resection samples.
To determine whether the quantification of certain neuroendocrine and proliferative markers would help in the prognostic evaluation of prostatic adenocarcinomas obtained during transurethral resection of the prostate (TURP). Samples from two groups of patients with prostate cancer were examined. One group comprised 23 patients, of whom 12 were stage IV and 11 stage III, all with Gleason scores of > or = 7; this group was designated as high-grade, high-stage (HGHS). The second group comprised 10 consecutive patients with stage T1a adenocarcinoma of the prostate with Gleason scores of < or = 6, designated as low-grade, low-stage (LGLS) tumours. Tumour tissue from each TURP was stained with MIB-1 (an indicator of cell proliferation), neuron-specific enolase (NSE), chromogranin A (ChA) and synaptophysin (Syn), and 1000 cells counted to determine the percentages of positive cells in both benign and malignant tissue. The percentage of MIB-1-positive cells was designated as the proliferative index (PI). Patients were clinically followed to evaluate tumour progression, documented by rising prostate-specific antigen (PSA) levels, X-ray evidence of recurrent or metastatic carcinoma, or tissue biopsy showing malignancy. The mean number of neuroendocrine cells (NEC) for each marker and the mean PI were greater in the HGHS tumours than in the LGLS tumours or surrounding benign tissue of either group (P < 0.01). The LGLS tumours were remarkable for a having mean PI of about twice that of the benign tissue (2.9 and 1.3, respectively, P < 0.01); the NEC in these cases were more frequent in the benign than in the malignant tissue. There was no significant difference between the mean PIs and the mean percentages of NEC in the 14 HGHS tumours that progressed and the nine HGHS tumours that did not (P values 0.37-0.96). Although the PI assessed by MIB-1 and the number of NEC-positive cells were much higher in HGHS than LGLS tumours, this finding did not appear to have independent prognostic significance. The significance of the higher PI in LGLS tumours than in corresponding benign tissue is uncertain; LGLS tumours had fewer NEC than the surrounding benign tissue. The quantification of any of these four markers (MIB-1, NSE, ChA, Syn) was not prognostically helpful in these groups of cancers present in TURP specimens.


Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients.
Statin therapy is associated with important benefits for patients at risk of, and with, established cardiovascular disease. There is widespread interest in whether intensive dosing of statins yields larger treatment effects. We aimed to determine if intensive dosing is clinically important using a meta-analysis of randomized clinical trials (RCTs). We conducted comprehensive searches of electronic databases from inception to December 2010. We included any RCT evaluating a larger dose with a clinically common dose. Two reviewers independently extracted data, in duplicate. We performed random-effects meta-analysis and a trial sequential analysis. We identified 10 RCTs enrolling a total of 41 778 participants. Trials followed patients for a mean of 2.5 years. We did not find statistically significant effects on all-cause mortality [relative risk (RR) 0.92, 95% confidence interval (CI), 0.83-1.03, P = 0.14, I(2) = 38%] or cardiovascular disease (CVD) deaths (RR 0.89, 95% CI, 0.78-1.01, P = 0.07, I(2) = 34%). When we pooled the composite endpoint of coronary heart disease (CHD) death plus non-fatal myocardial infarction (MI), we found a significant protective effect of intensive statin dosing (RR 0.90, 95% CI, 0.84-0.96, P ≤ 0.0001, I(2) = 0%). We also found a significant effect on non-fatal MIs (RR 0.82, 95% CI, 0.76-0.89, P ≤ 0.0001, I(2) = 0%) and a significant reduction in the composite of fatal and non-fatal strokes (excluding transient ischaemic attacks) reported in 10 RCTs (RR 0.86, 95% CI, 0.77-0.96, P = 0.006, I(2) = 0%). A subgroup analysis of three trials examining acute coronary syndrome patients found significant effects on all-cause (RR 0.75, 95% CI, 0.61-0.91, P = 0.005, I(2) = 0%) and CVD mortality (RR 0.74, 95% CI, 0.59-0.94, P = 0.013, I(2) = 0%) with intensive dosing. Applying an analysis of optimal information size on the primary analysis, we found that the evidence for CHD death plus non-fatal MIs is conclusive. The evidence for CVD deaths alone is not yet conclusive. Available evidence suggests that intensive statin therapy reduces the risk of non-fatal events and may have a role in reducing mortality.


Mutations in PIGL in a patient with Mabry syndrome.
Mabry syndrome, hyperphosphatasia mental retardation syndrome (HPMRS), is an autosomal recessive disease characterized by increased serum levels of alkaline phosphatase (ALP), severe developmental delay, intellectual disability, and seizures. Recent studies have revealed mutations in PIGV, PIGW, PIGO, PGAP2, and PGAP3 (genes that encode molecules of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway) in patients with HPMRS. We performed whole-exome sequencing of a patient with severe intellectual disability, distinctive facial appearance, fragile nails, and persistent increased serum levels of ALP. The result revealed a compound heterozygote with a 13-bp deletion in exon 1 (c.36_48del) and a two-base deletion in exon 2 (c.254_255del) in phosphatidylinositol glycan anchor, class L (PIGL) that caused frameshifts resulting in premature terminations. The 13-bp deletion was inherited from the father, and the two-base deletion was inherited from the mother. Expressing c.36_48del or c.254_255del cDNA with an HA-tag at the C- or N-terminus in PIGL-deficient CHO cells only partially restored the surface expression of GPI-anchored proteins (GPI-APs). Nonsynonymous changes or frameshift mutations in PIGL have been identified in patients with CHIME syndrome, a rare autosomal recessive disorder characterized by colobomas, congenital heart defects, early onset migratory ichthyosiform dermatosis, intellectual disability, and ear abnormalities. Our patient did not have colobomas, congenital heart defects, or early onset migratory ichthyosiform dermatosis and hence was diagnosed with HPMRS, and not CHIME syndrome. These results suggest that frameshift mutations that result in premature termination in PIGL cause a phenotype that is consistent with HPMRS.


Normal pituitary gland: 1. Macroscopic anatomy-CT correlation.
To improve the radiologic recognition of pituitary microadenomas that have subtle or no mass effect, the appearance of the normal pituitary gland on computed tomographic (CT) images was studied. Thirteen autopsy specimens of the pituitary gland and sella turcica were examined by coronal CT and histologically sectioned in similar coronal planes. The CT and histologic findings were correlated, then compared with the coronal CT images of 30 normal pituitary glands in vivo, most of which were contrast-enhanced. The normal pituitary gland had a nonhomogeneous CT appearance with a variety of frequently predictable patterns. This heterogeneity was in part the result of gross anatomic structural interrelations between the anterior lobe, para intermedia, and posterior lobe.


Hirschsprung's disease in Japan: analysis of 3852 patients based on a nationwide survey in 30 years.
The introduction of laparoscope and transanal endorectal pull-through has caused a revolution in the operative procedures for Hirschsprung's disease. To study the changing profile of Hirschsprung's disease in Japan, the authors carried out a national survey. Patient data were collected in 3 phases: group 1, 1628 patients between 1978 and 1982; group 2, 1121 patients between 1988 and 1992; and group 3, 1103 patients between 1998 and 2002, respectively. The incidence was 1:4697, 1:5544, and 1:5343 and the male/female ratio was 3.0:1, 3.4:1, and 3.0:1 in each group, respectively. Patients weighing less than 2500 g at birth increased to 10.4% in group 3, whereas they were 6.5% in group 2 and 5.5% in group 1. The patients with a family history also increased to 6.0% in group 3, in comparison with 2.8% in group 2 and 3.0% in group 1. The incidence of associated anomalies increased over time, 11.1% in group 1, 16.3% in group 2, and 21.2% in group 3. Mutations of genes were found in 4 of the 23 patients examined. The extent of aganglionosis was almost the same in each group. Regarding the definitive operation, the procedures without laparotomy, including transanal endorectal pull-through, increased up to 42.6% in group 3 but 0% in groups 1 and 2. The frequency that a primary operation without stoma was performed also increased. The age at definitive operation decreased in group 3. The incidence of preoperative and postoperative enterocolitis also decreased over time. The mortality was decreased over time, 7.1%, 4.9%, and 3.0% for groups 1, 2, and 3, respectively. The authors analyzed 3852 Japanese patients over 3 decades. The ratio of patients with a low birth weight, associated anomalies, or a family history was increased in the last 10 years. A primary operation without laparotomy has thus become the procedure of choice for a definitive operation.


Angels of mercy? The legal and professional implications of withdrawal of life-sustaining treatment by nurses in England and Wales.
In circumstances where life-sustaining treatment appears merely to be drawing out the inevitable, it is usual practice for the healthcare team to withdraw aggressive life-sustaining measures, once agreement is reached with the patient and their family. Common law gives doctors several defences to allegations of criminality or malpractice in taking the key actions that withdraw treatment and result in the patient's death; however, the legal defensibility of nurses undertaking this role has not been explored. In the absence of a specific body of law related to nurses taking the actions that withdraw life-sustaining treatment, I discuss the probable legal response by considering parallel cases. Examining some of the circumstances in which doctors are allowed to take life, I argue that the legal dispensation by which doctors are permitted to perform these tasks rests largely on their identity as doctors rather than any distinctive feature of their activities themselves. This uniqueness means that medical law for nurses is quite distinct from that for doctors. While it may nevertheless give nurses practical exemption from the legal consequences of their actions in withdrawal, it depends upon a judicial view that nurses are instruments of doctors. This judicial position is at odds with nurses' professional responsibilities, which envisage them as independent professionals who are liable for their own actions, inviting potentially adverse consequences from their professional registrar.


Application of colloidal gas aphron suspensions produced from Sapindus mukorossi for arsenic removal from contaminated soil.
Colloidal gas aphron dispersions (CGAs) can be described as a system of microbubbles suspended homogenously in a liquid matrix. This work examines the performance of CGAs in comparison to surfactant solutions for washing low levels of arsenic from an iron rich soil. Sodium Dodecyl Sulfate (SDS) and saponin, a biodegradable surfactant, obtained from Sapindus mukorossi or soapnut fruit were used for generating CGAs and solutions for soil washing. Column washing experiments were performed in down-flow and up flow modes at a soil pH of 5 and 6 using varying concentration of SDS and soapnut solutions as well as CGAs. Soapnut CGAs removed more than 70% arsenic while SDS CGAs removed up to 55% arsenic from the soil columns in the soil pH range of 5-6. CGAs and solutions showed comparable performances in all the cases. CGAs were more economical since it contains 35% of air by volume, thereby requiring less surfactant. Micellar solubilization and low pH of soapnut facilitated arsenic desorption from soil column. FT-IR analysis of effluent suggested that soapnut solution did not interact chemically with arsenic thereby facilitating the recovery of soapnut solution by precipitating the arsenic. Damage to soil was minimal arsenic confirmed by metal dissolution from soil surface and SEM micrograph.


Gestational diabetes: maternal weight gain in relation to fetal growth, treatment modality, BMI and glycemic control.
We sought to determine the impact of maternal weight gain on fetal growth in gestational diabetes (GDM) in relation to treatment modality, body mass index (BMI) and glycemic control. Two thousand four hundred fifty-four GDMs were evaluated. Obesity was defined as BMI >29; good glycemic control ≤ 100 mg/dl; maternal age < and >30 years; parity ± 1; large for gestational age (LGA) >90th percentile and small for gestational age (SGA) <10th percentile. SGA rates were similar in all groups. Obese/overweight diet-treated women in glycemic control showed a four-fold higher rate of LGA compared to insulin-treated women. A 36-lb weight gain in insulin-treated patients had a six-fold higher risk. In poor glycemic control, LGA rates were higher in all BMI/weight gain categories. Logistic regressions for LGA/SGA revealed that level of glycemia, weight gain, parity, obesity and treatment (for LGA only) were significant. Different thresholds used for different maternal BMI categories in addition to the achievement of glycemic control and pharmacological therapy will enhance pregnancy outcome.


Validation of a new continuous geographic isolation scale: A tool for rural health disparities research.
The purpose of this study was to develop and test a new continuous measure for rural health disparities research that characterizes geographic areas according to a perspective of access to resources. We call the measure Isolation and anticipate it will be useful as an alternative to commonly used rural classification schemes (e.g., the Census Bureau's measure). Following the best known standards for measuring rurality, it captures the trade-off between access to resource-rich, high-population-density areas and the cost of travel to those areas; thus even intrinsically low-resource areas may have high access to nearby resources. Validity was tested with proxies such as distance to hospitals, physician availability, and access to high quality food. The Isolation scale demonstrated good construct validity (i.e., both convergent and criterion validity). Fit statistics indicated that, compared to other commonly-used urban/rural definitions, the Isolation scale was the best overall measure when predicting several proxies for rurality, even when categorized. We also show that the measure does a substantially better job at explaining national health outcome data at the state level. This new continuous Isolation scale shows considerable promise for improving our conceptualization, theorization, and measurement of the features of rurality that are pertinent to rural health disparities research, and can also be useful to policy makers who may find value in using isolation thresholds that are most relevant to their policy planning needs.


Evaluation of DNA damage in construction-site workers occupationally exposed to welding fumes and solvent-based paints in Turkey.
In this study, the comet assay was used to evaluate whether welding fume and solvent base paint exposure led to DNA damage in construction-site workers in Turkey. The workers (n = 52) were selected according to their exposure in the construction site and controls (n = 26) from the general population, with no history of occupational exposure. The alkaline comet assay, a standard method for assessing genotoxicity, has been applied in peripheral lymphocytes of all subjects. The mean percentages of DNA in tail (%DNA(T)) of each group were evaluated, including the comparisons between smokers in each different group and the duration of exposure. Significant increase in the mean %DNA(T) (p < 0.01) was observed in all exposed subjects (12.34 ± 2.05) when compared with controls (6.64 ± 1.43). Also %DNA(T) was significantly high (p < 0.01) in welders (13.59 ± 1.89) compared with painters (11.10 ± 1.35). There was a statistical meaningful difference in % DNA(T) between control and exposed smokers. Our findings indicate that exposure to welding fumes and paints induce genotoxic effect in peripheral lymphocytes, indicating a potential health risk for workers. Therefore, to ensure maximum occupational safety, biomonitoring is of great value for assessing the risk for construction workers.


The importance of mass spectrometric dereplication in fungal secondary metabolite analysis.
Having entered the Genomic Era, it is now evident that the biosynthetic potential of filamentous fungi is much larger than was thought even a decade ago. Fungi harbor many cryptic gene clusters encoding for the biosynthesis of polyketides, non-ribosomal peptides, and terpenoids - which can all undergo extensive modifications by tailoring enzymes - thus potentially providing a large array of products from a single pathway. Elucidating the full chemical profile of a fungal species is a challenging exercise, even with elemental composition provided by high-resolution mass spectrometry (HRMS) used in combination with chemical databases (e.g., AntiBase) to dereplicate known compounds. This has led to a continuous effort to improve chromatographic separation in conjunction with improvement in HRMS detection. Major improvements have also occurred with 2D chromatography, ion-mobility, MS/MS and MS(3), stable isotope labeling feeding experiments, classic UV/Vis, and especially automated data-mining and metabolomics software approaches as the sheer amount of data generated is now the major challenge. This review will focus on the development and implementation of dereplication strategies and will highlight the importance of each stage of the process from sample preparation to chromatographic separation and finally toward both manual and more targeted methods for automated dereplication of fungal natural products using state-of-the art MS instrumentation.


A Latent Profile Analysis of Lie-Telling to Parents and Friends during Adolescence.
Adolescence has been suggested to be a time of heightened lie-telling. The current study used a latent profile analysis to examine unique patterns of lie-telling for lies told to parents and friends during adolescence as well as whether adjustment indicators (relationship quality, depressive symptoms, social anxiety, externalizing problems) could be used to predict group membership. These patterns were examined among 828 10- to 16- year-olds (Mage = 12.39, SD = 1.69, 49.9% male). In both relationships, 5-profile solutions emerged; most adolescents reported very infrequent lie-telling, while a small portion (less than 5%) told high rates of lies. Adjustment indicators predicted group membership. Depressive symptoms, social anxiety, parent relationship quality, and externalizing problems predicted group membership for lying to parents. Depressive symptoms and social anxiety predicted group membership for lying to friends. The findings indicate that high rates of lie-telling found in previous research may be driven by a small number of prolific lie-tellers.


Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1.
The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T37/T46, followed by T70 and S65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is a goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, (54)YXXXXLΦ(60) (motif 1) but lack known phosphorylation sites. We report here a 2.1-Å crystal structure of mouse eIF4E in complex with m(7)GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP150-84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S65 and T70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1-mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. The binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.


Three therapeutic communities. A prospective controlled study of narcotic addiction treatment: process and two-year follow-up results.
The efficacy of three different residential therapeutic communities for male veterans addicted to heroin was studied, comparing 181 subjects who were randomly assigned to one of the communities with 166 subjects briefly hospitalized only for the treatment of withdrawal symptoms. At two-year follow-up, subjects from both a professionally staffed community and a peer confrontation community were found significantly more likely than the withdrawal-only group to be working or attending school and less likely to have been convicted of a crime. An eclectic program employing both professionals and paraprofessionals was not found to exceed the withdrawal-only group on any of the major outcome variables. The two relatively successful communities, although different in structure and style, were both perceived by their residents to have greater program clarity, order, staff control, and orientation to personal problems than the unsuccessful program.


A rapid review of measures to support people in isolation or quarantine during the Covid-19 pandemic and the effectiveness of such measures.
This rapid review aimed to identify measures available to support those in isolation or quarantine during the coronavirus disease 2019 (Covid-19) pandemic, and determine their effectiveness in improving adherence to these recommendations and or reducing transmission. The rapid review consisted of two elements, the first was a review of guidance published by national and international agencies relating to measures to support those in isolation (due to case status) or quarantine (due to close contact status) during the Covid-19 pandemic. Five categories of support measures were identified in the international guidance, they were: Psychological, addiction and safety supports, Essential supplies, Financial aid, Information provision and Enforcement. The second element was a rapid literature review of the effectiveness of measures used to support individuals in isolation or quarantine during any pandemic or epidemic setting, due to respiratory pathogens. A systematic search of published peer-reviewed articles and nonpeer-reviewed pre-prints was undertaken from 1 January 2000 to 26 January 2021. Two Australian publications met the inclusion criteria, both based on data from a survey undertaken during the 2009 H1N1 pandemic. The first reported that 55% of households were fully compliant with quarantine recommendations, and that there was increased compliance reported in households that understood what they were meant to do compared with those who reported that they did not (odds ratio [OR]: 2.27, 95% confidence interval [CI]: 1.35-3.80). The second reported that access to paid sick and or carer's leave did not predict compliance with quarantine recommendations (OR: 2.07, 95% CI: 0.82-5.23). Neither reported on reduction in transmission.


Informal payments in the health sector: a case study from Turkey.
The practice of making informal payments in the health sector is common in a number of countries. It has become an important policy issue around the world. These payments can jeopardize governments' attempts to improve equity and access to care and policies targeted to the poor. It is widely believed that a considerable amount of out-of-pocket payment in the health sector in Turkey is informal. To examine this issue, we used a questionnaire adopted from a wider international study. We concluded that informal payments in Turkey are significant and have important implications for health care reform.


Computerized tomography angiography in patients with subarachnoid hemorrhage: from aneurysm detection to treatment without conventional angiography.
The purpose of this study was to determine prospectively whether and to what extent computerized tomography (CT) angiography can serve as the sole imaging method for a preoperative workup in patients with ruptured intracranial aneurysms. During a 1-year period, all patients who presented to the authors' hospital with subarachnoid hemorrhage demonstrated by unenhanced CT scanning or lumbar puncture underwent CT angiography. Two radiologists evaluated the CT angiography source images and maximum intensity projection slabs and arrived at a consensus. They categorized the quality of the CT angiography as adequate or inadequate and classified aneurysms that were detected as definitely or possibly present. The parent artery of anterior communicating artery aneurysms was identified by asymmetrical anterior cerebral artery size and asymmetrical aneurysm location. The parent artery was indicated by the larger A1 segment in cases of asymmetrical A1 size. Only CT angiograms of adequate quality that revealed aneurysms classified as definitely present and with an unequivocal parent artery were presented to the neurosurgeons, who decided whether preoperative digital subtraction (DS) angiography should still be performed. Forty-nine of the 100 studied patients did not undergo surgery because of poor clinical condition, nonaneurysmal cause of the hemorrhage, or endovascular treatment of the ruptured aneurysm. Of the 51 patients who underwent surgery, radiologists required DS angiography in 17 patients; the imaging technique provided greater certainty in 13 instances. The neurosurgeons required DS angiography 11 times; this provided additional information in two instances. Twenty-three (45%) of the 51 patients were surgically treated successfully on the basis of CT angiography findings alone. Computerized tomography angiography can replace DS angiography as the preoperative neuroimaging technique in a substantial proportion of patients with ruptured intracranial aneurysms.


Effects of nitrogen supply on hydrogen-oxidizing bacterial enrichment to produce microbial protein: Comparing nitrogen fixation and ammonium assimilation.
To investigate the effects of nitrogen source supply on microbial protein (MP) production by hydrogen-oxidizing bacteria (HOB) under continuous feed gas provision, a sequencing batch culture comparison (N2 fixation versus ammonium assimilation) was performed. The results confirmed that even under basic cultivation conditions, N2-fixing HOB (NF-HOB) communities showed higher levels of CO2 and N2 fixation (190.45 mg/L Δ CODt and 11.75 mg/L Δ TNbiomass) than previously known, with the highest biomass yield being 0.153 g CDW/g COD-H2. Rich ammonium stimulated MP synthesis and the biomass accumulation of communities (increased by 7.4 ~ 14.3 times), presumably through the enhancement of H2 and CO2 absorption. The micro mechanism may involve encouraging the enrichment of species like Xanthobacter and Acinetobacter then raising the abundance of nitrogenase and glutamate synthase to facilitate the nitrogen assimilation. This would provide NF-HOB with ideas for optimizing their MP synthesis activity.


Object-independent image-based wavefront sensing approach using phase diversity images and deep learning.
This paper proposes an image-based wavefront sensing approach using deep learning, which is applicable to both point source and any extended scenes at the same time, while the training process is performed without any simulated or real extended scenes. Rather than directly recovering phase information from image plane intensities, we first extract a special feature in the frequency domain that is independent of the original objects but only determined by phase aberrations (a pair of phase diversity images is needed in this process). Then the deep long short-term memory (LSTM) network (a variant of recurrent neural network) is introduced to establish the accurate non-linear mapping between the extracted feature image and phase aberrations. Simulations and an experiment are performed to demonstrate the effectiveness and accuracy of the proposed approach. Some other discussions are further presented for demonstrating the superior non-linear fitting capacity of deep LSTM compared to Resnet 18 (a variant of convolutional neural network) specifically for the problem encountered in this paper. The effect of the incoherency of light on the accuracy of the recovered wavefront phase is also quantitatively discussed. This work will contribute to the application of deep learning to image-based wavefront sensing and high-resolution image reconstruction.


The evolving practice of developmental care in the neonatal unit: a systematic review.
Many neonatal intensive care units (NICUs) are experiencing changes in their approaches to preterm infant care as they consider and incorporate the philosophy of individualized developmental care. The aim of this systematic review is to research current literature documenting the short-term effects of developmental care and the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). The following databases were reviewed: PubMED, CINAHL, and PsychINFO by using the keywords developmental care, individualized care, preterm infant, early intervention, and NIDCAP. Fifty-four articles were found with a total of 15 matching the selection criteria. All 15 articles were assessed using a research design developed by the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM). Twelve of the 15 articles contained strong Levels of Evidence (I or II). Our findings suggest evidence supporting developmental care and NIDCAP, however, further research documenting outcomes for preterm infants receiving developmental care and/or NIDCAP is needed.


Implementation of participatory organizational change in long term care to improve safety.
Long Term Care (LTC) facilities are fast-paced, demanding environments placing workers at significant risk for injuries. Health and safety interventions to address hazards in LTC are challenging to implement. The study assessed a participatory organizational change intervention implementation and impacts. This was a mixed methods implementation study with a concurrent control, conducted from 2017 to 2019 in four non-profit LTC facilities in Ontario, Canada. Study participants were managers and frontline staff. Intervention sites implemented a participatory organizational change program, control sites distributed one-page health and safety pamphlets. Program impact data were collected via Survey (self-efficacy, control over work, pain and general health) and observation (Quick Exposure Checklist). Interviews/focus groups were used to collect program implementation data. Participants described program impacts (hazard controls through equipment purchase/modification, practice changes, and education/training) and positive changes in culture, communication and collaboration. There was a statistically significant difference in manager self-efficacy for musculoskeletal disorder (MSD) hazards between the control and intervention sites over time but no other statistical differences were found. Key program implementation challenges included LTC hazards, staff shortage/turnover, safety culture, staff time to participate, and communication. Facilitators included frontline staff involvement during implementation, management support, focusing on a single unit, training, and involving an external program facilitator. A participatory program can have positive impacts on identifying and reducing MSD hazards. Key to success is involving frontline staff in identifying hazards and creating solutions and management encouragement on a unit working together. High turnover rates, staffing shortages, and time constraints were barriers as they are for all organizational change efforts in LTC. The implementation findings are likely applicable in any jurisdiction. Practical Application: Implementing a participatory organizational change program to reduce MSD hazards is feasible in LTC and can improve communication and aid in identification and control of hazards.


Catalytic methanolysis of hydrazine borane: a new and efficient hydrogen generation system under mild conditions.
Safe and efficient hydrogen storage is a major obstacle for using hydrogen as an energy carrier. Therefore, intensive efforts have been focused on the development of new materials for chemical hydrogen storage. Of particular importance, hydrazine borane (N(2)H(4)BH(3)) is emerging as one of the most promising solid hydrogen carriers due to its high gravimetric hydrogen storage capacity (15.4 wt%) and low molecular weight. Herein, we report metal catalyzed methanolysis of hydrazine borane (N(2)H(4)BH(3), HB) as a fast hydrogen generation system under mild conditions. When trace amounts of nickel(ii) chloride (NiCl(2)) is added to the methanol solution of hydrazine borane ([HB]/[Ni] ≥ 200) the reaction solution releases 3 equiv. of H(2) with a rate of 24 mol H(2) (mol Ni min)(-1) at room temperature. The results reported here also includes (i) identification of the reaction products by using ATR-IR, DP-MS, (1)H and (11)B NMR spectroscopic techniques and the establishment of the reaction stoichiometry, (ii) investigation of the effect of substrate and catalyst concentrations on the hydrogen generation rate to determine the rate law for the catalytic methanolysis of hydrazine borane, (iii) determination of the activation parameters (E(a), ΔH(#), and ΔS(#)) for the catalytic methanolysis of hydrazine borane by using the temperature dependent rate data of the hydrogen generation.


Suppression of Melanose Caused by Diaporthe citri on Citrus Leaves Pretreated with Bio-sulfur.
Melanose, caused by Diaporthe citri, is one of severe diseases in citrus, a major economic resource in Jeju island. To reduce the usage amount of organic synthetic fungicide, bio-sulfur was tested as an alternative chemical to control citrus melanose in the present study. Direct antifungal activity of bio-sulfur against D. citri was determined through in vitro experiment using artificial nutrient media. Disease severity of melanose on bio-sulfur pretreated citrus leaves was lower than that on untreated ones. To illustrate the mechanism of disease suppression by bio-sulfur, infection structures were observed with a fluorescent microscope and a scanning electron microscope. In fluorescent microscopic observation, most conidia rarely germinated. In addition, hyphal growth on leaves pretreated with bio-sulfur was inhibited compared to that on untreated ones. In scanning electron microscope images of bio-sulfur pretreated leaves, surfaces of most conidia were shrunk while hyphae were morphologically changed and frequently branched. Such microscopic observations were also found for leaves pretreated with a commercial fungicide Dithianon. These results suggest that bio-sulfur may be used to control citrus melanose as an environment friendly alternative to organic synthetic fungicides.


Adolescent outcomes and opportunities in a Canadian province: looking at siblings and neighbors.
Well-organized administrative data with large numbers of cases (building on linked files from several government departments) and a population registry facilitate new studies of population health and child development. Analyses of family relationships and a number of outcomes--educational achievement, health, teen pregnancy, and receipt of income assistance--are relatively easy to conduct using several birth cohorts. Looking both at means/proportions and at sibling correlations enriches our study of opportunity and well-being in late adolescence. With observational research possibly exaggerating the causal effects of risk factors, sibling comparisons involving individuals sharing both many family characteristics and many genes help deal with such criticisms. This paper uses a rich dataset from one Canadian province (Manitoba) covering a wide range of geographical areas (cities to rural regions). Influences on opportunity and well-being are analyzed looking at both means/proportions and sibling correlations. We measure a variety of outcomes that may reflect different causal influences. A creative application of linear programming advances the use of data on residential location. Predicting educational achievement using available variables was much easier than predicting adolescent health status (R-square of .200 versus R-square of .043). Low levels of educational achievement, high levels of teenage pregnancy, and high sibling correlations outside Winnipeg and within Winnipeg's lower income areas highlight inequalities across socioeconomic and geographic backgrounds. Stratifying our analyses by different variables, such as income quintiles, reveals differences in means and correlations within outcomes and across groups. Particular events--changes in mother's marital status and in place of residence--were associated with less favorable outcomes in late adolescence. Our findings suggest a paradox: Canadian developmental outcomes through late adolescence appear quite similar to those in the United States, even though intergenerational mobility in Canada is closer to mobility in the Nordic countries than to that in the United States.


Margarine consumption and allergy in children.
Dietary fat consumption is hypothesized to influence atopy development by modulation of IgE production. The aim of our study was to assess whether margarine consumption is associated with allergic sensitization and diseases in children. Data of a cross-sectional health survey in 1998-1999 comprising 2,348 children age 5 to 14 yr were analyzed. Information on type of fat used as spread during the past 12 mo, children's health, and sociodemographic factors were gathered by questionnaire. Allergic sensitization to common aeroallergens was assessed by specific serum IgE. Compared with butter consumption, margarine consumption was associated with allergic sensitization (adjusted odds ratio 1.30 [95% confidence interval: 1.01 to 1.67]) and with rhinitis symptoms during the past 12 mo (1.41 [1.01 to 1.97]). Sex-stratified analysis showed that these associations were limited to boys (boys: sensitization 1.57 [1.12 to 2.20], rhinitis symptoms 1.76 [1.12 to 2.78]; girls: sensitization 0.99 [0.67 to 1.46], rhinitis symptoms 1.03 [0.63 to 1.70]). No statistically significant relation was observed between exclusive margarine consumption and ever physician-diagnosed hay fever or asthma in all children. In conclusion, the sex difference in the association of margarine consumption with allergic sensitization was in accordance with the higher IgE concentrations and atopy prevalence in boys compared with girls. Increased intake of certain polyunsaturated fatty acids might further stimulate IgE production in boys.


In available scientific literature, the impact of organizational trust and perceived organizational support on employees' wellbeing has mainly been investigated without focusing on the different targets they can refer to. The aim of the study is to test the direct role of these variables as precursors of well-being, job satisfaction and turnover intentions, by distinguishing two different levels in trust and support: the first one stemming from the employees' own team (in which employees have direct and daily interpersonal relationships, and within which they build their work experience), the second stemming from the organization itself. In this study, a survey was administered to more than 1,000 employees of a Sicilian hospital. The relationships between the variables were studied through the use of hierarchical regression analysis. Trust and perceived support are both significant predictors of mental and physical health (team trust: β=.088; organizational trust: β=.110; team support: β=.245; organizational support: β=.082), job satisfaction (team trust: β=.245; organizational trust: β=.222; team support: β=.209; organizational support: β=.168) and turnover intentions (team trust: β=- .086; organizational trust: β=-.164; team support: β=-.166; organizational support: β=.064). However, the support at the team level is a more important predictor, while trust is a stronger predictor at the organizational level. Distinguishing between team and organizational levels of trust and support allows to better understand the relationship between trust and support and wellbeing and organizational outcomes such as job satisfaction and turnover intentions. Practical implications, as well as future research, should therefore refer to the different levels of such predictors.


Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis.
Glucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs. MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events. Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily.Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped. GLP-1 agonists are effective in improving glycaemic control and promoting weight loss.


Therapeutically relevant blood pressure differences with two nifedipine (60 mg) osmotic delivery systems of differing design: three case reports.
During the introduction of a new once-daily nifedipine 60 mg osmotic delivery tablet to Canada in 2009, several patients previously maintained at target blood pressure on regimens that included nifedipine 60 mg daily were observed to have > 10 mmHg rises in their systolic pressure during follow-up. The only difference noted in their medication and clinical status was a substitution with the new 60 mg nifedipine formulation by their pharmacists. Three patients agreed to report home blood pressure for N of 1 studies in which all clinical parameters remained the same, but their nifedipine was repeatedly switched between the original and alternate formulations each week. Of 14 recorded switches, systolic pressure was higher on the alternate formulation 13 times. In at least some patients, the alternate pump technology appears less effective. This highlights the need for better bioequivalence criteria for comparing differing delivery technologies that artificially retard absorption of the drug.


Lactobacillus formosensis sp. nov., a lactic acid bacterium isolated from fermented soybean meal.
A Gram-reaction-positive, catalase-negative, facultatively anaerobic, rod-shaped lactic acid bacterium, designated strain S215(T), was isolated from fermented soybean meal. The organism produced d-lactic acid from glucose without gas formation. 16S rRNA gene sequencing results showed that strain S215(T) had 98.74-99.60 % sequence similarity to the type strains of three species of the genus Lactobacillus (Lactobacillus farciminis BCRC 14043(T), Lactobacillus futsaii BCRC 80278(T) and Lactobacillus crustorum JCM 15951(T)). A comparison of two housekeeping genes, rpoA and pheS, revealed that strain S215(T) was well separated from the reference strains of species of the genus Lactobacillus. DNA-DNA hybridization results indicated that strain S215(T) had DNA related to the three type strains of species of the genus Lactobacillus (33-66 % relatedness). The DNA G+C content of strain S215(T) was 36.2 mol%. The cell walls contained peptidoglycan of the d-meso-diaminopimelic acid type and the major fatty acids were C18 : 1ω9c, C16 : 0 and C19 : 0 cyclo ω10c/C19 : 1ω6c. Phenotypic and genotypic features demonstrated that the isolate represents a novel species of the genus Lactobacillus, for which the name Lactobacillus formosensis sp. nov. is proposed. The type strain is S215(T) ( = NBRC 109509(T) = BCRC 80582(T)).


Effectiveness of E-learning on clinical application of dental injection anatomy via simulation manikins.
E-learning is frequently integrated into dental education, yet little is known on the effectiveness of e-learning in both instilling foundational knowledge and facilitating translation of newly acquired knowledge and skill into clinical application. The objective of this study was to investigate the impact of learning modality on acquisition of knowledge and translation to clinical skill using objective feedback from oral anesthesia manikins and subjects' self-reported confidence scores. This mixed-method study involved first year dental students (n = 52) who volunteered to participate in a learning intervention, simulation exercise, and survey in 2022. Students were randomly assigned to lecture (n = 26) or e-learning (n = 26) cohorts and then participated in the intervention, postintervention assessment, and a simulation to evaluate correct approaches for each dental block and attempts to success. All subjects scored significantly higher on post-intervention assessment compared to pre-intervention assessment (8.2 vs. 5.9; p < 0.0001) with no significant differences between intervention groups when comparing preintervention and postintervention scores. Furthermore, there were no significant differences between the two cohorts when comparing abilities to correctly approach each dental block or attempts to success. Finally, all students reported a significant increase in confidence in most categories following intervention and simulation, with no significant differences between lecture and e-learning cohorts. Our findings suggest students learning via e-learning are equally capable as those learning via lecture at demonstrating newly acquired knowledge and skill in both assessments and clinical simulations. Results support incorporating supplemental e-learning and oral anesthesia manikin exercises for students learning the anatomy of dental injections.


Sequence Analysis of Novel Staphylococcus aureus Lineages from Wild and Captive Macaques.
Staphylococcus aureus is a widespread and common opportunistic bacterium that can colonise or infect humans as well as a wide range of animals. There are a few studies of both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolated from monkeys, apes, and lemurs, indicating a presence of a number of poorly or unknown lineages of the pathogen. In order to obtain insight into staphylococcal diversity, we sequenced strains from wild and captive individuals of three macaque species (Macaca mulatta, M. assamensis, and M. sylvanus) using Nanopore and Illumina technologies. These strains were previously identified by microarray as poorly or unknown strains. Isolates of novel lineages ST4168, ST7687, ST7688, ST7689, ST7690, ST7691, ST7692, ST7693, ST7694, ST7695, ST7745, ST7746, ST7747, ST7748, ST7749, ST7750, ST7751, ST7752, ST7753, and ST7754 were sequenced and characterised for the first time. In addition, isolates belonging to ST2990, a lineage also observed in humans, and ST3268, a MRSA strain already known from macaques, were also included into the study. Mobile genetic elements, genomic islands, and carriage of prophages were analysed. There was no evidence for novel host-specific virulence factors. However, a conspicuously high rate of carriage of a pathogenicity island harbouring edinB and etD2/etE as well as a higher number of repeat units within the gene sasG (encoding an adhesion factor) than in human isolates were observed. None of the strains harboured the genes encoding Panton-Valentine leukocidin. In conclusion, wildlife including macaques may harbour an unappreciated diversity of S. aureus lineages that may be of clinical relevance for humans, livestock, or for wildlife conservation, given the declining state of many wildlife populations.


Cytology, colposcopy and cervical neoplasia.
There have been suggestions that the failure to reduce the incidence of cervical carcinoma in New Zealand is due to a failure to take cervical smears from women at risk, and to appropriately manage those with abnormal smears. Review of data collected from a clinic in Christchurch over a four-year interval found that the majority of those with invasive cancer had never had a smear taken, or had not had smears taken frequently enough. There was evidence that cytology does not always correlate with definitive histology, and that patients with abnormal smears sometimes experienced lengthy delays before being referred for management. Comments are made on who should have smears, how often, and how women with abnormal smears should be managed.


Candidosis: the most common postmortem cerebral mycosis in an endemic fungal area.
To determine the recent postmortem character of cerebral mycoses, 1,752 consecutive complete autopsies done in the endemic fungal area of central Kentucky from 1964 through 1973 were reviewed. Fourteen patients (0.8%) had histologically confirmed fungal infections in the brain. The most prevalent fungus was Candida spp. which was observed in six patients. Cryptococcosis was recognized in three patients; histoplasmosis in two; zygomycosis in two; and blastomycosis in one. In every patient these fungi were also seen in tissues outside the central nervous system and were identified microbiologically in nine. Unlike the pathogenic yeasts, Candida spp. and the zygomycetes produced intracerebral lesions without any significant meningeal reactions. Cerebral candidosis was recognized only at autopsy in patients compromised by previous multiple antibiotic therapy for gram-negative infections. On the other hand, immunosuppression was associated more commonly with the non-candidal fungal infections. An experimental model for systemic candidosis in adult Sprague-Dawley rats likewise demonstrated its difficult antemorten recognition even with cerebral lesions. Although clinical consequences from candidemia seem often inapparent, the associated intracerebral lesions may further compromise the altered host. Their frequency and significance remain to be elucidated.


Redefinition of the genus Allonychiurus Yoshii, 1995 (Collembola, Onychiuridae) with description of a new species from China.
In this paper, we describe a new species of the genus Allonychiurus Yoshii, 1995, characterized by the presence of an apical swelling on the fourth antennal segment as well as a combination of chaetotaxic and pseudocellar characters. The genus Allonychiurus is redefined. Four of its species are considered as incertae sedis: Allonychiurus michelbacheri (Bagnall, 1948), Allonychiurus spinosus (Bagnall, 1949), Allonychiurus caprariae (Dallai, 1969) and Allonychiurus sensitivus (Handschin, 1928). The three species Allonychiurus borensis (Beruete, Arbea & Jordana, 1994), Allonychiurus sensilatus (Thibaud & Massoud, 1979) and Allonychiurus vandeli (Cassagnau, 1960) are removed from Allonychiurus and placed in Micronychiurus Bagnall, 1949, Thalassaphorura Bagnall, 1949 and Spinonychiurus Weiner, 1996 respectively. The synonymy of Thibaudichiurus Weiner, 1996 with Allonychiurus is rejected and Allonychiurus foliatus (Rusek, 1967) and Allonychiurus mariangeae (Thibaud & Lee, 1994) are re-allocated to Thibaudichiurus. List and identification key to the world species of the genus are given.


Solid lipid nanoparticles improve octyl gallate antimetastatic activity and ameliorate its renal and hepatic toxic effects.
Metastasis is the main cause of cancer-related death and requires the development of effective treatments with reduced toxicity and effective anticancer activity. Gallic acid derivatives have shown significant biological properties including antitumoral activity as shown in a previous study with octyl gallate (G8) in vitro. Thus, the aim of this work was to evaluate the antimetastatic effect of free and solid lipid nanoparticle-loaded G8 in mice in a lung metastasis model. Animals inoculated with melanoma cells presented metastasis in lungs, which was significantly inhibited by treatment with G8 and solid lipid nanoparticle-loaded G8, named G8-NVM. However, G8-treated mice showed an increase in several toxicological parameters, which were almost completely circumvented by G8-NVM treatment. This study supports the need for pharmacological studies on new potential medicinal plants to treat cancer and can provide new perspectives on using nanotechnology to improve biological activities while decreasing the chemotherapy toxicological effects of anticancer drugs.


[State of Dogiel type II neurons in the wall of the cat small intestine following a single exposure to gravitational stress].
Under study was the nervous apparatus of the small intestine in 22 cats subjected to a single gravitation stress by rotation in a centrifuge of 1,5 m radius. The stress was equal to 10 units, duration from 2,5 to 3,5 min., and was of head-pelvis direction. The material was treated after Nissl and Gomori in Chilingarian's modification. Within 1-3 days after exposure to gravitation stresses in the Auerbach plexus there appeared changes in the shape of the body of the type II Dogiel cells, such as pericellular oedema, vacuoles in the cytoplasm, chromatolysis and varicous thickenings of nerve fibres. Terminal structures of the dendrites of the type II Dogiel cells are thickened. The changes are most pronounced within the 4th-7th days after exposure to gravitation and are observed as late as the 14th day, being sharply diminished by the 30th day.


Transanal endoscopic microsurgery: a systematic review.
The aim of this study was to systematically review the evidence relating to the safety and efficacy of transanal endoscopic microsurgery, a relatively new technique used to locally excise rectal tumors, compared with existing techniques such as anterior resections and abdominoperineal resections or local excisions. We conducted a systematic review of comparative studies and case series of transanal endoscopic microsurgery from 1980 to August 2002. Three comparative studies (including one randomized, controlled trial) and 55 case series were included. The first area of study was the safety and efficacy of adenomas. In the randomized, controlled trial, no difference could be detected in the rate of early complications between transanal endoscopic microsurgery (10.3 percent) and direct local excision (17 percent) (relative risk, 0.61; 95 percent confidence interval, 0.29-1.29). Transanal endoscopic microsurgery resulted in less local recurrence (6/98; 6 percent) than direct local excision (20/90; 22 percent) (relative risk, 0.28; 95 percent confidence interval, 0.12-0.66). The 6 percent rate of local recurrence for transanal endoscopic microsurgery in this trial is consistent with the rates found in case series of transanal endoscopic microsurgery (median, 5 percent). The second area of study was the safety and efficacy of carcinomas. In the randomized, controlled trial, no difference could be detected in the rate of complications between transanal endoscopic microsurgery and direct local excision (relative risk for overall early complication rates, 0.56; 95 percent confidence interval, 0.22-1.42). No differences in survival or local recurrence rate between transanal endoscopic microsurgery and anterior resection could be detected in either the randomized, controlled trial (hazard ratio,1.02 for survival) or the nonrandomized, comparative study. There were 2 of 25 (8 percent) transanal endoscopic microsurgery recurrences in the randomized, controlled trial, but no figures were given for recurrence after anterior resection. In the case series, the median local recurrence rate for transanal endoscopic microsurgery was 8.4 percent, ranging from 0 percent to 50 percent. The third comparison was cost of the procedures. Transanal endoscopic microsurgery had both a lower recurrence rate and a lower cost than local excision or anterior resection for adenomas. Although the effectiveness of transanal endoscopic microsurgery could not be established for carcinomas, costs were lower than those for either anterior resection or abdominoperineal resection. The evidence regarding transanal endoscopic microsurgery is very limited, being largely based on a single relatively small randomized, controlled trial. However, transanal endoscopic microsurgery does appear to result in fewer recurrences than those with direct local excision in adenomas and thus may be a useful procedure for several small niches of patient types--e.g., for large benign lesions of the middle to upper third of the rectum, for T1 low-risk rectal cancers, and for palliative, not curative, use in more advanced tumors.


Testing for GW501516 (cardarine) in human hair using LC/MS-MS and confirmation by LC/HRMS.
GW501516, also known as GW-1516 or cardarine and endurobol, is a peroxisome proliferator-activated receptor delta (PPAR-δ) agonist. Activation of the receptor will increase fat-burning capacity and muscle production, as it changes the body's fuel preference from glucose to lipids. GW501516 has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10 to 20 mg per day, for 6 to 8 weeks. Both athletes and amateurs can abuse GW501516 as the drug can be easily obtained via the Internet. Since January 2009, the list of prohibited substances and methods of doping as established by the World Anti-Doping Agency includes GW-501516, first as a gene doping substance and now in the S4.5 Metabolic modulators class. It is prohibited at all times. Using LC/MS-MS and confirmation by LC/HRM, after methanol incubation of 20 mg with ultrasound for 1 hour, GW501516 was identified in the hair of a male abuser at 32 and 22 pg/mg in 2 × 2 cm segments. The result is the first evidence that this compound with a carboxylic acid function is incorporated in human hair.


Carbon dioxide homeostasis during transperitoneal or extraperitoneal laparoscopic pelvic lymphadenectomy: a real-time intraoperative comparison.
The primary goal of this study was to evaluate differences in carbon dioxide metabolism between patients undergoing transperitoneal or extraperitoneal laparoscopic pelvic lymph node dissection (L-PLND) for staging of adenocarcinoma of the prostate (CaP). Eighteen candidates undergoing L-PLND were divided between the transperitoneal (N = 12) and extraperitoneal (N = 6) approaches. End-tidal partial pressure of CO2 (PeCO2) and minute volume of expired CO2 (VCO2) were considered indicators of CO2 absorption. These two parameters were monitored intraoperatively utilizing a metabolic cart and Ohmeda Rascal-II. The cardiostimulatory effect of increasing serum CO2 and the ventilatory countermeasures used to correct the iatrogenic hypercapnia associated with CO2 insufflation were also measured. With the exception of the region of CO2 insufflation, the operative procedure and perioperative care were identical for the two groups. Preoperative patient characteristics were similar. The mean time of CO2 insufflation was 136 minutes for the transperitoneal group and 120 minutes for the extraperitoneal group. The absorption of CO2 was significantly greater and more rapid during extraperitoneal L-PLND. This may be attributable to more profound CO2 absorption from the parietal peritoneal surface compounded by subcutaneous CO2 emphysema. Disruption of microvascular and lymphatic channels during the development of the extraperitoneal working space facilitates direct CO2 absorption into the intravascular space. A minor increase in heart rate and systolic blood pressure was noted during CO2 insufflation. In all but one patient (extraperitoneal group), hypercarbia and acidemia were prevented by an increased ventilatory rate. The potential dysrhythmogenicity of hypercarbia may contraindicate the extraperitoneal approach in patients with cardiopulmonary disease.


[Endocannabinoid system and energy metabolism: physiology and pathophysiology].
The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system has recently been shown to control several metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, therefore drugs interfering with this overactivation by blocking CB1 receptor are considered as valuable candidates for the treatment of obesity and related cardiometabolic risk factors.


Redesigning team-based learning facilitation for an online platform to deliver preclinical curriculum: A response to the COVID-19 pandemic.
This article was migrated. The article was marked as recommended. Due to the increasing number of COVID-19 cases globally, and the need for critical containment, Duke-NUS Medical School, Singapore, moved all of its preclinical classes online, keeping with national and university guidelines. The sudden move from face-to-face to online learning posed several challenges to the school's team-based learning (TBL) pedagogy. In TBL, student engagement is key to promote peer-to-peer learning. The educational faculty found that it was challenging to ensure student engagement through an online platform. Additionally, online TBL is heavily dependent on the use of technology. Technological and internet connectivity issues were potential obstacles to the learning process. This manuscript proposes practical tips for a facilitator of an online TBL class to engage learners in this new format. To overcome technical complications, a dedicated centralized administrative team managed the logistics of hosting TBL online. Working synergistically, the facilitator, and the administrative team were instrumental in recreating the learning environment of a face-to-face TBL in an online platform.


Measles infection and Parkinson's disease.
A case-control analysis of Parkinson's disease and infections in childhood was conducted in a cohort of 50,002 men who attended Harvard College (Cambridge, MA) or the University of Pennsylvania (Philadelphia, PA) between 1916 and 1950 and who were followed in adulthood for morbidity and mortality data. Cases of Parkinson's disease were identified from responses to mailed questionnaires and death certificates through 1978. Four controls from the same population were selected for each case. A reduced risk of Parkinson's disease was associated with most childhood viral infections. The negative association was statistically significant for a history of measles prior to college entrance (exposure odds ratio = 0.53; 95% confidence limits: 0.31, 0.93). The reduced risk of Parkinson's disease among subjects with a positive history of measles in childhood may reflect an adverse effect of measles in adulthood or of subclinical or atypical measles. Furthermore, a negative history of measles, especially if associated with a lack of other common diseases, could be a marker for negative influenza history before 1918 and thus a higher risk of infection during the 1918 influenza epidemic, because of the lack of partial influenza immunity. These data may also suggest a truly protective effect of measles, compatible with some complex interaction between measles virus and the virus of the 1918 influenza epidemic.


[The determination of C. pylori in patients with gastroduodenal diseases].
A total of 46 gastric mucosa biopsy specimens obtained during surgery and 90 gastric juice samples from patients with gastroduodenal diseases were examined. Campylobacter-like microorganisms were detected in 84.6 percent of biopsy specimens and in 73.9 percent of gastric juice samples (in gram-stained smears). Urease activity was detected in 75.9 and 13.3 percent, respectively. C. pylori growth in solid nutrient medium in microaerophilic conditions was observed in 44.2 and 5.7 percent of the examined samples, respectively. The studies have demonstrated the efficacy of using disks with urea from standard kits manufactured by the Research Institute for Epidemiology and Microbiology in the city of Gorky in the urease test.


Use of monoclonal fluorescent antibodies for the detection of B. pertussis and B. parapertussis.
While it has been said that PCR is likely to replace DFA as the test of choice, accessibility to and cost of the technique may limit the number of laboratories that are able to implement the process. Still, the advantage of DFA staining relative to other diagnostic methods, including PCR, is the provision of a rapid result and lower overall cost. The laboratory diagnosis of pertussis remains problematic, and polyclonal DFA reagents for its detection have brought into question the utility of DFA. However, the integration of a commercially available monoclonal DFA reagent, in combination with the development and standardization of existing procedures, should provide clinicians with an improved method for the diagnosis and epidemiology of pertussis.


Infant mortality: some international comparisons.
Comparison of infant mortality rates (IMRs) among the world's countries requires assessment of completeness and accuracy of data. The United Nations Statistical Office classifies as "C", complete, meaning at least 90% of events are actually recorded, 1994 data supplied by 80 governments, comprising one fourth of the world's population, ie, 1,450,000,000 people, and as incomplete the other three fourths, 4,180,000,000. All the "C" countries officially accept the World Health Organization definition of a live birth (any product of gestation showing any sign of life), but it has been argued that some countries routinely report as stillbirths infants counted as live births in the United States (US), thus understating their IMRs. In 1994, 22 countries had IMRs varying from 4.2 for Japan to 8.0 for the US, a remarkable achievement in the light of IMRs of 124.0 and 60.0 for these two countries in 1930. Compensating for possible underreporting of live births by excluding all deaths in the first hour of life would reduce the US IMR to about 7, still higher than 17 other countries. Between 1930 and 1994 the IMR in the US declined more slowly than several other countries, particularly during the time period 1951 through 1965, when the US rate declined by 16% and the Japanese rate, for instance, declined by 68%. Between 1983 and 1994, decline in Puerto Rico was slower than in Chile, Cuba, and the US. IMRs in all the "C" countries are lower than the US rate was in 1930. IMRs in most of the world, estimated from surveys and special studies, vary from 27 to 190. Correlation studies suggest that a high rate of teenage pregnancies has relatively little effect on IMRs but that high total fertility rates are accompanied by high infant mortality.


Microinstability of the Hip-Gaining Acceptance.
The hip has generally been considered an inherently stable joint. However, the femoral head moves relative to the acetabulum. Although the bones are primarily important in hip stability, the importance of the soft tissues has recently been demonstrated. Symptomatic microinstability of the hip is defined as extraphysiologic hip motion that causes pain with or without symptoms of hip joint unsteadiness and may be the result of bony deficiency and/or soft-tissue damage or loss. Recent work has helped improve the ability to identify microinstability patients preoperatively. Initial management begins with activity modification and strengthening of the periarticular musculature. Failing nonsurgical management, surgical intervention can be beneficial, focusing on treatment of the underlying cause of microinstability, as well as associated intra-articular pathology. Bony deficiency may be treated with a redirectional osteotomy, whereas those with adequate bony coverage may be treated with capsular plication, capsular reconstruction, and/or labral reconstruction.


Agenda setting and visit openings in primary care visits involving patients taking opioids for chronic pain.
Agenda setting is associated with more efficient care and better patient experience. This study develops a taxonomy of visit opening styles to assess use of agenda and non-agenda setting visit openings and their effects on participant experience. This observational study analyzed 83 video recorded US primary care visits at a single academic medical center in California involving family medicine and internal medicine resident physicians (n = 49) and patients (n = 83) with chronic pain on opioids. Using conversation analysis, we developed a coding scheme that assessed the presence of agenda setting, distinct visit opening styles, and the number of total topics, major topics, surprise patient topics, and returns to prior topics discussed. Exploratory quantitative analyses were conducted to assess the relationship of agenda setting and visit opening styles with post-visit measures of both patient experience and physician perception of visit difficulty. We identified 2 visit opening styles representing agenda setting (agenda eliciting, agenda reframing) and 3 non-agenda setting opening styles (open-ended question, patient launch, physician launch). Agenda setting was only performed in 11% of visits and was associated with fewer surprise patient topics than visits without agenda setting (mean (SD) 2.67 (1.66) versus 4.28 (3.23), p = 0.03). In this study of patients with chronic pain, resident physicians rarely performed agenda setting, whether defined in terms of "agenda eliciting" or "agenda re-framing." Agenda setting was associated with fewer surprise topics. Understanding the communication context and outcomes of agenda setting may inform better use of this communication tool in primary care practice.


The use of blends of cassava flour and extruded full-fat soybeans in diets for broiler chickens.
A study was conducted to determine the effects of blending different levels of a low-prussic acid cassava flour with extruded full-fat soybeans in diets for growing broiler chickens. The full-fat soybeans contribute oil which increases the energy content of the diet, aids in overcoming the dusty nature of cassava, and provide high-quality protein. One-third, two-thirds, and all of the maize was replaced by cassava in diets with none, 12.5 and 25% extruded full-fat soybeans. Diets were fed in pelleted form to broiler chickens for a 47-day feeding trial. Replacement of one-third of the maize with cassava had no adverse effects on body weight gains in this study with a reduction in weight at higher levels at the conclusion of the study. Feed utilization was reduced more severely than was anticipated. However, growth rate on the higher levels of cassava was reasonably good, indicating that producers might feed these diets for a slightly longer period of time and produce chickens more economically if cassava meal were available at a cost significantly less than that of maize.