Ketoprofen Microemulsion for Improved Skin Delivery and In Vivo Anti-inflammatory Effect.
We have designed a microemulsion (ME) containing Ketoprofen (KET) for anti-inflammatory effect evaluated using the rat paw edema model. The ME was prepared by adding propylene glycol (PG) loaded with 1% KET/water (3:1, w/w), to a mixture of sorbitan monooleate and polysorbate 80 (47.0%) at 3:1 (w/w) and canola oil (38.0%). The physicochemical characterization of KET-loaded ME involved particle size and zeta potential determination, entrapment efficiency, calorimetric analysis, and in vitro drug release. The in vivo anti-inflammatory study employed male Wistar rats. Measurement of the foot volume was performed using a caliper immediately before and 2, 4, and 6 h after injection of Aerosil. KET-loaded ME showed particle size around 20 nm, with zeta potential at -16 mV and entrapment efficiency at 70%. Moreover, KET was converted to the amorphous state when loaded in the formulation and it was shown that the drug was slowly released from the ME. Finally, the in vivo biological activity was similar to that of the commercial gel, but ME better controlled edema at 4 h. These results demonstrated that the ME formulation is an alternative strategy for improving KET skin permeation for anti-inflammatory effect. Furthermore, our findings are promising considering that the developed ME was loaded with only 1% KET, and the formulation was able to keep a similar release profile and in vivo effect compared to the commercial gel with 2.5% KET. Therefore, the KET-loaded developed herein ME is likely to have a decreased side effect compared with that of the commercial gel, but both presented the same efficacy.


My radius is broken - do I need a cast or is a splint enough?
The treatment of many distal radius fractures has shifted from casting to splinting or the application of a soft dressing. This review includes a review of the types of pediatric distal radius fractures and the most recent literature on the management of these injuries. Many nondisplaced distal radius fractures may be treated with removable splints or bandages. This mitigates complications with cast immobilization. Additionally, many of these injuries do not require follow-up treatment and thereby reduce healthcare costs. This update on distal radius fractures in the pediatric population highlights changes in the treatment paradigm and demonstrates an opportunity to diminish healthcare costs.


A Phylogenomic Study of Acanthamoeba polyphaga Draft Genome Sequences Suggests Genetic Exchanges With Giant Viruses.
Acanthamoeba are ubiquitous phagocytes predominant in soil and water which can ingest many microbes. Giant viruses of amoebae are listed among the Acanthamoeba-resisting microorganisms. Their sympatric lifestyle within amoebae is suspected to promote lateral nucleotide sequence transfers. Some Acanthamoeba species have shown differences in their susceptibility to giant viruses. Until recently, only the genome of a single Acanthamoeba castellanii Neff was available. We analyzed the draft genome sequences of Acanthamoeba polyphaga through several approaches, including comparative genomics, phylogeny, and sequence networks, with the aim of detecting putative nucleotide sequence exchanges with giant viruses. We identified a putative sequence trafficking between this Acanthamoeba species and giant viruses, with 366 genes best matching with viral genes. Among viruses, Pandoraviruses provided the greatest number of best hits with 117 (32%) for A. polyphaga. Then, genes from mimiviruses, Mollivirus sibericum, marseilleviruses, and Pithovirus sibericum were best hits in 67 (18%), 35 (9%), 24 (7%), and 2 (0.5%) cases, respectively. Phylogenetic reconstructions showed in a few cases that the most parsimonious evolutionary scenarios were a transfer of gene sequences from giant viruses to A. polyphaga. Nevertheless, in most cases, phylogenies were inconclusive regarding the sense of the sequence flow. The number and nature of putative nucleotide sequence transfers between A. polyphaga, and A. castellanii ATCC 50370 on the one hand, and pandoraviruses, mimiviruses and marseilleviruses on the other hand were analyzed. The results showed a lower number of differences within the same giant viral family compared to between different giant virus families. The evolution of 10 scaffolds that were identified among the 14 Acanthamoeba sp. draft genome sequences and that harbored ≥ 3 genes best matching with viruses showed a conservation of these scaffolds and their 46 viral genes in A. polyphaga, A. castellanii ATCC 50370 and A. pearcei. In contrast, the number of conserved genes decreased for other Acanthamoeba species, and none of these 46 genes were present in three of them. Overall, this work opens up several potential avenues for future studies on the interactions between Acanthamoeba species and giant viruses.


The attentional window modulates capture by audiovisual events.
Visual search is markedly improved when a target color change is synchronized with a spatially non-informative auditory signal. This "pip and pop" effect is an automatic process as even a distractor captures attention when accompanied by a tone. Previous studies investigating visual attention have indicated that automatic capture is susceptible to the size of the attentional window. The present study investigated whether the pip and pop effect is modulated by the extent to which participants divide their attention across the visual field We show that participants were better in detecting a synchronized audiovisual event when they divided their attention across the visual field relative to a condition in which they focused their attention. We argue that audiovisual capture is reduced under focused conditions relative to distributed settings.


Dual Identity Development and Adjustment in Muslim Minority Adolescents.
Dual identity (e.g., strong ethnic and national identity) is a psychological resource for minority groups, but how it develops during adolescence is less clear. In this 3-wave longitudinal study, a person-oriented approach was used to examine dual identity development in a sample of 2145 Muslim adolescents (MT1 = 15 years, 51% female) in four Western European countries. The results of a growth-mixture model pointed toward four distinct developmental Classes: (1) "Dual identity", (2) "Separation to dual identity", (3) "Assimilation to dual identity", and (4) "Separation". Multiple group comparisons further showed that adolescents in Class 1 were well adjusted, but well-being (e.g., internalizing problems, life satisfaction) and health were even higher among adolescents in Class 2. Adolescents in Class 3 had consistently lower levels of well-being, and adolescents in Class 4 had lower levels of socio-cultural adjustment (e.g., problem behaviour at school, delinquent behaviour, and lack of intergroup contact). The findings underscore that most Muslim minority adolescents in Western Europe develop a dual identity, and that the developmental process, not simply the outcome, matters for adjustment.


Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2.
Transarterial chemoembolization (TACE) is recommended for patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B. However, because of the heterogeneity of HCC in BCLC stage B; various subclassification systems have been proposed to predict the prognosis of patients. Previously, we proposed the Kinki criteria for precise classification of HCC cases in BCLC stage B. In this study, we compared the time to TACE refractoriness in HCC patients with Kinki criteria substages B1 and B2-HCC. Between January 2006 and December 2013, 592 HCC patients (substage B1, n = 118; substage B2, n = 170) underwent TACE. Time to progression under TACE treatment was defined as the time to untreatable progression (TTUP). TTUP and changes in liver function were analyzed in patients with substages B1 and B2-HCC. The median TTUP was 25.7 months (95% CI 19.3-37.3) and 16.4 months (95% CI 13.1-20.2) in patients with substage B1-HCC and substage B2-HCC, respectively (p = 0.0050). In patients with substage B2-HCC, median Child-Pugh scores after the first TACE session was significantly different from those after third and fifth TACE sessions (first-third, p = 0.0020; first-fifth, p = 0.0008). Key Message: TACE refractoriness occurred earlier in patients with substage B2-HCC than those with substage B1-HCC; deterioration of liver function with repeated TACE was more obvious in HCC cases with stage-B1 tumor. Shorter TTUP and impaired liver function due to repeated TACE could be responsible for the shorter survival in patients with substage B2-HCC.


Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance.
Obesity and metabolic syndrome result from excess calorie intake and genetic predisposition and are mechanistically linked to type II diabetes and accelerated body aging; abnormal nutrient and insulin signaling participate in this pathologic process, yet the underlying molecular mechanisms are incompletely understood. Mice lacking the p66 kDa isoform of the Shc adaptor molecule live longer and are leaner than wild-type animals, suggesting that this molecule may have a role in metabolic derangement and premature senescence by overnutrition. We found that p66 deficiency exerts a modest but significant protective effect on fat accumulation and premature death in lepOb/Ob mice, an established genetic model of obesity and insulin resistance; strikingly, however, p66 inactivation improved glucose tolerance in these animals, without affecting (hyper)insulinaemia and independent of body weight. Protection from insulin resistance was cell autonomous, because isolated p66KO preadipocytes were relatively resistant to insulin desensitization by free fatty acids in vitro. Biochemical studies revealed that p66shc promotes the signal-inhibitory phosphorylation of the major insulin transducer IRS-1, by bridging IRS-1 and the mTOR effector p70S6 kinase, a molecule previously linked to obesity-induced insulin resistance. Importantly, IRS-1 was strongly up-regulated in the adipose tissue of p66KO lepOb/Ob mice, confirming that effects of p66 on tissue responsiveness to insulin are largely mediated by this molecule. Taken together, these findings identify p66shc as a major mediator of insulin resistance by excess nutrients, and by extension, as a potential molecular target against the spreading epidemic of obesity and type II diabetes.


Specific inhibitory action of anisodamine against a staphylococcal superantigenic toxin, toxic shock syndrome toxin 1 (TSST-1), leading to down-regulation of cytokine production and blocking of TSST-1 toxicity in mice.
Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vbeta2+ T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-kappaB activation was also demonstrated. In contrast, no significant inhibition of Vbeta2+ T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vbeta2+ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.


Preparation of Chitosan Okra Nanoparticles: Optimization and Evaluation as Mucoadhesive Drug Delivery System.
To prepare chitosan-okra gum nanoparticles and their evaluation as mucoadhesive drug delivery system for intranasal delivery of esculin. Esculin loaded chitosan-okra gum based nanoparticles were prepared using ionic gelation method. The preparation method was optimized using Box-Behnken experimental design employing okra gum concentration, chitosan concentration, pH and stirring speed as independent variables and particle size, encapsulation efficiency and zeta potential of the formulation were selected as dependent variables. The optimized formulation was characterized using FTIR, SEM and TEM. The nanoparticles were evaluated for their bioadhesive strength and in vitro drug release studies. The optimized intranasal formulation was administered to rats and the pharmacokinetic profile and biodistribution studies were carried out to calculate the targeting efficiency of the formulation in the brain. The nanoparticles were found to depict particle size in the range of 294.0 to 613.4 nm. The concentration of gums was found to significantly influence the particle size and encapsulation efficiency. The nanoparticles depicted bioadhesive strength of 32±2%. The in vitro drug release studies showed 96.4±4.2% release of esculin from nanoparticles in 4h. The drug targeting of NPs to brain was found to be nearly double that of esculin given as simple solution. The nanoparticles prepared using chitosan-okra gum were found to possess good mucoadhesive strength with and high brain targeting efficiency.


Specific Anti-hostility Effects of Atypical Antipsychotics in Persons with Schizophrenia: From Clozapine to Cariprazine.
After participating in this activity, learners should be better able to:• Evaluate the anti-hostility effects of available atypical antipsychotic agents. In addition to hallucinations and delusions, persons with schizophrenia may exhibit hostility. In clinical trials of antipsychotics, hostility is routinely measured as part of rating scales such as the Brief Psychiatric Rating Scale or Positive and Negative Syndrome Scale. The availability of the atypical antipsychotic clozapine in 1989 led to the observation that it is possible to have a treatment effect on hostility that is independent of the treatment effect on hallucinations or delusions, and independent of general sedative effects. The data supporting this notion of a specific anti-hostility effect are the most robust for clozapine as the data include specifically designed randomized, controlled clinical trials. A specific anti-hostility effect is also observable to various degrees with most of the other atypical antipsychotics, as evidenced in post hoc analyses of clinical trials originally conducted for regulatory purposes, supplemented by post hoc analyses of large effectiveness trials. The generalizability of these studies, however, may be limited. Participants in these trials were not selected for aggressive and hostile behavior. Some of the studies also excluded patients with substance use disorders. The latter is particularly important because alcohol and substance use are well known to increase risk for hostility and aggression. Nevertheless, the repeated demonstrations of the specificity of an anti-hostility effect (in terms of statistical independence of effects on other positive symptoms and of sedation) are of potential clinical importance.


Genes and QTLs controlling inflorescence and stem branch architecture in Leymus (Poaceae: Triticeae) Wildrye.
Grass inflorescence and stem branches show recognizable architectural differences among species. The inflorescence branches of Triticeae cereals and grasses, including wheat, barley, and 400-500 wild species, are usually contracted into a spike formation, with the number of flowering branches (spikelets) per node conserved within species and genera. Perennial Triticeae grasses of genus Leymus are unusual in that the number of spikelets per node varies, inflorescences may have panicle branches, and vegetative stems may form subterranean rhizomes. Leymus cinereus and L. triticoides show discrete differences in inflorescence length, branching architecture, node number, and density; number of spikelets per node and florets per spikelet; culm length and width; and perimeter of rhizomatous spreading. Quantitative trait loci controlling these traits were detected in 2 pseudo-backcross populations derived from the interspecific hybrids using a linkage map with 360 expressed gene sequence markers from Leymus tiller and rhizome branch meristems. Alignments of genes, mutations, and quantitative trait loci controlling similar traits in other grass species were identified using the Brachypodium genome reference sequence. Evidence suggests that loci controlling inflorescence and stem branch architecture in Leymus are conserved among the grasses, are governed by natural selection, and can serve as possible gene targets for improving seed, forage, and grain production.


Therapeutic cancer vaccines in combination with conventional therapy.
The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation of cells of the immune system. In addition, a range of tumor antigens have been characterized to allow targeting of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma.


Interpreting Google flu trends data for pandemic H1N1 influenza: the New Zealand experience.
For the period of the spread of pandemic H1N1 influenza in New Zealand during 2009, we compared results from Google Flu Trends with data from existing surveillance systems. The patterns from Google Flu Trends were closely aligned with (peaking a week before and a week after) two independent national surveillance systems for influenza-like illness (ILI) cases. It was much less congruent with (delayed by three weeks) data from ILI-related calls to a national free-phone Healthline and with media coverage of pandemic influenza. Some patterns were unique to Google Flu Trends and may not have reflected the actual ILI burden in the community. Overall, Google Flu Trends appears to provide a useful free surveillance system but it should probably be seen as supplementary rather than as an alternative.


Social attainment in survivors of pediatric central nervous system tumors: a systematic review and meta-analysis from the Children's Oncology Group.
Improved therapies for pediatric central nervous system (CNS) tumors have increased survival rates; however, many survivors experience significant long-term functional limitations. Survivors of pediatric CNS tumors can experience deficits in social attainment. The aim of this review was to systematically amalgamate findings pertaining to social attainment (i.e., educational attainment, marriage, employment outcomes) in survivors of pediatric CNS tumors. PubMed (web-based), PsycINFO (EBSCO), EMBASE (Ovid), and Web of Science (Thomson Reuters) were used to identify articles published between January 2011 and September 2018. Eligible studies reported outcomes for survivors of pediatric CNS tumors diagnosed before age 21 years and > 5 years from diagnosis and/or > 2 years off therapy. All data were independently abstracted by two reviewers. Random-effects meta-analyses were performed using Review Manager 5.0. The search yielded 7021 unique publications. Forty-six were included in the current review. Meta-analyses revealed survivors of CNS tumors were significantly more likely to have completed compulsory education only (OR = 1.87, 95% CI = 1.66, 2.12, p < 0.00001), less likely to be married (OR = 4.70, 95% CI = 3.89, 5.68, p < 0.00001), and more likely to be unemployed (OR = 2.84, 95% CI = 2.62, 3.08, p < 0.00001) compared to non-cancer controls. Cranial radiation therapy, neurocognitive deficits, and younger age at diagnosis were associated with poorer outcomes. Hearing loss and bilateral blindness were also related to poorer outcomes. Sex did not impact social attainment outcomes. Survivors of pediatric CNS tumors are at elevated risk for poor attainment of key adult social outcomes. There is a critical need to develop interventions to support survivors in becoming independent and productive adults.


Acetylcholine synthesis and release is enhanced by dibutyryl cyclic AMP in a neuronal cell line derived from mouse septum.
Cholinergic properties of the SN56.B5.G4 cell line derived from the fusion of neurons of the mouse postnatal day 21 septum and the murine neuroblastoma cell line N18TG2 were investigated and correlated with morphological differentiation. In basal serum-containing growth medium, few cells developed neurites. Neurite extension occurred in cells grown for 2 d with forskolin or dibutyryl cAMP (dbcAMP) but not with butyrate. In cells treated with these compounds, the activity of ChAT and ACh content were two- to threefold higher relative to controls. The cells synthesized ACh from choline taken up by the sodium-dependent high-affinity transport. Forskolin-, dbcAMP-, and butyrate-treated cells (but not the controls) were capable of spontaneous and depolarization-evoked ACh release. The results indicate that the morphological and the neurochemical aspects of SN56.B5.G4 cell differentiation are independently regulated.


Fabrication and In Vitro/In Vivo Performance of Mucoadhesive Electrospun Nanofiber Mats Containing α-Mangostin.
This study aimed to fabricate mucoadhesive electrospun nanofiber mats containing α-mangostin for the maintenance of oral hygiene and reduction of the bacterial growth that causes dental caries. Synthesized thiolated chitosan (CS-SH) blended with polyvinyl alcohol (PVA) was selected as the mucoadhesive polymer. α-Mangostin was incorporated into the CS-SH/PVA solution and electrospun to obtain nanofiber mats. Scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and tensile strength testing were used to characterize the mats. The swelling degree and mucoadhesion were also determined. The nanofiber mats were further evaluated regarding their α-mangostin content, in vitro α-mangostin release, antibacterial activity, cytotoxicity, in vivo performance, and stability. The results indicated that the mats were in the nanometer range. The α-mangostin was well incorporated into the mats, with an amorphous form. The mats showed suitable tensile strength, swelling, and mucoadhesive properties. The loading capacity increased when the initial amount of α-mangostin was increased. Rapid release of α-mangostin from the mats was achieved. Additionally, a fast bacterial killing rate occurred at the lowest concentration of nanofiber mats when α-mangostin was added to the mats. The mats were less cytotoxic after use for 72 h. Moreover, in vivo testing indicated that the mats could reduce the number of oral bacteria, with a good mouth feel. The mats maintained the amount of α-mangostin for 6 months. The results suggest that α-mangostin-loaded mucoadhesive electrospun nanofiber mats may be a promising material for oral care and the prevention of dental caries.


Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.
Differing opinions about the value of ventilation-perfusion lung scanning have created controversy concerning the correct approach to the diagnosis of pulmonary embolism. In a prospective study of 305 consecutive patients with clinically suspected pulmonary embolism and abnormal perfusion lung scans, we evaluated the role of ventilation-perfusion lung scanning, pulmonary angiography, and objective testing for venous thrombosis in the diagnostic process. Segmental or greater perfusion defects with ventilation mismatch have a high probability (86 percent) of pulmonary embolism. Contrary to current clinical practice, however, the approach of ruling against pulmonary embolism by a "low probability" scan pattern is incorrect, even with an improved technique for ventilation imaging; the frequency of pulmonary embolism in these patients ranged from 25 to 40 percent. Objective testing for venous thrombosis provides a practical alternative to performing pulmonary angiography in the diagnostic work-up; by providing an endpoint for commencing anticoagulant therapy, a positive result obviates the need for further testing in 20 to 30 percent of patients.


Biological relationship between Central and South American Chibchan speaking populations: evidence from mtDNA.
We examined mitochondrial DNA (mtDNA) haplogroup and haplotype diversity in 188 individuals from three Chibchan (Kogi, Arsario, and Ijka) populations and one Arawak (Wayuú) group from northeast Colombia to determine the biological relationship between lower Central American and northern South American Chibchan speakers. mtDNA haplogroups were obtained for all individuals and mtDNA HVS-I sequence data were obtained for 110 samples. Resulting sequence data were compared to 16 other Caribbean, South, and Central American populations using diversity measures, neutrality test statistics, sudden and spatial mismatch models, intermatch distributions, phylogenetic networks, and a multidimensional scaling plot. Our results demonstrate the existence of a shared maternal genetic structure between Central American Chibchan, Mayan populations and northern South American Chibchan-speakers. Additionally, these results suggest an expansion of Chibchan-speakers into South America associated with a shift in subsistence strategies because of changing ecological conditions that occurred in the region between 10,000-14,000 years before present.


Traumatic birth and childbirth-related post-traumatic stress disorder: International expert consensus recommendations for practice, policy, and research.
Research suggests 1 in 3 births are experienced as psychologically traumatic and about 4% of women and 1% of their partners develop post-traumatic stress disorder (PTSD) as a result. To provide expert consensus recommendations for practice, policy, and research and theory. Two consultations (n = 65 and n = 43) with an international group of expert researchers and clinicians from 33 countries involved in COST Action CA18211; three meetings with CA18211 group leaders and stakeholders; followed by review and feedback from people with lived experience and CA18211 members (n = 238). Recommendations for practice include that care for women and birth partners must be given in ways that minimise negative birth experiences. This includes respecting women's rights before, during, and after childbirth; and preventing maltreatment and obstetric violence. Principles of trauma-informed care need to be integrated across maternity settings. Recommendations for policy include that national and international guidelines are needed to increase awareness of perinatal mental health problems, including traumatic birth and childbirth-related PTSD, and outline evidence-based, practical strategies for detection, prevention, and treatment. Recommendations for research and theory include that birth needs to be understood through a neuro-biopsychosocial framework. Longitudinal studies with representative and global samples are warranted; and research on prevention, intervention and cost to society is essential. Implementation of these recommendations could potentially reduce traumatic births and childbirth-related PTSD worldwide and improve outcomes for women and families. Recommendations should ideally be incorporated into a comprehensive, holistic approach to mental health support for all involved in the childbirth process.


Evidence that the mature leaves contribute auxin to the immature tissues of pea (Pisum sativum L.).
In plants such as the garden pea (Pisum sativum L.), it is widely thought that the auxin indole-3-acetic acid (IAA) is synthesised mainly in the immature tissues of the apical bud and then transported basipetally to other parts of the plant. Consistent with this belief are results showing that removal of the apical bud markedly reduces the IAA content in the stem. However, it has also been suggested that the mature leaves may synthesise substantial amounts of IAA, which enters the basipetal transport stream after being transported to the shoot apex in the phloem (Cambridge and Morris in Planta 99:583-588, 1996). To examine this theory, we defoliated pea plants and measured the effect on IAA content in the remaining shoot tissues. IAA levels were reduced in the internodes, and to a lesser extent in the apical bud, after defoliation, suggesting that mature leaves are indeed an important source of auxin for the shoot. Consistent with this idea, we have demonstrated that mature, fully expanded leaves are capable of de novo IAA synthesis. Furthermore, we report evidence for the presence of IAA in the phloem sap of pea. Together these results support those of Cambridge and Morris, suggesting that mature leaves are a source of the IAA in the basipetal transport stream.


My paper 20 years later: Effect of positive end-expiratory pressure on right ventricular function in humans.
In 1992, we published a report on the effect of positive end-expiratory pressure (PEEP) on right ventricular (RV) function in humans. We measured RV volumes and pressures and pericardial pressure (Ppc) as PEEP was increased from zero to 15 cm H20 in 12 patients after thoracotomy, using a pulmonary arterial catheter equipped with a rapid responding thermistor that allowed measurement of RV ejection fraction (RVef), while Ppc was measured via a pericardial balloon catheter. RV end-diastolic volume (EDV) was estimated as the ratio of stroke volume (SV) to RVef, whereas RV end-systolic volume (ESV) were estimated as RV EDV-SV. PEEP increased Ppc and Pra, but RVef unaltered. There was no relation between either RV filling pressure (Pra-Ppc) and EDV or the change in RV filling pressure and EDV, although EDV varied significantly with PEEP (p < 0.05). The relations between EDV and both SV and RVef were weak (r = 0.54 and 0.55, respectively). RVef varied inversely with ESV (r = -0.77), although it showed no relation to transmural peak pulmonary artery pressure (r = 0.28). However, both absolute and relative changes in EDV corresponded closely with respective ESV values (r = 0.94). We concluded that EDV varies independently of changes in filling pressure and that changes in ESV occur independently of changes in ejection pressure. These data can be explained by assuming that the RV shape changes can dissociate changes in RV EDV from changes in RV wall stress (preload). Thus, changes in RV EDV may or may not alter SV but should proportionately change ESV to a degree dependent on election pressure and contractility. Subsequent studies confirmed our findings which can be summarized as 1) RV filling is independent of Pra; thus central venous pressure cannot be used to estimate RV preload; and 2) for cardiac output to increase by the Starling mechanism the RV must dilate increasing RV ESV. Since the pericardium limits absolute biventricular volume, there is a finite limit to which cardiac output can increase by the Starling mechanism defined not by left ventricular contractility but by RV function. And 3) if fluid loading causes Pra to increase without increasing cardiac output, then resuscitation should stop as the patient is going into acute cor pulmonale. These truths help bedside clinicians understand the echocardiographic and hemodynamic signatures of both RV failure and volume responsiveness.


A simple gamma-backbone modification preorganizes peptide nucleic acid into a helical structure.
Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA, developed more than a decade ago in which the naturally occurring sugar phosphate backbone has been replaced by the N-(2-aminoethyl) glycine units. Unlike DNA or RNA in the unhybridized state (single strand) which can adopt a helical structure through base-stacking, although highly flexible, PNA does not have a well-defined conformational folding in solution. Herein, we show that a simple backbone modification at the gamma-position of the N-(2-aminoethyl) glycine unit can transform a randomly folded PNA into a helical structure. Spectroscopic studies showed that helical induction occurs in the C- to N-terminal direction and is sterically driven. This finding has important implication not only on the future design of nucleic acid mimics but also on the design of novel materials, where molecular organization and efficient electronic coupling are desired.


A systematic process to prioritize prevention activities sustaining progress toward the reduction of military injuries.
To sustain progress toward injury reduction and other health promotion goals, public health organizations need a systematic approach based on data and an evaluation of existing scientific evidence on prevention. This paper describes a process and criteria developed to systematically and objectively define prevention program and policy priorities. Military medical surveillance data were obtained and summarized, and a working group of epidemiology and injury experts was formed. After reviewing the available data, the working group used predefined criteria to score leading military unintentional injury causes on five main criteria that assessed factors contributing to program and policy success: (1) importance of the problem, (2) effectiveness of existing prevention strategies, (3) feasibility of establishing programs and policies, (4) timeliness of implementation and results, and (5) potential for evaluation. Injury problems were ranked by total median score. Causes with the highest total median scores were physical training (34 points), military parachuting (32 points), privately-owned vehicle crashes (31 points), sports (29 points), falls (27 points), and military vehicle crashes (27 points). Using a data-driven, criteria-based process, three injury causes (physical training, military parachuting, and privately owned-vehicle crashes) with the greatest potential for successful program and policy implementation were identified. Such information is useful for public health practitioners and policymakers who must prioritize among health problems that are competing for limited resources. The process and criteria could be adapted to systematically assess and prioritize health issues affecting other communities.


Dorsal longitudinal foreskin cut is associated with reduced risk of HIV, syphilis and genital herpes in men: a cross-sectional study in Papua New Guinea.
Various forms of penile foreskin cutting are practised in Papua New Guinea. In the context of an ecological association observed between HIV infection and the dorsal longitudinal foreskin cut, we undertook an investigation of this relationship at the individual level. We conducted a cross-sectional study among men attending voluntary confidential HIV counselling and testing clinics. Following informed consent, participants had a face-to-face interview and an examination to categorize foreskin status. HIV testing was conducted on site and relevant specimens collected for laboratory-based Herpes simplex type-2 (HSV-2), syphilis, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) testing. Overall, 1073 men were enrolled: 646 (60.2%) were uncut; 339 (31.6%) had a full dorsal longitudinal cut; 72 (6.7%) a partial dorsal longitudinal cut; and 14 (1.3%) were circumcised. Overall, the prevalence of HIV was 12.3%; HSV-2, 33.6%; active syphilis, 12.1%; CT, 13.4%; NG, 14.1%; and TV 7.6%. Compared with uncut men, men with a full dorsal longitudinal cut were significantly less likely to have HIV (adjusted odds ratio [adjOR] 0.25, 95%CI: 0.12, 0.51); HSV-2 (adjOR 0.60, 95%CI: 0.41, 0.87); or active syphilis (adjOR 0.55, 95%CI: 0.31, 0.96). This apparent protective effect was restricted to men cut prior to sexual debut. There was no difference between cut and uncut men for CT, NG or TV. In this large cross-sectional study, men with a dorsal longitudinal foreskin cut were significantly less likely to have HIV, HSV-2 and syphilis compared with uncut men, despite still having a complete (albeit morphologically altered) foreskin. The protective effect of the dorsal cut suggests that the mechanism by which male circumcision works is not simply due to the removal of the inner foreskin and its more easily accessible HIV target cells. Exposure of the penile glans and inner foreskin appear to be key mechanisms by which male circumcision confers protection.Further research in this unique setting will help improve our understanding of the fundamental immunohistologic mechanisms by which male circumcision provides protection, and may lead to new biomedical prevention strategies at the mucosal level.


The Incidence Rate of Liver Cancer in Saudi Arabia: An Observational Descriptive Epidemiological Analysis of Data from the Saudi Cancer Registry (2004-2014).
This study describes the epidemiological pattern of liver cancer in all regions of Saudi Arabia. It explores the frequency of cases diagnosed, the age-specific incidence rate (AIR), the crude incidence rate (CIR), and the age-standardised incidence rate (ASIR) stratified by age group, year of diagnosis, and region. A retrospective descriptive epidemiological analysis of all liver cancer cases documented in the Saudi Cancer Registry (SCR) between 2004 and 2014 was performed. The data were analysed using descriptive statistics, t-test, Kruskal-Wallis, and sex ratio with the Statistical Package for the Social Sciences version 20.0 (SPSS). A total of 4723 liver cancer cases were registered in the SCR between January 2004 and December 2014. The highest overall ASIR of liver cancer among Saudi males was observed in the regions of Riyadh, Najran, and Tabuk at 10.4, 7.7, and 7.0 per 100,000 males, respectively. Furthermore, Riyadh, Eastern Region, and Tabuk recorded the highest overall ASIR among Saudi females at 4.9, 2.8, and 2.6 per 100,000 females, respectively. Jazan had the lowest overall ASIR (1.7 per 100,000 males) of liver cancer among male Saudis, while the Northern region and Baha had the lowest overall ASIR (0.6 and 0.9 per 100,000 females, respectively) of liver cancer among female Saudis. However, the overall ASIR of liver cancer was statistically higher in males than females (P-value <0.05), and the overall male-to-female ratio in ASIR of liver cancer in Saudi Arabia was 2.4 per 100,000. There was a slight increase in the CIRs and ASIRs of liver cancer in Saudi Arabia between 2004 and 2014. Riyadh, Najran, and Tabuk were the areas most affected by liver cancer among Saudi males, and Riyadh, Eastern Region, and Tabuk among female Saudis. The areas least affected by liver cancer were observed in Jazan among Saudi males, and the Northern region and Baha among Saudi females. The rates of liver cancer in Saudi Arabia were significantly higher among males compared with female Saudis.


Emerging pharmacotherapeutic strategies for cholangiocarcinoma.
Although of limited clinical benefit, chemotherapy represents the cornerstone of management for patients with inoperable cholangiocarcinoma. The literature on chemotherapy in advanced cholangiocarcinoma is difficult to interpret because of the heterogeneity of cholangiocarcinoma, the use of various chemotherapeutic agents in different combinations and dosing regimens, and the small size of existing patient cohorts. The authors discuss the major advances in the therapy of cholangiocarcinoma over the past decade. The audience will become familiarized with the contemporary medical management of cholangiocarcinoma and potentially useful agents/combinations for the therapy of this entity in the future. In recent years, gemcitabine-based chemotherapy has improved overall survival in advanced cholangiocarcinoma. Although gemcitabine-cisplatin combination represents the largely accepted standard for biliary cancers at present, very few studies so far have looked at the results in cholangiocarcinoma patients only. Therefore, large multicenter, randomized clinical trials are essential to identify the optimal treatment strategy for this rare tumor. In addition, regimens employing gemcitabine with oxaliplatin and/or fluoropyrimidines have shown promising results and warrant additional investigation in cholangiocarcinoma. The efficacy of a variety of newer agents is also now being tested in clinical trials.


Probabilistic assessment of clone overlaps in DNA fingerprint mapping via a priori models.
We construct a combinatorially exact probability distribution for the problem of a priori clone overlap assessment in DNA fingerprint mapping. It is implemented as a general enumeration methodology using Bell's exponential polynomials. Established computational metrics do not consider the conditional nature of the problem. They dramatically overpredict actual match probabilities as a consequence. This elevates the rate of false-negative overlap declarations, which is consistent with previous validation studies. Increased measurement resolution does not significantly improve accuracy. We describe general trends in error behavior for intermediate-size DNA clones and discuss corresponding limits on the ability to assess certain overlaps.


Bioinspired heterostructured bead-on-string fibers via controlling the wet-assembly of nanoparticles.
A kind of bioinspired heterostructured bead-on-string fiber (BHBF), composed of poly-(methyl methacrylate) (PMMA) and titanium tetrachloride (TiCl4) hydrolyzed nanoparticles, was prepared via integrating a wet-assembly system, including PMMA electrospinning, fog of nanoparticles and water coalescence at multi-stages. The wet-assembly of BHBF was regulated by the difference in surface energy and Laplace pressure. Especially, BHBF is characteristic of a hydrophilic rough bead for excellent water collection ability.


Identification and analysis of a gene (abpA) encoding a major amylase-binding protein in Streptococcus gordonii.
Oral streptococci such as Streptococcus gordonii bind the abundant salivary enzyme alpha-amylase. This interaction may be important in dental plaque formation and metabolism, thus contributing to the initiation and progression of dental caries and periodontal disease, the two most common plaque-mediated diseases. The conjugative transposon Tn916 was used to insertionally inactivate gene(s) essential to the expression of amylase-binding components of S. gordonii Challis, and a mutant deficient in amylase-binding (Challis Tn1) was identified. While wild-type strains of S. gordonii released both 20 kDa and 82 kDa amylase-binding proteins into culture supernatants, Challis Tn1 expressed the 82 kDa but not the 20 kDa protein. The 20 kDa amylase-binding protein was isolated from culture supernatants of S. gordonii Challis by hydroxyapatite chromatography. A partially purified, functionally active 20 kDa protein was sequenced from blots, and the N-terminal sequence obtained was found to be DEP(A)TDAAT(R)NND. A novel strategy, based on the single-specific-primer polymerase chain reaction technique, enabled the gene inactivated by Tn916 to be cloned. Analysis of the resultant nucleotide sequence revealed an open reading frame of 585 bp, designated amylase-binding protein A (abpA), encoding a protein of 20 kDa (AbpA), immediately downstream from the insertion site of Tn916. This protein possessed a potential signal peptide followed by a region having identity with the N-terminal sequence of the 20 kDa amylase-binding protein. These results demonstrate the role of the 20 kDa protein in the binding of amylase to S. gordonii. Knowledge of the nature of amylase-binding proteins may provide a better understanding of the role of these proteins in the colonization of S. gordonii in the oral cavity.


[Hygienic evaluation of the combined effect of electromagnetic fields and pesticides in experimental conditions].
The paper deals with the evaluation of combined effects of some natural and anthropogenic factors that are typical of the Kursk magnetic anomaly region by means of dispersion analysis in the experiments on albino rats and mice. The resultant signs were the indices of animal deaths, nonspecific protective factors, immune responses, changes in body weight, etc. A higher geomagnetic field can modify the biological effects of exposure to agricultural chemicals. The combined effects of a static electromagnetic field with induction of 300 microT to 0.3 T and of chlorpyrifos at various concentrations (0.1, 1, 50, and 100 mg/kg) were found to potentiate the toxic properties of the pesticide. The proportion of the potentiation effects increased as the intensity of the studied factors rose. The dispersion analysis established a predominant role of chlorpyrifos in the combined effects of the factors on the death of animals, serum complementary activity, antibody- and rosette-forming cells of the spleen and other lymphoid organs. The role of a static electromagnetic field is prevalent in the formation of effects of the intensity and completeness of phagocytosis.


Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.
To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.


Management of carbon monoxide poisoning in the absence of hyperbaric oxygenation chamber.
Manifestations of carbon monoxide poisoning are mostly attributable to acute hypoxic insult. In the absence of immediately available hyperbaric oxygen chamber, 100% oxygen should be delivered to the patient until carboxyhemoglobin levels in the blood are less than 5%. Presence of abnormal motor activity or prolonged abnormal consciousness are indications for proceeding with hypothermia and mechanical ventilation. Reversal of these manifestations was achieved in 3 reported cases though induction of hypothermia was delayed for as long as 24 hours. However, no beneficial effects were obtained in a fourth patient who did not receive hypothermia until 5 days after exposure. The duration of hypothermia varied between 60-70 hours in patients who showed near-complete recovery.


An approach to studying social disparities in health and health care.
We explored methods and potential applications of a systematic approach to studying and monitoring social disparities in health and health care. Using delayed or no prenatal care as an example indicator, we (1) categorized women into groups with different levels of underlying social advantage; (2) described and graphically displayed rates of the indicator and relative group size for each social group; (3) identified and measured disparities, calculating relative risks and rate differences to compare each group with its a priori most-advantaged counterpart; (4) examined changes in rates and disparities over time; and (5) conducted multivariate analyses for the overall sample and "at-risk" groups to identify particular factors warranting attention. We identified at-risk groups and relevant factors and suggest ways to direct efforts for reducing prenatal care disparities. This systematic approach should be useful for studying and monitoring disparities in other indicators of health and health care.


Distinct impacts of high intensity caregiving on caregivers' mental health and continuation of caregiving.
Although high-intensity caregiving has been found to be associated with a greater prevalence of mental health problems, little is known about the specifics of this relationship. This study clarified the burden of informal caregivers quantitatively and provided policy implications for long-term care policies in countries with aging populations. Using data collected from a nationwide five-wave panel survey in Japan, I examined two causal relationships: (1) high-intensity caregiving and mental health of informal caregivers, and (2) high-intensity caregiving and continuation of caregiving. Considering the heterogeneity in high-intensity caregiving among informal caregivers, control function model which allows for heterogeneous treatment effects was used.This study uncovered three major findings. First, hours of caregiving was found to influence the continuation of high-intensity caregiving among non-working informal caregivers and irregular employees. Specifically, caregivers who experienced high-intensity caregiving (20-40 h) tended to continue with it to a greater degree than did caregivers who experienced ultra-high-intensity caregiving (40 h or more). Second, high-intensity caregiving was associated with worse mental health among non-working caregivers, but did not have any effect on the mental health of irregular employees. The control function model revealed that caregivers engaging in high-intensity caregiving who were moderately mentally healthy in the past tended to have serious mental illness currently. Third, non-working caregivers did not tend to continue high-intensity caregiving for more than three years, regardless of co-residential caregiving. This is because current high-intensity caregiving was not associated with the continuation of caregiving when I included high-intensity caregiving provided during the previous period in the regression. Overall, I noted distinct impacts of high-intensity caregiving on the mental health of informal caregivers and that such caregiving is persistent among non-working caregivers who experienced it for at least a year. Supporting non-working intensive caregivers as a public health issue should be considered a priority.


BMP-mediated specification of the erythroid lineage suppresses endothelial development in blood island precursors.
The developmental relationship between the blood and endothelial cell (EC) lineages remains unclear. In the extra-embryonic blood islands of birds and mammals, ECs and blood cells are closely intermixed, and blood island precursor cells in the primitive streak express many of the same molecular markers, leading to the suggestion that both lineages arise from a common precursor, called the hemangioblast. Cells within the blood island of Xenopus also coexpress predifferentiation markers of the blood and EC lineages. However, using multiple assays, we find that precursor cells in the Xenopus blood island do not normally differentiate into ECs, suggesting that classic hemangioblasts are rare or nonexistent in Xenopus. What prevents these precursor cells from developing into mature ECs? We have found that bone morphogenetic protein (BMP) signaling is essential for erythroid differentiation, and in the absence of BMP signaling, precursor cells adopt an EC fate. Furthermore, inhibition of the erythroid transcription pathway leads to endothelial differentiation. Our results indicate that bipotential endothelial/erythroid precursor cells do indeed exist in the Xenopus blood island, but BMP signaling normally acts to constrain EC fate. More generally, these results provide evidence that commitment to the erythroid lineage limits development of bipotential precursors toward an endothelial fate.


The predictive value of memory strategies for Alzheimer's disease in subjects with mild cognitive impairment.
Subjects with Alzheimer's disease (AD) show impaired learning strategies. Whether impaired learning strategies are already present in subjects with prodromal AD remains unknown. The aim of the present study was to investigate the predictive accuracy of learning strategies for AD in subjects with Mild Cognitive Impairment (MCI). Subjects with MCI (n = 202) were selected from the Maastricht Memory Clinic. Subjects were reassessed over a period of 10 years. Fifty-five of the 202 subjects converted to AD. Learning strategies investigated were subjective organization and serial clustering. Lower scores of subjective organization were associated with a higher risk for AD (OR = 2.1, p = .002). Serial clustering did not predict AD. Prodromal AD is characterized by a decreased use of effortful learning strategies. This finding may have implications for the early detection of AD in MCI subjects and for the development of cognitive training programs.


Short-term clinical outcomes of postoperative intrapelvic bleeding after extended pelvic surgery: a single institute experience.
Intrapelvic bleeding after extended pelvic surgery is fatal, but few reports have addressed this serious situation. The objective of the present study was to evaluate the short-term clinical outcome of this complication. This study was a retrospective medical chart review of 130 patients who underwent extended pelvic surgery between 2000 and 2012 at our Institute. Based on the classification of the bleeding pelvic artery, how initial hemostasis and control of secondary pelvic abscess were mainly evaluated. In 6 patients, bleeding involved a peripheral artery (peripheral group) and 4 a main artery (central group). For initial hemostasis, interventional radiology was efficacious. Compared to the peripheral group, even if initial hemostasis succeeded, unsatisfactory abscess drainage easily became fatal in the central group. Aggressive surgical abscess drainage should be considered at an appropriate time for optimal survival in patients with involvement of a main artery with insufficient tube drainage.


Reduced CPU Workload for Human Pose Detection with the Aid of a Low-Resolution Infrared Array Sensor on Embedded Systems.
Modern embedded systems have achieved relatively high processing power. They can be used for edge computing and computer vision, where data are collected and processed locally, without the need for network communication for decision-making and data analysis purposes. Face detection, face recognition, and pose detection algorithms can be executed with acceptable performance on embedded systems and are used for home security and monitoring. However, popular machine learning frameworks, such as MediaPipe, require relatively high usage of CPU while running, even when idle with no subject in the scene. Combined with the still present false detections, this wastes CPU time, elevates the power consumption and overall system temperature, and generates unnecessary data. In this study, a low-cost low-resolution infrared thermal sensor array was used to control the execution of MediaPipe's pose detection algorithm using single-board computers, which only runs when the thermal camera detects a possible subject in its field of view. A lightweight algorithm with several filtering layers was developed, which allowed the effective detection and isolation of a person in the thermal image. The resulting hybrid computer vision proved effective in reducing the average CPU workload, especially in environments with low activity, almost eliminating MediaPipe's false detections, and reaching up to 30% power saving in the best-case scenario.


Evaluation of Serum Pregnancy Associated Plasma Protein-A & Plasma D-Dimer in Acute Coronary Syndrome.
Acute coronary syndrome (ACS), a spectrum comprising unstable angina pectoris, ST Elevated Myocardial Infarction (STEMI) & Non ST Elevated Myocardial Infarction (NSTEMI) is the major cause of presentation in Emergency Department today. Though ECG and cardiac enzymes are used for diagnosis, they mislead the diagnosis sometimes and delay in treatment initiation. This leads us to search certain new parameters which reflect the pathophysiology of ACS. Markers of plaque stability like Pregnancy Associated Plasma Protein-A and D-Dimer, a marker of ongoing thrombosis are found to be better markers in early diagnosis. To evaluate the diagnostic competence of PAPP-A and D-Dimer in acute coronary syndrome over CK-MB and to compare with the inflammatory marker High Sensitive C-Reactive Protein (hs-CRP) which is associated with atherosclerosis. Fifty patients presenting with acute onset of chest pain to Emergency Department with or without ECG changes served as cases and 50 healthy people served as controls. Serum PAPP-A is measured by Enzyme Linked Immunosorbent Assay (ELISA), D-Dimer and hs-CRP by using Latex Turbidimetry method. A statistical significant difference of PAPP-A and D-Dimer was noted between the ACS and controls (p < 0.001) whereas CK-MB shows no much difference (p 0.09). Statistically significant positive correlation is noted between parameters. PAPP-A marker of plaque instability and D-Dimer marker of ongoing thrombosis are raised in acute coronary syndrome and thus can be considered as one of the marker in ACS for diagnosis.


Endoscopic management of dumping syndrome after Roux-en-Y gastric bypass: a large international series and proposed management strategy.
Roux-en-Y gastric bypass (RYGB) is refractory to lifestyle and pharmacotherapy measures, requiring reversal of the patient's bariatric surgery. Reversal can lead to weight regain and recrudescence of their comorbidities. Our aim was to report a multicenter experience on the endoscopic management of refractory dumping syndrome with endoscopic transoral outlet reduction (TORe). A multicenter international series of consecutive patients who underwent TORe with a full-thickness endoscopic suturing device was analyzed for technical success, improvement in Sigstad scores, and weight trajectories after the procedure. Failure was defined as needing an enteral feeding tube, surgical reversal, or repeat TORe. One hundred fifteen patients across 2 large academic centers in Germany and the United States underwent TORe for dumping syndrome. Patient age was mean 8.9 ± 1.1 years from their initial RYGB with an average percent total body weight loss of 31% ± 10.6% at the time of endoscopy. Three months postprocedure, the Sigstad score improved from a mean of 17 ± 6.1 to 2.6 ± 1.9 (paired t test P = .0001) with only 2% of patients (n = 2) experiencing weight gain. Mean weight loss and percentage of total body weight loss 3 months post-TORe were 9.47 ± 3.6 kg and 9.47% ± 2.5%, respectively. Six patients (5%) failed initial endoscopic therapy, with 50% (n = 3) successfully treated with a repeat TORe. Three patients underwent surgical reversal, indicating an overall 97% endoscopic success rate. TORe as an adjunct to lifestyle and pharmacologic therapy for refractory dumping syndrome is safe and effective at improving dumping syndrome and reducing rates of surgical revision.


Clinical and molecular diagnosis of Alport syndrome.
Alport syndrome is an inherited disorder of collagen that affects the kidney, the eye, and the cochlea. The disease exhibits variability in its clinical and pathological manifestations, and is genetically heterogeneous. The X-linked dominant form of Alport syndrome arises from mutation in the COL4A5 gene, which encodes the alpha 5 chain of type IV collagen. The autosomal recessive form is caused by mutation in the COL4A3 gene, which encodes the alpha 3 chain of type IV collagen, or in the COL4A4 gene, which encodes the alpha 4 chain of type IV collagen. An autosomal dominant variety of Alport syndrome also exists, but mutations in this form of the disease have not yet been described. Cotransmission of X-linked dominant Alport syndrome and diffuse leiomyomatosis in some families results from deletions involving the COL4A5 gene and the contiguous COL4A6 gene. The clinical and pathologic features of Alport syndrome are attributable to abnormalities in the basement membrane collagen network composed of the alpha 3, alpha 4, and alpha 5 chains of type IV collagen, although the mechanism by which mutation in the gene encoding one of these chains effects the other two chains is not yet known. In addition, the processes that lead to progressive glomerular scarring and renal failure are incompletely understood. While diagnosis of Alport syndrome still rests on clinical and pathologic evaluation, immunohistochemical and molecular genetic tools can augment diagnostic precision.


Ly-4.2: a cell membrane alloantigen of murine B lymphocytes. I. Population studies.
The Ly-4 locus defines an alloantigenic specificity present on the surface of lymphocytes of some mouse strains and detected in lymphocytotoxicity tests by an antiserum (BALB/c times SWR)F1 anti-B10.D2. In this paper are presented results which indicate that Ly-4.2 is predominantly represented on B cells and not T cells. In cytotoxicity tests with rabbit complement, the distribution of Ly-4.2 is restricted: thymus 5%, TDL 12%, spleen 60%, lymph node 30%, bone marrow 36%, Peyer's patches 55%, peritoneal exudate cells 35%, and peripheral lymphocytes 35%. This distribution is the reciprocal of that obtained with anti-Thy-1 antiserum. Further, when both reagents were used together, almost all cells in these tissues were lysed, excepting those with bone marrow. When anti-Ly-4.2 and anti-Thy-1.2 were used sequentially, it was apparent that these specificities were present on different cell populations. As Thy-1 is a marker for T cells, Ly-4 is therefore, presumably, a marker for B cells. This conclusion was confirmed by testing mice depleted of T cells ("nude"; thymectomy + anti-lymphocyte serum treatment; thymectomy, irradiation + reconstitution with bone marrow) where the majority of lymphocytes were Ly-4.2+, Thy-1.2-; and by testing tumors, where, for the most part, this reciprocal relationship held true. Appropriate studies indicate that the Ly-4.2 antibody does not detect a surface immunoglobulin allotype. Anti-Ly-4.2 anti-serum may provide a useful alloantigenic marker distinct from immunoglobulin, mouse-specific bone marrow-derived lymphocyte anti;en, and "beta" for detecting some or all, B cells.


Synthesis of Novel C/D Ring Modified Bile Acids.
Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure-activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro-furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.


Predicting explorative motor learning using decision-making and motor noise.
A fundamental problem faced by humans is learning to select motor actions based on noisy sensory information and incomplete knowledge of the world. Recently, a number of authors have asked whether this type of motor learning problem might be very similar to a range of higher-level decision-making problems. If so, participant behaviour on a high-level decision-making task could be predictive of their performance during a motor learning task. To investigate this question, we studied performance during an explorative motor learning task and a decision-making task which had a similar underlying structure with the exception that it was not subject to motor (execution) noise. We also collected an independent measurement of each participant's level of motor noise. Our analysis showed that explorative motor learning and decision-making could be modelled as the (approximately) optimal solution to a Partially Observable Markov Decision Process bounded by noisy neural information processing. The model was able to predict participant performance in motor learning by using parameters estimated from the decision-making task and the separate motor noise measurement. This suggests that explorative motor learning can be formalised as a sequential decision-making process that is adjusted for motor noise, and raises interesting questions regarding the neural origin of explorative motor learning.


Is the distribution of training practices appropriate for the needs of general practice?
The distribution of practices that train general practitioners in the west of Scotland was examined. The concentration of training practices is lowest in conurbations that are grossly deprived. Several topics require debate: should trainees be given experience in such areas as an elective? Should the criteria for selecting training practices be similar in all areas? Should practices in deprived areas be encouraged to apply to become training practices?


Comparison of minimally invasive direct coronary artery bypass surgery with implantation of drug-eluting stentsin patients with left anterior descending coronary artery disease.
: Bypass surgery and percutaneous coronary interventions improve the clinical status of patients with left anterior descending coronary artery disease. However, these techniques differ in invasiveness and in the need for subsequent reinterventions. The development of minimally invasive direct coronary artery bypass (MIDCAB) surgery and of drug-eluting stents (DES) offers perspectives to close this gap. : We compared the long-term clinical outcome of 308 patients after revascularization for isolated left anterior descending coronary artery disease. One hundred fifty-four patients were treated with MIDCAB and 154 with percutaneous coronary interventions and DES implantation. : Both groups were similar in age (63 ± 13 and 62 ± 10 years), Euroscore (3.3 ± 2.8 and 3.4 ± 2.6), and mean duration of follow-up (30 ± 17 and 24 ± 10 months). Two-year survival was similar after MIDCAB and after DES (97.4% and 94.8%). During follow-up, four patients (2.6%) of the MIDCAB group and 21 patients (13.6%) of the DES group needed subsequent revascularization of the target vessel (P = 0.001). Revascularization of a nontarget vessel was needed in 11 patients (7%) of the MIDCAB group and in 17 patients (11%) of the DES group (NS). Neurologic complications included two transient ischemic accidents and two strokes in the MIDCAB group but three fatal cerebral hemorrhages and one stroke in the DES group. Major adverse coronary and cerebrovascular events rates were 14% in the MIDCAB and 31% in the DES group. : MIDCAB and DES implantation showed similar rates of mortality but a higher reintervention rate after DES. Anticoagulation implications remain critical for the future of DES.


Exposure of cotton workers in an experimental cardroom with reference to airborne endotoxins.
Workers from cotton mills were exposed to cotton dust during carding in an experimental cardroom. Cotton from different geographical locations with varying amounts of endotoxin were used. Exposure levels ranged from 0.6 to 3.6 mg dust/m3 (from a vertical elutriator) and from 0.1 to 8.0 micrograms/m3 of endotoxin. No relationship was found between the decrease in FEV1 over the workshift and the amount of airborne dust. Airborne endotoxin correlated with the decrease in FEV1 and the increase in blood neutrophils. The FEV1 decrease was more pronounced among smokers. The data suggest that the amount of airborne endotoxin determines the risk for development of the acute symptoms in the byssinosis syndrome.


Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.
Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome. A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023. 28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis. Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.


Resistance to tomato yellow leaf curl geminivirus in Nicotiana benthamiana plants transformed with a truncated viral C1 gene.
The C1 gene of tomato yellow leaf curl geminivirus (TYLCV) encodes a multifunctional protein (Rep) involved in replication. A truncated form of this gene, capable of expressing the N-terminal 210 amino acids (aa) of the Rep protein, was cloned under the control of the CaMV 35S promoter and introduced into Nicotiana benthamiana using Agrobacterium tumefaciens. The same sequence was also cloned in antisense orientation. When self-pollinated progeny of 19 primary transformants were tested for resistance to TYLCV by agroinoculation, some plants proved to be resistant, particularly in the sense lines. Two such lines were further studied. The presence of the transgene was verified and its expression was followed at intervals. All plants that were resistant to TYLCV at 4 weeks postinoculation (wpi) contained detectable amounts of transgenic mRNA and protein at the time of infection. Resistance was overcome in a few plants at 9 wpi, and in most at 15 wpi. Infection of leaf discs derived from transgenic plants showed that expression of the transgene correlated with a substantial reduction of viral DNA replication. Cotransfections of tobacco protoplasts demonstrated that inhibition of viral DNA replication requires expression of the truncated Rep protein and suggested that the small ORF C4, also present in our construct, plays no role in the resistance observed. The results obtained using both transient and stable gene expression systems show that the expression of the N-terminal 210 aa of the TYLCV Rep protein efficiently interferes with virus infection.


Factors in Pulmonary Embolus Diagnosis via CT Pulmonary Angiogram in Patients Undergoing Repair of Proximal Femur Fractures.
As imaging technology improves small Pulmonary Emboli (PE) of debatable clinical relevance are increasingly detected leading to higher numbers of patients receiving anticoagulation. Although PE are an important cause of morbidity and mortality in patients undergoing repair of proximal femur fractures, this cohort of patients are at increased falls risk and are therefore largely unsuitable for long term anticoagulant therapy. 1. To review sequential Computed Tomography Pulmonary Angiograms (CTPA) performed in patients who underwent repair of proximal femur fractures at our institution. 2. To establish the perioperative CT imaging performed. A retrospective cross sectional study of all patients undergoing proximal femur fracture repair at a single tertiary referral. The theatre database was interrogated to reveal all patients undergoing proximal femur fracture repair over a 28 month period from 01/01/12 to 07/04/14 inclusive. This was cross-referenced with the Picture Archiving Communication System (PACS) to establish all imaging undertaken in the perioperative period. CTPA studies performed within the time period of 1 week prior to and 6 months post proximal femur fixation were included. CTPA studies and reports were assessed for quality and findings. D-Dimer results, if performed within 72 hours of the CTPA study, were recorded. 1388 patients underwent neck of femur fracture repair in the 28-month study period. Of this cohort 71 CTPA studies were performed in 71 patients (5.2%) with a mean age of 77.8 years (range 38 - 100). 53 (74.6%) of studies were negative for embolus and 17 (23.9%) studies revealed clot in a pulmonary artery (1 saddle embolus, 2 main pulmonary artery emboli, 7 lobar vessel emboli, 2 segmental artery emboli, 5 subsegmental emboli). Overall PE detection rate was 1.2% of our total study population. In all 71 studies, Houndsfield Unit (HU) in the main pulmonary artery (PA) was >200; which is considered to be of satisfactory quality to assess for segmental pulmonary emboli. 32% of patients had D Dimer levels performed, however no relationship with presence of PE on CTPA was demonstrated. The rate of positive CTPA studies in patients undergoing proximal femur fracture repair is 23.9% in our patient population, comparing favorably to published data. This is likely to reflect good compliance with prevention measures at ward level. D-Dimer results are unreliable for PE prediction.


Familial resemblance in humoral immune response to defined and crude Schistosoma mansoni antigens in an endemic area in Brazil.
This study addressed whether the humoral immune response to crude and defined Schistosoma mansoni antigens aggregates within families. The sample included 155 siblings from 42 nuclear families in Brazil. Sera examined by ELISA for antibody isotypes reactive to defined schistosome antigens and crude schistosome antigens (soluble adult worm antigen preparation and soluble egg antigen) demonstrated that there was a difference in sibling-pair correlations between defined and crude S. mansoni antigens. In contrast to the finding with crude antigens, egg-positive sibling pairs showed significant familial resemblance for all IgG subclasses and IgE to adult-stage antigens Smp20.8 and Smp50. Only the IgE and IgG4 isotypes showed familial resemblance to the egg-stage antigen, Smp40. Egg-negative sibling pairs showed significant familial resemblance only for IgE and IgG4 to Smp40. That both the IgE and IgG4 response to defined S. mansoni antigens showed familial resemblance is interesting in light of the converging evidence for the role of IgE and IgG4 in human susceptibility and resistance to reinfection.


Retinal mechanisms of visual adaptation in the skate.
Electrical potentials were recorded from different levels within the skate retina. Comparing the adaptive properties of the various responses revealed that the isolated receptor potential and the S-potential always exhibited similar changes in sensitivity, and that the b-wave and ganglion-cell thresholds acted in concert. However, the two sets of responses behaved differently under certain conditions. For example, a dimly iluminated background that had no measurable effect on the senitivities of either of the distal responses, raised significantly the thresholds of both the b-wave and the ganglion cell responses. In addition, the rate of recovery during the early, "neural" phase of dark adaptation was significantly faster for the receptor and S-potentials than for the b-wave or ganglion cell discharge. These results indicate that there is an adaptive ("network") mechanism in the retina which can influence significantly b-wave and gaglion cell activity and which behaves independently of the receptors and horizontal cells. We conclude that visual adaptation in the skate retina is regulated by a combination of receptoral and network mechanisms.


PACAP through EGFR transactivation preserves human corneal endothelial integrity.
The corneal endothelium is composed of a single hexagonal-shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal-scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase-activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK/ERK1/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co-operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.


Electrochemical in situ investigations of SEI and dendrite formation on the lithium metal anode.
This comparative work studies the self-enforcing heterogeneity of lithium deposition and dissolution as the cause for dendrite formation on the lithium metal anode in various liquid organic solvent based electrolytes. In addition, the ongoing lithium corrosion, its rate and thus the passivating quality of the SEI are investigated in self-discharge measurements. The behavior of the lithium anode is characterized in two carbonate-based standard electrolytes, 1 M LiPF6 in EC/DEC (3 : 7) and 1 M LiPF6 in EC/DMC (1 : 1), and in two alternative electrolytes 1 M LiPF6 in TEGDME and 1 M LiTFSI in DMSO, which have been proposed in the literature as promising electrolytes for lithium metal batteries, more specifically for lithium/air batteries. As a result, electrolyte decomposition, SEI and dendrite formation at the lithium electrode as well as their mutual influences are understood in the development of overpotentials, surface resistances and lithium electrode surface morphologies in subsequent lithium deposition and dissolution processes. A general model of different stages of these processes could be elaborated.


Evaluation of connectivity measures to identify Seizure Onset and Propagation Zones in Refractory Epilepsy: A Case study with two different Post- Surgical Outcomes.
High Frequency Oscillations (HFO) have been found very useful in refractory epilepsy. They have been used to identify the epileptogenic zone and as a promising clinical biomarker for presurgical evaluation in childhood epilepsy. There is controversy about whether there is a spread of HFOs and their propagation. Some researchers reinforce the idea of dealing with epilepsy as a network disorder, so the fact of propagation can promote this research. The hypothesis of this study is that connectivity methods can be useful to detect the seizure onset and propagation zones. Methodology has been applied to two cases where the clinical outcomes after surgery were free of seizures and not free. Promising results were obtained to understand both situations. A future study with more cases is necessary to obtain strong conclusions.Clinical Relevance- This exploratory study shows the relationship between connectivity measures and the propagation of HFOs and this can be useful to know the epileptogenic function of these waves that, nowadays, are unknown. Connectivity features in conjunction with other multivariate estimators can be a tool to help in identifying the regions of interest in refractory epilepsy.


Community residential segregation and the local supply of federally qualified health centers.
To examine associations between community residential segregation by income and race/ethnicity, and the supply of federally qualified health centers (FQHCs) in urban areas. Area Resource File (2000-2007) linked with 2000 U.S. Census on U.S. metropolitan counties (N = 1,786). We used logistic and negative binomial regression models with state-level fixed effects to examine how county-level characteristics in 2000 are associated with the presence of FQHCs in 2000, and with the increase in FQHCs from 2000 to 2007. Income and racial/ethnic residential segregation were measured by poverty and the non-white dissimilarity indices, respectively. Covariates included measures of federal criteria for medically underserved areas/populations. Counties with a high non-white dissimilarity index and a high percentage of minorities were more likely to have an FQHC in 2000. When we examined the addition of new FQHCs from 2000 to 2007, the effects of both poverty and non-white dissimilarity indices were positive and significant. Residential segregation likely produces geographic segregation of health services, such that provider maldistribution may explain the association between residential segregation and FQHC supply. Metropolitan areas that fail to achieve greater integration of poor and minority communities may require FQHCs to compensate for provider shortages.


Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients.
To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.


Biochemical, biological and molecular characterization of an L-Amino acid oxidase (LAAO) purified from Bothrops pictus Peruvian snake venom.
An L-amino acid oxidase from Peruvian Bothrops pictus (Bpic-LAAO) snake venom was purified using a combination of size-exclusion and ion-exchange chromatography. Bpic-LAAO is a homodimeric glycosylated flavoprotein with molecular mass of ∼65 kDa under reducing conditions and ∼132 kDa in its native form as analyzed by SDS-PAGE and gel filtration chromatography, respectively. N-terminal amino acid sequencing showed highly conserved residues in a glutamine-rich motif related to binding substrate. The enzyme exhibited optimal activity towards L-Leu at pH 8.5, and like other reported SV-LAAOs, it is stable until 55 °C. Kinetic studies showed that the cations Ca2+, Mg2+ and Mn2+ did not alter Bpic-LAAO activity; however, Zn2+ is an inhibitor. Some reagents such as β-mercaptoethanol, glutathione and iodoacetate had inhibitory effect on Bpic-LAAO activity, but PMSF, EDTA and glutamic acid did not affect its activity. Regarding the biological activities of Bpic-LAAO, this enzyme induced edema in mice (MED = 7.8 μg), and inhibited human platelet aggregation induced by ADP in a dose-dependent manner and showed antibacterial activity on Gram (+) and Gram (-) bacteria. Bpic-LAAO cDNA of 1494 bp codified a mature protein with 487 amino acid residues comprising a signal peptide of 11 amino acids. Finally, the phylogenetic tree obtained with other sequences of LAAOs, evidenced its similarity to other homologous enzymes, showing two well-established monophyletic groups in Viperidae and Elapidae families. Bpic-LAAO is evolutively close related to LAAOs from B. jararacussu, B. moojeni and B. atrox, and together with the LAAO from B. pauloensis, form a well-defined cluster of the Bothrops genus.


A novel monoclonal antibody against porcine macrophage colony-stimulating factor (CSF1) detects expression on the cell surface of macrophages.
Macrophage colony-stimulating factor (CSF1) controls the proliferation and differentiation of cells of the mononuclear phagocyte system through binding to the receptor CSF1R. The expression and function of CSF1 has been well-studied in rodents and humans, but knowledge is lacking in other veterinary species. The development of a novel mouse anti-porcine CSF1 monoclonal antibody (mAb) facilitates the characterisation of this growth factor in pigs. Cell surface expression of CSF1 was confirmed on differentiated macrophage populations derived from blood and bone marrow monocytes, and on lung resident macrophages, the first species for this to be confirmed. However, monocytes isolated from blood and bone marrow lacked CSF1 expression. This species-specific mAb delivers the opportunity to further understanding of porcine myeloid cell biology. This is not only vital for the role of pigs as a model for human health, but also as a veterinary species of significant economic and agricultural importance.


Diffuse alveolar damage: uncommon manifestation of pulmonary involvement in patients with connective tissue diseases.
Diffuse alveolar damage (DAD) is a relatively common finding on surgical lung biopsy and can result from a variety of causes. We studied nine consecutive patients with connective tissue disease (CTD) and DAD diagnosed on surgical lung biopsy to examine this association and clinical implications. The median age was 63 years (range, 35 to 76 years), and seven of the patients were women (78%). Underlying CTDs included rheumatoid arthritis in five patients, polymyositis in two patients, and one patient each with systemic sclerosis and mixed CTD. In seven patients (78%), CTD had been diagnosed before the onset of DAD; six of these patients had a preexisting interstitial lung disease (ILD) related to their CTD. DAD was the presenting manifestation leading to a new CTD diagnosis in two patients (22%). CT of the chest revealed ground-glass opacities and/or consolidation bilaterally with or without honeycombing. In all patients, surgical lung biopsy revealed DAD for which no cause could be identified other than the underlying CTD. Seven patients (78%) were receiving mechanical ventilatory support at the time of the surgical lung biopsy. Four patients (44%) survived to hospital discharge and included one patient with preexisting ILD and all three patients without chronic ILD. We conclude that DAD can complicate the clinical course of patients with CTD-related chronic ILD, or can occasionally occur as a presenting manifestation of CTDs. When DAD occurs in patients with CTDs, the outcome appears to be worse for those with preexisting chronic ILD compared to those without ILD.


Study of potential mechanisms of traumatic rupture of the aorta using insitu experiments.
Traumatic rupture of the aorta (TRA) is an important transportation-related injury. This study investigated TRA mechanisms using in situ human cadaver experiments. Four quasi-static tests and one dynamic test were performed. The quasi-static experiments were conducted by perturbing the mediastinal structures of the cadavers. The mechanisms investigated included anterior, superior, and lateral displacement of the heart and aortic arch. The resulting injuries ranged from partial tears to complete transections. All injuries occurred within the peri-isthmic region. Intimal tears were associated with the primary injuries. The average failure load and stretch were 148 N and 30 percent for the quasi-static tests. This study illustrates that TRA can result from appropriate application of nominal levels of longitudinal load and tension. The results demonstrate that intraluminal pressure and whole-body acceleration are not required for TRA to occur. The results suggest that the role of the ligamentum arteriosum is likely limited, and that TRA can occur in the absence of pulmonary artery injury. Tethering of the descending thoracic aorta by the parietal pleura is a principal aspect of this injury.


Caring for patients with lived experience of homelessness.
To guide family physicians working in a range of primary care clinical settings on how to provide care and support for patients who are vulnerably housed or experiencing homelessness. The approach integrates recommendations from evidence-based clinical guidelines, the views of persons with lived experience of homelessness, the theoretical tenets of the Patient's Medical Home framework, and practical lessons learned from family physicians working in a variety of clinical practice settings. Family physicians can use simple and effective approaches to identify patients who are homeless or vulnerably housed; take initial steps to initiate access to housing, income assistance, case management, and treatment for substance use; and work collaboratively using trauma-informed and anti-oppressive approaches to better assist individuals with health and social needs. Family physicians also have a powerful advocacy voice and can partner with local community organizations and people with lived experience of homelessness to advocate for policy changes to address social inequities. Family physicians can directly address the physical health, mental health, and social needs of patients who are homeless or vulnerably housed. Moreover, they can champion outreach and onboarding programs that assist individuals who have experienced homelessness in accessing patient medical homes and can advocate for broader action on the underlying structural causes of homelessness.


A recyclable chiral Ru catalyst for enantioselective olefin metathesis. Efficient catalytic asymmetric ring-opening/cross metathesis in air.
The synthesis and structure of a new chiral bidentate imidazolinylidene ligand and a derived chiral Ru-based carbene are disclosed. The Ru complex is stereogenic at the metal center; it can be prepared in >98% diastereoselectivity and purified by silica gel chromatography with undistilled solvents. The air-stable Ru complex efficiently catalyzes ring-closing and ring-opening metathesis and is recyclable. The chiral complex is highly effective (0.5-10 mol % loading) in promoting enantioselective ring-opening/cross metathesis reactions (up to >98% ee). These enantioselective transformations can be effected in air, with unpurified solvent and with substrates that would only polymerize with Mo-based catalysts.


Post-liver transplant intrahepatic cholestasis: etiology, clinical presentation, therapy.
Post-liver transplant intrahepatic cholestasis is consequent to the impairment of bile flow or formation. It may develop in the early (within 6 months) or in the late (more than 6 months) post-liver transplant period and different causes may be recognized according to the time elapsed from a liver transplant. The raise at various degrees of serum bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase, with or without increased transaminases levels, are common hematochemical findings. Liver histology is helpful for diagnostic assessment, and sometimes crucial to differentiate among possible causes of cholestasis. Although timely treatment of underling conditions as well as supportive care may resolve post-liver transplant intrahepatic cholestasis, the risk of graft loss and retransplantation are remarkable. For this reason, post-liver transplant intrahepatic cholestasis should be managed in collaboration with the LT center, and treatment should be devolved to expert hepatologists.


A nursing care classification system for assessing workload and determining optimal nurse staffing in a teaching hospital in China: A pre-post intervention study.
We aimed to evaluate the effectiveness of a nursing care classification system for re-assessing nurse workload and determining staffing needs. Adequate bed-nurse ratios help manage hospital cost-efficiency, quality of care and patient safety. A prospective pre-post intervention study was conducted from January 2010 to December 2012 in 16 medical-surgical units of a tertiary teaching hospital. Nursing tasks were classified into four grades of care reflecting actual workload. Units were re-staffed accordingly and bed-nurse ratios compared with government-authorized bed-nurse ratios. Patient satisfaction, hospital stays and mortality were evaluated pre- and poststaffing changes. Average bed-nurse ratio (1:0.41) exceeded the national standard (1:0.40) in 16 units, but was inadequate in five units. Re-staffing increased average bed-nurse ratio from 1:0.41 to 1:0.48. Patients' satisfaction increased from 96.9% to 97.6%, and hospital stays decreased significantly. Nursing care classification effectively distributes nurse staffing to match patients' care levels, improving patient outcomes.


Relationship between smoking and health and education spending in Chile.
To estimate the degree to which tobacco consumption is associated with spending on a set of goods and services in Chile, especially health and education, for the total population as well as for specific subgroups. A seemingly unrelated regression equation system was used to estimate the statistical relationship between having tobacco expenditures and the budget share allocated to other items for the total population and for specific subgroups in Chile (eg, households within the bottom/top 33% by total expenditures). The use of household-level data allows for the control of a number of sociodemographic characteristics. The nationally representative 2012 Chilean Household Expenditure Survey was used for the analysis. Tobacco consumption is associated with lower budget shares allocated to healthcare, education and housing expenses, especially for poorer households. In the case of health, not consuming tobacco is related to higher health expenditures: up to 32% for the total population. Similarly, in the case of education, not consuming tobacco is statistically related to higher education expenditures: up to 16% for the total population. For all groups, tobacco consumption is also related to a significantly higher budget share allocated to alcoholic beverages. The strong significant statistical relationship found between tobacco consumption and resources allocated to healthcare and education consumption may be indicative of the existence of a crowding out effect of tobacco. This effect, in turn, may increase the burden that the rest of society must bear for the increased healthcare that they require because of tobacco consumption.