A systematic review of qualitative evidence on factors enabling and deterring uptake of HIV self-testing in Africa.
More than 40% of adults in Sub-Saharan Africa are unaware of their HIV status. HIV self-testing (HIVST) is a novel approach with a potential to increase uptake of HIV testing and linkage to care for people who test HIV positive. We explored HIV stakeholder's perceptions about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing of adult users in Africa. This systematic review of qualitative evidence included articles on qualitative studies published or made available between January 1998 to February 2018 on perspectives of key stakeholders, including HIV policymakers, HIV experts, health care providers, and adult men and women (18 years and above) about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing among adult users. We searched CINAHL, MEDLINE in Pubmed, EMBASE, AJOL, PsycINFO, Social Science Citation Index (SSCI), and Web of Science for articles in English on HIVST with qualitative data from different African countries. In total, 258 papers were retrieved, and only nine (9) studies conducted in 5 African countries were eligible and included in this synthesis. Perceived facilitators of the uptake of HIVST were autonomy and self-empowerment, privacy, confidentiality, convenience, opportunity to test, including couples HIV testing, and ease of use. The perceived barriers included the cost of buying self-test kits, perceived unreliability of test results, low literacy, fear and anxiety of a positive test result, and potential psychological and social harms. HIV stakeholder's concerns about HIVST included human right issues, lack of linkage to care, lack of face-to-face counseling, lack of regulatory and quality assurance systems, and quality of self-test kits. Actual HIVST users expressed preference of oral-fluid self-testing because of ease of use, and that it is less invasive and painless compared to finger-stick/whole blood-based HIV tests. Lack of clear instructions on how to use self-test kits, and existing different products of HIVST increases rates of user errors. Overcoming factors that may deter HIV testing, and HIVST, in particular, is complex and challenging, but it has important implications for HIV stakeholders, HIVST users, and public health in general. Research is warranted to explore the actual practices related to HIVST among different populations in Africa.


Generation of targeted Chlamydia trachomatis null mutants.
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects hundreds of millions of individuals globally, causing blinding trachoma and sexually transmitted disease. More effective chlamydial control measures are needed, but progress toward this end has been severely hampered by the lack of a tenable chlamydial genetic system. Here, we describe a reverse-genetic approach to create isogenic C. trachomatis mutants. C. trachomatis was subjected to low-level ethyl methanesulfonate mutagenesis to generate chlamydiae that contained less then one mutation per genome. Mutagenized organisms were expanded in small subpopulations that were screened for mutations by digesting denatured and reannealed PCR amplicons of the target gene with the mismatch specific endonuclease CEL I. Subpopulations with mutations were then sequenced for the target region and plaque-cloned if the desired mutation was detected. We demonstrate the utility of this approach by isolating a tryptophan synthase gene (trpB) null mutant that was otherwise isogenic to its parental clone as shown by de novo genome sequencing. The mutant was incapable of avoiding the anti-microbial effect of IFN-γ-induced tryptophan starvation. The ability to genetically manipulate chlamydiae is a major advancement that will enhance our understanding of chlamydial pathogenesis and accelerate the development of new anti-chlamydial therapeutic control measures. Additionally, this strategy could be applied to other medically important bacterial pathogens with no or difficult genetic systems.


Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival.
The incidence of melanoma continues to dramatically increase in most Western countries with predominantly Caucasian populations. However, only limited therapies for the metastatic stage of the disease are currently available. The main purpose of this study is to determine approaches that can substantially increase radiosensitivity of melanoma cells. The PI3K-AKT, NF-kappaB and COX-2 pathways, which are involved in the radioprotective response, are highly active in melanoma cells. Pharmacological suppression of COX-2 and PI3K-AKT, or RNAi-mediated knockdown of COX-2, substantially increased levels of G2/M arrest of the cell cycle and decreased clonogenic survival of gamma-irradiated melanomas, predominantly via a necrotic mechanism. On the other hand, resveratrol, a polyphenolic phytoalexin, selectively targets numerous cell signaling pathways, decreasing clonogenic survival primarily via an apoptotic mechanism. In melanoma cells, resveratrol inhibits STAT3 and NF-kappaB-dependent transcription, culminating in suppression of cFLIP and Bcl-xL expression, while activating the MAPK- and the ATM-Chk2-p53 pathways. Resveratrol also upregulates TRAIL promoter activity and induces TRAIL surface expression in some melanoma cell lines, resulting in a rapid development of apoptosis. Sequential treatment of melanoma cells, first with gamma-irradiation to upregulate TRAIL-R surface expression, and then with resveratrol to suppress antiapoptotic proteins cFLIP and Bcl-xL and induce TRAIL surface expression, had dramatic effects on upregulation of apoptosis in some melanoma lines, including SW1 and WM35. However, for melanoma lines exhibiting suppressed translocation of TRAIL to the cell surface, a necrotic mechanism of cell death was primarily involved in radiation response. Hence, surface expression of TRAIL induced by resveratrol appears to be a decisive event, one which determines an apoptotic versus a necrotic response of melanoma cells to sequential treatment.


Steroids and steroid metabolism in plant tissue cultures.
The steroids which have been isolated from plant callus and suspension cultures are reviewed. In addition, the research involving the use of plant tissue cultures to investigate steroid biosynthesis and metabolism is summarized.


Best Practices for Building a Bimodal/Bilingual Child Language Corpus.
This article addresses the special challenges associated with collecting longitudinal samples of the spontaneous sign language and spoken language production by young bimodal bilingual children. We discuss the methods used in our study of children in the United States and Brazil. Since one of our goals is to observe both sign language and speech, as well as any language mixing, it is important for us to address issues of language choice and techniques for directing the child participant toward primary use of the target language in each session. Suggestions and guidelines for achieving this in effective yet respectful ways are presented. We are especially dependent on the participation, flexibility, and direction of our participant children's parents, who work with us to elicit samples that are genuinely representative of their children's linguistic abilities. We illustrate our procedures for training parents and other interlocutors in data-collection sessions. In return for their generous participation in our research, we address parents' questions and concerns about language development, especially in bimodal bilingual contexts. We take very seriously the need to negotiate with participants regarding their expectations for the use of the data they provide, and we abide by their wishes in this matter. The strategies presented here improve the quality of the investigations we can conduct by making the experiences of the participant families as pleasant as possible.


Prognostic value of p53 protein expression in giant cell tumor of bone.
Giant cell tumor of bone (GCTB) is a benign tumor with a tendency for local recurrence. GCTB may cause lung metastases, and secondary malignant GCTB is rare. Its histological appearance does not predict local aggressiveness and/or the metastatic potential of the tumor. We aimed to investigate the prognostic value of the Ki-67 proliferative index and p53 protein expression in GCTB in predicting local recurrence, lung metastasis, and malignant transformation. We retrospectively reviewed 42 cases of GCTB. The p53 expression was positive in 20 cases. We used 10% as a cut-off value for p53 expression. In 10 cases, there were local recurrences. Lung metastases were found in three cases and malignant transformation was found in one case with classical GCTB located in the sacrum three years following diagnosis. The Ki-67 index was higher in cases with recurrence, but this difference was not statistically significant. Of the recurrent cases, two had no p53 staining while eight had moderate-to-strong staining. The staining was usually weakly positive in the non-recurrent cases. In conclusion, we believe that p53 may be used as a marker for the biological behavior of GCTB.


A fluorescent reporter protein containing AtRMR1 domains is targeted to the storage and central vacuoles in Arabidopsis thaliana and tobacco leaf cells.
To develop a new strategy to target recombinant proteins to the vacuolar storage system in transgenic plants, the ability of the transmembrane and cytosolic domains of Arabidopsis receptor homology-transmembrane-RING H2-1 (AtRMR1) was evaluated. A secreted version of RFP (secRFP) and a fusion of it to the transmembrane and cytosolic domains of AtRMR1 (RFP-TMCT) were produced and studied both in transient and stable expression assays. Transient expression in leaves of Nicotiana tabacum showed that secRFP is secreted to the apoplast while its fusion to TMCT of AtRMR1 is sufficient to prevent secretion of the reporter. In tobacco leaves, RFP-TMCT reporter showed an endoplasmic reticulum pattern in early expression stages while in late expression stages, it was found in the vacuolar lumen. For the first time, the role of TM and CT domains of AtRMR1 in stable expression in Arabidopsis thaliana is presented; the fusion of TMCT to secRFP is sufficient to sort RFP to the lumen of the central vacuoles in leaves and roots and to the lumen of PSV in cotyledons of mature embryos. In addition, biochemical studies performed in extract from transgenic plants showed that RFP-TMCT is an integral membrane protein. Full-length RFP-TMCT was also found in the vacuolar lumen, suggesting internalization into destination vacuole. Not colocalization of RFP-TMCT with tonoplast and plasma membrane markers were observed. This membrane vacuolar determinant sorting signal could be used for future application in molecular pharming as an alternative means to sort proteins of interest to vacuoles.


Patient accounts and CQI--one department's experiences.
When people think of the quality revolution in health care, most probably will not consider the patient accounts area as the leader. Patient accounts professionals seeking to rectify this reputation need to encourage healthcare facility management staff to pay more attention to the monthly volume of patient complaints. Customer satisfaction levels can be controlled by a CQI-invested patient accounts department that effectively manages the patient billing process.


Safety and immunogenicity of single dose of tetanus-diphtheria (Td) vaccine among non/partially immune children against diphtheria and/or tetanus, Hyderabad, India, 2007.
In Hyderabad, India, diphtheria is common among children aged 5-19 years. On account of low coverage of diphtheria vaccine boosters recommended under the universal immunization programme, a large proportion of children were susceptible/partially immune against diphtheria and/or tetanus. We evaluated immunogenicity and safety of single dose of indigenously developed tetanus-diphtheria (Td) vaccine (diphtheria-toxoid < or =5 Lf) among 483 school children from Hyderabad aged 7-17 years and susceptible/partially immune against diphtheria and/or tetanus. Serological testing 6 weeks after vaccination indicated that vaccine was highly immunogenic with >96% sero-protected against both antigens. The immune response observed indicated a booster response to previously acquired immunity. Administration of additional dose of Td vaccine to the older school children and replacing the tetanus toxoid vaccine with Td in the school health programme would considerably reduce diphtheria burden in Hyderabad.


Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies.
Despite the wide diffusion of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP), only few studies comparing the results of these techniques with the retropubic radical prostatectomy (RRP) are currently available. To evaluate the perioperative, functional, and oncologic results in the comparative studies evaluating RRP, LRP, and RALP. A systematic review of the literature was performed in January 2008, searching Medline, Embase, and Web of Science databases. A "free-text" protocol using the term radical prostatectomy was applied. Some 4000 records were retrieved from the Medline database; 2265 records were retrieved from the Embase database;, and 4219 records were retrieved from the Web of Science database. Three of the authors reviewed the records to identify comparative studies. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK). Thirty-seven comparative studies were identified in the literature search, including a single, randomised, controlled trial. With regard to the perioperative outcome, LRP and RALP were more time consuming than RRP, especially in the initial steps of the learning curve, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates all favoured LRP. With regard to the functional results, LRP and RRP showed similar continence and potency rates. Similarly, no significant differences were identified between LRP and RALP, while a single, nonrandomised, prospective study suggested advantages in terms of both continence and potency recovery after RALP, compared with RRP. With regard to the oncologic outcome, LRP and RALP were associated with positive surgical margin rates similar to those of RRP. The quality of the available comparative studies was not excellent. LRP and RALP are followed by significantly lower blood loss and transfusion rates, but the available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. Further high-quality, prospective, multicentre, comparative studies are needed.


Safety and efficacy of a high-adhesion whitening strip under extended wear regimen.
This randomized, parallel group, single centre clinical trial was conducted to evaluate the safety and compare the whitening efficacy for an extended wear of an experimental 9.5% H₂O₂ high-adhesion whitening strip, relative to a marketed 10% H₂O₂ control strip. Twenty-nine eligible adult volunteers were randomly assigned to either a treatment series with an experimental 9.5% H₂O₂ high-adhesion whitening strip at home for 2h, once a day, for 8 days; or a marketed 10% H₂O₂ whitening strip for 30 min, on a similar daily regimen. Tooth color/whitening progression was recorded under standardized lighting conditions at baseline, day 3, day 5, and day 9, via digital imaging. Outcomes were reported using the CIELAB system. Usage safety was also assessed at each follow-up visit. Whitening efficacy for each group was investigated using a paired-difference t-test. The treatment groups were compared among each other using the analysis of covariance, with the baseline value and age as the covariates. Both treatment groups demonstrated statistically significant mean color improvement from baseline for b* (yellow ness) and L* (lightness) at each post-baseline visit. In addition, the 2-h high-adhesion strips demonstrated significantly greater improvement in b* and L* relative to the 30-min strip group at each follow-up visit. The 2-h regimen for the 9.5% H₂O₂ high-adhesion whitening strip was more efficient for tooth whitening than the 30-min regimen of 10% H₂O₂ whitening strip. Both treatments were well tolerated and the use of the test products during the study time frame was considered safe. Extending the daily wear time of whitening strips can improve the efficacy of the treatment and ultimately shorten the length of the treatment without any significant adverse effects.


COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures.
A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another four countries. To help control the spread of the virus, a "cordon sanitaire" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.


The secondary and recurrent abdominal compartment syndrome.
The Secondary Abdominal Compartment Syndrome (SACS) refers to cases of the ACS that do not originate from the abdominopelvic region. With greater awareness of the physiologic consequences of raised intra-abdominal hypertension (IAH), cases of the SACS are being increasingly described. The prior treatment or the presence of a partially open abdomen does not preclude the ACS if the abdomen and viscera continue to swell or the clinician is not vigilant in monitoring intra-abdominal pressure (IAP). Such recurrent cases (RACS) have been defined as those which redevelop following the previous medical or surgical treatment of primary or SACS. Although there has been a diverse range of etiologies implicated, these cases seem to be linked by the common occurrence of severe shock requiring aggressive fluid resuscitation. The aim of this paper is to thus to review the historical background, awareness, definitions, pathophysiological implications and treatment options for SACS and RACS. This review will focus on the available literature regarding SACS and RACS. A Medline and Pubmed search was performed using the keywords; secondary abdominal compartment syndrome AND secondary AND tertiary AND recurrent AND abdominal compartment syndrome AND intra-abdominal pressure AND intra-abdominal hypertension. Bibliographies of recovered papers were hand-searched for other appropriate references. The resulting references were included in the current review on the basis of relevance and scientific merit Results: There has been remarkably little specific study of these entities outside of specific groups such as those injured by thermal or traumatic injury. The epidemiology, risk factors for, treatment of and most importantly, strategies for prevention all remain scientifically unknown and therefore based on opinion. Notable, although small, studies suggest that specific resuscitation practices may avert these conditions. ACS can occur in any patient who is critically ill and subject to visceral and somatic swelling, regardless of whether the inciting pathology is extra-abdominal. The ACS may also reoccur with recurrent shock and swelling even if previous therapies had partially addressed IAH. Therefore IAP measurements should be considered a routine monitoring for the critically ill, especially those subjected to shock and requiring a subsequent resuscitation. Much further study is required to understand the differences in etiology, diagnosis, pathophysiology, and treatment for all cases of the ACS.


Challenges for research on polyphenols from foods in Alzheimer's disease: bioavailability, metabolism, and cellular and molecular mechanisms.
Polyphenols are the most abundant antioxidants in diet. Indeed, fruits, vegetables, beverages (tea, wine, juices), plants, and some herbs are loaded with powerful antioxidant polyphenols. Despite their wide distribution, research on human health benefits truly began in the mid-1990s (Scalbert, A.; Johnson, I. T.; Saltmarsh, M. Am. J. Clin. Nutr. 2005, 81, S15S-217S). Phenolic compounds have been receiving increasing interest from consumers and manufacturers because numerous epidemiological studies have suggested associations between consumption of polyphenol-rich foods or beverages and the prevention of certain chronic diseases such as cancers and cardiovascular diseases (Manach, C.; Mazur, A.; Scalbert, A. Curr. Opin. Lipidol. 2005, 16, 77-84; Duthie, S. J. Mol. Nutr. Food Res. 2007, 51, 665-674). Furthermore, in the past 10 years, research on the neuroprotective effects of dietary polyphenols has developed considerably. These compounds are able to protect neuronal cells in various in vivo and in vitro models through different intracellular targets (Ramassamy, C. Eur. J. Pharmacol. 2006, 545, 51-64). However, it is not at all clear whether these compounds reach the brain in sufficient concentrations and in a biologically active form to exert beneficial effects. On the other hand, it has become clear that the mechanisms of action of these polyphenols go beyond their antioxidant activity and the attenuation of oxidative stress. Therefore, there is a need for more research on their intracellular and molecular targets as special pathways underlying distinct polyphenol-induced neuroprotection. The focus of this review is aimed at presenting the role of some polyphenols from fruits, vegetables, and beverages in neuroprotection and particularly in Alzheimer's disease and the research challenges in this area.


The prevalence and effects of hunger in an emergency department patient population.
Little is known about the prevalence and health effects of hunger among ED patients. The objectives of this study were to determine the prevalence of hunger among patients in a large urban ED and to examine whether it has adverse health effects. A survey about hunger, choices between buying food and buying medicine, and adverse health outcomes related to food adequacy over the preceding 12 months was administered to a convenience sample of adult non-critically ill ED patients from afternoon and evening shifts. The study was conducted in the ED of Hennepin County Medical Center in Minneapolis, Minnesota. Of the 302 eligible patients who were asked to participate, 297 (98%) agreed. Eighteen percent reported not having enough to eat at least once in the preceding 12 months: 14% reported that they had "gotten sick" as a result of not being able to afford their medicine, resulting in an ED visit or hospital admission 50% of the time. Predictors of making choices about buying food vs medicine include having a chronic health condition, lack of private health insurance, having a reduction in food stamps, having an annual income less than $10,000, and lack of alcohol use. By patient report, a reduction in food stamps was a predictor of ED visits and hospitalizations as a result of making choices about buying food over medicine. The ED patients in this urban setting have high rates of hunger and many must make choices between buying food and medicine, which patients report results in otherwise preventable ED visits and hospitalization. Loss or reduction of food stamps is associated with increased hunger and increased perceived adverse health outcomes as a result of not being able to afford medicine.


Theoretical study of hydrogen-bonded complexes of chlorophenols with water or ammonia: Correlations and predictions of pKa values.
A simple practical method for predicting the acidity constants (as pKa values) of chlorophenols is proposed based on density functional theory calculations of a series of hydrogen-bonded complexes of phenol and 19 different congeners of chlorophenol, with a single probe molecule, either water or ammonia. Relevant structural parameters and molecular properties of these complexes, primarily involving the acidic hydroxyl group, are examined and plotted against the known pKa values of 14 chlorophenols and phenol. Strong linear correlations are found for these compounds. Such correlations are used to determine the pKa values of five chlorophenols whose experimental acidities have large uncertainties. Similar predicted pKa values are obtained by using different structural parameters and molecular properties for the complexes with either probe molecule. The study may be extended to determine the acidity of other compounds with a single acidic functional group.


Unusual solvation through both p-orbital lobes of a carbene carbon.
As a result of a configurational space search done to explain the experimental evidence of transient specific solvation of singlet fluorocarbene amide with tetrahydrofuran, we found that the most stable structures consist in a group in which each oxygen of two tetrahydrofuran molecules act as electron donor to its respective empty p-orbital lobe of the carbene carbon atom, located at each side of the carbene molecular plane. This kind of species, which to our knowledge has not been reported before, explains very well the particular experimental characteristics observed for the transient solvation of this system. We postulate that the simultaneous interaction to both p-orbital lobes seems to confer a special stability to the solvation complexes, because this situation moves away the systems from the proximity of the corresponding transition states for the ylide products. Additionally, we present an analysis of other solvation complexes and a study of the nature of the involved interactions.


Chimerism resulting from parthenogenetic activation and dispermic fertilization.
Whole-body human chimerism is the result of two zygotes giving rise to one individual, and is a rarely detected condition. We have studied the molecular background and discuss the likely mechanism for the chimerism in a patient with a 46,XX/47,XY,+14 karyotype and ambiguous genitalia, cryptorchidism, pigment anomalies, and normal psychomotor development. We have used karyotyping, interphase-FISH and array-CGH analysis as well as molecular analysis of polymorphic markers from 48 loci in order to define the origin and percentage of 47,XY,+14 cells in different tissues. Based on the findings of two paternal alleles and the detection of homozygous maternal alleles without evidence of crossing-over, and the fact that four alleles were never detected, our results indicate that the chimerism in our patient is the result of dispermic fertilization of a parthenogenetically activated oocyte. Our report underlines that cytogenetic findings suggesting mosaicism might actually indicate chimerism as an underlying mechanism in patients. It also highlights the difficulties in predicting the clinical outcome in patients with genetic aberrations in mosaic or chimeric form.


Blood brain barrier in hypoxic-ischemic conditions.
The blood brain barrier (BBB) plays an important role in the homeostatic regulation of the brain microenvironment and maintains the immune-privileged status of the brain by restricting the entry of T lymphocytes. Structurally, the BBB is formed by tight junctions between the endothelial cells. Astrocytes, pericytes and perivascular microglia surround the endothelial cells contributing to proper functioning of the BBB. Hypoxia, associated with disorders such as stroke, cardiac arrest, respiratory distress, carbon monoxide poisoning among many others, disrupts the BBB. Alterations in the endothelial cells such as increased pinocytotic vesicles and derangement of the tight junction proteins may be responsible for increased permeability at the BBB resulting in swelling of astrocyte end feet. The disruption of BBB in hypoxic conditions is multifactorial and may involve factors such as enhanced production of vascular endothelial growth factor (VEGF), nitric oxide (NO) and inflammatory cytokines. Although future research is needed to look into possible therapeutic strategies to improve the functioning of BBB in hypoxic conditions, experimental studies so far have reported beneficial effect of curcumin, melatonin, simvastatin and minocycline in ameliorating the increased BBB permeability in hypoxic conditions.


Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children.
Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown dogtick Rhipicephalus sanguineus. Nearly four hundred cases are reported every year (mainly from June to September) on the Italian island of Sicily. The aim of the study was to analyze the clinical and laboratory characteristics of patients with MSF and the efficacy of the drugs administered. Our study was carried out on 415 children with MSF, during the period January 1997-December 2004, at the "G. Di Cristina" Children's hospital in Palermo, Sicily, Italy. On admission patients' clinical history, physical and laboratory examination and indirect immunofluorescence antibody test (IFAT) for Rickettsia conorii were performed. Diagnosis was considered confirmed if the patients had an MSF diagnostic score greater than or equal to 25 according to the Raoult's scoring system. All patients were treated with chloramphenicol or with macrolides (clarithromycin or azithromycin). Fever, rash and tache noire were present in 386 (93%), 392 (94.5%) and 263 (63.4%) cases respectively. Eighteen (4.6%) children showed atypical exanthema. Chloramphenicol and newer macrolides all appeared to be effective and safe therapies. Clinical features of 415 children with MSF were similar to those reported by other authors except for a lower incidence of headache, arthralgia and myalgia and a higher frequency of epato-splenomegaly. Concerning therapy, clarithromycin can be considered a valid alternative therapy to tetracyclines or chloramphenicol especially for children aged < eight years.


π-Extended isomeric and expanded porphyrins.
The phenomenon of π-extension has been widely applied to, and exploited within, the field porphyrin chemistry. The development of reliable synthetic routes to various useful starting materials has facilitated the underlying preparative work. The chemical resemblance between porphyrins and expanded and isomeric porphyrins, as well as the increasing accessibility of the requisite starting materials is giving birth to the hybrid field of π-extended expanded and isomeric porphyrins. This tutorial review is intended to provide an overview of up-to-date published synthetic efforts and to summarize the effect of annulation on the properties of expanded and isomeric porphyrins.


Diastereoselective [3 + 2] Cycloaddition of Quinoxalin-2(1H)-ones with Donor-Acceptor Cyclopropanes: Efficient Synthesis of Tetrahydro pyrrolo[1,2-a]quinoxalin-4(5H)-ones.
A ytterbium triflate-catalyzed diastereoselective [3 + 2] cycloaddition of quinoxalinones with donor-acceptor cyclopropanes and cyclobutanes is described. A series of tetrahydropyrrolo-quinoxalinone derivatives were obtained in high yields (up to 96%) with excellent diastereoselectivities (up to 46:1). Other medicinally important heterocycles like benzoxazinone, isoquinoxalinone, and dibenzoxazepine derivatives were also suitable for the desired annulation reaction. The current method is applicable for the scale-up reaction. Further, the utility of this annulation reaction is demonstrated by the synthesis of densely functionalized proline derivatives.


Nutritional Laboratory Markers in Malnutrition.
Serum visceral proteins such as albumin and prealbumin have traditionally been used as markers of the nutritional status of patients. Prealbumin is nowadays often preferred over albumin due to its shorter half live, reflecting more rapid changes of the nutritional state. However, recent focus has been on an appropriate nutrition-focused physical examination and on the patient's history for diagnosing malnutrition, and the role of inflammation as a risk factor for malnutrition has been more and more recognized. Inflammatory signals are potent inhibitors of visceral protein synthesis, and the use of these proteins as biomarkers of the nutritional status has been debated since they are strongly influenced by inflammation and less so by protein energy stores. The current consensus is that laboratory markers could be used as a complement to a thorough physical examination. Other markers of the nutritional status such as urinary creatinine or 3-methylhistidine as indicators of muscle protein breakdown have not found widespread use. Serum IGF-1 is less influenced by inflammation and falls during malnutrition. However, its concentration changes are not sufficiently specific to be useful clinically as a marker of malnutrition, and serum IGF-1 has less been used in clinical trials. Nevertheless, biomarkers of malnutrition such as prealbumin may be of interest as easily measurable predictors of the prognosis for surgical outcomes and of mortality in severe illnesses.


Targeting malaria parasites with novel derivatives of azithromycin.
The spread of artemisinin resistant Plasmodium falciparum parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites via two mechanisms: 'delayed death' by inhibiting the bacterium-like ribosomes of the apicoplast, and 'quick-killing' that kills rapidly across the entire blood stage development. Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against P. falciparum (the most virulent human malaria) and P. knowlesi (a monkey parasite that frequently infects humans). Seventeen analogues showed improved quick-killing against both Plasmodium species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for P. falciparum and P. knowlesi, respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of P. falciparum parasites (<12 hrs treatment) and were >5-fold more selective against P. falciparum than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite Toxoplasma gondii and the gram-positive bacterium Streptococcus pneumoniae did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment. The azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quick-killing antimalarial activity.


Determination of endurance capacity and prediction of exercise intensities for training and competition in marathon runners.
Male and female marathon runners (n = 34) were studied in incremental and continuous running tests under both laboratory and field conditions. Aerobic capacity was determined based on the relationship between the lactate concentration and running velocity. We also analyzed the acid-base balance after the laboratory test of continuous running for 45 min. The individual running velocities in the incremental field test at given lactate concentrations were correlated with the marathon running velocities. Training workouts for six female runners were analyzed, and running speed during endurance training was compared with the lactate-velocity relationship in an incremental laboratory test. The main findings are summarized below. There is a very close relationship between the velocities determined at 2.5, 3, and 4 mmol/l in the incremental field test and the marathon running velocity (r = 0.88-0.99, P less than 0.001). The highest correlation between test and marathon velocities was found at a lactate concentration of 2.5 and 3.0 mmol/l. In field and laboratory running tests lasting 44 and 45 min at a speed chosen in accordance with the runner's current marathon time, lactate levels reached a steady state at approximately 3 mmol/l. A slight increase in blood lactate levels was compensated via respiratory mechanisms. In the continuous treadmill test (n = 8), we recorded the following changes after the first blood sample collection (i.e., 10 min) and post-exercise: blood lactate concentrations rose from 2.2 +/- 0.93 to 3.5 +/- 1.45 mmol/l; the negative base excess increased from -1.2 +/- 3.2 to -3.4 +/- 1.7 mval/l.(ABSTRACT TRUNCATED AT 250 WORDS)


Xeroradiography and ionography: new technologies to replace the x-ray film.
Novel methods of radiogram imaging are described and compared with conventional means. They include: xeoradiography, low- and high-pressure ionography and liquid phase ionography. The possibility of real time operation is considered also. Of these systems, xeroradiography is already in use for a limited range of applications. High pressure gas ionography shows great promise and practical systems may be expected to appear in the near future.


Expression of Mastoparan B, a Venom Peptide, Via Escherichia coli C43 (DE3) Coupled with an Artificial Oil Body-Cyanogen Bromide Technology Platform.
Mastoparan B (MPB) is a venom peptide isolated from Vespa basalis (black-bellied hornet), one of the dangerous vespine wasps found in Taiwan. MPB is a tetradecapeptide (LKLKSIVSWAKKVL), amphiphilic venom peptide, with a molecular mass of 1.6 kDa. MPB belongs to an evolutionarily conserved component of the innate immune response against microbes. In this study, we attempted to modify a reliable oleosin-based fusion expression strategy coupled with the artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce bioactive MPB. The aim of this study was to develop an artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce the bioactive form of mastoparan B (MPB), which in a manner identical to that of its native counterpart. The plasmid pET30-His6-rOle(127M→L)-MPB was constructed, and then four different E. coli strains- BL21(DE3), BL21(DE3)pLysS, C41(DE3), and C43(DE3) were tested to identify the most suitable host for the pET30-His6-rOle(127M→L)-MPB fusion protein expression. We optimized the expression conditions by testing different growth temperatures, isopropyl-β-D-thiogalactoside (IPTG) concentrations, and post-induction collection times. Afterwards, the His6-rOle(127M→L)-MPB protein was purified by one-step nickel-chelated affinity chromatography (Ni2+-NTA) under denaturing conditions. The purified His6-rOle(127M→L)-MPB was selectively cleaved by thrombin protease to remove the His6-tag and the leader peptide from the N-terminus. Subsequently, rOle(127M→L)-MPB protein was constituted into AOB and incubated with CNBr for a cleavage reaction, which resulted in the release of the MPB from rOle(127M→L)-MPB protein via AOB. The purified MPB was identified by MALDI-MS and HPLC analysis, and its bioactivity was examined by antimicrobial testing. After a 2-h induction period, the E. coli C43(DE3) was found to be superior to BL21(DE3) and the other protease-deficient strains as an expression host. And, the optimal His6-rOle(127M→L)-MPB expression at 37°C for 2 h after induction with 5 µM IPTG. The purified MPB showed that a single major peak was detected by HPLC/UV detection with a retention time of 22.5 minutes, which was approximately 90% pure. The putative MPB, and over two-third of the peptide sequence was verified by the MALDI-MS analysis. Finally, the purified MPB was examined by a broth dilution-antimicrobial susceptibility test. These results indicated that the purified MPB was bioactive and very effective in anti-bacterial (E. coli J96) activity. Here, we successfully used the oleosin-based fusion expression strategy coupled with the artificial oil body (AOB)-cyanogen bromide (CNBr) platform to produce bioactive MPB peptide which, in a manner identical to that of its native counterpart. In this study, the recombinant oleosin based fusion strategy coupled with AOB-CNBr purification platform open a new avenue for the production of active MPB and facilitate the studies and applications of the peptide in the future for medicinal applications such as hypotension and antibacterial effect.


Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD.
Cancer affects millions of people each year and imposes a huge economic and social burden worldwide. Cuproptosis is a recently discovered novel mode of cell death. The exact function of the cuproptosis-related gene dihydrolipoamide dehydrogenase (DLD) and its role in pan-cancer is unknown. Data were retrieved from the GTEx, TCGA, and multiple online websites. These data were used to assess the expression, prognosis, and diagnostic value of DLD in various tumors. The relationship of DLD with immune microenvironment immunomodulators, immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI), and oncology drug sensitivity was explored by correlation analysis. The mRNA and protein expression of DLD differs in most cancers. Survival analysis showed that DLD was associated with prognosis with KIRC, KIRP, KICH, and UCS. DLD had a strong diagnostic value in KIRC, GBM, PAAD, and LGG (AUC > 0.9). DLD promoter methylation affects the aberrant expression of LIHC, LUSC, PAAD, READ, and THCA. DLD was negatively correlated with stromal score, immune score, and ESTIMATE score in UCEC, TGCT, LUSC, and SARC. In UCS, resting memory CD4 T cells and activated NK cells were significantly correlated with DLD expression. Significant correlations were also observed between DLD expression and immunomodulators, immune checkpoints, TMB, and MSI in various cancers. Importantly, we also identified a number of potential drugs that may target DLD. DLD expression is associated with a variety of tumor prognoses and plays an integral role in tumorigenesis, tumor metabolism, and immunity.


Future of the nurse labor market according to health executives in high managed-care areas of the United States.
To understand how the work environment of nurses is changing in states with high enrollment in health maintenance organizations (HMOs), the underlying forces driving change, and how these forces are expected to affect employment and earnings of nurses in the future. Financing and delivery systems that have developed in some states with high enrollment in HMOs are generally regarded as indicative of the future for all the United States. Survey in 1995 of a convenience sample of 62 health executives in 11 states with high enrollment in HMOs. Executives included officials in state governments, state and metropolitan hospital associations, professional and nonprofessional nursing associations, state boards of nursing, community and public health, home health care, nursing homes, other non-acute care associations, and leading HMOs. Through structured telephone interviews, executives were asked about changes in nurse employment, earnings, collective bargaining, fringe benefits, nurses' roles, substitution of licensed practical nurses (LPNs) and aides for RNs, patient severity, quality of patient care, and expectations for nurse employment during the remainder of the decade. Executives perceive a mostly positive and fast-changing nurse labor market but they are concerned about the aging RN work force, possible development of an RN shortage, and linking quality of patient care to the provision of nursing services. They doubt the ability of nurse educators to respond quickly to the need to prepare nurses for rapidly changing employer requirements. Public and private forces are causing rapid, profound changes in health care delivery and throughout the nurse labor market. These changes are most evident in the shift in employment of nurses from hospitals to home health. Despite anxiety associated with these changes, no evidence of an "employment disaster" exists in the views of health executives.


Brainstem ganglioglioma in an infant: Case report and review of literature.
Gangliogliomas are well differentiated, usually low grade, neuroepithelial tumors that comprise of neoplastic ganglion cells in combination with neoplastic glial cells. Occasionally, glial cells may show anaplastic features and are then labeled as anaplastic gangliogliomas. Most of the reported gangliogliomas are supratentorial tumors, predominantly in the temporal lobe. Brainstem location has been reported infrequently. As with cortically based gangliogliomas, though the primary treatment is resection, this is often not possible due to the eloquence of surrounding involved parenchyma. Here, we report a case of brainstem tumor in an 8-month-old child that was substantially resected and was histopathologically Grade 1 ganglioglioma. As per review of English literature, there has been no case of brainstem ganglioglioma reported in an infant (less than 1 year age). We discuss the surgical difficulties in the radical excision of such benign tumors and review literature on pediatric brainstem gangliogliomas.


PHANTASTICA regulates development of the adaxial mesophyll in Nicotiana leaves.
Initiation and growth of leaf blades is oriented by an adaxial/abaxial axis aligned with the original axis of polarity in the leaf primordium. To investigate mechanisms regulating this process, we cloned the Nicotiana tabacum ortholog of PHANTASTICA (NTPHAN) and generated a series of antisense transgenics in N. sylvestris. We show that NSPHAN is expressed throughout emerging blade primordia in the wild type and becomes localized to the middle mesophyll in the expanding lamina. Antisense NSPHAN leaves show ectopic expression of NTH20, a class I KNOX gene. Juvenile transgenic leaves have normal adaxial/abaxial polarity and generate leaf blades in the normal position, but the adaxial mesophyll shows disorganized patterns of cell division, delayed maturation of palisade, and ectopic reinitiation of blade primordia along the midrib. Reversal of the phenotype with exogenous gibberellic acid suggests that NSPHAN, acting via KNOX repression, maintains determinacy in the expanding lamina and sustains the patterns of cell proliferation critical to palisade development.


Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2.
ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.


Dissociated neurons from normal and mutant Drosophila larval central nervous system in cell culture.
A primary dissociated cell culture of Drosophila larval central nervous system is reported. Divisions of neuroblasts and vigorous outgrowth of neurites could be observed in culture. Within 24 hr cultured cells exhibited characteristic neuronal morphology and unimpaired ability to synthesize and accumulate acetylcholine. This cell culture system renders easy access to experimental analysis of normal neuronal properties and the altered mechanisms in neurological mutants. Single-channel currents induced by acetylcholine and regenerative action potentials were studied in the somata of the dissociated neurons. The appearance of Na channels in these cultured neurons was demonstrated by the cell lethality induced by veratridine and inhibition of the effect by tetrodotoxin. Dissociated neurons from a temperature-sensitive paralytic mutant napts, in which nerve conduction fails at high temperature, were studied in culture. Neuronal growth was not affected by this mutation, nor by tetrodotoxin. However, napts neurons showed greatly reduced sensitivity to veratridine even at 21 degrees C, a temperature at which napts individuals behave normally. This finding indicates expression of the napts phenotype at a level of isolated single cells and provides independent evidence that napts affects Na channel function.


Breast feeding and resilience against psychosocial stress.
Some early life exposures may result in a well controlled stress response, which can reduce stress related anxiety. Breast feeding may be a marker of some relevant exposures. To assess whether breast feeding is associated with modification of the relation between parental divorce and anxiety. Observational study using longitudinal birth cohort data. Linear regression was used to assess whether breast feeding modifies the association of parental divorce/separation with anxiety using stratification and interaction testing. Data were obtained from the 1970 British Cohort Study, which is following the lives of those born in one week in 1970 and living in Great Britain. This study uses information collected at birth and at ages 5 and 10 years for 8958 subjects. Class teachers answered a question on anxiety among 10 year olds using an analogue scale (range 0-50) that was log transformed to minimise skewness. Among 5672 non-breast fed subjects, parental divorce/separation was associated with a statistically significantly raised risk of anxiety, with a regression coefficient (95% CI) of 9.4 (6.1 to 12.8). Among the breast fed group this association was much lower: 2.2 (-2.6 to 7.0). Interaction testing confirmed statistically significant effect modification by breast feeding, independent of simultaneous adjustment for multiple potential confounding factors, producing an interaction coefficient of -7.0 (-12.8 to -1.2), indicating a 7% reduction in anxiety after adjustment. Breast feeding is associated with resilience against the psychosocial stress linked with parental divorce/separation. This could be because breast feeding is a marker of exposures related to maternal characteristics and parent-child interaction.


Structurational divergence theory as explanation for troublesome outcomes in nursing communication.
Structurational divergence (SD) theory captures negative communication cycles resulting from interpenetration of incompatible meaning structures. It is estimated that 12-15% of practicing nurses suffer from a problematic level of SD. With a sample of 713 nurses (57 departments) in a large hospital, this study tests a model positing SD as a root explanation of nursing job satisfaction and turnover. A number of variables long presumed to be explanations for job satisfaction and turnover were hypothesized as mediators between SD and those outcomes. Path analysis showed support for burnout, role conflict, bullying, and organizational identification as useful mediators, explaining 68% of the variance in job satisfaction, and 45% in intentions to leave. The study also explores relationships between SD and hospital quality indicators. SD is a concern because it powerfully explains a number of poor outcomes and provides an underlying explanation for a number of factors that predict job satisfaction and turnover.


Myths and realities of ageism and nursing.
Ageism is pervasive throughout society, and it is an especially important issue for nurses because the nursing workforce is aging rapidly. This article explores ageism as it applies to women and nurses, along with the myths and realities about this prevalent attitude. It also presents strategies for managing and educating the aging nursing workforce.


Light emitting diode-generated blue light modulates fibrosis characteristics: fibroblast proliferation, migration speed, and reactive oxygen species generation.
Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED-BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED-BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen-species (ROS) generation. Irradiation of adult human skin fibroblasts using commercially-available LED-BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time-lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student's t-test. Human skin fibroblasts treated with LED-BL fluences of 5, 10, 15, 30, and 80 J/cm(2) demonstrated statistically significant dose-dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED-BL fluences of 5, 30, 45, and 80 J/cm(2) decreased fibroblast migration speed to 95 ± 7.0% (P = 0.64), 81.3 ± 5.5% (P = 0.021), 48.5 ± 2.7% (P < 0.0001), and 32.3 ± 1.9% (P < 0.0001), respectively, relative to matched controls. LED fluences of 5, 10, 30, and 80 J/cm(2) resulted in statistically significant increases in reactive oxygen species of 110.4%, 116.6%, 127.5%, and 130%, respectively, relative to bench controls. At the fluences studied, LED-BL can inhibit adult human skin dermal fibroblast proliferation and migration speed, and is associated with increased reactive oxygen species generation in a dose-dependent manner without altering viability. LED-BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.


Proposed disk diffusion susceptibility criteria for ofloxacin.
Disk diffusion zone diameter breakpoint criteria for ofloxacin were tentatively established by correlating MICs with 1-, 3-, and 5-micrograms disk inhibitory zone diameters for 638 bacterial isolates representing 36 species. We recommend use of 5-micrograms disks with the following breakpoints: susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 16 mm; intermediate (MIC, 4.0 micrograms/ml), 13 to 15 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 12 mm.


Current State of Sarcoma Care in Germany: Results of an Online Survey of Physicians.
Sarcoma treatment is a complex and multidisciplinary process. Little is known about the actual status of sarcoma care in Germany. We evaluated: (1) on an institutional level, which physician diagnosed and treated sarcomas; (2) whether guidelines and tumor board recommendations were routinely implemented; and (c) access to which diagnosis and treatment options was regarded as problematic. We also examined factors that were associated with access problems. A cross-sectional online survey was employed among German sarcoma physicians between June 2017 and February 2018 with convenience sampling. Two hundred fourteen physicians participated; 46% were oncologists and 27% surgeons, 38% worked in hospitals of maximum care, 34% were office based and 27% worked in other hospitals, 68% of all of the physicians consulted established guidelines, and 93% presented their patients in multidisciplinary tumor boards. The most common access problems were: isolated limb perfusion (39%), deep-wave hyperthermia (33%), and FDG-PET (27%), and 42% reported no access problems at all. Those physicians who treat more than 100 patients per year reported "no access problems" more frequently compared to centers with lower patient numbers (vs. 0-10 patients, OR 0.14; 95% CI 0.03-0.61; vs. 11-100 patients, OR 0.21; 95% CI 0.06-0.73). Access to multidisciplinary tumor boards seems to be largely guaranteed in the participants of our survey. The use of guidelines could be further implemented and expanded. The number of treated patients appears to be a significant factor to avoid access problems to treatment options.


The role of dopamine in motor flexibility.
Humans carry out many daily tasks in a seemingly automatic fashion. However, when unexpected changes in the environment occur, we have the capacity to inhibit prepotent behavior and replace it with an alternative one. Such behavioral flexibility is a hallmark of executive functions. The neurotransmitter dopamine is known to be crucial for fast, efficient, and accurate cognitive flexibility. Despite the perceived similarities between cognitive and motor flexibility, less is known regarding the role of dopamine within the motor domain. Therefore, the aim of this study was to determine the role of dopamine in motor flexibility. In a double-blind, five-session, within-subject pharmacological experiment, human participants performed an RT task within a probabilistic context that was either predictable or unpredictable. The probabilistic nature of the predictable context resulted in prediction errors. This required participants to replace the prepotent or prepared action with an unprepared action (motor flexibility). The task was overlearned, and changes in context were explicitly instructed, thus controlling for contributions from other dopamine-related processes such as probabilistic or reversal learning and interactions with other types of uncertainty. We found that dopamine receptor blockade by high-dose haloperidol (D1/D2 dopamine receptors) impaired participants' ability to react to unexpected events occurring in a predictable context, which elicit large prediction errors and necessitate motor flexibility. This effect was not observed with selective D2 receptor blockade (sulpiride), with a general increase in tonic dopamine levels (levodopa), or during an unpredictable context, which evoked minimal prediction error. We propose that dopamine is vital in responding to low-level prediction errors about stimulus outcome that requires motor flexibility.


Understanding Dispute Resolution Processes for American and Australian Public Wildlands: Towards a Conceptual Framework for Managers.
/ The last 20 years have seen the successful application of environmental dispute resolution processes, where people voluntarily negotiate toward mutually acceptable solutions, to many environmental disputes. The effects of contextual influences, such as the number of parties and presence of deadlines, on outcomes are known and frequently described. Less well documented and understood are the interaction processes themselves. This paper draws on two case studies to develop a conceptual framework describing these processes. Disputes associated with management planning for the Bob Marshall Wilderness Complex in the United States and Fitzgerald River National Park in Australia provided the cases. The conceptual framework derived had eight sequential stages: (1) joint definition of problems, (2) uncertainty about what to do, (3) agreement on group procedures, (4) realization of interdependence, (5) enthusiasm about collective possibilities, (6) commitment to working together, (7) consolidation of the group, and (8) implementation of a resolution. The framework provides new insights for managers of public wildlands, especially the need for varying but ongoing managerial involvement in dispute resolution processes. High levels of involvement and influence are essential at the beginning in problem definition and group procedure design and at the end in implementing resolutions. Conversely, agency members must be willing to exert less influence, while still being involved and committed to collective purposes, during the middle stages. Also apparent from the conceptual framework is the importance of developing shared understandings and of allowing sufficient time for understanding to develop, if successful resolution is to be achieved. KEY WORDS: Environmental dispute resolution; Conceptual framework; Public wildlands; Shared understandings; Australia


Synergism between IL-33 and MRGPRX2/FcεRI Is Primarily Due to the Complementation of Signaling Modules, and Only Modestly Supplemented by Prolonged Activation of Selected Kinases.
Skin mast cells (MCs) express high levels of MRGPRX2, FcεRI, and ST2, and vigorously respond to their ligands when triggered individually. IL-33/ST2 also potently synergizes with other receptors, but the molecular underpinnings are poorly understood. Human skin-derived MCs were stimulated via different receptors individually or jointly in the presence/absence of selective inhibitors. TNF was quantified by ELISA. Signaling cascades were studied by immunoblot. TNF was stimulated by FcεRI ≈ ST2 > MRGPRX2. Surprisingly, neither FcεRI nor MRGPRX2 stimulation elicited NF-κB activation (IκB degradation, p65 phosphorylation) in stark contrast to IL-33. Accordingly, TNF production did not depend on NF-κB in FcεRI- or MRGPRX2-stimulated MCs, but did well so downstream of ST2. Conversely, ERK1/2 and PI3K were the crucial modules upon FcεRI/MRGPRX2 stimulation, while p38 was key to the IL-33-elicited route. The different signaling prerequisites were mirrored by their activation patterns with potent pERK/pAKT after FcεRI/MRGPRX2, but preferential induction of pp38/NF-κB downstream of ST2. FcεRI/MRGPRX2 strongly synergized with IL-33, and some synergy was still observed upon inhibition of each module (ERK1/2, JNK, p38, PI3K, NF-κB). IL-33's contribution to synergism was owed to p38 > JNK > NF-κB, while the partner receptor contributed through ERK > PI3K ≈ JNK. Concurrent IL-33 led to slightly prolonged pERK (downstream of MRGPRX2) or pAKT (activated by FcεRI), while the IL-33-elicited modules (pp38/NF-κB) remained unaffected by co-stimulation of FcεRI/MRGPRX2. Collectively, the strong synergistic activity of IL-33 primarily results from the complementation of highly distinct modules following co-activation of the partner receptor rather than by altered signal strength of the same modules.


Phototherapy, psoriasis, and the age of biologics.
Over 10 years have passed since the first approval of a biologic agent for the treatment of psoriasis. No one can argue that the arrival of this entirely new, highly effective class of medications has not forever changed the therapeutic landscape for psoriasis. Traditional treatments such as phototherapy, however, remain both viable and effective therapies, both as standalone treatments and in combination with biologics. In general, synergistic effects are noted for combinations utilizing phototherapy; however, the long-term impact of these combinations on skin cancer development has yet to be fully determined. Increasing financial pressures for cost-effective therapies augment the appeal of phototherapy and other traditional treatments as compared with the more costly biologics. Phototherapy also remains strong outside the realm of psoriasis, in the management of atopic dermatitis, vitiligo, and cutaneous T-cell lymphoma, among other conditions. Phototherapy will remain a cornerstone in the management of psoriasis as well as nonpsoriatic skin conditions, as its efficacy is well known, its financial cost is reasonable, it is readily compatible with other therapeutics, and its utility is historically proven.


The Dual Descriptor Reveals the Janus-Faced Behaviour of Diiodine.
The Janus-faced ligand behavior of diiodine (I2) was evidenced after applying the dual descriptor (DD or second-order Fukui function), thus providing additional support to the work performed by Rogachev and Hoffmann in 2013. Along with its capacity to reveal sites susceptible to undergo attacks simultaneously of nucleophilic and electrophilic types, another advantage of DD lies in being an orbital-free descriptor. That means it is based only upon total electron densities when written in its most accurate operational formula. This quality is not exclusive of DD because when Fukui functions are written in terms of electron densities instead of densities of frontier molecular orbitals, they become orbital-free descriptors too. Furthermore, the present work is an application of the generalized operational formula of the dual descriptor published in 2016 that takes into account any possible degeneracy in frontier molecular orbitals. As a proof about capabilities of DD, the possible sites for a favorable interaction between I2 with two organometallic compounds [Rh2(O2CCF3)4] and [(C8H11N2)Pt (CH3)] were correctly revealed by overlapping the biggest lobe for receiving nucleophilic attacks of one molecule with the biggest lobe for receiving electrophilic attacks of the other molecule, so allowing to predict the same coordination modes as experimentally known: linear "end-on" for the [(C8H11N2)Pt (CH3)]…I2, and bent "end-on" for the [Rh2(O2CCF3)4]…I2 interactions.


When is switching warranted among biologic therapies in rheumatoid arthritis?
Switching among biologic therapies is common practice in patients with rheumatoid arthritis who have an inadequate response or intolerable adverse events. Evidence from observational studies and association guidelines supports the use of sequential biologic therapy for these reasons. Owing to recent economic pressures on healthcare budgets, patients with rheumatoid arthritis who are well controlled on and tolerant of their current biologic therapy may be switched to alternative biologics, despite limited evidence supporting this practice. Clinical research and experience suggest that TNF antagonists are not interchangeable, as meaningful differences have been observed in their efficacy and safety profiles. Additional research is needed to assess the risk:benefit ratio of specific sequences of biologic therapies and the validity of switching biologic therapies for nonclinical purposes.


Effectiveness of a primary school-based intervention to reduce overweight.
The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children. A cluster randomized controlled design was used over one school year with schools as unit of randomization. In total 20 schools and 2,622 children aged 6-12 years (grades 3-8) from multi-ethnic, low income inner-city neighbourhoods in Rotterdam, Netherlands, participated. The intervention, named Lekker Fit! (Enjoy being fit!) was a multi-component intervention based on behavioural and ecological models. Main components of the intervention are the implementation of three physical education (PE) sessions a week by a professional PE teacher, additional sport and play activities outside school hours and an educational program. Main primary outcome measures were weight status, body mass index (BMI), waist circumference and fitness (20 m shuttle run). Significant positive intervention effects were found for percentage overweight children (OR 0.53; 95% CI 0.36-0.78), waist circumference (-1.29 cm; 95% CI -2.16 to -0.42 cm) and 20 m shuttle run (0.57 laps; 95% CI 0.13-1.01 laps) among pupils of grades 3-5 (6-9-year olds). The prevalence of overweight in grades 3-5 increased by 4.3% in the control group and by 1.3% in the intervention group. No significant effects were found for BMI or for grades 6-8 (9-12-year olds). Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit! among pupils of grades 3-5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity. [ISRCTN84383524].


Hazardous complications of animate foreign bodies in otology practice.
Animate foreign bodies in the ear are frequent occurrences in otology practice. Such foreign bodies may lead to hazardous complications. This paper describes a retrospective study of six patients with a recent history of an insect in the ear who presented with various complications following intervention received elsewhere. An insect was retrieved from the external auditory canal in four cases and from the antrum in two cases. The patients presented with progressive otological complications: two patients who presented with orbital apex syndrome and cavernous sinus thrombosis succumbed to the disease; three patients suffered sensorineural hearing loss; and two patients had persistent facial palsy. One patient with sigmoid sinus thrombosis, who presented early, experienced complete recovery. Insects in the ear can lead to hazardous complications. Animate foreign bodies should preferably be managed by a trained otologist, even in an emergency setting. Patients with delayed presentation and complications have a guarded prognosis.


Development of tissue-simulating optical phantoms: poly-N-isopropylacrylamide solution entrapped inside a hydrogel.
The average turbid optical properties of the N-isopropylacrylamide (NIPA) polymer solution entrapped inside a polyacrylamide hydrogel (called an NIPA/PAAM gel system) were studied using a multiwavelength oblique-incidence reflectometer. The turbidity of such a system can be drastically changed by simply switching the temperature from below the low critical solution temperature of the NIPA, around 33 degrees C, to above. The absorption coefficient and the reduced scattering coefficient were obtained as a function of wavelength for samples with selected NIPA and blue dextran concentrations. It is found that the scattering of the optical phantom comes from the NIPA polymer chains and the absorption from the blue dextran. The turbid optical properties of an NIPA/PAAM gel system can be tuned to simulate biological tissues at a specific wavelength by varying compositions of NIPA and blue dextran and further modified by controlling the temperature.


[Mechanism of action of sodium oxybutyrate in experimental myocardial infarction].
Effect of sodium hydroxybutyrate on lipid metabolism was studied in experimental infarction of rabbit myocardium. Administration of 80 mg of sodium hydroxybutyrate per kg of body mass caused a decrease of free fatty acids content in the infarction zone, in surrounding zones and in blood. Treatment of the experimental animals with sodium hydroxybutyrate normalized distinctly the phospholipid composition of the ischemized myocardium. Content of phosphatidyl choline, phosphatidyl ethanolamine and cardiolipine was increased in the infarction zone and in surrounding zones of myocardium. Concentration of lysolecithines was decreased in the both zone studied. In the animals treated with sodium hydroxy butyrate after the infarction output of myocardial creatine kinase into circulation was decreased.


Regulation of swimming in the Culex pipiens (Diptera, Culicidae) pupa: kinematics and locomotory trajectories.
High-speed videography was used to investigate swimming kinematics and locomotory trajectories during escape responses in the pupa of Culex pipiens (Diptera, Culicidae). The pupa can perform straight-line motion despite undergoing backward and forward somersaults through 400 degrees at a rate of 20 s(-)(1). For linear motion to occur, the effective stroke of the abdomen must be delivered during the part of each cycle when the body is facing forwards, allowing passive rotation to carry the body round to the correct position for the start of the next half-stroke. On-off motion of the abdomen is regulated by a click mechanism based on stressed integumentary plates which buckle at strategic points in the cycle. The importance of self-inertia as a component in positional regulation was demonstrated by increasing the kinematic viscosity of the medium: this retarded rotation and resulted in somersaulting on the spot. Whereas normally the pupa invariably directs its swimming downwards, reversal of the usual light gradient produced upward paths as well. It is concluded that straight-line motion is generated automatically by the locomotory machine without any need for sensory feedback about body orientation during each cycle, but that swimming direction can be influenced by sensory cues such as light.


Mesothelioma: a review.
Mesothelioma is an insidious disease with long latency after asbestos exposure. New cases are continually diagnosed, although levels are declining with recognition of the asbestos risk and efforts to remove asbestos from the workplace. Treatment for early stage disease with surgery and radiation is potentially curative, but many patients either are too ill to undergo aggressive surgery or present with advanced disease. Chemotherapy with cisplatin and pemetrexed is considered standard, although relapse is common. Second-line therapy is disappointing. New targeted therapies may pose promise and are being addressed in various clinical trial settings. Palliative care remains an important component of the management of this devastating illness.


Cigarette Consumption and Nutrient Intake in Indonesia: Study of Cigarette-Consuming Households.
This study aims to investigate the impact of cigarette consumption on household's nutrition adequacy (NA). This study also examines the opportunity cost of cigarette expenditure to children's nutritional adequacy. We used an Indonesian cross-sectional household level nationwide data of 2018 National Socio-Economic Survey (SUSENAS). Using multivariate Ordinary Least Square (OLS) regression, we estimated the impact of cigarette consumption on household's NA as defined by household protein and energy intakes. With the same specification, we further ran a segregated OLS regression by household quintile expenditure. While the opportunity cost of cigarette consumption to children's nutrition adequacy defined the estimated forgone nutrition due to cigarette consumption by following the Ministry of Health (MOH) definition of Recommended Dietary Allowance (RDA) for children aged 4 - 6. Cigarette consumption decreases household's protein and energy intakes. We found statistically significant correlation between household's cigarette consumption and household's per capita protein intake while no statistically significant correlation on energy intake. Furthermore, the segregated estimate is significant for both protein and energy intakes among 60% lowest household quintile expenditure groups. The lower the quintile expenditure, the higher the decline in household NA due to cigarette consumption. With the average cigarette expenditure of IDR12,956 per household per day, giving up daily cigarette spending could meet children's energy intake by 27% - 85,4% of RDA and protein intake by 180.12% - 300.48% of RDA. Household cigarette consumption has negative impact on household's daily energy and protein intakes. The poorest group is most vulnerable to nutrition inadequacy due to cigarette consumption. Giving up household's cigarette expenditure daily could result in a substantial nutrition gain for children at their critical growth stages.


Cultivable bacterial diversity along the altitudinal zonation and vegetation range of tropical Eastern Himalaya.
The Northeastern part of India sprawls over an area of 262 379km2 in the Eastern Himalayan range. This constitutes a biodiversity hotspot with high levels of biodiversity and endemism; unfortunately, is also a poorly known area, especially on its microbial diversity. In this study, we assessed cultivable soil bacterial diversity and distribution from lowlands to highlands (34 to 3 990m.a.s.l.). Soil physico-chemical parameters and forest types across the different altitudes were characterized and correlated with bacterial distribution and diversity. Microbes from the soil samples were grown in Nutrient, Muller Hinton and Luria-Bertani agar plates and were initially characterized using biochemical methods. Parameters like dehydrogenase and urease activities, temperature, moisture content, pH, carbon content, bulk density of the sampled soil were measured for each site. Representative isolates were also subjected to 16S rDNA sequence analysis. A total of 155 cultivable bacterial isolates were characterized which were analyzed for richness, evenness and diversity indices. The tropical and sub-tropical forests supported higher bacterial diversity compared to temperate pine, temperate conifer, and sub-alpine rhododendron forests. The 16S rRNA phylogenetic analysis revealed that Firmicutes was the most common group followed by Proteobacreria and Bacteroidetes. Species belonging to the genera Bacillus and Pseudomonas were the most abundant. Bacterial CFU showed positive but insignificant correlation with soil parameters like pH (r=0.208), soil temperature (r=0.303), ambient temperature (r=0.443), soil carbon content (r=0.525), soil bulk density (r=0.268), soil urease (r=0.549) and soil dehydrogenase (r=0.492). Altitude (r=-0.561) and soil moisture content (r=-0.051) showed negative correlation. Altitudinal gradient along with the vegetation and soil physico-chemical parameters were found to influence bacterial diversity and distribution. This study points out that this is a biome with a vast reservoir of bacteria which decrease with increasing altitudes, and highlights the microbiological importance of the poorly studied Eastern Himalayan range, justifying efforts to explore the prevalence of novel species in the biome.


Utility of the Cell Index in Predicting External Ventricular Drain-Related Ventriculo-Meningitis.
Ventriculo-meningitis (VM) is an important complication of external ventricular drains (EVDs) in neurosurgical patients. Consequences include increased morbidity, mortality, and duration of hospital stay. Early diagnosis of EVD-associated VM allows earlier treatment intervention. The cell index (CI) may provide a simple measure that overcomes the limitations of isolated cerebrospinal fluid (CSF) parameters and other diagnostic tests, allowing earlier prediction of VM. All patients admitted to a tertiary hospital and requiring EVD insertion during 2015 and 2016 were assessed for inclusion in this retrospective case-control study. Patients with a known or suspected intracranial infection were excluded. Of the 186 patients who underwent EVD insertion, 95 patients were included in the final cohort. Data pertaining to patient characteristics and laboratory indices were extracted from health records and the microbiology laboratory database. The CI was calculated as the ratio of temporally related CSF leukocytes/erythrocytes to peripheral blood leukocytes/erythrocytes. Data from patients with microbiologically confirmed VM were analyzed in comparison with those not developing VM during the course of their stay. Categorical and continuous variables with skewed distributions were analyzed by Chi square and Mann-Whitney tests, respectively. EVD-associated VM developed in 7.4% of patients. The highest CSF CI (within 3 days prior to diagnosis of VM or at any time for those not developing VM) differed significantly between the two groups (16; IQR 10.8-48.5 vs. 3.3; IQR 1.0-12.8, respectively; p = .046). The area under the receiver operating characteristic curve (AUROC) for the highest CI was 0.727 (95% confidence interval [CI] 0.526-0.929; p = .027). A CI of 10.4 provided a sensitivity and specificity of 80.5% and 70.5%, respectively, for the early diagnosis of VM. In neurosurgical patients with an EVD, the CSF CI significantly predicted the development of VM.


Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children.
HIV-infected and uninfected children who survived their first year of life were prospectively followed in Malawi to assess levels of mortality and related risk factors during the second and third years of life. Children with known HIV status from an earlier perinatal intervention trial were enrolled. These children [HIV-infected (Group A); HIV-uninfected but born to HIV-seropositive mothers (Group B); and children born to HIV-seronegative mothers (Group C)] were followed every 3 months until age 36 months. Mortality data were collected at each visit. Immunologic data (CD4+ percent) were collected at or immediately after enrollment. Overall 702 children were enrolled and 83 children died during follow-up. The mortality rate per 1000 person years of observation was 339.3 among Group A children, 46.3 among Group B children and 35.7 among Group C children. Among HIV-infected children the cumulative proportion surviving to age 24 months was 70% and those surviving to age 36 months was 55%. By age 32 months none of the severely immunosuppressed (CD4% < 15%) children had survived. The mortality differentials between HIV-infected and uninfected children persisted after adjusting for several risk factors. The major causes of death among infected children (n = 52) were wasting and respiratory conditions. Although all HIV-infected children had received childhood immunizations, mortality was high. Management of these children should include aggressive antimicrobial treatment, and evaluation of prophylactic regimens should be considered.


Brief communication: histological age estimation using rib and clavicle.
Histological methods for estimating age at death using osteon population densities for the rib, clavicle, and rib and clavicle combined are presented. Predicting formulas were generated from a sample of 40 individuals of known age, sex, and race. Independent samples of 12 ribs and 7 clavicles were used to test the formulas. Mean differences between known and predicted ages were 1.1 years, 2.6 years, and 3.4 years for the clavicle, rib and clavicle combined, and rib formulas respectively. An analysis of variance found no significant differences among the means for predicted and known ages. Since the formula based upon rib and clavicle combined has the higher standard error and r2, and includes data from different bones, it should provide better overall accuracy and reliability, and is recommended whenever both bones are available.


Transplantation of fetal rat islets into the cerebral ventricles of alloxan-diabetic rats. Amelioration of diabetes by syngeneic but not allogeneic islets.
Syngeneic fetal rat islets were isolated and transplanted into alloxan-diabetic inbred male Lewis rats. The effect of transplantation of islets into the cerebral ventricles on the diabetic state of the recipients was compared with that of the conventional transplantation of islets homeotypically into the liver via the portal vein. Fourteen of fourteen rats surviving after stereotaxic implantation of islets into the ventricles returned to normoglycemia; normoglycemia has been maintained for up to 34 wk. Glucose tolerance tests revealed an improved, although not completely normalized, pattern. Histologic examination of the brains of these recipients revealed clusters of intact islets in the ventricle. These data provided a physiologic basis for further investigation of the immunologically privileged nature of the intraventricular space as a site for implantation of allogeneic pancreatic islets. Islets from Wistar-Furth rats (major histocompatibility difference) or Fischer 344 rats (minor histocompatibility difference) were transplanted into the ventricles of alloxan-diabetic Lewis rats. There were only small and unsustained changes in body weight and blood and urine glucose of any of the rats receiving the allogeneic islets. Histologic examination of the ventricles of these rats 3 wk after transplantation revealed only glial scar tissue. These data suggest that the cerebral ventricles cannot serve as a privileged site for islet transplantation, at least using the type of islet preparation employed in these experiments.


Association of hepatitis C virus genotype 2 spread with historic slave trade and commerce routes in Western Africa.
The hepatitis C virus genotype 2 (HCV2) is endemic in Western and Central Africa. The HCV2 evolutionary origins remain uncertain due to the paucity of available genomes from African settings. In this study, we investigated the molecular epidemiology of HCV infections in rural Guinea, Western Africa, during 2004 and 2014. Broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR)-based screening of sera from 1,571 asymptomatic adults resulted in the detection of 25 (1.5 per cent; 95 per cent confidence interval 0.9-2.3) positive samples, with a median viral load of 2.54E + 05 IU/ml (interquartile range 6.72E + 05). HCV-infected persons had a median age of 47 years, and 62.5 per cent were male and 37.5 per cent were female. The full polyprotein-encoding genes were retrieved by a combination of high throughput and Sanger sequencing from 17 samples showing sufficiently high viral loads. Phylogenetic analysis and sequence distances ≥13 per cent averaged over the polyprotein genes compared to other HCV2 subtypes revealed nine previously unknown HCV2 subtypes. The time to the most recent common ancestor of the Guinean HCV2 strains inferred in a Bayesian framework was 493 years (95 per cent Highest posterior density (HPD) 453-532). Most of the Guinean strains clustered poorly by location on both the level of sampling sites within Guinea and the level of countries in the phylogenetic reconstructions. Ancestral state reconstruction provided decisive support (Bayes factor > 100) for an origin of HCV2 in Western Africa. Phylogeographic reconstructions in a Bayesian framework pointed to a radial diffusion of HCV2 from Western African regions encompassing today's countries like Ghana, Guinea Bissau, or Burkina Faso, to Central and Northern African regions that took place from the 16th century onwards. The spread of HCV2 coincided in time and space with the main historic slave trade and commerce routes, supported by Bayesian tip-association significance testing (P = 0.01). Our study confirms the evolutionary origins of HCV2 in Western Africa and provides a potential link between historic human movements and HCV2 dispersion.


Uses of process evaluation in the Maryland WIC 5-a-day promotion program.
Using a crossover design, the authors conducted a 6-month intervention program aimed at increasing fruit and vegetable consumption among women served by the Women, Infants, and Children program in Baltimore City and six Maryland counties. The theoretical framework for the interventions was the Transtheoretical Model of Change. At 2 months postintervention, mean daily consumption had increased significantly more in intervention participants than in control participants. Extensive process evaluation data were collected to assess the quantity and quality of program services delivered. These included participant nutrition session evaluation forms and attendance logs, focus groups of attenders and nonattenders of sessions, information about peer educators, and postintervention surveys. Many lessons were learned about program delivery, factors affecting attendance, and the obstacles to dietary change. Strategies to increase participants' consumption of fruits and vegetables were modified based on these lessons and the process evaluations.


The Riks-Stroke story: building a sustainable national register for quality assessment of stroke care.
Riks-Stroke, the Swedish Stroke Register, is the world's longest-running national stroke quality register (established in 1994) and includes all 76 hospitals in Sweden admitting acute stroke patients. The development and maintenance of this sustainable national register is described. Riks-Stroke includes information on the quality of care during the acute phase, rehabilitation and secondary prevention of stroke, as well as data on community support. Riks-Stroke is unique among stroke quality registers in that patients are followed during the first year after stroke. The data collected describe processes, and medical and patient-reported outcome measurements. The register embraces most of the dimensions of health-care quality (evidence-based, safe, provided in time, distributed fairly and patient oriented). Annually, approximately 25,000 patients are included. In 2009, approximately 320,000 patients had been accumulated (mean age 76-years). The register is estimated to cover 82% of all stroke patients treated in Swedish hospitals. Among critical issues when building a national stroke quality register, the delicate balance between simplicity and comprehensiveness is emphasised. Future developments include direct transfer of data from digital medical records to Riks-Stroke and comprehensive strategies to use the information collected to rapidly implement new evidence-based techniques and to eliminate outdated methods in stroke care. It is possible to establish a sustainable quality register for stroke at the national level covering all hospitals admitting acute stroke patients. Riks-Stroke is fulfilling its main goals to support continuous quality improvement of Swedish stroke services and serve as an instrument for following up national stroke guidelines.


[Partial purification and properties of a mitogenic factor from Mycoplasma arthritidis].
M. arthritidis PG6 in a dose of 10(7) colony-forming units per ml was shown to produce a highly pronounced mitogenic effect, linked with a thermolabile factor, on the splenocytes of mice and rats. The mitogenic factor was absent in the lipid fraction and in the fraction formed by easily extractable mycoplasmal proteins. The supernatant fluid obtained after the sedimentation of M. arthritidis globular proteins with ammonium sulfate stimulated lymphocytes as actively as the intact culture of M. arthritidis. The fractionation of the supernatant fluid in columns packed with Sephadex G-200 revealed that the greatest mitogenic effect was produced by the fraction with a molecular weight of 240,000 daltons. It seems that the arthritogenic properties of M. arthritidis are linked precisely with this subcomponent.


Evaluation of biofilm-specific antimicrobial resistance genes in Pseudomonas aeruginosa isolates in Farabi Hospital.
Biofilm produced from Pseudomonas aeruginosa is the cause of infection induced by contact lenses, trauma and post-surgery infection. The aim of this study was to evaluate biofilm formation and the presence of the genes ndvB and tssC1 in ocular infection isolates of P. aeruginosa. A total of 92 P. aeruginosa strains were collected from patients with ocular infection referred to Farabi Hospital between March 2014 and July 2015. Antibiotic susceptibility patterns were evaluated by the agar disc-diffusion method according to CLSI guidelines. PCR assays were used to detect ndvB and tssC1, genes associated with resistance in biofilm-producing P. aeruginosa isolates. Biofilm formation ability was examined by crystal violet microtitre plate assay. During the period of study, 92 P. aeruginosa were isolated from ocular infections including keratitis (n=84) and endophthalmitis (n=8). The highest resistance rates were seen against colistin (57.6 %) and gentamicin (50 %) and the lowest resistance rates were seen against imipenem (3.3 %), aztreonam (4.3 %), piperacillin-tazobactam (4.3 %), ceftazidime (4.3 %) and ciprofloxacin (5.4 %). Biofilm production ability was found in 100 % of the isolates. PCR assays showed that of the 92 P. aeruginosa isolates, 96.7 and 90.2 % harboured the genes ndvB and tssC1, respectively. Our results showed a considerable ability of biofilm production, as well as the occurrence of biofilm-specific antimicrobial resistance genes (ndvB and tssC1), in P. aeruginosa isolates from ocular infections in Farabi Hospital.


Risk factors, DNA damage, and disease progression in Barrett's esophagus.
Esophageal adenocarcinoma develops on a background of Barrett's esophagus. A number of risk factors have been linked to both conditions, including gastroesophageal reflux and smoking. However, the molecular mechanisms by which these factors influence disease progression remain unclear. One possibility is that risk factors generate promutagenic DNA damage in the esophagus. The comet assay was used to measure DNA damage in esophageal (Barrett's and squamous) and gastric mucosa of Barrett's patients with (n = 24) or without (n = 50) associated adenocarcinoma or high-grade dysplasia in comparison with control patients (squamous mucosa) without Barrett's esophagus (n = 64). Patients completed a questionnaire detailing exposure to some of the known risk factors for Barrett's esophagus and adenocarcinoma. In Barrett's esophagus patients, DNA damage was higher in Barrett's mucosa compared with normal esophageal and gastric mucosa (P < 0.001). In addition, the highest quartile of DNA damage in Barrett's mucosa was associated with an increased risk (odds ratio, 9.4; 95% confidence interval, 1.1-83.4; P = 0.044) of developing adenocarcinoma or high-grade dysplasia compared with DNA damage levels in the lowest quartile. Smoking was associated with higher DNA damage in squamous epithelium in all patient groups (P < 0.01) and in Barrett's mucosa (P < 0.05) in Barrett's esophagus patients only. In controls only, current reflux was associated with higher DNA damage, whereas anti-inflammatory drug use resulted in lower levels. Collectively, these data imply a genotoxic insult to the premalignant Barrett's mucosa that may explain the genetic instability in this tissue and the progression to adenocarcinoma. There is an indication for a role for smoking in inducing DNA damage in esophageal mucosa but an understanding of the role of reflux requires further investigation.


Lumbar nerve root compression and interstitial cystitis--response to decompressive surgery.
An identifiable lumbar nerve root compression appears to cause urological dysfunction consistent with interstitial cystitis. Ten patients (9 females, 1 male) were evaluated for chronic pelvic pain. Cystoscopic and histological appearances were consistent with a diagnosis of interstitial cystitis. Magnetic resonance studies of the lower spine consistently demonstrated a lateral compression of the L5 dorsal nerve root. Decompression of the lateral foramina of L5 resulted in immediate relief of pain in 9 patients, who have been followed up for 6 months without a recurrence. Possible mechanisms involving sympathetic dystrophy of the pelvic plexus are reviewed.