Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies.
Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence.


Associations between different types of physical activity and teachers' perceived mental, physical, and work-related health.
The teaching profession is characterized by high levels of stress and physical complaints, which might be improved through regular participation in physical activity (PA). However, the effect of PA on mental and physical health is not always consistent and depends on the type of PA performed. The aim of this study was to examine the mental, physical, and work-related health of Flemish secondary school teachers and identify the impact on those health variables by demographic and teaching-related factors and various types of PA. This study included an online survey conducted across a representative sample of secondary school teachers (n = 1066, average age 40 years; 68 percent female). Level of PA and sitting time were estimated using the International Physical Activity Questionnaire, and perceived mental health and physical health were estimated using the Short Form 36. Work-related factors such as job satisfaction, occupational stress, and absenteeism were also collected. T-tests, ANOVAs, and linear regression analyses were performed. Flemish secondary school teachers have poorer perceived mental and physical health than a general healthy population. This difference is particularly evident among female teachers, who reported lower perceived health, more occupational stress, and more absent days compared to their male colleagues. Higher participation in leisure-time PA was associated with a more positive perceived health. In contrast, higher levels of occupational PA and sitting time had a negative impact on perceived health. Total amount of PA, total amount of moderate-to-vigorous PA, transportation-related PA, and PA at home were not associated to teachers' perceived health. Because secondary school teachers' levels of perceived health are low, they are an important target group for interventions aiming to improve health. Only leisure-time PA was associated with more positive perceived health. This finding may indicate that teachers performing more exercise during leisure time, or in a more autonomous way, may be more resistant to physical and mental health problems. Future research should verify whether promoting leisure-time PA among teachers has the potential to improve their mental and physical health, and counteract the negative associations between teachers' health and their occupational PA.


[Pituitary-gonadal function following therapy of testicular relapse in boys with acute lymphoblastic leukemia].
Testicular function was evaluated in 8 boys with acute lymphoblastic leukemia (ALL) and testicular relapse following another course of intensive chemotherapy with unilateral or bilateral orchidectomy and/or testicular irradiation. LH- and FSH-secretion was studied in all using a standardized LHRH-test. In addition, a HCG-test was performed in 6 boys. In prepuberty, all boys examined showed normal LH- and FSH-values. Beginning at 9 to 10 years, elevated basal and/or stimulated LH- and FSH-values were occasionally noted in contrast to the consistently elevated values after the age of 12. Using the HCG-test, we found a testosterone response only in patients receiving gonadal irradiation of 1 100 and 1 500 rads (2 patients). No response was elicited in those with radiation doses of 2 400 and 3 000 rads. We conclude that high dose gonadal irradiation and chemotherapy cause temporary and possibly permanent impairment of spermatogenesis and Leydig cell function in boys with ALL and testicular relapse.


NS5 Conservative Site Is Required for Zika Virus to Restrict the RIG-I Signaling.
During host-virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defending pathogen infections. NS5 subsequently represses K63-linked polyubiquitination of RIG-I, attenuates the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3), and inhibits the expression and production of interferon-β (IFN-β), thereby restricting the RIG-I signaling pathway. Interestingly, we demonstrate that the methyltransferase (MTase) domain of NS5 is required for the repression of RIG-I ubiquitination, IRF3 activation, and IFN-β production. Detailed studies further reveal that the conservative active site D146 of NS5 is critical for the suppression of the RIG-I signaling. Therefore, we uncover an essential role of NS5 conservative site D146 in ZIKV-mediated repression of innate immune system, illustrate a distinct mechanism by which ZIKV evades host immune responses, and discover a potential target for anti-viral infection.


Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with pathogenic congeners.
Vibrio fischeri belongs to the Vibrionaceae, a large family of marine gamma-proteobacteria that includes several dozen species known to engage in a diversity of beneficial or pathogenic interactions with animal tissue. Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported. Nonpathogenic members of the genus Vibrio, including a number of beneficial symbionts, make up the majority of the Vibrionaceae, but none of these species has been similarly examined. Here we report the genome sequence of V. fischeri ES114, which enters into a mutualistic symbiosis in the light organ of the bobtail squid, Euprymna scolopes. Analysis of this sequence has revealed surprising parallels with V. cholerae and other pathogens.


Adaptive trade-offs in juvenile salmonid metabolism associated with habitat partitioning between coho salmon and steelhead trout in coastal streams.
1. Adaptive trade-offs are fundamental to the evolution of diversity and the coexistence of similar taxa and occur when complimentary combinations of traits maximize efficiency of resource exploitation or survival at different points on environmental gradients. 2. Standard metabolic rate (SMR) is a key physiological trait that reflects adaptations to baseline metabolic performance, whereas active metabolism reflects adaptations to variable metabolic output associated with performance related to foraging, predator avoidance, aggressive interactions or migratory movements. Benefits of high SMR and active metabolism may change along a resource (productivity) gradient, indicating that a trade-off exists among active metabolism, resting metabolism and energy intake. 3. We measured and compared SMR, maximal metabolic rate (MMR), aerobic scope (AS), swim performance (UCrit) and growth of juvenile hatchery and wild steelhead and coho salmon held on high- and low-food rations in order to better understand the potential significance of variation in SMR to growth, differentiation between species, and patterns of habitat use along a productivity gradient. 4. We found that differences in SMR, MMR, AS, swim performance and growth rate between steelhead trout and coho salmon were reduced in hatchery-reared fish compared with wild fish. Wild steelhead had a higher MMR, AS, swim performance and growth rate than wild coho, but adaptations between species do not appear to involve differences in SMR or to trade-off increased growth rate against lower swim performance, as commonly observed for high-growth strains. Instead, we hypothesize that wild steelhead may be trading off higher growth rate for lower food consumption efficiency, similar to strategies adopted by anadromous vs. resident brook trout and Atlantic salmon vs. brook trout. This highlights potential differences in food consumption and digestion strategies as cryptic adaptations ecologically differentiating salmonid species. 5. We hypothesize that divergent digestive strategies, which are common and well documented among terrestrial vertebrates, may be an important but overlooked aspect of adaptive strategies of juvenile salmonids, and fish in general.


Structural and electronic transport properties of a SiC chain encapsulated inside a SiC nanotube: first-principles study.
Silicon carbide (SiC) chains and silicon carbide nanotubes (SiCNTs), as promising one-dimensional nanostructures, have potential applications in more controllable nanoelectronic devices. In this paper, we design a completely new hybrid structure with encapsulation of a linear SiC chain inside a SiCNT, using first-principles calculation and the non-equilibrium Green's function formalism to systematically investigate the structural stability and electronic properties, particularly the quantum transport properties. It is found that, due to the nanotube-chain interaction, the stability of this structure is mainly provided by the charge transfer from the hosting tube to the guest chain. Furthermore, the transport properties of the hybrid structure confirm that encapsulation of a SiC chain within a SiCNT can significantly enhance the electronic transport of the component system in a wide range of high voltage. The distance and the unique coupling configuration between the encapsulated system and the electrodes are demonstrated to be other important factors that affect the transport behaviours. We hope that our study of encapsulation may offer a significant starting point for the design of new materials related to low-dimensional SiC nanostructures and possibly open a novel path towards stability and conductivity enhancement.


Irritable bowel syndrome and hypersensitivity to food.
Food hypersensitivity as a cause of irritable bowel syndrome was investigated by means of exclusion diet and blind provocation. Twelve atopic and twelve non-atopic individuals entered into the study. Skin prick testing with 20 foods and food additives and RAST specific for food only, were done in all cases. Serum IgE level was also measured. In 14 patients one or several food or additives were shown to induce the typical symptoms of IBS. In at least nine cases of atopy, an IgE-mediated mechanism could be incriminated. Among other potential pathogenetic mechanisms, the presence in the intestinal tract of yeast (Candida albicans, Geotrichum candidum) seems to be of major importance. Yeast apparently favor the development of allergic as well as pseudo-allergic reactions, at least in some patients. Finally, at least in atopic patients complaining of IBS, it is of importance to search for a food component. Dramatic clinical improvements can result from the introduction of an adequate exclusion diet.


Development of an optical flow through detector for bubbles, crystals and particles in oils.
The characterisation of bubbles or particles in an oil poses some unique challenges. In contrast to water solutions, the use of electrochemical detection approaches is more difficult in an oil. However, optical sensing systems have considerable potential in this area. Here we use a flow through channel approach and monitor the light propagation through this structure in an optical transmission sensor arrangement (OTS). This simple approach is demonstrated to be useful at detecting bubbles produced in the oil as a result of cavitation induced by high intensity ultrasound (HIU). The optical technique is shown to have an analytical basis. Bubble detection from an operating HIU source is shown to depend on position of the sensor with respect to the source. Critically, the bubble population can be followed for extended time periods after the ultrasonic source has been terminated. The detection of crystals is also demonstrated. Hence, this technique is ideal for the study of the effects of HIU on oils as they crystallise over extended time periods.


T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis.
Mutations in T-box genes are the cause of several congenital diseases and are implicated in cancer. Tbx20-null mice exhibit severely hypoplastic hearts and express Tbx2, which is normally restricted to outflow tract and atrioventricular canal, throughout the heart. Tbx20 mutant hearts closely resemble those seen in mice overexpressing Tbx2 in myocardium, suggesting that upregulation of Tbx2 can largely account for the cardiac phenotype in Tbx20-null mice. We provide evidence that Tbx2 is a direct target for repression by Tbx20 in developing heart. We have also found that Tbx2 directly binds to the Nmyc1 promoter in developing heart, and can repress expression of the Nmyc1 promoter in transient transfection studies. Repression of Nmyc1 (N-myc) by aberrantly regulated Tbx2 can account in part for the observed cardiac hypoplasia in Tbx20 mutants. Nmyc1 is required for growth and development of multiple organs, including the heart, and overexpression of Nmyc1 is associated with childhood tumors. Despite its clinical relevance, the factors that regulate Nmyc1 expression during development are unknown. Our data present a paradigm by which T-box proteins regulate regional differences in Nmyc1 expression and proliferation to effect organ morphogenesis. We present a model whereby Tbx2 directly represses Nmyc1 in outflow tract and atrioventricular canal of the developing heart, resulting in relatively low proliferation. In chamber myocardium, Tbx20 represses Tbx2, preventing repression of Nmyc1 and resulting in relatively high proliferation. In addition to its role in regulating regional proliferation, we have found that Tbx20 regulates expression of a number of genes that specify regional identity within the heart, thereby coordinating these two important aspects of organ development.


Navigating the landscape of psoriasis therapy: novel targeted pathways and emerging trends.
Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics. This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms. A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.


Photosynthesis and photoprotection in Nicotiana tabacum L. in vitro-grown plantlets.
Nicotiana tabacum L. plantlets were cultured in vitro photoautotrophically (0% sucrose) and photomixotrophically (3% or 5% sucrose) at two irradiances (80 or 380 mumol m-2 s-1) with the aim of investigating the effect of these culture conditions on photosynthetic parameters and on protective systems against excess excitation energy. In plantlets grown photoautotrophically under higher irradiance photoinhibition was demonstrated. These plantlets had a decreased chlorophyll (Chl) a + b content and Chl a/b ratio, an increased content of xanthrophyll cycle pigments and a higher deepoxidation state, a decreased maximum photochemical efficiency of photosystem II (PS II) and actual photochemical efficiency of PS II, and an increased non-photochemical quenching. In the photoautotrophically grown plantlets and those photomixotrophically grown with 3% sucrose, the increase of growth irradiance from 80 to 380 mumol m-2 s-1 stimulated the activities of ascorbate-glutathione cycle enzymes with the exception of ascorbate peroxidase. Ascorbate peroxidase activity was not affected by the increase in growth irradiance but a significant decrease with increasing sucrose concentration was evident. The higher concentration of sucrose in the medium (5%) in combination with the higher irradiance inhibited photosynthesis (decrease in Chl a + b content and net photosynthetic rate) but no significant changes in activities of ascorbate-glutathione cycle enzymes were found. These results suggest that exogenous sucrose added to the medium improved high irradiance and oxidative stress resistance of the plantlets but the effect of sucrose is concentration dependent.


Prolactin levels during long-term risperidone treatment in children and adolescents.
This analysis was designed to investigate prolactin levels in children and adolescents on long-term risperidone treatment and explore any relationship with side effects hypothetically attributable to prolactin (SHAP). Data from 5 clinical trials (total N = 700) were pooled for this post hoc analysis. Children and adolescents aged 5 to 15 years with subaverage intelligence quotients and conduct or other disruptive behavior disorders received risperidone treatment (0.02-0.06 mg/kg/day) for up to 55 weeks. Outcome measures analyzed included serum prolactin levels, reported adverse events, and the conduct problem subscore of the Nisonger Child Behavior Rating Form. Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 (N = 358) and 13.0 ng/mL at weeks 52 to 55 (N = 42). There was no relationship between pro-lactin levels and age. Females returned to a mean value within the normal range (</= 30 ng/mL) by weeks 8 to 12, and males were close to normal values (</= 18 ng/mL) by weeks 16 to 24. At least 1 SHAP was reported by 13 (2.2%) of 592 children. There was no direct correlation between prolactin elevation and SHAP. With long-term risperidone treatment in children and adolescents, serum prolactin levels tended to rise and peak within the first 1 to 2 months and then steadily decline to values within or very close to the normal range by 3 to 5 months.


A novel neuroendocrine intracellular signaling pathway.
Expression of many components of the secretory pathway in peptidergic neuroendocrine cells is precisely controlled in response to secretagogues. Regulated endocrine-specific protein (RESP18) was identified as a dopamine-regulated intermediate pituitary transcript. Although the amino acid sequence of RESP18 initially suggested that it might be a novel preprohormone, its widespread expression in peptide-producing neurons and endocrine cells and its localization to the lumen of the endoplasmic reticulum suggested that it subserves a unique function. Subtractive hybridization of a pituitary corticotrope AtT-20 cell line engineered for inducible RESP18 expression demonstrated a RESP18-dependent induction of several transcripts. Regulation of RESP18 expression in vitro and in vivo was accompanied by changes in the same transcripts. Several cDNAs encoding transcripts up-regulated by RESP18 were analyzed by DNA sequencing, searching the GenBank databases for homologous proteins, and Northern blotting. One novel clone showed a tissue distribution nearly identical to that of RESP18. One clone was identical to rat LIMK2, a protein kinase containing modular protein-protein interaction LIM (lin-11, isl-1, mec-3) domains. Another clone was similar to monomeric bacterial isocitrate dehydrogenases. Like the unfolded protein response, these data demonstrate a novel signaling pathway from the secretory pathway lumen to the nucleus. RESP18 acts as a lumicrine peptide (an intracellular luminal autocrine hormone) inducing this pathway.


Wrist arthritis associated with scaphoid nonunion.
Patients with old scaphoid nonunion have a high risk of developing wrist arthritis. Although some patients remain asymptomatic, some will have pain sufficient to seek treatment. There are several treatment options available. The authors prefer wrist arthrodesis for most of these patients.


Genome-Wide Prioritization and Transcriptomics Reveal Novel Signatures Associated With Thiazide Diuretics Blood Pressure Response.
Thiazide diuretics are among the most commonly prescribed antihypertensives. However, <50% of thiazide-treated patients achieve blood pressure (BP) control. Herein, we used different omics (genomics and transcriptomics) to identify novel biomarkers of thiazide diuretics BP response. Genome-wide analysis included 228 white hypertensives with BP determined at baseline and after 9 weeks of hydrochlorothiazide. Single-nucleotide polymorphisms with P <5×10-5 were prioritized according to their biological function, using RegulomeDB, haploreg, and Genome-Wide Annotation of Variants. The results from the prioritization approach revealed rs10995 as the most likely functional single-nucleotide polymorphism, among single-nucleotide polymorphisms tested, that has been associated with hydrochlorothiazide BP response. The rs10995 G-allele was associated with better BP response to hydrochlorothiazide versus noncarriers (Δ systolic BP/Δ diastolic BP: -12.3/-8.2 versus -6.8/-3.5 mm Hg, respectively, Δ systolic BP P=3×10-4, Δ diastolic BP P=5×10-5). This association was replicated in independent participants treated with chlorthalidone. In addition, rs10995 G-allele was associated with increased mRNA expression of VASP (vasodilator-stimulated phosphoprotein). Moreover, baseline expression of the VASP mRNA was significantly higher in 25 good responders to hydrochlorothiazide compared with 25 poor responders (P=0.01). This finding was replicated in independent participants treated with chlorthalidone (P=0.04). Last, allelic-specific expression analysis revealed a significant but modest imbalance with rs10995 and rs10156, a single-nucleotide polymorphism in high linkage disequilibrium (r2=0.7) with rs10995, which both could contribute to the observed genetic effects by affecting VASP mRNA expression. This study highlights the strength of using different omics to identify novel biomarkers of drug response and suggests VASP as a potential determinant of thiazide diuretics BP response. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00246519 and NCT01203852.


Enhanced methamphetamine metabolism in rhesus macaque as compared with human: an analysis using a novel method of liquid chromatography with tandem mass spectrometry, kinetic study, and substrate docking.
Methamphetamine (MA), which remains one of the widely used drugs of abuse, is metabolized by the cytochrome P450 (P450) family of enzymes in humans. However, metabolism of methamphetamine in macaques is poorly understood. Therefore, we first developed and validated a very sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using solid phase extraction of rhesus plasma with a lower limit of quantitation at 1.09 ng/ml for MA and its metabolites, 4-hydroxy methamphetamine (4-OH MA), amphetamine (AM), 4-OH amphetamine (4-OH AM), and norephedrine. We then analyzed plasma samples of MA-treated rhesus, which showed >10-fold higher concentrations of AM (∼29 ng/ml) and 4-OH AM (∼28 ng/ml) than MA (∼2 ng/ml). Because the plasma levels of MA metabolites in rhesus were much higher than in human samples, we examined MA metabolism in human and rhesus microsomes. Interestingly, the results showed that AM and 4-OH AM were formed more rapidly and that the catalytic efficiency (Vmax/Km) for the formation of AM was ∼8-fold higher in rhesus than in human microsomes. We further examined the differences in these kinetic characteristics using three selective inhibitors of each human CYP2D6 and CYP3A4 enzymes. The results showed that each of these inhibitors inhibited both d- and l-MA metabolism by 20%-60% in human microsomes but not in rhesus microsomes. The differences between human and rhesus CYP2D6 and CYP3A4 enzymes were further assessed by docking studies for both d and l-MA. In conclusion, our results demonstrated an enhanced MA metabolism in rhesus compared with humans, which is likely to be caused by differences in MA-metabolizing P450 enzymes between these species.


Immunoreactivity for Taurine Characterizes Subsets of Glia, GABAergic and non-GABAergic Neurons in the Neo- and Archicortex of the Rat, Cat and Rhesus Monkey: Comparison with Immunoreactivity for Homocysteic Acid.
The cerebral cortex is an area rich in taurine (2-aminoethanesulphonic acid), but only limited information exists regarding its cellular distribution. We therefore examined taurine-like immunoreactivity in the cerebral cortex of the rat, cat and macaque monkey using antiserum directed against glutaraldehyde-conjugated taurine. Immunostaining was assessed at the light and electron microscopic level, and patterns obtained in light microscopic studies were compared to those produced with antiserum to gamma-aminobutyric acid (GABA) and homocysteic acid (HCA). In all three species, strong taurine-like immunoreactive perivascular endothelial cells, pericytes and oligodendrocytes were found. These cells were located throughout the neuropil, which itself showed a low level of immunoreactivity. In rats and cats, a small number of weakly taurine-enriched neurons were observed, particularly in superficial layers. In all cortical areas of the macaque, however, glial staining was matched by strong, selective staining of subpopulations of cortical neurons which were distributed in a bilaminar pattern involving layers II/III and VI. In addition, in primary visual cortex, area 17, immunopositive neurons were also present in sublayer IVCbeta, while in the hippocampus strongly taurine-positive neurons were most conspicuous in the granule cell layer of the dentate gyrus. In all regions, strongly taurine-positive neurons constituted only a subpopulation of the neurons occupying a given layer. Examination of adjacent sections for GABA immunoreactivity showed that the most strongly taurine-positive neurons in layers II/III were immunoreactive for GABA. The cells located in layers IVCbeta and VI, and the granule cells of the dentate gyrus, however, were GABA-negative. The morphological features of these latter groups suggested that the antiserum to taurine identifies subsets of spiny stellate, small pyramidal and dentate granule cells. None of these neurons showed immunoreactivity with antiserum to HCA in the primate; HCA-positive glia were found along the pial and white matter boundaries of the cortex, and showed no overlap with strongly taurine-positive glial elements. Although a transmitter role for taurine may be unlikely, particularly in view of its enrichment in subpopulations of both inhibitory and excitatory cells, the capacity of taurine to influence membrane-associated functions in excitable tissues, and its selective distribution demonstrated here, provides the potential for a contribution to communication between cortical cells.


Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery of aciclovir: influence of fatty and non-fatty additives.
Aciclovir (acicloguanosine) has been demonstrated to be effective in the treatment of intraocular pathologies such as herpes simplex virus retinitis and acute retinal necrosis. Although intravitreal injections have been used with fewer side-effects than intravenous administration, the risk of complications increases with the frequency of intravitreous injections. For this reason, a biodegradable drug-delivery system, such as microspheres, able to promote prolonged release of the drug, offers a good alternative to multiple intraocular administrations. In this work, aciclovir-containing poly (D,L-lactide-co-glycolide) microspheres were prepared by the solvent evaporation method. Seven additives were incorporated in the microspheres to modulate the in vitro release rate of the drug: four non-fatty substances (polyethylene glycol 300, polyethylene glycol 1500, hydroxypropyl methylcellulose and gelatin) and three fatty substances (isopropyl myristate, vitamin E and Labrafil M 1944 CS). Morphology of microspheres was evaluated by scanning electron microscopy. Granulometric analysis showed that particle size distribution was significantly influenced by the incorporation of additives. Loading efficiency decreased when fatty substances were added, whereas non-fatty additives promoted higher incorporation of the drug. Infrared and differential scanning calorimetry analyses indicated that microspheres prepared by the solvent evaporation process were not influenced by the type of additive used. In all cases, the initial burst resulted less than 5%. Additive-free microspheres showed a slow release within the first days, but when additives were incorporated, in general, the release rates of the drug were increased. Best release results were obtained for gelatin-containing microspheres. The release of aciclovir from these microspheres was adjusted to a zero-order kinetic from 1 to 49 days with a release constant of 1.13 microg/day/mg microspheres. A dose of 0.74 mg microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses (MIC 0.1 microg/ml) and 7.4 mg for varicella zoster virus (MIC 1 microg/ml) treatment in an animal model.


Quality of life of young adults and adolescents with chronic kidney disease.
To elicit utility-based quality of life (QOL) in adolescents and young adults with chronic kidney disease (CKD). A cross-sectional study was conducted among patients aged 12-25 years with CKD stage 3-5 and 5D from 6 centers in Australia. QOL was measured using a visual analogue scale, and 3 utility-based QOL measures: Health Utilities Index Mark 2 and 3 (HUI2/3), Kidney Disease Quality of Life, incorporating the short form (SF)-12 transformed to SF-6D, and time trade-off (TTO). Multiple linear regression was used to define predictors for TTO QOL weights, SF-6D, and visual analogue scale scores. On a utility scale, with extremes of 0 (death) to 1 (full health), the 27 participants had a mean TTO QOL weight of 0.59 (SD = 0.40), HUI2 of 0.73 (SD = 0.28), HUI3 of 0.74 (SD = 0.26), and SF-6D of 0.70 (SD = 0.14). QOL weights were consistently low across the 4 utility-based instruments with widest variability in TTO responses. Mean QOL weights were higher among predialysis participants. The HUI2 indicated variability in the domain of emotion. From the Kidney Disease Quality of Life measures, decrements were observed in all QOL domains though dialysis patients reported a significantly higher burden attributed to kidney disease. Adolescent and young adults with CKD report low QOL values. Their utility-based QOL scores imply they are willing to trade considerable life expectancy for perfect health. Holistic care to improve QOL and minimize disease burden are imperative for optimizing health outcomes in young people with CKD, particularly those on dialysis.


Migration health research in the United Kingdom: A scoping review.
One in seven people living in the United Kingdom (UK) is an international migrant, rendering migrants an important population group with diverse and dynamic health and healthcare needs. However, there has been no attempt to map contemporary trends within migration health research conducted in the UK. The aim of this scoping review was to describe trends within migration health research and identify gaps for future research agendas. PubMed and Embase were systematically searched for empirical research with a primary focus on the concepts "health" and "migrants" published between 2001 and 2019. Findings were analysed using the UCL-Lancet Commission on Migration and Health Conceptual Framework for Migration and Health. In total, 399 studies were included, with almost half (41.1%; 164/399) published in the last five years of the study period between 2015 and 2019 and a third (34.1%; 136/399) conducted in London. Studies included asylum seekers (14.8%; 59/399), refugees (12.3%; 49/399), and undocumented migrants or migrants with insecure status (3.5%; 14/399), but most articles (74.9%; 299/399) did not specify a migrant sub-group. The most studied health topics were specific disease outcomes such as infectious diseases (24.1% of studies) and mental health (19.1%) compared to examining systems or structures that impact health (27.8%), access to healthcare (26.3%), or specific exposures or behaviours (35.3%). There has been a growing interest in migration health. Ensuring a diverse geographic distribution of research conducted in the UK and disaggregation by migrant sub-group is required for a nuanced and region-specific understanding of specific health needs, interventions and appropriate service delivery for different migrant populations. More research is needed to understand how migration policy and legislation intersect with both the social determinants of health and access to healthcare to shape the health of migrants in the UK.


P19ARF inhibits the functions of the HPV16 E7 oncoprotein.
The E7 oncoprotein encoded by high-risk types of human papillomavirus (HPV) plays a significant role in the development of HPV-related cancers. E7 is a potent stimulator of S phase and host DNA replication. These functions of E7 are linked to the deregulation of the Rb family of proteins. For example, E7 binds and induces proteolysis of Rb through the ubiquitin-proteasome pathway. Despite advances in our understanding of E7, reagents that inhibit E7 with promise in therapy have not been developed or identified. Here, we provide evidence that the tumor suppressor ARF can inhibit E7. We show that the expression of ARF causes a relocalization of E7 from the nucleoplasm to the nucleolus. Two distinct regions in ARF overlapping with the MDM2-binding sites are necessary for the relocalization of E7. Furthermore, we show that ARF blocks the proteolysis of Rb induced by E7. In addition, ARF expression inhibits DNA replication induced by E7. Although it is not known whether the endogenous ARF, which is expressed at a low level, interferes with E7, our results suggest that ARF is an effective inhibitor of E7. We speculate that ARF or an ARF-derived molecule might have a significant impact in therapy against HPV-related tumors.


Immunological evaluation of captive green sea turtle (Chelonia mydas) with ulcerative dermatitis.
Ulcerative dermatitis (UD) is common in captive sea turtles and manifests as skin erosions and ulcers associated with gram-negative bacteria. This study compared clinically healthy and UD-affected captive turtles by evaluating hematology, histopathology, immunoglobulin levels, and delayed-type hypersensitivity assay. Turtles with UD had significantly lower weight, reduced delayed-type hypersensitivity (DTH) responses, and higher heterophil:lymphocyte ratios. This study is the first to assay DTH in green turtles (Chelonia mydas) and suggests that UD is associated with immunosuppression.


Variations of a group coaching intervention to support early-career biomedical researchers in Grant proposal development: a pragmatic, four-arm, group-randomized trial.
Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features. This 2 × 2, unblinded, group-randomized study compares the effectiveness of variations of an NIH-focused, grant writing, group coaching intervention for biomedical postdoctoral fellows and early-career faculty. The key study outcomes are proposal submission rates and funding rates. Participants, drawn from across the United States, are enrolled as dyads with a self-selected scientific advisor in their content area, then placed into coaching groups led by senior NIH-funded investigators who are trained in the intervention's coaching practices. Target enrollment is 72 coaching groups of 4-5 dyads each. Groups are randomized to one of four intervention arms that differ on two factors: [1] duration of coaching support (regular dose = 5 months of group coaching, versus extended dose = regular dose plus an additional 18 months of one-on-one coaching); and [2] mode of engaging scientific advisors with the regular dose group coaching process (unstructured versus structured engagement). Intervention variations were informed by programs previously offered by the NIH National Research Mentoring Network. Participant data are collected via written surveys (baseline and 6, 12, 18, and 24 months after start of the regular dose) and semi-structured interviews (end of regular dose and 24 months). Quantitative analyses will be intention-to-treat, using a 2-sided test of equality of the effects of each factor. An inductive, constant comparison analysis of interview transcripts will be used to identify contextual factors -- associated with individual participants, their engagement with the coaching intervention, and their institutional setting - that influence intervention effectiveness. Results of this study will provide an empirical basis for a readily translatable coaching approach to supporting the essential grant writing activities of faculty, fellows, and other research trainees, including those from underrepresented groups.


Timing of expression of blood coagulation abnormality in patients treated with warfarin and s-1 concomitantly.
Although S-1 is frequently used in cancer chemotherapy, the drug interaction with warfarin, an anticoagulant agent, is not fully paid attention. In the present study, we investigated retrospectively the timing of expression of blood coagulation abnormality in nine patients treated with warfarin and S-1 concomitantly. In five patients, the dose of warfarin was reduced or interrupted after concomitant use of S-1. The International Normalized Ratio (INR) was significantly increased after combination with S-1 compared with the former value. In all patients, the INR was increased in three weeks after combination with S-1. On the other hand, serum creatinine, aspartate aminotransferase, alanine aminotransferase or serum albumin was not different before and after combination with S-1. These results suggest that the careful monitoring of the blood coagulation ability is necessary in all patients receiving warfarin and S-1 concomitantly.


Expression of genes involved in carbohydrate-lipid metabolism in muscle and fat tissues in the initial stage of adult-age obesity in fed and fasted mice.
C57Bl mice exhibit impaired glucose metabolism by the late adult age under standard living conditions. The aim of this study was to evaluate white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle expression of genes involved in carbohydrate-lipid metabolism at postpubertal stages preceding the late adult age in C57Bl mice. Muscle mRNA levels of uncoupling protein 3 (Ucp3) and carnitine palmitoyltransferase 1 (Cpt1) (indicators of FFA oxidation), WAT mRNA levels of hormone-sensitive lipase (Lipe) and lipoprotein lipase (Lpl) (indicators of lipolysis and lipogenesis), muscle and WAT mRNA levels of the type 4 glucose transporter Slc2a4 (indicators of insulin-dependent glucose uptake), and BAT mRNA levels of uncoupling protein 1 (Ucp1) (indicator of thermogenesis) were measured in fed and 16 h-fasted mice in three age groups: 10-week-old (young), 15-week-old (early adult), and 30-week-old (late adult). Weight gain from young to early adult age was not accompanied by changes in WAT and BAT indexes and biochemical blood parameters. Weight gain from early to late adult age was accompanied by increased WAT and BAT indexes and decreased glucose tolerance. Muscle Ucp3 and Cpt1 mRNA levels and WAT Lipe and Slc2a4 mRNA levels increased from young to early adult age and then sharply decreased by the late adult age. Moreover, BAT Ucp1 mRNA level decreased in the late adult age. Fasting failed to increase muscle Cpt1 mRNA levels in late adult mice. These transcriptional changes could contribute to impaired glucose metabolism and the onset of obesity in late adult mice during normal development.


Investigation of a maxillary nerve block technique in guinea pigs (Cavia porcellus): A cadaveric study comparing two injectate volumes.
To investigate and describe an extraoral approach to perform a maxillary nerve block in guinea pigs. Prospective, randomized, blinded, descriptive, cadaveric study. A total of 14 adult guinea pig cadavers. Two cadavers were used for anatomic dissection and determination of maxillary nerve block approach. A maxillary nerve block via infraorbital approach was then performed in 12 cadavers. A low volume (0.1 mL) or high volume (0.2 mL) of diluted methylene blue injectate was randomly assigned to the right or left side, with the other volume used for the contralateral side. The maxillary nerve was dissected after each injection by an investigator blinded to injectate volume. The region of dye distribution was identified, and the degree of staining assigned an accuracy score (0-2). Nerve coverage was considered adequate if ≥6 mm of circumferential staining was present. Accuracy evaluation indicated successful dye deposition in 10/12 [2 (0-2), median (range)] injections in the low volume group and 8/12 [2 (1-2)] injections in the high volume group. The majority (79.2%) of injections resulted in adequate nerve staining. There were no statistically significant differences between injectate volumes for accuracy (p = 0.64) or adequacy (p > 0.99) of staining. The infraorbital approach is a simple and practical method for maxillary nerve blockade in guinea pigs. An injectate volume of 0.1 mL results in adequate maxillary nerve coverage; however, additional studies are needed to assess the efficacy in clinical use.


Increased intracellular survival of Mycobacterium smegmatis containing the Mycobacterium leprae thioredoxin-thioredoxin reductase gene.
The thioredoxin (Trx) system of Mycobacterium leprae is expressed as a single hybrid protein containing thioredoxin reductase (TR) at its N terminus and Trx at its C terminus. This hybrid Trx system is unique to M. leprae, since in all other organisms studied to date, including other mycobacteria, both TR and Trx are expressed as two separate proteins. Because Trx has been shown to scavenge reactive oxygen species, we have investigated whether the TR-Trx gene product can inhibit oxygen-dependent killing of mycobacteria by human mononuclear phagocytes and as such could contribute to mycobacterial virulence. The gene encoding M. leprae TR-Trx was cloned into the apathogenic, fast-growing bacterium Mycobacterium smegmatis. Recombinant M. smegmatis containing the gene encoding TR-Trx was killed to a significantly lesser extent than M. smegmatis containing the identical vector with either no insert or a control M. leprae construct unrelated to TR-Trx. Upon phagocytosis, M. smegmatis was shown to be killed predominantly by oxygen-dependent macrophage-killing mechanisms. Coinfection of M. smegmatis expressing the gene encoding TR-Trx together with Staphylococcus aureus, which is known to be killed via oxygen-dependent microbicidal mechanisms, revealed that the TR-Trx gene product interferes with the intracellular killing of this bacterium. A similar coinfection with Streptococcus pyogenes, known to be killed by oxygen-independent mechanisms, showed that the TR-Trx gene product did not influence the oxygen-independent killing pathway. The data obtained in this study suggest that the Trx system of M. leprae can inhibit oxygen-dependent killing of intracellular bacteria and thus may represent one of the mechanisms by which M. leprae can deal with oxidative stress within human mononuclear phagocytes.


All-optically controllable random laser based on a dye-doped polymer-dispersed liquid crystal with nano-sized droplets.
This study elucidates for the first time an all-optically controllable random laser in a dye-doped polymer-dispersed liquid crystal (DDPDLC) with nano-sized LC droplets. Experimental results demonstrate that the lasing intensity of the random laser can be controlled to decrease by increasing irradiation time/intensity of one green beam, and increase by increasing the irradiation time of one red beam. The all-optical controllability of the random laser is attributed to the green (red)-beaminduced isothermal nematic-->isotropic (isotropic-->nematic) phase transition in LC droplets by trans-->cis (cis-->trans back) isomerization of azo dyes. This isomerization may decrease (increase) the difference between the refractive indices of the LC droplets and the polymer, thereby increasing (decreasing) the diffusion constant (or transport mean free path), subsequently decreasing the scattering strength and, thus, random lasing intensity.


Physiological and pathobiological significance of ocular glycoproteins. I. Studies using fluorescein labelled glycine max.
Cell surface carbohydrates play an important role in several biological, immunological, and neoplastic phenomena including development, growth regulation, cellular locomotion, receptor activation, and tumour metastasis. Fluorescein labelled lectins which bind to specific carbohydrate residues in glycoproteins and glycolipids are being increasingly used as chemical probes to study cell components. Several different preparations of ocular tissues from human, rabbit, and rat were examined for the distribution of N-acetyl-D-galactosamine (D-gal NAc) by means of fluorescein-labelled lectin from soybean (glycine max). A very strong fluorescence was observed in the corneal epithelium; Descemet's membrane and corneal endothelium were also strongly fluorescent. The conjunctival epithelium similarly showed a strong reaction, as did the goblet cells. The iris epithelium and the dilator pupillae were only weakly fluorescent, but the ciliary body showed strong fluorescence, as did the blood vessels. As compared with lens fibres the lens epithelium was strongly fluorescent. The outer retina, that is, the photoreceptors, the pigment epithelium, and Bruch's membrane, showed a very strong reactivity. The optic nerve showed moderate fluorescence, but reaction with extraocular muscles was variable. The skin of the upper and lower eyelids, hair follicles, and blood vessels showed strong lectin binding. Sections of retinoblastoma and malignant melanoma showed no reaction. The physiological and pathological significance of these findings is discussed.


Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China.
Human enterovirus 68 (HEV-68) is an enterovirus associated with respiratory illness. In China, no information about HEV-68 is available for children yet. This study aimed to investigate the presence of HEV-68 in mainland China between 2009 and 2012 and to explore the migration events of HEV-68 across the world. Among 1565 samples tested from children, 41 (2.6%) were positive for HEV and 223 (14.3%) for human rhinovirus (HRV). Seven (17.1%) of 41 HEVs were HEV-68. Two HEV-68- and five HRV-positive samples were detected in 585 adult samples. HEV-68 is the predominant type of enterovirus in children with acute respiratory tract infection (ARTI), followed by HEV-71 and coxsackievirus A6. Three HEV-68-infected children presented with severe pneumonia and one presented with a severe asthma attack. The viruses were attributed to two novel distinct sublineages of HEV-68 based on phylogenetic analysis of partial VP1 gene sequences. Migration events analysis showed that the USA and the Netherlands were possible geographical sources of HEV-68, from where three strains migrated to China. In conclusion, HEV-68 may play a predominant role among the enteroviruses associated with ARTI in children. Additional surveillance is needed to clarify the reason why HEV-68 causes such a wide spectrum of disease, from asymptomatic to severe respiratory disease and even death.


Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy.
Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the phosphorylation of histone H3 at serine-10. These specific activities are demonstrated both in vitro and in primary neonatal rat cardiomyocytes. Activation of CaMKII signaling by hypertrophic agonists increases H3 phosphorylation in primary cardiac cells and is accompanied by concomitant cellular hypertrophy. Conversely, specific silencing of nuclear CaMKII using RNA interference reduces both H3 phosphorylation and cellular hypertrophy. The hyper-phosphorylation of H3 associated with increased chromatin binding of CaMKII occurs at specific gene loci reactivated during cardiac hypertrophy. Importantly, H3 Ser-10 phosphorylation and CaMKII recruitment are associated with increased chromatin accessibility and are required for chromatin-mediated transcription of the Mef2 transcription factor. Unlike phosphorylation of H3 by other kinases, which regulates cellular proliferation and immediate early gene activation, CaMKII-mediated signaling to H3 is associated with hypertrophic growth. These observations reveal a previously unrecognized function of CaMKII as a kinase signaling to histone H3 and remodeling chromatin. They suggest a new epigenetic mechanism controlling cardiac hypertrophy.


Presynaptic inhibitory effect of acetylcholine in the hippocampus.
(1) In order to investigate the effects of acetylcholine (ACh) on synaptic transmission in the rat hippocampus, extracellular and intracellular recordings were made from pyramidal neurons in an in vitro slice preparation while synaptic inputs to the cell population were stimulated. ACh was applied ionophoretically into somatic and dendritic layers of the slice. (2) ACh applied into the apical dendritic layer of the CA1 region reduced the size of the locally evoked field excitatory postsynaptic potential (EPSP) without altering the size of the afferent fiber volley. Likewise, dendritically applied ACh reduced the size of intracellularly recorded EPSPs. This effect of ACh appeared to be muscarinic since it was not affected by hexamethonium (up to 3 X 10-5 M) but was antagonized by atropine in a dose-dependent manner. (3) The distribution of Ach-sensitive sites matched closely the spatial distribution of activated synapses on the pyramidal cell dendrites as shown by ionophoretic mapping experiments. (4) In contrast to the effects of dendritic applications of ACh, ionophoresis of ACh into the cell layer resulted in an increase and prolongation of EPSPs and a transient decrease in the size of recurrent somatic inhibitory postsynaptic potentials (IPSPs). These effects on synaptic potentials could not be explained by the observed changes in membrane potential and input resistance following somatic application of ACh. (5) Short dendritic applications of ACh had no consistent effect on the membrane potential or slope conductance of pyramidal neurons and did not attenuate the depolarization evoked by brief dendritic applications of glutamate. In addition, the time course of ACh-reduced EPSPs was not different from control. (6) We conclude that ACh exerts a presynaptic inhibitory effect on both excitatory and inhibitory afferents to hippocampal pyramidal neurons. This effect of ACh is widespread, occurring in all regions of Ammon's horn tested as well as in stratum moleculare of fascia dentata.


[Contribution of petroleum-processing plants to the total level of atmospheric air pollution].
On the basis of results of field studies the means to reveal the contribution of oil extracting and processing enterprises (the main components of discharges are similar to the common prevalent impurities in the air of residential areas) into the total level of ambient air pollution has been developed. The method takes into account the relationship between average annual concentrations of oil hydrocarbons and carbon oxide.


Prognostic factors in small cell carcinoma of the lung: a cancer and leukemia group B study.
Prognostic factors were studied in 224 patients with small cell carcinoma of the lung entered in a Cancer and Leukemia Group B protocol. Extent of disease was the major predictor of complete remission (CR) frequency and survival greater than 2 years, with CR rates being 40% for patients with limited disease (LD) and 10% for those with extensive disease. Patients who were classified as having extensive disease on the basis of isotope scan evidence of a single bone metastasis had survival characteristics and response rates similar to those of patient with LD. A multivariate analysis of various factors, which may influence overall survival, reveals a good-risk population to be defined as having LD and an initial performance status less than or equal to 2, with or without a single metastatic focus on bone scan. Furthermore, this risk definition fairly successfully predicted which patients had the greatest chance of achieving a CR (45%). Age less than 70 years was shown to be a significantly adverse factor on survival in these multivariate analyses after adjusting for risk. When long-term survivors (less than 24 months) were investigated by multivariate analyses, the new risk system was found to be the only significant pretreatment factor. Interestingly, sex was the next marginally influential factor on long-term survival. Future stratification by these risk categories should lead to more homogeneous subgroups for comparison of different therapeutic approaches and should provide some indication as to how much better the newer treatment program is within each risk group.


Changes in BMI and blood pressure after a school based intervention: the CHILDREN study.
Identification of the behavioural, normative and control beliefs influencing children's behaviour is an important prerequisite in designing effective interventions. The current study aims to evaluate the effectiveness of an intervention program, based on the Theory of Planned Behaviour (TPB), on obesity indices and blood pressure (BP) in Ioannina, Greece. Participants were 646 fifth grade pupils (360 girls and 286 boys). The intervention group (IG) consisted of 321 children in 13 randomly selected schools while the rest (n = 325 children) served as the control group (CG). Based on the outcome of the TPB questionnaire, the intervention focused on overcoming the barriers in accessing physical activity areas, increasing the availability of fruits and vegetables and increasing parental support. General linear mixed model and mediating variable analysis were used to evaluate the differences between the two groups and to test whether changes in certain dietary, physical activity and anthropometrical indices mediated the effect of the intervention on BP. IG had higher consumption of fruits and lower consumption of fats/oils and sweets/beverages compared with the CG. Intervention's effect on BMI could be explained by the changes in fruit and fats/oils intake whereas the reduction of systolic and diastolic BP could be explained by the reduction of BMI. The findings indicate favourable changes in BP and obesity indices after the implementation of a 1-year school-based intervention program based on the TPB. These results highlight the importance of developing a social and physical environment that promotes balanced eating behaviours and extra-curricular access to physical activity venues.


Investigating rates and predictors of viral blips, low-level viraemia and virological failure in the Australian HIV observational database.
Australia has made significant progress towards achieving the UNAIDS's 95-95-95 cascade targets including HIV viral suppression. To investigate the burden of HIV viraemia, we assessed viral blips, low-level viraemia (LLV) and virologic failure (VF) in an Australian cohort. We studied the proportion of people with viral suppression, viral blips, LLV and VF in the Australian HIV observational database (AHOD) between 2010 and 2021. The association between blips or LLV, and VF was investigated using Cox regression, and predictors of viral blips and LLV were assessed using repeated-measured logistic regression. Among 2544 AHOD participants who were in follow-up and on antiretroviral therapy (ART) from 1 January 2010 (88.7% male), 444 had experienced VF (incidence rate: 2.45 [95% CI: 2.23-2.69] per 100 person-years [PY]) during 18,125 PY of follow-up (a median of 7.6 years). The proportion of people with VF decreased over time, whereas rates of blips and LLV remained stable. Participants with blips (hazard ratio, 2.89; 95% CI: 2.31-3.61) and LLV (4.46; 95% CI: 3.38-5.89) were at increased risk of VF. Hepatitis B co-infection, longer documented treatment interruption duration, younger age and lower CD4 at ART initiation, and protease inhibitors-based initial regimen were associated with an increased risk of VF. Common predictors of blips and LLV such as higher HIV-1 RNA and lower CD4 at ART initiation, longer treatment interruption, more VL testing and types of care settings (hospitals vs. sexual health services) were identified. Blips and LLV predict subsequent VF development. We identified important predictors of HIV viraemia including VF among individuals on INSTI-based regimens to help direct HIV management plans.


Anatomicohistological characteristics of the genital tubular organs of the female brush-tailed porcupine (Atherurus africanus, Gray 1842) from Gabon.
The present study examines the anatomic and histological characteristics of the female genital tract of the wild brush-tailed porcupine (Atherurus africanus). A description of the macroscopic and microscopic features of the tubular genital organs based on observations made in 18 wild adult females is presented. The histological stains used were haematoxylin and eosin, 1% toluidine blue, PAS-haematoxylin and Masson's trichrome. Observations indicate that the fimbriated infundibulum of the oviduct completely surrounds and is attached to the entire ovarian surface. The uterus is bicornuate, being composed of two uterine horns separated by a velum uteri, a small uterine body and a cervix. In both pregnant and non-pregnant females, the uterine horns and body of the uterus present a pseudostratified, columnar ciliated epithelium containing sparse simple tubular glands. In pregnant females, the endocervical canal is filled by a viscous cervical secretion. The different patterns observed in the endometrium and myometrium of the uterine horns and in the vaginal epithelium suggest a relationship with the reproductive state of the brush-tailed porcupine female.


Posterior tibial tendon insufficiency. Its Diagnosis, Management, and Treatment.
Posterior tibial tendon dysfunction, once thought to be a rare clinical entity, has been observed to be a major cause of acquired flatfoot deformity in adults. Several risk factors have been identified, ranging from inflammatory conditions to obesity. A physical examination using a series of tests, including the single-limb rise, first-metatarsal rise sign, and the "too-many-toes" sign, used in combination with selected radiographic imaging techniques, allows classification of the severity of disease. This staging system then serves as the basis for formulating the treatment options, which include nonoperative as well as operative alternatives. Conservative treatment involves rest, anti-inflammatory medication, orthotic devices, and modifications to shoes. Operative options are numerous and include primary tendon repair, tendon transfer, osteotomies, and arthrodesis.


Neuronal locus specificity: trans-repolarization of Xenopus embryonic retina after the time of axial specification.
Signaling within an embryonic Xenopus eye comprised of two fused eye fragments can reprogram, in turn, the anteroposterior and dorsoventral axes of one of the fragments. The responding fragment, subsequently isolated and allowed to round up and innervate the brain, shows corresponding inversions in its retinotectal map. This is the first evidence of trans-repolarization of presumptive retina and provides an assay system for analysis of positional signaling within the retinal field.


Differential integration of Ca2+-calmodulin signal in intact ventricular myocytes at low and high affinity Ca2+-calmodulin targets.
Cardiac myocyte intracellular calcium varies beat-to-beat and calmodulin (CaM) transduces Ca2+ signals to regulate many cellular processes (e.g. via CaM targets such as CaM-dependent kinase and calcineurin). However, little is known about the dynamics of how CaM targets process the Ca2+ signals to generate appropriate biological responses in the heart. We hypothesized that the different affinities of CaM targets for the Ca2+-bound CaM (Ca2+-CaM) shape their actions through dynamic and tonic interactions in response to the repetitive Ca2+ signals in myocytes. To test our hypothesis, we used two fluorescence resonance energy transfer-based biosensors, BsCaM-45 (Kd = approximately 45 nm) and BsCaM-2 (Kd = approximately 2 nm), to monitor the real time Ca2+-CaM dynamics at low and high affinity CaM targets in paced adult ventricular myocytes. Compared with BsCaM-2, BsCaM-45 tracks the beat-to-beat Ca2+-CaM alterations more closely following the Ca2+ oscillations at each myocyte contraction. When pacing frequency is raised from 0.1 to 1.0 Hz, the higher affinity BsCaM-2 demonstrates significant elevation of diastolic Ca2+-CaM binding compared with the lower affinity BsCaM-45. Biochemically detailed computational models of Ca2+-CaM biosensors in beating cardiac myocytes revealed that the different Ca2+-CaM binding affinities of BsCaM-2 and BsCaM-45 are sufficient to predict their differing kinetics and diastolic integration. Thus, data from both experiments and computational modeling suggest that CaM targets with low versus high Ca2+-CaM affinities (like CaM-dependent kinase versus calcineurin) respond differentially to the same Ca2+ signal (phasic versus integrating), presumably tuned appropriately for their respective and distinct Ca2+ signaling pathways.


A sibling-pair analysis of fasting lipids and anthropometric measurements and their relationship to hypertension.
Fifty non-diabetic, young Chinese hypertensives were compared to their normotensive siblings with respect to body fat distribution and fasting lipid and glucose (FPG) profiles. Sitting BP in hypertensives met conventional hypertension criteria after a 4-week washout period on placebo. Hypertensives had greater body mass index (BMI), subscapular skin-fold thickness (SFT), waist circumference (W), waist-to-height (WHtR) and waist-to-hip ratio (WHR), p<0.0001 for all. Higher triglycerides (p=0.004) and lower HDL-cholesterol (p=0.015) concentrations were also observed. Weight, W, WHtR and BMI were higher in hypertensives in both male (n=9) and female gender-concordant sibling pairs (n=21). Higher WHR, hip circumference and subscapular SFT were only seen in the male hypertensives. Hypertension is associated with central adiposity and adverse lipid profiles in this group of young hypertensives, supporting the hypothesis that obesity, particularly central, is closely associated with hypertension in Chinese as in other ethnic groups.


Is minimal access spine surgery more cost-effective than conventional spine surgery?
Systematic review. To summarize and critically review the economic literature evaluating the cost-effectiveness of minimal access surgery (MAS) compared with conventional open procedures for the cervical and lumbar spine. MAS techniques may improve perioperative parameters (length of hospital stay and extent of blood loss) compared with conventional open approaches. However, some have questioned the clinical efficacy of these differences and the associated cost-effectiveness implications. When considering the long-term outcomes, there seem to be no significant differences between MAS and open surgery. PubMed, EMBASE, the Cochrane Collaboration database, University of York, Centre for Reviews and Dissemination (NHS-EED and HTA), and the Tufts CEA Registry were reviewed to identify full economic studies comparing MAS with open techniques prior to December 24, 2013, based on the key questions established a priori. Only economic studies that evaluated and synthesized the costs and consequences of MAS compared with conventional open procedures (i.e., cost-minimization, cost-benefit, cost-effectiveness, or cost-utility) were considered for inclusion. Full text of the articles meeting inclusion criteria were reviewed by 2 independent investigators to obtain the final collection of included studies. The Quality of Health Economic Studies instrument was scored by 2 independent reviewers to provide an initial basis for critical appraisal of included economic studies. The search strategy yielded 198 potentially relevant citations, and 6 studies met the inclusion criteria, evaluating the costs and consequences of MAS versus conventional open procedures performed for the lumbar spine; no studies for the cervical spine met the inclusion criteria. Studies compared MAS tubular discectomy with conventional microdiscectomy, minimal access transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion, and multilevel hemilaminectomy via MAS versus open approach. Overall, the included cost-effectiveness studies generally supported no significant differences between open surgery and MAS lumbar approaches. However, these conclusions are preliminary because there was a paucity of high-quality evidence. Much of the evidence lacked details on methodology for modeling, related assumptions, justification of economic model chosen, and sources and types of included costs and consequences. The follow-up periods were highly variable, indirect costs were not frequently analyzed or reported, and many of the studies were conducted by a single group, thereby limiting generalizability. Prospective studies are needed to define differences and optimal treatment algorithms. 3.


Consolidation therapies revisited: weekly paclitaxel.
Most patients with advanced ovarian cancer exhibit clinically relevant objective and subjective responses to platinum/paclitaxel-based combination, which is now considered the standard chemotherapeutic regimen. Unfortunately, responses are generally of limited duration, and long-term disease-free survival is experienced by few patients. Efforts should be taken to maintain such a response as long as possible, where it realistically might be hoped that continuation of chemotherapy could consolidate the absence of clinically detectable disease. In this regard, the administration of paclitaxel on a weekly schedule seems to be particularly attractive, especially after the demonstration that a weekly regimen in heavily pretreated women bearing metastatic breast, head, and neck or lung cancers was proven to be well tolerated without the requirement of granulocyte colony-stimulating factors, with limited neurotoxicity and with substantial anticancer activity, thanks to its pro-apoptotic and antiangiogenesis properties. In Italy, a multi-institutional phase II prospective study (After-6 Protocol 2) has been initiated to verify the effectiveness of paclitaxel, administered on a weekly schedule (60 mg/m2 for 21 courses), in patients bearing microscopic residual disease detected at second-look operation to define its effectiveness after completing their primary platinum/paclitaxel chemotherapy treatment. When possible, patients were surgically re-evaluated thorough a third-look operation to evaluate the percentage of conversion of microPR into a pathological complete remission status. An interim evaluation based on 534 cycles administered to 41 patients showed than only one patient experienced grade 4 anemia, 7.4% grade 2 transient peripheral neurotoxicity, and 2.7% delay in treatment delivery. Therefore, weekly paclitaxel has been proven to be easily administered even in heavily pretreated patients, with acceptable hematological and neurological toxicity.


Predictors of subjective and objective caregiving burden in older female caregivers of adults with intellectual disabilities.
Informal, unpaid, and lifelong older caregivers of adults with intellectual disabilities (ID) are usually female and most often are mothers of adults with ID. However, research exploring different predictors of subjective and objective burden among these older female caregivers is sparse. The objective of this study was to examine whether the subjective and objective burden as well as positive appraisals are predicted by the same or different variables linked to the caregivers and the adults with ID. Face-to-face interview questionnaires were administered in a city in Taiwan in 2006-2007 and 350 female family caregivers aged 55 years and older completed the interview in their homes. The independent variables included adult care demands and caregiver variables, while the dependent variables were caregivers' subjective burden, caregivers' objective burden and caregivers' positive appraisals. The results demonstrated that adult care demands were associated more with the objective than the subjective caregiving burden. The strongest predictors of both subjective and objective burden were the care recipient's instrumental activities of daily living functionality, caregiver's age, and caregiver's health status. The significant predictors for positive caregiving appraisals were the caregiver's age and the caregiver's level of social support. The results indicate that both the subjective and objective burdens were mostly related to the same factors, that is, to the characteristics of the older female caregivers and the recipients of care with ID. On the other hand, positive attitudes towards caregiving roles were only associated with caregiver variables.


Peak nasal inspiratory flow; normal range in adult population.
Measurement of Peak Nasal Inspiratory Flow (PNIF) seems to be a cheap, simple, easily performed method to assess nasal patency. The purpose of this study is to establish normative PNIF data for a healthy adult population and provide charts relating PNIF normal values with age, height and sex in adults. Repeated measurements of PNIF were performed in 170 volunteers. In total, 137 of these fulfilled the study criteria (66 females and 50 males) and all of them were non-smokers, non-asthmatic, without nose and paranasal sinuses problems, with ages ranging from 16 to 84 years. Data were statistically analysed and tables were produced relating PNIF to age, sex and height. There was no interaction of sex with age or height. There was considerable residual variability of PNIF between individuals not explained by any of the variables studied. We conclude that PNIF could be a useful method to study nasal patency in both primary and secondary care to aid diagnosis of nasal disease. The study provides normative data for a Caucasian population. Further variables need to be explored to predict expected PNIF values more accurately.


Ambient temperature catalyst-free light-induced preparation of macrocyclic aliphatic polyesters.
The light induced, catalyst-free ambient temperature preparation of macrocyclic aliphatic polyesters is pioneered. Based on the photo-induced Diels-Alder reaction of orthoquinodimethane and acrylate moieties, cyclic polyesters of high purity are readily synthesized. Considering the high tolerance to functional groups and the orthogonality of the ligation, the reported protocol can be easily transferred to a large range of polymers, complex topologies (tadpole, sun-shaped, jellyfish, etc.) and applications.


Educational needs of patients with rheumatic and musculoskeletal diseases attending a large health facility in Austria.
Patient education is an important part of the management of rheumatic and musculoskeletal diseases. Given that patients with diverse diseases do not have the same needs, it is crucial to assess the educational requirements of targeted groups to provide tailored educational interventions. The aim of our study was to assess educational needs of a large cohort of patients with different rheumatic and musculoskeletal diseases attending a health facility in Austria. We assessed educational needs, via an online survey of patients with fibromyalgia (FMS), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) recruited from an Austrian health-care facility, using the Austrian version of the Educational Needs Assessment Tool (OENAT). For our sample of 603 patients, AS (62%), RA (15%), and FMS (24%), there were no educational need differences for the domains of movements, disease process, and self-help measures. Patients with FMS had less need for pain management education and greater need for education about feelings, than other disease groups. Patients with RA had a greater need for education related to treatments than other groups, and patients with AS had a greater need for treatment education than patients with FMS. Patients with AS reported greater need for support system education than other patient groups. Educational needs vary by disease groups, suggesting that health-care professionals should assess disease-specific needs for education to provide optimal assistance in disease management for patients.


Leptospirosis-associated acute kidney injury.
Leptospirosis is the most important zoonosis in the world. Patients are typically young men. Several factors are involved in acute kidney injury (AKI) in leptospirosis, including direct nephrotoxic action of the leptospira, hyperbilirubinemia, rhabdomyolysis and hypovolemia. The major histological findings are acute interstitial nephritis and acute tubular necrosis. Leptospirosis-induced AKI is usually nonoliguric and hypokalemic. Tubular function abnormalities precede a decline in the glomerular filtration rate, which could explain the high frequency of hypokalemia. Antibiotic treatment is efficient in the early and late and/or severe phases. For critically ill leptospirosis patients, the following measures are recommended: early and daily hemodialysis; low volume infusion (due to the risk of pulmonary hemorrhage); and lung-protective strategies. Mortality in leptospirosis-associated AKI is around 22%.


[The characteristic of stomatologic service manpower in Omsk region].
The article considers the network and manpower characteristics of stomatologic service in Omsk oblast during 2006-3011. The results are presented concerning statistical analysis of dynamics of manpower size and staffing of specialists in stomatologic rooms (departments) in state (budget) health institutions. The differences are demonstrated concerning the accessibility of stomatologic care to residents of city and rural regions of oblast.


Reviewing the Pathogenic Potential of the Otitis-Associated Bacteria Alloiococcus otitidis and Turicella otitidis.
Alloiococcus otitidis and Turicella otitidis are common bacteria of the human ear. They have frequently been isolated from the middle ear of children with otitis media (OM), though their potential role in this disease remains unclear and confounded due to their presence as commensal inhabitants of the external auditory canal. In this review, we summarize the current literature on these organisms with an emphasis on their role in OM. Much of the literature focuses on the presence and abundance of these organisms, and little work has been done to explore their activity in the middle ear. We find there is currently insufficient evidence available to determine whether these organisms are pathogens, commensals or contribute indirectly to the pathogenesis of OM. However, building on the knowledge currently available, we suggest future approaches aimed at providing stronger evidence to determine whether A. otitidis and T. otitidis are involved in the pathogenesis of OM. Such evidence will increase our understanding of the microbial risk factors contributing to OM and may lead to novel treatment approaches for severe and recurrent disease.


An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration.
Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype.


The work of the nursing team in the operating room and the health-related damages.
to analyze the work of the nursing team in the operating room and the physical, psychological, and social damage related to occupational health. quantitative study conducted from November 2017 to January 2018 in the operating room of a university hospital. The sample consisted of 160 nursing workers who responded to the Work-Related Damage Assessment Scale. Data were analyzed using the Student's t test, One-Way analysis of variance (ANOVA) followed by Pearson's chi-square test. psychological and social damage were assessed by workers as low risk by 86.8% (139) and 87.4% (140), respectively. Physical damage was considered a medium risk by 57.9% (93) of the sample. the results direct the attention of managers and the occupational medicine service to physical damage, preventing them from getting worse and thus promoting improvements in working conditions and occupational health.


Segregation analysis of 231 Ashkenazi Jewish families for evidence of additional breast cancer susceptibility genes.
Between 5 and 10% of breast cancer is attributable to inherited cancer susceptibility genes. Mutations in the genes BRCA1 and BRCA2 account for two-thirds of hereditary breast cancer cases. Using segregation analysis, families of cases without BRCA1/2 mutations were studied for statistical evidence of another major breast cancer gene in a community-based sample of Jewish probands tested previously for the presence of three BRCA founder mutations. A total of 231 probands with breast cancer, who do not carry a founder mutation, reported complete data on 602 female first-degree relatives of probands over age 20; 78 of these relatives had breast cancer. Segregation analysis was used to evaluate the likelihood of various genetic and nongenetic models. Sporadic, environmental, and general Mendelian genetic models fit the family data poorly and were rejected. A Mendelian recessive model fit better than dominant and codominant models, although none of these could be rejected. Cumulative incidence curves predicted by the recessive and codominant models fit observed incidence among first-degree relatives well. The assumption of Mendelian transmission of a major recessive gene(s) is compatible with the data. The recessive model predicts that 4% of women would carry the high-risk genotype, with 85% of them developing breast cancer by age 70. There was significant heterogeneity between these families and the 114 BRCA1/2 mutation-positive families from the same study population, implying that this apparent recessive effect is not because of undetected BRCA1/2 mutations. The study adds support for a major autosomal recessive component to breast cancer susceptibility.


Low-Dose Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey Disease).
Familial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare and debilitating genetic dermatosis characterized by chronic, recurrent vesicles, erosions, and maceration in flexural areas. Despite the reported therapeutic modalities, such as topical and systemic corticosteroids, systemic immunomodulators, topical and systemic retinoids, and laser, HHD can still be markedly difficult to control. To assess low-dose naltrexone hydrochloride in the treatment of recalcitrant HHD. In this case series, 3 patients with biopsy-proven recalcitrant HHD were evaluated in the outpatient dermatology clinic at the Cleveland Clinic. Each patient was treated with low-dose naltrexone hydrochloride at a dosage of 1.5 to 3.0 mg per day. No laboratory monitoring was necessary. Clinical response (healing of erosions, improvement in erythema, and alleviation of pain), adverse effects, and subjective quality of life were monitored throughout the treatment. The study dates were January 2016 to January 2017. Objective clinical response as assessed by the treating dermatologist, subjective quality of life as reported by the patient, and recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months. The 3 patients included a woman in her 40s and 2 men in their 60s. Each patient exhibited at least an 80% improvement in extent of disease, with one patient demonstrating 90% clearance. All 3 patients had substantial improvement in quality of life, with one patient reporting improvement in his depression. No adverse effects were recorded. Low-dose naltrexone may represent a low-cost and low-risk alternative or adjunct in the treatment of HHD.


Effect of land preparation methods on growth, seed yields of Jasmine 105 paddy rice (Oryza sativa L.) and growth of weeds, grown in Northeast Thailand.
This experiment was carried out on a grower's paddy field, Ban Som Hoeng Village, Kantarawichai, Mahasarakham Province, Northeast Thailand with the use of Roi-Et soil series (Oxic Paleustults) in the rainy season of the 2006 (May to November) to investigate effect of land preparation methods on rice plant heights, amounts of weeds and seed yields of Jasmine 105 aromatic paddy rice (Oryza sativa L.). The experiment was laid in a Randomized Complete Block Design (RCBD) with four replications. The results showed that plant height due to treatments was significantly highest for T3 but T3 was similar to T2, whilst T1 (control) was the least. Mean values of dry weight of narrow leaf type of weeds, in most cases, were significantly lowest with T3 followed by T2 and T3, particularly at the final two sampling periods. Broad leaf type of weeds was significantly highest with T2 throughout the experimental period, whilst T1 and T3, in most cases, were similar. Unfilled seeds were significantly highest with T3 but similar to T1 but T2 was the lowest, whilst filled seeds were significantly highest with T3, both T1 and T2 gave a similar weight. Numbers of panicles m(-2) were significantly highest with T3 but T3 was similar to T2, whilst T1 was the least. Seed size or 1000-seed weight was significantly highest with T3, whilst T2 and T1 were similar. Seed yield was highest and highly significant with T3 (1,136.25 kg ha(-1)) but T3 was similar to T2 (1,083.31 kg ha(-1)), whilst T1 was the lowest (487.50 kg ha(-1)). Land preparation method of T3 treatment may be recommended as the first choice, whilst T2 may be used as an alternative choice.


Endovascular treatment of lower extremity ischemia in chronic renal failure patients on dialysis: early and intermediate term results.
Peripheral arterial occlusive disease is common in patients with chronic renal failure requiring dialysis. Despite the increasing use of endovascular revascularization for lower extremity ischemia, the success rates of treating lower extremity ischemia in this challenging population remain obscure. To assess the results of endovascular revascularization for lower extremity ischemia in dialysis patients. We conducted a retrospective review of all dialysis patients who underwent endovascular treatment for critical limb ischemia (CLI) in our institution between 2007 and 2011. Data collected included comorbidities, clinical presentation, anatomic distribution of vascular lesions, amputation and survival rates. We identified 50 limbs (41 patients). Indications included gangrene in 22%, non-healing wounds in 45%, rest pain in 31%, and debilitating claudication in 4%. Mean follow-up was 12 months (1-51 months). Nineteen patients required amputations. Freedom from amputation at 5 years was 40%. Factors associated with amputation included non-healing wounds or gangrene (68% and 36% respectively) and diabetes (P < 0.05). The survival rate was 80% after 5 years. Despite improvement in endovascular techniques for lower extremity revascularization, the incidence of limb salvage among dialysis patients remains poor, resulting in a high rate of major amputations.


The effects of visual and cognitive distractions on operational and tactical driving behaviors.
This study tested the effects of two fundamental forms of distraction, including visual-manual and cognitive-audio distraction, with comparison under both operational and tactical driving. Strategic control remains for future study. Driving is a complex control task involving operational, tactical, and strategic control. Although operational control, such as lead-car following, has been studied, the influence of in-vehicle distractions on higher levels of control, including tactical and strategic, remains unclear. Two secondary tasks were designed to independently represent visual-manual and cognitive-audio distractions, based on multiple resource theory. Drivers performed operational vehicle control maneuvers (lead-car following) or tactical control maneuvers (passing) along with the distraction tasks in a driving simulator. Response measures included driving performance and visual behavior. Results revealed drivers' ability to accommodate either visual or cognitive distractions in following tasks but not in passing. The simultaneous distraction condition led to the greatest decrement in performance. Findings support the need to assess the impacts of in-vehicle distraction on different levels of driving control. Future study should investigate driver distraction under strategic control.


Exercise-induced heat injury: diagnosis and management.
Exertional heat illness represents a spectrum of conditions ranging from the benign to the life-threatening. Prompt assessment and treatment can prevent fatalities in those who present as a heat casualty. More importantly, however, these injuries can be prevented from occurring altogether. This article reviews the physiology of thermoregulation and the pathophysiology of heat injuries associated with exercise. Current approaches toward the diagnosis, treatment, and prevention of exercise-induced heat injuries will also be discussed.


Catchment scale assessment of macroplastic pollution in the Odaw river, Ghana.
Catchment-scale plastic pollution assessments provide insights in its sources, sinks, and pathways. We present an approach to quantify macroplastic transport and density across the Odaw catchment, Ghana. We divided the catchment into the non-urban riverine, urban riverine, and urban tidal zones. Macroplastic transport and density on riverbanks and land were monitored at ten locations in December 2021. The urban riverine zone had the highest transport, and the urban tidal zone had the highest riverbank and land macroplastic density. Water sachets, soft fragments, and foam fragments were the most abundant items. Our approach aims to be transferable to other catchments globally.


OnabotulinumtoxinA and AbobotulinumtoxinA Dose Conversion: a Systematic Literature Review.
This systematic review was performed to elucidate dosing practices, dosing conversions, and related outcomes from randomized controlled trials that directly compared onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO) at various dose conversion ratios for therapeutic use in movement disorders. A systematic review of 3 medical literature databases (PubMed, the Cochrane Library, and EMBASE) was performed to identify relevant comparative clinical studies, systematic reviews, and meta-analyses published in the English language between January 1991 and January 2015. Studies that met predefined inclusion criteria were selected for formal data extraction and quality assessment. A total of 182 manuscripts were identified, of which 4 were included for analysis. Targeted clinical applications included neurological disorders. The studies compared ONA to ABO dose conversion ratios of 1:2.5 (n=1), 1:3 (n=2), and 1:4 (n=2). One study compared both 1:3 and 1:4 ratios. An ONA:ABO conversion factor of 1:2.5 was associated with similar efficacy and side effects. An ONA:ABO ratio of 1:3 provided similar or higher efficacy but an increased rate of adverse effects, and an ONA:ABO ratio of 1:4 was associated with higher efficacy but with an excessive rate of intolerable side effects. A dose conversion ratio of ONA to ABO between 1:2.5 and 1:3.0 provides comparable safety and efficacy for therapeutic movement disorders chemodenervation procedures.


Effect of EDTA and QMIX Ultrasonic Activation on the Reduction of Microorganisms and Endotoxins in Ex Vivo Human Root Canals.
The present study aimed to compare the effectiveness of QMiX and 17% EDTA associated to passive ultrasonic irrigation (PUI) or manual agitation (MA) on the reduction of E. faecalis, E. coli and LPS from root canals. Forty single rooted human teeth were randomly divided into four groups (n=10), according to the final irrigation protocol: EDTA+MA, QMiX+MA, EDTA+PUI, QMiX+PUI. Sample collections were obtained from the root canal content immediately before preparation (baseline-S1), after instrumentation (S2), after final irrigation protocol (S3) and 7 days after instrumentation and final irrigation (S4). The antimicrobial effectivity and on endotoxin content were analyzed by culture procedure (CFU/mL) and LAL assay (EU/mL), respectively. The results were statistically analyzed by Kruskal-Wallis and Friedman test (α=5%). QMiX+MA and QMiX+PUI reduced 100% of E. coli and E. faecalis bacteria and also prevented E. faecalisregrowth at S4. EDTA significantly reduced E. coli, but it was not effective in reducing E. faecalis. All protocols reduced EU/mL when compared to S1, however at S4 there was a significant reduction of EU/mL only in the QMiX+MA and QMiX+PUI groups in relation to S3 and S2, respectively. Final irrigation with QMiX associated with MA or PUI had superior antibacterial efficacy compared to EDTA, eliminating 100% of E. coli and E. faecalis strains. In addition, QMiX+PUI reduced 97.61% of the initial content of LPS.


Isolation and Genomics of Futiania mangrovii gen. nov., sp. nov., a Rare and Metabolically Versatile Member in the Class Alphaproteobacteria.
Mangrove microorganisms are a major part of the coastal ecosystem and are directly associated with nutrient cycling. Despite their ecological significance, the collection of culturable mangrove microbes is limited due to difficulties in isolation and cultivation. Here, we report the isolation and genome sequence of strain FT118T, the first cultured representative of a previously uncultivated order UBA8317 within Alphaproteobacteria, based on the combined results of 16S rRNA gene similarity, phylogenomic, and average amino acid identity analyses. We propose Futianiales ord. nov. and Futianiaceae fam. nov. with Futiania as the type genus, and FT118T represents the type species with the name Futiania mangrovii gen. nov, sp. nov. The 16S rRNA gene sequence comparison reveals that this novel order is a rare member but has a ubiquitous distribution across various habitats worldwide, which is corroborated by the experimental confirmation that this isolate can physiologically adapt to a wide range of oxygen levels, temperatures, pH and salinity levels. Biochemical characterization, genomic annotation, and metatranscriptomic analysis of FT118T demonstrate that it is metabolically versatile and active in situ. Genomic analysis reveals adaptive features of Futianiales to fluctuating mangrove environments, including the presence of high- and low-affinity terminal oxidases, N-type ATPase, and the genomic capability of producing various compatible solutes and polyhydroxybutyrate, which possibly allow for the persistence of this novel order across various habitats. Collectively, these results expand the current culture collection of mangrove microorganisms, providing genomic insights of how this novel taxon adapts to fluctuating environments and the culture reference to unravel possible microbe-environment interactions. IMPORTANCE The rare biosphere constitutes an essential part of the microbial community and may drive nutrient cycling and other geochemical processes. However, the difficulty in microbial isolation and cultivation has hampered our understanding of the physiology and ecology of uncultured rare lineages. In this study, we successfully isolated a novel alphaproteobacterium, designated as FT118T, and performed a combination of phenotypic, phylogenetic, and phylogenomic analyses, confirming that this isolate represents the first cultured member of a previously uncultivated order UBA8317 within Alphaproteobacteria. It is a rare species with a ubiquitous distribution across different habitats. Genomic and metatranscriptomic analyses demonstrate that it is metabolically versatile and active in situ, suggesting its potential role in nutrient cycling despite being scarce. This work not only expands the current phylogeny of isolated Alphaproteobacteria but also provides genomic and culture reference to unravel microbial adaptation strategies in mangrove sediments and possible microbe-environment interactions.