Sex Differences in the Acute Effects of Oral THC: A Randomized, Placebo-Controlled, Crossover Human Laboratory Study.
Cannabis is one of the most commonly used psychoactive substances, and recent reports have shown increased use among women, leading to growing concerns about cannabis use disorder. Some evidence suggests a faster progression to addiction in women, known as the "telescoping effect." While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the response to oral tetrahydrocannabinol (THC) in humans. 55 healthy men and women with prior exposure to cannabis but no history of cannabis use disorder participated in a randomized, placebo-controlled, double-blind, counter-balanced study, receiving a single 10 mg dose of oral THC (dronabinol). Subjective intoxicating effects were assessed by the Visual Analog Scale (VAS) of "high", psychotomimetic effects by the Clinician-Administered Dissociative Symptoms Scale (CADSS) and Psychotomimetic States Inventory (PSI), cognitive effects by Rey Auditory Verbal Learning Test (RAVLT), and physiologic effects by heart rate. Outcomes were regularly measured on the test day, except for the RAVLT, which was assessed once. Peak differences from baseline were analyzed using a nonparametric method for repeated measures. Oral THC demonstrated significant dose-related effects in psychotomimetic and physiologic domains, but not in cognition. A notable interaction between THC dose and sex emerged concerning the subjective "high" scores, with women reporting heightened sensations (ATS=3.81, num df=1, p=0.05). No other significant effects of sex and THC dose interaction were observed. Oral THC yields similar psychotomimetic and physiologic effects across sexes, but women may experience a pronounced subjective intoxicating effect. Given the escalating accessibility of cannabinoids, further research is needed to identify individual vulnerabilities and facilitate tailored interventions addressing cannabis use disorder.


Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells.
Immune spleen cells from LCM virus-infected (CBA X C57BL/6)F1 radiation chimeras entirely repopulated with CBA-T6 lymphocytes were cytotoxic for allogeneic, LCM virus infected C57BL/6 mouse-derived target cells. Normal C57BL/6 targets were not lysed. CBA-T6 lymphocytes derived from (CBA X C57BL/6) radiation chimeras sensitized in vitro against TNP-conjugated C57BL/6 spleen cells lysed TNP-conjugated C57BL/6 targets. However normal C57BL/6 mouse-derived targets were not destroyed. The magnitude of virus-specific (or TNP-specific) cytotoxic responses against H-2 incompatible targets was lower compared to that against H-2 compatible targets. These data are considered to support and to extend the altered self concept, but are not consistent with the dual recognition concept.


Large tunable optical delays via self-phase modulation and dispersion.
We demonstrate all-optically tunable delays in optical fiber via a dispersive stage and two stages of nonlinear spectral broadening and filtering. With this scheme, we achieve continuously tunable delays of 3.5- ps pulses and advancements over a total range of more than 1200 pulsewidths. Our technique is applicable to a wide range of pulse durations and delays.


The Impact of SARS-CoV-2 Infection on Patients with Aortic Stenosis.
To investigate the potential treatments for aortic stenosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using bioinformatics and systems biology. Observational study. Place and Duration of the Study: Jiading District Central Hospital affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China, from August to December 2022. GSE147507 was chosen as the SARS-CoV-2 infection dataset from the Biotechnology Information (NCBI) GEO database, while GSE153555 was chosen as the dataset of patients with aortic stenosis (AS). This analysis predicted protein-drug interactions (PDIs) and found therapeutic compounds for AS and COVID-19. One hundred and four DEGs were shared between the two datasets. Researchers built a PPI network to identify 10 hub genes from the network. Researchers discovered that COVID-19 and AS shared certain pathogenic pathways and found a relationship between hub genes and transcription factors and miRNAs, as well as a connection between hub genes and proposed treatments. Hub genes were identified as potential pathogenic pathways in SARS-CoV-2 infection and AS. In addition, new prescription medication options for treating both illnesses were provided. SARS-CoV-2 infection, COVID-19, Aortic stenosis, Differentially expressed genes, Hub genes, Gene-disease, Drug molecule.


Anterior spinal artery syndrome with chronic traumatic aortic aneurysm.
Shortly after severe blunt chest trauma, a young man experienced neurological symptoms suggestive of a spinal cord lesion at the lower thoracic level. The symptoms resolved at first, but then recurred 3 years later and progressed slowly. Neurological workup failed to define the cause until a thoracic aortogram showed an aneurysm in the middle portion of the descending aorta in close proximity to a vessel supplying the anterior spinal artery. After the operative repair with precautions taken to avoid further neurological injury, the neurologic deficit resolved partially. Because of the potential for symptomatic spinal cord ischemia resulting from lesions of the aorta, angiographic delineation of the spinal cord blood supply is valuable in planning operative repair.


Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels.
To report a novel cell surface autoantigen of encephalitis that is a critical regulatory subunit of the Kv4.2 potassium channels. Four patients with encephalitis of unclear etiology and antibodies with a similar pattern of neuropil brain immunostaining were selected for autoantigen characterization. Techniques included immunoprecipitation, mass spectrometry, cell-base experiments with Kv4.2 and several dipeptidyl-peptidase-like protein-6 (DPPX) plasmid constructs, and comparative brain immunostaining of wild-type and DPPX-null mice. Immunoprecipitation studies identified DPPX as the target autoantigen. A cell-based assay confirmed that all 4 patients, but not 210 controls, had DPPX antibodies. Symptoms included agitation, confusion, myoclonus, tremor, and seizures (1 case with prominent startle response). All patients had pleocytosis, and 3 had severe prodromal diarrhea of unknown etiology. Given that DPPX tunes up the Kv4.2 potassium channels (involved in somatodendritic signal integration and attenuation of dendritic back-propagation of action potentials), we determined the epitope distribution in DPPX, DPP10 (a protein homologous to DPPX), and Kv4.2. Patients' antibodies were found to be specific for DPPX, without reacting with DPP10 or Kv4.2. The unexplained diarrhea led to a demonstration of a robust expression of DPPX in the myenteric plexus, which strongly reacted with patients' antibodies. The course of neuropsychiatric symptoms was prolonged and often associated with relapses during decreasing immunotherapy. Long-term follow-up showed substantial improvement in 3 patients (1 was lost to follow-up). Antibodies to DPPX are associated with a protracted encephalitis characterized by central nervous system hyperexcitability (agitation, myoclonus, tremor, seizures), pleocytosis, and frequent diarrhea at symptom onset. The disorder is potentially treatable with immunotherapy.


Interfacility Transfer of Medicare Beneficiaries With Acute Type A Aortic Dissection and Regionalization of Care in the United States.
The feasibility and effectiveness of delaying surgery to transfer patients with acute type A aortic dissection-a catastrophic disease that requires prompt intervention-to higher-volume aortic surgery hospitals is unknown. We investigated the hypothesis that regionalizing care at high-volume hospitals for acute type A aortic dissections will lower mortality. We further decomposed this hypothesis into subparts, investigating the isolated effect of transfer and the isolated effect of receiving care at a high-volume versus a low-volume facility. We compared the operative mortality and long-term survival between 16 886 Medicare beneficiaries diagnosed with an acute type A aortic dissection between 1999 and 2014 who (1) were transferred versus not transferred, (2) underwent surgery at high-volume versus low-volume hospitals, and (3) were rerouted versus not rerouted to a high-volume hospital for treatment. We used a preference-based instrumental variable design to address unmeasured confounding and matching to separate the effect of transfer from volume. Between 1999 and 2014, 40.5% of patients with an acute type A aortic dissection were transferred, and 51.9% received surgery at a high-volume hospital. Interfacility transfer was not associated with a change in operative mortality (risk difference, -0.69%; 95% CI, -2.7% to 1.35%) or long-term mortality. Despite delaying surgery, a regionalization policy that transfers patients to high-volume hospitals was associated with a 7.2% (95% CI, 4.1%-10.3%) absolute risk reduction in operative mortality; this association persisted in the long term (hazard ratio, 0.81; 95% CI, 0.75-0.87). The median distance needed to reroute each patient to a high-volume hospital was 50.1 miles (interquartile range, 12.4-105.4 miles). Operative and long-term mortality were substantially reduced in patients with acute type A aortic dissection who were rerouted to high-volume hospitals. Policy makers should evaluate the feasibility and benefits of regionalizing the surgical treatment of acute type A aortic dissection in the United States.


Glucagon-like peptide-1 receptor expression after myocardial infarction: Imaging study using 68Ga-NODAGA-exendin-4 positron emission tomography.
Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling protects against cardiac dysfunction and remodeling after myocardial infarction (MI). The aim of the study was to evaluate 68Ga-NODAGA-exendin-4 positron emission tomography (PET) for assessment of GLP-1R expression after MI in rats. Rats were studied at 3 days, 1 and 12 weeks after permanent coronary ligation or a sham-operation. Rats were injected with 68Ga-NODAGA-exendin-4 and scanned with PET and contrast-enhanced computed tomography (CT) followed by digital autoradiography and histology of left ventricle tissue sections. 68Ga-NODAGA-exendin-4 PET/CT showed focally increased tracer uptake in the infarcted regions peaking at 3 days and continuing at 1 week after MI. Pre-treatment with an unlabeled exendin-4 peptide significantly reduced 68Ga-NODAGA-exendin-4 uptake. By autoradiography, 68Ga-NODAGA-exendin-4 uptake was 8.6-fold higher in the infarcted region and slightly increased also in the remote, non-infarcted myocardium at 1 week and 12 weeks post-MI compared with sham. Uptake of 68Ga-NODAGA-exendin-4 correlated with the amount of CD68-positive macrophages in the infarcted area and alpha-smooth muscle actin staining in the remote myocardium. 68Ga-NODAGA-exendin-4 PET detects up-regulation of cardiac GLP-1R expression during healing of MI in rats and may provide information on the activated repair mechanisms after ischemic myocardial injury.


Y-STR typing of an Austrian population sample using a 17-loci multiplex PCR assay.
Y-chromosomal STR haplotypes were determined from a sample of 135 unrelated men and 70 sons from Tirol (Austria) using the AmpFlSTR Yfiler PCR amplification kit (Applied Biosystems) that coamplifies 17 Y-STRs. The panel of markers includes the 9-loci European minimal haplotype (minHt) and, in addition, the markers DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 (Y GATA C4) and Y GATA H4. A total of 130 different haplotypes (125 were unique) were identified by the 17 Y-STR markers, an increase of 19 compared with the minHt. The gene diversity of DYS635, DYS456 and DYS458 exceeded 0.75 and only that of the duplicated marker DYS385 (0.86) was higher. Consistently high haplotype diversity values were found in all tested Y-SNP haplogroups. Because the simultaneous analysis of 17 Y-STR systems offers a high power of discrimination at minimum sample consumption, the Yfiler kit is a promising tool for forensic applications.


From framework to action: the DESIRE approach to combat desertification.
It has become increasingly clear that desertification can only be tackled through a multi-disciplinary approach that not only involves scientists but also stakeholders. In the DESIRE project such an approach was taken. As a first step, a conceptual framework was developed in which the factors and processes that may lead to land degradation and desertification were described. Many of these factors do not work independently, but can reinforce or weaken one another, and to illustrate these relationships sustainable management and policy feedback loops were included. This conceptual framework can be applied globally, but can also be made site-specific to take into account that each study site has a unique combination of bio-physical, socio-economic and political conditions. Once the conceptual framework was defined, a methodological framework was developed in which the methodological steps taken in the DESIRE approach were listed and their logic and sequence were explained. The last step was to develop a concrete working plan to put the project into action, involving stakeholders throughout the process. This series of steps, in full or in part, offers explicit guidance for other organizations or projects that aim to reduce land degradation and desertification.


Unfairness and Radicalization.
This article reviews the relationship between people's perceptions of unfairness and their tendencies to think, feel, and act in radicalizing ways. Various theories of radicalization processes are reviewed that examine key aspects of the psychology of perceived unfairness. The review shows that experienced group deprivation and perceived immorality are among the core judgments that can drive Muslim radicalization, right-wing radicalization, and left-wing radicalization. Symbols of injustice, the legitimization of revolutionary thought, and the experience of unfair treatment can also increase radicalization. The review also examines core moderators (e.g., uncertainty and insufficient self-correction) and mediators (e.g., externally oriented emotions) of the linkage between perceived unfairness and core components of radicalization (e.g., rigidity of thoughts, hot-cognitive defense of cultural worldviews, and violent rejection of democratic principles and the rule of law). The review discusses how the study of unfairness and radicalization contributes to a robust and meaningful science of psychology.


Self-induced gate dielectric for graphene field-effect transistor.
We report the electronic characteristics of an avant-garde graphene-field-effect transistor (G-FETs) based on ZnO microwire as top-gate electrode with self-induced dielectric layer. Surface-adsorbed oxygen is wrapped up the ZnO microwire to provide high electrostatic gate-channel capacitance. This nonconventional device structure yields an on-current of 175 μA, on/off current ratio of 55, and a device mobility exceeding 1630 cm(2)/(V s) for holes and 1240 cm(2)/(V s) for electrons at room temperature. Self-induced gate dielectric process prevents G-FETs from impurity doping and defect formation in graphene lattice and facilitates the lithographic process. Performance degradation of G-FETs can be overcome by this avant-garde device structure.


Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures.
A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.


[Fibrillary glomerulonephritis and immunotactoid nephropathy: the current view of the pathomorphological substrate of disease].
Fibrillary glomerulonephritis (FGN) and immunotactoid nephropathy (ITN) are diseases diagnosed only by electron microscopy. Until recently, information on the diseases has reached as reports on some cases. Much information, including the authors' observations, has been presently gathered so as there is a chance of attempting to pool and analyze it. It is quite obvious that investigators do not agree to evaluate FGN and ITN. Some authors are inclined to believe that these are one disease and propose to use the general term "fibrillary-immunotactoid nephropathy", we, like others, consider FGN and ITN as two different diseases. Our findings suggest that there are two diseases (FGN and ITN). We provide support for the data available in the literature on that the deposits are polyclonal in FGN and monoclonal in ITN. It is most likely that no sharp distinction can be made between FGN and ITN from the diameter of microtubules making up deposits (less or more than 30 nm); the procedure of their package and, to be sure, their chemical composition are of importance in establishing the diagnosis.


ZpdN, a Plasmid-Encoded Sigma Factor Homolog, Induces pBS32-Dependent Cell Death in Bacillus subtilis.
The ancestral Bacillus subtilis strain 3610 contains an 84-kb plasmid called pBS32 that was lost during domestication of commonly used laboratory derivatives. Here we demonstrate that pBS32, normally present at 1 or 2 copies per cell, increases in copy number nearly 100-fold when cells are treated with the DNA-damaging agent mitomycin C. Mitomycin C treatment also caused cell lysis dependent on pBS32-borne prophage genes. ZpdN, a sigma factor homolog encoded by pBS32, was required for the plasmid response to DNA damage, and artificial expression of ZpdN was sufficient to induce pBS32 hyperreplication and cell death. Plasmid DNA released by cell death was protected by the capsid protein ZpbH, suggesting that the plasmid was packaged into a phagelike particle. The putative particles were further indicated by CsCl sedimentation but were not observed by electron microscopy and were incapable of killing B. subtilis cells extracellularly. We hypothesize that pBS32-mediated cell death releases a phagelike particle that is defective and unstable. Prophages are phage genomes stably integrated into the host bacterium's chromosome and less frequently are maintained as extrachromosomal plasmids. Here we report that the extrachromosomal plasmid pBS32 of Bacillus subtilis encodes a prophage that, when activated, kills the host. pBS32 also encodes both the sigma factor homolog ZpdN that is necessary and sufficient for prophage induction and the protein ComI, which is a potent inhibitor of DNA uptake by natural transformation. We provide evidence that the entire pBS32 sequence may be part of the prophage and thus that competence inhibition may be linked to lysogeny.


Mexican immigration to the U.S., the occurrence of violence and the impact of mental disorders.
To study immigration, U.S. nativity, and return migration as risk factors for violence among people of Mexican origin in the U.S. and Mexico. Cross-sectional surveys in the United States (2001-2003; n=1,213) and Mexico (2001-2002; n=2,362). Discrete time survival models were used. The reference group was Mexicans living in Mexico without migrant experience or a migrant relative. Mexican immigrants in the U.S. have lower risk for any violence (hazard ratio [HR] = 0.5, 95% confidence interval [95%CI] 0.4-0.7). U.S.-born Mexican-Americans were at higher risk for violence victimization of a sexual nature (for sexual assault, HR = 2.5, 95%CI 1.7-3.7). Return migrants were at increased risk for being kidnapped or held hostage (HR = 2.8, 95%CI 1.1-7.1). Compared to those without a mental disorder, those with a mental disorder were more likely to suffer any violence (HR = 2.3, 95%CI 1.9-2.7), regardless of the migrant experience. The impact of immigration on the occurrence of violence is more complex than usually believed. Return migrants are more likely to suffer violence such as being held hostage or beaten by someone other than a partner.


Relativistic jet activity from the tidal disruption of a star by a massive black hole.
Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.


Home visiting by a geriatric department.
The practice of home visiting by the geriatrician in an inner city area is described. Visiting was of two kinds: domiciliary consultations made at the request of the general practitioner, and visits made with the consent of the general practitioner to see whether hospital admission was essential. Since 1962, 4,000 visits have been made, and in a sample of 100 visits made in 1977, 45 were domiciliary consultations and 55 followed requests for admission. Fifty-six patients were admitted at once and five following a subsequent outpatient appointment. The patients were referred by 51 general practitioners. At none of the consultations was the geriatrician accompanied by the general practitioner. Referral information given by the general practitioners was analysed. Information about acute physical disease and social conditions was commonly given but reference to psychological state, chronic disabilities, and drug therapy was much less common. Drugs were mentioned in only 27 referrals. More complete referrals would have been valuable to the geriatrician and to the general practitioner in deciding their courses of action. More accompanied visits and reference to a check-list consisting of acute physical disease, psychological state, social conditions, chronic disabilities, and drug therapy is suggested to improve communication and the quality of referrals.


What are the prospects for using complexes of copper(ii) and zinc(ii) to suppress the vital activity of Mycolicibacterium smegmatis?
New complexes of zinc(ii) and copper(ii) with 2-furoic acid (Hfur), acetic acids and N-donor ligands with the compositions [Zn2(fur)4] n (1), [Zn2(fur)4(NH2py)2] (2, NH2py = 3-aminopyridine), [Zn(fur)2(neoc)] (3, neoc = 2,9-dimethyl-1,10-phenantroline), [Zn(OAc)2(neoc)] (4, OAc = acetat-anion), and [Cu(fur)2(neoc)(H2O)] (5) were synthesized. The structures of the compounds were established by single crystal X-ray diffraction analysis. Complexes 1 and 2 are binuclear; whereas 3-5 are mononuclear. The stabilization of supramolecular architectures in crystals for compounds 1-5 occurs due to π-π-bonding between heterocycles and hydrogen interactions that provide good solubility in aqueous solutions. The stability of the complexes upon dissolution in 5% dextrose and 0.9% NaCl was confirmed by UV-vis spectroscopic and NMR (1H) data. The study of in vitro biological activity was carried out against the non-pathogenic strain of Mycolicibacterium smegmatis that is a model for M. tuberculosis. The synergistic effect of ligands is observed for complexes 3-5 and is characterized by an increase in the biological activity values. On passage from Zn2+ to Cu2+ complexes, the biological activity increases and the maximum effect is observed for compound [Cu(fur)2(phen)]. Analysis of the transcriptomic profiles of the M. smegmatis mc 2 155 strain under the pressure of the copper complex [Cu(fur)2(phen)] made it possible to isolate 185 genes, one quarter of which are associated with the compensation of iron deficiency in the bacterial strain. Genes associated with the transport and metabolism of heavy metals, biosynthesis of fatty and amino acids, biodegradation and transport of urea were also isolated.


Adult neurogenesis and brain regeneration in zebrafish.
Adult neurogenesis is a widespread trait of vertebrates; however, the degree of this ability and the underlying activity of the adult neural stem cells differ vastly among species. In contrast to mammals that have limited neurogenesis in their adult brains,zebrafish can constitutively produce new neurons along the whole rostrocaudal brain axis throughout its life.This feature of adult zebrafish brain relies on the presence of stem/progenitor cells that continuously proliferate,and the permissive environment of zebrafish brain for neurogenesis. Zebrafish has also an extensive regenerative capacity, which manifests itself in responding to central nervous system injuries by producing new neurons to replenish the lost ones. This ability makes zebrafish a useful model organism for understanding the stem cell activity in the brain, and the molecular programs required for central nervous system regeneration.In this review, we will discuss the current knowledge on the stem cell niches, the characteristics of the stem/progenitor cells, how they are regulated and their involvement in the regeneration response of the adult zebrafish brain. We will also emphasize the open questions that may help guide the future research.


Solution conformations of oligomers of alpha-aminoisobutyric acid.
The N-acetyl(Aib)nN'-methylamides (with n = 1, 2 and 3) and the N-acetyl-(Aib)3 methyl ester have been synthesized using an oxazolone procedure. An experimental conformational analysis of this series of oligomers has been carried out in water, DMSO-d6 and CDCl3 using n.m.r. techniques, and in chloroform using i.r. spectroscopy. Deuterium exchange rates of amide protons in DMSO-d6 and the rates of these proton chemical shifts with temperature in water, DMSO-d6 and CDCl3 indicate that the oligomeric N'-methylamides adopt conformations that have no hydrogen bonds when n = 1, one hydrogen bond when n = 2, and two hydrogen bonds when n = 3, and that Ac(Aib)3OMe has a conformation with one hydrogen bond. An analysis of the N-H stretching region of the i.r. spectra of these compounds in CHCl3 also suggests the existence of these conformational states. These data imply that the peptides adopt the 3(10)-helical and not the alpha-helical conformation in solution. This conclusion supports the hypothesis that the Aib residue has asymmetric geometry at the C alpha atom in solution, similar to that reported in the literature for the crystalline state.


How do ethnicity and primary language spoken at home affect management practices and outcomes in children and adolescents with asthma?
Lower rates of preventive medication use and higher rates of hospitalization and emergency department use have been documented among Latino children and adolescents with asthma. However, little is known about how language barriers influence asthma management practices and outcomes. To examine the effects of language on asthma management practices and asthma-related outcomes. Cross-sectional survey of asthma management practices, perceived efficacy, asthma knowledge, family functioning, and health-related quality of life in 405 white non-Latino, African American non-Latino, and Latino children and adolescents from English- and Spanish-speaking homes. Latino children and adolescents from Spanish-speaking homes had lower rates of goal setting and peak flow monitoring, poorer asthma knowledge, and greater negative family impact than white children and adolescents (P < .05 for all). Although Latino children and adolescents from English-speaking homes did worse than their non-Latino white peers, the decrements were modest and not statistically significant (P>.16 for all). Management practices and outcomes for non-Latino African American children and adolescents closely approximated those of white children and adolescents. Language barriers seem to contribute to poorer asthma management practices and knowledge among Latino children and adolescents. Efforts to increase knowledge in this group may enhance asthma self-care and limit the morbidity associated with asthma.


Age difference in the response to synthetic luteinizing hormone-releasing hormone (LHRH) in androgenized rats with special reference to the dose of testosterone propionate for androgenization.
Five-day-old female rats were androgenized with 1,000 or 100 microgram testosterone propionate and were examined regarding the response to LHRH at 4, 7 and 12 weeks of age by measuring peripheral LH concentrations. The order of magnitude in LH release was 7 greater than 4 greater than 12 weeks old, whereas in normal rats, 4 greater than 12 greater than 7 weeks old. LH release in 4- and 7-week-old rats was higher than that in normal controls at the respective age, but was much lower than that in normal controls 12 weeks old. The LH release by Des-Gly10-(D-Ala6)-LHRH-ethylamide (TAP127) was greater than that by natural LHRH both in normal and androgenized rats at 7 or 12 weeks old. The results indicate that the pituitary gland in androgenized rats responds to LHRH to a much larger extent during the premature period and its responsiveness declines during the course of maturation. A marked hypersensitivity was observed in 7-week-old rats androgenized with 100 microgram testosterone propionate. The process of androgenization may include the induction of alterations in the sensitivity of the pituitary to LHRH and probably in the LH synthesizing ability of the pituitary.


Relational approach in managing construction project safety: a social capital perspective.
Existing initiatives in the management of construction project safety are largely based on normative compliance and error prevention, a risk management approach. Although advantageous, these approaches are not wholly successful in further lowering accident rates. A major limitation lies with the approaches' lack of emphasis on the social and team processes inherent in construction project settings. We advance the enquiry by invoking the concept of social capital and project organisational processes, and their impacts on project safety performance. Because social capital is a primordial concept and affects project participants' interactions, its impact on project safety performance is hypothesised to be indirect, i.e. the impact of social capital on safety performance is mediated by organisational processes in adaptation and cooperation. A questionnaire survey was conducted within Hong Kong construction industry to test the hypotheses. 376 usable responses were received and used for analyses. The results reveal that, while the structural dimension is not significant, the mediational thesis is generally supported with the cognitive and relational dimensions affecting project participants' adaptation and cooperation, and the latter two processes affect safety performance. However, the cognitive dimension also directly affects safety performance. The implications of these results for project safety management are discussed.


Optimal management of severe mpox in patients with uncontrolled human immunodeficiency virus.
In May 2022, a cluster of nontravel-related cases of human mpox were reported in the United Kingdom. The outbreak has since spread worldwide infecting over 85 000 patients and causing over 100 deaths. Recent data clearly suggest that patients infected with human immunodeficiency virus (HIV) with CD4 counts less than 200 cells per mm3 suffer significantly worse outcomes than immunocompetent patients. The available countermeasures lack robust clinical data and are deployed based on in vitro and animal studies as well as extrapolations from use against other poxviruses. In many cases, despite administration of these available treatments, initiation of antiretroviral therapy (ART), and management of suspected immune reconstitution inflammatory syndrome after initiating ART, patients die. This review summarizes available data, identifies knowledge gaps and proposes recommendations on the management of severe mpox in people living with HIV.


Modifiable risk factors associated with tuberculosis disease in children in Pune, India.
India accounts for the largest burden of tuberculosis (TB) worldwide, with 26% of the world's cases. To assess the association between novel modifiable risk factors and TB in Indian children. Cases were children aged ≤ 5 years with confirmed/probable TB based on World Health Organization definitions (definition 1). Controls were healthy children aged ≤ 5 years. Logistic regression was performed to estimate the adjusted odds ratio (aOR) of being a TB case given exposure, including indoor air pollution (IAP; exposure to tobacco smoke and/or biomass fuels) and vitamin D deficiency. Cases were re-analyzed according to a new consensus research definition of pediatric TB (definition 2). Sixty cases and 118 controls were enrolled. Both groups had high levels of vitamin D deficiency (55% vs. 50%, P = 0.53). In multivariable analysis, TB was associated with household TB exposure (aOR 25.41, 95%CI 7.03-91.81), household food insecurity (aOR 11.55, 95%CI 3.33-40.15) and IAP exposure (aOR 2.67, 95%CI 1.02-6.97), but not vitamin D deficiency (aOR 1.00, 95%CI 0.38-2.66). Use of definition 2 reduced the number of cases to 25. In multivariate analysis, TB exposure, household food insecurity and IAP remained associated with TB. Household TB exposure, exposure to IAP and household food insecurity were independently associated with pediatric TB.


[Cyclosporine in inflammatory bowel disease].
Inflammatory Bowel Disease (IBD), as Ulcerative Colitis (UC) as well as Crohn's Disease (CD), can appear as severe outbreak resistant to steroid treatment. These cases require surgery or immunosupressive therapy (mercaptopurine or azathioprine). Cyclosporine A (CYA) is a selective, reversible immunosupressor of the T helper lymphocites, used in the treatment of organ transplants and in certain autoimmune diseases. CYA is not a first line therapy for IBD. In spite of the positive results obtained in some uncontrolled studies, only one randomized trial has shown the superiority of CYA over the placebo in the treatment of UC and avoided colectomy in one third of the patients with the severe form of this disease. It can also contribute to the healing of resistault CD fistulaes. The potential toxicity of CYA and the few controlled clinical trials limit its use. However CYA needs to define its role in the treatment of IBD through II more controlled trials.


Hybkit: a Python API and command-line toolkit for hybrid sequence data from chimeric RNA methods.
Experimental methods using microRNA/target ligation have recently provided significant insights into microRNA functioning through generation of chimeric (hybrid) RNA sequences. Here, we introduce Hybkit, a Python3 API, and command-line toolkit for analysis of hybrid sequence data in the "hyb" file format to enable customizable evaluation and annotation of hybrid characteristics. The Hybkit API includes a suite of python objects for developing custom analyses of hybrid data as well as miRNA-specific analysis methods, built-in plotting of analysis results, and incorporation of predicted miRNA/target interactions in Vienna format. Hybkit is provided free and open source under the GNU GPL license at github.com/RenneLab/hybkit and archived on Zenodo (doi.org/10.5281/zenodo.7834299). Hybkit distributions are also provided via PyPI (pypi.org/project/hybkit), Conda (bioconda.github.io/recipes/hybkit/README.html), and Docker (quay.io/repository/biocontainers/hybkit).


A 5-year retrospective longitudinal study on the incidence and the risk factors of osteonecrosis of the jaws in patients treated with zoledronic acid for bone metastases from solid tumors.
The aim of this study was to evaluate the incidence and the risk factors of osteonecrosis of the jaw (ONJ) in a group of patients treated with zoledronic acid (ZA) for bone metastases from solid tumors and enrolled in a preventive dental program. This 5-year retrospective longitudinal study included all consecutive oncological patients who underwent at least one infusion with ZA between 2004 and 2011 for bone metastases due to solid neoplasms. Of the 156 patients enrolled in the study, 17 developed ONJ (10.89%). At the multivariate analysis, severe periodontal disease (P=0.025), tooth extraction (P<0.0001) and starting the preventive dental program after the beginning of ZA therapy (P=0.02) were the only factors which showed a significant association with the occurrence of ONJ. This study demonstrated the importance of beginning dental prevention before zoledronic acid exposure in reducing ONJ occurrence, especially in the long term. The results of this research show that control of periodontal disease and an increase in the time between tooth extraction and the first ZA administration are recommended in order to reduce the risk of ONJ development.


[Addicted patients. Attitude of nursing personnel].
Inside the realm of therapeutic relationships, one recognizes the importance of the nurse's attitude towards patients as one of those elements bearing influence on the objectives desired by the nursing profession. This study compares the attitudes towards via parenteral drug addicts held by nursing students and non specialized nurses. By means of a pilot study which used a selfadministered Litcker scale questionnaire developed by the study authors, two samples were selected: a student sample (n = 40) and a non specialized nurse sample (n = 40). These variables were evaluated in the two samples: age, professional experience, and the frequency in sporadic care for via parenteral drug addicts. The conclusion drawn from this study is that the attitude of nursing students is significantly more positive towards via parenteral drug addicts than the attitude held by non specialized nurses. The adoption of a more negative attitude towards these patients occurs at the start of a nurse's professional career.


High expression of the transcriptional co-activator p300 predicts poor survival in resectable non-small cell lung cancers.
To investigate the correlation between p300 (a transcriptional co-activator) expression and clinical/prognostic characteristics in surgically resected NSCLC patients for the purpose of identifying patients with increased risk of cancer recurrence and providing them with tailored therapy. One hundred and sixty-nine completely resected NSCLC patients were included in this study. Paraffin-embedded primary tumour tissues of patients were supplied to produce a tissue microarray, and immunohistochemistry was used for the evaluation of p300 expression. The clinical/prognostic significance of p300 expression was analysed for statistical significance. Survival was calculated by the Kaplan-Meier method, and the log-rank test was used to assess differences in survival between the groups. The prognostic impact of clinicopathologic variables and p300 expression was evaluated using a Cox proportional hazards model. High expression of p300 was associated with poor disease-free survival (p = 0.027) and overall survival (p = 0.006) in NSCLC patients. Further analysis suggested that this difference in overall survival also existed in patients with T2 (p = 0.040), positive lymph nodes (p = 0.023), stage IIIA (p = 0.003), adenocarcinoma (p = 0.021), and a well-differentiated histological grade score (p = 0.011). The multivariate Cox regression analysis showed that low p300 expression is an independent marker of better disease-free survival (relative risk = 0.628, p = 0.047) and overall survival (relative risk = 0.545, p = 0.024) in operable NSCLC patients. Low p300 expression is an independent prognostic marker of better survival in operable NSCLC patients. The combination of clinicopathological TNM staging classification with p300 expression may be useful in identifying patients with increased risk of cancer recurrence to provide them with tailored therapy.


Hong Kong Chinese perceptions of the experience of unrelated bone marrow donation.
This paper presents a qualitative perspective of the Chinese experience of unrelated bone marrow donation. A total population of 37 Chinese men and women, residing in Hong Kong who had donated bone marrow to an unrelated recipient were interviewed and asked their retrospective perceptions and experiences during the process of unrelated bone marrow donation. The majority was female (60%) and single (59.3%). The median age was 30.9 years. The main themes drawn from thematic content analysis included: association with bad and good fortune, religious concerns associated with complete bodies, barriers posed by the extended family, fulfilling personal identities linked to perceptions of altruism, reciprocity and generosity and the differences between the expectations and reality of the experience of bone marrow donation. These accounts indicate how, for Chinese populations, the act of body fluid donation cannot be isolated from the experiences of life-long immersion in the dominant social and cultural processes of the time. In addition, Confucian notions of the body, the power of body fluids to pollute, the importance of blood and bones as sources of vital energy and the process of bodily transference into the after life are highlighted. Furthermore, what is also identifiably Chinese is that donation is more of a self-fulfilling act than a social act with very little familial or social recognition being accorded in the public world. The conclusion highlights how donors entered into the decision to donate with little awareness of the long-term consequences. The process, however, was seen by the donors to be beneficial. A compelling argument is made for more educational and emotional support regarding the experience of bone marrow donation from Hong Kong's formal service providers.


A data-driven sparse GLM for fMRI analysis using sparse dictionary learning with MDL criterion.
We propose a novel statistical analysis method for functional magnetic resonance imaging (fMRI) to overcome the drawbacks of conventional data-driven methods such as the independent component analysis (ICA). Although ICA has been broadly applied to fMRI due to its capacity to separate spatially or temporally independent components, the assumption of independence has been challenged by recent studies showing that ICA does not guarantee independence of simultaneously occurring distinct activity patterns in the brain. Instead, sparsity of the signal has been shown to be more promising. This coincides with biological findings such as sparse coding in V1 simple cells, electrophysiological experiment results in the human medial temporal lobe, etc. The main contribution of this paper is, therefore, a new data driven fMRI analysis that is derived solely based upon the sparsity of the signals. A compressed sensing based data-driven sparse generalized linear model is proposed that enables estimation of spatially adaptive design matrix as well as sparse signal components that represent synchronous, functionally organized and integrated neural hemodynamics. Furthermore, a minimum description length (MDL)-based model order selection rule is shown to be essential in selecting unknown sparsity level for sparse dictionary learning. Using simulation and real fMRI experiments, we show that the proposed method can adapt individual variation better compared to the conventional ICA methods.


Factors associated with Americans' ratings of health care quality: what do they tell us about the raters and the health care system?
Consumer satisfaction ratings of health care quality represent a commonly used measure of health care performance. Identifying factors associated with ratings will help us understand the relative influence of individuals' sociodemographic and health characteristics on satisfaction level, thus informing policy making and clinical practice. Existing research has yielded mixed results on key predictors of consumer ratings. Using nationally representative data, this study aims to identify factors associated with Americans' ratings of health care quality. Data from 2008 Health Information National Trends Survey (HINTS) were analyzed using weighted multinomial logistic regressions to estimate consumer ratings. Predictor variables included demographics, health status, care access, and attitude and perceptions about health. Overall ratings were positively skewed; 70% of respondents rated care as "excellent" or "very good." Minority race, psychological distress, not having had cancer, not having a regular health care provider, not having health insurance, lacking confidence in self-care, and avoidance of doctors were significantly associated with lower ratings. The study identifies the psychosocial characteristics associated with lower consumer ratings. The results highlight the importance of using multiple approaches to assess quality of care, including considering patient characteristics, and contribute to the evidence base for evaluating overall quality of care at the dawn of health care reform.


Silicon-Tethered Strategies for C-H Functionalization Reactions.
Selective and efficient functionalization of ubiquitous C-H bonds is the Holy Grail of organic synthesis. Most advances in this area rely on employment of strongly or weakly coordinating directing groups (DGs) which have proven effective for transition-metal-catalyzed functionalization of C(sp2)-H and C(sp3)-H bonds. Although most directing groups are important functionalities in their own right, in certain cases, the DGs become static entities that possess very little synthetic leverage. Moreover, some of the DGs employed are cumbersome or unpractical to remove, which precludes the use of this approach in synthesis. It is believed, that development of a set of easily installable and removable/modifiable DGs for C-H functionalization would add tremendous value to the growing area of directed functionalization, and hence would promote its use in synthesis and late-stage functionalization of complex molecules. In particular, silicon tethers have long provided leverage in organic synthesis as easily installable and removable/modifiable auxiliaries for a variety of processes, including radical transformations, cycloaddition reactions, and a number of TM-catalyzed methods, including ring-closing metathesis (RCM) and cross-coupling reactions. Employment of Si-tethers is highly attractive for several reasons: (1) they are easy to handle/synthesize and are relatively stable; (2) they utilize cheap and abundant silicon precursors; and (3) Si-tethers are easily installable and removable/modifiable. Hence, development of Si-tethers for C-H functionalization reactions is appealing not only from a practical but also from a synthetic standpoint, since the Si-tether can provide an additional handle for diversification of organic molecules post-C-H functionalization. Over the past few years, we developed a set of Si-tether approaches for C-H functionalization reactions. The developed Si-tethers can be categorized into four types: (Type-1) Si-tethers possessing a reacting group, where the reacting group is delivered to the site of functionalization; (Type-2) Si-tethers possessing a DG, designed for selective C(sp2)-H functionalization of arenes; (Type-3) reactive Si-tethers for C-H silylation of organic molecules; and finally, (Type-4) reactive Si-tethers containing a DG, developed for selective C-H silylation/hydroxylation of challenging C(sp3)-H bonds. In this Account, we outline our advances on the employment of silicon auxiliaries for directed C-H functionalization reactions. The discussion of the strategies for employment of different Si-tethers, functionalization/modification of silicon tethers, and the methodological developments on C-C, C-X, C-O, and C-Si bond forming reactions via silicon tethers will also be presented. While the work described herein presents a substantial advance for the area of C-H functionalization, challenges still remain. The use of noble metals are required for the C-H functionalization methods presented herein. Also, the need for stoichiometric use of high molecular weight silicon auxiliaries is a shortcoming of the presented concept.


Implementing mentor mothers in family practice to support abused mothers: study protocol.
Intimate partner violence is highly prevalent and mostly affects women with negative consequences for their physical and mental health. Children often witness the violence which has negative consequences for their well-being too. Care offered by family physicians is often rejected because abused women experience a too high threshold. Mentor mother support, a low threshold intervention for abused mothers in family practice, proved to be feasible and effective in Rotterdam, the Netherlands. The primary aim of this study is to investigate which factors facilitate or hinder the implementation of mentor mother support in family practice. Besides we evaluate the effect of mentor mother support in a different region. An observational study with pre- and posttests will be performed. Mothers with home living children or pregnant women who are victims of intimate partner violence will be offered mentor mother support by the participating family physicians. The implementation process evaluation consists of focus groups, interviews and questionnaires. In the effect evaluation intimate partner violence, the general health of the abused mother, the mother-child relationship, social support, and acceptance of professional help will be measured twice (t = 0 and t = 6 months) by questionnaires, reporting forms, medical records and interviews with the abused mothers. Qualitative coding will be used to analyze the data from the reporting forms, medical records, focus groups, interviews, and questionnaires. Quantitative data will be analyzed with descriptive statistics, chi square test and t-test matched pairs. While other intervention studies only evaluate the feasibility and effectiveness of the intervention, our primary aim is to evaluate the implementation process and thereby investigate which factors facilitate or hinder implementation of mentor mother support in family practice.


[The role of muscarinic receptor antagonists in the treatment of men with lower urinary tract symptoms secondary to BPH].
Use of antimuscarinic agents in male patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and with symptoms of overactive bladder (OAB) has become increasingly relevant over the last few years. Prescription of these drugs is in conflict with a long-established concept learnt in Medical School: antimuscarinics are contraindicated in patients with BPH. Several factors, however, have placed this issue under constant review. The description of OAB syndrome and the scientific research carried out over recent years have provided epidemiological and pathophysiological data worthwhile reviewing, most importantly in order to understand why a review of such a solidly established concept has been raised. This paper reviews the prevalence of OAB in men with BPH, the role of urodynamics to evaluate men with OAB and the existing evidence on the effect antimuscarinics have in terms of efficacy and safety on male patients with detrusor obstruction and overactivity.


Role of the renin-angiotensin system in the development of hemodynamic and clinical tolerance to long-term prazosin therapy in patients with severe chronic heart failure.
Right heart catheterization was performed before and during long-term therapy with prazosin in 27 patients with severe chronic heart failure who underwent serial hemodynamic studies during 3 to 12 weeks of treatment with the drug. Doses of digoxin and furosemide remained constant during the trial; in addition, 11 of the 27 patients were assigned to concomitant therapy with spironolactone, while the remaining 16 patients did not receive the aldosterone antagonist. First doses of prazosin produced marked increases in cardiac index and marked decreases in mean arterial pressure, left ventricular filling pressure and systemic vascular resistance in both groups of patients (all p less than 0.01), but these effects became rapidly attenuated (p less than 0.01) in both groups after 48 hours and remained attenuated during long-term therapy. After 3 to 12 weeks, values for cardiac index returned to pretreatment levels and did not decrease when the drug was withdrawn; values for mean arterial pressure, left ventricular filling pressure and systemic vascular resistance remained significantly decreased (although attenuated) after 3 to 12 weeks (p less than 0.01) and increased to pretreatment values when the drug was withdrawn. The magnitude and time course of these responses were not altered by concomitant therapy with spironolactone. Complete loss of hemodynamic efficacy (prazosin tolerance) was noted in 14 (58%) of the 24 patients who underwent long-term hemodynamic study and was not accompanied by long-term changes in plasma renin activity or body weight. These data indicate that prazosin produces long-term hemodynamic and clinical benefits in only 30 to 40% of patients with severe chronic heart failure and do not support a role for the renin-angiotensin system in the development of tolerance to alpha-adrenergic blockade. This low response rate explains why most randomized double-blind trials of prazosin in heart failure have not been able to demonstrate a significant difference between patients treated with placebo and those receiving active drug.


Predictors of repeat cesarean delivery after trial of labor: do any exist?
We evaluated the predictive value of risk factors for repeat cesarean delivery identified in retrospective studies. We identified 175 consecutive patients who underwent trial of labor (TOL) and compared detailed admission, intrapartum, and postpartum characteristics of those who required repeat cesarean delivery with those who had vaginal births. We calculated relative risks, positive predictive values, and sensitivities for potentially predictive admission characteristics. We also performed multiple logistic regression and classification analyses. Ninety-five percent of eligible patients underwent a TOL, and 85 percent of them delivered vaginally. Patients who had labor induced and patients with high fetal station on admission were significantly more likely to require repeat cesarean section (relative risk [RR]=2.9 and 2.1; 95 percent confidence interval [CI]=1.5 to 5.3, 1.1 to 4.2, respectively), but even these patients had high rates of vaginal birth (67 percent and 75 percent, respectively). A subgroup of patients who underwent labor induction and had large fetuses (estimated weight 3,800 g or more) had a 75 percent risk of cesarean delivery (RR=2.5, 95 percent CI=0.9 to 7.5). Multivariate models using different combinations of admission characteristics could not correctly identify which patients would require repeat cesarean delivery. Admission characteristics with statistically significant risk ratios have low predictive values because of the extremely low rate of repeat cesarean delivery in this population. A larger series is needed to study TOL outcomes in patients with large fetuses who are being induced. We conclude that until risk factors with high predictive value for repeat cesarean delivery are identified, all eligible patients should be encouraged to undergo a TOL.


Chromatin signatures of pluripotent cell lines.
Epigenetic genome modifications are thought to be important for specifying the lineage and developmental stage of cells within a multicellular organism. Here, we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC) and their differentiated progeny. Silent, lineage-specific genes replicated earlier in pluripotent cells than in tissue-specific stem cells or differentiated cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4. Unusually, in ES cells these markers of open chromatin were also combined with H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells is characterized by a specific epigenetic profile where lineage-specific genes may be accessible but, if so, carry repressive H3K27 trimethylation modifications. H3K27 methylation is functionally important for preventing expression of these genes in ES cells as premature expression occurs in embryonic ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage-specific genes are primed for expression in ES cells but are held in check by opposing chromatin modifications.


Effect of Lactobacillus rhamnosus NCDC 298 with FOS in Combination on Viability and Toxin Production of Enterotoxigenic Escherichia coli.
The present study was to investigate the utilization of prebiotics by Lactobacillus rhamnosus NCDC 298 and its synergistic adversary effect on both population and production of heat-labile (LT) toxin in enterotoxigenic Escherichia coli (ETEC). To select suitable prebiotic in order to enhance functionality, its utilization and the prebiotic activity score was examined. Antivirulence effect on ETEC was inspected by its inactivation rate and heat-labile toxin production in presence of different synbiotic combination. L. rhamnosus NCDC 298 strain grown well on media supplemented with fructooligosaccharides (FOS) and galactooligosaccharides (GOS), whereas significant inactivation of ETEC was observed when FOS was added to the co-culture medium. Significant decrease in LT enterotoxin was seen through GM1 ganglioside enzyme linked immunoassay (GM1 ELISA), when ETEC has grown with L. rhamnosus NCDC 298 and FOS. Short-chain FOS proved to be the most effective substrate, improving antagonistic activity for L. rhamnosus NCDC 298. Both L. rhamnosus NCDC 298 with FOS can be used as an effective synbiotic combination for secretory antidiarrheal fermented dairy formulations.


Estimation of dietary intake of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls from the Thai total diet study in 2019.
Dietary intakes of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were assessed in the Thai Total Diet Study (TDS) in 2019. Food samples including portable water (n = 1048) were collected from four regions of Thailand to represent a whole diet of Thai population, prepared as consumed and analyzed. To estimate the dietary intakes of PCDD/Fs and DL-PCBs, the concentrations in 18 food groups were combined with the respective food consumption from the national consumption data of Thailand and with a mean body weight of 57.57 kg for Thai population aged ≥ 3 years. The dietary intakes of PCDD/Fs, DL-PCBs and ∑PCDD/Fs/DL-PCBs were estimated to be 8.09, 4.93 and 13.02 pg WHO2005-TEQ kg-1 body weight month-1, respectively (upper bound). The major contributors to the total dietary intake were marine animals, followed by milk and milk products, freshwater animals, pork and pork products, and eggs, corresponding to 26, 22, 21, 10 and 9%, respectively. In comparison to health-based guidance value (HBGV), the intake of ∑PCDD/Fs/DL-PCBs (upper bound) was equal to 19% of the provisional tolerable monthly intake set by JECFA in 2001. Moreover, a comparison with other HBGVs was additionally presented and discussed.


Dual balloon adjustable continence therapy for urinary incontinence.
Dual balloon adjustable continence therapy (DBACT) has emerged as a promising option for treating stress urinary incontinence. DBACT is a minimally invasive and easily reversible procedure in which two periurethral balloons are placed just distal to the bladder neck to increase bladder outflow resistance. The device is connected to a small titanium port placed under the scrotal or labial skin. The port is used for adjustment to balloon volume in the clinic setting, allowing for refinement and optimization of urinary continence. DBACT placement is typically performed under general anesthesia and is considered an outpatient procedure. Several studies have evaluated the effectiveness of DBACT in treating urinary incontinence, and the results are promising. DBACT was effective in 91% of patients who underwent the procedure, 80% reported a significant improvement in their symptoms, and 70% reported being completely dry after the procedure. DBACT is a safe procedure with few reported complications. The most common complication is mild pain or discomfort at the site of device placement, which usually resolves within a few days. Overall, DBACT is minimally invasive, adjustable, and highly successful in restoring urinary continence.


Prefailure and failure mechanics of the porcine ascending thoracic aorta: experiments and a multiscale model.
Ascending thoracic aortic aneurysms (ATAA) have a high propensity for dissection, which occurs when the hemodynamic load exceeds the mechanical strength of the aortic media. Despite our recognition of this essential fact, the complex architecture of the media has made a predictive model of medial failure-even in the relatively simple case of the healthy vessel-difficult to achieve. As a first step towards a general model of ATAA failure, we characterized the mechanical behavior of healthy ascending thoracic aorta (ATA) media using uniaxial stretch-to-failure in both circumferential (n = 11) and axial (n = 11) orientations and equibiaxial extensions (n = 9). Both experiments demonstrated anisotropy, with higher tensile strength in the circumferential direction (2510 ± 439.3 kPa) compared to the axial direction (750 ± 102.6 kPa) for the uniaxial tests, and a ratio of 1.44 between the peak circumferential and axial loads in equibiaxial extension. Uniaxial tests for both orientations showed macroscopic tissue failure at a stretch of 1.9. A multiscale computational model, consisting of a realistically aligned interconnected fiber network in parallel with a neo-Hookean solid, was used to describe the data; failure was modeled at the fiber level, with an individual fiber failing when stretched beyond a critical threshold. The best-fit model results were within the 95% confidence intervals for uniaxial and biaxial experiments, including both prefailure and failure, and were consistent with properties of the components of the ATA media.


Yeast colonies synchronise their growth and development.
The ability to emit and receive signals over long distances is one of the characteristic attributes of multicellular organisms. Such communication can be mediated in different manners (by chemical compounds, light waves, acoustic waves etc.) and usually is reflected in the behaviour of the communicating organisms. Recently, we reported that individual yeast colonies, organised multicellular structures, can also communicate at long distance by means of volatile ammonia, which is produced by colonies in pulses separated by acidification of the medium. Here, we demonstrate that the colony that first reached the stage of intense ammonia production induces ammonia production response in surrounding colonies regardless of their age, causing the synchronisation of their NH(3) pulses and, consequently, the mutual affection of their growth. Also an artificial source of ammonia (but neither NH(4)(+) nor NaOH gradients) can immediately induce the ammonia production even in the colony starting its acidic stage of the development. The repeated transition of Candida mogii colonies from the acidic phase to the phase of intensive ammonia production is accompanied by dramatic changes in colony morphology and also in cell morphology and growth. Relatively smooth colonies in the acidic phase are formed by growing pseudohyphae. After ammonia induction, pseudohyphae decompose into non-dividing yeast-like cells, which rearrange themselves into ruffled spaghetti-like structures. The synchronisation of colony growth, that also exists between yeast colonies of different genera, could be important in establishing their optimal distribution in a natural habitat.


miR‑29a ameliorates ischemic injury of astrocytes in vitro by targeting the water channel protein aquaporin 4.
Ischemic stroke is the main cause of brain injury and results in a high rate of morbidity, disability and mortality. In the present study, we aimed to determine whether miR‑29a played a protective role in oxygen glucose deprivation (OGD) injury via regulation of the water channel protein aquaporin 4 (AQP4). Real‑time PCR and western blotting were used to assess miR‑29a levels and AQP4 protein levels, respectively. Apoptosis was detected by flow cytometry, and lactate dehydrogenase (LDH) was determined by enzyme‑linked immunosorbent assay (ELISA). Overexpression of miR‑29a was significantly downregulated in OGD‑induced primary astrocytes, and transfection with a miR‑29a mimic decreased LDH release and apoptosis, and improved cell health in OGD‑induced astrocytes. AQP4 was the target of miR‑29a, which suppressed AQP4 expression, and knockdown of AQP4 mitigated OGD‑induced astrocyte injury. Furthermore, miR‑29a regulated AQP4 expression in OGD‑induced astrocytes. AQP4 exacerbated astrocyte injury following ischemic stroke, and knockdown of AQP4 protected OGD/RX‑induced primary cultured astrocytes against injury. The effect of miR‑29a inhibitor on primary astrocytes was lost following AQP4 knockdown. These findings indicated that miR‑29a prevented astrocyte injury in vitro by inhibiting AQP4. Thus, miR‑29a may protect primary cultured astrocytes after OGD‑induced injury by targeting AQP4, and may be a potential therapeutic target for ischemic injury of astrocytes.


Glutamatergic signaling maintains the epithelial phenotype of proximal tubular cells.
Epithelial-mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrangement in cells of the central nervous system, but whether it helps maintain the epithelial phenotype of the proximal tubule is unknown. Here, knockdown of NMDAR1 in a proximal tubule cell line (HK-2) induced changes in cell morphology, reduced E-cadherin expression, and increased α-SMA expression. Induction of EMT with TGF-β1 led to downregulation of both E-cadherin and membrane-associated β-catenin, reorganization of F-actin, expression of mesenchymal markers de novo, upregulation of Snail1, and increased cell migration; co-treatment with NMDA attenuated all of these changes. Furthermore, NMDA reduced TGF-β1-induced phosphorylation of Erk1/2 and Akt and the activation of Ras, suggesting that NMDA antagonizes TGF-β1-induced EMT by inhibiting the Ras-MEK pathway. In the unilateral ureteral obstruction model, treatment with NMDA blunted obstruction-induced upregulation of α-SMA, FSP1, and collagen I and downregulation of E-cadherin. Taken together, these results suggest that NMDAR plays a critical role in preserving the normal epithelial phenotype and modulating tubular EMT.


Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions.
Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues. In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets. Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival. Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.


Intramolecular charge transfer with N-benzoylaminonaphthalenes. 1-Aminonaphthalene versus 2-aminonaphthalene as electron donors.
N-(substituted-benzoyl)-1-aminonaphthalenes and N-(substituted-benzoyl)-2-aminonaphthalenes (1-NBAs and 2-NBAs) with varied substituents at the para- or meta-position of benzoyl phenyl ring were prepared to probe the difference between 1-aminonaphthalene (1-AN) and 2-aminonaphthalene (2-AN) as electron donors, using benzanilide-like charge transfer as a probe reaction. An abnormal long-wavelength emission was found for all of the prepared aminonaphthalene derivatives in cyclohexane and was assigned to the CT state by the observation of a substantial red shift with increasing solvent polarity or with increasing electron-withdrawing ability of the substituent. The CT emission energies were found to follow a linear relationship with the Hammett constant of the substituent and the value of the linear slope for 1-NBAs (-0.45 eV) was higher than that of 2-NBAs (-0.35 eV), the latter being close to that of the aniline derivatives (BAs, -0.345 eV). This pointed to a higher extent of charge separation in the CT state of 1-NBAs in which a full charge separation was established by the reduction potential dependence of the CT emission energy with a linear slope of -1.00. The possible contribution of the difference in the steric effect and the electron donating ability of the donors in 1-NBAs and 2-NBAs was ruled out by the observation that the corresponding linear slopes of benzoyl-substituted BAs remained unchanged when para-, meta-, ortho-, or ortho,ortho-methyls were introduced into the aniline moiety. It was therefore concluded that 1-AN enhanced the charge transfer in 1-NBAs and the proximity of its 1La and 1Lb states was suggested to be responsible. Results showed that the charge transfers in 1-NBAs and 2-NBAs were not the same and 1-AN and 2-AN as electron donors were different not only in electron donating ability but in shaping the charge transfer pathway as well.


Regulation of cell division in Escherichia coli: SOS induction and cellular location of the sulA protein, a key to lon-associated filamentation and death.
Mutations in sulA (sfiA) block the filamentation and death of capR (lon) mutants that occur after treatments that either damage DNA or inhibit DNA replication and thereby induce the SOS response. Previous sulA-lacZ gene fusion studies showed that sulA is transcriptionally regulated by the SOS response system (lexA/recA). SulA protein has been hypothesized to be additionally regulated proteolytically through the capR (lon) protease, i.e., in lon mutants lacking a functional ATP-dependent protease there would be more SulA protein. A hypothesized function for SulA protein is an inhibitor of cell septation. To investigate aspects of this model, we attempted to construct lon, lon sulA, and lon sulB strains containing multicopy plasmids specifying the sulA+ gene. Multicopy sulA+ plasmids could not be established in lon strains because more SulA protein accumulates than in a lon+ strain. When the sulA gene was mutated by a mini Mu transposon the plasmid could be established in the lon strains. In contrast, sulA+ plasmids could be established in lon+, lon sulA, and lon sulB strains. The sulA+ plasmids caused lon sulA and lon sulB cells to exist as filaments without SOS induction and to be sensitive to UV light and nitrofurantoin. Evidence implicated higher basal levels of SulA protein in these lon plasmid sulA+ strains as the cause of filamentation. We confirmed that the SulA protein is an 18-kilodalton polypeptide and demonstrated that it was induced by treatment with nalidixic acid. The SulA protein was rapidly degraded in a lon+ strain, but was comparatively more stable in vivo in a lon sulB mutant. Furthermore, the SulA protein was localized to the membrane by several techniques.


A telementored trans-rectal ultrasound guided prostate biopsy.
The purpose of this project was to demonstrate the efficacy and feasibility of a real-time telementored transrectal ultrasound-guided prostate biopsy. The physician (P) was located at a remote site while the physician's extender (PE) was with the patient at another location. The (P) directed and guided the (PE) through the biopsy procedures utilizing video and audio contact, and viewing electronically transmitted ultrasound images. This procedure occurred at Walter Reed Army Medical Center in Washington, DC where the patient and (PE) were located in a surgical suite, and the (P) was located in another part of the hospital. Audio, video and ultrasound images were transmitted via a simulated T1 line. The success of this procedure demonstrates both feasibility and efficacy of invasive procedures telementored by a (P) from a remote location while the (PE) is with the patient and receiving remote instruction. The achievement of a real-time telementored biopsy has significance in increasing access to care by those populations living in geographically remote areas or urban socioeconomically isolated areas. It also has significance for physicians whose primary clinical responsibilities are in urban or university environments who also desire to provide care to these underserved, difficult to serve or expensive to serve populations. This telementored procedure was the first step in development of a large program with the Medical University of South Carolina. The intent of the program is to conduct prostate screening and biopsy where the physician and patient can maintain visual and audio contact for consultation while the physician is simultaneously viewing ultrasound images and electronic patient records. The overall effectiveness of the program will be evaluated in terms of improvement in clinical process of care, improved health outcomes, improved access to care, and patient/physician satisfaction with the experience.


Dentistry is making a career comeback.
Technology took some of the bloom off dentistry as a career choice. Ironically, it's the same force that has given new status to the profession and made dentistry the career of the future.


Sociability and susceptibility to the common cold.
There is considerable evidence that social relationships can influence health, but only limited evidence on the health effects of the personality characteristics that are thought to mold people's social lives. We asked whether sociability predicts resistance to infectious disease and whether this relationship is attributable to the quality and quantity of social interactions and relationships. Three hundred thirty-four volunteers completed questionnaires assessing their sociability, social networks, and social supports, and six evening interviews assessing daily interactions. They were subsequently exposed to a virus that causes a common cold and monitored to see who developed verifiable illness. Increased sociability was associated in a linear fashion with a decreased probability of developing a cold. Although sociability was associated with more and higher-quality social interactions, it predicted disease susceptibility independently of these variables. The association between sociability and disease was also independent of baseline immunity (virus-specific antibody), demographics, emotional styles, stress hormones, and health practices.


Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series.
Some juveniles who engage in sexual offenses may have a paraphilia, a psychiatric disorder characterized by a pervasive pattern of deviant and impairing sexual fantasies, thoughts, and/or behaviors. Though there is no known cure for these conditions, paraphilias can be effectively managed using a multimodal treatment approach. This may include the use of psychotherapeutic and pharmacological treatment interventions, including antiandrogen medications. One such agent, leuprolide acetate (leuprolide), a luteinizing hormone-releasing-hormone agonist, has been shown to be effective in reducing paraphilic symptoms in adult patients. To date, however, there is no published data on its use and effectiveness in adolescent and young adult paraphilic patients. This study consists of a case report series of six young adult patients treated with leuprolide. All subjects had been diagnosed with at least one paraphilia (i.e., Pedophilia, Sexual Sadism, Frotteurism, and Paraphilia Not Otherwise Specified). All subjects had been refractory to treatment in a residential program for adolescent sex offenders prior to initiation of leuprolide. All six subjects reported a reduction in sexually deviant symptoms following treatment with leuprolide. Clinicians rated four as much improved and two as moderately improved. The treatment was well tolerated in all six subjects. This preliminary case series supports the conclusion that leuprolide deserves further examination as a potentially safe and effective component in the treatment of young adult patients with paraphilia.


Nomograms for predicting overall survival and cancer-specific survival in patients with surgically resected intrahepatic cholangiocarcinoma.
To develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with surgically resected intrahepatic cholangiocarcinoma (ICC). The nomograms were developed using a development cohort of 947 ICC patients after surgery selected from Surveillance, Epidemiology, and End Results database, and externally validated using a training cohort of 159 patients admitted at our institution. Nomograms for OS and CSS were established based on the independent prognostic factors identified by COX regression models and Fine and Grey's models, respectively. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), and calibration plot, and compared with that of AJCC 8th edition TNM staging system by using c-index and decision curve analysis. Age, T stage, M stage, lymph node ratio (LNR) level and tumor grade were independent prognostic predictors for OS in ICC patients, while T stage, M stage, LNR level and tumor grade were independent prognostic predictors for CSS. Nomogram predicting OS was with a c-index of 0.751 on internal validation and 0.725 up to external validation, while nomogram for CSS was with a c-index of 0.736 on internal validation and 0.718 up to external validation. Calibration plots exhibited that the nomograms-predicted and actual OS/CSS probabilities were fitted well on both internal and external validation. Additionally, the nomograms exhibited superiority over AJCC 8th edition TNM staging system with higher c-indices and net benefit gains, in predicting OS and CSS in ICC patients after surgery. The constructed nomograms could predict OS and CSS with good performance, which could be served as an effective tool for prognostic evaluation and individual treatment strategies optimization in ICC patients after surgery in clinical practice.


General method for the preparation of beta,beta-difluoroacrylates using BrF3.
Various esters were reacted with base, carbon disulfide, and methyl iodide, producing 2-carboalkoxy-1,1-bis(methyl sulfide)-1-alkenes (2). The reaction of 2 with BrF(3), followed by oxidation with HOF.CH(3)CN gave the bromodifluorosulfonyl derivatives 5. Subsequent treatment with Raney nickel led to alpha-substituted beta,beta-difluoroacrylates 6 in overall yields of 50-80%.


Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA.
During the Omicron pandemic in China, a significant proportion of patients with Coronavirus Disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) necessitated admission to intensive care unit (ICU) and experienced a high mortality. To explore the clinical risk factors and the application/indication of microbiological examinations of CAPA in ICU for timely diagnosis are very important. This prospective study included patients with COVID-19 admitted to ICU between December 1, 2022, and February 28, 2023. The clinical data of influenza-associated pulmonary aspergillosis (IAPA) patients from the past five consecutive influenza seasons (November 1, 2017, to March 31, 2022) were collected for comparison. The types of specimens and methods used for microbiological examinations were also recorded to explore the efficacy in early diagnosis. Among 123 COVID-19 patients, 36 (29.3%) were diagnosed with probable CAPA. CAPA patients were more immunosuppressed, in more serious condition, required more advanced respiratory support and had more other organ comorbidities. Solid organ transplantation, APACHEII score ≥20 points, 5 points ≤SOFA score <10 points were independent risk factors for CAPA. Qualified lower respiratory tract specimens were obtained from all patients, and 84/123 (68.3%) patients underwent bronchoscopy to obtain bronchoalveolar lavage fluid (BALF) specimens. All patients' lower respiratory tract specimens underwent fungal smear and culture; 79/123 (64.2%) and 69/123 (56.1%) patients underwent BALF galactomannan (GM) and serum GM detection, respectively; metagenomic next-generation sequencing (mNGS) of the BALF was performed in 62/123 (50.4%) patients. BALF GM had the highest diagnostic sensitivity (84.9%), the area under the curve of the mNGS were the highest (0.812). The incidence of CAPA was extremely high in patients admitted to the ICU. CAPA diagnosis mainly depends on microbiological evidence owing to non-specific clinical manifestations, routine laboratory examinations, and CT findings. The bronchoscopy should be performed and the BALF should be obtained as soon as possible. BALF GM are the most suitable microbiological examinations for the diagnosis of CAPA. Due to the timely and accuracy result of mNGS, it could assist in early diagnosis and might be an option in critically ill CAPA patients.


Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium.
The main olfactory epithelium (MOE) in mammals is a specialized organ to detect odorous molecules in the external environment. The MOE consists of four types of cells: olfactory sensory neurons, supporting cells, basal cells, and microvillous cells. Among these, development and function of microvillous cells remain largely unknown. Recent studies have shown that a population of microvillous cells expresses the monovalent cation channel Trpm5 (transient receptor potential channel M5). To examine functional differentiation of Trpm5-expressing microvillous cells in the MOE, we investigated the expression and function of Skn-1a, a POU (Pit-Oct-Unc) transcription factor required for functional differentiation of Trpm5-expressing sweet, umami, and bitter taste bud cells in oropharyngeal epithelium and solitary chemosensory cells in nasal respiratory epithelium. Skn-1a is expressed in a subset of basal cells and apical non-neuronal cells in the MOE of embryonic and adult mice. Two-color in situ hybridization revealed that a small population of Skn-1a-expressing cells was co-labeled with Mash1/Ascl1 and that most Skn-1a-expressing cells coexpress Trpm5. To investigate whether Skn-1a has an irreplaceable role in the MOE, we analyzed Skn-1a-deficient mice. In the absence of Skn-1a, olfactory sensory neurons differentiate normally except for a limited defect in terminal differentiation in ectoturbinate 2 of some of MOEs examined. In contrast, the impact of Skn-1a deficiency on Trpm5-expressing microvillous cells is much more striking: Trpm5, villin, and choline acetyltransferase, cell markers previously shown to identify Trpm5-expressing microvillous cells, were no longer detectable in Skn-1a-deficient mice. In addition, quantitative analysis demonstrated that the density of superficial microvillous cells was significantly decreased in Skn-1a-deficient mice. Skn-1a is expressed in a minority of Mash1-positive olfactory progenitor cells and a majority of Trpm5-expressing microvillous cells in the main olfactory epithelium. Loss-of-function mutation of Skn-1a resulted in complete loss of Trpm5-expressing microvillous cells, whereas most of olfactory sensory neurons differentiated normally. Thus, Skn-1a is a critical regulator for the generation of Trpm5-expressing microvillous cells in the main olfactory epithelium in mice.


Prenatal Exposure to Toxic Metals and Neural Tube Defects: A Systematic Review of the Epidemiologic Evidence.
Neural tube defects (NTDs) affect >300,000 pregnancies worldwide annually. Few nongenetic factors, other than folate deficiency, have been identified that may provide intervenable solutions to reduce the burden of NTDs. Prenatal exposure to toxic metals [arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn) and lead (Pb)] may increase the risk of NTDs. Although a growing epidemiologic literature has examined associations, to our knowledge no systematic review has been conducted to date. Through adaptation of the Navigation Guide systematic review methodology, we aimed to answer the question "does exposure to As, Cd, Hg, Mn, or Pb during gestation increase the risk of NTDs?" and to assess challenges to evaluating this question given the current evidence. We selected available evidence on prenatal As, Cd, Hg, Mn, or Pb exposure and risk of specific NTDs (e.g., spina bifida, anencephaly) or all NTDs via a comprehensive search across MEDLINE, Embase, Web of Science, and TOXLINE databases and applied inclusion/exclusion criteria. We rated the quality and strength of the evidence for each metal. We applied a customized risk of bias protocol and evaluated the sufficiency of evidence of an effect of each metal on NTDs. We identified 30 studies that met our criteria. Risk of bias for confounding and selection was high in most studies, but low for missing data. We determined that, although the evidence was limited, the literature supported an association between prenatal exposure to Hg or Mn and increased risk of NTDs. For the remaining metals, the evidence was inadequate to establish or rule out an effect. The role of gestational As, Cd, or Pb exposure in the etiology of NTDs remains unclear and warrants further investigation in high-quality studies, with a particular focus on controlling confounding, mitigating selection bias, and improving exposure assessment. https://doi.org/10.1289/EHP11872.


Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute.
This Quick Reference Guide for Clinicians highlights the conclusions and recommendations from Cardiac Rehabilitation, Clinical Practice Guideline No. 17, which was formulated by a panel representing the major health care disciplines involved in cardiac rehabilitation. The conclusions and recommendations were derived from an extensive and critical review of the scientific literature pertaining to cardiac rehabilitation, as well as from the expert opinion of the panel. This guide addresses the role of cardiac rehabilitation and the potential benefits to be derived in the comprehensive care of the 13.5 million patients with heart disease in the United States, as well as the 4.7 million patients with heart failure and the several thousand patients undergoing heart transplantation. This Quick Reference Guide for Clinicians highlights the major effects of multifactorial cardiac rehabilitation services: medical evaluation; prescribed exercise; cardiac risk factor modification; and education, counseling, and behavioral interventions. The outcomes of and recommendations for cardiac rehabilitation services are categorized as to their effects on exercise tolerance, strength training, exercise habits, symptoms, smoking, lipids, body weight, blood pressure, psychological well-being, social adjustment and functioning, return to work, morbidity and safety issues, mortality and safety issues, and pathophysiologic measures. Patients with heart failure and after cardiac transplantation, as well as elderly patients, are specifically addressed. Alternate approaches to the delivery of cardiac rehabilitation services are presented.


Driving behaviors and accident risk under lifetime license revocation.
This study explored the driving behaviors and crash risk of 768 drivers who were under administrative lifetime driver's license revocation (ALLR). It was found that most of the ALLR offenders (83.2%) were still driving and only a few (16.8%) of them gave up driving completely. Of the offenders still driving, 67.6% experienced encountering a police roadside check, but were not detained or ticketed by the police. Within this group, 50.6% continued driving while encountering a police check, 18.0% of them made an immediate U-turn and 9.5% of them parked and exited their car. As to crash risk, 15.2% of the ALLR offenders had at least one crash experience after the ALLR had been imposed. The results of the logistic regression models showed that the offenders' crash risk while under the ALLR was significantly correlated with their personal characteristics (personal income), penalty status (incarceration, civil compensation and the time elapsed since license revocation), annual distance driven, and needs for driving (working, commuting and driving kids). Low-income offenders were more inclined to have a crash while driving under the ALLR. Offenders penalized by being incarcerated or by paying a high civil compensation drove more carefully and were less of a crash risk under the ALLR. The results also showed there were no differences in crash risk under the ALLR between hit-and-run offences and drunk driving offences or for offenders with a professional license or an ordinary license. Generally, ALLR offenders drove somewhat more carefully and were less of a crash risk (4.3 crashes per million km driven) than legal licensed drivers (23.1 crashes per million km driven). Moreover, they seemed to drive more carefully than drivers who were under short-term license suspension/revocation which previous studies have found.


The Influence of Weather on the Occurrence of Aflatoxin B1 in Harvested Maize from Kenya and Tanzania.
A study was conducted using maize samples collected from different agroecological zones of Kenya (n = 471) and Tanzania (n = 100) during the 2013 maize harvest season to estimate a relationship between aflatoxin B1 concentration and occurrence with weather conditions during the growing season. The toxins were analysed by the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Aflatoxin B1 incidence ranged between 0-100% of samples in different regions with an average value of 29.4% and aflatoxin concentrations of up to 6075 µg/kg recorded in one sample. Several regression techniques were explored. Random forests achieved the highest overall accuracy of 80%, while the accuracy of a logistic regression model was 65%. Low rainfall occurring during the early stage of the maize plant maturing combined with high temperatures leading up to full maturity provide warning signs of aflatoxin contamination. Risk maps for the two countries for the 2013 season were generated using both random forests and logistic regression models.


Comparison between 2D and 3D dosimetry protocols in 90Y-ibritumomab tiuxetan radioimmunotherapy of patients with non-Hodgkin's lymphoma.
We compared the radiation-absorbed dose obtained from a two dimensional (2D) protocol, based on planar whole-body (WB) scans and fixed reference organ masses with dose estimates, using a 3D single-photon emission computed tomography (SPECT) imaging protocol and patient-specific organ masses. Six (6) patients with follicular non-Hodgkin's lymphoma underwent a computed tomography (CT) scan, 5 2D planar WB, and 5 SPECT scans between days 0 and 6 after the injection of (111)In-ibritumomab tiuxetan. The activity values in the liver, spleen, and kidneys were calculated from the 2D WB scans, and also from the 3D SPECT images reconstructed, using quantitative image processing. Absorbed doses after the administration of (90)Y-ibritumomab tiuxetan were calculated from the (111)In WB activity values combined with reference organ masses and also from the SPECT activity values and organ masses as estimated from the patient CT scan. To assess the quantitative accuracy of the WB and SPECT scans, an abdominal phantom was also studied. The differences between organ masses estimated from the patient CT and from the reference MIRD models were between -10% and +98%. Using the phantom, errors in organ and tumor activity estimates were between -86% and 10% for the WB protocol and between -43% and -6% for the SPECT protocol. Patient liver, spleen, and kidney activity values determined from SPECT were systematically less than those from the WB scans. Radiation-absorbed doses calculated with the 3D protocol were systematically lower than those calculated from the WB protocol (29%+/-26%, 73%+/-26%, and 33%+/-53% differences in the liver, spleen, and kidney, respectively), except in the kidneys of 2 patients and in the liver of 1 patient. Accounting for patient-specific organ mass and using SPECT activity quantification have both a great impact on estimated absorbed doses.


Substance use disorder a bio-directional subset of reward deficiency syndrome.
This commentary is to inform clinicians challenged with an increase in people seeking treatment for Substance Use Disorder (SUD), that the ninety percent revolving door, is, in part, due to post-withdrawal, untreated neurotoxicity. This impairment attenuates neurotransmitter signaling and compromises resting state functional connectivity, leading to unwanted sequelae including depression, sleep disturbances, sensation seeking, lack of satisfaction and impulsivity. Neuroimaging studies indicate that neurobiological recovery can take years. Like a "double edge sword" SUD has a biological bi -directional (bio-directional) effect on the brain reward circuitry. The acute intake of psychoactive drugs results in heightened dopaminergic activity, while, the opposite, hypodopaminergia occurs following chronic abuse. Individuals with SUD can have a genetic predisposition, compounded by stress and neurotoxically induced, epigenetic insults that impact recovery from protracted abstinence. Follow-up post -short-term recovery usually includes supportive therapies and programs like 12 -steps and other fellowships. However, relapse will usually occur if post -short-term recovery hypodopaminergia is not treated with attempts at epigenetic manipulation of compromised brain neurochemistry using some manner of pro-dopamine regulation.