Short-term effect of pollen exposure on antiallergic drug consumption.
Several studies have investigated the association between pollen exposure and asthma emergency admissions, but only 2 have investigated the effect of airborne allergens on consultations for rhinitis or conjunctivitis and none has used drug consumption as the health indicator. To analyze the short-term association between pollen exposure and antiallergic drug consumption in the urban area of Clermont-Ferrand, France, taking into account the potentially confounding effect of air pollution and meteorological factors. We used the French health insurance database to select all individuals from the Clermont-Ferrand urban area having benefited from reimbursement for antiallergic treatment from January 1, 2000, through December 31, 2001, and from January 1, 2003, through December 31, 2004. An episode of treated allergic rhinitis, rhinosinusitus, or conjunctivitis (ARC) was defined as the association of an oral antihistamine and a local antiallergic drug on the same prescription. The relations between daily changes in pollen concentrations and daily changes in the number of treated ARC cases were analyzed using a Poisson regression model with penalized spline functions. The risk of treated ARC associated with an interquartile increase in pollen concentration increased significantly for Poaceae (5%, P < .001), Fraxinus (7%, P < .001), Betula (7%, P < .001), and Corylus (2%, P < .02). This increase was significant in all age groups for Poaceae and Fraxinus pollen and in people younger than 65 years for Betula pollen. The effect was mainly concentrated on the present day, except for Poaceae pollens, for which the risk remained significantly (P < .001) increased until 3 days lag time. This study showed a significant increase in treated ARC cases related to Poaceae, Fraxinus, and Betula. Specific risks are difficult to evaluate for species that share the same pollination period. Time-series studies based on drug consumption are useful to highlight and to supervise pollen-related diseases requiring ambulatory care.


Myelination patterns on magnetic resonance of children with developmental delay.
Magnetic resonance (MR) imaging was performed in 30 children with unexplained developmental delay who had associated neurological abnormalities such as seizures, spasticity, hypotonia, ataxia or poor vision. No child had a history of regression, preterm birth or neonatal cerebral injury. CT scans were performed before MR in all cases and were either normal or showed only mild atrophy. At least two MR sequences were obtained for all patients. Nine children had delayed or absent myelination on MR, one had patchy white-matter abnormalities, and in one patient myelination was topographically normal, but of inappropriately low signal intensity. MR was abnormal in six of seven children who had abnormal brainstem auditory evoked potentials (BAEP), and was normal in nine of 11 patients who had a normal BAEP. MR may have a useful rôle in demonstrating abnormal white-matter maturation in children with unexplained neurodevelopmental delay, particularly when abnormalities are found on BAEP studies.


Characteristics of Patients with Pressure Injuries in a COVID-19 Referral Hospital.
This retrospective study aimed to describe the characteristics of patients treated at a COVID-19 referral hospital from March 2020 to June 2021 who experienced pressure injuries (PIs) either before or after admission. The researchers collected and analyzed data on patients' demographic characteristics, symptoms, comorbidities, location and severity of PI, laboratory values, oxygen therapy, length of stay, and vasopressor use. During the study period, 1,070 patients were hospitalized for COVID-19 with varying degrees of severity, and 12 patients were diagnosed with PI. Eight (66.7%) of the patients with PI were men. The median age was 60 (range, 51-71) years, and half of the patients had obesity. Eleven of the patients with PI (91.4%) had at least one comorbid condition. The sacrum and gluteus were the two most commonly affected sites. Those with stage 3 PI had a substantially greater median d-dimer value (7,900 ng/mL) than patients with stage 2 PI (1,100 ng/mL). The average length of stay was 22 (range, 9.8-40.3) days. Health professionals should be aware of an increase in d-dimer in patients with COVID-19 and PI. Even though PIs in these patients might not result in mortality, an increase in morbidity can be avoided with the right care.


Renal dialysis: counting the cost versus counting the need.
The relatively "lean and mean" provision of renal dialysis in Britain is a notorious example of "covert rationing", apparently achieved by a lack of central policy. Then in its first experiment in "target-setting" in the NHS in 1984, central government used the profession's preferred measure of need, thus promoting expansion of renal services, at almost exactly the time when the "quality-adjusted life year" (QALY) developed by health economists indicated that renal dialysis scored low in cost-benefit terms. This chapter examines these conundrums in terms of centre-periphery relations, clinical autonomy versus collective direction, and the politics of competing ways of counting need and cost.


Effects of self-management interventions for cancer patients with pain: A systematic review of randomised controlled trials.
To evaluate the effects of self-management interventions targeting individuals with cancer-related pain on pain intensity, self-efficacy, quality of life (QoL), pain medication adherence, and pain-related knowledge and provide recommendations for the content and format of self-management interventions based on the existing evidence. A systematic review of randomised controlled trials (RCTs) and narrative synthesis. A search of six electronic databases, including Medline, PsycINFO, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus. This systematic review followed the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published from January 2011 to March 2022 in English were retrieved. The Cochrane Risk of Bias Tool was used to assess quality. Data were summarised using narrative synthesis. This systematic review included six RCTs involving 748 patients with cancer-related pain. The results support the effectiveness of the intervention on QoL and pain-related knowledge. Mixed results were observed in the effectiveness on pain intensity, self-efficacy and medication adherence. Overall, the quality of the evidence was low. The content of self-management interventions varied across studies but with similar formats (face-to-face coaching and telephone follow-up). The existing evidence supports the effectiveness of self-management interventions on pain-related knowledge and QoL. Further high-quality RCTs are needed to determine the most effective interventions. Self-management is recommended to improve cancer patients' pain awareness, self-management behaviour and adaptability. Components for self-management of cancer pain, including patient attitude and knowledge assessment, nurse coaching and counselling, reinforcement during follow-up period, and provision of supplementary materials on pain management and medication adherence, could be covered in the intervention. In the future, it is worthwhile exploring an effective intervention using Internet-based information technology, for example WeChat, to aid the delivery of self-management intervention. This systematic review does not necessarily involve patients or public members in this work.


Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections.
The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem fibers from prefrontal cortical regions that are associated with different aspects of emotion, motivation, cognition processing, and decision-making. This large fiber bundle is abnormal in several psychiatric illnesses and a major target for deep brain stimulation. Yet, we have very little information about where specific prefrontal fibers travel within the bundle. Using a combination of tracing studies and diffusion MRI in male nonhuman primates, as well as diffusion MRI in male and female human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions within the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar disorder were detected when FA was averaged in the ALIC segment that carries ventrolateral prefrontal cortical connections. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and demonstrate the utility of applying connectivity profiles of large white matter bundles based on animal anatomic studies to human connections and associating disease abnormalities in those pathways with specific connections. The ability to functionally segment large white matter bundles into their components begins a new era of refining how we think about white matter organization and use that information in understanding abnormalities.SIGNIFICANCE STATEMENT The anterior limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus and brainstem and is abnormal in psychiatric illnesses. However, we know little about the location of specific prefrontal fibers within the bundle. Using a combination of animal tracing studies and diffusion MRI in animals and human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions. We then demonstrated that differences in FA values between bipolar disorder patients and healthy control subjects were specific to a given segment. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and for refining how we think about white matter organization in general.


Polyphenols in red wine aged in acacia (Robinia pseudoacacia) and oak (Quercus petraea) wood barrels.
Polyphenolic composition of two Syrah wines aged during 6 or 12 months in medium toasting acacia and oak 225L barrels was studied by LC-DAD-ESI/MS. A total of 43 nonanthocyanic phenolic compounds were found in all wines, and other 15 compounds only in the wines from acacia barrels. Thus, the nonanthocyanic phenolic profile could be a useful tool to identify the wines aged in acacia barrels. Among all of them the dihydrorobinetin highlights because of its high levels, but also robinetin, 2,4-dihydroxybenzaldehyde, a tetrahydroxydihydroflavonol, fustin, butin, a trihydroxymethoxydihydroflavonol and 2,4-dihydroxybenzoic acid were detected at appreciable levels in wines during aging in acacia barrels, and could be used as phenolic markers for authenticity purposes. Although longer contact time with acacia wood mean higher concentrations of phenolic markers found in wines, the identification of these wines will also be easy after short aging times due the high levels reached by these compounds, even after only 2 months of aging.


Definitions of Chronic Low Back Pain From a Scoping Review, and Analyses of Narratives and Self-Reported Health of Adults With Low Back Pain.
Among those with low back pain (LBP), individuals with chronic LBP (CLBP) face different treatment recommendations and incur the majority of suffering and costs. However, the way CLBP has been defined varies greatly. This study used a scoping review and qualitative and quantitative analyses of data from LBP patients to explore this variation. CLBP in most recent randomized controlled trials (RCTs) was defined by duration of pain, most commonly ≥3 months. However, individuals with LBP most often define CLBP by frequency. CLBP has also been defined using a combination of duration and frequency (16% of RCTs and 20% of individuals), including 6% of recent RCTs that followed the NIH Pain Consortium research task force (RTF) definition. Although not a defining characteristic of CLBP for individuals, almost 15% of recent RCTs required CLBP to have a healthcare provider diagnosis. In our LBP sample moving from ≥3 months to the RTF definition reduced the CLBP group size by 25% and resulted in a group that used more pain management options and reported worse health across all outcome measures. A pain duration definition offers ease of application. However, refinements to this definition (eg, RTF) can identify those who may be better intervention targets. PERSPECTIVE: This article presents the definitions used for CLBP by researchers and individuals, and the impact of these definitions on pain management and health outcomes. This information may help researchers choose better study inclusion criteria and clinicians to better understand their patients' beliefs about CLBP.


Autophagy and Ciliogenesis.
Autophagy is a major intracellular degradation system and plays important roles in various physiological processes such as metabolic adaptation and intracellular homeostasis. It degrades intracellular components both randomly and selectively. Autophagic activity is tightly regulated primarily by nutrient availability, but also by other extracellular and intracellular signals. Growing evidence suggests that there are multiple links between autophagy and the primary cilium. The primary cilium is an organelle present on the cell surface and is important for keeping cellular integrity by transducing extracellular stimuli inside the cell. Recent studies have revealed that autophagy selectively degrades the ciliogenesis inhibitory proteins OFD1 and MYH9, promoting ciliogenesis. Conversely, autophagy also inhibits ciliogenesis under growth conditions. The primary cilium can also regulate autophagic activity. These findings suggest that the relationship between autophagy and the primary cilia is bidirectional, and that both are important for maintaining the normal function of various organs.


[The effect of rithmocor on the structural and functional state of erythrocyte membranes and athlete's adaptation to intensive training loads].
Intensive training process is accompanied by the oxidative stress with alteration of homeostatic balance and functional possibility of cardio-vascular system followed by decrease of oxygen transport and tissue hypoxia. The tissue hypoxia and increase of oxygen active forms level worsen structural and functional status of erythrocyte membranes that led to the temporary anaemia. In this article was shown that Rithmocor corrected these alterations and increased adaptation of sportsmen to the intensive training load (increase of endurance). An improvement of erythrocyte membranes status resulted in the increase of intracorpuscular haemoglobin content the critical parameter for the anaemia development. It has been established that Rithmocor causes an increased of sportsmen endurance to the intensive training load and therefore could be recommended for use in this situation.


Predicting Successful Phase Advancement and Regulatory Approval in Multiple Myeloma From Phase I Overall Response Rates.
Drug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval. Seventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval. The median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I trials in multiple myeloma, but not the success rate, significantly increased over the period studied. The proportion of industry-sponsored trials also steadily increased over that same period. The ratio of initial dose to maximum tolerated dose was 0.29, suggesting that many patients were undertreated. Investigational agents with higher ORRs in phase I trials were more likely to advance to phase II trials and achieve US Food and Drug Administration approval. Our results suggest that designing phase I trials to maximize the antimyeloma efficacy of a given compound may lead to more successful and cost-effective drug development.


Clinico-pathologic disparities of breast cancer in Hispanic/Latina women.
Breast cancer is the leading cause of cancer death in Hispanic/Latina women nationwide. Limited cancer research has been conducted in this population. El Paso, Texas is a large border city with a population of around 900,000, of which 85% are Latinos and would provide a suitable setting for this study. The aim of this study is to evaluate ethnic differences and cancer characteristics in Hispanic/latina women with breast cancer. After IRB approval, we retrospectively analyzed the variables of patients with breast cancer treated consecutively at a large tertiary medical center in El Paso, TX between 2005-2015. Descriptive statistics, bivariate, and multivariable analyses were conducted. 1,252 patients were identified. Mean age at diagnosis was 57 years. 1074 were Hispanics/Latinas (86%). When comparing Hispanics versus non-Hispanics, 31% of Hispanics compared to 24% Non-Hispanics were diagnosed at age <50 (P = 0.043). More Hispanics are uninsured (34%) compared to Non-Hispanics (25%) (p = 0.008). Hispanics presenting with advanced stages were more likely to be uninsured (P = 0.02). This analysis confirms that Hispanics/Latinas are diagnosed with breast cancer at a younger age and are more commonly uninsured than Non-Hispanics. We did not observe significant differences in the prevalence of ER+, triple negative or Her2 -neu positive disease or stages at presentation between the 2 groups in this cohort, however the non-Hispanic group was constituted only 14% of the studied population. A larger multi-institutional comparative study is being conducted to confirm these findings.


New-onset and relapsed Graves' disease following COVID-19 vaccination: a comprehensive review of reported cases.
Global Coronavir us disease 2019 (COVID-19) vaccination efforts are being intensified to combat the pandemic. As the frequency of immunization against COVID-19 has increased, some adverse effects related to vaccination have emerged. Within this context, this article reviewed 62 Graves' disease (GD) cases following COVID-19 vaccination, to probe the potential association between the vaccination and the onset of GD. A comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted to collect GD cases following COVID-19 vaccination up to June 7, 2023. Among the 62 GD cases included in this review, there were 33 (53.2%) new-onset GD and 10 (16.1%) relapsed GD patients following mRNA vaccination, 14 (22.6%) new-onset GD and 4 (6.5%) relapsed GD patients following viral vector vaccination, and 1 (1.6%) relapsed GD patients following inactivated vaccination. Median durations to symptoms onset for new-onset and relapsed GD were 12 (range: 1-60) and 21 (range: 5-30) days following mRNA vaccination, while 7 (range: 1-28) and 14 (range: 10-14) days following viral vector vaccination, respectively. While the definitive pathogenesis of GD following COVID-19 vaccination remains unclear, it might be associated with cross-immune responses triggered by molecular mimicry, and an adjuvant-induced autoimmune/inflammatory syndrome. However, due to the limited number of observed GD cases following COVID-19 vaccination and the lack of systematic experimental studies, a causal relationship between COVID-19 vaccination and the onset of GD has not been definitively confirmed. It should be highlighted that most of GD patients following COVID-19 vaccination experienced positive outcomes after treatment. In the broader context of ending the COVID-19 pandemic and reducing mortality rates, the benefits of COVID-19 vaccination significantly outweigh mild risks such as treatable GD. Adherence to the COVID-19 vaccination schedule is therefore imperative in effectively managing the pandemic.


Expression of androgen, estrogen, and progesterone hormone receptors in the penile tissues of children with different types of hypospadias.
Androgen (AR), Estrogen (ER) and Progesterone (PR) hormones play an important role in the prenatal and postnatal development of urogenital tract and especially the penis. The expressions of AR, ER and PR receptors in penile tissues in children with hypospadiases had also been shown previously. In this leading study, to demonstrate of the sex hormone receptor expression in cases with different types of hypospadias were aimed. This study was designed in children operated due to hypospadiases without DSD. Biopsy samples of 3 mm's were obtained from three different sytes as the lateral parameatal tissue and the anterior corner of the prepuce, and inner layer of posterior prepuce. The presence of AR, ER and PR receptors was investigated immunehistochemically. Mean age was 5.4 years in 18 children with hypospadiases; in totally 33 specimens were taken in 5 subcoronal as 5 specimens, and 7 penile as 15 specimens, and 6 penoscrotal as 13 specimens. According to sytes of samples; 13 samples were from lateral para-meatal tissues, and 13 were from anterior corners of prepuces, and 7 were from inner layers of posterior prepuces. In regard to receptor expression; ER and AR receptors were positive in 29 (87.8%) and 12 (36.4%) respectively; PR receptors were negative. This study emphasized the dominant expression of estrogen receptors in penile tissues of children with hypospadias. Although there was not a manifest correlation of androgen receptors absence in regard to the severity of hypospadias patients, there was a marked estrogen receptors presence in penile tissues. These findings suggest that the disrupted androgen and estrogen receptor interaction and/or balance could play a role during the development of external genitalia in hypospadias patients. Progesterone receptor was not present and therefore the active role in the postnatal development of hypospadias is still debatable.


PCR-based analysis of alpha-thalassemia in Southern Taiwan.
The Southeast Asia type deletion of alpha-thalassemia-1 (--SEA) is the most common type of alpha-thalassemia-1 in Taiwan. There are 2 less common types, Filipino type (--FIL) and Thai type (--THAI). In the current study, we screened 754 cases of alpha-thalassemia-1 in Southern Taiwan using a polymerase chain reaction (PCR)-based method. Our results show that the prevalence of the (--SEA) type is 90.6%, followed by the (--FIL) type (8.6%), the (--THAI) type (0.5%), and the (-alpha(3.7/-alpha(3.7)) type (0.3%). We also analyzed the genotypes of 96 patients with hemoglobin (Hb) H disease and 48 cases of hydrops fetalis with Hb Bart's. The frequencies of the genotypes of the alpha-thalassemia-1 allele in Hb H disease are in accordance with the results of analyses of alpha-thalassemia-1 cases. The alpha-thalassemia-2 allele includes alpha(4.2), alpha(G), alpha(CS), and alpha(QS)alpha. Forty-one cases, 6 cases, and 1 case of hydrops fetalis with Hb Bart's were caused by --SEA/--SEA, --SEA/--FIL and --SEA/--THAI respectively. The genotypes and frequencies of alpha-thalassemia in this study are different from those in previous studies in Taiwan and Hong Kong. These differences may be attributed to the diverse genetic origin among different ethnic groups and the extensive inclusion of the (--FIL) and (--THAI) alpha-thalassemia-1 types.


Relative frequency of human papillomavirus genotypes and related sociodemographic characteristics in women referred to a general hospital in Tehran, 2014-2015: A cross-sectional study.
Human papilloma virus (HPV) is one of the major public health problems and the main causes of cervical cancer. The prevalence HPV infection in developing countries with low financial resources is high. This study aimed to determine the relative frequency of HPV genotypes and its sociodemographic characteristics in women referred to a general hospital in Tehran, Iran from 2014-2015. This cross-sectional study was performed in 400 women with Pap smear samples, referring to to a general hospital in Tehran, Iran from 2014-2015. The detection of 28 HPV genotypes was performed by using the Multiplex PCR technique. The sociodemographic survey was conducted for each HPV positive woman. HPV-positive infection was detected in 155 (38.75%) women aged 17-85 years. HPV 16 (19.1%) was the most prevalent type, followed by HPV 39 (12.5%) and HPV 18 (8.9%). The highest rate of HPV infection was observed at the age of 36 years (7.7%). The level of education and economic situation of each woman were showed most of HPV-positive women had a high school diploma (34.6%) and average economic situation (67,9%). 60.9% of these women were a housewife, and 67.3% lived in the capital . Determination of HPV genotype and risk factor related to HPV infection in each geographical region can lead to the production of effective vaccines against the HPV virus. It can also be useful for disease management and high sensitivity diagnosis of cervical intraepithelial neoplasia.


Development of a programmable standard of ultra-low capacitance values.
A set of ultra-low value capacitance standards together with a programmable coaxial multiplexer (mux) have been developed. The mux allows the connection of these capacitances in parallel configuration and they together form the programmable capacitance standard. It is capable of producing decadic standard capacitances from 10 aF to at least 0.1 pF, which are later used to calibrate commercial precision capacitance bridges. This paper describes the realization and the characterization of this standard together with results obtained during the calibration of Andeen-Hagerling AH2700A bridges with a maximum uncertainty of 0.8 aF for all the capacitances generated ranging from 10 aF to 0.1 pF, at 1 kHz. These latter could be then integrated to functionalized AFMs or probe stations for quantitative capacitance measurements. Sources of uncertainties of the programmable capacitance standard, such as parasitic effects due to stray impedances, are evaluated and a method to overcome these hindrances is also discussed.


Phosphatase-mediated heavy metal accumulation by a Citrobacter sp. and related enterobacteria.
A Citrobacter sp. was reported previously to accumulate heavy metals as cell-bound heavy metal phosphates. Metal uptake is mediated by the activity of a periplasmic acid-type phosphatase that liberates inorganic phosphate to provide the precipitant ligand for heavy metals presented to the cells. Amino acid sequencing of peptide fragments of the purified enzyme revealed significant homology to the phoN product (acid phosphatase) of some other enterobacteria. These organisms, together with Klebsiella pneumoniae, previously reported to produce acid phosphatase, were tested for their ability to remove uranium and lanthanum from challenge solutions supplemented with phosphatase substrate. The coupling of phosphate liberation to metal bioaccumulation was limited to the metal accumulating Citrobacter sp.; therefore the participation of species-specific additional factors in metal bioaccumulation was suggested.


Coinfection and genetic recombination between HIV-1 strains: possible biological implications in Australia and South East Asia.
It has been recognised that human immunodeficiency virus (HIV) mutates rapidly and that nucleotide substitutions, deletions, insertions, and rearrangements resulting from recombination events are the main factors that result in variation of the HIV-1 genome. Together, these processes are actively contributing to the diversity and virulence of viral forms comprising the acquired immune deficiency syndrome (AIDS) pandemic. There are 9 HIV-1 subtypes recognised (A-H and O), based on the envelope region segments. Inter-subtype recombination has been already described, whereas intra-subtype recombination has been difficult to detect. In this study, we have identified in vivo genetic recombination between HIV-1 strains belonging to subtype B in a patient who presented both intravenous drug use (IVDU) and homosexual sex as risk factors. Genetic analysis of viral strains in the hypervariable V3 region of the envelope gene indicated the presence of three distinct sequence groups categorized according to their respective tetrapeptide motifs-GPGR, GLGR and GPGK. Detailed genetic and phylogenetic analyses suggested the recombination occurring only between sequence groups with GPGR and GPGK tetrapeptide motifs. These data suggest that coinfection with closely related strains can occur in vivo, and the generation of hybrid HIV-1 genomes via genetic recombination between subtype B strains can result in further antigenic diversity which may thwart diagnosis and future vaccine efforts. Since HIV-1 subtype B is still the most commonly found subtype around the globe, the hybrid genomes between different subtype B strains may result in epidemiologic shifts and altered pathogenesis.


World sleep society international sleep medicine guidelines position statement endorsement of "behavioral and psychological treatments for chronic insomnia disorder in adults: An American Academy of sleep medicine clinical practice guidelines".
This paper summarizes the position statement of the World Sleep Society (WSS) International Guidelines Committee regarding the Clinical Practice Guidelines on the Behavioral and Psychological Treatments for Chronic Insomnia Disorder in Adults prepared by a task force of the American Academy of Sleep Medicine (AASM). The practice guidelines were reviewed for their relevance and applicability to the practice of sleep medicine around the world. The WSS Work Group endorsed the AASM strong recommendation for Multicomponent Cognitive Behavioral Therapy as the treatment of choice for Insomnia Disorder and conditional endorsement for its single-therapy components (sleep restriction, stimulus control, relaxation); use of sleep hygiene education as single therapy was not endorsed due to lack of evidence for its efficacy. The strong recommendation for multicomponent CBT-I applied to patients with chronic insomnia disorder with or without comorbid psychiatric and medical conditions. Main caveats with regard to CBT-I remains the lack of adequately trained therapists and variability in terms of training available in different parts of the world. Unanswered questions about the applicability, availability, accessibility and potential sociodemographic (age, sex, ethnicity, regions) moderators of treatment outcomes were discussed. Despite growing evidence documenting the benefits of digital CBT-I, individual, in-person CBT-I delivered by a trained professional (mental health) provider is regarded as the optimal method to deliver CBT-I.


Temporal scale effect of loading data on instream nitrate-nitrogen load computation.
The temporal scale effect of loading data on nitrate-nitrogen load computation was examined using outputs of watershed modeling tool Hydrologic Simulation Program-FORTRAN (HSPF) for the Amite River in Louisiana, USA. The daily nitrate-nitrogen concentrations simulated using the HSPF were employed first to obtain daily, weekly, bi-weekly, and monthly average data and then to develop load duration curves for the data with four different temporal scales. The duration curves exhibited high variability in the load estimated using daily data as compared with those based on bi-weekly and monthly data. According to daily data, the nitrate-nitrogen load in the winter was found to be 2,780 kg. The nitrate-nitrogen load decreased with increasing temporal (daily, weekly, bi-weekly, and monthly) scale (commonly used in water quality monitoring) of the data. The coefficient of variation, used to quantify the effect of temporal scale on the load, was found to be linearly and inversely correlated with the logarithm of the time scale. Based on the finding, empirical equations were proposed to extrapolate near real-time data for flow and nitrate-nitrogen, greatly simplifying nutrient monitoring and reducing the cost involved in water quality monitoring.


Systematic review of sensory integration therapy for individuals with disabilities: Single case design studies.
Sensory integration therapy (SIT) is a controversial intervention that is widely used for people with disabilities. Systematic analysis was conducted on the outcomes of 17 single case design studies on sensory integration therapy for people with, or at-risk of, a developmental or learning disability, disorder or delay. An assessment of the quality of methodology of the studies found most used weak designs and poor methodology, with a tendency for higher quality studies to produce negative results. Based on limited comparative evidence, functional analysis-based interventions for challenging behavior were more effective that SIT. Overall the studies do not provide convincing evidence for the efficacy of sensory integration therapy. Given the findings of the present review and other recent analyses it is advised that the use of SIT be limited to experimental contexts. Issues with the studies and possible improvements for future research are discussed including the need to employ designs that allow for adequate demonstration of experimental control.


Post-legalization Consumption of Cannabis at Massachusetts General Hospital Dental Group.
The aim of this study was to evaluate the profile of patients undergoing dental treatment in relation to cannabis use. A comprehensive questionnaire was used to address the type of cannabis preparations, route of intake, frequency of usage, and potential reasoning for use (recreational vs medical use) of patients from the MGH Dental Group. Seventy-six adult patients completed the survey. Sixty-one percent of the participants were female, with the majority (59%) of the participants being ≥51 years or older. Twelve of the 76 participants (16%) were 18-30 years old. The remaining 19 patients (25%) who participated in the study were 31-50 years old. The sample included participants who were predominately non-Hispanic (63 patients, 83%) and White (59 patients, 78%). The majority of patients either had their first use of cannabis prior to 18 years of age (36%) or did not respond to this question (34%) at all. The predominant age at consistent cannabis use was 18-30 years (13%). The most common method of cannabis intake in the preceding year for participants was smoking, followed by ingesting, using cannabidiol (CBD), and vaping (least common). Recreational cannabis use was reported in 47% of the participants vs 28% of participants who reported cannabis intake for medical use. This preliminary study characterized the profile of patients undergoing dental treatment in relation to marijuana use. Diminishing restraints to cannabis use may affect the dental profession. It is important for dentists to understand cannabis-related oral health conditions to provide customized patient treatments.


Purification of different lipases from Aspergillus niger by using a highly selective adsorption on hydrophobic supports.
In this manuscript, we have purified three different lipases from crude preparations from Aspergillus niger in a simple fashion, secluding the esterases and other enzymes presented in the preparation. Firstly, the crude was offered at low ionic strength to octyl agarose. The support specifically adsorbed two lipases, with molecular weights of 43 and 65 kDa. Desorption with a gradient of Triton X-100 permitted to fully purify both lipases. The addition of octadecyl-Sepabeads support to the non-adsorbed proteins on octyl-agarose permitted to selectively adsorb a third lipase, having a molecular weight of 31 kDa. Desorption of the enzyme using Triton X-100 permitted to have also a pure sample of this enzyme. A significant percentage of esterase activity remains in the supernatant, derived from esterases or lipases unable to become adsorbed on the employed supports. Furthermore, these purified lipases were immobilized via ionic adsorption on DEAE-Sepharose and their selectivity was analyzed in the kinetic resolution of (+/-)-O-2-butyryl-2-phenylacetic acid and (+/-)-mandelic acid methyl ester. In the resolution of (+/-)-O-2-butyryl-2-phenylacetic acid, the crude extract preparation gave a low enantioselectivity value (E = 9), whereas the three immobilized preparations of purified lipases exhibited an increase in E-value from 11 (43 kDa lipase) to > 100 (31 kDa lipase). When (+/-)-mandelic acid methyl ester was used, the crude extract preparation presented low enantioselectivity hydrolyzing the S enantiomer quicker, while the purified lipase preparations preferred the R one. In this case, the 65 kDa lipase was the most selective enzyme (E = 20).


Short communication: effects of serum obtained from dairy cows with low or high body condition score on in vitro embryo development.
The objective of the study was to determine whether the serum obtained from animals differing in body condition score (BCS) affects in vitro embryo development. After in vitro fertilization, serum obtained from dairy cows of either low (L-BCS; 2.1 ± 0.14 on a scale of 1 to 5) or high BCS (H-BCS; 4.0 ± 0.0), or commercially available bovine serum (control) was added at 5% concentration to the in vitro culture medium. Use of serum obtained from H-BCS cows increased the cleavage rates compared with control serum at both 24 and 48 h after in vitro fertilization (78.3 vs. 71.9% and 79.9 vs. 75.1%, respectively), whereas use of serum obtained from L-BCS cows increased the blastocyst rate compared with control serum at 7d (23.8 vs. 19.1%), but this difference was not evident at 8 or 9 d after in vitro fertilization. As nonesterified fatty acid concentrations were highest in control serum, followed by serum from L-BCS and H-BCS cows (621, 559, and 272 μEq/L, respectively), a high concentration of nonesterified fatty acids might adversely affect the very early stages of embryo development, and its negative effects might be greater immediately after fertilization compared with developmental stages after morula formation. Our findings also indicate that factors promoting early stage embryo development do not necessarily promote blastocyst development. Serum obtained from animals under different physiological conditions may be used for in vitro embryo culture to study the effects of nutritional management of dairy cattle on embryo development.


Targeting the programmed cell death-1 pathway in rheumatoid arthritis.
Since the introduction of TNF-α inhibitors and other biologic agents, the clinical outcome for many treated rheumatoid arthritis patients has significantly improved. However, there are still a substantial proportion of patients that are intolerant, or have inadequate responses, with current agents that have become the standards of care. While the majority of these agents are designed to affect the inflammatory features of the disease, there are also agents in the clinic that instead target lymphocyte subsets (e.g., rituximab) or interfere with lymphocyte co-receptor signaling pathways (e.g., abatacept). Due in part to their ability to orchestrate downstream inflammatory responses that lead to joint damage and disease progression, pathogenic expansions of T and B lymphocytes are appreciated to play key roles in the pathogenesis of rheumatoid arthritis. New insights into immune regulation have suggested novel approaches for the pharmacotherapeutic targeting of lymphocytes. In this review, we discuss deepening insights into human genetics and our understanding of the interface with rheumatoid arthritis pathogenesis providing a strong rationale for exploiting the co-inhibitory receptor programmed cell death-1 signaling pathway as a better approach for the treatment of this chronic, often progressive destructive joint disease.


Median sternotomy approach for chronic bovine experiments.
Lateral thoracotomy is the traditional surgical approach for preclinical animal testing of various ventricular assist devices. Median sternotomy, however, is regarded from a functional standpoint as the most appropriate approach for cardiac surgical procedures, particularly for device implantation. The purpose of this study was to evaluate the outcomes of performing a median sternotomy in chronic bovine studies. Three chronic studies using the sternotomy approach were performed. Surgical access was compared to the lateral thoracotomy approach used in three other animal experiments. Postoperative speed of recovery, pain management, sternotomy incision, and monitoring line exit site healing and infection were also evaluated. With sternotomy, better surgical access to all cardiac chambers and great vessels and more room for device placement were achieved. The recovery time was similar to that using the lateral thoracotomy approach, with no additional difficulties observed in standing or recumbency and no need for increased pain management. At the time of autopsy, the sternum was well healed without any sign of infection. In conclusion, these studies showed that a median sternotomy can be used successfully for chronic bovine studies. This approach will be used for our future biventricular assist device implantation surgeries.


Forensic age estimation based on development of third molars: a staging technique for magnetic resonance imaging.
The development of third molars can be evaluated with medical imaging to estimate age in subadults. The appearance of third molars on magnetic resonance imaging (MRI) differs greatly from that on radiographs. Therefore a specific staging technique is necessary to classify third molar development on MRI and to apply it for age estimation. To develop a specific staging technique to register third molar development on MRI and to evaluate its performance for age estimation in subadults. Using 3T MRI in three planes, all third molars were evaluated in 309 healthy Caucasian participants from 14 to 26 years old. According to the appearance of the developing third molars on MRI, descriptive criteria and schematic representations were established to define a specific staging technique. Two observers, with different levels of experience, staged all third molars independently with the developed technique. Intra- and inter-observer agreement were calculated. The data were imported in a Bayesian model for age estimation as described by Fieuws et al. (2016). This approach adequately handles correlation between age indicators and missing age indicators. It was used to calculate a point estimate and a prediction interval of the estimated age. Observed age minus predicted age was calculated, reflecting the error of the estimate. One-hundred and sixty-six third molars were agenetic. Five percent (51/1096) of upper third molars and 7% (70/1044) of lower third molars were not assessable. Kappa for inter-observer agreement ranged from 0.76 to 0.80. For intra-observer agreement kappa ranged from 0.80 to 0.89. However, two stage differences between observers or between staging sessions occurred in up to 2.2% (20/899) of assessments, probably due to a learning effect. Using the Bayesian model for age estimation, a mean absolute error of 2.0 years in females and 1.7 years in males was obtained. Root mean squared error equalled 2.38 years and 2.06 years respectively. The performance to discern minors from adults was better for males than for females, with specificities of 96% and 73% respectively. Age estimations based on the proposed staging method for third molars on MRI showed comparable reproducibility and performance as the established methods based on radiographs.


Perrault Syndrome with progressive nervous system involvement.
A 21-year-old woman with a Perrault Syndrome (PS) presented with progressive ataxia. PS comprises gonadal dysgenesis and sensorineural deafness in females. More recent studies have asked whether the neurologic signs in some of the patients are a coincidental finding or part of the syndrome. Magnetic resonance imaging in PS patients shows high intensity signals in the periventricular and the subcortical white substance, as well as in the centrum ovale, suggestive for cerebral leucodystrophy, which is one of a wide spectrum of neurologic symptoms found in PS. The fluorodeoxyglucose positron emission tomography (PET) of our patient brought results indicating a progressive heredoataxia. PET is helpful in the early detection of the progressive central nervous involvement of PS.


Exploring parish nursing from an ethnographic perspective.
This study examined a parish program as an evolving nursing specialty. This is an ethnographic study of a parish nursing program in a southeastern U.S. city that included interviews with key informants, participant observations, and document analysis. Data were content analyzed. FINDINGS AND RESULTS: Findings indicate positive perceptions of the parish nursing program. Cultural themes include the process of discovery, commitment to the parish nurse and program, and fit with values and missions. Taxonomies of parish nurse attributes, actions, offerings, roles, and entrance requirements were derived. Parish nursing offers nurses the opportunity to bridge physical, social, emotional, and spiritual lives into one caregiving experience. Findings provide clinical guidance for parish nurses.


Synthesis of a ketone analogue of biotin via the intramolecular Pauson-Khand reaction.
We report an improved synthesis of 5-(5-oxohexahydrocyclopenta[c]thiophen-1-yl)pentanoic acid (ketone biotin, 1) based on the intramolecular Pauson-Khand cyclization. The synthesis proceeds in eight steps and in 2.7% overall yield from cyclohexene.


Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States.
Southeast Asian immigrants, with a high prevalence of both hepatitis B and latent tuberculosis, constitute a large proportion of immigrants to the United States. Isoniazid hepatotoxicity may be associated with hepatitis B. This study was conducted to document the prevalence and interaction of hepatitis B, latent tuberculosis, and isoniazid toxicity. Hepatitis B surface antigen (HBsAg) and tuberculin skin testing was done on 743 Vietnamese immigrants to the Midwest between January, 1991 and December, 1999. HBsAg positive cases were tested for hepatitis B e antigen (HBeAg). All tuberculin skin test-positive patients were treated with isoniazid, unless contraindicated. Complications of isoniazid treatment and compliance with hepatitis B virus immunization recommendations were evaluated. One hundred three subjects (13.86%) had HBsAg, and 43 (5.7%) HBeAg. Prevalences of latent tuberculosis were similar in HBsAg positive (53%) and HBsAg negative (45%) subjects. Sixty-two percent of HBeAg positive versus 19% of HBeAg negative subjects had hepatotoxic side effects requiring discontinuation of treatment (relative risk [RR] = 11.38, CI = 5.49 < RR < 23.59, p < 0.001). Three cases of severe isoniazid hepatitis occurred in 21 HBeAg positive subjects, versus no cases in 121 HBeAg negative cases treated with isoniazid (RR = 7.72, CI = 5.02 < RR < 11.88, p < 0.001). Only 58% of subjects at risk of developing hepatitis B virus infection were appropriately immunized. Vietnamese immigrants have a high prevalence of hepatitis B and latent tuberculosis. HBeAg positive cases have a 7.7-fold increased risk of serious isoniazid toxicity and an 11.3-fold increased risk of isoniazid side effects requiring discontinuation of treatment. HBeAg represents an important risk factor for severe isoniazid hepatitis.


End of life customs among immigrants from Eritrea.
Eritrean immigrants bring expectations and resources to meet the challenge of illness and death. This study, undertaken in cooperation with the Cross Cultural Health Care Program of Seattle, sought to learn about both the expectations and the resources. A literature search demonstrated that although Eritreans have much in common with Ethiopians, they must be seen as a separate people. Open-ended interviews were conducted with 2 Eritrean immigrants. Resulting tape transcriptions were studied to identify themes and values. Values included the importance of respect, the centrality of faith and of family, the use of herbs and home remedies, and the importance of visiting. Implications for health care within institutional and community settings were derived from these values with the help of Madeleine Leininger's culture care theory.


Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats.
Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3',5-Triiodo-L-thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats. Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed. Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T3 compared to vehicle-treated animals. T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.


Myogenic and adipogenic properties of goat skeletal muscle stem cells.
The aims of the present study were to establish a culture system for goat skeletal muscle stem cells and to examine their myogenic and adipogenic properties in vitro. Cells were isolated from the skeletal muscle of the Shiba goat and cultured in vitro. Most of the cells were positive for myogenic markers, such as Pax7, MyoD, and desmin, and immunocytochemistry revealed they differentiated to form myotubes expressing myosin heavy chain, indicating they were highly myogenic. Myogenic differentiation was strongly suppressed by the addition of basic fibroblast growth factor, while proliferation was unaffected. When the cells were cultured in adipogenic differentiation medium, some of the cells differentiated into mature adipocytes that stained with Oil Red-O. These cells were immunocytochemically positive for adipogenic markers, including peroxisome proliferator-activated receptor-gamma (PPAR gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP alpha). These results clearly demonstrate the presence of both myogenic and adipogenic stem cells in goat skeletal muscle.


The critical role of mast cells in allergy and inflammation.
Mast cells are well known for their involvement in allergic and anaphylactic reactions, but recent findings implicate them in a variety of inflammatory diseases affecting different organs, including the heart, joints, lungs, and skin. In these cases, mast cells appear to be activated by triggers other than aggregation of their IgE receptors (FcepsilonRI), such as anaphylatoxins, immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines leading to selective release of mediators without degranulation. These findings could explain inflammatory diseases, such as asthma, atopic dermatitis, coronary inflammation, and inflammatory arthritis, all of which worsen by stress. It is proposed that the pathogenesis of these diseases involve mast cell activation by local release of corticotropin-releasing hormone (CRH) or related peptides. Combination of CRH receptor antagonists and mast cell inhibitors may present novel therapeutic interventions.


[Pharmacokinetics of human interferons].
Interferon in the blood was rapidly cleared from the circulation after intravenous injection. Intramuscular injection of alpha-interferon caused low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon was never detected consistently in the blood after intramuscular or subcutaneous administration. Intraarterial administration of beta-interferon also caused low but stable interferon levels in the blood. Our studies suggest that beta-interferon should be given intravenously to see clinical beneficial. No difference in pharmacokinetics was seen between natural interferon and recombinant interferon. No difference was also noted between partially purified interferon and highly purified interferon.


31 P NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent Effects in Trapping.
Intralipid is a lipid emulsion used in photodynamic therapy (PDT) for its light scattering and tissue-simulating properties. The purpose of this study is to determine whether or not Intralipid undergoes photooxidation, and we have carried out an Intralipid peroxide trapping study using a series of phosphines [2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 3-(diphenylphosphino)benzenesulfonate, triphenylphosphine-3,3',3''-trisulfonate and triphenylphosphine]. Our new findings are as follows: (1) An oxygen atom is transferred from Intralipid peroxide to the phosphine traps in the dark, after the photooxidation of Intralipid. 3-(Diphenylphosphino)benzenesulfonate is the most suitable trap in the series owing to a balance of nucleophilicity and water solubility. (2) Phosphine trapping and monitoring by 31 P NMR are effective in quantifying the peroxides in H2 O. An advantage of the technique is that peroxides are detected in H2 O; deuterated NMR solvents are not required. (3) The percent yield of the peroxides increased linearly with the increase in fluence from 45 to 180 J cm-2 based on our trapping experiments. (4) The photooxidation yields quantitated by the phosphines and 31 P NMR are supported by the direct 1 H NMR detection using deuterated NMR solvents. These data provide the first steps in the development of Intralipid peroxide quantitation after PDT using phosphine trapping and 31 P NMR spectroscopy.


Shift handover qualification in obstetric unit during the pandemic period: reinventions and learning.
Qualify the shift handover in an Obstetric Unit during the COVID-19 pandemic period, through Permanent Health Education. Action research conducted in southern Brazil. The research was conducted from interviews with healthcare professionals and students and the data were analyzed using the Reflexive technique. Interventions took place in different work shifts, with the support of a serial album as a didactic and educational resource. The data analysis made it possible to record experiences and the delineation of two thematic categories: From traditional approaches to the reinvention of learning in healthcare work; and From conformism to professional growth. The shift handover in the Obstetric Unit, through Permanent Health Education, enabled autonomous, interactive, and cooperative learning; awakened the desire to transcend the work routine; and highlighted the need to continuously (re)signify the healthcare work process.


Synthesis and HPLC assessment of N-nitrosoderivatives from six beta-adrenergic antagonists.
At first N-nitrosoderivatives from six beta-adrenergic antagonists of large consumption were prepared. Secondly the standard nitrosation reactions recommended by WHO were performed to get information about their possible in vivo production and the yields of N-nitrosoderivatives were evaluated by HPLC analyses. Pharmacological tests confirm the potential risk to man of the N-nitrosoderivatives studied.


Gastric-tube versus whole-stomach esophagectomy for esophageal cancer: A systematic review and meta-analysis.
To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical technique of esophagectomy. A comprehensive literature search was performed using PubMed, EMBASE, ScienceDirect, Ovid MEDLINE, Cochrane Library, Web of Science, Google Scholar, and Scopus. Clinical trials that compared the gastric-tube versus whole-stomach for esophageal cancer were selected. The clinical endpoints included anastomotic leakage, anastomotic stenosis, reflux esophagitis, pneumonia, delayed gastric emptying, and thoracic stomach syndrome. A total of 6 articles (1571 patients) were included. Compared to the whole-stomach approach, the gastric-tube approach was associated with a lower incidence of reflux esophagitis (95% confidence interval [CI]: 0.16 to 0.81, p = 0.01) and thoracic stomach syndrome (95% CI: 0.17 to 0.55, p < 0.0001). The rates of anastomotic leakage, anastomotic stenosis, pneumonia, and delayed gastric emptying did not significantly differ between the two groups. The gastric-tube esophagectomy is superior to the whole-stomach approach, as it is associated with a lower incidence of postoperative reflux esophagitis and thoracic stomach syndrome. Our findings must be validated in large-scale randomized controlled trials.


Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy.
To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma. Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used. MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells. MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.


Factors affecting length of hospital stay for femoropopliteal bypass. Implications of the DRGs.
We compared the length of hospitalization of 329 patients undergoing femoropopliteal bypass during 1982 with that allowed under Medicare's diagnosis-related groups (DRGs) for major reconstructive vascular surgery (DRGs 110 and 111). The mean length of stay was found to be related to the patients' age, increasing at a rate of about 1 percent per year. The site of distal anastomosis, a factor not considered in establishing the criteria for these DRGs, was also important. The lengths of stay for above-the-knee popliteal, below-the-knee popliteal, and tibioperoneal anastomoses were significantly different (F = 3.31; P less than 0.05), with lengths of stay increasing for more distal anastomoses. More distal anastomoses were also associated with increased rates of postoperative morbidity, reoperation, and mortality. Significant differences were noted among the patients treated by different surgeons, with respect to their age, the percentage with previous ipsilateral surgery, the frequency of tibial bypass, and the rates of morbidity, reoperation, and mortality. The most highly qualified surgeons dealt with the sickest patients. We conclude that the DRG system does not take account of important variables influencing the length of hospitalization for femoropopliteal bypass, that it favors younger patients undergoing proximal bypass, and that it is biased against distal bypass for limb salvage.


Plasma fatty acyl-carnitines during 8 weeks of overfeeding: relation to diet energy expenditure and body composition: the PROOF study.
Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed patterns of fatty acyl carnitines.


Effects of the action of microwave-frequency electromagnetic radiation on the spike activity of neurons in the supraoptic nucleus of the hypothalamus in rats.
Acute experiments on white rats anesthetized with Nembutal (40 mg/kg, i.p.) were performed with extracellular recording and analysis of background spike activity from neurons in the supraoptic nucleus of the hypothalamus after exposure to electromagnetic radiation in the millimeter range. The distribution of neurons was determined in terms of the degree of regularity, the nature of the dynamics of neural streams, and the modalities of histograms of interspike intervals; the mean neuron spike frequency was calculated, along with the coefficient of variation of interspike intervals. These studies demonstrated changes in the background spike activity, predominantly affecting the internal structure of the spike streams recorded. The major changes were in the duration of interspike intervals and the degree of regularity of spike activity. Statistically significant changes in the mean spike frequencies of neuron populations in individual frequency ranges were also seen.


'Inner voices': the cerebral representation of emotional voice cues described in literary texts.
While non-verbal affective voice cues are generally recognized as a crucial behavioral guide in any day-to-day conversation their role as a powerful source of information may extend well beyond close-up personal interactions and include other modes of communication such as written discourse or literature as well. Building on the assumption that similarities between the different 'modes' of voice cues may not only be limited to their functional role but may also include cerebral mechanisms engaged in the decoding process, the present functional magnetic resonance imaging study aimed at exploring brain responses associated with processing emotional voice signals described in literary texts. Emphasis was placed on evaluating 'voice' sensitive as well as task- and emotion-related modulations of brain activation frequently associated with the decoding of acoustic vocal cues. Obtained findings suggest that several similarities emerge with respect to the perception of acoustic voice signals: results identify the superior temporal, lateral and medial frontal cortex as well as the posterior cingulate cortex and cerebellum to contribute to the decoding process, with similarities to acoustic voice perception reflected in a 'voice'-cue preference of temporal voice areas as well as an emotion-related modulation of the medial frontal cortex and a task-modulated response of the lateral frontal cortex.


Performance Characteristics of Commercial Immunoassays for the Detection of IgG and IgM Antibodies to β2 Glycoprotein I and an Initial Assessment of Newly Developed Reference Materials for Assay Calibration.
To investigate the performance characteristics and impact of newly developed reference calibrators on the commutability between anti-β2 glycoprotein I (anti-β2 GPI) immunoassays in antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). Immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-β2 GPI immunoassays from four manufacturers were evaluated. Serum samples from 269 patients (APS only, n = 31; SLE and APS, n = 83; SLE only, n = 129; pregnancy-related clinical manifestations without APS, n = 26) and 162 women with histories of successful pregnancies were tested. Results were expressed in kit-specific arbitrary units and in the calibrator reference units (RUs) based on 99th percentile cutoff values. Diagnostic accuracies, correlation between kits, and specific clinical manifestations in APS were investigated. The sensitivities of the assays ranged from 15.8% to 27.2% (IgG) and 12.3% to 15.8% (IgM) while specificities ranged from 79.4% to 86.5% (IgG) and 80.6% to 84.5% (IgM). There was moderate to almost perfect interassay reliability (Cohen κ, 0.69-0.98), and Spearman correlation coefficients were generally improved when results of the IgG determinations were expressed in RUs. Although qualitative agreements between immunoassays for both antibody isotypes are acceptable, correlations with APS clinical manifestations were kit dependent. Only the use of IgG reference material improved quantitative correlations between assays.


Procedural and mathematical considerations in urea dilution estimation of body composition in lambs.
Two experiments (n = 46 and 56, respectively) were conducted to evaluate urea dilution as an estimator of body composition in lambs and to address certain procedural and mathematical considerations in this technique. In Exp. 1, 14 blood samples were taken over 240 min after urea infusion. The equation describing the urea clearance curve was: delta PUN = 9.7e-.1727(min) + 10.4e-.0021(min), pools 1 and 2, respectively (r2 = .99, P less than .001; individual lamb effects removed). In the combined experiments, urea space (US) was related to percentage of empty body water (PEBH2O) by the equation 31.7 + .471 US (empty body weight basis; r2 = .56, P less than .001). The regression equation indicates that the US-PEBH2O relationship in lambs is different from that reported in cattle, even though urea clearance kinetics are similar. Although the prediction equations appeared to be biologically valid, considerable error was associated with the composition estimates. The PEBH2O was predicted as well by live weight (r2 = .69; SEy.x = 3.0) as by US in these experiments. The two-sample method (T12 minus T0) to determine the change in marker concentration was shown to be related more closely (r2 = .56) to PEBH2O than the standard multisample extrapolation to T0 method (r2 = .0 and .38 for pools 1 and 2, respectively). An equilibration time of 9 to 12 min provided the best estimate of body composition in lambs.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Dancer-Specific Biomechanics on Adolescent Ballet Dancers' Posture En Pointe and Factors Related to Pointe Readiness: A Cross-Sectional Study.
There are no universally accepted requirements or uniform protocols to determine when dancers can safely commence dancing en pointe (shod relevé). The purpose of this study was to examine dancer-specific biomechanics of adolescent pointe dancers and explore factors that may help determine pointe readiness. Dancers (n=26; median age 14 yrs [IQR=13-16]) were stratified into two groups based on the ability to stand on the pointe shoe box as per a plumb line (Group 1: on the box; Group 2: not on the box) during parallel, shod relevé. Measurements included unshod weight-bearing range of motion (ROM) of ankle plantarflexion (PF) and first metatarsophalangeal (MTP) extension and shod posture assessment during first position elevé (rising into relevé with turned out, straight legs). Qualisys 3D motion capture and AMTITM force plates recorded dancers performing 10-15 repetitions of first position elevé. Comparison of three kinematic and three kinetic variables aimed to describe group differences during unshod and shod conditions. Wilcoxon signed-rank test assumed no difference between groups with a Bonferroni correction (p<0.0083). During unshod parallel relevé, ROM was different between groups for first MTP extension (deg; MedGroup1: 90°, IQR 80°-90°; MedGroup 2: 70°, IQR: 70°-80°, p<0.0001) but no statistical difference in ankle PF (deg; p=0.0098). There were no differences in C7 displacement (m; p=0.5055), ankle PF moment (p=0.1484), or hip mediolateral and anteroposterior moments (p=0.8785 and 0.8785, respectively) during shod first position relevé, indicating that both groups tend to engage the same dominant muscle groups (trunk extensors, ankle dorsiflexors, hip flexors, and hip abductors) during elevé. Dancers in Group 1 demonstrated greater first MTP extension during unshod relevé compared to dancers in Group 2. Weight-bearing ROM could be a valuable tool in predicting pointe readiness of adolescent ballet dancers.


Experimental inhibition of proliferative vitreoretinopathy in retinal detachment using daunorubicin.
Proliferative vitreoretinopathy (PVR) remains the most common cause of failure in retinal detachment surgery. Surgical procedures for its repair entails complex and extensive instrumentation besides technical skill. The success rate varies widely with high incidence of redetachment. Keeping this in view, we evaluated the role of intravitreal daunorubicin as an anti-mitiotic agent in the inhibition of PVR. Our study concluded that 5 micrograms of intravitreal daunorubicin effectively inhibited PVR in the rabbit eye and the dosage was safe and nontoxic. The half-life of the drug was determined to be about 140 minutes, suggesting a prolonged intravitreal concentration sufficient to prevent fibroblast proliferation.


Pyoderma gangrenosum associated with selective hereditary IgA deficiency.
A case of pyoderma gangrenosum is described in a girl aged 4. The condition was associated with selective IgA deficiency. The father and the 2 brothers suffered from the same deficiency (autosomal dominant transmission). Treatment with prednisolone and clofazimine produced an excellent clinical response.


[Gender dysphoria in adolescents: difficulties in treatment].
In many children and adolescents with gender dysphoria only minor or no psychopathology is found. 43% of patients seen in the Frankfurt University Gender Identity Clinic for children and adolescents suffer from major psychopathology. To demonstrate difficulties in treatment of these patients courses of treatment in four such patients are presented. In two natal females major psychopathology made decision for reassignment very difficult. Two natal males were in addition not able to follow recommended treatment steps, in these patients diagnostic doubts arose.


Critical factors responsible for the therapeutic effect of mesenchymal stem/stromal cells in central nervous system disorders.
Nowadays it is observed that the number of stem-cell based experimental therapies in neurodegenerative disorders is massively increasing. Most of the clinical trials registered to date have been based on autologous mesenchymal stem/stromal cells (MSC) obtained from somatic tissues. In the conducted clinical trials neither serious side effects, nor statistically significant improvement were observed. The lack of statistical significance could result from a relatively small number of patients involved in clinical trials or highly incoherent study protocols. However, most clinical groups describe a trend towards improvement in MSC-treated patients. Hence, the question arises which factors associated with MSC-based therapy may be the key and result in better therapeutic response. In the presented paper, we summarize, in our opinion, the most important factors that could increase the effectiveness of this therapy.


Follow the time course of inflammation caused by intraperitoneal administration of multi-wall carbon nanotubes in mice.
Understand the progress of inflammation over time caused by multi-walled carbon nanotubes (MWCNT). Two types of MWCNTs were administered to C57BL/6N mice via intraperitoneal administration at low and high doses (0.05 and 1.0 mg/mouse, respectively). Inflammation was evaluated until 6 months after administration based on cytokine levels and pathological observations. The abdominal cavity lavage fluid was collected and analyzed 1 week, 1, 3, and 6 month(s) after administration. IL-6 expression markedly increased 3 months after the administration of high-dose MWCNT-7. Notable inflammation was observed in the groups administered with one of the MWCNT, MWCNT-7. On the other hand, inflammation in another MWCNT-treated group was milder than that in the MWCNT-7-treated group. MWCNT-7 induced pronounced inflammation but did not induce tumor formation during the experimental period. Inflammation reaction is one of the most important biological responses to MWCNT. Three months post-exposure becomes a turning point for the harmful effects of the intraperitoneally administered MWCNT-7.


Investigation of genetic diversity and inbreeding in a Japanese native horse breed for suggestions on its conservation.
Because native breeds can serve as genetic resources for adapting to environment changes, their conservation is important for future agroecosystems. Using pedigree analysis, we investigated genetic diversity and inbreeding in Japanese Hokkaido native horses, which have adapted to a cold climate and roughage diet. Genetic diversity was measured as the number of founders and the effective number of founders, ancestors and genomes. All metrics imply a decrease in genetic diversity. A comparison of these metrics suggested that pedigree bottlenecks contributed more than did random gene losses to the reduction of genetic diversity. Estimates of marginal contributions of ancestors suggest that the bottlenecks arose mainly because related stallions had been used for breeding. A tendency for an increase in inbreeding coefficients was observed. F-statistics revealed that a small effective population size majorly contributed to this increase, although non-random mating in particular regions also contributed. Because the bottlenecks are thought to have reduced the effective population size, our results imply that mitigation of bottlenecks is important for conservation. To this end, breeding should involve genetically diverse stallions. In addition, to prevent non-random mating observed in particular regions, efforts should be made to plan mating with consideration of kinships.


(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids.
A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.


Characterization of the IFN-gamma-responsive element in the 5' flanking region of the C1 inhibitor gene.
Treatment of a variety of cell lines with IFN-gamma leads to enhanced synthesis and secretion of C1 inhibitor (C1inh). The induction of C1inh synthesis by IFN-gamma is primarily regulated at the transcriptional level, and is controlled by elements in the 5' flanking region and the first intron of the C1inh gene. Hep3B cells transfected with reporter constructs containing truncated segments between -738 and -81 of the 5' flanking region and stimulated with IFN-gamma expressed increased levels of chloramphenicol acetyl transferase. These data as well as the data obtained from studies using constructs with mutated IFN-gamma-activated sequence (GAS) indicate that the most proximal GAS element (GAS 4) that mapped to nucleotides -126 to -118 is responsible for this IFN-gamma responsiveness. Electrophoretic mobility shift assays using GAS 4 yielded a single band that appeared within 5 min after stimulation with IFN-gamma. In competition experiments, both GAS 4 and consensus GAS probes, but not a mutated GAS probe, competed for the GAS binding protein present in Hep3B and U-937 cell extracts. The identity of the GAS binding protein was confirmed using anti-STAT-1alpha Abs in supershift assays. The results indicate that STAT-1alpha binds to GAS 4, which is the primary element in the 5' flanking region responsible for IFN-gamma induction of the C1inh gene.


Diagnosis and Management of Intraoperative Colorectal Anastomotic Leaks: A Global Retrospective Patient Chart Review Study.
This targeted chart review study reports the first ever detailed global account of clinical approaches adopted to detect and manage anastomotic leaks identified during surgery in routine clinical practice. 156 surgeons from eight countries retrospectively extracted data from surgical records of 458 patients who underwent colorectal surgery with an identified intraoperative leak at the circular anastomosis. Demographic details, procedures, and outcomes were analyzed descriptively, by country. Most surgeries were performed laparoscopically (57.6%), followed by open surgeries (35.8%). The burden of intraoperative leaks on the healthcare system is driven in large part by the additional interventions such as using a sealant, recreating the anastomosis, and diverting the anastomosis to a colostomy bag, undertaken to manage the leak. The mean duration of hospitalization was 19.9 days. Postoperative anastomotic leaks occurred in 62 patients (13.5%), most frequently 4 to 7 days after surgery. Overall, country-specific differences were observed in patient characteristics, surgical procedures, method of diagnosis of intraoperative leak, interventions, and length of hospital stay. The potential cost of time and material needed to repair intraoperative leaks during surgery is substantial and often hidden to the healthcare system, potentially leading to an underestimation of the impact of this complication.


[History of foster care in the Czech Republic].
"The enlightment period" in the second half of the 18th century brought new view on the negative results of the institutional care in orphanages. The aim to improve the care of orphans and unattended children in the region of former Austrian Empire resulted in the year 1789 in the new law about the foster care. The law incorporated ten principles how to provide, control and finance the foster care in our region.


Is substance use associated with HIV cascade outcomes in Latin America?
The HIV care cascade has improved in Latin America over the last decade. However, the influence of alcohol and noninjected drug use (NIDU) on cascade outcomes is mostly unknown. This study estimated the association of alcohol and NIDU with retention in care, loss to follow up (LTFU), and virologic failure (VF). Individuals ≥18 years attending routine HIV clinic visits and completing the Rapid Screening Tool (RST; evaluating NIDU and ART adherence in 7-day recall period) during 2012-13 were followed up to 2015 in the Caribbean, Central and South America network for HIV epidemiology. Adjusted odds ratios (aOR) were calculated for the association of alcohol consumption and NIDU with retention in care by logistic regression; adjusted hazard ratios (aHR) were estimated for the associations with LTFU and VF by Cox regression. Among 3604 individuals, the proportions retained in care for one year were 84%, 79%, 72%, and 69% for patients reporting non-use, alcohol use, NIDU, and both alcohol and NIDU, respectively. For the same patient groups, the proportions LTFU over 18 months were 6%, 8%, 12%, and 13%, respectively. There were 1901 patients (53%) with HIV RNA results; VF proportions were similar between users and nonusers (ranging from 14-16%). After controlling for age, sex, study site, HIV transmission mode, time on ART, AIDS status, and CD4 count, neither alcohol use (aOR = 1.1, CI = 0.9-1.4; aHR = 1.0, CI = 0.8-1.3) nor NIDU (aOR = 1.3, CI = 0.9-1.8; aHR = 1.4, CI = 0.9-2.1) were significantly associated with retention or VF, respectively. However, both alcohol use (aHR = 1.2, CI = 1.02-1.4) and NIDU (aHR = 1.3, CI = 1.00-1.8) were associated with increased LTFU. Alcohol use and NIDU in a 7-day recall period increased the risk of being LTFU during the next 18 months, highlighting the need for routine screening and targeted interventions to keep these individuals in care and on ART.


Applicability of ELISA on buffer-eluates of capillary blood spotted on filter papers for the diagnosis and clinical staging of human schistosomiasis.
The relative concentrations of IgM and IgG antibodies (Ab) to Schistosoma mansoni soluble egg antigen (SEA) were evaluated in paired samples of venous blood sera and buffer-eluates of capillary blood drops dried on filter papers. The samples were obtained from school children at early and chronic stages of schistosomiasis diagnosed on the basis of history, clinical symptomatology and parasitological criteria. Enzyme-linked immunosorbent assay (ELISA), simultaneously performed, revealed paired samples to display comparable Ab levels in all cases. Samples from children with early schistosomiasis had specific IgM:IgG ratios greater than 1 [optical densities (O.D.) in sera and blood eluates of 0.77 +/- 0.32 and 0.68 +/- 0.30, respectively for IgM and 0.52 +/- 0.25 and 0.50 +/- 0.25 for IgG]. This ratio, however, was less than 1 in samples from chronically infected children (O.D. of 0.20 +/- 0.11 and 0.20 +/- 0.11 for IgM and 0.69 +/- 0.33 and 0.73 +/- 0.32 for IgG). The specific advantages of this simplified technique are the use of anti-SEA Abs in fingerstick blood eluates, rather than sera of venous blood to serologically diagnose schistosomiasis and to differentiate early from chronic infections particularly when used for mass screening, such as epidemiologic surveys.


Review of transforming teamwork: Cultivating collaborative cultures.
Teams, especially interdisciplinary teams, are now common in integrated care settings. Many behavioral health providers and physicians will work in teams for much of their careers. Transforming Teamwork: Cultivating Collaborative Cultures is a timely publication that aims to help teams improve by offering the rationale and guidance for enhancing teams and teamwork. The book is broadly applicable to organizations that want to learn how to improve teams, including organizations with diverse, interdisciplinary team members. The authors, with backgrounds in education, leadership development, and instruction, provide practical help to leaders and team members to improve their collective efficacy and produce actionable learning. Transforming Teamwork is framed around a "triple helix" of transformational teamwork: psychological safety, constructive conflict, and actionable team learning. The book unpacks the why and how of effective teamwork, providing useful tools and techniques for groups and individuals to apply in real-world settings. Part 1 explores how psychological safety underlies transformative teamwork by allowing for open exchange of different ways of thinking among team members. Part 2 describes the important role of conflict in teamwork and how team members can cultivate productive responses to conflict. Part 3 aims to guide teams past personal biases to carefully ask questions, listen, develop coherent team knowledge, and take action. Proficiency scales throughout the book clearly illustrate what unproductive, productive, and transformative types of teamwork look like. This practical guide satisfactorily provides answers to questions about the why and how of effective teams and teamwork. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Lutein-Based pH and Photo Dual-Responsive Novel Liposomes Coated with Ce6 and PTX for Tumor Therapy.
Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from -45.45 to -28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.


Association of acute myocardial infarction with seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.
The aim of this nationwide age- and sex matched longitudinal follow up study is to determine the risk of acute myocardial infarction (AMI) associated with the seropositive rheumatoid arthritis (RA) population in Korea. Patient data were collected from the National Health Insurance Service Health Screening cohort. RA was identified using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD). A total of 2,765 patients were enrolled in the seropositive RA group from January 1, 2004 to December 31, 2015 from the NHIS. The control group consisted of 13,825 subjects. The 12-years AMI incidence rate for each group was calculated using the Kaplan-Meier method. A Cox proportional-hazards regression analysis was used to estimate the hazard ratio of AMI. During the follow-up period, 39 patients (1.41%) in the seropositive RA group and 111 (0.80%) in the control group experienced AMI (P = 0.003). The hazard ratio of AMI in the seropositive RA group was 3.879 (95% confidence interval (CI): 2.64-5.68) after adjusting for age and sex. The adjusted hazard ratio of AMI in the seropositive RA group was 4.212 (95% CI: 2.86-6.19) after adjusting for demographics and comorbid medical disorders. According to subgroup analysis, in male and female and the non-diabetes and non-hypertension and hypertension and dyslipidemia and non-dyslipidemia subgroups, AMI incidence rates were significantly higher in the seropositive RA group than in the control group. Our nationwide longitudinal study suggests an increased risk of AMI in seropositive RA patients.


Bacterial β-ketoacyl-acyl carrier protein synthase III (FabH) as a target for novel antibacterial agents design.
In bacterial type II fatty acid biosynthesis (FAS-II), β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) initiates the first condensation of acyl-CoA and malonyl-ACP to form acetoacetyl-ACP. Its key role for organism survival and specificity to bacteria make it as an essential target for the discovery of novel antibacterial agents. Over the last decade, several structures of FabH from diverse microorganisms have been solved, giving detailed information about the three-dimensional features of the catalytic pocket. This has facilitated the rational design of FabH inhibitors, which provides a framework for future development of antibiotics against multi-drug resistant strains. This review covers recent advances in the biochemical and structural research of FabH and updates the main families of related inhibitors.


Spectroscopic and ab initio investigation of 2,6-difluorophenylacetylene-amine complexes: coexistence of C-H···N and lone-pair···π complexes and intermolecular coulombic decay.
Binary complexes of 2,6-difluorophenylacetylene with methylamine, dimethylamine, trimethylamine and triethylamine were investigated using one colour resonant two photon ionization and infrared-optical double resonance spectroscopic techniques combined with high level ab initio calculations. All four amines form CAc-H···N hydrogen-bonded complexes. Additionally trimethylamine and triethylamine form complexes characterized by Lp···π interactions, due to the electron deficient nature of the phenyl ring of 2,6-difluorophenylacetylene. The Lp···π interacting structure of the 2,6-difluorophenylacetylene-trimethylamine complex is about 1.5 kJ mol(-1) higher in energy than the CAc-H···N hydrogen-bonded structure, which is the global minimum. Energy decomposition analysis indicates that the electrostatics and dispersion interactions favour the formation of CAc-H···N and Lp···π complexes, respectively. Interestingly the CAc-H···N hydrogen-bonded complex of 2,6-difluorophenylacetylene-triethylamine showed a smaller shift in the acetylenic C-H stretching frequency than the 2,6-difluorophenylacetylene-trimethylamine complex. The observed fragmentation of the binary complexes of 2,6-difluorophenylacetylene with the four amines following resonant two-photon ionization can be explained on the basis of the intermolecular coulombic decay process.


One-pot synthesis of redox-responsive polymers-coated mesoporous silica nanoparticles and their controlled drug release.
A versatile one-pot strategy for the preparation of reversibly cross-linked polymer-coated mesoporous silica nanoparticles (MSNs) via surface reversible addition-fragmentation chain transfer (RAFT) polymerization is presented for the first time in this paper. The less reactive monomer oligo(ethylene glycol) acrylate (OEGA) and the more reactive cross-linker N,N'-cystaminebismethacrylamide (CBMA) are chosen to be copolymerized on the external surfaces of RAFT agent-functionalized MSNs to form the cross-linked polymer shells. Owing to the reversible cleavage and restoration of disulfide bonds via reduction/oxidation reactions, the polymer shells can control the on/off switching of the nanopores and regulate the drug loading and release. The redox-responsive release of doxorubicin (DOX) from this drug carrier is realized. The protein adsorption, in vitro cytotoxicity assays, and endocytosis studies demonstrate that this biocompatible vehicle is a potential candidate for delivering drugs. It is expected that this versatile grafting strategy may help fabricate satisfying MSN-based drug delivery systems for clinical application.


Erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition in critically ill patients.
The purpose of this study is to evaluate erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric enteral nutrition (EN). Twenty critically ill patients with a gastric residual >150 mL while receiving EN were randomized to receive 4 intravenous doses of erythromycin 250 mg or metoclopramide 10 mg, each administered every 6 hours. Acetaminophen 975 mg was administered enterally at baseline and after the fourth dose. Acetaminophen peak plasma concentration (Cmax), concentration at 60 minutes (C(60)), time to Cmax (Tmax), and area under the concentration-time curve from 0 to 60 minutes (AUC(0-60)) were determined. Residual volumes and feeding rates were recorded. Compared with baseline, erythromycin increased Cmax (9.5 +/- 6.1 mg/L to 17.7 +/- 11.9 mg/L, P < .01), C(60) (5.4 +/- 3.5 mg/L to 12.9 +/- 7.6 mg/L, P < .01), and AUC(0-60) (3.5 +/- 3.0 mg.h/L to 12.5 +/- 8.7 mg.h/L, P < .01), while metoclopramide increased only AUC(0-60) (4.4 +/- 2.8 mg.h/L to 9.5 +/- 3.8 mg.hr/L, P < .05). Neither agent significantly reduced Tmax. Both erythromycin and metoclopramide reduced residual volumes (122 +/- 48 mL to 36 +/- 48 mL, P < .01, and 103 +/- 88 mL to 21 +/- 23 mL, P < .05, respectively) and allowed increased feeding rates (17 +/- 23 mL/h to 45 +/- 21 mL/h, P < .05, and 14 +/- 17 mL/h to 44 +/- 22 mL/h, P < .05, respectively). Both agents facilitate tolerance to intragastric EN, but erythromycin may be more effective than metoclopramide for enhancing gastric motility.


Pexelizumab and survival in cardiac surgery.
A recent international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care included pexelizumab, a recombinant monoclonal antibody to the component 5 of the complement system, among the ancillary (i.e. non-surgical) drugs/techniques/strategies that might influence survival rates in patients undergoing cardiac surgery. The consensus conferences state that "A subgroup analysis of a meta-analysis of randomized controlled trials suggested that pexelizumab might reduce mortality (longest follow up available, up to 6 months) in patients undergoing coronary artery bypass grafting. Pexelizumab was not included among the most important topics of the consensus conference as it was the only topic that did not receive a sufficient percentage of votes from the audience (32% at the first round and 35% at the second round). Pexelizumab is no longer on the market, however, the concept of reducing the generalized inflammatory process accompanying cardiopulmonary bypass deserves further investigation.


Localization of beta catenin across the domain of odontogenic lesions: A systematic review.
CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell. Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result. Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours. High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.