Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems.
The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidylglycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45 nm. Depending on the initial protein concentration, the loading of insulin in SNEDDS varied between 0.27 and 1.13 wt%. The therapeutic protein was found to be efficiently protected from enzymatic degradation by intestinal enzymes (i.e., trypsin, α-chymotrypsin). The SNEDDS formulation exhibited increased mucus permeability and did not appear to be affected by ionic strength. The incorporation of INS/DMPG in SNEDDS prevented an initial burst release of insulin. INS/DMPG loaded SNEDDS were found to be non-cytotoxic up to a concentration of 2mg/ml. According to the reported results, the incorporation of the hydrophobic ion pair of INS/DMPG in SNEDDS could be regarded as a promising strategy for the oral delivery of insulin.


[Unusual garland-like lichen planopilaris of the face].
Report about two male patients with uncommon lichen planopilaris of the face. The disease resolved with garland-like vermiculate scars.


Papillary tumor of the pineal region in pediatric populations: An additional case and systematic review of a rare tumor entity.
Papillary tumors of the pineal region (PTPR) are a rare tumor entity first described in 2003, later codified in the 2007 WHO tumor classification system. PTPRs most commonly occur in the third and fourth decades, with exceedingly rare presentations in pediatric populations. Herein, we present an additional case of a 10-year-old female found to have PTPR in conjunction with Trisomy 21 managed successfully with cerebrospinal fluid diversion and gross total resection (GTR). Three years after resection she has returned to baseline without recurrence. We also performed a comprehensive review of the current literature discussing the diagnosis, treatment, and pathophysiologic correlations in children. Diagnosis and management of PTPRs is a topic that is increasingly garnering attention in the literature given the recent characterization of this tumor entity. However, relatively little is known about the presentation of PTPRs in pediatric populations. In adults, PTPRs have been linked with several chromosomal and genetic abnormalities; however this correlation is limited in pediatric literature. Although GTR is the mainstay for treatment, the application of adult treatment protocols may not be advisable due to age and the developmental changes of the CNS in children.


Monte Carlo simulation of expected outcomes with the AcrySof toric intraocular lens.
To use a Monte Carlo simulation to predict postoperative results with the AcrySof Toric lens, evaluating the likelihood of over- or under-correction using various toric lens selection criteria. Keratometric data were obtained from a large patient population with preoperative corneal astigmatism <= 2.50D (2,000 eyes). The probability distributions for toric marking accuracy, surgically induced astigmatism and lens rotation were estimated using available data. Anticipated residual astigmatism was calculated using a Monte Carlo simulation under two different lens selection scenarios. This simulation demonstrated that random errors in alignment, surgically induced astigmatism and lens rotation slightly reduced the overall effect of the toric lens. Residual astigmatism was statistically significantly higher under the simulation of surgery relative to an exact calculation (p < 0.05). The simulation also demonstrated that more aggressive lens selection criteria could produce clinically significant reductions in residual astigmatism in a high percentage of patients. Monte Carlo simulation suggests that surgical variability and lens orientation/rotation variability may combine to produce small reductions in the correction achieved with the AcrySof Toric IOL. Adopting more aggressive lens selection criteria may yield significantly lower residual astigmatism values for many patients, with negligible overcorrections. Surgeons are encouraged to evaluate their AcrySof Toric outcomes to determine if they should modify their individual lens selection criteria, or their default surgically induced astigmatism value, to benefit their patients.


In vitro activity of an essential oil against Leishmania donovani.
The in vitro antileishmanial effect of the essential oil from Chenopodium ambrosioides against Leishmania donovani was investigated. The product showed significant activity against promastigotes and amastigotes, with a 50% effective concentration of 4.45 and 5.1 microg/mL, respectively. The essential oil caused an irreversible inhibition of the growth of promastigotes after a treatment with 100 or 10 microg/mL for 1 or 24 h, respectively. The phagocytic activity of the macrophages was preserved at a concentration toxic to the parasite. The essential oil from C. ambrosioides may be a potential candidate drug to development a new agent to combat this parasitic disease.


An economic evaluation of the cost of diabetic foot ulcers: results of a retrospective study on 239 patients.
To evaluate the cost of foot ulcers in diabetic patients. Retrospective pharmacoeconomic study using direct and indirect costs (sick leave days) from the perspective of French social security system. 239 patients were included in the study by 80 physicians who treat diabetic patients suffering from foot ulcers. Initially identified by telephone survey, these physicians were primarily endocrinologists/diabetologists, general practitioners and surgeons. Average monthly costs in the treatment of foot ulcers were 697 euro; for outpatient care, 1556.20 euro; for hospital care (day treatment and short stays), and 34.76 euro; for sick leaves. When hospitalization was required, it represented approximately 70% of the average cost for foot ulcers. The portion of outpatient costs was principally generated by medical and paramedical treatments, and interventions carried out by healthcare personnel. On the other hand, medication only represented 10% of total costs. The initial severity of the pathology was a determinant clinical factor of high healthcare costs. In addition, the more recent the lesion was, the higher the cost of treatment. Amputation and follow-up by specialists were correlated to high costs as well, a logical result of these clinical factors. This analysis is the first to evaluate the cost of treating foot ulcers in such a large population of diabetic patients. The economic outcomes should help direct public authorities in their choices, particularly as regards the interest of treating these diabetes-related complications as early as possible.


Thermodynamic parameters for adsorption equilibrium of heavy metals and dyes from wastewater with low-cost adsorbents.
This note revisits the literature evaluating the thermodynamic parameters of adsorption equilibrium uptakes of heavy metals and dyes from water and wastewater streams using low-cost adsorbents derived from agricultural waste, industrial wastes, inorganic particulates, or some natural products. We highlighted the possible flaws in some adsorption studies when their thermodynamic parameters were assessed, since compensation effects during enthalpy and entropy evaluation were possibly overlooked.


Asian Hate, Minority Stress, and Religious Coping: A Study of Asian and Asian American Adults in the USA During the COVID-19 Pandemic.
Despite long being the target of racism, Asians and Asian Americans remain an understudied group regarding the mental health implications of racism. Even less is known about how Asians and Asian Americans may use religion to cope with racism and the resulting mental health implications. In this study, 330 Asian and Asian American adults from various regions of the USA were surveyed. The study results suggest that negative religious coping was associated with worsening depression, anxiety, and stress, particularly among Asian Indians, Asian Hindus, and Asian Muslims. In addition, negative religious coping may have exacerbated the deleterious effects of racism on mental health. Surprisingly, positive religious coping failed to provide any protection against racism-related mental health problems during the COVID-19 pandemic.


SAM50, a side door to the mitochondria: The case of cytotoxic proteases.
SAM50, a 7-8 nm diameter β-barrel channel of the mitochondrial outer membrane, is the central channel of the sorting and assembly machinery (SAM) complex involved in the biogenesis of β-barrel proteins. Interestingly, SAM50 is not known to have channel translocase activity; however, we have recently found that this channel is necessary and sufficient for mitochondrial entry of cytotoxic proteases. Cytotoxic lymphocytes eliminate cells that pose potential hazards, such as virus- and bacteria-infected cells as well as cancer cells. They induce cell death following the delivery of granzyme cytotoxic proteases into the cytosol of the target cell. Although granzyme A and granzyme B (GA and GB), the best characterized of the five human granzymes, trigger very distinct apoptotic cascades, they share the ability to directly target the mitochondria. GA and GB do not have a mitochondrial targeting signal, yet they enter the target cell mitochondria to disrupt respiratory chain complex I and induce mitochondrial reactive oxygen species (ROS)-dependent cell death. We found that granzyme mitochondrial entry requires SAM50 and the translocase of the inner membrane 22 (TIM22). Preventing granzymes' mitochondrial entry compromises their cytotoxicity, indicating that this event is unexpectedly an important step for cell death. Although mitochondria are best known for their roles in cell metabolism and energy conversion, these double-membrane organelles are also involved in Ca2+ homeostasis, metabolite transport, cell cycle regulation, cell signaling, differentiation, stress response, redox homeostasis, aging, and cell death. This multiplicity of functions is matched with the complexity and plasticity of the mitochondrial proteome as well as the organelle's morphological and structural versatility. Indeed, mitochondria are extremely dynamic and undergo fusion and fission events in response to diverse cellular cues. In humans, there are 1500 different mitochondrial proteins, the vast majority of which are encoded in the nuclear genome and translated by cytosolic ribosomes, after which they must be imported and properly addressed to the right mitochondrial compartment. To this end, mitochondria are equipped with a very sophisticated and highly specific protein import machinery. The latter is centered on translocase complexes embedded in the outer and inner mitochondrial membranes working along five different import pathways. We will briefly describe these import pathways to put into perspective our finding regarding the ability of granzymes to enter the mitochondria.


Estimation of correlation of lactate dehydrogenase subunits mole quota based on differences in substrate inhibition.
A kinetic method of estimating the mole quota ratios of the human lactate dehydrogenase (LDH) H and M subunits based on differences in substrate inhibition of LDH isoenzymes by lactate is porposed. Stability of kinetic constants for a prolonged period of time is demonstrated. The dependence of the activity ratios on the contribution of the mole quota of the M-subunit of LDH is studied under conditions of low and high substrate concentrations. The experimental and theoretical values show the following correlation: r = 0.998; p less than 0.001. A comparison of the method proposed with the electrophoretic method of LDH subunit estimation is made, the values obtained being in good agreement. No effect of the components of human diploid cell homogenate and only an insignificant effect of the blood serum components on the kinetic constants of LDH isoenzymes are shown. The applicability of the method to the estimation of the quantitative content of both LDH subunits in natural samples is demonstrated. The informational value of the method is compared to that of other standard methods of LDH isoenzyme estimation.


Daily life physical activity in patients with chronic stage IV sarcoidosis: A multicenter cohort study.
Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DLPA). The aim of this prospective study was to measure DLPA in patients with chronic sarcoidosis and to determine its relationship to clinical and functional parameters. Fifty-three patients with chronic sarcoidosis and 28 healthy control subjects were enrolled in this multicenter prospective study. Two markers of DLPA (number of steps walked per day [SPD]) and total daily energy expenditure (TEE) were assessed for five consecutive days with a physical activity monitor. Pulmonary function, aerobic capacity (maximal oxygen uptake [VO2max]), exercise capacity (6-min walk test [6MWT]), and quality of life (self-reported questionnaires) were also evaluated. Comparisons of DLPA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DLPA parameters and patient characteristics were assessed in multivariable linear regression models. Patients with sarcoidosis walked significantly fewer SPD than did the control subjects (6395 ± 4119 and 11 817 ± 3600, respectively; P < 0.001 after adjustment for age, BMI, and sex). TEE was not significantly different between patients with sarcoidosis and healthy controls (median [interquartile range]: 2369 [2004-2827] and 2387 [2319-2876] kcal/day, respectively, P = 0.054 adjusted for age, BMI, and sex). SPD showed significant positive correlations with 6MWT distance (Pearson's correlation, r = 0.32, 95% confidence intervals [95%CI] = 0.06, 0.55; P = 0.019), VO2max (r = 0.44, 95%CI = 0.17, 0.65; P = 0.002), and Visual Simplified Respiratory Questionnaire score (r = 0.44, 95%CI = 0.19, 0.64; P = 0.001), and a significant negative correlation with modified Medical Research Council questionnaire score (r = -0.38, 95%CI = -0.60, -0.10; P = 0.009). TEE was significantly correlated with BMI (r = 0.38, 95%CI = 0.13, 0.59; P = 0.004), forced expiratory volume in 1 second (r = 0.55, 95%CI = 0.33, 0.71; P < 0.001), total lung capacity (r = 0.44, 95%CI = 0.18, 0.64; P = 0.001), and forced vital capacity (r = 0.56, 95%CI = 0.34, 0.72; P < 0.001). In multivariable analysis, SPD remained associated only with VO2max. Patients with chronic sarcoidosis appear to have reduced DLPA mainly because of compromised VO2max.


Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients.
Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients. Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible. We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance. Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments.


Comparison of the effects of abstinence on MDMA and cocaine self-administration in rats.
3,4-Methylenedioxymethamphetamine (MDMA) preferentially increases synaptic serotonin (5HT). This response was attenuated following repeated exposure but there was recovery as a result of abstinence. Effects of abstinence on self-administration of many drugs have been documented but the impact on MDMA self-administration is unknown. This study compared the effects of abstinence on MDMA and cocaine self-administration. Six-hour daily MDMA or cocaine sessions were conducted until a total of 350 mg/kg had been self-administered. Following this, rats were randomly assigned to either a 0- or 14-day abstinence group. Self-administration testing then continued for an additional 7 days. The latency to self-administer 350 mg/kg was shorter for rats that self-administered cocaine. The temporal distribution of responding within each test session also differed; MDMA self-administration was high during the first hour of each session, and decreased during subsequent hours, whereas cocaine self-administration was evenly distributed throughout each hour of the session. Abstinence decreased MDMA but not cocaine self-administration. The selective reduction of MDMA self-administration following abstinence is consistent with the idea that MDMA-stimulated 5-HT release is inhibitory to MDMA self-administration.


Effects of flowering plant's patch size on species composition of pollinator communities, foraging strategies, and resource partitioning in bumblebees (Hymenoptera: Apidae).
In 4 common Middle-European mainly bumblebee-pollinated plant species (Impatiens glandulifera, Echium vulgare, Aconitum napellus, Symphytum officinale) the influence of patch size on species composition of the pollinator community was studied. Short-tongued species were most dominant in large patches, while small patches were frequented by middle- and long-tongued bumblebees. This phenomenon was extremely obvious in Symphytum officinale and Aconitum napellus, where short-tongued species had bitten a hole in nearly every flower of large patches. Long-tongued species were forced to small patches, where nectarrobbing occurred only exceptionally. In small patches visitationrate (Number of visits per flower per hour) was not lower but either equal or even higher then in large patches. Nectar measurements in Echium vulgare showed, that not only the mean quantity of nectar but also the variance was lower in small patches. As a result, the possible gain can be predicted much more precisely in a small patch than in a large one, and bumblebees have less difficulties in making the right foraging decisions. According to this, foraging strategies depend on patch size. This was confirmed by a computer simulation. The conclusion can be drawn, that many bumblebee species are able to share the same resource by using different patch sizes. Since large flower patches occur mainly in man-made habitats, the dominance of short-tongued species in many bumblebee communities studied by other authors may be unnatural.


Nucleotide-Level Profiling of m⁵C RNA Methylation.
Mapping the position and quantifying the level of 5-methylcytosine (m(5)C) as a modification in different types of cellular RNA is an important objective in the emerging field of epitranscriptomics. Bisulfite conversion has long been the gold standard for detection of m(5)C in DNA but it can also be applied to RNA. Here, we detail methods for bisulfite treatment of RNA, locus-specific PCR amplification and detection of candidate sites by sequencing on the Illumina MiSeq platform.


Exudative epidermitis and porcine circovirus-2 infection in a Swedish SPF-herd.
An outbreak of exudative epidermitis (EE) among piglets in a Swedish SPF-herd initiated a survey for indications as to the cause of disease. The herd was established by caesarean section and has been closed to all new animal material, with the exception of semen for artificial insemination (AI). The study comprised serum samples from the SPF-herd over a 10-year period (n=109) and a close monitoring of animals in the herd during the period after the EE outbreak. Serum samples from conventional boars at the AI-station servicing the herd were also included (n=9). All serum samples were tested for antibodies to porcine circovirus-2 (PCV-2). In addition, 3-week-old piglets from three litters (n=24) farrowed close after the initial EE outbreak were closely monitored for clinical signs of skin disease, sampled for Staphylococcus hyicus, tested for antibodies to porcine parvovirus and in sequentially collected serum samples tested for interferon-alpha (IFN-alpha) and interleukin-6. The PVC-2 serology showed that animals in the herd were sero-negative at least until 2 months prior to the EE outbreak. During the period close after the EE outbreak the animals showed varying levels of antibodies to PCV-2 but all the tested animals had sero-converted 4 months later. The AI boars were also sero-positive to PCV-2 at the time of the EE outbreak. Animals in the SPF-herd remained sero-positive to PCV-2 during the following 7 years. In the monitored litters, one piglet had clinical EE and 15 piglets displayed defined erythemas on the abdomen. Fourteen of the piglets also had IFN-alpha in serum on one or more occasions during the study, indicating viral activity among the animals. S. hyicus was isolated from all of the piglets from the earliest sampling point (3 days of age) and onwards, irrespective of clinical signs. PCV-2 was isolated from lymph node tissue collected from one of the EE affected pigs.Further, increases in the number of stillborn piglets, small litters (<6 piglets) and repeat breeders could be correlated to the time of PCV-2 sero-conversion. Coincidence of active viral infection and sero-conversion to PCV-2 points to the virus as the cause of the EE outbreak and reproductive disturbances.


Impact of modified bladder neck suspension on early recovery of continence after robot-assisted radical prostatectomy (RARP).
The incontinence after RARP significantly decreases the quality of life in prostate cancer patients. A number of techniques have been introduced for the recovery of continence after RARP. Although, the mechanism of the continence recovery is still unclear. We aimed to evaluate the early recovery of continence after RARP by inducing early anterior adhesion and reducing the hypermobility of the urethra through the modified bladder neck suspension (BNS) procedure. From March 2018 to February 2020, a total of 227 consecutive patients who underwent RARP (by single surgeon) were included. Patients were divided into two groups based on operation procedure (Standard procedure vs BNS procedure). Demographics, perioperative variables, and pathologic outcome were analyzed. We assessed recovery of continence at 1, 3, 6 and 9 months after surgery. Postoperative recovery of continence defined as the use of no pad during 24 h. Multivariable logistic regression analyses were performed to evaluate independent predictors of the early recovery of continence at 1 month. We performed RARP with standard procedure (n = 106) or BNS procedure (n = 121). There was no statistical difference in perioperative variables between the two groups except anastomosis time (21.6 ± 12.9 vs 17.0 ± 7.6, p = 0.003). The pad free continence rate were 80.2% (standard group) and 91.3% (BNS group) at 9 month after RARP (p = 0.037). However, early continence rate (1mo) were significantly higher in the BNS group (12.3% vs 29.1%, p = 0.004). On multivariate logistic analyses, BNS procedure (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.03-7.45, p = 0.0426), age (OR 0.92, CI 0.86-0.98, p = 0.0154) were independent factor for early recovery of continence after RARP. The modified bladder neck suspension procedure showed significantly better outcomes than the standard procedure in terms of the early recovery of urinary continence.


Nitrogen Chemistry and Coke Transformation of FCC Coked Catalyst during the Regeneration Process.
Regeneration of the coked catalyst is an important process of fluid catalytic cracking (FCC) in petroleum refining, however, this process will emit environmentally harmful gases such as nitrogen and carbon oxides. Transformation of N and C containing compounds in industrial FCC coke under thermal decomposition was investigated via TPD and TPO to examine the evolved gaseous species and TGA, NMR and XPS to analyse the residual coke fraction. Two distinct regions of gas evolution are observed during TPD for the first time, and they arise from decomposition of aliphatic carbons and aromatic carbons. Three types of N species, pyrrolic N, pyridinic N and quaternary N are identified in the FCC coke, the former one is unstable and tends to be decomposed into pyridinic and quaternary N. Mechanisms of NO, CO and CO2 evolution during TPD are proposed and lattice oxygen is suggested to be an important oxygen resource. Regeneration process indicates that coke-C tends to preferentially oxidise compared with coke-N. Hence, new technology for promoting nitrogen-containing compounds conversion will benefit the in-situ reduction of NO by CO during FCC regeneration.


Author Correction: Treatment in myositis.
In the originally published version of this article, several references in Table 1 were incorrect. These errors have now been corrected in the HTML and PDF versions of the manuscript.


[Refraction after Implantation of Multifocal and Presbyopia-Correcting Intraocular Lenses].
Nowadays, further developments in the field of intraocular lenses offer a higher level of spectacle independence for our patients. As light gets scattered on different focal points a wider range of defocus is created. This greater defocus area makes it more difficult for us to determine the objective or subjective refraction. This contribution is concerned with the difficulties of measuring visual acuity in different intraocular lens designs and different measurement distances. Measuring refraction after implantation of a multifocal intraocular lens is a complex procedure and the experience of the examiner plays a crucial role. Retinoscopy, keratometry and the defocus curve are reliable methods for testing, while the auto refractometer, bichromatic testing and the cross-cylinder have limitations.


PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.
At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.


Familial coarctation of the aortic arch with bilateral ptosis: a new syndrome?
A Newfoundland family with the apparently unique syndrome of complex coarctation of the aortic arch, bilateral stenoses of the subclavian arteries, bilateral ptosis, sensorineural deafness, and bronchial asthma is reported. This syndrome appears to have affected at least four generations, and has the characteristics of autosomal dominant inheritance.


Examining Racial/Ethnic Disparities in Tobacco Dependence Treatment Among Medicaid Beneficiaries Using Fifty State Medicaid Claims, 2009-2014.
In the USA, low-income racial/ethnic minority groups experience higher smoking rates and greater smoking-related disease burden than their White counterparts. Despite the adverse effects, racial/ethnic minorities are less likely to access tobacco dependence treatment (TDT). Medicaid is one of the largest payers of TDT in the USA and covers predominantly low-income populations. The extent of TDT use among beneficiaries from distinct racial/ethnic groups is unknown. The objective is to estimate racial/ethnic differences in TDT use among Medicaid fee-for-service beneficiaries. Using a retrospective study design and 50 state (including the District of Columbia) Medicaid claims (2009-2014), we employed multivariable logistic regression models and predictive margin methods to estimate TDT use rates among adults (18-64) enrolled (≥ 11 months) in Medicaid fee-for-service programs (January 2009-December 2014) by race/ethnicity. The population included White (n = 6,536,004), Black (n = 3,352,983), Latinx (n = 2,264,647), Asian (n = 451,448), and Native American/Alaskan Native (n = 206,472) beneficiaries. Dichotomous outcomes reflected service use in the past year. Any TDT use was operationalized as any smoking cessation medication fill, any smoking cessation counseling visit, or any smoking cessation outpatient visit. In secondary analyses, we disaggregated TDT use into three separate outcomes. Results suggested that Black (10.6%; 95% CI = 9.9-11.4%), Latinx (9.5%; 95% CI = 8.9-10.2%), Asian (3.7%; 95% CI = 3.4-4.1%), and Native American/Alaskan Native (13.7%; 95% CI = 12.7-14.7%) beneficiaries had lower TDT use rates compared to White beneficiaries (20.6%). Similar racial/ethnic treatment disparities were identified across all outcomes. By identifying significant racial/ethnic disparities in TDT use between 2009 and 2014, this study provides a benchmark against which to measure recent interventions in state Medicaid programs improving equity in smoking cessation interventions.


Determination of thiols and disulfides via HPLC quantification of 5-thio-2-nitrobenzoic acid.
This work presents an assay for total thiols and total disulfides in biological samples via HPLC quantification of 5-thio-2-nitrobenzoic acid (TNB) derived from the reaction of thiols with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB, Ellman's reagent). This method also provides simultaneous quantification of glutathione (GSH) via the measurement of the GSH-DTNB adduct (GSH-TNB). By using 326nm as the detecting wavelength, the HPLC detection limit for TNB and the GSH-TNB adduct was determined to be 15 and 7.5pmol respectively. A recovery study with OVCAR-3 cells revealed that the recovery yields for TNB in the procedures for determining non-protein thiols, protein thiols, non-protein disulfides, and protein disulfides were 99.4+/-1.2% (n=3), 98.1+/-5.0% (n=3), 95.6+/-0.9% (n=3), and 96.6+/-2.3% (n=3) respectively. The recovery yield for GSH-TNB in the procedures for determining non-protein thiols, protein thiols, non-protein disulfides, and protein disulfides was 99.0+/-0.3% (n=3), 95.1+/-4.9% (n=3), 96.8+/-0.6% (n=3), and 95.1+/-2.9% (n=3) respectively. The reproducibility, expressed as the relative standard deviation for the analyte, for TNB was determined to be 2.8% (n=6) for non-protein thiols, 3.9% (n=6) for protein thiols, 3.6% (n=6) for non-protein disulfides and 4.6% (n=6) for protein disulfides. The reproducibility for GSH-TNB was determined to be 1.6% (n=6) for non-protein thiols and 2.6% (n=6) for non-protein disulfides. By comparing the amount of GSH determined in a biological sample before NaBH(4) reduction with that after the reduction, this method can provide information associated with thiol glutathionylation which would be useful for protein glutathionylation study. This method should be applicable to cellular, subcellular, protein, or other biomatrix samples for thiol and disulfide quantification and will be a useful analytical method in the study of thiol redox state and thiol glutathionylation.


Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure.
We investigated the possibility that major histocompatibility complex (MHC) class II antigens and interferon gamma, a product of activated T lymphocytes, play a role in human autoimmune oophoritis. MHC class II molecules initiate immune responses by presenting antigens to T-helper lymphocytes; interferon gamma can induce class II antigen expression at ectopic sites and has been implicated in the cause of various autoimmune disorders. We studied the expression of class II MHC antigens in ovaries from normal women of reproductive-age and from women with premature autoimmune ovarian failure. Immunoperoxidase technique applied to tissue sections of nine normal human ovaries revealed class II MHC antigen expression only on occasional cells of macrophage morphology; granulosa cells were negative regardless of stage of follicular maturation. In contrast, extensive and intense class II antigen expression was observed in granulosa cells in ovarian biopsy sections from four patients with premature autoimmune ovarian failure. Immunofluorescence and radioimmunoassay techniques used to detect and quantitate MHC antigens revealed that class II antigen expression could be induced and class I MHC antigen expression was enhanced in granulosa cell cultures after the addition of interferon gamma. These data provide evidence that autoimmune oophoritis is associated with ectopic expression of MHC class II antigens by ovarian granulosa cells, and that this phenomenon can be induced by the immunologic cytokine interferon gamma.


Specific heart muscle disease in diabetes mellitus--a functional structural correlation.
We report the morphology of diabetic myocardium obtained by endomyocardial biopsy in 16 diabetics. The material was divided into three groups. The first comprised six patients with unexplained cardiomegaly and obscure congestive cardiac failure. The second group, also of six patients, had no cardiac signs and symptoms but exhibited abnormal systolic time intervals. The third group, of 4 patients, was without any cardiac symptoms or signs and had normal systolic time intervals. The vascular and extravascular changes observed were more pronounced in the symptomatic group, intermediate in the asymptomatic patients with abnormal intervals and least in those without symptoms and normal intervals. This provides supporting evidence for the existence of a specific primary myocardial disease in diabetes with good functional structural correlation.


Effects of chronic administration of the novel endothelin antagonist J-104132 on endothelial dysfunction in streptozotocin-induced diabetic rat.
1. The biosynthesis of endothelin-1 is increased in the diabetic state. So this peptide may cause diabetic vascular complications. We tested this possibility by chronically administering J-104132, a potent orally active mixed antagonist of endothelin A and B (ET(A)/ET(B)) receptors to streptozotocin (STZ)-induced diabetic rats and focusing on changes in endothelial function. 2. The acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in diabetic rats and this impairment was significantly attenuated following chronic administration of J-104132 (10 mg kg(-1), p.o., daily for 4 weeks). 3. In an in vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was not changed by the presence of J-104132 (3 x 10(-9) M). 4. The expression levels of the mRNA for endothelial nitric oxide synthase was comparable among aortae from the three groups (control, diabetic and chronically J-104132-treated diabetic). 5. The amount of superoxide anion was significantly greater in aortae from diabetic rats than in controls. Chronic J-104132 treatment significantly decreased the level of superoxide anion in diabetic rats. 6. The expression of the p22phox mRNA for the NADH/NADPH oxidase subunit was significantly increased in STZ-induced diabetic rats and this increase was completely prevented by chronic administration of J-104132. 7. These results suggest that in STZ-induced diabetic rats, ET-1 may be directly involved in impairing endothelium-dependent relaxation via increased superoxide-anion production.


Family-level relationships among the Australasian marsupial "herbivores" (Diprotodontia: Koala, wombats, kangaroos and possums).
The marsupial order Diprotodontia includes 10 extant families, which occupy all terrestrial habitats across Australia and New Guinea and have evolved remarkable dietary and locomotory diversity. Despite considerable attention, the interrelations of these families have for the most part remained elusive. In this study, we separately model mitochondrial RNA and protein-coding sequences in addition to nuclear protein-coding sequences to provide near-complete resolution of diprotodontian family-level phylogeny. We show that alternative topologies inferred in some previous studies are likely to be artifactual, resulting from branch-length and compositional biases. Subordinal groupings resolved herein include Vombatiformes (wombats and koala) and Phalangerida, which in turn comprises Petauroidea (petaurid gliders and striped, feathertail, ringtail and honey possums) and a clade whose plesiomorphic members possess blade-like premolars (phalangerid possums, kangaroos and their allies and most likely, pygmy possums). The topology resolved reveals ecological niche structuring among diprotodontians that has likely been maintained for more than 40 million years.


Molecular cloning, characterization and expression analysis of the PKZ gene in rare minnow Gobiocypris rarus.
Double-stranded RNA-activated protein kinase (PKR) plays an important role in interferon-induced antiviral responses, and is also involved in intracellular signaling pathways, including the apoptosis, proliferation, and transcription pathways. In the present study, a PKR-like gene was cloned and characterized from rare minnow Gobiocypris rarus. The full length of the rare minnow PKR-like (GrPKZ) cDNA is 1946 bp in length and encodes a polypeptide of 503 amino acids with an estimated molecular mass of 57,355 Da and a predicted isoelectric point of 5.83. Analysis of the deduced amino acid sequence indicated that the mature peptide contains two Zalpha domains and one S_TKc domain, and is most similar to the crucian carp (Carassius auratus) PKR-like amino acid sequence with an identity of 77%. Quantitative RT-PCR analysis showed that GrPKZ mRNA expression is at low levels in gill, heart, intestine, kidney, liver, muscle and spleen tissues in healthy animals and up-regulated by viruses and bacteria. After being infected by grass carp reovirus, GrPKZ expression was up-regulated from 24h post-injection and lasted until the fish became moribund (P<0.05). Following infection with Aeromonas hydrophila, GrPKZ transcripts were induced at 24h post-injection (P<0.05) and returned to control levels at 120 h post-injection. These data imply that GrPKZ is involved in antiviral defense and Toll-like receptor 4 signaling pathway in bacterial infection.


Characterisation of beeswax in works of art by gas chromatography-mass spectrometry and pyrolysis-gas chromatography-mass spectrometry procedures.
Pyrolysis (Py) with in situ derivatisation with hexamethyldisilazane-gas chroma-break tography-mass spectrometry (GC-MS) and a gas chromatography-mass spectrometry procedure based on microwave-assisted saponification were used to identify the organic components in small sized beeswax samples. With the latter procedure quantitative recoveries can be made and hydrocarbons, alcohols and omega-1-diols in the neutral fraction, and fatty acids and omega-1-hydroxy acids in the acidic fraction can be efficiently separated and detected. Both procedures were used to characterise a wax anatomic sculpture "The Plague" (1691-1694) by Gaetano Zumbo, resulting in the identification of beeswax and a Pinaceae resin. The GC-MS analysis brought to light some essential differences in beeswax composition between the raw material and the old modelled wax thus giving some clear indications about the recipe used by the sculptor.


Open Seldinger-Guided Femoral Artery Cannulation Technique for Thoracic Aortic Surgery.
Debate regarding the optimal cannulation site for aortic surgery continues. We report our recent experience with a simple and rapid open Seldinger-guided technique for femoral cannulation. Aside from speed and simplicity (no need for arterial incision or suture closure), this technique has the added benefit that the distal limb continues to be perfused, as no arterial snare is required. We recently began routinely utilizing an open Seldinger-guided technique for femoral artery cannulation. The artery is exposed surgically but cannulated by guidewire inside a pursestring without arterial incision. The pursestring is simply tied when decannulation is performed. We report our experience with the routine application of this technique from August 2011 to April 2015. We reviewed the outcome of 337 consecutive peripheral arterial cannulations performed for thoracic aortic surgery (303 femoral, 34 axillary) using the open Seldinger technique. Within the femoral cannulation group, the hospital survival rate was 97% (295 of 303). The survival rate for elective operations was 98% (277 of 283), and 90% (18 of 20) for emergent/urgent. Seldinger-guided femoral cannulation was performed for replacement of the ascending/aortic arch in 88% (266 of 303), the descending thoracic aorta in 7% (22 of 303), and the thoracoabdominal aorta in 5% (15 of 303). There were no instances of intraoperative malperfusion phenomena, arterial dissection, or vascular injury or rupture. No patients had postoperative acute limb ischemia. Local wound complications were observed in 1% of patients (3 of 303). The stroke rate was 1.6% (5 of 303). The same open Seldinger technique was also used without complication in the axillary cannulation group. An open Seldinger-guided femoral (or axillary) cannulation technique is quick and easy to perform, with minimal vascular or other complications and extremely low risk of stroke. This technique is recommended for its speed, simplicity, and effectiveness, and for its preservation of distal arterial flow (which is occluded with the traditional arterial incision/arterial snare technique).


Emc, a negative HLH regulator with multiple functions in Drosophila development.
Expression and functional analyses of Emc have demonstrated that it is a prototype for a protein required for multiple processes in development. Initially characterized as a negative regulator of sensory organ development, it was later found to regulate many other developmental processes and cell proliferation. Its ability to block the function of bHLH proteins by forming heterodimers, which are ineffective in DNA binding, accounts for the role of Emc in preventing the acquisition of several cell fates which are under the control of bHLH proteins. However, while maintaining this repressive molecular mechanism, emc also appears to act as a positive regulator of differentiation.


Laboratory apparatus for studying visual space perception of the pilot in simulated night approaches to landing.
The device provides a relatively inexpensive means of assessing a number of perceptual and human factors parameters in the night approach to landing situation. A technique for modeling airport runway lighting is described along with electromechanical and optical systems for precise control of simulated approach speed, model slant, and direction in the visual field of the simulated radial approach axis. The realism of this display is enhanced by preservation of the natural relations of size and brightness of simulated runway lights to distance.


Low NK cell counts in peripheral blood are associated with inferior overall survival in patients with follicular lymphoma.
Host immune responses influence follicular lymphoma (FL) outcomes. To test our hypothesis that immune cells in blood reflect that response, we assessed by peripheral blood flow cytometry in 75 untreated FL patients the absolute counts of: lymphocytes (ALC), CD4(+)T (ACD4C), CD8(+)T (ACD8C) and natural killer (ANKC) cells. Low ANKC was the only parameter associated with inferior overall survival by univariate analysis (p=0.02), and trended to significance in multivariable analysis with ACD4C (p=0.08). Five (24%) patients with low initial ANKC died, while one (2%) with normal/high ANKC has died. In conclusion, evaluation of blood ANKC may be a useful indicator of outcome in previously untreated FL patients.


Chronic cough and a normal chest X-ray - a simple systematic approach to exclude common causes before referral to secondary care: a retrospective cohort study.
Chronic cough is common in the community and can cause significant morbidity. It is not clear how closely treatment guidelines are used in general practice, or how often specialist referral is indicated. We aimed to assess the management of chronic cough in primary care before referral to a cough clinic, and to assess the outcome of managing chronic cough with an approach of simple investigation and empirical treatment trials. Data were extracted from the records of all patients attending a district general hospital respiratory clinic over a two-year period with isolated chronic cough lasting ⩾8 weeks. The clinic assessed symptoms with a cough-severity visual analogue scale and the Leicester Cough Questionnaire. Among 266 patients, the most frequent diagnoses were asthma (29%), gastro-oesophageal reflux (22%) and angiotensin-converting enzyme inhibitor use (14%). In all, 12% had unexplained chronic cough. Common diagnoses had often not been excluded in primary care: only 21% had undergone spirometry, 86% had undergone chest radiography and attempts to exclude asthma with corticosteroids had been made only in 39%. In the clinic few investigations were conducted that were not available in primary care. Substantial improvements in symptoms occurred with a median (interquartile range) total of 2 (2-3) clinic visits. We estimated that 87% of patients could have been managed solely in primary care; we did not identify distinguishing characteristics among this group. Most cases of chronic cough referred to secondary care could be managed with a simple and systematic approach, which is potentially transferrable to a community setting.


Reduced use of diagnostic obstetric ultrasound in Norway. Result of consensus panel recommending routine screening in pregnancy?
To investigate the practice of obstetric ultrasound in Norway before and 2 years after a consensus conference recommending routine screening. Material, method: Two national representative materials sampled with a 2-year interval are compared. The average number of examinations was reduced from 2.46 to 2.2 (p = 0.014). Obstetrical institutions practising screening examined their patient less frequently than non-screening institutions (2.10 vs. 2.75 times, p less than 0.001 whereas in 1986 the converse was the case. Screening has become more widespread, and a more rational practice has developed.


Contribution of apoptosis to the phenotypic changes of adrenocortical cells in primary culture.
The aim of this study was to evaluate the occurrence and physiological consequences of apoptosis in primary cultures of bovine adrenocortical cells (of fasciculata-reticularis origin). Under ACTH-free culture conditions, we observed apoptotic cells in the cell layer and the accumulation of apoptotic bodies in the culture medium. These were hardly detectable in ACTH-supplemented cultures. Under ACTH-free conditions, the DNA content of apoptotic bodies collected over 48 h represented up to 10-15% of that of the cell layer at the onset of the culture (as compared to 3% in ACTH-supplemented cultures). Past the fourth day of culture in the absence of ACTh, most cells lacked several markers of their originating fasciculata-reticularis phenotype and progressively evolved to an undifferentiated phenotype. The vast majority of the apoptotic bodies released during the first 4 days of culture were immunoreactive for P450 17 alpha. Inversely, during the same period of time, the proliferating cells (PCNA-positive) did not appear to express P450 17 alpha. Therefore, apoptosis could contribute, together with dedifferentiation, to the phenotype shift observed in ACTH-depleted cultures of adrenal fasciculata-reticularis cells. These observations also characterize this endocrine cell system as an in vitro model for the study of hormone-repressed apoptosis.


Regeneration of axillary hair and related phenomena after removal of deep dermal and subcutaneous tissue by a special "shaving" technique.
A subcutaneous tissue "shaver" was used in the treatment of axillary bromhidrosis. Regeneration of axillary hair was observed postoperatively even if subcutaneous tissue and dermis were removed almost up to the level of sebaceous ducts. Hair regenerated more often in male patients whose sebaceous glands and follicular isthmus were designedly left intact than in female patients whose sebaceous glands were designedly removed completely. Some function of apocrine and eccrine glands tends to return over a two-year period.


Magnetic Resonance Elastography of the Brain.
Magnetic resonance elastography (MRE) is an emerging noninvasive technique, an alternative to palpation for quantitative assessment of biomechanical properties of tissue. In MRE, tissue stiffness information is obtained by a 3-step process, propagating mechanical waves in the tissues, measuring the wave propagation using modified magnetic resonance (MR) pulse sequences, and generating the quantitative stiffness maps from the MR images. MRE is clinically used in patients with liver diseases, whereas its applications in other organs are still being investigated. At present, the pediatric studies are in the initial stage and preliminary results promise to provide additional information about tissue characteristics.


Two-stage operation for synchronous triple primary cancer of the esophagus, stomach, and ampulla of Vater: report of a case.
A 69-year-old man with jaundice was diagnosed with cancer of the ampulla of Vater by endoscopic retrograde cholangiopancreatography and abdominal computed tomography. A screening gastrointestinal endoscopy showed middle thoracic esophageal cancer and early gastric cancer on the anterior wall of the lower gastric body. We chose a two-stage operation for synchronous triple primary cancer of the esophagus, stomach, and ampulla of Vater, in order to safely perform the curative resection of these three cancers. The first-stage operation consisted of a right transthoracic subtotal esophagectomy with mediastinal and cervical lymph node dissection, an external esophagostomy in the neck, and a gastrostomy. Thirty-five days after the first surgery, a total gastrectomy with regional lymph node dissection, and a pancreatoduodenectomy with Child's reconstruction were performed as the second-stage surgery. Esophageal reconstruction was achieved using the ileocolon via the percutaneous route without vascular anastomosis.


Speciation of iodine in high iodine groundwater in china associated with goitre and hypothyroidism.
Iodine intake affects the occurrence of disease in a population. Excessive iodine intake may be caused by a high iodine content of drinking water. Tap water in few locations in Europe contains up to 139 microg/L mostly bound to humic substances, probably leaching from marine sediments in the aquifers. Even higher iodine contents have been found in Chinese waters, previously shown to associate with goitre and hypothyroidism. The aims were to elucidate speciation of high iodine groundwater from deep wells in China and to compare with high iodine waters from Europe. Water was sampled from eight wells in five villages along Bohai Bay, China. Macro-molecules and low molecular weight (MW) substances were separated by size exclusion chromatography (high performance liquid chromatography, Superose 12 HR 10/30, buffer 0.1 M Tris, pH 7.0). Organic material was evaluated by A280 and iodine in fractions measured by the Ce/As method after alkaline incineration. Iodine content of well water varied from 135 to 880 microg/L (median 287 microg/L). The amount of organic material in water was low with A280, <1-5 mAU. The chromatographic traces were similar between samples: One peak of iodine eluted around K (AV) 0.65 corresponding to MW 5 kDa (humic substances) and one peak at V (total) (iodide/low MW substances). The fraction of iodine in macro-molecules, suggested to be humic substances, varied from 8% to 70% (median 27%). Iodine and peak absorbance were associated (p = 0.006). In conclusion, iodine in iodine-rich deep well water in northern China may have marine origin and may associate with humic substances, comparable to shallow well iodine-rich water in Europe. High iodine intake from iodine-rich water suggests the cause of endemic goitre and hypothyroidism in some areas in China being iodine.


Predicting who responds to spinal manipulative therapy using a short-time frame methodology: Results from a 238-participant study.
Spinal manipulative therapy (SMT) is among the nonpharmacologic interventions that has been recommended in clinical guidelines for patients with low back pain, however, some patients appear to benefit substantially more from SMT than others. Several investigations have examined potential factors to modify patients' responses prior to SMT application. The objective of this study was to determine if the baseline prediction of SMT responders can be improved through the use of a restricted, non-pragmatic methodology, established variables of responder status, and newly developed physical measures observed to change with SMT. We conducted a secondary analysis of a prior study that provided two applications of standardized SMT over a period of 1 week. After initial exploratory analysis, principal component analysis and optimal scaling analysis were used to reduce multicollinearity among predictors. A multiple logistic regression model was built using a forward Wald procedure to explore those baseline variables that could predict response status at 1-week reassessment. Two hundred and thirty-eight participants completed the 1-week reassessment (age 40.0± 11.8 years; 59.7% female). Response to treatment was predicted by a model containing the following 8 variables: height, gender, neck or upper back pain, pain frequency in the past 6 months, the STarT Back Tool, patients' expectations about medication and strengthening exercises, and extension status. Our model had a sensitivity of 72.2% (95% CI, 58.1-83.1), specificity of 84.2% (95% CI, 78.0-89.0), a positive likelihood ratio of 4.6 (CI, 3.2-6.7), a negative likelihood ratio of 0.3 (CI, 0.2-0.5), and area under ROC curve, 0.79. It is possible to predict response to treatment before application of SMT in low back pain patients. Our model may benefit both patients and clinicians by reducing the time needed to re-evaluate an initial trial of care.


Microscopic detection and identification of various substitute vegetable tissues in ground horseradish.
Turnip root, parsnip root, potato tuber, and corn kernels have been used as adulterants in the preparation of horseradish sauce and horseradish powder. The diagnostic histological features of horseradish root and its known adulterants are described and illustrated as viewed through a polarizing microscope with cross polars and a first order red plate. A procedure which can be used to detect any of the known adulterants in horseradish is described. The adaptation of a previously reported semiquantitative method is also discussed.


Neurohumoral response and stress hyperglycemia in myocardial infarction.
Hyperglycemia is associated with an increased risk for death in acute coronary syndromes. This could be related to underlying glucose metabolism abnormalities or be caused by a counter-regulatory stress response. However, there is a paucity of data on the relationship between stress hormones, hyperglycemia, and clinical outcomes in myocardial infarction. Single-center, prospective, observational study. Patients admitted to the coronary care unit with a diagnosis of myocardial infarction were included. On admission, blood samples were obtained to measure serum glucose, cortisol, and catecholamines. A second sample was obtained at 8 AM after 48 h from admission. There was a mild and positive correlation between serum cortisol and glucose (Spearman's rho = 0.24, p = 0.005), and no significant correlation was found between glucose and catecholamines. A similar correlation between cortisol and glucose among diabetics and non-diabetics was observed. Significantly higher serum cortisol and glucose levels were present in patients who developed heart failure or died during hospitalization. The association between glycemia and mortality lost significance in multivariate analysis, with a significant interaction term with cortisol (p = 0.003). Cortisol is a key responsible for stress hyperglycemia, and its deleterious effects on the cardiovascular system could be the cause for worst outcomes associated with hyperglycemia in ACS. Further research is warranted to ascertain this relationship and to investigate potential therapeutic targets.


Effect of reduced glutathione treatment on selenosis, blood selenium concentration and glutathione peroxidase activity after repeated short-term selenium exposure in buffalo calves.
Effects of repeated feeding of selenium, when given alone or along with reduced glutathione, on whole blood selenium levels, selenosis and glutathione peroxidase activity, was studied in buffalo calves. After feeding 2.5 mg/kg of BW sodium selenite, good correlation was found between the onset of selenosis and whole blood selenium concentrations. Adverse effects appeared when the whole blood selenium concentrations increased above 2 microg/ml and mortality occurred when they exceeded 3.4 microg/ml. Reduced glutathione, given i.v. at 5 mg/kg of BW arrested the progress of selenosis and prevented mortality which was 100% in the sodium selenite supplemented group; also a reduced whole blood selenium concentration was noted. Whole blood selenium concentrations were a better and more sensitive indicator of selenium status than glutathione peroxidase activity alone.


Osteoporosis after cranial irradiation for acute lymphoblastic leukemia.
A prospective study was conducted to investigate the possibility of osteoporosis after treatment for childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL had the trabecular bone density of the spine evaluated by quantitative computed tomography, 6 to 98 months (mean 42 months) after completion of chemotherapy. The ALL survivors had significantly lower bone density than age-, gender-, and race-matched nonleukemic control subjects had (10% less, p less than 0.001); this decrease was accounted for solely by the subset of patients who had received cranial irradiation (n = 30; p less than 0.001). The relative reduction in bone density in ALL survivors was unrelated to age at the time of diagnosis or time without therapy. The effects on bone density of 18 Gy and of 22.5 to 25.2 Gy were indistinguishable. We conclude that survivors of ALL commonly have reduced bone density in the lumbar spine and suggest that the diminution is related to nervous system irradiation, not to the disease or to chemotherapy.


Persistent intrathecal interleukin-8 production in a patient with SARS-CoV-2-related encephalopathy presenting aphasia: a case report.
Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia. An 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy. The cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.


Functional analysis of the C(-188)A polymorphism of the human leptin promoter.
Mutational analysis of the promoter region of the leptin gene in morbidly obese Finnish subjects had revealed a previously unidentified C(-188)A polymorphism in the proximal promoter that showed a weak association with elevated serum leptin levels in obese male carriers of the variant (-188A) allele. In this study we demonstrated that neither expression of reporter gene constructs driven by wild-type (-188C) or variant (-188A) proximal promoter regions, nor assay of binding of cellular proteins reveal a genotype-related difference in promoter activity.


The appearance of phagocytic microglia in the postnatal brain of Niemann Pick type C mice is developmentally regulated and underscores shortfalls in fine odor discrimination.
The loss of NPC1 or NPC2 function results in cholesterol and sphingolipid dyshomeostasis that impairs developmental trajectories, predisposing the postnatal brain to the appearance of pathological signs, including progressive and stereotyped Purkinje cell loss and microgliosis. Despite increasing evidence reporting the activation of pro-inflammatory microglia as a cardinal event of NPC1 disease progression at symptomatic stages both in patients and preclinical models, how microglia cells respond to altered neurodevelopmental dynamics remains not completely understood. To gain an insight on this issue, we have characterized patterns of microglia activation in the early postnatal cerebellum and young adult olfactory bulb of the hypomorphic Npc1nmf164 mouse model. Previous evidence has shown that both these areas display a number of anomalies affecting neuron and glial cell proliferation and differentiation, which largely anticipate cellular changes and clinical signs, raising our interest on how microglia interplay to these changes. Even so, to separate the contribution of cues provided by the dysfunctional microenvironment we have also studied microglia isolated from mice of increasing ages and cultured in vitro for 1 week. Our findings show that microglia of both cerebellum and olfactory bulb of Npc1nmf164 mice adopt an activated phenotype, characterized by increased cell proliferation, enlarged soma size and de-ramified processes, as well as a robust phagocytic activity, in a time- and space-specific manner. Enhanced phagocytosis associates with a profound remodeling of gene expression signatures towards gene products involved in chemotaxis, cell recognition and engulfment, including Cd68 and Trem2. These early changes in microglia morphology and activities are induced by region-specific developmental anomalies that likely anticipate alterations in neuronal connectivity. As a proof of concept, we show that microglia activation within the granule cell layer and glomerular layer of the olfactory bulb of Npc1nmf164 mice is associated with shortfalls in fine odor discrimination.


Promoting Ge Alloying Reaction via Heterostructure Engineering for High Efficient and Ultra-Stable Sodium-Ion Storage.
Germanium (Ge)-based materials have been considered as potential anode materials for sodium-ion batteries owing to their high theoretical specific capacity. However, the poor conductivity and Na+ diffusivity of Ge-based materials result in retardant ion/electron transportation and insufficient sodium storage efficiency, leading to sluggish reaction kinetics. To intrinsically maximize the sodium storage capability of Ge, the nitrogen doped carbon-coated Cu3Ge/Ge heterostructure material (Cu3Ge/Ge@N-C) is developed for enhanced sodium storage. The pod-like structure of Cu3Ge/Ge@N-C exposes numerous active surface to shorten ion transportation pathway while the uniform encapsulation of carbon shell improves the electron transportation, leading to enhanced reaction kinetics. Theoretical calculation reveals that Cu3Ge/Ge heterostructure can offer decent electron conduction and lower the Na+ diffusion barrier, which further promotes Ge alloying reaction and improves its sodium storage capability close to its theoretical value. In addition, the uniform encapsulation of nitrogen-doped carbon on Cu3Ge/Ge heterostructure material efficiently alleviates its volume expansion and prevents its decomposition, further ensuring its structural integrity upon cycling. Attributed to these unique superiorities, the as-prepared Cu3Ge/Ge@N-C electrode demonstrates admirable discharge capacity, outstanding rate capability and prolonged cycle lifespan (178 mAh g-1 at 4.0 A g-1 after 4000 cycles).


Broad specificity alkaline proteases efficiently reduce the visual scaling associated with soap-induced xerosis.
In xerotic skin, the proteolysis of desmosomes is reduced leading to the accumulation of corneocytes on the surface of the skin. The effect of proteases applied topically to soap-induced xerotic skin was evaluated using a five-point visual scale. The visual scaling associated with soap-induced xerosis could be ameliorated by the topical application of exogenous protease. Bovine pancreatic chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were all capable of facilitating the reduction in visual scaling in a short time. Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were the most weight-efficient at delivering this clinical effect. The reduction in scaling could be achieved either by occluded application of an aqueous enzyme solution or by a two-step unoccluded application first of an aqueous enzyme solution followed by a commercial moisturizer. Morphological and immunological analysis of bacterial enzyme-treated skin revealed that topically applied protease specifically induced the degradation of the desmosomes thereby promoting desquamation. These results indicate that topical application of protease can significantly and rapidly reduce the visual scaling associated with soap-induced xerosis by promoting desmosome degradation within the corneocyte clumps.


Protonic diffusion in high-pressure ice VII.
Near ambient pressures, molecular diffusion dominates protonic diffusion in ice. Theoretical studies have predicted that protonic diffusion will dominate at high pressures in ice. We measured the protonic diffusion coefficient for the highest temperature molecular phase of ice VII at 400 kelvin over its entire stable pressure region. The values ranged from 10(-17) to 10(-15) square meters per second at pressures of 10 to 63 gigapascals. The diffusion coefficients extrapolated to high temperatures close to the ice VII melting curve were less by a factor of 10(2) to 10(3) than a superionic criterion of approximately 10(-8) square meters per second, at which protons would diffuse freely.


The Clinical Application of Preexpanded and Prefabricated Super-Thin Skin Perforator Flap for Reconstruction of Post-Burn Neck Contracture.
Based on our previous animal study, we applied the "bridging effect" to the neighboring axial flap through preexpansion and prefabrication of a skin perforator flap as a new method to reconstruct a large skin defect after release of severe neck burn scar contracture. Twelve patients suffering from severe post-burn cervical contractures underwent reconstruction of large skin defects after surgical release of severe scar contractures with preexpanded and prefabricated super-thin skin perforator flaps supplied primarily by a number of perforators via the "bridging effect" from the branches of the adjacent arteries as 2-stage procedures. During the first-stage operation, 2 tissue expanders were placed accordingly, and this was followed by a subsequent second-stage procedure where an expanded super-thin skin perforator flap was transposed to reconstruct a large neck skin defect. Follow-up was between 6 months and 3 years in this series. All super-thin skin perforator flaps survived in this series with primary healing except one with a distal flap necrosis that was treated with a subsequent skin graft. All patients have had a good contour with improved range of motion in the neck. The preexpansion and prefabrication of a super-thin skin perforator flap can possibly improve the anastomoses between neighboring subdermal vascular plexuses and extend the supplying area of these vessels to the flap. This method may provide a favorable super-thin skin flap that can be used for reconstruction of large neck defects after release of post-burn cervical scar contracture as demonstrated in this case series.


Different Technical Applications of Carbon Nanotubes.
Carbon nanotubes have been of great interest because of their simplicity and ease of synthesis. The novel properties of nanostructured carbon nanotubes such as high surface area, good stiffness, and resilience have been explored in many engineering applications. Research on carbon nanotubes have shown the application in the field of energy storage, hydrogen storage, electrochemical supercapacitor, field-emitting devices, transistors, nanoprobes and sensors, composite material, templates, etc. For commercial applications, large quantities and high purity of carbon nanotubes are needed. Different types of carbon nanotubes can be synthesized in various ways. The most common techniques currently practiced are arc discharge, laser ablation, and chemical vapor deposition and flame synthesis. The purification of CNTs is carried out using various techniques mainly oxidation, acid treatment, annealing, sonication, filtering chemical functionalization, etc. However, high-purity purification techniques still have to be developed. Real applications are still under development. This paper addresses the current research on the challenges that are associated with synthesis methods, purification methods, and dispersion and toxicity of CNTs within the scope of different engineering applications, energy, and environmental impact.


An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger.
The intrarectal route has been shown to be an alternative to parenteral therapy for the treatment of acute uncomplicated malaria. We conducted an open randomized clinical study of intrarectal Quinimax (a Cinchona alkaloids association) (20 mg/kg, then 15 mg/kg every 8 h) vs. intravenous Quinimax (8 mg/ kg infused over 4 h every 8 h) for 2 d in 76 children (39 in the intrarectal and 37 in the infusion groups) with cerebral falciparum malaria in Niger. This treatment was followed by oral chloroquine (10 mg/kg/d for 3 d). The primary end points of the study were fatal outcome and coma recovery time. In the intrarectal group, 35 children were cured (90%) and 4 died. In the infused group, 28 were cured (76%) and 9 died; mean coma recovery times were 34.6 h (SD = 12.8) and 33.0 h (SD = 14.1) for the intrarectal and infused groups, respectively. None of the differences was significant. Both treatments were well tolerated and no anal irritation was observed with intrarectal Quinimax. These findings suggest that intrarectal Quinimax can be an alternative to intravenous administration for rapid onset childhood cerebral malaria in the rural tropics, where the safety of parenteral administration cannot be guaranteed.


Tetracycline-Cu(II) photo-induced fragmentation of serum albumin.
The protein-damaging potential of photosensitized tetracycline hydrochloride alone and in combination with the metal ion Cu(II) was assessed using serum albumin as a model protein. Exposure of tetracycline to white light in an aqueous solution triggered the generation of significant amounts of reactive oxygen species (ROS) and engendered substantial protein damage. The appearance of distinct low-molecular-mass protein bands on 10% SDS-polyacrylamide gel ascertained the tetracycline concentration-dependent fragmentation of albumin. Photoexcited tetracycline in combination with 100 microM Cu(II) enhanced the protein fragmentation process with concurrent increase in free radical production. The significant release of acid-soluble amino groups and carbonyl groups from treated albumin provided quantitative estimation of protein fragmentation at 0-1.0 mM concentrations of tetracycline. Cu(II) ions per se did not cause any perceptible protein damage. The results with free radical quenchers suggested the role of hydroxyl radicals (*OH) in tetracycline-Cu(II)-induced protein fragmentation, as no superoxide dismutase (SOD)-mediated quenching effect was noted. The generation of free radicals upon tetracycline photoexcitation and consequent protein fragmentation may be considered as important factors in augmentation of tetracycline-induced phototoxic responses.


Quantitative assessment of macular microvasculature and radial peripapillary capillary plexus in the fellow eyes of patients with retinal vein occlusion using OCT angiography.
To evaluate the macular microvasculature and radial peripapillary capillary (RPC) plexus in the fellow eyes of patients diagnosed with unilateral retinal vein occlusion (RVO), using optical coherence tomography angiography (OCTA). Seventy-two fellow eyes of patients with unilateral RVO and 74 healthy control eyes were consecutively enrolled. All subjects underwent a complete ophthalmological assessment, including optical coherence tomography (OCT) and OCTA measurements. Foveal avascular zone (FAZ) area, macular vessel density (VD), and perfusion density (PD) of the superficial capillary plexus (SCP) were measured. The perfusion and flux index (FI) of the RPC plexus were measured using a 4.5mm×4.5mm ONH angiography scan acquisition protocol. The mean macular ganglion cell-inner plexiform layer (GC-IPL), and retinal nerve fibre layer (RNFL) in the inferior quadrant were significantly thinner in the fellow eyes of RVO patients compared to control eyes (P=0.010 and P=0.043, respectively). The mean macular VD in the outer ring was significantly lower in fellow eyes of RVO patients compared to control eyes (P=0.027). The mean RPC perfusion showed no significant difference between fellow eyes of RVO patients and control eyes in the four quadrants (P>0.05, all). The mean peripapillary global, inferior and nasal FI were significant lower in the fellow eyes of RVO patients compared to control eyes (P=0.033, P=0.008, P=0.009, respectively). In the fellow eyes of RVO patients, macular VD was significantly lower in the outer region, and peripapillary structural and microvascular alterations were remarkable in the inferior quadrant. The results of this study showed that the presence of RVO might be related to retinal microvasculature changes in both the macular and peripapillary regions of the unaffected fellow eyes.


Predictors of vertigo in the emergency department: The preved study.
Acute vertigo (sense of motion) can be the sole manifestation of a posterior circulation stroke, and often gets missed in the emergency department (ED). The studies for evaluation of central vertigo have focused on physical exam findings, which require expertise and may not be suitable for rapid triage by a nurse in ED or by paramedics. This cross sectional study included retrospective chart review of patients 18 years of age and older who presented to the Adult ED with acute dizziness or vertigo during the calendar year 2017. All the patients with a diagnosis of central or peripheral vertigo were included in the final analysis. Sensitivity, specificity, Likelihood Ratio of positive result (LR (+)) and Likelihood Ratio of negative result (LR (-)) for central and peripheral vertigo were calculated for risk factors, symptoms and physical examination features. Chi-squared test and univariate logistic regression were used to evaluate statistical correlation and to calculate the prevalence odds ratio (POR). Two hundred and forty nine out of 505 (49.3%) patients presenting with dizziness had vertigo. Of these, 14 had central vertigo and 163 had peripheral vertigo. Statistically significant variables were: constant symptoms of vertigo (p 0.000- POR 8.7, 95% confidence interval (CI) 2.3-33.1), no change in symptoms with head movement (p 0.000- POR 10.2, 95% CI 3.0-35.4), dysmetria (p 0.000- POR 56.8, 95% CI 5.8-557.1), and unsteady gait (p 0.000- POR 13.3, 95% CI 3.3-54.3). The sensitivity and specificity to detect central vertigo were 100% and 66.4% respectively if the patient had either unsteady gait, constant symptoms, or no change in symptoms with head movement, [VAIN triad (Vertigo- Ataxia, Incessant, or Non-positional)]. We suggest that triage with VAIN triad can be used to design prospective studies to develop a triage algorithm for the detection of central vertigo in the ED.


Quality improvement strategies enhance primary care dietetics: A systematic review and meta-analysis.
Quality improvement strategies have been widely applied in health care; however, little is known about their use in primary care dietetics. This review aims to describe and evaluate the effectiveness of quality improvement strategies that seek to improve patient outcomes by enhancing dietetic care compared to standard dietetic care. The study employed a systematic review and meta-analysis design following PRISMA guidelines and included studies up to March 2021. Studies were included if they used a randomised controlled trial (RCT) design to evaluate the effect of a quality improvement strategy applied to care delivered by a dietitian on patient outcomes. A meta-analysis was conducted where there were sufficient studies with homogeneous populations and outcome measures. Twelve RCTs (n = 1604) met the inclusion criteria for review and five studies (n = 511) were eligible for meta-analysis for glycated haemoglobin in patients with type 2 diabetes. The most frequently reported quality improvement strategies addressed disease management programs (58%), patient education (67%), group care (42%) and patient self-management (42%). A positive intervention effect was reported in 50% of the included studies. A low grade of evidence supported a positive intervention effect for quality improvement intervention by a dietitian for glycated haemoglobin (pooled mean difference = -0.39% with 95% confidence interval = -0.70 to -0.08, p = 0.01) in n = 511 patients with type 2 diabetes mellitus. Interventions aimed at enhancing quality in primary care dietetic practice support improvements in patient outcomes. Further research on quality improvement interventions for patient outcomes is required to strengthen the evidence base in this important topic.


Electrically controlled Michael addition: Addressing of covalent immobilization of biological receptors.
Electrically addressed covalent immobilization of biomolecules to the defined electrodes of an electrode array is described. It is based on Michael addition of the thiol group of biomolecules to α,β-unsaturated carbonyl groups of benzoquinone. This "click" reaction was tested by immobilization of a number of thiolated compounds on the simplest array consisting of two gold electrodes coated by a self-assembled monolayer of benzoquinone-terminated hexanethiol. Electrically controlled binding of hexanethiol, ferrocenylhexanethiol, human serum albumin and thiol-terminated single-stranded DNA (ssDNA) was investigated. The binding was studied using cyclic voltammetry, X-ray photoelectron spectroscopy and surface plasmon resonance. The reaction requires the oxidized state of the benzoquinone moiety; this can be reached by applying of a moderate anodic potential to the electrode. Surface plasmon resonance measurements demonstrated that the thiol-modified ssDNA immobilized by this technique binds complementary synthetic oligonucleotides or PCR-amplified DNA fragments. The developed technology of electrical addressing of covalent immobilization can be applied for fabrication of sensor arrays.


Arthroscopic staple capsulorrhaphy for recurrent anterior shoulder instability.
Beginning in 1983, the principles of staple capsulorrhaphy of the shoulder utilizing arthroscopic techniques were applied to the treatment of patients with recurrent anterior shoulder instability. This paper describes the results of arthroscopic staple capsulorrhaphy of the shoulder in the first 25 consecutive cases in which these techniques were utilized. The patient population includes 4 females and 19 males, 2 of whom underwent bilateral staged procedures. Eleven of the patients had documented recurrent anterior dislocations while the remaining 12 patients were determined to have subluxation of the shoulder. The average age of the patient population was 23 years. Follow-up averaged 36 months. Results were determined by utilizing a strict 100 point rating scale as described by Rowe. Utilizing this scale, 67% of patients achieved good or excellent results. Five patients came to undergo additional surgical procedures. There were no complications of infection or neurovascular injury, but one patient suffered staple impingement upon the humeral head leading to excoriation thereof and secondary pain. An average loss of external rotation of 9 degrees, as compared to the contralateral shoulder, was noted postoperatively.


A developmental overview of child and youth sports in society.
This article provides a brief review of sport participation for children and adolescents from psychological, physical, and social developmental perspectives. The following areas are reviewed: the relationship between normal developmental readiness and sporting participation; the potential positive and negative aspects of athletic participation for the child and adolescent; the effects of sporting participation on self-concept; potential adverse physical and psychological effects; recent research regarding motivation for youth sports participation; proposed recommendations for guidelines in youth sport programs; a social perspective on sports in the United States; the current and future role of child and adolescent psychiatrists; and future challenges for sport psychiatry.


Multiscale time-frequency method for multiclass Motor Imagery Brain Computer Interface.
Motor Imagery Brain Computer Interface (MI-BCI) has become a promising technology in the field of neurorehabilitation. However, the performance and computational complexity of the current multiclass MI-BCI have not been fully optimized, and the intuitive interpretation of individual differences on motor imagery tasks is seldom investigated. In this paper, a well-designed multiscale time-frequency segmentation scheme is first applied to multichannel EEG recordings to obtain Time-Frequency Segments (TFSs). Then, the TFS selection based on a specific wrapper feature selection rule is utilized to determine optimum TFSs. Next, One-Versus-One (OvO)-divCSP implemented in divergence framework is used to extract discriminative features. Finally, One-Versus-Rest (OvR)-SVM is utilized to predict the class label based on selected multiclass MI features. Experimental results indicate our method yields a superior performance on two publicly available multiclass MI datasets with a mean accuracy of 80.00% and a mean kappa of 0.73. Meanwhile, the proposed TFS selection method can significantly alleviate the computational burden with little accuracy reduction, demonstrating the feasibility of real-time multiclass MI-BCI. Furthermore, the Motor Imagery Time-Frequency Reaction Map (MI-TFRM) is visualized, contributing to analyzing and interpreting the performance differences between different subjects.


Stable Isotope Sequential Derivatization for Linkage-Specific Analysis of Sialylated N-Glycan Isomers by MS.
Sialylated N-glycans play pivotal role in several important biological and pathological processes. Their sialyl-linkage isomers, mostly α-2,3- and α-2,6-linked, act differently during the cellular events and several diseases. While mass spectrometry (MS) technology is a powerful tool in N-glycome analysis, it still suffers from an inability to distinguish linkage isomers of native N-glycans. Herein, we described a sequential selective derivatization method, by which α-2,6- and α-2,3-linked sialic acids are sequentially labeled with methylamide incorporated with a different stable isotope. Isobaric labeling avoids inducing bias in ionization efficiency and chromatographic behavior. In optimized reaction conditions, high derivatization selectivity (∼99%) was achieved for both α-2,3- and α-2,6-linked sialic acid. High accuracy of quantitation within a dynamic range of 2 orders of magnitude and high reproducibility (CV < 20%, n = 3) were demonstrated using standard glycans and multisialylated N-glycans. Finally, this method was applied in profiling the N-glycome of serum from CRC patients, where a level of six sialyl-linkage isomers were found to be altered significantly compared with that from healthy individuals.


CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer.
Infiltrating CD1a(+) dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (P<0.001), tumour size (P<0.01) and lymph node status (P<0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P=0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.


Cytogenetic analysis of azoospermic patients: karyotype comparison of peripheral blood lymphocytes and testicular tissue.
The objective was to compare the results of a complete chromosomal, genetic and histological investigation in 13 azoospermic men with the results of the intracytoplasmic sperm injection (ICSI) procedure. Peripheral blood samples were used for the measurement of follicle-stimulating hormone (FSH) levels, chromosomal analysis, microdeletions in the azoospermia factor (AZF) region of the Y chromosome and cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis. Testicular tissue was used for histological scoring and cytogenetic evaluation. Peripheral blood cytogenetic analysis revealed a normal male karyotype in all cases. Chromosomal analysis from testicular tissue revealed a mosaicism for the terminal deletion of chromosome 22 with a breakpoint site at 22q13 in one patient with congenital bilateral absence of the vas deferens (CBAVD). Deletions in the AZFa, ATFb, and AZFc regions were not detected. The CFTR mutational analysis showed normal results in all patients. Cytogenetic evaluation of testicular tissue should be performed in non-obstructive and obstructive azoospermic patients as well as in patients with multiple failed IVF and recurrent spontaneous abortion.


Sufficient vitamin D is favorable for children with persistent and chronic immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia in the absence of other disorders. Vitamin D (VD) has been shown to modulate the immune system and its deficiency is linked to many immunological disorders. Supplementation with VD in ITP has promising results. This work aims at evaluating VD values in children with persistent and chronic ITP and the effect of its deficiency on disease severity and treatment response. A case-control study including 50 persistent and chronic ITP patients and 50 healthy controls was conducted. 25 OH vitamin D level was determined using ELISA technique. VD median value was significantly higher among the control group than that of the patients' group (28 vs 21.5 and p = 0.002). Severe deficiency was detected significantly more among the patients' group than the control group (12 (24%) vs 3 (6%), p = 0.048) respectively. Forty-four percent of complete responders belong to sufficient VD category ((15/34) ~ 44% (p = 0.005)) representing all patients with sufficient VD status (n = 15). Also, a positive correlation between serum level of vitamin D and mean PLT count was observed (r = 0.316, p value = 0.025). Sufficient vitamin D was associated with better treatment response and less disease severity. Vitamin D supplementation may be a new therapeutic option for chronic ITP.


Effect of temperature and sunlight on the leachability potential of BPA and phthalates from plastic litter under marine conditions.
This study investigates the leaching potential of several additives embedded in six different plastic types when exposed to extreme simulated marine conditions for 140 days. The findings achieved herein contribute to a better understanding of the impact of macro- and microplastics leaching harmful compounds (bisphenol A (BPA) and phthalates) in the marine environment when exposed to harsh climatic conditions. Leachability experiments showed that bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and BPA were detected in seawater (SW) samples. Furthermore, while analysing 100 mL of SW per each sample, the total leachate concentrations of the identified compounds ranged from 5 μg/L to 123 μg/L, after 140 days of exposing a total of 120 plastic samples (96 samples micro- and 24 macro-plastics) to SW conditions It was observed that the leaching of DEHP was promoted by wave abrasion, high temperature and sunlight, while the leaching of DBP was favoured by wave abrasion. Findings showed that polypropylene (PP) was the most attributable plastic type in the leaching of DBP with an average concentration of 5.3 μg/L, whereas high-density polyethylene (HDPE) was the most responsible plastic-type for the leaching of DEHP, with an average concentration of 123 μg/L. Our results suggest that most of the phthalates and BPA will, ultimately, leach out to the SW environment after a longer period.


Avidity as a criterion for diagnosis of human strongyloidiasis increases specificity of IgG ELISA.
This study evaluates the inclusion of the IgG avidity index in ELISA to detect anti-Strongyloides stercoralis IgG. The ELISA index revealed 70% of specificity. With the inclusion of screening AI, specificity increased to 80%. IgG avidity complemented traditional IgG ELISA by eliminating some of the suspected or false positive cases.


Evaluation of World Health Organization partograph implementation by midwives for maternity home birth in Medan, Indonesia.
to assess the effectiveness of promoting the use of the World Health Organization (WHO) partograph by midwives for labour in a maternity home by comparing outcomes after birth. Medan city, North Sumatera Province, Indonesia. 20 midwives who regularly conducted births in maternity homes, randomly allocated into two equal groups. cluster randomised-control trial. under supervision from a team of obstetricians, midwives in the intervention group were introduced to the WHO partograph, trained in its use and instructed to use it in subsequent labours. there were 304 eligible women with vertex presentations among 358 labouring women in the intervention group and 322 among 363 in the control group. Among the intervention group, 304 (92.4%) partographs were correctly completed. From 71 women with the graph beyond the alert line, 42 (65%) were referred to hospital. Introducing the partograph significantly increased referral rate, and reduced the number of vaginal examinations, oxytocin use and obstructed labour. The proportions of caesarean sections and prolonged labour were not significantly reduced. Apgar scores of less than 7 at 1min was reduced significantly, whereas Apgar scores at 5mins and requirement for neonatal resuscitation were not significantly different. Fetal death and early neonatal death rates were too low to compare. a training programme with follow-up supervision and monitoring may be of use when introducing the WHO partograph in other similar settings, and the findings of this study suggest that the appropriate time of referral needs more emphasis in continuing education. the WHO partograph should be promoted for use by midwives who care for labouring women in a maternity home.


[Ethics in clinical research: contextualizing and reductionist problem definitions, forms of ethical reflection and some particular implications].
The present paper starts off with a short outline of issues, conflicts, and goals of ethical reflection about clinical research. It is then argued that non-reductionist, patient-centred ethics should critically reflect on medically preformed problem definitions, ways of problem solution, and evaluations. The shortcomings of such preformed perceptions and interpretations are illustrated using the examples of dementia research, and the complexities of the notion of risk. A more comprehensive approach including the perceptions, interpretations, and evaluations of the patients' perspective necessitates a form of ethical reflection which takes into account the social and cultural contexts of clinical research, and which therefore relies on concepts and methods of the cultural sciences (in particular history, sociology, and cultural anthropology). The decision for a reductionist, or for a contextualising mode of ethical reflection represents in itself a value decision and needs to be explicitly justified.


Perception of Portuguese nurses: clinical supervision and quality indicators in nursing care.
to describe nurses' perception of the influence of clinical supervision on improving quality indicators in nursing care. exploratory research with a qualitative approach, carried out with 16 nurses using the focus group. Data processing emerged from lexicographical textual analysis, resorting to Descending Hierarchical Classification and similarity analysis. 80.0% retention of 185 text segments with six-class construction. The words were represented by four graphs (supervisor, audit, care, and process); and three subgraphs (implementation, sharing and knowledge). in the perception of nurses, supervision influences quality indicators in nursing care.


Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands.
Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class of mu opioid receptor agonists.


Projecting global oil palm expansion under zero-deforestation commitments: Direct and indirect land use change impacts.
In the last three decades, global production of oil palm has boomed, which has partly come at the expense of tropical rainforests. Recognizing this, many companies operating in the palm oil industry have committed to eliminate deforestation from their operations, often referred to as zero-deforestation commitments (ZDCs). Here, we estimate that if ZDCs are fully adopted and enforced across all sectors and geographies, the global extent of oil palm plantations may be 11 M ha or 40% smaller in 2030 than in a business-as-usual (BAU) scenario that assumes no compliance with ZDCs. As a result of such land-sparing effects, we estimate that 96 M ha of forests are saved from conversion, of which, 17% would otherwise have been converted (directly or indirectly) due to expanding oil palm plantations. Overall, these figures suggest that ZDCs have the potential to deliver major environmental benefits if they are fully adopted and enforced.