Induction of the synthesis of an additional family of long-chain dolichols in the yeast Saccharomyces cerevisiae. Effect of starvation and ageing.
The yeast Saccharomyces cerevisiae strain W303 synthesizes in the early logarithmic phase of growth dolichols of 14-18 isoprene residues. The analysis of the polyisoprenoids present in the stationary phase revealed an additional family which proved to be also dolichols but of 19-24 isoprene residues, constituting 39% of the total dolichols. The transfer of early logarithmic phase cells to a starvation medium lacking glucose or nitrogen resulted in the synthesis of the longer chain dolichols. The additional family of dolichols represented 13.8% and 10.3% of total dolichols in the glucose and nitrogen deficient media, respectively. The level of dolichols in yeast cells increased with the age of the cultures. Since both families of dolichols are present in stationary phase cells we postulate that the longer chain dolichols may be responsible for the physico-chemical changes in cellular membranes allowing yeast cells to adapt to nutrient deficient conditions to maintain long-term viability.


Developmental delay: identification and management at primary care level.
Developmental delays are common in childhood, occurring in 10%-15% of preschool children. Global developmental delays are less common, occurring in 1%-3% of preschool children. Developmental delays are identified during routine checks by the primary care physician or when the parent or preschool raises concerns. Assessment for developmental delay in primary care settings should include a general and systemic examination, including plotting growth centiles, hearing and vision assessment, baseline blood tests if deemed necessary, referral to a developmental paediatrician, and counselling the parents. It is important to follow up with the parents at the earliest opportunity to ensure that the referral has been activated. For children with mild developmental delays, in the absence of any red flags for development and no abnormal findings on clinical examination, advice on appropriate stimulation activities can be provided and a review conducted in three months' time.


Technique Tricks for the Gleich-Koutsogiannis Surgical Procedure for Correction of the Adult Acquired Flatfoot.
Gleich-Koutsogiannis is a widely known extra-articular closing calcaneal osteotomic technique for correction of the adult flatfoot. Absolute care must be observed during each procedural step to avoid undesirable drawbacks, such as nerves and tendons lesions, incorrect fixation, and hardware painful prominence. It is the purpose of this report to introduce tricks to critical steps in order to improve the technique and minimize potential surgical complications.


Analysis of biofilm production and expression of adhesion structures of circulating Clostridioides difficile strains from Mexico.
Clostridioides difficile biofilms are believed to protect the pathogen from antibiotics, in addition to potentially contributing to recurrent infections. Biofilm production of 102 C. difficile isolates was determined using the crystal violet staining technique, and detachment assays were performed. The expression levels of cwp84 and slpA genes were evaluated by real-time PCR on selected isolates. More than 70% of isolates (75/102) were strong biofilm producers, and the highest detachment of biofilm was achieved with the proteinase K treatment (>90%). The overall mean expression of cwp84 was higher in RT027 than in RT001 (p=0.003); among strong biofilm-producing strains, the slpA expression was lower in RT027 than in RT001 (p<0.000). Proteins seem to have an important role in the biofilm's initial adherence and maturation. slpA and cwp84 are differentially expressed by C. difficile ribotype and biofilm production level.


[Laparoscopic management for nonpalpable testis].
In this series, we investigated the efficacy and advantage of laparoscopy for management of nonpalpable testis. Laparoscopic examination was performed in 10 boys, involving one with bilateral nonpalpable testis and 9 with a unilateral nonpalpable testis and a contralateral normal one, between August 1991 and September 1993 in our institution. Three testis were diagnosed as intraabdominal and 8 testis were diagnosed as probably intracanalicular with laparoscopy. Two boys with 3 intracanalicular testis underwent laparoscopic clipping of testicular vessels, and about 6 months later, they underwent the second stage of 2-stage Fowler-Stephens orchiopexy. Eight boys, diagnosed as probably intracanalicular type by laparoscopy, underwent surgical exploration with inguinal incision. Of 8 patients, only 1 boy underwent 1-stage orchiopexy, and the other 7 boys underwent orchiectomy because their gonads were extremely hypoplastic. About 1 year after orchiopexy, 3 testes were normal in both size and location. Laparoscopy seems to be useful for both evaluation and treatment of the nonpalpable testis.


Fatigue in military aviation shift workers: survey results for selected occupational groups.
Shift workers are particularly vulnerable to increased sleepiness, chronic fatigue, and decreased performance, which can adversely impact productivity and safety in military flight operations. This study examined the association of specific risk factors including work context and shift system details (squadron: remotely piloted aircraft [RPAI vs. manned aircraft [MA]), work/rest guidelines (career field: crewmember vs. maintainer), and participation in deployed operations (environment: home base vs. deployed) on subjective fatigue using standardized and validated fatigue questionnaires. A cross-sectional survey of 172 U.S. Air Force (USAF) personnel was conducted from October 2004 to May 2005. The study sample was recruited from four different USAF occupational groups involved in some form of shift work to include irregular, rotational, or fixed shifts. Participants reported a mean (SD) of 6.6 (1.8) hours of sleep per day with no differences by squadron, career field, or environment. Mean daily sleep did not correlate with scores on the fatigue questionnaires. Mean scores on the fatigue questionnaires were associated with squadron (mean fatigue score: RPA > MA), but not with career field or environment. There were no significant interaction effects, nor were there significant effects based on the covariates age, gender, and rank. Work context, shift system details, or both appeared to best explain the observed differences in fatigue between USAF shift worker populations. Crewmember work/rest guidelines did not appear to be useful for mitigating fatigue associated with shift work. Shift work is intrinsically fatiguing, regardless of whether the shift worker is at home base or deployed.


A novel route to 2,3-pyrazol-1(5H)-ones via palladium-catalyzed carbonylation of 1,2-diaza-1,3-butadienes.
[reaction--see text] A novel Pd(0)-catalyzed carbonylation of both isolable 1,2-diaza-1,3-butadienes and those generated in situ by extrusion of SO(2) and CO(2) from heterocyclic precursors is described. The reaction proceeds at room temperature to 110 degrees C under 1-2 atm of CO to afford 2,3-pyrazol-1(5H)-ones in good to excellent yields. The effect of catalyst structure and stability on the carbonylation reaction is evaluated.


Association of socioeconomic and practical unmet needs with self-reported nonadherence to cancer treatment appointments in low-income Latino and Black cancer patients.
Treatment adherence, with minimal numbers of missed appointments, is an important determinant of survival among cancer patients. This study aims to determine if unmet financial, logistic, and supportive care needs predict self-reported adherence to cancer treatment appointments of chemotherapy and/or radiation among low-income ethnic minority patients. The sample included 1098 underserved Latino and Black patients recruited from cancer clinics in New York City through the Cancer Portal Project. Participants completed a survey which included sociodemographic, health-related questions and a needs assessment, in their preferred language. Patients' adherence to chemotherapy and/or radiation treatment appointments was assessed using a self-report. A sample of 1098 patients (581 Latino and 517 Black cancer patients) was recruited. Forty-two Latino cancer patients (7.4%) and 78 Black cancer patients (15.5%) reported missing treatment appointments. Patients, who experienced four or more unmet needs (odds ratios [OR] = 2.02-3.36), and those with unmet housing needs (OR = 3.10-3.31), were more likely to report missing cancer treatment appointments, regardless of their ethnicity/race. Black patients with unmet supportive care (OR = 2.27) and health insurance needs (OR = 3.80) were more likely to miss appointments. Amongst Latinos, legal health-related issues (OR = 2.51) was a significant predictor of missed appointments. Among ethnic minority cancer patients, unmet socioeconomic and supportive care needs, housing needs in particular, predicted patient-reported missed radiation, and/or chemotherapy appointments. Future research should focus on exploring the impact of practical and supportive unmet needs on adherence and development of interventions aiming to improve cancer treatment adherence.


Disturbances in the voluntary recruitment order of anterior tibial motor units in bradykinesia of Parkinsonism.
The recruitment of motor units is studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies that the recruitment order is different in tonic and in phasic activities; in tonic activity the recruitment order is stable and low frequency units are always recruited before high frequency units; in phasic activity, however, the recruitment order is unstable and units with a higher frequency range may be recruited before units with lower frequency range. In this investigation the shifts between tonic and phasic recruitment order in voluntary contraction were compared in normal subjects and in patients with severe bradykinesia of Parkinsonism. Upon initiation of a voluntary contraction in a normal subject, phasic recruitment order may be used for a few 100 msec but tonic recruitment order then takes over. In bradykinetic patients, however, this shift from phasic to tonic recruitment order is delayed. After termination of tonic voluntary contraction in a normal subject, phasic recruitment order can again be used after a few seconds. In bradykinetic patients, however, the shift back from tonic to phasic recruitment order is also delayed. In favourable experimental situations the shift from phasic to tonic recruitment order can be normalized by passive stretch of the muscle and the shift from tonic to phasic recruitment pattern by unloading the muscle. It is discussed whether the pathological recruitment in bradykinesia might be due to disturbed gamma loop function.


Distributed measurement of birefringence dispersion in polarization-maintaining fibers.
A new method to measure the birefringence dispersion in high-birefringence polarization-maintaining fibers is presented using white-light interferometry. By analyzing broadening of low-coherence interferograms obtained in a scanning Michelson interferometer, the birefringence dispersion and its variation along different fiber sections are acquired with high sensitivity and accuracy. Birefringence dispersions of two PANDA fibers at their operation wavelength are measured to be 0.011 ps/(km nm) and 0.018 ps/(km nm), respectively. Distributed measurement capability of the method is also verified experimentally.


Rates of root and organism growth, soil conditions, and temporal and spatial development of the rhizosphere.
Roots growing in soil encounter physical, chemical and biological environments that influence their rhizospheres and affect plant growth. Exudates from roots can stimulate or inhibit soil organisms that may release nutrients, infect the root, or modify plant growth via signals. These rhizosphere processes are poorly understood in field conditions. We characterize roots and their rhizospheres and rates of growth in units of distance and time so that interactions with soil organisms can be better understood in field conditions. We review: (1) distances between components of the soil, including dead roots remnant from previous plants, and the distances between new roots, their rhizospheres and soil components; (2) characteristic times (distance(2)/diffusivity) for solutes to travel distances between roots and responsive soil organisms; (3) rates of movement and growth of soil organisms; (4) rates of extension of roots, and how these relate to the rates of anatomical and biochemical ageing of root tissues and the development of the rhizosphere within the soil profile; and (5) numbers of micro-organisms in the rhizosphere and the dependence on the site of attachment to the growing tip. We consider temporal and spatial variation within the rhizosphere to understand the distribution of bacteria and fungi on roots in hard, unploughed soil, and the activities of organisms in the overlapping rhizospheres of living and dead roots clustered in gaps in most field soils. Rhizosphere distances, characteristic times for solute diffusion, and rates of root and organism growth must be considered to understand rhizosphere development. Many values used in our analysis were estimates. The paucity of reliable data underlines the rudimentary state of our knowledge of root-organism interactions in the field.


Shingles vaccination: background and advice for community nurses.
Shingles (or zoster) is a reactivation of an existing varicella-zoster virus (VZV) infection. During the initial infection, VZV causes a systemic disease known as varicella or chickenpox, and this initial infection normally occurs early in childhood in the absence of routine vaccination. Although varicella is normally a mild disease, shingles is associated with significant morbidity and some mortality, particularly in older people. The most significant severe consequence is post-herpetic neuralgia. There is an effective vaccine available for this, known as Zostavax, which is a live-attenuated VZV vaccine. Guidelines in the UK recommend that this is offered to everyone when they become 70 years of age, plus those aged 79 years as part of a catch-up campaign, with those between these ages not being eligible. It is important for all health-care professionals, including district and community nurses, to proactively promote this vaccine, so that those eligible can make an informed decision about whether to receive it.


The influence of fatty acids on the GpA dimer interface by coarse-grained molecular dynamics simulation.
The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA.


Improved free energy parameters for RNA pseudoknotted secondary structure prediction.
Accurate prediction of RNA pseudoknotted secondary structures from the base sequence is a challenging computational problem. Since prediction algorithms rely on thermodynamic energy models to identify low-energy structures, prediction accuracy relies in large part on the quality of free energy change parameters. In this work, we use our earlier constraint generation and Boltzmann likelihood parameter estimation methods to obtain new energy parameters for two energy models for secondary structures with pseudoknots, namely, the Dirks-Pierce (DP) and the Cao-Chen (CC) models. To train our parameters, and also to test their accuracy, we create a large data set of both pseudoknotted and pseudoknot-free secondary structures. In addition to structural data our training data set also includes thermodynamic data, for which experimentally determined free energy changes are available for sequences and their reference structures. When incorporated into the HotKnots prediction algorithm, our new parameters result in significantly improved secondary structure prediction on our test data set. Specifically, the prediction accuracy when using our new parameters improves from 68% to 79% for the DP model, and from 70% to 77% for the CC model.


Ab initio and AIM theoretical analysis of hydrogen-bond radius of HD (D = F, Cl, Br, CN, HO, HS and CCH) donors and some acceptors.
Recently, we defined 'hydrogen-bond radii' for various hydrogen-bond donors, DH where D = F, Cl, Br, CN, HO or CCH from an empirical analysis. It was shown that the A...H distances in B...HD complexes could be written as a sum of hydrogen bond radius for DH and a constant acceptor radius for A, which is the bonding atom/centre in B. This manuscript reports the determination of the hydrogen-bond radii for these molecules and H2S from ab initio and atoms in molecules (AIM) theoretical calculations. The results from ab initio calculations are consistent with the empirical estimates for the six molecules noted above and provide the first estimate for hydrogen bond radius (1.08 +/- 0.16 A) for H2S donor. The results from AIM theoretical analysis are in qualitative agreement with ab initio results. However, AIM analysis indicates that both hydrogen bond donor and acceptor radii vary in a systematic way from the strong to weak hydrogen bonds. Irrespective of the method used, the hydrogen bond donor radius increases in the order HF < HCl < H2O < HBr < HCN < HCCH < H2S, but mostly lie between Pauling's covalent and van der Waals radii of H atom. Interestingly, the acceptor radii for A in A...HD also increase in the same order. The AIM theoretical results on about 100 complexes have been reduced to suggest radii for H, F, O, N, C and S that are appropriate for strong, medium and weak hydrogen bonds. It is suggested that the use of a single van der Waals radius for D, H or A in determining the presence/absence of D-H...A hydrogen bonding be discontinued.


2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits fibroblast growth factor 10-induced prostatic bud formation in mouse urogenital sinus.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) dorsalizes the pattern of prostatic buds developing from the urogenital sinus (UGS) of male fetal mice, causing some buds to form in inappropriate positions while blocking formation of others. This teratogenic TCDD action significantly reduces prostate main duct number and causes ventral prostate agenesis in exposed males. The purpose of this study was to determine whether inhibition of fibroblast growth factor 10 (FGF10) signaling is mechanistically linked to mouse prostatic budding impairment by TCDD. In utero TCDD exposure induced aryl hydrocarbon receptor-responsive cytochrome P450 1b1 messenger RNA (mRNA) in ventral UGS regions where Fgf10 and fibroblast growth factor receptor 2 (Fgfr2) mRNA were expressed and where budding was most severely inhibited by TCDD. However, TCDD exposure did not reduce Fgf10 or Fgfr2 mRNA abundance in the UGS or alter their distribution. Addition of FGF10 protein to UGS organ culture media increased the abundance of UGS basal epithelial cells immunopositive for phosphorylated extracellular signal-regulated kinase (ERK). FGF10 also increased the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled UGS epithelial cells and increased the number of prostatic buds formed per UGS. Addition of TCDD to UGS organ culture media did not alter FGF10-induced ERK activation in UGS basal epithelium but prevented FGF10-induced BrdU incorporation and blocked FGF10-induced prostatic bud formation. These results identify basal urogenital sinus epithelium cells as the key site of FGF10 action during fetal prostate development and suggest that TCDD likely acts downstream of FGFR2 and ERK to restrict UGS epithelial cell proliferation and prevent prostatic bud formation.


Frequent cleft lip and palate in families with pathogenic germline CDH1 variants.
Pathogenic and likely pathogenic (P/LP) germline variants in the tumor suppressor gene CDH1 (E-cadherin) result in increased lifetime risk of diffuse-type gastric cancer and lobular breast cancer. CDH1 variants are also associated with hereditary cleft lip and palate (CLP), the mechanism of which is not well understood. We sought to determine the prevalence of CLP in families who carry P/LP CDH1 variants. Patients with P/LP CDH1 variants who were enrolled in a prospective clinical trial were reviewed (NCT03030404). The cohort included 299 individuals from 153 families that had 80 unique P/LP variants in CDH1. The rate of CLP was 19% (29/153) in families reporting CLP in at least one family member, and 2.7% (8/299) among individuals with confirmed germline CDH1 P/LP variants. There were 22 unique variants in CDH1 among the 29 families that reported CLP, or a CLP rate of 27.5% per variant (22/80). 10 of the variants were not previously reported to be associated with CLP. We observed that 24% (7/29) of CLP-associated gene variants involved large-scale (≥1 exon) deletions. Among families with CLP, 69% (20/29) had a member diagnosed with gastric cancer, and 79% (23/29) had a member with breast cancer, which were similar to rates observed in non-CLP families (p >0.3 for both). Our analysis suggests that the prevalence of CLP in families with germline CDH1 P/LP variants was high in this large cohort, and there was no genotype-phenotype pattern. Genetic testing for CDH1 variants should be considered in families with CLP and history of either diffuse-type gastric or lobular breast cancer.


Influencing Mechanism and Difference of Poultry Farmers' Willingness and Behavior in Breeding Scale-Evidence from Jianghan Plain, China.
This paper uses the Heckprobit two-stage econometric model to explore the influence mechanism of poultry farmers' willingness and behavior regarding scale based on 269 household survey data in the hinterland of Jianghan Plain, China. The results show that (1) family endowments, social capital, economic capital, product market prediction, and major public emergencies are the main influencing factors for farmers to engage in poultry farming; (2) economic capital, policy guarantees, product market prediction, and major public emergencies are the main factors that influence the changes in farmers' poultry breeding scale; and (3) sampled poultry farmers are inconsistent between their breeding willingness and breeding behavior in poultry decision-making and the factors that affect the willingness and behavior are varied. Based on these findings, this paper suggests that the government should pay attention to inducing corresponding assistance and subsidy policies, formulating financial support countermeasures, organizing training and exchange meetings of the breeding industry, and promoting poultry market informatization to help the poultry industry prosper.


[Hepatocyte-specific Pten deficient mice].
Histological findings of hepatocyte-specific Pten deficient(Pten KO) mice livers were consistent with the criteria of human nonalcoholic steatohepatitis(NASH). Therefore, Pten KO mice are a powerful animal model of NASH. In Pten KO mice livers, steatosis develops based on the increased expression of genes that promote fatty acids synthesis. The increased expression of beta, oxidation-related genes accumulates oxidative stress in Pten KO mice livers resulting in hepatitis based on lipid hyperoxidation of hepatocytes membranes. Onset and exacerbation of hepatitis are also related to endotoxins derived from intestinal bacteria. Oxidative DNA damage, hyperproliferation of hepatocytes induced by the activation of Akt and ERK, and the increasement of malignant potential based on the change of fatty acids composition in the livers contribute to the development of hepatocellular carcinoma in Pten KO mice. Since it is considered that the mechanism to induce hepatic lesions in some NASH patients is the same as that in Pten KO mice, the investigation using Pten KO mice gives us clues to clarify the pathogenesis or develop effective therapy of NASH.


Reliability and validity of the brief dimensional apathy scale.
Apathy is composed of different demotivational subtypes measurable by the dimensional apathy scale (DAS) and can be quickly assessed using the brief DAS (b-DAS). The aim was to determine the reliability and validity of the b-DAS. 53 amyotrophic lateral sclerosis (ALS) patients and 53 of their informants were recruited. Informants completed the b-DAS, the original informant/carer-rated DAS and behavioral interview about the patients (i.e., presence of behaviors such as apathy/inertia, loss of sympathy/empathy). Patients completed measures of depression, anxiety, emotional lability, cognitive functioning, and functional disability measures. The b-DAS showed good internal consistency, excellent test-retest reliability, significant positive correlation with the original DAS, and no significant correlations with depression, anxiety, emotional lability, cognitive functioning or functional disability measures. Semi-structured behavior interview showed patients with apathy/inertia had significantly higher b-DAS subscale scores and patients with loss of sympathy/empathy had significantly higher emotional apathy scores only. The b-DAS is a fast, reliable, and valid instrument for screening apathy subtypes independent of physical disability.


Conservative Treatment of Chronic Subdural Hematoma with Gorei-san.
Most asymptomatic patients with chronic subdural hematoma (CSDH) are followed conservatively but can require surgical treatment if the hematoma expands. We conducted a retrospective evaluation of the effect of Gorei-san on CSDH. This study included patients treated between April 2013 and March 2015. In total, 289 patients were diagnosed with CSDH and 110 patients received conservative management. Finally, 39 patients who met the requirements were registered. We retrospectively examined the age, gender, medical history, hematoma thickness, clarity of sulci below hematomas, and midline shift of the patients. The primary outcome was the median surgery-free interval, and the secondary results were the rate of CSDH shrinkage and surgery avoidance. A comparison of patient characteristics between the Gorei-san (G) and non-Gorei-san (NG) groups found no significant differences in the percentage of men, average ages, past history, thickness of CSDH (15.0 ± 3.1 mm vs. 15.3 ± 2.6 mm, p = 0.801), or midline shift (2.0 ± 2.7 mm vs. 4.0 ± 5.0 mm, p = 0.230). The median surgery-free interval was significantly different between the G and NG groups [n. r. vs. 41 days (95% CI: 5-79), log-rank p = 0.047]. The CSDH avoidance rate was not significantly different between the two groups (70.0% vs. 34.4%, p = 0.071). Additionally, the CSDH shrinkage rate was significantly different between the two groups (60.0% vs. 10.3%, p = 0.004). This retrospective study demonstrated that CSDH treatment with Gorei-san reduces hematoma significantly more than treatment that does not include Gorei-san.


[Application of the trend-surface analysis for studying the geographical distribution of lung cancer mortality].
To apply trend-surface analysis on lung cancer mortality in China. To overview the theory and approach of trend-surface analysis and to fit the first to fifth order regression equations, where dependent variables were latitude and longitude, and the independent one was the standardized mortality ratio (SMR) of lung cancer for various provinces. Data was from the second mortality survey in the whole country, then proper regression equation was chosen. Fifth-order regression equation was established for mortality of lung cancer in males with its fit goodness as 76.06%. The third-order regression equation was established for mortality of lung cancer in females with its fit goodness as 89.77%. There were positive residuals in Shanghai, Hubei and Tianjin, while the negative residuals were in Zhejiang, Anhui, Henan, Beijing and Guangxi for males. There were positive residuals in Tianjin, Hubei and Guangdong, while negative residuals appeared in Zhejiang, Shanxi, Guizhou, Hainan, Henan, Jilin and Neimenggu for females. The geographic distribution trend of lung cancer mortality between males and females appeared to be different. The mortality of lung cancer among males was high in the northeast provinces while the mortality of lung cancer for females was high in the southeast areas. In those areas where the residual values were anomalous, further studies need to be carried out.


A tutorial in assessing disclosure risk in microdata.
Statistical agencies are releasing statistical data to other agencies for research purposes or to inform public policy. Prior to data release, these agencies have a legal and ethical obligation to protect the confidentiality of individuals in the data. Agencies often release altered versions of the data, but there usually remains risks of disclosure. Many well-studied risk measures are available to assess risk; however, many agencies today continue to use subjective judgement, past experience, and ad hoc rules or checklists to assess disclosure risk. More recently, there has been a recognized demand for quantitative risk measures that provide a more objective criteria for data release. This tutorial provides an overview of the statistical disclosure control framework for microdata. We focus on the risk analysis stage within this framework by defining existing disclosure risk measures and how to estimate them with available software.


Adjunct aids in instructional prose: a multimedia study with deaf college students.
A computer-based science lesson was administered to 144 deaf college students grouped into low, middle, and high reading ability levels. Five instructional conditions were compared: (1) text only, (2) text and content movies, (3) text and sign movies, (4) text and adjunct questions, and (5) all of these together (full condition). The low reading level subjects in the adjunct question and full conditions demonstrated immediate, factual learning performance comparable to that of the high reading level subjects in the text-only condition. These and other results of this investigation suggest the compensatory potential of adjunct aids and associated mathemagenic activities to improve factual learning from instructional prose for low reading ability students.


Endoscopic transnasal resection of ectopic esthesioneuroblastoma in the pterygopalatine fossa: technical case report.
Esthesioneuroblastoma is a rare, malignant neoplasm arising from the olfactory neuroepithelium in the upper nasal cavity. Even more rare is ectopic esthesioneuroblastoma developing from the region outside the olfactory epithelium. In addition, tumors occurring in the pterygopalatine fossa (PPF) are uncommon, and the endoscopic transnasal approach for the resection of malignant tumors in this region is also uncommon. We describe an esthesioneuroblastoma arising from the left maxillary sinus and PPF. The tumor was resected using the endoscopic transnasal approach, followed by treatment with radiotherapy. The patient showed no evidence of recurrence 12 months postoperatively. The endoscopic transnasal approach could be successfully used for the complete removal of malignant tumors in the PPF. The PPF is an anatomic area that is difficult to access. The endoscopic transnasal approach improves access and visualization; it also has the potential to reduce complications compared with the open approach. The endoscopic transnasal approach might become the treatment of choice for malignant tumors in the PPF.


Comparative analyses of bioactive Mammea coumarins from seven parts of Mammea americana by HPLC-PDA with LC-MS.
Mammea americana L. is tropical plant in the Clusiaceae family that bears edible fruit. Mammea coumarins are isoprenylated derivatives of the lactones of the 2-hydroxy-Z-cinnamic acids that are bioactive and have limited distribution in three Clusiaceae genera. Qualitative and quantitative analyses were performed to determine the distribution of mammea coumarins in the seed nucleus, seed coat, fruit flesh, fruit skin, leaf, stem, and root of M. americana using high-performance liquid chromatography-photodiode array detector (HPLC-PDA) and liquid chromatography-mass spectrometry (LC-MS). Ten major mammea coumarins, mammea E/BD (1), mammea E/BC (2), mammea E/BA (3), mammea E/BB (4), mammea B/BA hydroxycyclo F (5), mammea B/BD (6), mammea B/BC (7), mammea B/BA (8), mammea B/BB (9), and mammea B/BA cyclo F (10), were isolated and identified from the seed nucleus of M. americana and employed as standards. The HPLC-PDA method was validated with respect to sensitivity, linearity, recovery, accuracy, and precision. The total content (w/w %) of the 10 major mammea coumarins in M. americana was determined to be highest in the root (0.75%), followed by the leaf (0.64%), seed nucleus (0.48%), fruit skin (0.11%), stem (0.08%), seed coat (0.02%), and fruit flesh (<0.01%). The leaf and seed nucleus are rich and sustainable natural sources of mammea coumarins. Additionally, the described HPLC-PDA and LC-MS methods are sensitive and accurate and can be applied to the analysis of mammea coumarins in other samples.


[Stress and prevention in the recurrence of coronary heart disease.].
A good deal of recent research suggests that a period of mounting life stress is a precursor of many physical illnesses, including episodes of coronary heart disease (CHD). It should be possible then, by monitoring levels of stress to predict when a high risk individual is likely to suffer a further illness episode, and in some cases to prevent the episode by alleviating stress producing problems. Based on this concept, we have telephone-monitored (at monthly intervals) 37 CHD patients discharged from the coronary unit of the Montreal General Hospital. Stress was measured using a 20-item, self-report scale (Goldberg), and charted for each patient over a seven month period. When a patient's stress rose above a critical level he received a home visit by the project nurse, who investigated his problems and attempted to alleviate them. Interventions varied from simple reassurance to referral for psychiatric treatment or legal aid. Monitoring stress in this way revealed a picture remarkably like the theoretical model. None of the 15 consistently low-scoring patients required rehospitalization. Eleven patients had low scores at the time of discharge, but their scores rose above the critical level in subsequent months. Nine of them responded in a gratifying way- to the home visit and subsequent intervention by the nurse, and none required rehospitalization. The one patient of this type who did require hospitalization had not received a home visit because no nurse was available at the time. Four of the nine patients with consistently high scores required eight rehospitalization s for CHD episodes. These patients seemed to be chronically stressed, and often required continuous support from the nurse. Our study suggests that life stress may be more important than the traditional physical risk factors (obesity, smoking, hypertension, family history of CHD, lack of exercise) in the etiology of recurrent CHD when patients receive adequate medical care. Some of our findings suggest that the nurse's interventions do reduce rehospitalizations, but a large scale controlled study is called for. We conclude that this technique is worth further evaluation, both as a research method and as a practical device for the prevention of rehospitalization of CHD patients and of other types of episodic illnesses.


Generation of Intestinal Organoids Suitable for Pharmacokinetic Studies from Human Induced Pluripotent Stem Cells.
Intestinal organoids morphologically resemble intestinal tissues and are expected to be used in both regenerative medicine and drug development studies, including pharmacokinetic studies. However, the pharmacokinetic properties of these organoids remain poorly characterized. In this study, we aimed to generate pharmacokinetically functional intestinal organoids from human induced pluripotent stem (iPS) cells. Human iPS cells were induced to differentiate into the midgut and then seeded on EZSPHERE plates (AGC Techno Glass Inc., Shizuoka, Japan) to generate uniform spheroids, and the floating spheroids were subsequently differentiated into intestinal organoids using small-molecule compounds. Exposure to the small-molecule compounds potently increased the expression of intestinal markers and pharmacokinetic-related genes in the organoids, and the organoids also included various intestinal cells such as enterocytes, intestinal stem cells, goblet cells, enteroendocrine cells, Paneth cells, smooth muscle cells, and fibroblasts. Moreover, microvilli and tight junctions were observed in the organoids. Furthermore, we detected not only the expression of drug transporters but also efflux transport activity through ABCB1/MDR1 and the induction of the drug-metabolizing enzyme CYP3A4 by ligands of nuclear receptors. Our results demonstrated the successful generation of pharmacokinetically functional intestinal organoids from human iPS cells. Thus, these intestinal organoids could be used as a pharmacokinetic evaluation system in drug development studies.


Effect of Bacillus natto solid-state fermentation on the functional constituents and properties of Ginkgo seeds.
In the present investigation, fibrinolytic Ginkgo seeds were produced by solid-state fermentation (SSF) with Bacillus natto strains, and some parameters of the fermentation processes were investigated. Under optimal fermentation conditions, the fibrinolytic activity of Ginkgo seeds reached 3,682 ± 43 IU/g with the fermentation parameters of relative humidity 80%, initial water content 73%, fermentation temperature 38°C, inoculation volume 18%, and fermentation time 38 hr, respectively. The fermented Ginkgo seeds possessed a superior potential for the production of Nattokinase. What's more, the fermented Ginkgo seeds possessed higher total flavonoid and lower ginkgolic acids contents, which could enhance bioactivity and guarantee food safety. Sensory evaluations indicated that Ginkgo seeds produced by SSF could also be consumed as a kind of popular food. PRACTICAL APPLICATIONS: Fermented food is popular in countries. It can not only improve the sensory properties of the products, reduce undesirable constituents, and make nutrients easily absorbable, but also improve the nutritional properties. Ginkgo biloba L is one of the oldest species that has existed on earth for more than 200 million years. However, the application of Ginkgo seeds has been limited because of the ginkgolic acids. In a previous study, immobilized Bacillus natto acted upon Ginkgo seeds to enhance the bioactivity and safety of fermented Ginkgo seeds. However, separating the fermented Ginkgo seeds from the liquid needs a large amount of energy. The solid-state fermentation of Ginkgo seeds is a good choice to produce functional Ginkgo seed products.


Is the site of action of grayanotoxin the sodium channel gating of squid axon?
An attempt was made to elucidate the site of action of grayanotoxin (GTX) in the nerve membrane by using various endopeptidases. The experiment was conducted on squid axons isolated from Doryteuthis bleekeli with both voltage clamp and internal perfusion methods. Intracellular application of various endopeptidases for more than 30 min eliminated the gating action from both Na current and K current systems. When GTX (100 microM) was subsequently applied to the internal medium, the membranes could depolarize to various extents. This finding strongly suggests that the site of action of GTX is not confined to the channel gating but is present in a part of the Na channel having both voltage sensor and ion filter functions. With the application of trypsin, St. fradiae trypsin, pronase, BPN', and St. fradiae protease (group B), GTX-induced depolarization was much smaller than that with the application of alpha-chymotrypsin, N-protease, and thermolysin (group A). The difference in the sensitivity to GTX between group A and group B became remarkable as the time for application of the enzymes was prolonged. Since all enzymes belonging to group B retain trypsin-like activity and are more effective in removing the sensitivity to GTX, it is suggested that the molecular moiety around the binding site of GTX is rich in basic amino acids or the essential part for opening the Na channel should be protected by basic amino acids.


Therapeutic Drug Monitoring of Tigecycline in 67 Infected Patients and a Population Pharmacokinetics/Microbiological Evaluation of A. baumannii Study.
The widespread use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria such as multidrug-resistant Acinetobacter baumannii (AB). Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broad-spectrum antibiotic which remains highly effective to treat AB infections. To confirm the TGC treatment dosage and effectiveness to treat AB infections in the Chinese population by performing therapeutic drug monitoring (TDM). This study was performed from October 2018 through March 2019 at the PLA General Hospital. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated and employed to determine the plasma concentrations of TGC in patients with infectious diseases. The minimum inhibitory concentration (MIC) of TGC to clinically isolated AB was determined by broth microdilution method, agar dilution method, and disk diffusion method. Moreover, a model of population pharmacokinetics/pharmacodynamics (PPK/PD) was constructed. A total of 186 plasma samples from 67 patients were detected by the validated HPLC-MS/MS method. The MIC values determined by the broth microdilution method were more sensitive and accurate than the other two methods. The microbial and clinical PK/PD breakpoints were reached when the maintenance dose of TGC was 100 mg. Our study established a validated HPLC-MS/MS method to monitor the plasma concentrations of TGC. In view of the MIC range to AB isolates in our hospital and the PPK/PD modeling results, we recommend a relatively high dose of 100 mg q12h regimen to achieve the optimal clinical efficacy and antimicrobial response.


DNA quantification in colorectal carcinoma using flow and image analysis cytometry.
Numerous studies using flow cytometry (FCM) have shown that DNA quantification and ploidy classification can provide information of prognostic significance for patients with colorectal carcinoma; recent advances in image analysis cytometry (image cytometry, ICM) provide a new, alternative technique for DNA quantification. This study investigated whether (1) patients with colorectal carcinomas that exhibit a diploid pattern of DNA distribution have improved five-year survival statistics as compared to their non-diploid counterparts and (2) ICM provides quantitative data comparable to that obtained by FCM. DNA quantification and ploidy classification of 27 cases of primary colorectal carcinoma was performed on archival paraffin-embedded tissue by both FCM and ICM; 70% (19) of the tumors were classified as nondiploid by ICM while 56% (15) were similarly classified by FCM. Diploid tumors were associated with Dukes' stage A while nondiploid tumors were associated with Dukes' stage D. The overall five-year survival rate was 75% for patients with ICM diploid tumors and 67% for patients with FCM diploid tumors. The five-year survival was only 53% for patients with nondiploid tumors identified by both techniques. This study confirmed that DNA quantification is an important prognostic indicator for patients with colorectal carcinoma. It also showed that ICM provides data comparable to that of FCM and may be more sensitive.


Muscle mass and functional recovery in women with hip fracture.
To investigate the association between muscle mass and functional recovery in women with hip fracture. A total of 200 of 230 women with hip fracture admitted consecutively to a rehabilitation hospital were investigated in this survey study. Lean mass (LM) was assessed by dual-energy x-ray absorptiometry, 23.1 +/- 7.9 (mean +/- SD) days after fracture occurrence. Appendicular LM (aLM) was calculated as the sum of LM in arms and legs. Because metal implants (prostheses and nails) affect the regional assessment of body composition, aLM was corrected by substituting LM in the unfractured leg for LM in the fractured leg: corrected aLM = (LM in unfractured leg x 2) + LM in arms. We used two approaches to adjust corrected aLM for body size: corrected aLM divided by height squared (aLM/ht), and corrected aLM adjusted for height and fat mass (residuals). Functional recovery was assessed by using Barthel index scores. After adjustment for body size, corrected aLM was neither significantly correlated with Barthel index scores nor with the change in Barthel index scores after rehabilitation. Also, after stratification for quintiles of aLM/ht and residuals, no significant differences in functional recovery were found among the five groups. LM assessed after hip fracture is not associated with functional outcome in women.


Clustering and negative feedback by endocytosis in planar cell polarity signaling is modulated by ubiquitinylation of prickle.
The core components of the planar cell polarity (PCP) signaling system, including both transmembrane and peripheral membrane associated proteins, form asymmetric complexes that bridge apical intercellular junctions. While these can assemble in either orientation, coordinated cell polarization requires the enrichment of complexes of a given orientation at specific junctions. This might occur by both positive and negative feedback between oppositely oriented complexes, and requires the peripheral membrane associated PCP components. However, the molecular mechanisms underlying feedback are not understood. We find that the E3 ubiquitin ligase complex Cullin1(Cul1)/SkpA/Supernumerary limbs(Slimb) regulates the stability of one of the peripheral membrane components, Prickle (Pk). Excess Pk disrupts PCP feedback and prevents asymmetry. We show that Pk participates in negative feedback by mediating internalization of PCP complexes containing the transmembrane components Van Gogh (Vang) and Flamingo (Fmi), and that internalization is activated by oppositely oriented complexes within clusters. Pk also participates in positive feedback through an unknown mechanism promoting clustering. Our results therefore identify a molecular mechanism underlying generation of asymmetry in PCP signaling.


The tempo and mode of evolution: body sizes of island mammals.
The tempo and mode of body size evolution on islands are believed to be well known. It is thought that body size evolves relatively quickly on islands toward the mammalian modal value, thus generating extreme cases of size evolution and the island rule. Here, we tested both theories in a phylogenetically explicit context, by using two different species-level mammalian phylogenetic hypotheses limited to sister clades dichotomizing into an exclusively insular and an exclusively mainland daughter nodes. Taken as a whole, mammals were found to show a largely punctuational mode of size evolution. We found that, accounting for this, and regardless of the phylogeny used, size evolution on islands is no faster than on the continents. We compared different selection regimes using a set of Ornstein-Uhlenbeck models to examine the effects of insularity of the mode of evolution. The models strongly supported clade-specific selection regimes. Under this regime, however, an evolutionary model allowing insular species to evolve differently from their mainland relatives performs worse than a model that ignores insularity as a factor. Thus, insular taxa do not experience statistically different selection from their mainland relatives.


Pre-emptive local anesthesia for needlescopic video-assisted thoracic surgery: a randomized controlled trial.
Studies in other surgical specialties have suggested that pre-emptive wound infiltration using a local anesthetic may reduce post-operative pain. We report the first randomized trial to assess the use of pre-emptive local anesthesia in video-assisted thoracic surgery (VATS). Thirty-one consecutive patients undergoing bilateral needlescopic VATS sympathectomy for palmar hyperhidrosis were studied prospectively. Each patient acted as their own control. For each patient, one side was randomized to receive 10ml 0.5% bupivicaine injected to the port sites before incision, and the contralateral control side to receive 10ml saline. Pain severity on a visual analog scale (VAS) was recorded for each chest side at 4h, 1 day and 7 days following surgery. All patients were blinded to the results of randomization throughout the study. Follow up was complete for all patients. At 7 days after surgery, wound pain was significantly reduced by pre-emptive local anesthesia, with 10 (62.5%) of the 16 patients having residual pain reporting less pain on the pre-treated side (p=0.039). There was a trend for reduced pain on the pre-treated side at the other time points. Pain reduction by pre-emptive local anesthesia was not correlated with any demographic or clinical variable. Chest wall paresthesia distinct from localized wound pain was noted by six patients (19.4%), but was not reduced by pre-emptive local anesthesia. Overall, the post-operative discomforts felt by the patients after needlescopic VATS were mild, and did not cause significant functional disturbances. Pre-emptive wound infiltration with a local anesthetic may reduce post-operative wound pain in needlescopic VATS procedures.


Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers.
Plasma and milk concentrations of pseudoephedrine and triprolidine were determined (by radioimmunoassay) in three lactating mothers over 12-48 h after ingestion of a combination medication containing 60 mg of pseudoephedrine hydrochloride and 2.5 mg of triprolidine hydrochloride monohydrate. Pseudoephedrine concentrations in milk were consistently higher than those in plasma. The total amount of drug in milk, as judged by areas under the respective curves (AUC), was two to three times greater than in plasma. Triprolidine concentrations in milk and plasma were more variable between subjects than those of pseudoephedrine. AUC values for milk and plasma were similar for one subject, while the plasma value exceeded that for milk in another woman. The fraction of the dose excreted in milk was estimated to be 0.4-0.7% for pseudoephedrine and 0.06-0.2% for triprolidine.


Electron transport in silver-semiconductor nanocomposite films exhibiting multicolor photochromism.
In the multicolor photochromism of TiO2 nanoporous films loaded with photocatalytically deposited Ag nanoparticles, visible light-induced electron transfer from Ag to oxygen molecules plays an essential role. Here we examined the effect of TiO2 on the electron transfer. We found that not only photocatalytically deposited Ag, but also electrodeposited Ag and commercially available Ag nanoparticles in a nanoporous TiO2 film exhibit the multicolor photochromism. The electrodeposited Ag exhibits the multicolor photochromism also in a nanoporous ZnO film, but not in nanoporous indium-tin oxide (ITO) and SiO2 matrices. Photoelectrochemical measurements for the Ag-TiO2 nanocomposite elucidated that some of the photo-excited electrons on Ag are transferred to oxygen molecules via TiO2 and non-excited Ag. Thus, an n-type semiconductor plays an important role in the charge separation between the excited electrons and Ag+. Non-excited Ag on TiO2 also plays an important role in the charge separation and/or catalysis of oxygen reduction. Replacement of the non-excited Ag with Pt accelerated the electron transport from the photo-excited Ag to oxygen molecules and the photochromic behavior.


Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.
Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.


Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.
ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.


Isolated intracranial Whipple's disease--report of a rare case and review of the literature.
Whipple's disease (WD) is a rare multisystemic infectious disease that can involve a variety of organs namely the gastrointestinal tract, lymphatic system, heart and nervous system. Myorhythmia is a hallmark of WD. Isolated CNS involvement is very rare. We present a 50 year-old African-American woman with rapid cognitive decline, visual hallucinations, insomnia, dysarthria, and gait unsteadiness. She subsequently developed pendular nystagmus and gaze paresis. Serial brain MRI scans showed T2 hyperintense lesions in the left striatum and right parahippocampal gyrus. FDG-PET scan showed marked increase of glucose uptake in the left putamen. Serum and CSF PCR for Tropheryma whipplei was negative. Stereotactic biopsy of the lesion and tissue PCR was consistent with WD. A systematic review identified 24 cases of isolated intracranial presentation of WD since 1975. Cases with systemic and extracranial manifestations were excluded. In patients with rapidly progressive cognitive decline with negative workup for common etiologies, there should be a high index of suspicion for WD. Diagnosis of WD remains a challenge as traditional methods commonly fail to culture T. whipplei. PET scans can help in identifying areas of inflammation that can be biopsied. Our case proves that a negative serum and CSF PCR should not exclude CNS WD and a brain biopsy of the lesion with PCR assay should be performed when possible.


Prospective risk factors for adolescent PTSD: sources of differential exposure and differential vulnerability.
There are two types of risk factors for developing PTSD: factors that increase the likelihood of experiencing a potentially traumatizing event and factors that increase the likelihood of developing symptoms following such events. Using prospective data over a two-year period from a large, diverse sample of urban adolescents (n = 1242, Mean age = 13.5), the current study differentiates these two sources of risk for developing PTSD in response to violence exposure. Five domains of potential risk and protective factors were examined: community context (e.g., neighborhood poverty), family risk (e.g., family conflict), behavioral maladjustment (e.g., internalizing symptoms), cognitive vulnerabilities (e.g., low IQ), and interpersonal problems (e.g., low social support). Time 1 interpersonal violence history, externalizing behaviors, and association with deviant peers were the best predictors of subsequent violence, but did not further increase the likelihood of PTSD in response to violence. Race/ethnicity, thought disorder symptoms, and social problems were distinctly predictive of the development of PTSD following violence exposure. Among youth exposed to violence, Time 1 risk factors did not predict specific event features associated with elevated PTSD rates (e.g., parent as perpetrator), nor did interactions between Time 1 factors and event features add significantly to the prediction of PTSD diagnosis. Findings highlight areas for refinement in adolescent PTSD symptom measures and conceptualization, and provide direction for more targeted prevention and intervention efforts.


Applications of Telemedicine in the Middle East and North Africa Region: Benefits Gained and Challenges Faced.
Information and communication technology has left a print on all fields of life, including medicine and the health care system. Telemedicine is the perfect way to ensure adequate healthcare delivery to all people at any time, particularly during pandemics, regardless of any geographic or economic considerations. This article investigates the different types, categories, and benefits in addition to the barriers to telemedicine implementation, especially in the Middle East and North Africa (MENA) region. After a thorough review of medical literature related to telemedicine using PubMed, Google Scholar, and some other gray literature, it has been found that telemedicine has been involved in almost all medical specialties with a positive influence on healthcare delivery and medical education and research. It had a major role during the COVID-19 pandemic. However, many obstacles prevent its proper application and need to be addressed carefully by the government and relevant authorities. Due to the rapidly growing population, unequal distribution of healthcare services, and social distancing of the COVID-19 pandemic, the role of telemedicine has become increasingly essential. Regarding medical education and research, telemedicine facilitates the exchange of information and ideas between physicians and professionals from all over the world, bringing these various minds together on a single platform.


Australian sexual health nurses: variations in practice.
The study aimed to describe the scope of practice of Australian Sexual Health Nurses in order to inform development of nationally consistent role functions. Descriptive cross sectional survey of 201 sexual health nurses utilising an anonymous self-administered questionnaire with reply paid envelope which was sent to members of the Australian Sexual Health Nurses Association along with a letter which encouraged them to ask non member sexual health nurses to also complete a questionnaire. Despite the fact that most Australian Sexual Health Nurses are employed in sexual health centres and family planning clinics, this study showed the scope of their practice to be extremely varied both in and between states/territories. The scope of practice of Australian sexual health nurses is varied. While questions remain as to the reasons for difference, the authors argue that the specialty needs to work toward a national model for basic sexual health nursing care. It is recommended that this model be based on knowledge of and rationales for variations in practice.


Prosthodontic Complications of Metal-Ceramic and All-Ceramic, Complete-Arch Fixed Implant Prostheses with Minimum 5 Years Mean Follow-Up Period. A Systematic Review and Meta-Analysis.
The purpose of this systematic review and meta-analysis was to review and analyze the prosthodontic complications, survival, and success of metal-ceramic (MC) and all-ceramic (AC) complete-arch fixed implant dental prostheses (CFIDPs) with a minimum mean follow-up period of 5 years. A structured literature search was conducted using 3 electronic databases (MEDLINE, the Cochrane Library, Web of Science) for clinical studies reporting on prosthodontic complications of metal-ceramic and/or all-ceramic CFIDPs published between 2000 and 2016. This was complemented with hand searching in relevant journals, references, as well as searching in grey literature. Risk of bias analysis for randomized controlled trials was done following the recommendations from the Cochrane Collaboration. Quality appraisal for nonrandomized studies was executed according to the Newcastle-Ottawa scale (NOS). The final selection included only studies with a minimum mean follow-up time of 5 years. The electronic databases search yielded 1804 relevant titles and abstracts; 11 studies were finally selected (9 for MC and 2 for AC CFIDPs). Risk of bias in most selected studies was low. Heterogeneity across studies of MC CFIDPs was within acceptable range but not among AC CFIDP studies, so no meta-analysis was performed for the latter. Regarding MC CFIDPs, most studies recorded 100% survival rate (survival range: 92.4-100%, success range: 47-96.7%), with veneer fracture being the most-common complication. Five- and 10-year cumulative complication rates for MC CFIDP veneer fractures were 22.1% and 39.3%, respectively, but with variable confidence intervals. The 2 studies included for AC CFIDPs reported 100% survival rates but differed in success rates, with the one using predominantly monolithic zirconia restorations reporting 90.9%, and the one using bi-layered zirconia reporting 60.4%, with complications attributed to veneer fracture. MC and AC CFIDPs presented with veneer fractures as primary complication. This may require significant maintenance. Other complications were negligible after a mean follow-up period of at least 5 years. More long-term studies, especially on all-ceramic CFIDPs are needed.


[Bronchoscopies in neonatal intensive care units: safety and efficiency].
The aim of our study is to asses the risks and complications in bronchoscopies at Neonatal Intensive Care Units (NICU). Between 1991 and 1999, we performed 142 bronchoscopies at the NICU. The mean age was 1.6 +/- 1.4 months (2 days-6 months) and mean weight was 2.5 +/- 1 kg (530 g-4.7 kg). We analysed the complications, arterial oxygen saturation and inspired oxygen fraction (FiO2) during bronchoscopy and we compared them related to weight, type of anesthesia and type of bronchoscope used. Mean basal saturation was 92 +/- 8.9% and end saturation was 92.8 +/- 10%. The basal FiO2 was 0.5 +/- 0.3 (0.21-1). There were more complications in patients weighting less than 1500 g and in those procedures made with rigid bronchoscopy (p < 0.05). There were no differences according to the anesthesia. Children who weight fewer than 1500 g and those who underwent rigid bronchoscopy suffered a descent in arterial oxygen saturation and needed higher FiO2 (p < 0.05). Bronchoscopy is a very useful technique and it is well tolerated in neonatal patients. We conclude that flexible fiberoptic bronchoscopy is safer than the rigid bronchoscopy, specially in children fewer under 1500 g.


TNF potentiates anticancer activity of bortezomib (Velcade) through reduced expression of proteasome subunits and dysregulation of unfolded protein response.
Bortezomib (Velcade) exploits proteasome inhibition as a unique mechanism of anticancer activity. The effectiveness of bortezomib is, however, limited, therefore, the search for therapeutic regimens combining bortezomib with other agents. In the present work we demonstrate enhanced anticancer activity of bortezomib by its combination with tumor necrosis factor (TNF) in the experimental model of C-26 colon carcinoma in mice. This interaction likely relies on the induction of a dysregulated response to ER stress, leading to apoptosis of cancer cells, evidenced by caspase-3 cleavage, p53 accumulation as well as increased SAPK/JNK phosphorylation. ER stress induced by the combination of TNF and bortezomib is corroborated by upregulation of BiP, PDI and calnexin as well as cleavage of caspase-12; however, in contrast to the classic pathway, it is also associated with decreased phosphorylation of eIF2 alpha and prevention of XBP-1 splicing. TNF prevented the upregulation of Hsp27 induced by bortezomib, which may contribute to enhanced ER stress. Moreover, TNF interfered with bortezomib-induced upregulation of distinct subunits of the 26S proteasome. Bortezomib concentration used in this study was not sufficient to prevent TNF from inducing nuclear translocation of p65/RelA; however, the combination of both agents reduced total p65/RelA levels. Combined treatment of tumor-bearing mice with bortezomib and TNF not only inhibited tumor growth but also significantly prolonged animal survival. Therefore, combination of bortezomib with TNF is an attractive option for further clinical studies.


Consequences for maternal nutrition of reproductive stress across consecutive pregnancies.
Frequent cycles of reproduction increase the risk that lactation will overlap with pregnancy and shorten the duration of the recuperative interval (nonpregnant and nonlactating portion) within the reproductive cycle, thereby increasing the risk of maternal nutritional depletion. Nutritional responses to these stresses have been demonstrated by contrasting groups of women with different experiences; however, these relationships may be spurious and the result of third factors. In this study, responses to changing stress over consecutive pregnancies were studied and contrasted within individual Guatemalan women; biases caused by factors constant to women were eliminated. Stress was assessed by examining responses in maternal supplement intake, maternal fat stores, and birth weight. Overlap and short recuperative intervals were found to be stressful (in that order) for mothers as shown by increased supplement intake and reduced fat stores. Birth weight in term gestations was not affected, indicating that fetal growth is being protected at the cost of maternal nutritional status.


Saisonale Variation von Deuterium und Sauerstoff-18 in Luftfeuchte und Niederschlag über Antarktika.
Abstract D and (18)O distributions were investigated in Antarctic precipitation (falling snow) and in water vapour to study their dependance on season and sampling site. Long-term sampling at the former German Georg Forster Station during 1978-93 and at the Japanese Syowa Station during 1994-97 allow conclusions about the present seasonal isotopic variations in the water inflow to Antarctica. The δD and δ(18)O values of precipitation at these East Antarctic coastal stations were compared with corresponding data from the West Antarctic Georg von Neumayer and Halley stations. The monthly means of these long-term data sets show typical hysteresis-like seasonal patterns of isotopic composition. Significant time lags exist regarding station temperatures, while water vapour δD values do not show such hysteresis patterns. Here, half-yearly and even quarter-yearly time components were found by Fourier analysis. Attempts were made to describe the variation in δD and δ(18)O values of water vapour and precipitation as well as in the resulting deuterium excess by the mixed cloud isotopic model (MCIM) of Ciais and Jouzel.


Some Bayesian experimental design theory for risk reduction in extrapolation.
Decision problems depending on extrapolation promise to become increasingly important. The key problem is determining if the model being used for extrapolation is going to give reasonable results, or err in a dangerous manner. Ideally, as one proceeds from investigation to decision, some guidance should be present based on the goal as to which investigation will reduce the risk the most given the cost. In this report, a very simple version of the problem is formalized and examined. The result is, interestingly, that the best evidence in support of the favored model is a null result in the experiment most likely to raise doubt over that model. The theory is applied to a simple example drawn from accelerated testing.


Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections.
Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.


A Novel Antibody-Drug Conjugate Targeting Nectin-2 Suppresses Ovarian Cancer Progression in Mouse Xenograft Models.
Ovarian cancer is the fifth leading cause of cancer, followed by front line is mostly platinum agents and PARP inhibitors, and very limited option in later lines. Therefore, there is a need for alternative therapeutic options. Nectin-2, which is overexpressed in ovarian cancer, is a known immune checkpoint that deregulates immune cell function. In this study, we generated a novel anti-nectin-2 antibody (chimeric 12G1, c12G1), and further characterized it using epitope mapping, enzyme-linked immunosorbent assay, surface plasmon resonance, fluorescence-activated cell sorting, and internalization assays. The c12G1 antibody specifically bound to the C2 domain of human nectin-2 with high affinity (KD = 2.90 × 10-10 M), but not to mouse nectin-2. We then generated an antibody-drug conjugate comprising the c12G1 antibody conjugated to DM1 and investigated its cytotoxic effects against cancer cells in vitro and in vivo. c12G1-DM1 induced cell cycle arrest at the mitotic phase in nectin-2-positive ovarian cancer cells, but not in nectin-2-negative cancer cells. c12G1-DM1 induced ~100-fold cytotoxicity in ovarian cancer cells, with an IC50 in the range of 0.1 nM~7.4 nM, compared to normal IgG-DM1. In addition, c12G1-DM1 showed ~91% tumor growth inhibition in mouse xenograft models transplanted with OV-90 cells. These results suggest that c12G1-DM1 could be used as a potential therapeutic agent against nectin-2-positive ovarian cancers.


Bone marrow transplantation demonstrates medullar origin of CD34+ fibrocytes and ameliorates hepatic fibrosis in Abcb4-/- mice.
Bone marrow (BM)-derived stem cells and CD34(+) fibrocytes are associated with fibrogenesis in several organs. In an Abcb4(-/-) mouse model for sclerosing cholangitis alpha-smooth muscle actin-positive (alpha-SMA(+)) myofibroblasts are thought to play a pivotal role in hepatic fibrogenesis. The aim of this study was 2-fold: (1) to demonstrate that the origin of an important fibrogenetic cell population is the BM; and (2) to investigate whether transplantation of BM (BM-Tx) affects liver function, staging, and grading. Surrogate markers for fibrogenesis and regulation of hepatic stellate cells (HSC) as well as progenitor-cell-derived fibrocytes in liver tissue were analyzed by quantitative real-time polymerase chain reaction (PCR) and immunohistology. After lethal irradiation of recipient mice, BM-Tx was carried out by way of tail vein injection of BM cells from marker protein donors (green fluorescent protein, GFP(+)) or Abcb4(-/-) mice as control (syngeneic Tx). Parameters of liver function were assessed serologically and histologically. Activated HSC of alpha-SMA(+)/CRP2(+) phenotype were expressed in approximately 50% of proliferating bile ducts, whereas fibrotic liver parenchyma showed no expression thereof. Epithelial mesenchymal transfer (EMT) was visualized in the areas of proliferating bile ducts. The hematopoietic origin of CD34(+) fibrocytes was demonstrated immunohistologically in livers of BM chimeric mice. These CD34(+) cells infiltrated hepatic lobules from portal fields and developed a desmin(+) phenotype expressing collagen type I in fibrotic parenchyma as well as in vitro after isolation by magnetic cell separation. Transplantation of GFP(+)/Abcb4(+) BM improved liver function and staging compared with sham transplantation, but no significant differences were noticed among allogeneic and syngeneic Tx. The present study is the first to identify that both BM-derived fibrocytes and HSC are involved in biliary fibrogenesis in Abcb4(-/-) mice. Our data suggest that changes in immunity subsequent to BM-Tx may alter hepatic fibrosis.


Efficacy of Adjuvant Chemotherapy Following Curative Resection of Colorectal Cancer Liver Metastases.
Routine use of adjuvant chemotherapy (AC) following hepatectomy for colorectal liver metastases (CRLM) is not universally practiced because of the lack of supporting evidence. Therefore, we investigated the efficacy of AC following curative CRLM resection. Among the 742 patients who underwent their first hepatectomy for CRLM at our institution, 335 were stratified into surgery alone (SA; n=162) and AC (n=173) groups. Poor prognostic factors for SA were identified using multivariate logistic regression analysis. Propensity score matching was used to compare the clinical outcomes between SA and AC groups according to the number of prognostic factors. Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) levels (≥10 ng/ml; p=0.01), primary lymph node metastases (≥1; p=0.0001), and the number (n≥4; p=0.01) and maximum diameter (≥5 cm; p=0.00001) of CRLM tumours were independent poor prognostic factors for overall survival (OS) in the SA group. Patients with ≥3 risk factors were categorized as being high risk. After propensity score matching, the 5-year OS rate was significantly higher in the AC group (n=13) than that in the SA group (n=15; 47.9% vs. 7.3%; p=0.03) among high-risk patients. Adjuvant chemotherapy after curative CRLM resection may improve the prognosis of patients with three or more risk factors including preoperative CEA levels ≥10 g/ml, primary lymph node metastases ≥1, number (≥4) and maximum diameter (≥5 cm) of CRLM tumours.


[Multiple schwannoma of the penis].
Schwannoma or neurilemmoma designate a tumour that originates in the Schwann cells of peripheral nerves, therefore occurring anywhere in the body. They are very rare in the penis. In the literature are reported twenty seven cases of penile schwannoma. We report a case of multiple schwannoma of the penis and make a brief literature revision about this rare pathology.


Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cells.
This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans-specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell-cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections.


Modern imaging of cholangitis.
Cholangitis refers to inflammation of the bile ducts with or without accompanying infection. When intermittent or persistent inflammation lasts 6 months or more, the condition is classified as chronic cholangitis. Otherwise, it is considered an acute cholangitis. Cholangitis can also be classified according to the inciting agent, e.g. complete mechanical obstruction, which is the leading cause of acute cholangitis, longstanding partial mechanical blockage, or immune-mediated bile duct damage that results in chronic cholangitis.The work-up for cholangitis is based upon medical history, clinical presentation, and initial laboratory tests. Whereas ultrasound is the first-line imaging modality used to identify bile duct dilatation in patients with colicky abdominal pain, cross-sectional imaging is preferable when symptoms cannot be primarily localised to the hepatobiliary system. CT is very useful in oncologic, trauma, or postoperative patients. Otherwise, magnetic resonance cholangiopancreatography is the method of choice to diagnose acute and chronic biliary disorders, providing an excellent anatomic overview and, if gadoxetic acid is injected, simultaneously delivering morphological and functional information about the hepatobiliary system. If brush cytology, biopsy, assessment of the prepapillary common bile duct, stricture dilatation, or stenting is necessary, then endoscopic ultrasound and/or retrograde cholangiography are performed. Finally, when the pathologic duct is inaccessible from the duodenum or stomach, percutaneous transhepatic cholangiography is an option. The pace of the work-up depends upon the severity of cholestasis on presentation. Whereas sepsis, hypotension, and/or Charcot's triad warrant immediate investigation and management, chronic cholestasis can be electively evaluated.This overview article will cover the common cholangitides, emphasising our clinical experience with the chronic cholestatic liver diseases.


Parent Preferences and Experiences with Psychological Treatment: Results from a Direct-to- Consumer Survey using the Marketing Mix Framework.
Direct-to-consumer (DTC) marketing strategies represent an increasingly popular approach to promote patient awareness of psychological treatments (PTs). The Marketing Mix is a well-established framework used to inform marketing decisions consisting of four "P's": Product (or Service), Promotion, Place, and Price. We conducted the first DTC marketing survey using the Marketing Mix framework to explore how parents concerned about their adolescents' behavioral health receive information about PTs. A sample of 411 parents (51% girls, 82% Non-Hispanic White) of 12- to 19-year-old adolescents completed an online survey asking how they would prefer to receive information about PTs, including five questions spanning the Promotion, Price, and Place dimensions of The Marketing Mix. A subsample of 158 parents also reported on how they had received PT information during their adolescent's most recent therapy experience, allowing us to compare ideal versus actual therapy experiences. We explored the extent to which experiences varied as a function of parent race/ethnicity, income per capita, parent education level, and adolescent treatment history. Bivariate analyses and multivariate logistic regressions were used to examine which of these variables were associated with parents' responses to specific survey items. Analyses revealed that parent preferences varied as a function of income per capita, education level, and history of treatment. In addition, there were significant gaps between parents' ideal and most recent therapy experiences. Implications for the marketing of PTs are discussed.


Gene networks as a tool to understand transcriptional regulation.
Gene regulatory networks, or simply gene networks (GNs), have shown to be a promising approach that the bioinformatics community has been developing for studying regulatory mechanisms in biological systems. GNs are built from the genome-wide high-throughput gene expression data that are often available from DNA microarray experiments. Conceptually, GNs are (un)directed graphs, where the nodes correspond to the genes and a link between a pair of genes denotes a regulatory interaction that occurs at transcriptional level. In the present study, we had two objectives: 1) to develop a framework for GN reconstruction based on a Bayesian network model that captures direct interactions between genes through nonparametric regression with B-splines, and 2) to demonstrate the potential of GNs in the analysis of expression data of a real biological system, the yeast pheromone response pathway. Our framework also included a number of search schemes to learn the network. We present an intuitive notion of GN theory as well as the detailed mathematical foundations of the model. A comprehensive analysis of the consistency of the model when tested with biological data was done through the analysis of the GNs inferred for the yeast pheromone pathway. Our results agree fairly well with what was expected based on the literature, and we developed some hypotheses about this system. Using this analysis, we intended to provide a guide on how GNs can be effectively used to study transcriptional regulation. We also discussed the limitations of GNs and the future direction of network analysis for genomic data. The software is available upon request.


Anomalous primary radiation from the Leksell Gamma Knife Unit.
The Leksell Gamma Knife Unit, Type U, utilizes 201 separate 60Co sources intersecting at a common focus for radiosurgical treatment of the brain. It has been generally understood that all primary unattenuated radiation beams are confined within the protective housing during all phases of Gamma Knife operation. We have found that when the unit's shielding door is lowered for treatment, twelve primary beams exit the unit's door opening. Furthermore, in the original Gamma Knife unit design, two of the twelve primary beams failed to be attenuated by either the unit base or the unit wings. This has implications for the design of structural shielding and the protection of personnel during emergency procedures. Engineering modifications to eliminate the problem are discussed.


[MALT gastric lymphoma--principles of morphological diagnosis].
MALT gastric lymphoma presents difficulties for morphological diagnosis as it is represented by neoplastic elements having morphology of mature cells. 75 MALT-lymphomas of the stomach with polymorphous tumour infiltrate are reported. The infiltrate was analyzed by cell composition, cell atypia, the presence of lymphoepithelial lesions (LEL) and lymphoid follicles, blast cells and "blast" LEL. Immunohistochemistry may be necessary for diagnosis when clear-cut morphological characteristics are lacking.


Control of DNA Replication Initiation by Ubiquitin.
Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by numerous pathways. A key step in this process is the initiation of DNA replication in which certain regions of DNA are marked as competent to replicate. Moreover, initiation of DNA replication needs to be coordinated with other cell cycle processes. At the molecular level, initiation of DNA replication relies, among other mechanisms, upon post-translational modifications, including the conjugation and hydrolysis of ubiquitin. An example is the precise control of the levels of the DNA replication initiation protein Cdt1 and its inhibitor Geminin by ubiquitin-mediated proteasomal degradation. This control ensures that DNA replication occurs with the right timing during the cell cycle, thereby avoiding re-replication events. Here, we review the events that involve ubiquitin signalling during DNA replication initiation, and how they are linked to human disease.


Synthesis and cationic polymerization of halogen bonding vinyl ether monomers.
Halogen bonding is rapidly becoming recognized as a viable and useful intermolecular interaction in supramolecular chemistry. While various monomers amenable to radical polymerization methods containing halogen bonding donors have been developed, this study aims to expand the type of monomers that incorporate this intermolecular interaction to facilitate use of cationic polymerization by developing three novel vinyl ether monomers containing halogen bonding donor moieties: 2,3,5,6-tetrafluoro-4-iodophenoxyethyl vinyl ether (C2I), 2,3,5,6-tetrafluoro-4-iodophenoxybutyl vinyl ether (C4I), and 2-(2,3,5,6-tetrafluoro-4-iodophenoxyethoxy)ethyl vinyl ether (O3I). Well controlled cationic polymerization is achievable through the use of a proton trap, 2,6-di-tert-butylpyridine. The use of SnCl4 as a co-Lewis acid was found to accelerate the reaction. Between the three monomers, the difference in the chain length is shown to influence the reaction rate, with the longest chain demonstrating the fastest polymerization. Initial studies of the halogen bonding ability shows that halogen bonding exists for all three monomers but is most pronounced in C4I. The polymerized vinyl ethers also exhibit halogen bonding. Due to the ease of synthesis and polymerization, these are promising new monomers to increase functionality available for polymers synthesized using cationic polymerization.


Ring-opening metathesis/oxy-cope rearrangement: a new strategy for the synthesis of bicyclic medium ring-containing compounds.
Ring-opening/ring-closing metathesis on cyclobutene-containing substrates with angular oxygen functionality provides a stereospecific introduction of 1,5-bis-dienes required for an anion-accelerated oxy-Cope rearrangement. The reaction sequence offers generally a stereocontrolled preparation of a variety of medium ring-containing bicyclic ring systems, while rearrangement to the bicyclo[7,3,0]dodecane (9-5) system leads to a mixture of olefin isomers.


Dentistry for Mexicans with special needs: a commentary.
There are more than 2 million residents with disabilities in Mexico. Despite national legislation to assure individuals with disabilities needed services, including education and employment, social inclusion of these individuals is difficult since societal views exclude them from functioning as members of a community. While there are no national studies of the dental needs of individuals with disabilities in Mexico, reports of the general population indicate limited use of dental services and the need for increased restorative services. Examples of dental education accreditation standards in other countries are used as models for the improvement in the preparation of dental students to provide services for individual with special needs.


Stigma and Barriers in Health Care Among a Sample of Transgender and Gender-Diverse Active Duty Service Members.
Transgender and/or gender-diverse (TGD) persons are vulnerable to stigma and health care inequities; however, data are particularly limited among TGD active duty military service members despite ongoing changes to service policies. TGD-related stressors may impede access to and utilization of health care due to fear of potential discrimination and distress, thereby adversely impacting military readiness. We examined stigma and barriers in health care and associations with physical and mental health in an online sample of 177 active duty service members who self-identified as TGD. To assess associations between stigma and barriers in health care with mental and physical health, linear regressions were conducted adjusting for age, gender identity, race, and rank. Over half (65%) of the participants reported at least 1 instance of stigma and/or barrier in health care. Stigma and barriers to health care were significantly associated with greater self-reported depressive symptoms (β=0.20, P =0.03), anxiety (β=0.21, P =0.03), stress (β=0.30, P =0.001), and poorer overall mental health (β=-0.23, P =0.007), after adjusting for covariates. Nearly one-quarter of participants had not disclosed their gender identity to their primary care clinician. Findings suggested that stigma and barriers to affirming health care were prevalent among active duty service members identifying as TGD, specifically, difficulty accessing gender-affirming care and negative assumptions from clinicians. These experiences may adversely affect mental health and impede the quality of health care received by a population already vulnerable to health inequities. Given recent changes to military policy, efforts may be warranted to improve access to timely, affirming care and clinician training.


Comparison of sulfuric acid treatment and multi-layer silica gel column chromatography in cleanup methods for determination of PCDDs, PCDFs and dioxin-like PCBs in foods.
Two typical cleanup methods, sulfuric acid treatment and multi-layer silica gel column chromatography, for the determination of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) in seventeen food samples were examined and compared. Vegetables, fruits, cereals, fish, meat and dairy foods were extracted by conventional methods (shaking with acetone/n-hexane or with n-hexane after alkaline treatment). The extracts were cleaned up by sulfuric acid treatment or multi-layer silica gel column chromatography, followed by several column chromatographic steps. Of the samples treated, the vegetable, fruit and cereal samples could be directly applied to the multi-layer silica gel column after extraction. However, the samples containing fats and oils such as fish, meat and dairy foods needed to be treated several times with concentrated sulfuric acid before multi-layer column chromatography, because these samples plugged the column with oily residues. Both cleanup methods gave similar values of isomeric concentrations and showed similar efficiency of purification, and the recoveries ranged from 40 to 120%. These results are considered to provide useful data for the efficient analysis of dioxins in foods which have wide-ranging compositions.


Simulation models of sugary drink policies: A scoping review.
Simulation modeling methods are an increasingly common tool for projecting the potential health effects of policies to decrease sugar-sweetened beverage (SSB) intake. However, it remains unknown which SSB policies are understudied and how simulation modeling methods could be improved. To inform next steps, we conducted a scoping review to characterize the (1) policies considered and (2) major characteristics of SSB simulation models. We systematically searched 7 electronic databases in 2020, updated in 2021. Two investigators independently screened articles to identify peer-reviewed research using simulation modeling to project the impact of SSB policies on health outcomes. One investigator extracted information about policies considered and key characteristics of models from the full text of included articles. Data were analyzed in 2021-22. Sixty-one articles were included. Of these, 50 simulated at least one tax policy, most often an ad valorem tax (e.g., 20% tax, n = 25) or volumetric tax (e.g., 1 cent-per-fluid-ounce tax, n = 23). Non-tax policies examined included bans on SSB purchases (n = 5), mandatory reformulation (n = 3), warning labels (n = 2), and portion size policies (n = 2). Policies were typically modeled in populations accounting for age and gender or sex attributes. Most studies focused on weight-related outcomes (n = 54), used cohort, lifetable, or microsimulation modeling methods (n = 34), conducted sensitivity or uncertainty analyses (n = 56), and included supplementary materials (n = 54). Few studies included stakeholders at any point in their process (n = 9) or provided replication code/data (n = 8). Most simulation modeling of SSB policies has focused on tax policies and has been limited in its exploration of heterogenous impacts across population groups. Future research would benefit from refined policy and implementation scenario specifications, thorough assessments of the equity impacts of policies using established methods, and standardized reporting to improve transparency and consistency.


Model-Based Clustering with Measurement or Estimation Errors.
Model-based clustering with finite mixture models has become a widely used clustering method. One of the recent implementations is MCLUST. When objects to be clustered are summary statistics, such as regression coefficient estimates, they are naturally associated with estimation errors, whose covariance matrices can often be calculated exactly or approximated using asymptotic theory. This article proposes an extension to Gaussian finite mixture modeling-called MCLUST-ME-that properly accounts for the estimation errors. More specifically, we assume that the distribution of each observation consists of an underlying true component distribution and an independent measurement error distribution. Under this assumption, each unique value of estimation error covariance corresponds to its own classification boundary, which consequently results in a different grouping from MCLUST. Through simulation and application to an RNA-Seq data set, we discovered that under certain circumstances, explicitly, modeling estimation errors, improves clustering performance or provides new insights into the data, compared with when errors are simply ignored, whereas the degree of improvement depends on factors such as the distribution of error covariance matrices.


Force and time control in the production of rhythmic movement sequences in Parkinson's disease.
This study investigated force and time control in rhythm production in Parkinson's disease. Patients and age-matched controls reproduced rhythms consisting of equal (600 ms) or alternating (400 and 800 ms) intervals, produced with equal (12 N) or alternating (8 and 16 N) forces, under paced (synchronization) and unpaced (continuation) conditions. Performance was assessed in terms of accuracy and variability. Reproduction of force amplitudes was less accurate in patients than in controls when either time or force alternated but did not deteriorate further when force and time alternated. In contrast, interval timing was least accurate in patients compared with controls when rhythm alternated on both dimensions. The ratio between alternating force levels was better maintained by controls than by patients, without influence of timing requirements in either group. In contrast, the ratio between alternating intervals was relatively preserved in patients when force remained constant but was severely compromised when force alternated. Timing variability was greater in the patient group, especially in the more affected side, but there was no difference in timing variability between groups as a function of rhythm, and there were no differences between groups in variability of force. The results show that force and time control in patients are affected in different ways. We interpret the preserved timing of rhythms with alternation on one dimension as evidence of intact ability to organize movements in a sequence. The data are compatible with a basal ganglia role in the coregulation of time and force, but do not support a general timing function of the basal ganglia.