Correlation among lens opacities classification system III grading, visual function index-14, pentacam nucleus staging, and objective scatter index for cataract assessment.
To investigate the relationship among Lens Opacities Classification System III (LOCS III) grading score, Visual Function Index-14 (VF-14) score, average lens density by the Pentacam Nucleus Staging system, and the objective scatter index measured by the Optical Quality Analysis System in age-related cataract patients. Prospective, single-center, cross-sectional study. Thirty-six subjects (60 eyes) with age-related cataract were recruited. Subjects with any corneal anomaly potentially affecting intraocular scatter were excluded. The best-corrected visual acuity (BCVA), LOCS III nuclear opalescence score and cortical cataract score, VF-14 score, average lens density, and objective scatter index were obtained. Correlations among these parameters were analyzed. The LOCS III nuclear opalescence score was correlated with the BCVA (r = 0.438; P = .001), objective scatter index (r = 0.543; P < .001), and average lens density (r = 0.621; P < .001). The objective scatter index was also correlated with the BCVA (r = 0.779; P < .001) and the average lens density (r = 0.320; P = .013). The VF-14 score had the strongest correlation with the objective scatter index (r = -0.712; P < .001). The difference between groups with objective scatter index<3.0 and ≥3.0 was significant with regard to BCVA, average lens density, LOCS III nuclear opalescence score, and VF-14 score. LOCS III grading remains an economical and effective method to assess lens opacities, especially in the formation of early cortex cataracts. The objective scatter index can be a useful parameter to objectively analyze the correlation between ocular examination findings and patient concerns. Furthermore, the objective scatter index scores ≥3.0 can be a possible objective cut-off for preoperative decision making.


Phylogeography of the neotropical sand fly Lutzomyia longipalpis inferred from mitochondrial DNA sequences.
Sand flies in the Lutzomyia longipalpis species complex include the primary vector of Leishmania chagasi, the etiologic agent of visceral leishmaniasis in the Neotropics. Twelve L. longipalpis populations from South and Central America were compared using the cytochrome c oxidase I (COI) gene from the mitochondrial genome. The haplotype profiles for each population revealed that the majority of sequence variation was inter-population (98%) rather than intra-population, suggesting that sequence polymorphisms at the COI locus should provide excellent characters for the study of phylogenetic relationships among populations. Phylogenetic reconstruction using distance (neighbor-joining) and maximum parsimony analysis revealed the existence of four clades among the L. longipalpis populations studied: (1) Laran, (2) Brazilian, (3) cis-Andean and (4) trans-Andean. We suggest that these clades represent species. A biogeographical interpretation of the molecular phylogeny suggests that the process of speciation in the L. longipalpis complex began in the Pliocene, from a sub-Andean-Amazonian gene pool resulting from the Andean orogeny (formation of the East Andean Cordillera). The four clades probably diverged as a result of vicariance events that occurred throughout the late Pliocene and Pleistocene. We propose and discuss several historical scenarios, based on the biogeography and historical geology of Central and South America.


Subcellular fractionation of human intestinal mucosa by large-scale zonal centrifugation. Characteristics of lysosomes and brush border membranes in the distal ileum of a patient with Crohn's disease.
Lysosomes and brush border membranes from diseased ileal mucosa of a patient with Crohn's disease were separated by rate zonal density gradient centrifugation. The organelles were located and characterized in the density gradient of assay of marker enzymes, and their enzyme content compared to that of similar organelles from normal tissue. The activity and latency of lysosomal enzymes (N-acetyl-beta-glucosaminidase and acid phosphatase) was significantly increased, whereas the activity of brush border alkaline phosphatase was rather decreased. The possible relevance of these findings to the pathophysiology of Crohn's disease is discussed.


MicroRNA-19b downregulates insulin 1 through targeting transcription factor NeuroD1.
MiR-17-92 cluster miRNAs are disclosed to contribute to the development of multiple organs and tumorigenesis, but their roles in pancreas development remains unclear. In this study, we found that miR-19b, a member of miR-17-92, was highly expressed in the pancreatic progenitor cells, and miR-19b could target the 3' UTR of NeuroD1 mRNA to decrease its protein and mRNA levels. Functional analysis showed that miR-19b exerted little effect on the proliferation of pancreatic progenitors, whereas it inhibited the expression of insulin 1, but not insulin 2 in MIN6 cells. These results suggest that miR-19b can downregulate insulin 1 expression through targeting transcription factor NeuroD1, and thus regulate the differentiation and function of β-cells.


Fitting unbranching skeletal structures to objects.
Representing an object by a skeletal structure can be powerful for statistical shape analysis if there is good correspondence of the representations within a population. Many anatomic objects have a genus-zero boundary and can be represented by a smooth unbranching skeletal structure that can be discretely approximated. We describe how to compute such a discrete skeletal structure ("d-s-rep") for an individual 3D shape with the desired correspondence across cases. The method involves fitting a d-s-rep to an input representation of an object's boundary. A good fit is taken to be one whose skeletally implied boundary well approximates the target surface in terms of low order geometric boundary properties: (1) positions, (2) tangent fields, (3) various curvatures. Our method involves a two-stage framework that first, roughly yet consistently fits a skeletal structure to each object and second, refines the skeletal structure such that the shape of the implied boundary well approximates that of the object. The first stage uses a stratified diffeomorphism to produce topologically non-self-overlapping, smooth and unbranching skeletal structures for each object of a population. The second stage uses loss terms that measure geometric disagreement between the skeletally implied boundary and the target boundary and avoid self-overlaps in the boundary. By minimizing the total loss, we end up with a good d-s-rep for each individual shape. We demonstrate such d-s-reps for various human brain structures. The framework is accessible and extensible by clinical users, researchers and developers as an extension of SlicerSALT, which is based on 3D Slicer.


Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis.
Cardiomyocyte apoptosis is critical for the development of viral myocarditis (VMC), which is one of the leading causes of cardiac sudden death in young adults. Our previous studies have demonstrated that elevated calpain activity is involved in the pathogenesis of VMC. This study aimed to further explore the underlying mechanisms. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin were infected with coxsackievirus B3 (CVB3) to establish a VMC model. Apoptosis was detected with flow cytometry, TUNEL staining, and western blotting. Cardiac function was measured using echocardiography. Mitochondrial function was measured using ATP assays, JC-1, and MitoSOX. Mitochondrial morphology was observed using MitoTracker staining and transmission electron microscopy. Colocalization of dynamin-related protein 1 (Drp-1) in mitochondria was examined using immunofluorescence. Phosphorylation levels of Drp-1 at Ser637 site were determined using western blotting analysis. We found that CVB3 infection impaired mitochondrial function as evidenced by increased mitochondrial ROS production, decreased ATP production and mitochondrial membrane potential, induced myocardial apoptosis and damage, and decreased myocardial function. These effects of CVB3 infection were attenuated by inhibition of calpain both by PD150606 treatment and calpastatin overexpression. Furthermore, CVB3-induced mitochondrial dysfunction was associated with the accumulation of Drp-1 in the outer membrane of mitochondria and subsequent increase in mitochondrial fission. Mechanistically, calpain cleaved and activated calcineurin A, which dephosphorylated Drp-1 at Ser637 site and promoted its accumulation in the mitochondria, leading to mitochondrial fission and dysfunction. In summary, calpain inhibition attenuated CVB3-induced myocarditis by reducing mitochondrial fission, thereby inhibiting cardiomyocyte apoptosis. Calpain is activated by CVB3 infection. Activated calpain cleaves calcineurin A and converts it to active form which could dephosphorylate Drp-1 at Ser637 site. Then, the active Drp-1 translocates from the cytoplasm to mitochondria and triggers excessive mitochondrial fission. Eventually, the balance of mitochondrial dynamics is broken, and apoptosis occurs.


Portal vein resection.
The American Hepato-Pancreatico-Biliary Association and Society of Surgical Oncology published a consensus statement in 2009 on the subject of vein resection and reconstruction during pancreaticoduodenectomy (PD), and concluded that PD with vein resection and reconstruction is a viable option for treatment of some pancreatic adenocarcinomas. This article describes the current approaches and recent advances in the management, staging, and surgical techniques regarding portal vein resection. With proper patient selection, a detailed understanding of the anatomy of the root of mesentery, and adequate surgeon experience, vascular resection and reconstruction can be performed safely and does not impact survival duration. Isolated venous involvement is not a contraindication to PD when performed by experienced surgeons at high-volume centers as part of a multidisciplinary and multimodal approach to localized pancreatic cancer.


[Aicardi-Goutieres syndrome: a family case due to alteration of the RNASEH2B gene].
Aicardi-Goutieres syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. The Aicardi-Goutieres syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.


Lumbar axial rotation kinematics in men with non-specific chronic low back pain.
Lumbar flexion, coupled with rotation, is a dominant factor in the etiology and exacerbation of low back pain. Yet, no study has examined its kinematics in patients with non-specific chronic low back pain (NSCLBP). The aim of the study was to evaluate the lumbar rotation kinematics in neutral standing and with full flexion in men with NSCLBP. ROM, average velocity, maximum velocity and maximal acceleration of lumbar rotation in neutral standing and with full flexion were measured using an industrial lumbar motion monitor in 50 men (25 with NSCLBP and 25 controls). VAS and Rolland Morris questionnaire were also included. All examined kinematical parameters were significantly lower in men with NSCLBP compared with controls (↓ROM = 29%-45%; ↓AV = 40%-68%; ↓MV = 25%-50%; ↓MA = 20%-37%). Left rotation manifested smaller kinematic values (except for MA) than right rotation (Δ ROM = 35%; Δ AV = 66%; Δ MV = 19%) in NSCLBP. Most kinematical parameters significantly decreased from neutral standing to standing with flexion (right rotation: ↓ROM = 43%-45%, ↓AV = 38%-45%, ↓MV = 24%-27%, ↓MA for the NSCLBP group = 21%; left rotation: ↓ROM = 25%-38%, ↓AV in the control group: =34%, ↓MV in the control group: =23%, ↓MA in the control group = 25%). No correlations were found between all measured kinematical parameters, VAS and RMQ total score in the NSCLBP group. The kinematic parameters of lumbar rotation were reduced in men with NSCLBP compared with controls both in neutral standing and with fully forward bending. Most lumbar rotation kinematics decreased from neutral standing to standing with flexion.


Effects of the geomagnetic field time-varying components compensation as evidenced by heart rate variability of healthy males.
Evolutionarily, a human organism is adapted to the natural geomagnetic environment and its slight alterations. However, during geomagnetic storms (GMSs), the strength of the geomagnetic field (GMF) sharply increased hundreds of times and can pose a serious threat to people. We examine the effects of controlled compensation in the time-varying components of the GMF, using a specially created experimental setup with electrically shielding solutions, providing an electromagnetically quiet environment. The measurement of heart rate variability (HRV) on 25 healthy young male volunteers was carried out in the laboratory using the experimental setup at different levels of outdoor geomagnetic activity (GMA). The geomagnetic K-index was used to characterize the magnitude of GMSs; volunteers were tested during quiet magnetic days (K = 1-3), days with K = 4, and days with GMSs (K ≥ 5) in the period of solar cycle maximum. During quiet magnetic days, the comparison between HRV baseline values with values measured under GMF time-varying components compensation mode (CM) did not reveal any changes. On days with K = 4 some HRV indices shifted from their initial values, but it was statistically not significant. However, on days with GMSs statistically significant changes in SDNN* (p = 0.033) and LF* (p = 0.011) indices of HRV were observed in the GMS CM compared to their baseline values. The experiments showed that GMSs cause a sensitive reaction of the heart rate regulatory mechanism, the effect of which can be canceled in the GMS CM. The efficiency of the used technology is supported by the results of this study. * SDNN (Standard Deviation Normal to Normal R-R of cardiointervals), LF (Low frequency spectral band of cardiointervals).


Influence of corneal shape parameters on corneal deformation responses measured with a Scheimpflug camera.
To investigate the effect of corneal shape parameters on corneal deformation responses measured with a Scheimpflug camera. A total of 241 eyes of 241 participants were enrolled in this study. The anterior and posterior corneal curvature radii (CCR), anterior and posterior corneal Q-values, and corneal diameters of the participants were measured using the Pentacam HR. A total of 17 corneal deformation parameters including time, velocity, deflection amplitude, length, and area during ingoing applanation, highest concavity, and outgoing applanation were recorded by corneal visualization using Scheimpflug technology (Corvis ST). The effect of corneal shape parameters on corneal deformation responses was evaluated using multivariate regression models. Multivariate regression analyses showed that six, five, four, and three corneal deformation parameters were significantly correlated with anterior CCR, posterior CCR, anterior Q-value, and posterior Q-value, respectively. Steeper anterior corneal curvature was associated with faster velocity during ingoing applanation and greater deformation during outgoing applanation. Steeper posterior corneal curvature was correlated with faster velocity during outgoing applanation and greater deformation during ingoing applanation. Eyes that had steeper corneal curvatures were associated with less stiff corneas. More negative anterior Q-value corresponded with faster velocity and greater deformation during ingoing applanation. Eyes that had more prolate posterior corneal surfaces showed more resistance to corneal deformation at the highest concavity. However, corneal diameter was not selected in any corneal deformation parameters models. Corneal deformation response is significantly influenced by anterior and posterior corneal curvature and corneal asphericity, but not corneal diameter.


Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review.
Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28 months (range, 6-90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3-4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.


Long-term kidney transplant graft survival-Making progress when most needed.
Current short-term kidney post-transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000-2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014-2017 (1995-1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995-1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995-1999 to an estimated 19.2 years for transplants in 2014-2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.


Ethanolic extract of Coelogyne cristata Lindley (Orchidaceae) and its compound coelogin promote osteoprotective activity in ovariectomized estrogen deficient mice.
Coelogyne cristata Lindley (CC) family Orchidaceae is an Indian medicinal plant used for the treatment of fractured bones in folk-tradition of Kumaon region, Uttarakhand, India. In continuation of our drug discovery program, feeding of ethanolic extract to ovariectomized estrogen deficient mice led to significant restoration of trabecular micro architecture in both femoral and tibial bones, better bone quality and also devoid of any uterine estrogenicity. Subsequently, coelogin, a pure compound was isolated from ethyl acetate fraction of C. cristata and evaluated in in vitro osteoblast cell cultures. Treatment of coelogin to osteoblasts led to enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen and RUNX-2. Based on these results, we propose that ethanolic extract of C. cristata and its pure compound coelogin have potential in the management of post menopausal osteoporosis.


A High-Value Care Initiative to Reduce the Use of Intravenous Magnesium Sulfate Through an Electronic Indication-Based Order Set.
Intravenous (IV) magnesium sulfate (MgSO4) supplementation is common despite limited indications. Oral magnesium oxide (MgO) is an effective, lower-cost alternative. This project aimed to reduce IV MgSO4 use by 20% among the Internal Medicine (IM) service. Electronic health record (EHR) orders for MgSO4 and MgO within the IM service were replaced with an indication-based EHR order panel. The project team educated clinicians regarding indications for IV MgSO4 and relative costs. The mean of daily 2 g MgSO4 administrations per week and the mean of weekly proportion of 2 g MgSO4 administrations nine months before and after intervention were compared between IM and Emergency Medicine (EM) (control group). Statistical process control analysis was used to assess for special cause variation in daily MgSO4 per week and weekly proportion of MgSO4 administrations. The mean of daily 2 g IV MgSO4 administrations per week decreased among IM (19.3 vs. 12.1, p < 0.0001) but not EM (3.1 vs. 4.8, p < 0.0001). The mean of weekly proportions of IV MgSO4 administrations decreased among both IM (83.6% vs. 60.7%, p < 0.0001) and EM (97.0% vs. 93.1%, p = 0.0004). For IM, the change in daily MgSO4 per week and weekly proportion of MgSO4 occurred as a discrete initial decline consistent with special cause variation; for EM, changes in both measures were not consistent with special cause variation. Replacing stand-alone IV MgSO4 orders with an indication-based order panel along with clinician education reduced IV MgSO4 administrations and may offer a significant opportunity to reduce low-value care.


Developmental origin of fat: tracking obesity to its source.
The development of obesity not only depends on the balance between food intake and caloric utilization but also on the balance between white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specialized for energy expenditure. In addition, some sites of white fat storage in the body are more closely linked than others to the metabolic complications of obesity, such as diabetes. In this Review, we consider how the developmental origins of fat contribute to its physiological, cellular, and molecular heterogeneity and explore how these factors may play a role in the growing epidemic of obesity.


Test/Retest Reliability and Validity of Remote vs. In-Person Anthropometric and Physical Performance Assessments in Cancer Survivors and Supportive Partners.
(1) Background: Anthropometric and physical performance testing is commonly done in lifestyle research and is traditionally performed in-person. To expand the scalability of lifestyle interventions among cancer survivors, in-person assessments were adapted to remote means and evaluated for feasibility, safety, validity, and reliability. (2) Methods: Cancer survivors and supportive partners were approached to participate in three anthropometric and physical performance testing sessions (two remote/one in-person). Correlations, concordance, and differences between testing modes were evaluated. (3) Results: 110-of-112 individuals approached for testing participated (98% uptake); the sample was 78% female, 64% non-Hispanic White, of mean age 58 years and body mass index = 32.4 kg/m2. ICCs for remote assessments ranged from moderate (8' walk = 0.47), to strong (8' get-up-and-go = 0.74), to very strong (30 s chair stand = 0.80; sit-and-reach = 0.86; 2 min step test = 0.87; back scratch = 0.90; weight = 0.93; waist circumference = 0.98) (p-values < 0.001). Perfect concordance (100%) was found for side-by-side and semi-tandem balance, and 87.5-90.3% for tandem balance. No significant differences between remote and in-person assessments were found for weight, 8' walk, and 8' get-up-and-go. No adverse events occurred and 75% indicated no preference or preferred virtual testing to in-person. (4) Conclusions: Remote anthropometric and physical performance assessments are reliable, valid, acceptable, and safe among cancer survivors and supportive partners.


Host-pathogen interaction involving cytoskeleton changes as well as non-coding regulation as primary mechanisms for SRS resistance in Atlantic salmon.
The salmonid rickettsial syndrome (SRS) is a systemic bacterial infection caused by Piscirickettsia salmonis that generates significant economic losses in Atlantic salmon (Salmo salar) aquaculture. Despite this disease's relevance, the mechanisms involved in resistance against P. salmonis infection are not entirely understood. Thus, we aimed at studying the pathways explaining SRS resistance using different approaches. First, we determined the heritability using pedigree data from a challenge test. Secondly, a genome-wide association analysis was performed following a complete transcriptomic profile of fish from genetically susceptible and resistant families within the challenge infection with P. salmonis. We found differentially expressed transcripts related to immune response, pathogen recognition, and several new pathways related to extracellular matrix remodelling and intracellular invasion. The resistant background showed a constrained inflammatory response, mediated by the Arp2/3 complex actin cytoskeleton remodelling polymerization pathway, probably leading to bacterial clearance. A series of biomarkers of SRS resistance, such as the beta-enolase (ENO-β), Tubulin G1 (TUBG1), Plasmin (PLG) and ARP2/3 Complex Subunit 4 (ARPC4) genes showed consistent overexpression in resistant individuals, showing promise as biomarkers for SRS resistance. All these results together with the differential expression of several long non-coding RNAs show the complexity of the host-pathogen interaction of S. salar and P. salmonis. These results provide valuable information on new models describing host-pathogen interaction and its role in SRS resistance.


Repressing the repressor: Ezh2 mediates macrophage activation.
In this issue of JEM, Zhang et al. (https://doi.org/10.1084/jem.20171417) show that the suppressive epigenetic enzyme Ezh2 is an important regulator of macrophage activation. The absence of Ezh2 leads to reduced cytokine secretion and suppresses macrophage-dependent disease development. They identify the antiinflammatory factor Socs3 as an important target for Ezh2 and thus show that regulation of suppressive histone modifications controls macrophage activation in disease.


Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of controlled human intervention trials.
A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. Our findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.


Mesenteric inflammatory myofibroblastic tumor mimicking acute appendicitis: A case report.
An Inflammatory myofibroblastic tumor, a neoplasm of intermediate biological potential, of the small bowel mesentery, is a rare tumor, most commonly reported in but not confined to the pediatric age group. This case report underlines a case of a (small bowel) mesentery IMT in an adult female presenting with recurrent symptoms similar to acute appendicitis. It can present with symptoms similar to acute appendicitis necessitating a high index of suspicion for its prompt diagnosis. Treatment primarily includes surgical resection with recent advances in targeted therapy with tyrosine kinase inhibitors showing promising results. IMTs can present as clinical as well as histopathological mimickers of a variety of diseases especially in the abdomen. Prompt diagnosis requires both imaging and histopathological examination.


Management of children with urinary tract infections: the Stanford experience.
Two hundred seventy-eight female children with urinary tract infections have been evaluated at Stanford division of urology. All children were followed up for a period of not less than twelve months. Age of onset of infection, clinical presentation, and nature of infecting organisms were observed. The group consisted of 144 children without ureteral reflux and 134 children with ureteral reflux. Sixty-one of the female children with ureteral reflux had ureteral reimplantation, while 73 received medical treatment alone. A study of infection rates in each of the three groups of children indicated a similar infection rate, although those children with reflux experienced a higher incidence of clinical pyelonephritis. Correction of ureteral reflux did not alter the infection rate; however, infections after surgical correction were generally of a type usually associated with children without reflux. Twenty-nine children had urethral dilatation, and the infection rate prior to and following urethral dilatation indicated a similar rate of infection pre- and posturethral dilatation. One hundred nonrefluxing kidneys were observed radiologically: 97 were normal and 3 showed clubbing and scarring. Of 110 refluxing renal units observed, 62 were clubbed and scarred and 48 were normal. Following surgical correction of reflux, renal clubbing and scarring were not observed in previously normal renal units. Of those renal units found to be abnormal at time of surgery, 66 per cent showed progression of clubbing and scarring after surgical correction of reflux. It was observed that the greater the degree of reflux present, the higher the incidence of renal damage. This study suggests that children who experience recurrent urinary tract infections who do not have ureteral reflux are seldom at renal risk; similar children who do have ureteral reflux are at risk unless the infections are controlled or the reflux either disappears or is corrected surgically.


Influence of Genetic Counseling Graduate Program Websites on Student Application Decisions.
This study investigated how genetic counseling educational program websites affect application decisions via an online survey sent to current students and recent graduates. Program leadership: directors, assistant directors, associate directors, were also surveyed to determine where their opinions coincided or differed from those reported by students and recent graduates. Chi square analysis and t-tests were used to determine significance of results. A two-sample t-test was used to compare factors students identified as important on a 5-point Likert scale with those identified by directors. Thematic analysis revealed three major themes students consider important for program websites: easy navigation, website content, and website impression. Directors were interested in how prospective students use their program website and what information they found most useful. Students indicated there were specific programs they chose not to apply to due to the difficulty of using the website for that program. Directors significantly underestimated how important information about application requirements was to students in making application decisions. The information reported herein will help individual genetic counseling graduate programs improve website functionality and retain interested applicants.


Epithelium-linked smooth muscle hyperresponsiveness in ferret tracheae exposed to acrolein.
The effects of acrolein exposure on tissue uptake and airway responses to substance P (SP) and nitroprusside (NIP) were determined in excised ferret tracheae exposed for 60 min to a constant flow of air or 0.3 and 3.5 ppm acrolein-air mixtures. Histological examination indicated that whereas the epithelium of an air-exposed trachea was intact with no apparent injury, acrolein-induced epithelium damage was more pronounced at 3.5 than at 0.3 ppm vapor concentration. The fractional uptake of acrolein into the tracheal tissue continually decreased during the 1 h of exposure and was found to be significantly concentration dependent at the 60 min measurement point. This suggests that the uptake process of acrolein in the mucosal layer is not linear and is dominated by irreversible reaction. In the absence of the neutral endopeptidase inhibitor, phosphoramidon, acrolein significantly increased the maximal response to SP. Pretreatment with phosphoramidon abolished the differential effect of acrolein on airway smooth muscle response to SP. Nitroprusside relaxed acrolein-exposed tracheal rings precontracted with carbachol to their baseline tone, but it induced relaxation of air-exposed tracheal rings below their initial resting tension, indicating the presence of endogenous as well as induced tone. Pretreatment with NIP also abolished the differential effect of acrolein on airway response to carbachol and modified the potency of this agonist. We conclude that acrolein-induced hyperresponsiveness of the underlying airway smooth muscle is linked to inactivation of neutral endopeptidase synthesis as well as to loss of epithelium-derived relaxation factor.


Micro Spectroscopic Photoacoustic (μsPA) imaging of advanced carotid atherosclerosis.
Atherosclerosis is a lipid-driven and an inflammatory disease of the artery walls. The composition of atherosclerotic plaque stratifies the risk of a specific plaque to cause a cardiovascular event. In an optical resolution photoacoustic microscopy setup, of 45 μm resolution, we extracted plaque lipid photoacoustic (PA) spectral signatures of human endarterectomy samples in the range of 1150-1240 nm, using matrix assisted laser desorption ionization mass spectrometry imaging as a reference. We found plaque PA signals to correlate best with sphingomyelins and cholesteryl esters. PA signal spectral variations within the plaque area were compared to reference molecular patterns and absorption spectra of lipid laboratory standards. Variability in the lipid spectroscopic features extracted by principal component analysis of all samples revealed three distinct components with peaks at: 1164, 1188, 1196 and 1210 nm. This result will guide the development of PA-based atherosclerosis disease staging capitalizing on lipidomics of atherosclerotic tissue.


A novel drug-eluting stent using bioabsorbable polymer technology: two-year follow-up of the CURAMI registry.
There are safety concerns on drug-eluting stents (DESs) using durable polymer. The long-term outcome of next generation DESs using bioabsorbable polymer technology remains unknown. From March to June, 2005, a novel sirolimus-eluting (170 microg/cm2), bioabsorbable polymer (PLA and PLGA, eroded over 45 days) coated stent was implanted for treatment of acute myocardial infarction (AMI) in 49 patients (male 86%, age 55+10 years, diabetes 31%). All culprits were de novo lesions in the native coronary artery. On discharge, aspirin and clopidogrel for 3 months followed by life-long aspirin were prescribed. Angiographic follow-up was performed at 8 months. Clinical follow-up was performed at 4, 9 and 24 months. Angiographic success rate was 100%. In-hospital adverse events consisted of 1 death (2%). All except one patient (due to aspirin allergy) were compliant to the 3 months dual antiplatelet therapy, and there was no adverse event during this period. One patient developed re-infarction in another coronary territory at 6 months. Twenty-seven patients (56%) underwent 8-month angiographic follow-up (Table 3). At 24 months, 6 patients had 7 major adverse cardiac events (12.2%, 1 death, 2 re-infarctions and 4 target lesion revascularizations). There were no incidences of subacute or late stent thrombosis. The Cura stent, using bioabsorbable polymer technology, appears to be safe at 2 years follow-up. Although the angiographic follow-up parameters were unfavorable, this report paves the way for further studies on DES using bioabsorbable polymer technology.


Determination of partition ratios for allylisopropylacetamide during suicidal processing by a phenobarbital-induced cytochrome P-450 isozyme from rat liver.
Allylisopropylacetamide is shown to be a suicide substrate for the phenobarbital-inducible cytochromes P-450. In phenobarbital-induced rat liver microsomes about 70% of the cytochrome P-450-mediated N,N-dimethylaniline N-demethylase activity is sensitive to allylisopropylacetamide inactivation; the residual 30% of the N-demethylase activity is incapable of allylisopropylacetamide turnover and insensitive to allylisopropylacetamide inactivation. The partition number for inactivation of the susceptible population of cytochrome P-450 indicates turnover of 201 molecules of allylisopropylacetamide per molecule of P-450 inactivated. A purified phenobarbital-induced isozyme of cytochrome P-450, when reconstituted with purified rat liver cytochrome P-450 reductase, is also inactivated by allylisopropylacetamide in a suicide fashion with a corrected partition ratio of 184 turnovers of allylisopropylacetamide per inactivation event. This partition number is corrected for the competing O2-dependent autoinactivation of cytochrome P-450 which we have previously shown to occur with the purified isozyme (Loosemore, M., Light, D. R., and W#alsh, C. (1980) J. Biol. Chem. 255, 9017-9020). The 201 product molecules of cytochrome P-450-mediated turnover of allylisopropylacetamide in either the microsomal or purified enzyme system are probably the epoxide, are reactive toward alkylation of cellular nucleophiles, and covalently modify protein and exogenous calf thymus DNA molecules.


[Epigenetic therapies, a step beyond biologics for rheumatoid arthritis].
Over the last decade, the management of rheumatoid arthritis has evolved as a result of both the understanding of disease-related processes and the availability of the necessary high-throughput technology to provide patients with molecule-based therapies. New therapies allow the classification of patients into subsets as regards clinical response, at the same time adding to our knowledge of rheumatoid arthritis pathogenesis. New generations of molecules will likely soon be ready for "a la carte" treatment of patients. A promising field of research is epigenetics. Epigenetic regulatory mechanisms switch on and off the transcription of specific genes in individual cells. Acting as observers on non-adequate gene expression, these mechanisms yield protection against the development of tumours. The major achievement of epigenetic therapies could be their selective action on cells with altered epigenetic programs, and it is our challenge to recognize these alterations among patients with rheumatoid arthritis. Although safety concerns may arise, epigenetic drugs will likely be used to treat autoimmune diseases.


The presence of eosinophil aggregates correlates with increased postoperative prednisone requirement.
Failure after sinus surgery is multifactorial, but often due to recurrence of inflammatory mucosal disease. Postoperative steroid requirements for controlling mucosal inflammation may provide insight into predicting which patients require more aggressive medical therapy to prevent disease relapse. Retrospective chart review. A review was performed of patients who underwent functional endoscopic sinus surgery (FESS) for refractory chronic rhinosinusitis (CRS). Sino-Nasal Outcome Test-22 scores and cumulative prednisone dose (milligrams) requirements at 1, 3, and 6 months postoperatively were reviewed. A structured histopathology report of 11 variables was accessed to correlate histopathology with postoperative steroid requirements. One hundred one patients were reviewed including 42 CRS with nasal polyps and 59 CRS without nasal polyps patients. CRS patients with eosinophilia required greater cumulative steroids to control disease at 1-, 3-, and 6-month postoperative intervals (P < .026, P < .007, P < .013, respectively) compared to patients without eosinophilia. Patients with tissue eosinophil aggregates required the highest cumulative steroids at 1-, 3-, and 6-month postoperative intervals (P < .003, P < .001, P < .001, respectively). When removing patients with eosinophil aggregates from the eosinophilia group, no difference persisted between patients with eosinophilia and those without eosinophilia at all intervals (P = .664, P = .735, P = .800, respectively). No other histopathology variable correlated with postoperative steroid requirement. Tissue eosinophil aggregates appear to be the largest driving factor for increased prednisone requirements after sinus surgery to control mucosal disease than mere presence of eosinophils. This key finding may identify patients at high risk for failure after sinus surgery and guide more proactive postoperative management. 4 Laryngoscope, 129:794-799, 2019.


In vitro flexor tendon cell response to TGF-beta1: a gene expression study.
Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta1 (TGF-beta1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation. Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-beta1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase. We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta1.


A history of exploring cancer in context.
The concept that progression of cancer is regulated by interactions of cancer cells with their microenvironment was postulated by Stephen Paget over a century ago. Contemporary tumour microenvironment (TME) research focuses on the identification of tumour-interacting microenvironmental constituents, such as resident or infiltrating non-tumour cells, soluble factors and extracellular matrix components, and the large variety of mechanisms by which these constituents regulate and shape the malignant phenotype of tumour cells. In this Timeline article, we review the developmental phases of the TME paradigm since its initial description. While illuminating controversies, we discuss the importance of interactions between various microenvironmental components and tumour cells and provide an overview and assessment of therapeutic opportunities and modalities by which the TME can be targeted.


Identification of matrix metalloproteinase-10 as a key mediator of podocyte injury and proteinuria.
Podocyte injury or dysfunction plays an essential role in causing proteinuria and glomerulosclerosis in chronic kidney diseases. To search for new players involved in podocyte injury, we performed gene expression profiling in the glomeruli by RNA sequencing. This unbiased approach led us to discover matrix metalloproteinase-10 (MMP-10), a secreted zinc-dependent endopeptidase, as one of the most upregulated genes after glomerular injury. In animal models and patients with proteinuric chronic kidney diseases, MMP-10 was upregulated specifically in the podocytes of injured glomeruli. Patients with chronic kidney diseases also had elevated circulating levels of MMP-10, which correlated with the severity of kidney insufficiency. In transgenic mice with podocyte-specific expression of MMP-10, proteinuria was aggravated after injury induced by Adriamycin. This was accompanied by more severe podocytopathy and glomerulosclerotic lesions. In contrast, knockdown of MMP-10 in vivo protected mice from proteinuria, restored podocyte integrity and reduced kidney fibrosis. Interestingly, MMP-10 reduced podocyte tight junctional protein zonula occludens-1 (ZO-1) but did not affect its mRNA level. Incubation of purified ZO-1 with MMP-10 directly resulted in its proteolytic degradation in vitro, suggesting ZO-1 as a novel substrate of MMP-10. Thus, our findings illustrate that induction of MMP-10 could lead to podocyte injury by degrading ZO-1, thereby promoting proteinuria and glomerulosclerosis in chronic kidney diseases.


Predictors of improvement of left ventricular systolic function after catheter ablation of persistent atrial fibrillation in patients with heart failure with reduced ejection fraction.
Although several studies have suggested that catheter ablation (CA) of atrial fibrillation (AF) can improve left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF), the predictor of improvement of LVEF is unclear. A total of 401 patients with persistent AF underwent an initial CA between September 2014 and October 2019 in our hospital. Among them, we analyzed consecutive patients with moderately or severely reduced LVEF (< 50%) measured by transthoracic echocardiography (TTE) within 2 months before CA and underwent follow-up TTE during sinus rhythm at 6 months or more after CA. These patients were categorized into two groups: improve group (I group) with the absolute improvement of LVEF ≥ 10% at follow-up TTE, and non- improve group (NI group) with the absolute improvement of LVEF < 10% at follow-up TTE. We compared patient characteristics, ablation procedures, and clinical outcomes between the two groups. 81 patients were analyzed, and I group consisted of 48 patients (59%). In the univariate analysis, absence of ischemic cardiomyopathy, left ventricular end-diastolic diameter (LVEDD), and absence of recurrence of AF between 3 and 6 months after CA were associated with improvement of LVEF. A receiver operating characteristics analysis determined the suitable cut-off value for LVEDD was 53 mm (sensitivity: 62.2%, specificity: 86.2%, area under curve: 0.762). A multivariate analysis showed that LVEDD < 53 mm was independently associated with improvement of LVEF (odds ratio 2.58, 95% confidence interval 1.29-6.12; P = 0.021). In conclusion, LVEDD < 53 mm might be an independent predictor of improvement of LVEF after CA of persistent AF in HFrEF patients.


Nutrition Interventions in Pediatric Patients with Type 1 Diabetes: An Evidence Analysis Center Scoping Review.
The objective of this scoping review was to identify and characterize studies examining the effect of nutrition management interventions and effectiveness of medical nutrition therapy to improve nutrition-related outcomes in children and adolescents with type 1 diabetes. An in-depth electronic search was conducted by a medical librarian in six databases: Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, The Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection. The literature search resulted in 5,122 records, and five records were identified through hand search. Of these 5,127 records, 22 articles and eight systematic reviews met our inclusion criteria. An equal number of the studies were experimental (ie, randomized or nonrandomized controlled trials, or noncontrolled trials) (n = 11) and observational (cohort, case-control, and cross-sectional) (n = 11) with the remaining studies being systematic reviews/meta-analyses (n = 8). Most of these studies were conducted in United States or Europe. Based on this scoping review, the majority of studies focus on either carbohydrate counting or evaluation of dietary intake patterns with little emphasis on tailored patient education/counseling services specifically designed to meet a young child's or his/her family's individual needs. Indeed, only four studies in this scoping review used dietary counseling and/or medical nutrition therapy. As such, there remains a significant gap in the literature as it relates to the efficacy and long-term management implications of tailored nutrition interventions in young children with type 1 diabetes.


Natural history, duplex characteristics, and histopathologic correlation of arterial injuries in a canine model.
The treatment of patients with penetrating extremity trauma in proximity to major arteries as well as the nonoperative treatment of clinically occult arterial injuries remain controversial. Duplex ultrasonography (DUS) has recently been advocated in this setting. We therefore studied experimentally induced arterial injuries in dogs to correlate the natural history, duplex findings, and histopathologic condition of different injuries and to help define criteria for operation. Fifty-two canine femoral and carotid arteries were randomized to have surgically created intimal flaps (n = 15), crush injuries (n = 15), or lacerations (n = 15) or to be controls (n = 7). An experienced sonographer, blinded to the presence or type of injury, evaluated the vessels every 10 days for 1 month. Histopathologic study was performed 1 month after injury when the arteries were retrieved. The sensitivity (96.5%), specificity (86.4%), and accuracy (95.1%) of DUS in evaluating arterial injuries at 1 month correlated well with histopathologic evaluation. All arteries subjected to crush injuries showed abnormal duplex findings. These findings correlated well with the histologic picture of severe injury (arterial wall thickness = 2.72 x +/- 0.23 x control; intramural hemorrhage, 93%; mural thrombus, 60%). DUS and histologic study revealed healing of intimal flaps in 27% of the arteries. Other intimal flaps deteriorated (stenoses, 47%; dilation, 13%; occlusion, 13%). Most lacerations (86%) revealed duplex evidence of healing within 10 days of injury. This was confirmed by histologic study at 1 month in 73% of lacerated arteries. This study confirms the accuracy of DUS in diagnosing various arterial injuries and shows that the natural history of these injuries varies with the mechanism of injury.(ABSTRACT TRUNCATED AT 250 WORDS)


Vitamin D supplementation in patients with cystic fibrosis: A systematic review and meta-analysis.
Despite routine supplementation, vitamin D insufficiency is often seen in cystic fibrosis (CF) patients on account of pancreatic insufficiency. Vitamin D is a crucial component of bone health and affects nearly all cells of the immune system. However, clinical benefits or harms associated with supplementation are poorly documented. In this systematic review, we included randomized controlled trials (RCTs) that compared vitamin D supplementation with placebo (i.e. 'non-increased dose') in CF patients. Analysing the 8 included RCTs, the intervention group had significantly higher serum 25-hydroxyvitamin D (se25OHD) levels, but there were no significant differences found in the quantitative synthesis of clinical outcomes, including bone disease-, respiratory status- and immunological status-related outcomes. Based on our current results, while a higher vitamin D dose elevates se25OHD, it does not seem to influence clinical outcomes. Future RCTs should include outcomes of past studies and apply longer follow-up periods to document long-term patient-important outcomes.


The new Israeli law on the care of the terminally ill: conceptual innovations waiting for implementation.
Israel has recently enacted a law on the care of terminally ill patients. This law, the Patient Nearing Death Act, is the first of its kind in the world. The law divides terminally ill patients--upon their own wishes--into two separate groups: "those who wish their lives be prolonged," and those who do not. Doctors will have to abide by elaborate advanced directives and take into account various sources of information on the presumed wishes of the patient. The law sanctions discontinuation of mechanical ventilation should it become a "cyclical" rather than "continuous" therapy, a provision that has implications for the use of the already available paraPAC ventilators. The law exposes gaps in modern Judaism between the religious law and the attitudes of the observant population with regard to medical ethics.


Efficacy of BW759 (9-[[2-hydroxy-1(hydroxymethyl)ethoxy]methyl]guanine) against herpes simplex virus type 1 keratitis in rabbits.
A promising new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-guanine (BW759), which is structurally similar to acyclovir, was tested against acute herpetic keratitis in the rabbit ocular model. Topical 1-0.1% BW759 given 3-5x per day gave beneficial results in that corneal epithelial involvement, conjunctivitis, iritis, and corneal clouding were reduced even when chemotherapy was initiated at 3 days postinoculation. Under the same conditions, topical BW759 therapy gave slightly better results than acyclovir, and both were better than idoxuridine therapy. Mortality rate and colonization of the trigeminal ganglia by HSV-1 were unaffected by BW759 therapy. Duration of virus, shed into the tear film was reduced by BW759.


Squamous cell carcinoma in a postpneumonectomy cavity.
A 55-year-old woman was referred to our department with the diagnosis of a bronchopleural fistula and empyema. Her medical history revealed that she had undergone a left pneumonectomy 25 years prior due to a destroyed lung associated with tuberculosis. Open drainage and a biopsy was performed because of the large mass detected on thoracic computed tomography. Postoperative pathology revealed squamous cell carcinoma.


Depression in Chinese men with methamphetamine dependence: Prevalence, correlates and relationship with alexithymia.
The comorbidity between substance use disorder and major depressive disorder is a typical dual diagnosis in the field of substance addiction. However, the prevalence and correlates of depression in methamphetamine addicts and whether it is associated with drug craving and alexithymia have been rarely reported in the Chinese population. We recruited 585 methamphetamine-dependent males from a drug rehabilitation center in China and 203 healthy controls. Demographic and drug use data were collected. Depression was assessed using the Mini International Neuropsychiatric Interview (M.I.N·I.). Methamphetamine cravings and alexithymia were assessed using the Desire for Drugs Questionnaire (DDQ) and the Toronto Alexithymia Scale (TAS). The prevalence rate of depression in methamphetamine-dependent men was 16.58 % (97/585). The scores of DDQ desire and intention, DDQ negative reinforcement, total DDQ, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and total TAS score of depressed patients were higher than those of non-depressed patients. However, only DDQ negative reinforcement score, DIF, DDF, and total TAS score remained significant after Bonferroni correction. Additionally, logistic regression analysis found that age, DIF score, and DDQ negative reinforcement score were significant factors contributing to depression in methamphetamine-dependent men. Our findings suggest that the prevalence of depression is significantly higher in methamphetamine-dependent men than in the healthy Chinese population. Furthermore, age, components of alexithymia and drug craving are risk factors for depression in methamphetamine addicts.


Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin.
Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.


In-vitro Evaluations of Quality Control Parameters of Paracetamol Tablets Marketed in Gondar City, Northwest Ethiopia.
The aim of this research was to evaluate quality control parameters of available brands of paracetamol tablets in Gondar city since standard quality parameters are essential for a better quality of the product. The different brands of paracetamol tablets were obtained from local pharmacies in Gondar town and the University of Gondar (UOG) hospital pharmacies. Five brands of paracetamol, from each, 102 tablets were collected from private pharmacies, government health centers, and UOG pharmacies. The popular brands in the city, Panadol, Para-denk, Paramol, Paracetamol (EPHARM), and Cadimol, conventional tablets of 500 mg strength were chosen and the tablets were assessed for different quality parameters: weight variation, hardness, friability, disintegration, dissolution, and drug content (assay) using compendial methods. The tablets were evaluated to check if they comply with the specifications of USP (United States Pharmacopeia). From the results, it was observed that all the brands of paracetamol have passed the tests and met the specifications of USP. Results of weight variation, hardness, friability, and disintegration time ranged from 0.46 to 1.11%, 117.0 to 174.70 N, 0.07 to 0.63%, and 01 to 08 minutes for all the tablets, respectively. The dissolution profiles of all the brands are within the acceptable label claim. The assay results showed that the drug content of the paracetamol brands ranged from 95.04% to 106.81%. The dissolution rate was significantly different (p < 0.05) as compared to code 1 with all brands tested at 30 minutes. The disintegration time of different brands was also significantly different from the comparator (code 1) except code 2. Based on the finding from this study, there were no significant deviations from pharmacopeia standards and specifications. The brands studied were safe enough and could be used to achieve the desired therapeutic effect.


Harm reduction outcomes and practices in Housing First: A mixed-methods systematic review.
Harm reduction is a central tenet of Housing First. As the intervention has been shown to stably house people experiencing chronic homelessness across the lifespan with complex behavioural health needs, it is critical to understand the harm reduction outcomes and practices in Housing First. A systematic review following PRISMA guidelines was conducted of five databases: PsycINFO, MEDLINE, Embase, CINAHL, and Google Scholar. Harm reduction outcomes and practices in Housing First were examined in four domains: substance-related harms, viral health, sexual health, and harm reduction service use. A total of 35 articles were included in the review, 23 of which examined harm reduction outcomes and 12 of which investigated harm reduction practices in Housing First. Harm reduction outcome studies focused mostly on nonspecific substance use problems, with Housing First being found to have minimal effects in this domain. More severe harms, such as delirium tremens and substance use-related deaths, have been minimally explored, though preliminary evidence is promising. Viral health, sexual health, and harm reduction service use outcomes were the focus of few studies. Research on harm reduction practices highlighted that Housing First providers experience both flexibility and ambiguity in their work using a harm reduction approach, and the importance of empathetic working relationships for engagement in harm reduction work. Harm reduction outcomes in Housing First remain underexamined and any conclusions of the intervention's impacts in this domain would be premature. Effective harm reduction practices in Housing First require strong working relationships between staff and tenants.


Diarrhea in kidney transplant recipients: Etiology and outcome.
Diarrhea in kidney transplant recipients influences outcome of transplantation. Data from India in this regard are sparse and do not address the differential outcome of infective and non-infective diarrhea. We studied the demographic data, laboratory findings, treatment response, disease duration, and outcome of diarrhea in kidney transplant recipients, and the differential outcome between infective and non-infective diarrhea, if any. All kidney transplant recipients who were referred to the Division of Gastroenterology with diarrhea between June 2015 and February 2017 were prospectively included. Demographic, clinical and laboratory data, graft function, treatment administered, and outcome were noted, and the patients were followed up for 3 months. Forty-seven patients (median age 45 years, range 16-78; 34 men) with 64 episodes of diarrhea were studied. Thirty-three (51.5%) episodes were attributed to infections. Eleven (17%) were immunosuppressant-induced (mycophenolate 8, tacrolimus 2, cyclosporine 1). Twenty (31%) were due to other causes (antibiotics 6, laxatives 3, irritable bowel syndrome 3, sepsis 8). Fifty-three episodes (82%) had graft dysfunction during the diarrheal episodes. Mean increase in serum creatinine was 45% in the infectious diarrhea group and 95% in the non-infectious diarrhea group (p < 0.05). Median time to resolution of diarrhea was 3 days. With improvement in diarrhea, return to pre-diarrhea creatinine levels occurred in 87% of episodes at 3 months. One-half of episodes of diarrhea in kidney transplant recipients were non-infectious in origin. Seventeen percent were attributed to immunosuppressants, requiring dose modification. More than 80% were associated with worsening of graft function. Recovery of graft function to baseline was seen in a majority of cases with the resolution of diarrhea.


Selective capturing and detection of Salmonella typhi on polycarbonate membrane using bioconjugated quantum dots.
Present work demonstrates the utilization of surface modified polycarbonate (PC) membrane as solid phase and antibody conjugated CdSe/ZnS quantum dots (QDs) as fluorescent label for the sensitive and selective detection of Salmonella typhi (S. typhi) in water in a period of 2.5h. PC membrane was surface modified with glycine and activated by EDC/NHS for immobilization of S. typhi specific IgG. Antibody immobilized porous PC membrane was incubated with bacteria contaminated water for immunocapturing of S. typhi. Antibody conjugated QDs were also prepared by using carbodiimide chemistry. Both modified PC membrane and quantum dots were characterized by using various modern analytical tools. It was estimated that 1.95 molecules of QDs were successfully bio-conjugated per unit of IgG. PC membrane with captured bacteria was incubated with prepared IgG conjugated QDs for the formation of sandwich complex. Analysis of the regions of interest (ROI) in fluorescent micrographs showed that newly developed method based on PC and fluorescent QDs has 100 times higher detection sensitivity (100 cells/mL) as compared with detection using conventional dye (FITC) based methods.


Pathological Findings in Gastrointestinal Neoplasms and Polyps in 860 Cats and a Pilot Study on miRNA Analyses.
Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated.


NPNT promotes early-stage bone metastases in breast cancer by regulation of the osteogenic niche.
Patients with breast cancer are often afflicted by bone metastases, while the establishment and growth of bone metastases depend on interaction between cancer cells and the host environment. Moreover, osteoblasts, which play a vital role in cancer cells survival and colonization, can form an osteogenic niche in early stage of bone metastases. Also, it is widely accepted that there is a genetic determinant during bone metastases. Nephronectin (NPNT) is an extracellular matrix protein which has shown biological activities in breast cancer metastases and osteoblasts differentiation. But the role of NPNT in mediating breast cancer bone metastases remains elusive. In the present study, we revealed that up regulation of NPNT is associated with incidence of bone metastases. What's more, NPNT could significantly enhance the tumor cell clone formation but not proliferation and migration. We further demonstrated that NPNT significantly enhance osteoblast differentiation and tumor adhesion. Thus, we proposed that cancer secreted NPNT may be a novel marker with potential value of prediction and diagnosis of breast cancer bone metastases.


Placental localization of relaxin in the pregnant mare.
In situ hybridization employing a cRNA probe derived from a 428-bp fragment of equine relaxin was used to localize relaxin mRNA, and immunocytochemistry was used to localize relaxin itself, in tissues of the placenta-endometrium interface recovered between 33 and 153 days of gestation from mares carrying intraspecific horse, interspecific mule and extraspecific donkey conceptuses. Immunocytochemical staining was also used to localize trophoblast-specific and class I major histocompatibility complex (MHC) antigens on some specimens. Relaxin mRNA and relaxin were both present in the single-cell non-invasive trophoblast layer of the allantochorion between 45 and 153 days of gestation in all three types of equine pregnancy examined. Both, however, were absent from the invasive trophoblast cells of the progenitor chorionic girdle and the differentiated trophoblast cells of the endometrial cups throughout the latters' 60-80-day period of development and regression. Discrete and irregularly spaced clusters of elongated pseudostratified trophoblast cells on the allantochorion remained negative for relaxin mRNA and ligand, but stained strongly for equine trophoblast-specific antigens. These areolae-like structures of the mature horse placenta overlie the mouths of endometrial glands between adjacent microcotyledons and they are clearly involved with the uptake of uterine milk for fetal sustenance. It is speculated that their loose attachment to the endometrium and weak expression of class 1 MHC antigens may serve to tolerize the mother to the paternally-inherited histocompatibility antigens of the fetus.


Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study.
Women who develop pre-eclampsia in pregnancy are at increased risk of cardiovascular disease. The offspring from pregnancies complicated by pre-eclampsia have higher blood pressures during childhood, but little is known about their long-term health. We hypothesized that pre-eclampsia would lead to an increased risk of cardiovascular disease in the offspring. We traced 6410 babies born in Helsinki, Finland, from 1934 to 1944. We used the mothers' blood pressure levels and the presence of proteinuria during pregnancy to define pre-eclampsia and gestational hypertension without proteinuria according to modern criteria. Two hundred eighty-four of the pregnancies were complicated by pre-eclampsia (120 with nonsevere and 164 with severe disease) and 1592 by gestational hypertension. The crude hazard ratio for all forms of stroke among people whose mothers had pre-eclampsia was 1.9 (1.2 to 3.0; P=0.01); among people whose mothers had gestational hypertension, it was 1.4 (1.0 to 1.8; P=0.03). There was no evidence that these pregnancy disorders were associated with coronary heart disease in the offspring. Pre-eclampsia, in particular severe disease, was associated with a reduced mean head circumference at birth, whereas gestational hypertension was associated with an increased head circumference in relation to body length. People born after pregnancies complicated by pre-eclampsia or gestational hypertension are at increased risk of stroke. The underlying processes may include a local disorder of the blood vessels of the brain as a consequence of either reduced brain growth or impaired brain growth leading to "brain-sparing" responses in utero.


Facial nerve schwannomas: a report of four cases and a review of the literature.
To evaluate both the surgical approaches and results of the facial nerve schwannoma cases as diagnosed in our clinic in line with the literature. The files of 4 cases diagnosed in our clinic as facial nerve schwannoma between 1996 to 2002 were reviewed retrospectively. All the cases were evaluated with detailed history; ear, nose, and throat examination; computed tomography; and/or magnetic resonance imaging. If required, electromyography and audiometric evaluations were made. Fine-needle aspiration cytology was also performed in appropriate cases. The surgical approach used was determined depending on the tumor location and its extent. Facial nerve reconstruction was accomplished if the integrity of the nerve could not be protected. Cases were followed up for facial nerve function, complications, and recurrence. The tumors occurred in the vertical (n = 2), internal auditory canal (n = 1), and the peripheric segment (n = 1) of the nerve. As symptoms, facial paralysis (n = 2), hearing loss (n = 3), tinnitus (n = 1), otorrhea (n = 2), parotid mass (n = 2), and external auditory canal mass (n = 1) were observed. Radiologic investigations provided important informations. However, fine-needle aspiration cytology did not contribute to a correct preoperative diagnosis. The superficial parotidectomy approach (n = 1), retrosigmoid approach (n = 1), and transmastoid-superficial parotidectomy combined approach (n = 2) were used. The integrity of the nerve could not be protected in 3 of the cases. After the reconstruction surgery, the facial nerve function was evaluated as House-Brackmann grade 3 for all 3 cases at the mean 38.6 months follow-up time. No tumors have recurred during follow-up. Facial nerve schwannoma is a rare tumor. Through improved surgical and reconstruction techniques, postoperative morbidity is at acceptable levels. The rate of recurrence is low. It should be kept in mind for differential diagnosis of facial nerve paralysis.


Erratum: Neighborhood conditions and birth outcomes: understanding the role of perceived and extrinsic measures of neighborhood quality: Erratum.
[This corrects the article DOI: 10.1097/EE9.0000000000000224.].


Cancer incidence and mortality trends in Australian adolescents and young adults, 1982-2007.
Increasing incidence and lack of survival improvement in adolescents and young adults (AYAs) with cancer have led to increased awareness of the cancer burden in this population. The objective of this study was to describe overall and type-specific cancer incidence and mortality trends among AYAs in Western Australia from 1982-2007. Age-adjusted incidence and mortality rates were calculated for all malignancies combined and for each of the most common diagnostic groups, using five-year age-specific rates. Joinpoint regression analysis was used to derive annual percentage changes (APC) for incidence and mortality rates. The annual incidence rate for all cancers combined increased in males from 1982 until 2000 (APC = 1.5%, 95%CI: 0.9%; 2.1%) and then plateaued, whilst rates for females remained stable across the study period (APC = -0.1%; 95%CI: -0.2%; 0.4%) across the study period. For males, significant incidence rate increases were observed for germ cell tumors, lymphoblastic leukemia and thyroid cancer. In females, the incidence of Hodgkin's lymphoma, colorectal and breast cancers increased. Significant incidence rate reductions were noted for cervical, central nervous system and lung cancers. Mortality rates for all cancers combined decreased from 1982 to 2005 for both males (APC = -2.6%, 95%CI:-3.3%;-2.0%) and females (APC = -4.6%, 95%CI:-5.1%;-4.1%). With the exception of bone sarcoma and lung cancer in females, mortality rates for specific cancer types decreased significantly for both sexes during the study period. Incidence of certain AYA cancers increased, whilst it decreased for others. Mortality rates decreased for most cancers, with the largest improvement observed for breast carcinomas. Further research is needed to identify the reasons for the increasing incidence of certain cancers.


Detection of beta-amyloid (1-42) on protein array based on electrical detection technique using scanning tunneling microscopy.
In this study an immuno-array for Abeta42 based on scanning tunneling microscopy (STM) was developed using conjugated gold nanoparticle (Au-NP) and antibody (Ab) complex. Fragmented monoclonal Ab against Abeta42 was allowed to immobilize on the Au-dot arrays followed by its target protein Abeta42 and Au NP and Ab complex. The surface structure of Au-NP and Ab complex on Au-dots was investigated with Atomic Force Microscopy and the current profile of fabricated immunosensing element was investigated with STM. The power spectrum derived from the current profile was found to be increasing with higher concentrations of Abeta42 having a detection limit of 100 fg/ml. The proposed technique can be a promising method to construct the highly sensitive and efficient protein chip of immunosensors arrays.


Frequent nightmares in children: familial aggregation and associations with parent-reported behavioral and mood problems.
To conduct a systematic investigation on the prevalence, correlates, and familial aggregation of frequent nightmares in children, and to scrutinize the associations between frequent nightmares and parent-reported behavioral and mood problems in children. A cross-sectional study was conducted by collecting the data on sociodemographic, sleep, behavioral, and family-related information from a total of 6359 children (age: mean [SD]=9.2 [1.8] years; girls: 49.9%) and their reported biological parents. Community. N/A. Prevalence of frequent nightmares with a criterion of at least once per week was 5.2%. Multinomial regression analysis indicated that monthly family income, paternal and maternal nightmares, insomnia symptoms, parasomniac symptoms, and daytime consequences were significantly associated with nightmares in children. Frequent nightmares in children were significantly associated with hyper-activity (odds ratio [OR]=1.68, 95% CI 1.16-2.44), frequent temper outbursts/mood disturbance (OR=1.76, 95%CI 1.27-2.44), and poor academic performance (OR=1.62, 95% CI 1.11-2.36), after controlling for potential confounding factors. Approximately 20% of children with frequent nightmares experienced comorbid frequent insomnia. Comorbid nightmares and insomnia were associated with increased odds of hyperactivity (OR=4.13, 95% CI 2.13-8.00) and frequent temper outbursts/mood disturbance (OR=2.41, 95%CI 1.27-4.60). Frequent nightmares in children are associated with a constellation of child-, sleep-, and family-related factors, including comorbid sleep problems, such as insomnia and parasomnia, family economic status, and parental predisposition. Frequent nightmares are independently associated with emotional and behavioral problems in children.


Vaccine Hesitancy among Parents and Its Association with the Uptake of Measles Vaccine in Urban Settings in Khartoum State, Sudan.
Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parent Attitudes about Childhood Vaccines (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake, controlling for sociodemographic variables, and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was created, and the area under the curve (AUC) for the PACV was computed. Data were collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicts the uptake of measles vaccine after controlling for other potential social confounders, such as the mother's age and the number of children (aOR 1.055; 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded an area under the curve (AUC 0.686 (95% CI 0.620-0.751; p < 0.001)). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.


A Co-Learning Model for Community-Engaged Program Evaluation.
The development, implementation, and assessment of a masters-level program evaluation course designed to train future and current leaders of community-based organizations (CBOs) is described. In addition to sending students "out" into the community, staff from local community organizations were invited "in" to the classroom to take the course alongside students. Community partners selected a specific evaluation need within their organization that teams could address. The "final" for the course involved creating a comprehensive evaluation plan for each organization to implement. Student course evaluations and semistructured interviews with community partners were conducted and analyzed to assess how course goals were met.Results/Lessons Learned: The course goals were met, the partnering experience was highly valued, and insightful improvements were suggested. This program evaluation course provides an innovative, effective, flexible, and replicable partnership practice model that builds student skills and community capacity in evaluation research.


Impact of Post-EVAR Graft Limb Kinking in EVAR Limb Occlusion: Aetiology, Early Diagnosis, and Management.
Endograft limb occlusion is a potential complication of endovascular aneurysm repair (EVAR), being one of the major causes of secondary interventions and rehospitalisation. The aim of this review is to report on the impact of endograft kinking in endograft limb occlusion, as well as on risk factors, prevention, early diagnosis, and management. A systematic review and meta-analysis was conducted according to the recommendations of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement. After a MEDLINE and Scopus search, 55 articles (27,509 patients) were included in the qualitative analysis and eight in the quantitative analysis. In this meta-analysis, 179 at risk limbs were treated by pre-emptive stenting, which significantly reduced the risk of limb occlusion: not pre-emptively stenting limbs at risk had a negative impact on graft limb patency (odds ratio 4.30, 95% confidence interval 1.45-12.78). Post-operatively, a kink was identified in 422 patients (1.5%), contributing to 42.8% of all limb occlusions. Relevant data support that completion angiography is an inadequate means of diagnosing high risk limbs, proposing cone beam computed tomography and intravascular ultrasound as adjuncts. The post-operative limb occlusion rate ranged from 0% to 10.6%, affecting 984 patients. Several risk factors for limb occlusion have been identified. Regarding treatment, most patients were submitted to femorofemoral bypass (52.3%) or to deployment of a bare metal stent, either alone or associated with catheter directed thrombolysis or mechanical thrombectomy (26.4%). Complications and outcome after re-intervention for limb occlusion are described infrequently in the literature, but single studies have reported on re-occlusion, major amputation, and limb occlusion related mortality rates. Pre-EVAR planning should focus on identification of risk factors for kinking. Adjunctive stenting is an effective prophylaxis for selected high risk limbs, yet intra-operative identification remains problematic. Also, it is noteworthy that most limb occlusions occur in the first year after EVAR, emphasising the importance of careful early follow up of high risk patients.


Effects of 2-propyl 2-pentenoic acid on the acquisition of conditioned behavior with negative reinforcement in mice.
2-Propyl 2-pentenoic acid (PP delta), at a dose of 6 mg/kg (0.04 mM/kg), has a facilitating action on the acquisition of conditioned avoidance reactions. This effect of PP delta is correlated with increase of the level of brain gamma-aminobutyric acid, following administration of PP delta.


Invasion and metastasis.
Malignant tumours cause sickness and death largely because they invade and metastasize. Such spread is made possible by many cellular properties, including the ability of neoplastic cells to move and to release degradative enzymes. These properties enable tumour cells to break free of the primary tumour, penetrate blood or lymphatic vessels and, after being transported to distant sites, pass out of the vessels to establish new tumours. Not all cells in a tumour, however, are able to metastasize, so the process tends to select for greater malignancy in the secondary tumour. The heterogeneity of tumours probably accounts for the difficulty of providing effective treatment, in that the various subpopulations of cells arising from each tumour vary in their responses to chemotherapeutic agents. We do not yet understand the process sufficiently to treat cancer patients by interfering selectively with the metastatic mechanisms.


Intubation of the morbidly obese patient: GlideScope(®) vs. Fastrach™.
Several potential problems can arise from airway management in morbidly obese patients, including difficult mask ventilation and difficult intubation. We hypothesised that endotracheal intubation of morbidly obese patients would be more rapid using the GlideScope(®) (GS) (Verathon Inc Corporate Headquarters, Bothell, WA, USA) than with the Fastrach™ (FT) (The Laryngeal Mask Company Ltd, Le Rocher, Victoria, Mahe, Seychelles). One hundred patients who were scheduled for bariatric surgery were randomised to tracheal intubation using either a GS or an FT. The inclusion criteria were age 18-60 years and a body mass index of ≥ 35 kg/m(2) . The primary end point was intubation time, and if intubation was not achieved after two attempts, the other method was used for the third attempt. The mean intubation time was 49 s using the GS and 61 s using the FT (P = 0.86). A total of 92% and 84% of the patients were intubated on the first attempt using the GS and the FT, respectively. One tracheal intubation failed on the second attempt when the GS was used, and five failed on the second attempt when the FT was used. There were no incidents of desaturation and no differences between the groups in terms of mucosal damage or intubation difficulty. We experienced one oesophageal intubation using GS and six oesophageal intubations in five patients using FT. There was no difference between the pain scores or incidence of post-operative hoarseness associated with the two intubation techniques. No significant difference between the two methods was found. The GS and the FT may therefore be considered to be equally good when intubating morbidly obese patients.


End-tidal carbon dioxide after sodium bicarbonate infusion during mechanical ventilation or ongoing cardiopulmonary resuscitation.
End-tidal CO2 is used to monitor the ventilation status or hemodynamic efficacy during mechanical ventilation or cardiopulmonary resuscitation (CPR), and it may be affected by various factors including sodium bicarbonate administration. This study investigated changes in end-tidal CO2 after sodium bicarbonate administration. This single-center, prospective observational study included adult patients who received sodium bicarbonate during mechanical ventilation or CPR. End-tidal CO2 elevation was defined as an increase of ≥20% from the baseline end-tidal CO2 value. The time to initial increase (lag time, Tlag), time to peak (Tpeak), and duration of the end-tidal CO2 rise (Tduration) were compared between the patients with spontaneous circulation (SC group) and those with ongoing resuscitation (CPR group). Thirty-three patients, (SC group, n = 25; CPR group, n = 8), were included. Compared with the baseline value, the median values of peak end-tidal CO2 after sodium bicarbonate injection increased by 100% (from 21 to 41 mmHg) in all patients, 89.5% (from 21 to 39 mmHg) in the SC group, and 160.2% (from 15 to 41 mmHg) in the CPR group. The median Tlag was 17 s (IQR: 12-21) and the median Tpeak was 35 s (IQR: 27-52). The median Tduration was 420 s (IQR: 90-639). The median Tlag, Tpeak, and Tduration were not significantly different between the groups. Tduration was associated with the amount of sodium bicarbonate for SC group (correlation coefficient: 0.531, p = 0.006). The administration of sodium bicarbonate may lead to a substantial increase in end-tidal CO2 for several minutes in patients with spontaneous circulation and in patients with ongoing CPR. After intravenous administration of sodium bicarbonate, the use of end-tidal CO2 pressure as a physiological indicator may be limited.


Risk factors and outcomes of diffuse alveolar haemorrhage after allogeneic haematopoietic stem cell transplantation.
Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.


Enhancement of biogas production rate from bioplastics by alkaline pretreatment.
The effect of alkali-based pretreatment on the methanization of bioplastics was investigated. The tested bioplastics included PHB [poly(3-hydroxybutyrate)], PHBH [poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)], PHBV [poly(3-hydroxybutyrate-co-3-hydroxyvalerate], PLA (polylactic acid), and a PLA/PCL [poly(caprolactone)] 80/20 blend. Prior to methanization tests, the powdered polymers (500-1000 μm) at a concentration of 50 g/L were subjected to alkaline pretreatment using NaOH 1 M for PLA and PLA/PCL, and NaOH 2 M for PHB-based materials. Following 7 days of pretreatment, the amount of solubilized carbon for PLA and its blend accounted for 92-98% of the total initial carbon, while lower carbon recoveries were recorded for most PHB-based materials (80-93%), as revealed by dissolved total organic carbon analysis. The pretreated bioplastics were then tested for biogas production by means of mesophilic biochemical methane potential tests. Compared to unpretreated PHBs, methanization rates of pretreated PHBs were accelerated by a factor of 2.7 to 9.1 with comparable (430 NmL CH4/g material feed) or slightly lower (15% in the case of PHBH) methane yields, despite featuring a 1.4-2.3 times longer lag phases. Both materials, PLA and the PLA/PCL blend, were only extensively digested when pretreated, yielding about 360-380 NmL CH4 per gram of material fed. Unpretreated PLA-based materials showed nearly zero methanization under the timeframe and experimental conditions tested. Overall, the results suggested that alkaline pretreatment can help to enhance the methanization kinetics of bioplastics.


Estimating ideal body weight--a new formula.
A simple formula for estimating ideal body weight (IBW) in kilograms for both men and women is presented. The equation IBW = 22 x H2, where H is equal to patient height in meters, yields weight values midway within the range of weights obtained using published IBW formulae.


Stage of ovarian cancer at diagnosis. Does presentation as an emergency make a difference?
The purpose of this study is to evaluate whether presentation of ovarian cancer as an emergency compared to presentation via referral to diagnostic clinic has an impact on stage of disease at diagnosis. Secondary outcomes include the relationship between stage of diagnosis and age as well as socioeconomic status and type of presentation (emergency or clinic referral). Data were obtained from the central database for all new diagnoses of ovarian, fallopian tube or primary peritoneal malignancy at a tertiary teaching hospital for 2016-2018 (n = 147). The electronic patient records were manually reviewed to determine the patient's presentation. Age and stage at diagnosis were from the central records. Socioeconomic status was determined by the multiple deprivation index deciles obtained from patient postcode data. Non parametric chi squared analysis was used to assess for any significant results. 51 % of women presented through a gynaecology two-week wait service; 27 % presented as an emergency admission; 12 % through a routine gynaecology outpatient clinic and 10 % after initial referral to a non-gynaecological two-week wait service. There was a significant (p = 0.008) association with later stage disease and emergency presentation. Increased age was also strongly linked to later stage at diagnosis (p = 0.00001). There was no association between stage at diagnosis and socioeconomic status. Emergency presentations account for just over a quarter of new diagnoses and are significantly associated with later stage disease with increased morbidity and mortality. Older women were also more likely to present at an advanced stage. Socioeconomic status did not impact on staging at diagnosis.


Double barrelled common bile duct: a threat to biliary surgery.
The frequency of cholecystectomies has given the surgeon familiarity and confidence when dealing with biliary anomalies. Internal anomalies are not equally recognized, for they play little role in cholecystectomy. Recognition of internal anomalies is of prime importance, however, when the biliary tree is drained through the gallbladder. Radiographic confirmation of a patent drainage system, avoiding spillage of contrast material, should be routinely employed in these situations to obviate potentially lethal complications due to technical error.


[The isolation of enteritis causing Salmonellae from the sputum].
In the light of the author's diagnostic experience, attention is drawn to the fact that enteritis Salmonellae appear to be more frequently present in sputum than in generally supposed. The diagnostic and epidemiologic implications of this observation are discussed.