Mechanical properties of methyl functionalized graphene: a molecular dynamics study.
Molecular dynamics simulations have been performed to study the mechanical properties of methyl (CH(3)) functionalized graphene. It is found that the mechanical properties of functionalized graphene greatly depend on the location, distribution and coverage of CH(3) radicals on graphene. Surface functionalization exhibits a much stronger influence on the mechanical properties than edge functionalization. For patterned functionalization on graphene surfaces, the radicals arranged in lines perpendicular to the tensile direction lead to larger strength deterioration than those parallel to the tensile direction. For random functionalization, the elastic modulus of graphene decreases gradually with increasing CH(3) coverage, while both the strength and fracture strain show a sharp drop at low coverage. When CH(3) coverage reaches saturation, the elastic modulus, strength and fracture strain of graphene drop by as much as 18%, 43% and 47%, respectively.


[Evaluation of the activity of polymorphonuclear neutrophils against Entamoeba histolytica antigens].
This paper evaluates the production of superoxide as an indicator of the activity of neutrophils from healthy individuals, stimulated with Entamoeaba histolytica membrane antigens, chemical stimulators and antigens from other parasites. The kinetic nitroblue tetrazolium reduction test was used. No significant differences were observed in the control group as to superoxide production by neutrophils primed with Entamoeba histolytica antigens or Cisticercus cellulosae, Toxoplasma gondii and Giardia lamblia antigens. These results allow us to conclude that Entamoeba histolytica membrane antigens do not induce superoxide production by neutrophils, which contradicts previous statements on suppresed activity of neutrophils after they get in contact with Entamoeaba histolytica antigens.


Interactions of stem cells and T lymphocytes contribute to the physiological control of cell proliferation in rapidly renewing tissues.
Control of cell proliferation, in tissues which replicate rapidly, may be exercised, at least in part, by common populations of circulating cells. Thymus-derived (T) lymphocytes possess properties which would fit them for this purpose. Among these are the functional manifestations of 'help' and 'suppression' with respect to defined physiological processes, such as immunoglobulin production; and unique traffic patterns in blood and extra-vascular tissues, including those in non-lymphoid organs such as bone marrow, skin and gut epithelium. This tropism may involve specific chemotactic agents and result in a predominance of 'suppressor' cells in target tissues. A 'steady-state' of cell proliferation could be maintained by this mechanism which is subject to humoral modulation, for instance by corticosteroids. Influx of 'helper' T lymphocytes would stimulate cell production while an excess of 'suppressors' would diminish cell renewal, as has been observed in some forms of bone marrow aplasia. Fulfillment of these roles by T cells may depend on the expression of antigens in the HLA-DR complex and it has implications for further insight into the pathogenesis of auto-immunity and neoplasia.


Is complying with the recommendations of sodium intake beneficial for health in individuals at high cardiovascular risk? Findings from the PREDIMED study.
Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). It is unknown whether decreasing sodium intake to <2300 mg/d has an effect on CVD or all-cause mortality. The objective was to assess whether reductions in sodium intake to <2300 mg/d were associated with either an increased or a decreased risk of fatal and nonfatal CVD and all-cause mortality. This observational prospective study of the PREvención con DIeta MEDiterránea (PREDIMED) trial included 3982 participants at high CVD risk. Sodium intake was evaluated with a validated food-frequency questionnaire and categorized as low (<1500 mg/d), intermediate (≥1500 to ≤2300 mg/d), high (>2300 to ≤3400 mg/d), or very high (>3400 mg/d). Subsequently, 1-y and 3-y changes in sodium intake were calculated. Multivariate relative risks were assessed by using Cox proportional hazards ratios. Marginal structural models with inverse probability weighting were used to test the effect of changes in sodium intake and the Mediterranean diet (MedDiet). We documented 125 CVD events and 131 deaths after a 4.8-y median follow-up. Sodium intake <2300 mg/d was associated with a lower risk of all-cause mortality: 48% (HR: 0.52; 95% CI: 0.30, 0.91; P = 0.02) and 49% (HR: 0.51; 95% CI: 0.26, 0.98; P = 0.04) after 1 and 3 y, respectively. Increasing sodium intake after 1 y was associated with a 72% (HR: 1.72; 95% CI: 1.01, 2.91; P = 0.04) higher risk of CVD events. The incidence rate of CVD was reduced for those who reduced their sodium intake and were randomly assigned to MedDiet interventions [4.1/10,000 (95% CI: 3.1, 8.0) compared with 4.4/10,000 (95% CI: 2.7, 12.4) person-years; P = 0.002]. Decreasing sodium intake to <2300 mg/d was associated with a reduced risk of all-cause mortality, whereas increasing the intake to >2300 mg/d was associated with a higher risk of CVD. Our observational data suggest that sodium intake <2300 mg/d was associated with an enhanced beneficial effect of the MedDiet on CVD. These results should be interpreted with caution, and other confirmatory studies are necessary.


[Investigation of anti-R7V antibodies in HIV-infected patients under highly active antiretroviral therapy].
R7V is a seven-aminoacid peptide epitope derived from cellular beta-2 microglobulin, present on human immunodeficiency virus (HIV) virion surface in patients with HIV infection. Antibodies against R7V peptide have the property of neutralizing all strains of HIV, unrelated to genotype, phenotype, or geographical origin of the virus, even in the presence of anti-retroviral drug resistance. Patients that mount an anti-R7V antibody response have been shown to be slow or non-progressors and this epitope has been considered for vaccine and/or therapeutic uses. In this study, HIV-infected patients under highly active anti-retroviral therapy (HAART) at Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Infectious Diseases, were evaluated for the presence of anti-R7V antibodies. Thirty-three HIV positive patients and 10 healthy controls were enrolled to the study. For HIV-infected patients, determination of viral load and CD4+ T lymphocyte counts were performed by a commercial real-time PCR assay and flow cytometry, respectively. Anti-R7V antibodies were detected from serum samples by a commercial ELISA (Anti-R7V ELISA, Ivagen, France) test. Three HIV infected patients (3/33, 9.1%) displayed anti-R7V antibodies whereas the remaining 30 (90.9%) patients and all controls were interpreted as negative. No statistically significant difference was detected for HIV-RNA levels and CD4+ T lymphocyte counts between anti-R7V positive and negative patients (p= 0.871 and p= 0.287, respectively). These results indicate the presence of anti-R7V antibodies in our study population with HIV infection. No correlation with the presence of anti-R7V and disease progression were displayed in this study. Clinical impact of anti-R7V antibody assays for the management of HIV-infected patients will be revealed in the near future with the help of advanced studies.


A Research Note Investigating the Leg Tuck and Plank With Potential Impacts for Occupational Testing.
Gonzalez, SM, Withrow, KL, Rubin, DA, Lynn, SK, Dawes, JJ, Orr, RM, and Lockie, RG. A research note investigating the leg tuck and plank with potential impacts for occupational testing. J Strength Cond Res 37(10): 2076-2079, 2023-The U.S. Army recently replaced the leg tuck with the plank in their physical ability testing. There has been limited analysis of whether these 2 tests correlate, have any relationships with body composition and strength, or are sex-neutral. Forty-nine civilian college students (28 males, 21 females) were recruited as surrogates for tactical personnel. The following were measured: height, body mass, body fat percentage (BF%), and muscle mass percentage (MM%) measured through bioelectrical impedance analysis, grip strength, leg tuck, and plank. Independent t -tests were calculated to determine between-sex differences for all variables ( p < 0.05). Partial correlations controlling for sex were used to compute relationships between the leg tuck, plank, and other variables. Stepwise regression controlling for sex derived predictive relationships for the leg tuck and plank. Males were taller, had greater body mass, MM%, and were superior in grip strength and the leg tuck; females had greater BF%. There were no significant between-sex differences for the plank. The leg tuck correlated with BF%, MM%, grip strength, and the plank ( r = ±0.333-0.524). In addition to the leg tuck, the plank correlated with BF% ( r = -0.288). The leg tuck was predicted by sex, grip strength, and the plank (adjusted r2 = 0.662). No variables predicted the plank. As there were no between-sex differences and sex was not a plank predictor, it appears this test minimized sex differences on task performance in civilians. However, the leg tuck and plank likely measure different qualities; further research is needed on job task relationships.


Mucinous carcinoma of the endometrium.
Three cases of mucinous carcinoma of the endometrium are presented. These can be distinguished anatomically from endocervical carcinomas and histochemically from endometrial clear cell carcinomas. Clinically these patients do not differ significantly from others with endometrial carcinoma, but the tumors produce large amounts of extracellular and intracellular neutral and acid mucopolysaccharides. Mucinous carcinoma is regarded as a morphologic variant of endometrial carcinoma.


Antigen-specific inhibition of experimental autoimmune uveoretinitis by bone marrow-derived immature dendritic cells.
To investigate the effect of maturation status of bone marrow-derived dendritic cells (BMDCs) on the in vivo immune response to interphotoreceptor retinoid-binding protein (IRBP) 161-180 peptide in experimental autoimmune uveoretinitis (EAU). Immature and mature BMDCs were generated without or with the stimulation by lipopolysaccharide (LPS), and their mRNA cytokine profile and phenotype were analyzed by RNase protection assay and flow cytometry. The effect of immature and mature DCs in inducing antigen-specific T-cell proliferation and cytokine profile was further investigated in an IRBP peptide-induced model of EAU. BMDCs generated in granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature (i)DCs, as determined by flow cytometry and cytokine profile. However, stimulation with LPS induced these cells to become mature (m)DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules and higher mRNA expression of IL-1alpha, -1beta, -6, and -12. Subcutaneous administration of iDCs induced a state of relative tolerance to the peptide induced-EAU, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. In vitro, both iDCs and mDCs induced typical peptide-specific T-cell proliferation, but IFN-gamma production by uveitogenic T cells was markedly inhibited by iDCs. In vivo, peptide-loaded iDCs induced draining lymph node (DLN) cells to secrete a distinct pattern of cytokine: namely, increased IL-10 and IL-5 and decreased IFN-gamma and IL-2, indicating an altered immune responses to a low T-helper (Th) cell type 1 profile and a high Th2 profile after uveitogenic challenge. The data suggest that induction of tolerance to an autoantigen by peptide-loaded DCs requires presentation of antigen by iDCs and involves the generation of a high-level IL-10 and IL-5 immune response in DLN cells.


Superior Semicircular Canal Dehiscence Syndrome - Diagnosis and Surgical Management.
Introduction Superior semicircular canal dehiscence syndrome was described by Minor et al in 1998. It is a troublesome syndrome that results in vertigo and oscillopsia induced by loud sounds or changes in the pressure of the external auditory canal or middle ear. Patients may present with autophony, hyperacusis, pulsatile tinnitus and hearing loss. When symptoms are mild, they are usually managed conservatively, but surgical intervention may be needed for patients with debilitating symptoms. Objective The aim of this manuscript is to review the different surgical techniques used to repair the superior semicircular canal dehiscence. Data Sources PubMed and Ovid-SP databases. Data Synthesis The different approaches are described and discussed, as well as their limitations. We also review the advantages and disadvantages of the plugging, capping and resurfacing techniques to repair the dehiscence. Conclusions Each of the surgical approaches has advantages and disadvantages. The middle fossa approach gives a better view of the dehiscence, but comes with a higher morbidity than the transmastoid approach. Endoscopic assistance may be advantageous during the middle cranial fossa approach for better visualization. The plugging and capping techniques are associated with higher success rates than resurfacing, with no added risk of hearing loss.


Adaptive rood pattern search for fast block-matching motion estimation.
In this paper, we propose a novel and simple fast block-matching algorithm (BMA), called adaptive rood pattern search (ARPS), which consists of two sequential search stages: 1) initial search and 2) refined local search. For each macroblock (MB), the initial search is performed only once at the beginning in order to find a good starting point for the follow-up refined local search. By doing so, unnecessary intermediate search and the risk of being trapped into local minimum matching error points could be greatly reduced in long search case. For the initial search stage, an adaptive rood pattern (ARP) is proposed, and the ARP's size is dynamically determined for each MB, based on the available motion vectors (MVs) of the neighboring MBs. In the refined local search stage, a unit-size rood pattern (URP) is exploited repeatedly, and unrestrictedly, until the final MV is found. To further speed up the search, zero-motion prejudgment (ZMP) is incorporated in our method, which is particularly beneficial to those video sequences containing small motion contents. Extensive experiments conducted based on the MPEG-4 Verification Model (VM) encoding platform show that the search speed of our proposed ARPS-ZMP is about two to three times faster than that of the diamond search (DS), and our method even achieves higher peak signal-to-noise ratio (PSNR) particularly for those video sequences containing large and/or complex motion contents.


Cisplatin-Based Chemotherapy of Human Cancers.
Cisplatin (cis-diammine-dichloro-platinum II) was initially discovered to prevent the growth of Escherichia coli and was further recognized for its anti-neoplastic and cytotoxic effects on cancer cells. Administered intravenously to humans, cisplatin is used as first-line chemotherapy treatment for patients diagnosed with various types of malignancies, such as leukemia, lymphomas, breast, testicular, ovarian, head and neck, and cervical cancers, and sarcomas. Once cisplatin enters the cell it exerts its cytotoxic effect by losing one chloride ligand, binding to DNA to form intra-strand DNA adducts, and inhibiting DNA synthesis and cell growth. The DNA lesions formed from cisplatin-induced DNA damage activate DNA repair response via NER (nuclear excision repair system) by halting cisplatin-induced cell death by activation of ATM (ataxia telangiectasia mutated) pathway. Although treatment has been shown to be effective, many patients experience relapse due to drug resistance. As a result, other platinum compounds such as oxaliplatin and carboplatin have since been used and have shown some levels of effectiveness. In this review, the clinical applications of cisplatin are discussed with a special emphasis on its use in cancer chemotherapy.


Prediction of long-term success of orthopedic treatment in skeletal Class III malocclusions.
We investigated the long-term success of orthopedic treatment in skeletal Class III malocclusions, established a model to predict its long-term success, and verified previously reported success rates and prediction models. Fifty-nine patients who underwent successful facemask treatment and were followed until growth completion were evaluated. After completion of growth, the patients were divided into successful and unsuccessful groups according to overjet, overbite, and facial profile. Pretreatment cephalometric measurements were compared between groups, and logistic regression analysis was used to identify the predictors of long-term success. Four previously published articles were selected to verify the success rate and predictability of the prediction models with regard to our patient sample. The treatment success rate was 62.7%. The AB-mandibular plane angle, Wits appraisal, and the articular angle were identified as predictors. The success rates differed according to success criteria and patient characteristics. The prediction models proposed by the 4 previous studies and our study showed similar predictabilities (61.0%-64.4%) for our patient sample. The predictability for the unsuccessful group was low. Our results suggest that no particular method or factor can predict the long-term success of orthopedic treatment for skeletal Class III malocclusion.


Symptomatic hyponatremia during treatment of dehydrating diarrheal disease with reduced osmolarity oral rehydration solution.
In May 2002, the World Health Organization and the United Nations Children's Fund recommended that the formulation of oral rehydration solution (ORS) for treatment of patients with diarrhea be changed to one with a reduced osmolarity and that safety of the new formulation, particularly development of symptomatic hyponatremia, be monitored. To measure the rates of symptomatic hyponatremia during treatment of patients with diarrhea with reduced osmolarity ORS. A phase 4 trial conducted at the Dhaka hospital (December 1, 2002-November 30, 2003) and Matlab hospital (February 2, 2003-January 31, 2004) of the International Centre for Diarrhoeal Disease Research Bangladesh: Centre for Health and Population Research, Dhaka, Bangladesh. All patients admitted with uncomplicated watery diarrhea were treated with the newly recommended ORS and monitored. Patients developing neurological symptoms (seizure or altered consciousness) were transferred to the special care ward for treatment and investigated to identify the cause of the symptoms. Patient records of the Dhaka hospital were reviewed during the previous year when the old ORS formulation was used. Reduced osmolarity ORS. Incidence rate of symptomatic hyponatremia in a 1-year period. A total of 53,280 patients, including 22,536 children younger than 60 months, were monitored at the Dhaka and Matlab hospitals. Twenty-four patients, none older than 36 months, developed seizures or altered consciousness associated with hyponatremia, with an overall incidence rate of 0.05% (95% confidence interval [CI], 0.03%-0.07%) at the Dhaka hospital and 0.03% (95% CI, 0.01%-0.09%) at the Matlab hospital. During the previous year, 47 patients at the Dhaka hospital had symptoms associated with hyponatremia, for an estimated incidence rate of 0.10% (95% CI, 0.07%-0.13%). The reduction in the rates was statistically significant (odds ratio, 0.50; 95% CI, 0.29-0.85; P = .009). The risk of symptoms associated with hyponatremia in patients treated with the reduced osmolarity ORS is minimal and did not increase with the change in formulation.


Structure-activity relationships for the irreversible blockade of nicotinic receptor agonist sites by lophotoxin and congeneric diterpene lactones.
Lophotoxin, a diterpene lactone paralytic toxin from gorgonian corals of the genus Lophogorgia, inhibits [125I]-alpha-toxin binding to surface nicotinic receptors of BC3H-1 cells by irreversible occupation of the primary agonist sites. In contrast, receptor-bearing membrane fragments or detergent-solubilized receptors prepared from BC3H-1 cells are not susceptible to lophotoxin block. Thus, lophotoxin inhibition requires intact cells. However, when intact cells were incubated with lophotoxin, subsequent membrane-fragment preparation or detergent solubilization of the receptors did not diminish lophotoxin occupation of [125I]-alpha-toxin-binding sites, indicating that lophotoxin binds very tightly to nicotinic receptors. These studies further demonstrate that both surface and nonsurface nicotinic receptors of BC3H-1 cells are susceptible to irreversible occupation by lophotoxin, indicating that the lipophilic toxin freely permeates intact cells. We also examined several structural analogs of lophotoxin, one of which was equipotent with lophotoxin for inhibition of [125I]-alpha-toxin binding to intact cells and, notably, also blocked alpha-toxin binding to detergent-extracted receptor. Furthermore, this active analog inhibited [125I]-alpha-toxin binding to receptor-rich membrane fragments prepared from Torpedo electric organ, a preparation in which lophotoxin was inactive. Structure-activity relationships exhibited by the lophotoxin congeners suggest mechanisms for covalent bonding to the receptor by way of a Michael addition or by Schiff base formation.


Some characteristics of the Coagulation Factor Xa purified from human serum.
1. Coagulation Factor X was purified from human serum to apparent homogeneity in disc gel electrophoresis, sodium dodecyl sulphate-polacrylamide-gel electrophoresis, immunoelectrophoresis and analytical ultracentrifugation. The method used was a modification of that described by Gladhaug & Prydz (1970). 2. The method permits the isolation of an activated form of Factor X (Xa) which has a molecular weight of about 25000. 3. Factor Xa is a glycoprotein containing about 14% carbohydrate. A preliminary report of the amino acid composition is given.


Competition between functional signal peptides demonstrates variation in affinity for the secretion pathway.
We have developed a system for examining the relative affinity of two different signal peptides for the protein secretion pathway in Escherichia coli. This system involves the expression of a modified alkaline phosphatase which possesses two signal peptides arranged in tandem. When both signal peptides have the wild-type sequence, cleavage after the first and cleavage after the second occur with nearly equal frequency. In both cases the remainder of the protein is transported to the periplasm. Thus both signal peptides effectively compete with each other for entrance to the secretion pathway. When the hydrophobicity of the second signal peptide is altered by small increments, we find that the more hydrophobic signal peptide is preferentially utilized. Thus, a more hydrophobic signal peptide can outcompete even an efficient wild-type signal sequence. The crossover point, for utilization of the second to the first signal peptide, is marked and occurs over a very small change in hydrophobicity. Our results suggest that the small differences in the hydrophobicity of wild-type signal peptides may have critical consequences: preproteins with the more hydrophobic signals could dominate one pathway, leaving those with only slightly less hydrophobic signals to require additional factors such as chaperonins, SecB, and other binding proteins.


Defining the relationship between vaginal and urinary microbiomes.
Although the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions. To describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa. This multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual operational taxonomic units of paired samples. Canonical correlation analysis evaluated the association between clinical variables (including mixed urinary incontinence and control status) and vaginal and urinary operational taxonomic units, using the Canonical correlation analysis function in the Vegan package (R version 3.5). Linear discriminant analysis effect size was used to find taxa that discriminated between vaginal and urinary samples. Urinary and vaginal samples were collected from 212 women (mean age 53±11 years) and results from 197 paired samples were available for analysis. As operational taxonomic units in mixed urinary incontinence and control samples were related in canonical correlation analysis and since taxa did not discriminate between mixed urinary incontinence or controls in either vagina or urine, mixed urinary incontinence and control samples were pooled for further analysis. Canonical correlation analysis of vaginal and urinary samples indicated that that 60 of the 100 most abundant operational taxonomic units in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Although less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). Linear discriminant analysis effect size analysis identified Tepidimonas and Flavobacterium as bacteria that distinguished the urinary environment for both mixed urinary incontinence and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, P<.001, Flavobacterium effect size 2.15, P<.001). Although Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (linear discriminant analysis effect size effect size 2.72, P<.001). Significant associations between vaginal and urinary microbiomes were demonstrated, with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.


Cerebellar ataxia: torque deficiency or torque mismatch between joints?
Prior work has shown that cerebellar subjects have difficulty adjusting for interaction torques that occur during multi-jointed movements. The purpose of this study was to determine whether this deficit is due to a general inability to generate sufficient levels of phasic torque inability or due to an inability to generate muscle torques that predict and compensate for interaction torques. A second purpose was to determine whether reducing the number of moving joints by external mechanical fixation could improve cerebellar subjects' targeted limb movements. We studied control and cerebellar subjects making elbow flexion movements to touch a target under two conditions: 1) a shoulder free condition, which required only elbow flexion, although the shoulder joint was unconstrained and 2) a shoulder fixed condition, where the shoulder joint was mechanically stabilized so it could not move. We measured joint positions of the arm in the sagittal plane and electromyograms (EMGs) of shoulder and elbow muscles. Elbow and shoulder torques were estimated using inverse dynamics equations. In the shoulder free condition, cerebellar subjects made greater endpoint errors (primarily overshoots) than did controls. Cerebellar subjects' overshoot errors were largely due to unwanted flexion at the shoulder. The excessive shoulder flexion resulted from a torque mismatch, where larger shoulder muscle torques were produced at higher rates than would be appropriate for a given elbow movement. In the shoulder fixed condition, endpoint errors of cerebellar subjects and controls were comparable. The improved accuracy of cerebellar subjects was accompanied by reduced shoulder flexor muscle activity. Most of the correct cerebellar trials in the shoulder fixed condition were movements made using only muscles that flex the elbow. Our findings suggest that cerebellar subjects' poor shoulder control is due to an inability to generate muscle torques that predict and compensate for interaction torques, and not due to a general inability to generate sufficient levels of phasic torque. In addition, reducing the number of muscles to be controlled improved cerebellar ataxia.


Feature-enhanced synthetic aperture radar image formation based on nonquadratic regularization.
We develop a method for the formation of spotlight-mode synthetic aperture radar (SAR) images with enhanced features. The approach is based on a regularized reconstruction of the scattering field which combines a tomographic model of the SAR observation process with prior information regarding the nature of the features of interest. Compared to conventional SAR techniques, the method we propose produces images with increased resolution, reduced sidelobes, reduced speckle and easier-to-segment regions. Our technique effectively deals with the complex-valued, random-phase nature of the underlying SAR reflectivities. An efficient and robust numerical solution is achieved through extensions of half-quadratic regularization methods to the complex-valued SAR problem. We demonstrate the performance of the method on synthetic and real SAR scenes.


Supportive care of the lung cancer patients.
The care of lung cancer patients involves a specialized team approach. Complications arising from the underlying illness or its treatment are common occurrences that must be anticipated and treated properly. Psychosocial issues commonly arise in patients and their families during the course of the illness. Caregivers skilled in helping a patient and family members come to terms with this frequently fatal disease are integral members of a multidisciplinary team of cancer specialists.


Dickkopf1 and the Spemann-Mangold head organizer.
Work in amphibians indicates that inhibition of Wnt and BMP signals is essential for head development and that head induction by the Spemann-Mangold organizer may be mediated by secreted Wnt antagonists. Wnts are potent posteriorizing factors and antagonize the Spemann-Mangold organizer. Dickkopf1 (dkk1) encodes a secreted effector expressed in head organizing centers of Xenopus, mouse and zebrafish. It acts as a Wnt inhibitor and is able together with BMP inhibitors to induce the formation of ectopic embryonic heads in Xenopus. It anteriorizes both mesendoderm and neuroectoderm, promoting prechordal plate and forebrain fates. Injection of inhibitory antibodies leads to microcephaly and cyclopia. Dkk1 thus is an essential mediator of the vertebrate head organizer.


Chronic non-progressive pneumonia of sheep in New Zealand - a review of the role of Mycoplasma ovipneumoniae.
Chronic non-progressive pneumonia (CNP) is a common disease which affects lambs in New Zealand during late summer and autumn. Mycoplasma ovipneumoniae can be recovered from a high proportion of lesions but it is also present in some normal lungs. Bacteria, especially Pasteurella haemolytica, can also be recovered from more than half the lungs of affected animals. Isolates of M. ovipneumoniae are genetically heterogeneous, as demonstrated by examination of their DNA or total cellular proteins, and are serologically heterogeneous as shown by metabolic inhibition tests. The number of strains present in New Zealand is large and several distinguishable strains can be recovered from each affected lung. Mycoplasma ovipneumoniae has pathogenic potential as indicated by its ability to produce hydrogen peroxide, cause ciliostasis and by its possession of a capsule. Chronic non-progressive pneumonia can be transmitted consistently to over 50% of lambs by inoculation of pooled pneumonic lung homogenate and transmission can be suppressed by broad spectrum antibiotics. In contrast, penicillin does not prevent the development of lesions but diminishes their severity. Pooled lung homogenate treated with digitonin, which inactivates mycoplasmas, has failed to transmit CNP. Pure cultures of M. ovipneumoniae produce only mild lesions in some animals, whereas inoculation with pooled lung homogenate (from which no viruses were isolated) containing mixed strains of M. ovipneumoniae and free from bacteria, is more effective in producing lesions. Research work to date suggests that CNP may be initiated by colonisation of the lung by M. ovipneumoniae which causes ciliostasis and elicits an exudate allowing colonisation of the lungs by bacteria especially M. haemolytica and by other strains of M. ovipneumoniae. The immune response to the initial strain of M. ovipneumoniae may inhibit its replication but would be less effective in inhibiting heterologous strains of the organism allowing their sequential replication. Eventually production of a broad immune response to M. ovipneumoniae would lead to its elimination which in turn would facilitate the elimination of other microorganisms and the resolution of lesions. As natural immunity to CNP occurs within the first year, it may be possible to develop an effective and useful vaccine. Such a vaccine may need to include multiple strains of M. ovipneumoniae.


Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome.
Growing evidence has suggested that Type I Interferon (I-IFN) plays a potential role in the pathogenesis of Down Syndrome (DS). This work investigates the underlying function of MX1, an effector gene of I-IFN, in DS-associated transcriptional regulation and phenotypic modulation. We performed assay for transposase-accessible chromatin with high-throughout sequencing (ATAC-seq) to explore the difference of chromatin accessibility between DS derived amniocytes (DSACs) and controls. We then combined the annotated differentially expressed genes (DEGs) and enriched transcriptional factors (TFs) targeting the promoter region from ATAC-seq results with the DEGs in RNA-seq, to identify key genes and pathways involved in alterations of biological processes and pathways in DS. Binding motif analysis showed a significant increase in chromatin accessibility of genes related to neural cell function, among others, in DSACs, which is primarily regulated by members of the activator protein-1 (AP-1) transcriptional factor family. Further studies indicated that MX Dynamin Like GTPase 1 (MX1), defined as one of the key effector genes of I-IFN, is a critical upstream regulator. Its overexpression induced expression of AP-1 TFs and mediated inflammatory response, thus leading to decreased cellular viability of DS cells. Moreover, treatment with specific AP-1 inhibitor T-5224 improved DS-associated phenotypes in DSACs. This study demonstrates that MX1-mediated AP-1 activation is partially responsible for cellular dysfunction of DS. T-5224 effectively ameliorated DS-associated phenotypes in DSACs, suggesting it as a potential treatment option for DS patients.


Building Bridges Through Collaboration and Consensus: Expanding Awareness and Use of Peer Support and Peer Support Communities Among People With Diabetes, Caregivers, and Health Care Providers.
Diabetes, regardless of type, is a complex disease. Successful management to achieve both short- and long-term health goals and outcomes is highly dependent on learning, mastery, and regular implementation and execution of self-care behaviors. The importance of a positive mental outlook and minimization of psychosocial barriers to care is increasingly identified as important in managing the whole person with diabetes and, as appropriate, the caregivers. Ongoing support from HCP and increasingly ongoing support from peers are critical elements of quality diabetes care. With the availability of virtually accessible technologies for social media and networking, the volume of peer support among people with diabetes and their caregivers has increased exponentially and will likely continue to do so. With the value of ongoing peer support recognized as an important element in diabetes health, a growing number of peer support communities and increasing engagement in these communities among some diabetes educators, the American Association of Diabetes Educators (AADE) embarked on an initiative to more formally work with diabetes peer support communities and their leaders. To initiate this effort AADE held and supported a consensus meeting in 2017. This article reviews the history and goals of this effort and details the meeting outcomes. It also discusses the collaborations completed since the initial meeting along with plans for the near future. This collaboration is unique and presents a model for similar endeavors in diabetes or other chronic diseases.


A critical review on modulators of Multidrug Resistance Protein 1 in cancer cells.
Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux transporter, and responsible for the transport of a broad spectrum of xenobiotics, toxins, and physiological substrates across the plasma membrane. As an efflux pump, it plays a significant role in the absorption and disposition of drugs including anticancer drugs, antivirals, antimalarials, and antibiotics and their metabolites across physiological barriers in cells. MRP1 is also known to aid in the regulation of several physiological processes such as redox homeostasis, steroid metabolism, and tissue defense. However, its overexpression has been reported to be a key clinical marker associated with multidrug resistance (MDR) of several types of cancers including lung cancer, childhood neuroblastoma, breast and prostate carcinomas, often resulting in a higher risk of treatment failure and shortened survival rates in cancer patients. Aside MDR, overexpression of MRP1 is also implicated in the development of neurodegenerative and cardiovascular diseases. Due to the cellular importance of MRP1, the identification and biochemical/molecular characterization of modulators of MRP1 activity and expression levels are of key interest to cancer research and beyond. This review primarily aims at highlighting the physiological and pharmacological importance of MRP1, known MRP1 modulators, current challenges encountered, and the potential benefits of conducting further research on the MRP1 transporter.


GABP controls a critical transcription regulatory module that is essential for maintenance and differentiation of hematopoietic stem/progenitor cells.
Maintaining a steady pool of self-renewing hematopoietic stem cells (HSCs) is critical for sustained production of multiple blood lineages. Many transcription factors and molecules involved in chromatin and epigenetic modifications have been found to be critical for HSC self-renewal and differentiation; however, their interplay is less understood. The transcription factor GA binding protein (GABP), consisting of DNA-binding subunit GABPα and transactivating subunit GABPβ, is essential for lymphopoiesis as shown in our previous studies. Here we demonstrate cell-intrinsic, absolute dependence on GABPα for maintenance and differentiation of hematopoietic stem/progenitor cells. Through genome-wide mapping of GABPα binding and transcriptomic analysis of GABPα-deficient HSCs, we identified Zfx and Etv6 transcription factors and prosurvival Bcl-2 family members including Bcl-2, Bcl-X(L), and Mcl-1 as direct GABP target genes, underlying its pivotal role in HSC survival. GABP also directly regulates Foxo3 and Pten and hence sustains HSC quiescence. Furthermore, GABP activates transcription of DNA methyltransferases and histone acetylases including p300, contributing to regulation of HSC self-renewal and differentiation. These systematic analyses revealed a GABP-controlled gene regulatory module that programs multiple aspects of HSC biology. Our studies thus constitute a critical first step in decoding how transcription factors are orchestrated to regulate maintenance and multipotency of HSCs.


An update on distribution models for Rhipicephalus microplus in West Africa.
The cattle tick, Rhipicephalus microplus, which reached the West African region approximately 8 years ago, has established viable populations in Côte d'Ivoire and Benin and spread rapidly from the assumed points of introduction. However, existing maps of its distribution range do not agree on the areas at risk, most probably due to suboptimal modelling approaches. Therefore, we undertook a re-investigation of the potential distribution range based on a high-quality dataset from West Africa that includes information on 104 farms located all over Benin. Focussing on climate suitability and applying advanced modelling, a subset of representative and uncorrelated climate variables was selected and fed into Maxent software to obtain an estimate of climate suitability for West Africa. The resulting map was validated using an independent dataset of 13 farms along the apparent distribution edge. The entire southern part of West Africa (covering southern Nigeria, Benin, Togo and Ghana) features high climate suitability for R. microplus. All of Côte d'Ivoire is inside the distribution range of this tick and the southern rim of Burkina Faso is expected to be suitable for the establishment of R. microplus populations. The validation of the distribution, dated one year after the initial field visit, confirmed the predicted distribution range, although a small number of individuals of R. microplus were found north of the predicted limit. These low numbers might indicate that the climate is not suitable for the establishment of a viable tick population. An alternative explanation is the recent introduction by nomadic cattle herds passing through this location. In this region of the world, it is quite common for cattle owners to lead their livestock over distances of more than 500 km in search of food and water.


Expression of intermediate filaments at muscle insertions in human fetuses.
Desmin and vimentin are intermediate filaments that play crucial roles in the maturation, maintenance and recovery of muscle fibers and mesenchymal cells. The expression of these proteins has not been investigated extensively in human fetuses. In the present study, we examined the immunohistochemical expression of intermediate filaments in skeletal muscles of the head, neck and thorax in 12 mid-term human fetuses at 9-18 weeks of gestation. We also used immunohistochemistry to localize the expression of the myosin heavy chain and silver impregnation to identify the fetal endomysium. Expression of desmin and vimentin was already detectable in intercostal muscle at 9 weeks, especially at sites of muscle attachment to the perichondrium. At this stage, myosin heavy chain was expressed throughout the muscle fibers and the endomysium had already developed. Beginning with punctate expression, the positive areas became diffusely distributed in the muscle fibers. At 15-18 weeks, intermediate filament proteins were extensively expressed in all of the muscles examined. Expression at the bone-muscle interface was continuous with expression along the intramuscular tendon fibres. These results suggest that the development of intermediate filaments begins in areas of mechanical stress due to early muscle contraction. Their initially punctate distribution, as observed here, probably corresponds to the earliest stage of fetal enthesis formation.


Comparison of scoring systems for invasive pests using ROC analysis and Monte Carlo simulations.
Different international plant protection organisations advocate different schemes for conducting pest risk assessments. Most of these schemes use structured questionnaire in which experts are asked to score several items using an ordinal scale. The scores are then combined using a range of procedures, such as simple arithmetic mean, weighted averages, multiplication of scores, and cumulative sums. The most useful schemes will correctly identify harmful pests and identify ones that are not. As the quality of a pest risk assessment can depend on the characteristics of the scoring system used by the risk assessors (i.e., on the number of points of the scale and on the method used for combining the component scores), it is important to assess and compare the performance of different scoring systems. In this article, we proposed a new method for assessing scoring systems. Its principle is to simulate virtual data using a stochastic model and, then, to estimate sensitivity and specificity values from these data for different scoring systems. The interest of our approach was illustrated in a case study where several scoring systems were compared. Data for this analysis were generated using a probabilistic model describing the pest introduction process. The generated data were then used to simulate the outcome of scoring systems and to assess the accuracy of the decisions about positive and negative introduction. The results showed that ordinal scales with at most 5 or 6 points were sufficient and that the multiplication-based scoring systems performed better than their sum-based counterparts. The proposed method could be used in the future to assess a great diversity of scoring systems.


The effects of low-intensity resistance training with or without blood flow restriction on serum BDNF, VEGF and perception in patients with post-stroke depression.
Post-stroke depression (PSD) has a significant effect on patients' quality of life and is often accompanied by a decrease in serum brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) levels. Although exercise is an effective way to improve the body's endocrine environment, traditional high-intensity resistance exercise is not yet readily accepted. To compare the acute effects of high and low resistance training with or without blood flow restriction on perception, BDNF, and VEGF levels in patients with PSD. A total of 24 patients with PSD participated in 2 40% 1- Repetition Maximum (RM) low-intensity resistance training sessions (the low-intensity resistance training group (LOW group) had no blood flow restriction belt; the low-intensity blood flow restriction group (L-BFR group) was required to wear a 120-160 mmHg pressure cuff at the proximal end of the limb) and 1 80% 1-RM high-intensity resistance training session (HIGH group). Elbow venous blood was collected before and after exercise to test for ratings of perceived exertion (RPE), serum blood lactic acid (BLA), BDNF, and VEGF levels. There were no statistical differences between the RPE, BLA, BDNF, and VEGF levels of each group before exercise. After exercise, the RPE, BLA, and BDNF levels of the LOW group increased significantly (P < 0.05); the change in VEGF level of the LOW group was not significantly different from that before exercise (P > 0.05), and the indexes of the L-BFR group and the HIGH group were significant after the increase in exercise (P < 0.05). Analysis between groups showed that the changes in BLA, BDNF, and VEGF levels in the L-BFR group and HIGH group were higher than those in the LOW group, and the statistical difference was significant (P < 0.05); there was no change between the statistical difference of the L-BFR group and HIGH group (P > 0.05). The difference in RPE before and after exercise in the HIGH group was significantly higher than that in the L-BFR group (P < 0.05) and the difference in RPE before and after exercise in the L-BFR group was significantly higher than that in the LOW group (P < 0.05). Blood flow restriction resistance exercise may increase the serum BNDF and VEGF levels of PSD patients by increasing the body's BLA concentration. Although its effect is similar to that of traditional high-intensity resistance exercise, subjective physical strength is lower during blood flow restriction resistance exercise.


Construction of a ferritin reactor: an efficient means for trapping various heavy metal ions in flowing seawater.
An apparatus consisting of two pumps, a mixer, a ferritin reactor, and a spectrophotometer was constructed to study the ability to trap various heavy metal ions (M2+) and the dynamics of a reconstituted ferritin reactor in flowing seawater. Reconstituted pig spleen ferritin (PSFr) is assembled from apo-protein shell to form a reconstituted iron core. The main components of the PSFr are its core, which contains an Fe2+:Pi stoichiometry of 6.0 +/- 0.5, reconstituted from pig spleen apoferritin (apo PSF), Fe2+, inorganic phosphate (Pi), and O2 (0.6 atm). The Fe3+-Pi clusters within the PSFr core exhibit resistance to salt ranging from 1% to 6% NaCl. The ferritin reactor consists of PSFr and an oscillating bag. Using the reactor, M2+ ions such as Cd2+, Zn2+, Co2+, and Mn2+ are directly trapped by the ferritin. We found a 1:2 +/- 0.2 stoichiometry of the trapped M2+ to the released iron as measured by chemical analysis or atomic absorption spectrometry; nontransient elements such as Na+, K+, Ca2+, etc., were scarcely trapped by the reactor. This study provides basic conditions for establishing a ferritin reactor and a convenient means for monitoring the pollution of heavy metal ions in seawater.


Proteomic characterization of six Taiwanese snake venoms: Identification of species-specific proteins and development of a SISCAPA-MRM assay for cobra venom factors.
Deinagkistrodon acutus, Trimeresurus stejnegeri, Protobothrops mucrosquamatus, Daboia russelii siamensis, Bungarus multicinctus and Naja atra are the six medically important venomous snake species in Taiwan. In this study, we characterized and compared their venom protein profiles using proteomic approaches. The major snake venom proteins were identified by GeLC-MS/MS and the total venom proteome was characterized by in-solution digestion coupled with LC-MS/MS. A total of 27-52 proteins, categorized into 23 protein families, were identified in each snake's venom. The major venom components found in Viperidae species (D. acutus, T. stejnegeri, P. mucrosquamatus and D. russelii) were C-type lectin, snake venom serine proteinase, venom metalloproteinase and phospholipase A2, whereas three-finger toxin and phospholipase A2 were the major components detected in the venom of Elapidae snakes (B. multicinctus and N. atra). This study also provided the first demonstration of some low-abundance proteins in these six snake venoms, including 5'-nucleotidase, glutaminyl-peptide cyclotransferase and phosphodiesterase, among others. Furthermore, we found that cobra venom factor (CVF) is a cobra-specific protein. We produced anti-peptide antibodies against CVF and used it to develop a highly sensitive SISCAPA-MRM assay for quantifying CVF. The limit of detection and lower limit of quantification were 3.2 and 9.6 attomoles, respectively. This assay was used to precisely quantify CVF in 1 μg crude venom proteins from three Naja species and king cobra. The amount of CVF varied from 0.9 to 54.36 femtomoles (equivalent to 0.16-10.03 mg/g of venom protein). There are six medically significant venomous snakes in Taiwan. The venoms of the four Viperidae species (Deinagkistrodon acutus, Trimeresurus stejnegeri, Protobothrops mucrosquamatus and Daboia russelii siamensis) cause local tissue swelling; this symptom is also seen in N. atra envenomation in humans, potentially complicating the differential diagnosis of envenomation by N. atra and Viperidae species. Thus, characterization of the venom proteomes of the six Taiwanese snakes, including the relative abundance of the major components and species-specific protein(s) in each venom type, could be useful for future venom research, including the development of new assay(s) for detecting snake species-specific venom protein(s) and new type(s) of antivenom.


Evidence for the differentiation of wild-type alleles in different species of neurospora.
Wild-type alleles at the peak locus of Neurospora have been transferred by backcrossing from N. sitophila and N. tetrasperma to N. crassa. In the genomic background of N. crassa the different wild-type alleles show strikingly different dominance relations with Pk-4, a dominant peak mutation in N. crassa.


Transferable drug resistance associated with coliforms isolated from hospital and domestic sewage.
The incidence of antibiotic-resistant fecal coliforms in raw and treated hospital and municipal wastes was investigated to determine whether such wastes may serve as reservoirs for the spread of resistant bacteria and resistance transfer factors. Multiple resistance occurred in 87.8% of isolates from hospital and 42.6% of isolates from municipal wastes. Antibiotic resistance was transferable to Escherichia coli and Salmonella cholerae-suis recipient strains from 62.3% of resistant isolates from hospital and 90.9% of resistant isolates from municipal wastes, and from 56.2% of all isolates from hospital and 45.9% of all isolates from municipal wastes. Numbers of multiply-resistant fecal coliforms decreased during passage through a sewage treatment plant, but their proportion did not change appreciably, although proportions exhibiting resistance to 3, 4, 5, 6, and 7 drugs decreased. A study of transfer in sewage indicated that transfer of resistance from donors present in sewage to pathogenic Salmonella strains can occur under appropriate conditions. The data suggest that both raw and treated wastes, and especially those from hospitals, may serve as reservoirs for the spread of antibiotic-resistant bacteria and transferable resistance in the environment.


Management of type 2 diabetes: consensus of diabetes organizations.
Despite the advances in diabetes management, people with diabetes are not reaching their target glycemic goals. Healthcare professionals often fail to initiate, escalate, or de-intensify therapy when indicated. There are several organizations that provide guidance on the management of diabetes to assist the practitioner in achieving improved glycemic control, and this can cause confusion to the practitioner on which organizations' guidance to follow. Diabetes mellitus is associated with an elevated risk of cardiovascular disease, and there have been studies that suggest some antidiabetic medications increase cardiovascular risk and some reduce cardiovascular risk. Diabetes organizations recommend the individualization of treatment goals and choices of drug therapy that will be safe and effective. Healthcare professionals should be knowledgeable and equipped to decide on the best treatment regimen for each of their patients with type 2 diabetes (T2D) and be familiar with how to utilize the different organizations' philosophies in treating their patients.


Why Should Physicians Care About What Law Says About Turfing and Dumping Patients?
When a physician refers a patient for a nonclinical reason, that patient has been "turfed." There are numerous reasons why turfing is clinically, legally, and ethically problematic; a main one is that the practice is physician centered and does not serve or center the best interests of patients. Legally, turfing patients is distinct from dumping patients: there are no civil or criminal laws regulating turfing, unlike dumping. Clinically and ethically, however, both turfing and dumping are poor practice, express poor character, and damage patient-physician and interprofessional relationships. This manuscript canvasses clinical, legal, and ethical dimensions of turfing and dumping that deserve investigation.


The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction.
CART (cocaine- and amphetamine-regulated transcript) peptides are neuromodulators that are involved in feeding, drug reward, stress, cardiovascular function, and bone remodeling. CART peptides are abundant but discretely distributed in the brain, pituitary and adrenal glands, pancreas, and gut. High expression of CART in discrete hypothalamic nuclei associated with feeding has led to behavioral and pharmacological studies that strongly support an anorectic action of CART in feeding. Subsequent studies on humans and transgenic animals provide additional evidence that CART is important in the regulation of appetite as mutations in the CART gene are linked to eating disorders, including obesity and anorexia. The expression of CART in the mesolimbic dopamine circuit has lead to functional studies demonstrating CART's psychostimulant-like effects on locomotor activity and conditioned place preference in rats. These and other findings demonstrated that CART modulates mesolimbic dopamine systems and affects psychostimulant-induced reward and reinforcing behaviors. The link between CART and psychostimulants was substantiated by demonstrating alterations of the CART system in human cocaine addicts. CART seems to regulate the mesolimbic dopamine system, which serves as a common mechanism of action for both feeding and addiction. Indeed, recent studies that demonstrated CART projections from specific hypothalamic areas associated with feeding to specific mesolimbic areas linked to reward/motivation behaviors provide evidence that CART may be an important connection between food- and drug-related rewards. Given the enormous public health burden of both obesity and drug addiction, future studies exploring the pharmacotherapies targeting CART peptide represent an exciting and challenging research area.


XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality.
The event of X chromosome inactivation induced by XIST, which is physiologically observed in females, is retained in testicular germ cell tumors (TGCTs), as a result of a supernumerary X chromosome constitution. X chromosome inactivation also occurs in male germline, specifically during spermatogenesis. We aimed to analyze the promoter methylation status of XIST in a series of TGCT tissues, representative cell lines, and testicular parenchyma. Two independent cohorts were included, comprising a total of 413 TGCT samples, four (T)GCT cell lines, and 86 testicular parenchyma samples. The relative amount of methylated and demethylated XIST promoter fragments was assessed by quantitative methylation-specific PCR (qMSP) and more sensitive high-resolution melting (HRM) methylation analyses. Seminomas showed a lower amount of methylated XIST fragments as compared to non-seminomas or normal testis (p < 0.0001), allowing for a good discrimination among these groups (area under the curve 0.83 and 0.81, respectively). Seminomas showed a significantly higher content of demethylated XIST as compared to non-seminomas. The percentage of demethylated XIST fragment in cell lines reflected their chromosomal constitution (number of extra X chromosomes). A novel and strong positive correlation between the Johnsen's score and XIST demethylation was identified (r = 0.75, p < 0.0001). The X chromosome inactivation event and demethylated XIST promoter are promising biomarkers for TGCTs and for assessing spermatogenesis quality.


No guts, no glory? How risk-taking shapes dominance, prestige, and leadership endorsement.
Risk-taking can fuel innovation and growth, but it can also have devastating consequences for individuals and organizations. Here we examine whether risk-taking affords social-hierarchical benefits to risk-takers. Specifically, we investigate how risk-taking influences perceived dominance, prestige, and the willingness to endorse risk-takers' leadership. Integrating insights from costly signaling theory and the dominance/prestige framework of social rank, we theorized that risk-taking increases leadership endorsement to the degree that it fuels perceptions of prestige, but decreases leadership endorsement to the degree that it fuels perceptions of dominance. However, we also hypothesized that risk-induced perceptions of dominance do translate into leadership endorsement in competitive (rather than cooperative) intergroup settings. We tested these hypotheses in four studies involving different samples, methods, and operationalizations. In Study 1, participants performed an implicit association test (IAT) that revealed that people associate risk with leader positions, and safety with follower positions. Study 2 was a longitudinal field survey conducted during the September 2019 Israeli elections, which showed that voters' perceptions of politicians' risk-taking propensities prior to the elections positively predicted perceived dominance and prestige as well as voting behavior during the elections. Finally, Studies 3 and 4 demonstrated that people are willing to support risk-takers as leaders in the context of competitive (as opposed to cooperative) intergroup situations, because perceived dominance positively predicts leadership endorsement in competitive (but not cooperative) intergroup settings. We discuss implications for understanding the social dynamics of organizational rank and the perpetuation of risky behavior in organizations, politics, and society at large. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Long-term benefits. A retirement community grows by reaching out to area residents.
At St. Leonard Center, a retirement community in Dayton, OH, community benefit programs are such a critical part of daily operations that the organization could not continue to flourish without them. Founded in 1983, the center now serves more than 600 persons. St. Leonard offers independent living arrangements, as well as assisted living and skilled nursing care. From its beginning the center has depended on collaborative arrangements with local churches, agencies, and other organizations. As the center has grown, it has continued to work with others to enhance services to its clients and to local residents. Recent arrangements with St. Elizabeth Medical Center in Dayton have enabled the center to offer home healthcare, as well as outpatient and inpatient rehabilitation. Integrated pharmacy, medical supply, and laboratory services are also available, and a systemwide management information system is currently under development. St. Leonard Center also reaches out to local elderly residents through adult day care and respite programs, as well as through its Senior Network, a resource center (cosponsored by St. Elizabeth) with about 25,000 enrollees. The center also offers three special educational programs for children.


Photophysical properties of highly luminescent copper(I) halide complexes chelated with 1,2-bis(diphenylphosphino)benzene.
Studies on synthesis, structures, and photophysics have been carried out for a series of luminescent copper(I) halide complexes with the chelating ligand, 1,2-bis[diphenylphosphino]benzene (dppb). The complexes studied are halogen-bridged dinuclear complexes, [Cu(mu-X)dppb]2 (X = I (1), Br (2), Cl (3)), and a mononuclear complex, CuI(dppb)(PPh3) (4). These complexes in the solid state exhibit intense blue-green photoluminescence with microsecond lifetimes (emission peaks, lambdamax = 492-533 nm; quantum yields, Phi = 0.6-0.8; and lifetimes, tau = 4.0-10.4 mus) at 298 K. In 2-methyltetrahydrofuran (2mTHF) solutions at 298 K, only 1 and 4 show weaker emission (Phi = 0.009) with shorter lifetimes (tau = 0.35 and 0.23 mus) and red-shifted spectra (lambdamax = 543 and 546 nm). The emission in the solid state originates from the (M + X)LCT excited state with a distorted-tetrahedral conformation, in which emissive excited states, 1(M + X)LCT and 3(M + X)LCT, are in equilibrium with an energy difference of approximately 2 kcal/mol. On the other hand, the complexes in the 2mTHF solutions emit from the MLCT excited state with an energetically favorable flattened conformation in the temperature range of 298-130 K. The flattened geometry with equilibrated 1MLCT and 3MLCT states has a nonradiative rate at least 2 orders of magnitude larger than that of the distorted-tetrahedral geometry, leading to a much smaller emission quantum yield (Phi = 0.009) at 298 K. Since the flattening motion is markedly suppressed below 130 K, the emission observed in 2mTHF below 130 K is considered to occur principally from the (M + X)LCT state with a distorted-tetrahedral geometry. To interpret the photophysics of 1 and 4 in both the solid and solution states, we have proposed the "2-conformations with 2-spin-states model (2C x 2S model)". The electroluminescence device using (1) as a green emissive dopant showed a moderate EL efficiency; luminous efficiency = 10.4 cd/A, power efficiency = 4.2 lm/W at 93 cd/m(2), and maximum external quantum efficiency = 4.8%.


Acute massive pulmonary embolism with hemodynamic compromise treated successfully with thrombolytic therapy.
A 78 year-old woman presented with a history of 15 days of dyspnea and tachypnea at rest. A distended right ventricle with free-wall hypokinesis and displacement of the interventricular septum toward the left ventricle were shown on echocardiography. The patient suddenly arrested. She underwent cardiac catheterization and selective pulmonary angiography for suspected pulmonary embolism while undergoing cardiopulmonary resuscitation. With the diagnosis of pulmonary embolism confirmed, recombinant tissue plasminogen activator was given immediately in the catheterization room. This case shows how pulmonary embolism can be diagnosed with pulmonary angiography during cardiopulmonary resuscitation and the life-saving result from rapid thrombolysis with recombinant tissue plasminogen activator.


Deciphering the tumor-suppressive role of PSMB9 in melanoma through multi-omics and single-cell transcriptome analyses.
Skin cutaneous melanoma (SKCM) poses a significant challenge in skin cancers. Recent immunotherapy breakthroughs have revolutionized melanoma treamtment, yet tumor heterogeneity persists as an obstacle. Epigenetic modifications orchestrated by DNA methylation contributed to tumorigenesis, thus potentially unveiling melanoma prognosis. Here, we identified an interferon-gamma (IFN-g) sensitive subtype, which possesses favorable outcomes, robust infiltration CD8+T cells, and IFN-g score in bulk RNA-seq profile. Subsequently, we established an IFN-g sensitivity signature based on machine learning. We validated that PSMB9 is strongly correlated with immunotherapy response in both methylation and expression cohorts in this 10-probe signature. We assumed that PSMB9 acts as a putative melanoma suppressor, for its activation of CD8+T cell; capacity to modulate IFN-γ secretion; and dynamics altering IFN-g receptors in bulk tissue. We performed single-cell RNA-seq on immunotherapy patients' tissue to uncover the nuanced role of PSMB9 in activating CD8T + cells, enhancing IFN-g, and influencing malignant cells receptors and transcriptional factors. Overexpress PSMB9 in two SKCM cell lines to mimic the hypomethylated state to approve our conjecture. Strong cell proliferation and migration inhibition were detected on both cells, indicating that PSMB9 is present in tumor cells and that high expression is detrimental to tumor growth and migration. Overall, comprehensive integrated analysis shows that PSMB9 emerges as a vital prognostic marker, acting predictive potential regarding immunotherapy in melanoma. This evidence not only reveals the multifaceted impact of PSMB9 on both malignant and immune cells but also serves as a prospective target for undergoing immunotherapeutic strategies in the future.


Evaluation of transcendental meditation as a method of reducing stress.
Transcendental meditation is said to induce in its practitioners an altered state of consciousness resulting in relief of stress, an increased sense of awareness, and a sense of well-being. Release of catecholamines has been associated widely with stress and lends itself to quantitation. Plasma epinephrine and norephinephrine, as well as lactate, were measured in 12 volunteers before, during, and after meditation. Values were compared with those obtained from controls matched for sex and age who rested instead of meditating. Essentially the same results were obtained for the two groups, which suggests that meditation does not induce a unique metabolic state but is seen biochemically as a resting state.


Targeting Rho GTPase Signaling Networks in Cancer.
As key regulators of cytoskeletal dynamics, Rho GTPases coordinate a wide range of cellular processes, including cell polarity, cell migration, and cell cycle progression. The adoption of a pro-migratory phenotype enables cancer cells to invade the stroma surrounding the primary tumor and move toward and enter blood or lymphatic vessels. Targeting these early events could reduce the progression to metastatic disease, the leading cause of cancer-related deaths. Rho GTPases play a key role in the formation of dynamic actin-rich membrane protrusions and the turnover of cell-cell and cell-extracellular matrix adhesions required for efficient cancer cell invasion. Here, we discuss the roles of Rho GTPases in cancer, their validation as therapeutic targets and the challenges of developing clinically viable Rho GTPase inhibitors. We review other therapeutic targets in the wider Rho GTPase signaling network and focus on the four best characterized effector families: p21-activated kinases (PAKs), Rho-associated protein kinases (ROCKs), atypical protein kinase Cs (aPKCs), and myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs).


The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead.
Cancer is considered a group of diseases characterized by uncontrolled growth and spread of abnormal cells and is propelled by somatic mutations. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of enzymes are endogenous sources of somatic mutations found in multiple human cancers. While these enzymes normally act as an intrinsic immune defence against viruses, they can also catalyse 'off-target' cytidine deamination in genomic single-stranded DNA intermediates. The deamination of cytosine forms uracil, which is promutagenic in DNA. Key factors to trigger the APOBEC 'off-target' activity are overexpression in a non-normal cell type, nuclear localization and replication stress. The resulting uracil-induced mutations contribute to genomic variation, which may result in neutral, beneficial or harmful consequences for the cancer. This review summarizes the functional and biochemical basis of the APOBEC3 enzyme activity and highlights their relationship with the most well-studied cancers in this particular context such as breast, lung, bladder, and human papillomavirus-associated cancers. We focus on APOBEC3A, APOBEC3B and APOBEC3H haplotype I because they are the leading candidates as sources of somatic mutations in these and other cancers. Also, we discuss the prognostic value of the APOBEC3 expression in drug resistance and response to therapies.


[Conceptual approaches in quality evaluation, quality promotion and quality assurance].
Ten conceptual approaches make up most of the basis for attempts to deal with quality in healthcare. Quality assessment, quality approvement, and quality assurance are related to the instrumental categories for dealing with quality. At first glance, outcome analysis seems to be most logical. However, the process of healthcare-delivery is of considerable importance and should not be neglected in favor of outcome studies. Accreditation seems promising for obtaining about compliance with standards which serve as a certain degree of guarantee for the prevention of problems. Standards are most prominently connected with structure. With the help of guidelines the process of providing care can be improved. Indicators related to process and outcomes may serve as "flags" for problems. Without continuous evaluation, studies quite often result in no direct contribution to quality improvement and quality assurance.


Maternal allergy modulates cord blood hematopoietic progenitor Toll-like receptor expression and function.
Little is known regarding the prenatal determinants of innate immune responses in relation to infant allergic risk. Environmental exposures, including microbial stimuli, might predispose susceptible subjects to atopy and asthma in early infancy or even in utero. Because Toll-like receptors (TLRs) recognize microbial products and because cord blood (CB) progenitor alterations have been observed in neonates at risk for atopy, we investigated the expression and function of TLRs on CB hematopoietic progenitors in relation to atopic risk, as defined by maternal allergic sensitization. Thirty-two (15 with low and 17 with high atopic risk) infant CB samples were assessed for phenotypic and functional alterations in CD34(+) cells by means of flow cytometry and methylcellulose culture, respectively. CD34(+) hematopoietic progenitors were stained for TLR-2, TLR-4, TLR-9, GM-CSF receptor α, IL-5 receptor α, and IL-3 receptor α or cultured in methylcellulose assays for hematopoietic cytokine-stimulated eosinophil-basophil (Eo/B) colony-forming units (CFUs) with or without LPS. High-atopic-risk infants had significantly lower CB CD34(+) cell TLR-2, TLR-4, and TLR-9 expression (P = .009). High-risk infant progenitors gave rise to significantly more Eo/B CFUs (P = .002) with hematopoietic cytokine (IL-3, IL-5, or GM-CSF) stimulation ex vivo. Although LPS costimulation induced Eo/B CFUs from both low- and high-risk infant CB CD34(+) cells, this response was significantly (P = .020) muted in the high-risk CB progenitors. Neonatal CB CD34(+) hematopoietic progenitor cell TLR expression and functional responsiveness are altered in CB from atopic at-risk infants. Maternal allergic sensitization might modulate hematopoietic progenitor TLR expression and function in utero; specifically, Eo/B "lineage priming" at birth might be circumvented through engagement of TLR pathways in early life.


Interventions for autumn exacerbations of asthma in children.
Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere. To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period. We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication. We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger. We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period. Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment.A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December.Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses. Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.


[Menstrual disorders in athletes].
It is important to pay attention to bone metabolism in women long before the menopause. Irregular menstruation with anovulatory cycles or amenorrhoea persisting over several years have negative effects on bone formation and total bone mass already within a few years after menarche. They lead to a lack of oestradiol and are often associated with inadequate and unbalanced nutrition (e.g. lack of calcium and proteins). This results in severe impairment of bone formation and a net loss of bone mass. It is the duty of the doctors taking care of female athletes (as well as non-athletes) with irregular menstrual cycles or amenorrhoea to protect them against osteoporosis which may manifest itself 2-5 decades later. In the special case of female athletes a reduced bone mass is an important risk factor for stress fractures which can result in interruption or even in a premature termination of promising athletic careers. Athletes with retarded menarche, irregular menstrual cycles, or amenorrhoea must, therefore, be referred to a gynecologist for further diagnosis and treatment.


A Comparative Study on Shoulder Rotational Strength, Range of Motion and Proprioception between the Throwing Athletes and Non-athletic Persons.
The repetitive micro traumatic stresses placed on the athletes shoulder joint complex during the throwing motion challenge the surrounding tissues. The purpose of this study was to compare shoulder rotational strength, range of motion and proprioception between the throwing athletes and non-athletic persons. Fifteen throwing athletes and 15 non-athletes participated in a nonrandom case - control study. Strength of shoulder rotational movements was tested with a hand held dynamometer. The ranges of internal and external rotation of shoulder were measured by a standard goniometer. The ability of subjects to replicate the target position and kinesthetic sense was examined on the subjects' right shoulder by using a continuous passive motion device. Independent and paired t tests were used to statistically analyze between and within group differences. No significant difference was detected on the range of internal rotation between throwing athletes and non-athletic candidates (P=0.3). The range of external rotation was significantly more in athletic subjects (P=0.03). The results also showed that throwing athletes demonstrated a significantly higher isometric strength of shoulder external and internal rotation than the non-athletic group (P<0.05). However, the comparison of the internal and external rotation strength of dominant side in each group showed that throwing athletes showed a significant lower isometric strength of shoulder external rotation than internal rotation (P<0.001). It was also demonstrated higher joint position acuity in the throwing athletes than non athlete subjects (P=0.01). The repetitive nature of overhead throwing and the high forces that it causes result in adaptive changes of the dominant extremity. Throwing can lead to mobility, strength and neural adaptation.


[Intracoronary thrombolytic therapy of myocardial infarction].
The results of intracoronary thrombolytic therapy with avelysine given to 21 patients with acute myocardial infarction are described. Intracoronary thrombolysis was performed on the average 5 h and 30 min after myocardial infarction onset. Recanalization of the coronary artery was attained in 16 patients, with no lethal outcomes. One patient died out of the 5, in whom attempts to recanalize the artery ended in failure. Recanalization of the coronary arteries led to improvement of left ventricle function and appreciably accelerated the time-course of the enzymatic shifts (KPK and LDH) in blood of myocardial infarction patients. After successful recanalization of the coronary artery the disease in myocardial infarction patients took a far milder course as compared to those who did receive intracoronary thrombolytic therapy.


Plasmid-encoded VCC-1 β-lactamase in a clinical isolate of Aeromonas caviae.
Vibrio cholerae carbapenemase (VCC-1) is a chromosomal encoded class A carbapenemase thus far reported in environmental Vibrio cholerae isolates. Here, we report the first isolation of a blaVCC-1 -carrying Aeromonas caviae from a clinical sample in Israel. The isolate was resistant to all β-lactam agents, including carbapenems. The blaVCC-1 was located on a large plasmid. GC content suggests that the origin of the blaVCC-1 gene is neither Aeromonas nor Vibrio spp. but an unknown progenitor.


Periostin in Skin Tissue Skin-Related Diseases.
Extracellular matrix (ECM) is not only involved in the maintenance of normal physiological tissue but also in interactions with other ECM components, tissue remodeling, and modulating immune responses. The skin provides a distinctive environment characterized by rich fibroblasts producing various ECM proteins, epithelial-mesenchymal interactions, and immune responses induced by external stimuli. Recently, periostin-a matricellular protein-has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc) patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD), attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.


Diagnosing community-acquired pneumonia via a smartphone-based algorithm: a prospective cohort study in primary and acute-care consultations.
Community-acquired pneumonia (CAP) is an essential consideration in patients presenting to primary care with respiratory symptoms; however, accurate diagnosis is difficult when clinical and radiological examinations are not possible, such as during telehealth consultations. To develop and test a smartphone-based algorithm for diagnosing CAP without need for clinical examination or radiological inputs. A prospective cohort study using data from participants aged >12 years presenting with acute respiratory symptoms to a hospital in Western Australia. Five cough audio-segments were recorded and four patient-reported symptoms (fever, acute cough, productive cough, and age) were analysed by the smartphone-based algorithm to generate an immediate diagnostic output for CAP. Independent cohorts were recruited to train and test the accuracy of the algorithm. Diagnostic agreement was calculated against the confirmed discharge diagnosis of CAP by specialist physicians. Specialist radiologists reported medical imaging. The smartphone-based algorithm had high percentage agreement (PA) with the clinical diagnosis of CAP in the total cohort (n = 322, positive PA [PPA] = 86.2%, negative PA [NPA] = 86.5%, area under the receiver operating characteristic curve [AUC] = 0.95); in participants 22-<65 years (n = 192, PPA = 85.7%, NPA = 87.0%, AUC = 0.94), and in participants aged ≥65 years (n = 86, PPA = 85.7%, NPA = 87.5%, AUC = 0.94). Agreement was preserved across CAP severity: 85.1% (n = 80/94) of participants with CRB-65 scores 1 or 2, and 87.7% (n = 57/65) with a score of 0, were correctly diagnosed by the algorithm. The algorithm provides rapid and accurate diagnosis of CAP. It offers improved accuracy over current protocols when clinical evaluation is difficult. It provides increased capabilities for primary and acute care, including telehealth services, required during the COVID-19 pandemic.


Snail as a potential target molecule in cardiac fibrosis: paracrine action of endothelial cells on fibroblasts through snail and CTGF axis.
Ischemia/reperfusion (I/R) injury to myocardium induces death of cardiomyocytes and destroys the vasculature, leading to cardiac fibrosis that is mainly mediated by the transdifferentiation of fibroblasts to myofibroblasts and the collagen deposition. Snail involvement in fibrosis is well known; however, the contribution of Snail to cardiac fibrosis during I/R injury and its underlying mechanisms have not been defined. We showed that I/R injury to mouse hearts significantly increases the expression of Snail. An in vitro hypoxia/reoxygenation (Hy/Reoxy) experiment showed that the cell source of Snail induction is endothelial cells rather than cardiac fibroblasts (cFibroblasts) or cardiomyoblasts. When Snail was overexpressed in endothelial cells, they underwent endothelial-to-mesenchymal transition (EndMT) but showed very poor capacity for collagen synthesis. Instead, reoxygenation- or Snail overexpression-mediated EndMT-like cells noticeably stimulated transdifferentiation of fibroblasts to myofibroblasts via secretion of connective tissue growth factor (CTGF). The injection of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, a selective Snail inhibitor, remarkably suppressed collagen deposition and cardiac fibrosis in mouse I/R injury, and significantly improved cardiac function and reduced Snail and CTGF expression in vivo. Our findings suggested a new mechanism of cell-to-cell communication between EndMT-like cells and fibroblasts for fibrosis induction and implicated Snail as a potential target molecule in cardiac fibrosis after I/R injury.


Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells.
In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we have characterized the G protein-coupled receptors expressed in gastric Sst-RFP-positive cells and probed their effects on SST secretion in primary cell cultures. Surprisingly, besides SST, amylin and PYY were also highly enriched in the SST cells. Several receptors found to regulate SST secretion were highly expressed and/or enriched. 1) The metabolite receptors calcium-sensing receptor and free fatty acid receptor 4 (GPR120) functioned as positive and negative regulators, respectively. 2) Among the neurotransmitter receptors, adrenergic receptors α1a, α2a, α2b, and β1 were all highly expressed, with norepinephrine and isoproterenol acting as positive regulators. The muscarinic receptor M3 acted as a positive regulator, whereas M4 was conceivably a negative regulator. 3) Of the hormone receptors, the GLP-1 and GIP receptors, CCKb (stimulated by both CCK and gastrin) and surprisingly the melanocortin MC1 receptor were all positive regulators. 4) The neuropeptide receptors for calcitonin gene-related peptide, adrenomedullin, and vasoactive intestinal peptide acted as positive regulators, no effect was observed using galanin and nociceptin although transcripts for the corresponding receptors appeared highly expressed. 5) The SST receptors 1 and 2 functioned in an autocrine negative feedback loop. Thus, the article provides a comprehensive map of receptors through which SST secretion is regulated by hormones, neurotransmitters, neuropeptides and metabolites that act directly on the SST cells in the gastric mucosa.


Arterial malformations leading to bilateral spontaneous renal hemorrhage in a dog.
To describe the clinical presentation, diagnostic imaging, management, and follow-up of a dog that presented with sequential, bilateral, spontaneous, subcapsular and perirenal hemorrhage (Wunderlich syndrome) due to bilateral renal arterial malformations. A 9-year-old intact male Field Spaniel presented for acute onset abdominal pain following a possible syncopal episode. Abdominal ultrasonography, contrast-enhanced ultrasound, and computed tomography (CT) revealed right-sided perirenal hemorrhage that extended into the peritoneum. The dog was discharged following stabilization with analgesia, fluid therapy, and tranexamic acid. One month later, the patient presented with identical clinical signs. A CT scan at this stage revealed bilateral kidney infarcts with new left-sided perirenal hemorrhage. Abdominal ultrasound and contrast-enhanced ultrasound were repeated and showed similar findings. Follow up with four-dimensional CT angiography revealed bilateral renal arterial malformations, likely causing spontaneous renal hemorrhage and secondary subcapsular hematomas , retroperitoneal and peritoneal hemorrhage. This is the first reported case of both bilateral renal arterial malformations and bilateral spontaneous subcapsular and perirenal hemorrhage in the absence of neoplasia, coagulopathy, or trauma in a dog. Advanced imaging modalities, including selective angiography, were required to diagnose this condition successfully. Arterial malformations should be considered as a differential diagnosis in cases of hemoretroperitoneum. Nephrectomy due to perirenal hemorrhage should be cautiously considered, especially in the absence of angiography, because of the sequential bilateral nature of this case. Conservative management in this case resulted in a good long-term outcome 10 months later.


Fluctuations in the glutathione content of confluent cultured astrocytes and glioma cells.
Cultured astrocytes and glioma cells in a confluent state do not have a constant cellular concentration of glutathione. After exposure of the cells to fresh culture medium, the glutathione content of both cell types rose sharply and after a few days, fell back. For the glioma cells, the glutathione rise was higher and earlier and the fall was sharper than that of the astrocytes. Glutathione added to the culture medium had little effect on the cellular content of glutathione of astrocytes except at the highest concentrations (1 mM). Exogenous glutathione did increase the glutathione content of glioma cells and appeared to have a toxic effect at the highest concentrations. Both cell types maintained a low, constant concentration of reduced glutathione in the medium and consumed the added excess.


Lead Exposure Assessment among Pregnant Women, Newborns, and Children: Case Study from Karachi, Pakistan.
Lead (Pb) in petrol has been banned in developed countries. Despite the control of Pb in petrol since 2001, high levels were reported in the blood of pregnant women and children in Pakistan. However, the identification of sources of Pb has been elusive due to its pervasiveness. In this study, we assessed the lead intake of pregnant women and one- to three-year-old children from food, water, house dust, respirable dust, and soil. In addition, we completed the fingerprinting of the Pb isotopic ratios (LIR) of petrol and secondary sources (food, house-dust, respirable dust, soil, surma (eye cosmetics)) of exposure within the blood of pregnant women, newborns, and children. Eight families, with high (~50 μg/dL), medium (~20 μg/dL), and low blood levels (~10 μg/dL), were selected from 60 families. The main sources of exposure to lead for children were food and house-dust, and those for pregnant women were soil, respirable dust, and food. LIR was determined by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) with a two sigma uncertainty of ±0.03%. The LIR of mothers and newborns was similar. In contrast, surma, and to a larger extent petrol, exhibited a negligible contribution to both the child's and mother's blood Pb. Household wet-mopping could be effective in reducing Pb exposure. This intake assessment could be replicated for other developing countries to identify sources of lead and the burden of lead exposure in the population.


Patient-provider experiences with chronic non-communicable disease care during COVID-19 lockdowns in rural Uganda: A qualitative analysis.
Non-communicable diseases (NCDs) are a growing health burden in Sub-Saharan Africa and especially Uganda, where they account for over one third of all deaths. During the COVID-19 pandemic, public health control measures such as societal "lockdowns" had a significant impact on longitudinal NCD care though no studies have looked at the lived experience around NCD care during the pandemic. Our objective was to understand the experience of NCD care for both patients and providers in southwestern Uganda during the COVID-19 pandemic. We conducted in-depth, in-person qualitative interviews with 20 patients living with hypertension, diabetes, and/or cardiac disease purposefully selected from the outpatient clinics at Mbarara Regional Referral Hospital and 11 healthcare providers from public health facilities in Mbarara, southwestern Uganda. We analyzed transcripts according to conventional content analysis. We identified four major themes that emerged from the interviews; (1) difficulty accessing medication; (2) food insecurity; (3) barriers to the delivery of NCD clinical care and (4) alternative forms of care. Pre-existing challenges with NCD care were exacerbated during COVID-19 lockdown periods and care was severely disrupted, leading to worsened patient health and even death. The barriers to care were exacerbations of underlying systemic problems with NCD care delivery that require targeted interventions. Future work should leverage digital health interventions, de-centralizing NCD care, improving follow-up, providing social supports to NCD patients, and rectifying supply chain issues.