Effects of self-ligating brackets on oral hygiene and discomfort: a systematic review and meta-analysis of randomized controlled clinical trials.
Self-ligating brackets (SLBs) are widely adopted in clinic owing to their claimed superiorities. Here, we collected and analysed all randomized controlled clinical trials (RCTs) comparing SLBs with conventional brackets (CBs) and thereby investigated whether SLBs can relieve discomfort or promote oral hygiene. Electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese BioMedical Literature Database and the China National Knowledge Infrastructure were searched to find out RCTs comparing active or passive SLBs with CBs. Two reviewers extracted the data and assessed risks of bias independently. Any disagreement between them was resolved through discussion with a third reviewer. Meta-analysis was conducted on Review Manager 5.3. A total of 12 RCTs with 575 participants were included, and eight of the trials were synthesized quantitatively. Two trials were assessed as low risk of bias, whereas others as unclear risk of bias. Passive SLBs and CBs are not significantly different in plaque control. SLBs and CBs are not significantly different in discomfort reduction at any of four time points (4 h, 24 h, 3 days and 7 days). Clinical evidences from existing RCTs suggest that SLBs do not outperform CBs in reliving discomfort or promoting oral health in clinic.


[Child pleuropulmonary blastoma].
Pleuropulmonary blastoma is an extremely rare and aggressive thoracic tumour seen exclusively in children. The initial symptoms are respiratory and non specific and the chest X-ray done in that context reveals a thoracic mass. The chest CT scan then leads to the diagnosis of a cystic, mixt or solid mass. The diagnosis will be affirmed on anatomopathology of the tumour or biopsy. There are three different histological types: type I, cystic, type II, cystic and solid and type III, solid exclusively. Type I is less aggressive and its treatment is essentially surgical. Types II and III are highly aggressive and require surgery associated to polychemotherapy. In all cases, surgery is essential and should be the most complete possible. Extension and follow-up exams will include bone scan and brain imagery searching for metastasis as well as abdominal ultrasound searching associated renal lesions because 30% of pleuropulmonary blastoma are part of a familial predisposition syndrome.


Spontaneous Magnetic Ordering in the Fullerene Charge-Transfer Salt (TDAE)C60.
The zero-field muon spin relaxation technique has been used in the direct observation of spontaneous magnetic order below a Curie temperature (T(c)) of approximately 16.1 kelvin in the fullerene charge-transfer salt (tetrakisdimethylaminoethylene)C(60) [(TDAE)C(60)]. Coherent ordering of the electronic magnetic moments leads to a local field of 68(1) gauss at the muon site at 3.2 kelvin (parentheses indicate the error in the last digit). Substantial spatially inhomogeneous effects are manifested in the distribution of the local fields, whose width amounts to 48(2) gauss at the same temperature. The temperature evolution of the internal magnetic field below the freezing temperature mirrors that of the saturation magnetization, closely following the behavior expected for collective spin wave (magnon) excitations. The transition to a ferromagnetic state with a T(c) higher than that of any other organic material is now authenticated.


Actual versus perceived lifting ability in healthy young men (18-25 years).
Men under 25 years are at high risk of back injuries caused by manual handling. Self reports and functional capacity evaluations are commonly used to determine a worker's lifting capacity, however, amongst uninjured individuals, conflicting views exist regarding how perceived physical functioning matches actual functioning in the absence of fear of pain and/or re-injury. The aim of this study was to compare self-reports and actual lifting performance in a group of healthy young men aged 18-25 years. METHOD/PARTICIPANTS: A correlational prospective design compared perceived lifting capacity, using self-report and the Spinal Function Sort, and actual lifting capacity, using the EPIC Lift Capacity test in 31 subjects. Subjects' self-reported lifting capacity varied more widely than their actual scores, indicating that they were less accurate at predicting their lifting performance using the self-report measure. One third of subjects were able to accurately self-report their lifting performance, approximately one-third underestimated, and the remaining third overestimated their lifting ability. Only two significant relationships were identified between self-reported and actual lifting performance for frequent knuckle-shoulder and floor-shoulder lifts. These correlations were weak and well below the 0.75 level considered necessary to be clinically significant. This study found that self-report measures are not suitable when used in isolation. It is therefore recommended that self-report measures are used in conjunction with functional capacity evaluations to determine lifting capacity.


Immunohistochemical evaluation of type IV collagen and laminin-332 γ2 chain expression in well-differentiated oral squamous cell carcinoma and oral verrucous carcinoma: a new recommended cut-off.
Invasion and metastasis are two characteristics of malignant tumors, which perform by proteolytic destruction of the components of basement membrane (BM) and cell migration. The aim of this study was to evaluate the immunohistochemical (IHC) assessment of type IV collagen and laminin-332 γ2 (Ln-332 γ2) chain expression in well-differentiated oral squamous cell carcinoma (OSCC) and oral verrucous carcinoma (OVC), because these two lesions have same histopathologic findings whereas they have different biological behaviors. Destruction of BM and cell migration were evaluated by IHC in 15 cases of epithelial hyperplasia with no dysplasia (A group), 15 cases of OVC (B group) and 15 cases of well-differentiated OSCC (C group). There was a significant difference in type IV collagen immunohistochemical staining between three groups, but there were no significant differences between B and C groups. Expression of Ln-332 γ2 chain was not detected in A group. Ln-332 γ2 chain labeling index had significantly difference between B and C groups. The number of Ln-332 γ2 chain immunostaining positive cells was less than 5% in B group and over than 5% in C group which there were significantly differences between these two groups. Isolated immunohistochemical study of type IV collagen does not clearly define that a lesion is invasive or non-invasive and evaluation of Ln-332 γ2 chain expression (cut-off 5%) may be useful as a marker for description of biological differences and diagnosis of OVC from well-differentiated OSCC, especially in doubtful cases.


Efficacy of a genotype 2 Newcastle disease vaccine (Avinew) against challenge with highly virulent genotypes 5d and 3d.
Since 2002, following its introduction, the lineage 5d Newcastle disease virus (so-called Goose paramyxovirus - GPMV) strain has caused numerous disease outbreaks among commercial and backyard poultry in South Africa, raising questions about the ability of commercially available Newcastle disease vaccines to fully protect poultry against the strain. This study aimed to determine whether there are differences in the level of protection offered by Avinew Newcastle disease vaccine against GPMV virus as compared with a 3d Newcastle disease virus isolated in South Africa in 1993 (Rainbow challenge virus - RCV) strain. Six groups of 10-day-old, specific pathogen-free chickens were vaccinated with doses of 10(3.0), 10(4.5) and 10(6.0) EID50 of Avinew vaccine and challenged at 4 weeks of age intramuscularly at a dose of 10(5.3) EID50/0.2 ml/bird of GPMV and RCV. No statistically significant difference could be found in the protection offered by Avinew vaccine against GPMV as compared to RCV challenge. The protection offered against the ND challenge was found to be dose dependent. At the recommended field dose of 10(6.0) EID50 the vaccine gave 100% protection from mortality against both the challenge viruses, but not against infection and replication of the viruses, as gross lesions were evident even in apparently healthy birds that survived the challenge. The protective dose (PD90) of the Avinew vaccine against GPMV challenge was calculated at 10(4.38) and against that of RCV at 10(4.43).


Lack of deviation from Michaelis--Menten kinetics for pig heart fumarase.
Studies of steady-state kinetics of fumarase in the usual substrate-concentration range from 0.1 Km to 10 Km and in the high substrate-concentration range from 10 Km to 200 Km are described. The purpose is to investigate reports of substrate inhibition and oscillatory kinetics. In the normal substrate-concentration range, no deviations from hyperbolic kinetics were found, and in the extended concentration range, up to more than 200 times the Km value, no substrate inhibition was demonstrated. A discussion of the discrepancies between the mentioned reports of deviations from the hyperbolic kinetics and the present findings is given.


Phage-derived fully human monoclonal antibody fragments to human vascular endothelial growth factor-C block its interaction with VEGF receptor-2 and 3.
Vascular endothelial growth factor C (VEGF-C) is a key mediator of lymphangiogenesis, acting via its receptors VEGF-R2 and VEGF-R3. High expression of VEGF-C in tumors correlates with increased lymphatic vessel density, lymphatic vessel invasion, sentinel lymph node metastasis and poor prognosis. Recently, we found that in a chemically induced skin carcinoma model, increased VEGF-C drainage from the tumor enhanced lymphangiogenesis in the sentinel lymph node and facilitated metastatic spread of cancer cells via the lymphatics. Hence, interference with the VEGF-C/VEGF-R3 axis holds promise to block metastatic spread, as recently shown by use of a neutralizing anti-VEGF-R3 antibody and a soluble VEGF-R3 (VEGF-C/D trap). By antibody phage-display, we have developed a human monoclonal antibody fragment (single-chain Fragment variable, scFv) that binds with high specificity and affinity to the fully processed mature form of human VEGF-C. The scFv binds to an epitope on VEGF-C that is important for receptor binding, since binding of the scFv to VEGF-C dose-dependently inhibits the binding of VEGF-C to VEGF-R2 and VEGF-R3 as shown by BIAcore and ELISA analyses. Interestingly, the variable heavy domain (V(H)) of the anti-VEGF-C scFv, which contains a mutation typical for camelid heavy chain-only antibodies, is sufficient for binding VEGF-C. This reduced the size of the potentially VEGF-C-blocking antibody fragment to only 14.6 kDa. Anti-VEGF-C V(H)-based immunoproteins hold promise to block the lymphangiogenic activity of VEGF-C, which would present a significant advance in inhibiting lymphatic-based metastatic spread of certain cancer types.


Comparison of direct and concentrated acid-fast smears to identify specimens culture positive for Mycobacterium spp.
Microscopic examination of respiratory specimens for acid-fast bacilli (AFB) plays a key role in the initial diagnosis of tuberculosis, monitoring of treatment, and determination of eligibility for release from isolation. The objective of this study was to compare the sensitivity obtained with smears for detection of AFB (AFB smears) made directly from respiratory specimens (direct AFB smears) to that obtained with parallel smears made from concentrates of the specimens (concentrated AFB smears). A total of 2,693 specimens were evaluated; 1,806 were from the University of California Irvine Medical Center Medical Microbiology Laboratory (UCIMC), which serves a tertiary-care hospital with outpatient clinics, and 887 were from the Microbial Disease Laboratory at the California Department of Public Health (MDL), which receives specimens from outpatient facilities and clinics on Pacific islands. Of the 353 AFB culture-positive specimens at UCIMC, there was a statistically significant difference in the sensitivity of the direct AFB smear (34%) and that of the smear made from the concentrated specimen (58%) (P < 0.05). This was also true for the 208 specimens positive for Mycobacterium tuberculosis, for which the sensitivity of the direct smear was 42% (87 of 208) and that for the smear made from the concentrated specimen was 74% (154 of 208). At MDL, where all but 1 of the 45 culture-positive specimens grew M. tuberculosis, the sensitivity of the smear made from the concentrated specimen was 93% (42 of 45) and was not significantly higher than the sensitivity of the direct smear, which was 82% (37 of 45). By combining the results from both laboratories, 42 patients from whom at least three specimens were received were culture positive for M. tuberculosis. The cumulative results for the initial three specimens from these patients showed that the direct smear detected M. tuberculosis in 81% of these patients, whereas the smear made from the concentrate detected M. tuberculosis in 91% of these patients. In summary, when all culture-positive specimens are considered, the sensitivity of the direct smear compared to that of a smear made from the concentrated specimen was significantly different overall in the two different laboratory settings. However, this difference was reduced only if the cumulative results for the initial three specimens received from patients who were culture positive for M. tuberculosis were evaluated.


[The effect of a juvenile hormone mimetic on the ovarian function of allatectomized females of Labidura riparia (Insecta, Dermaptera].
The methyl-3, 7, 11-trimethyl-11-chlorine-2-dodecanoate, a Juvenile Hormone analogue, used at different doses on allatectomised females of Labidura riparia, starts a vitellogenesis, a rapid disappearance of follicular degenerations and in some cases an intensive eggs laying. However, neither the normal reproductive cycle nor the parental comportment have been reconstituted.


High-resolution cryo-EM structure of the F-actin-fimbrin/plastin ABD2 complex.
Many actin binding proteins have a modular architecture, and calponin-homology (CH) domains are one such structurally conserved module found in numerous proteins that interact with F-actin. The manner in which CH-domains bind F-actin has been controversial. Using cryo-EM and a single-particle approach to helical reconstruction, we have generated 12-A-resolution maps of F-actin alone and F-actin decorated with a fragment of human fimbrin (L-plastin) containing tandem CH-domains. The high resolution allows an unambiguous fit of the crystal structure of fimbrin into the map. The interaction between fimbrin ABD2 (actin binding domain 2) and F-actin is different from any interaction previously observed or proposed for tandem CH-domain proteins, showing that the structural conservation of the CH-domains does not lead to a conserved mode of interaction with F-actin. Both the stapling of adjacent actin protomers and the additional closure of the nucleotide binding cleft in F-actin when the fimbrin fragment binds may explain how fimbrin can stabilize actin filaments. A mechanism is proposed where ABD1 of fimbrin becomes activated for binding a second actin filament after ABD2 is bound to a first filament, and this can explain how mutations of residues buried in the interface between ABD2 and ABD1 can rescue temperature-sensitive defects in actin.


POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages.
Extracellular nucleotides can modulate the immunological response by activating purinergic receptors (P2Rs) on the cell surface of macrophages, dendritic, and other immune cells. In particular, the activation of P2X7R can induce release of cytokines and cell death as well as the uptake of large molecules through the cell membrane by a mechanism still poorly understood. Polyoxotungstate-1 (POM-1) has been proposed as a potent inhibitor of ecto-nucleotidases, enzymes that hydrolyze extracellular nucleotides, regulating the activity of P2Rs. However, the potential impact of POM-1 on P2Rs has not been evaluated. Here, we used fluorescent dye uptake, cytoplasmic free Ca2+ concentration measurement, patch-clamp recordings, scanning electron microscopy, and quantification of inflammatory mediators to investigate the effects of POM-1 on P2Rs of murine macrophages. We observed that POM-1 blocks the P2YR-dependent cytoplasmic Ca2+ increase and has partial effects on the cytoplasmic Ca2+, increasing dependence on P2XRs. POM-1 can inhibit the events related with ATP-dependent inflammasome activation, anionic dye uptake, and also the opening of large conductance channels, which are associated with P2X7R-dependent pannexin-1 activation. On the other hand, this compound has no effects on cationic fluorescent dye uptake, apoptosis, and bleb formation, also dependent on P2X7R. Moreover, POM-1 can be considered an anti-inflammatory compound, because it prevents TNF-α and nitric oxide release from LPS-treated macrophages.


Patients' expectations and satisfaction of complete denture therapy and correlation with locus of control.
Considering the importance of patients' satisfaction with complete denture therapy and the influence of psychosocial aspects and expectations regarding satisfaction with their dentures, the present study aimed to test for a correlation between locus of control profiles and expectations before and satisfaction after complete denture therapy. Sixty-four patients rated their expectations for aesthetic and functional results of complete denture therapy on a 10-cm visual analogue scale (VAS), using scores from 0 (worst results) to 10 (best results). A similar questionnaire was used regarding satisfaction after final denture adjustments. Patients also answered a locus of control questionnaire in the initial interview. ANOVA and a chi-squared test were used to test for correlations among ratings, patient gender and locus of control profiles. The significance level adopted was 0.05. The expectation ratings before treatment were significantly lower than the post-treatment completion ratings, both for aesthetics (P < 0.001) and function (P = 0.004). There was no correlation between locus of control profiles and patients' ratings or between gender and VAS scores. No correlation was found between locus of control profiles and scores for expectations before and satisfaction after complete dentures.


Sjögren's syndrome with myalgia is associated with subnormal secretion of cytokines by peripheral blood mononuclear cells.
To measure in vitro cytokine release from peripheral blood mononuclear cells (PBMC) and serum cytokines in patients with primary Sjögren's syndrome (SS) with and without myalgia, compared to patients with rheumatoid arthritis (RA) and healthy controls. Sixteen women with SS (8 with myalgia, 8 without pain), 15 women with RA, and 14 healthy women were studied. PBMC were isolated and cultured. Secretion of interleukin 1 beta (IL-1 beta), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-alpha) was measured in cell supernatants with or without stimulation with phytohemagglutinin, tetanus toxoid, or purified protein derivative (PPD). Enzyme-linked immunospot was used to enumerate interferon-gamma (IFN-gamma) and IL-4-secreting cells. Serum concentrations of IL-8 and IL-18 were analyzed by ELISA. PPD-stimulated PBMC from SS patients responded with less production of IL-10, TNF-alpha, and IFN-gamma compared to controls. Patients with SS and pain were hyporesponsive also with respect to IL-1 beta and IL-6. The generally subnormal cytokine release was statistically significant in myalgic patients with SS compared to healthy controls. Serum IL-18 was increased in both SS groups as well as in patients with RA, and the highest levels were found in myalgic patients with SS. Serum IL-8 was increased in RA but not in SS. Patients with SS, especially those with myalgia, had diminished PBMC cytokine release and increased serum IL-18. This finding suggests that impaired cytokine regulation may have pathogenetic importance for myalgia in SS.


Total parenteral nutrition in anuric children.
Six children who were anuric, intolerant of oral nutrition and depleted of body protein, were treated with total parenteral nutrition. Nitrogen utilization was studied during infusion of dextrose alone and dextrose with essential amino acids. An increase in non-protein (glucose) calories from 20 to 70 kcal/kg/day progressively reduced body protein catabolism; nitrogen balance became less negative. When essential amino nitrogen was added, net urea production decreased; protein nitrogen balance became positive. It is concluded that total parenteral nutrition with essential amino acids improves the nutritional status of severely ill, anuric children, and may influence recovery.


The C-terminal region of alpha' subunit of soybean beta-conglycinin contains two types of vacuolar sorting determinants.
In maturing seed cells, proteins that accumulate in the protein storage vacuoles (PSVs) are synthesized on the endoplasmic reticulum (ER) and transported by vesicles to the PSVs. Vacuolar sorting determinants (VSDs) which are usually amino acid sequences of short or moderate length direct the proteins to this pathway. VSDs identified so far are classified into two types: sequence specific VSDs (ssVSDs) and C-terminal VSDs (ctVSDs). We previously demonstrated that VSDs of alpha' and beta subunits of beta-conglycinin, one of major storage proteins of soybean (Glycine max), reside in the C-terminal ten amino acids. Here we show that both types of VSDs coexist within this region of the alpha' subunit. Although ctVSDs can function only at the very C-termini of proteins, the C-terminal ten amino acids of alpha' subunit directed green fluorescent protein (GFP) to the PSVs even when they were placed at the N-terminus of GFP, indicating that an ssVSD resides in the sequence. By mutation analysis, it was found that the core sequence of the ssVSD is Ser-Ile-Leu (fifth to seventh residues counted from the C-terminus) which is conserved in the alpha and beta subunits and some vicilin-like proteins. On the other hand, the sequence composed of the C-terminal three amino acids (AFY) directed GFP to the PSVs when it was placed at the C-terminus of GFP, though the function as a VSD was disrupted at the N-terminus of GFP, indicating that the AFY sequence is a ctVSD.


Genetic predictors of survival in behavioral variant frontotemporal degeneration.
To determine autosomal dominant genetic predictors of survival in individuals with behavioral variant frontotemporal degeneration (bvFTD). A retrospective chart review of 174 cases with a clinical phenotype of bvFTD but no associated elementary neurologic features was performed, with diagnosis either autopsy-confirmed (n = 57) or supported by CSF evidence of non-Alzheimer pathology (n = 117). Genetic analysis of the 3 most common genes with pathogenic autosomal dominant mutations associated with frontotemporal degeneration was performed in all patients, which identified cases with C9orf72 expansion (n = 28), progranulin (GRN) mutation (n = 12), and microtubule-associated protein tau (MAPT) mutation (n = 10). Cox proportional hazards regressions were used to test for associations between survival and mutation status, sex, age at symptom onset, and education. Across all patients with bvFTD, the presence of a disease-associated pathogenic mutation was associated with shortened survival (hazard ratio [HR] 2.164, 95% confidence interval [CI] 1.391, 3.368). In separate models, a GRN mutation (HR 2.423, 95% CI 1.237, 4.744), MAPT mutation (HR 8.056, 95% CI 2.938, 22.092), and C9orf72 expansion (HR 1.832, 95% CI 1.034, 3.244) were each individually associated with shorter survival relative to sporadic bvFTD. A mutation on the MAPT gene results in an earlier age at onset than a C9orf72 expansion or mutation on the GRN gene (p = 0.016). Our findings suggest that autosomal dominantly inherited mutations, modulated by age at symptom onset, associate with shorter survival among patients with bvFTD. We suggest that clinical trials and clinical management should consider mutation status and age at onset when evaluating disease progression.


Temporal trends in U. S. multiple cause of death mortality data: 1968 to 1977.
An analysis is made of the mortality trends over the period 1968 to 1977 indicated by two types of cause-specific mortality data. The first type of data is "underlying cause" of death data--the data heretofore used in national vital statistics reports on cause-specific mortality. The second type of data is "multiple cause" data which contain a listing of all medical conditions recorded on the death certificate. A comparison of trends in the two types of data yields useful insights on mortality declines over the study period for two reasons. First, these declines were largely due to a reduction in the mortality rates of circulatory diseases. Second, the multiple cause data contain considerably more information than the underlying cause data on the role of circulatory diseases, and many other chronic diseases, in causing death. This additional information is especially useful in examining mortality patterns among the elderly, where the prevalence at death of chronic degenerative diseases is high.


Socio-economic status and lifestyle factors are associated with achalasia risk: A population-based case-control study.
To evaluate the association between various lifestyle factors and achalasia risk. A population-based case-control study was conducted in Northern Ireland, including n = 151 achalasia cases and n = 117 age- and sex-matched controls. Lifestyle factors were assessed via a face-to-face structured interview. The association between achalasia and lifestyle factors was assessed by unconditional logistic regression, to produce odds ratios (OR) and 95% confidence interval (CI). Individuals who had low-class occupations were at the highest risk of achalasia (OR = 1.88, 95%CI: 1.02-3.45), inferring that high-class occupation holders have a reduced risk of achalasia. A history of foreign travel, a lifestyle factor linked to upper socio-economic class, was also associated with a reduced risk of achalasia (OR = 0.59, 95%CI: 0.35-0.99). Smoking and alcohol consumption carried significantly reduced risks of achalasia, even after adjustment for socio-economic status. The presence of pets in the house was associated with a two-fold increased risk of achalasia (OR = 2.00, 95%CI: 1.17-3.42). No childhood household factors were associated with achalasia risk. Achalasia is a disease of inequality, and individuals from low socio-economic backgrounds are at highest risk. This does not appear to be due to corresponding alcohol and smoking behaviours. An observed positive association between pet ownership and achalasia risk suggests an interaction between endotoxin and viral infection exposure in achalasia aetiology.


Efficacy of Three Low-Intensity, Internet-Based Psychological Interventions for the Treatment of Depression in Primary Care: Randomized Controlled Trial.
Primary care is a major access point for the initial treatment of depression, but the management of these patients is far from optimal. The lack of time in primary care is one of the major difficulties for the delivery of evidence-based psychotherapy. During the last decade, research has focused on the development of brief psychotherapy and cost-effective internet-based interventions mostly based on cognitive behavioral therapy (CBT). Very little research has focused on alternative methods of treatment for depression using CBT. Thus, there is a need for research into other therapeutic approaches. This study aimed to assess the effectiveness of 3 low-intensity, internet-based psychological interventions (healthy lifestyle psychoeducational program [HLP], focused program on positive affect promotion [PAPP], and brief intervention based on mindfulness [MP]) compared with a control condition (improved treatment as usual [iTAU]). A multicenter, 4-arm, parallel randomized controlled trial was conducted between March 2015 and March 2016, with a follow-up of 12 months. In total, 221 adults with mild or moderate major depression were recruited in primary care settings from 3 Spanish regions. Patients were randomly distributed to iTAU (n=57), HLP (n=54), PAPP (n=56), and MP (n=54). All patients received iTAU from their general practitioners. The main outcome was the Spanish version of the Patient Health Questionnaire-9 (PHQ-9) from pretreatment (time 1) to posttreatment (time 2) and up to 6 (time 3) and 12 (time 4) months' follow-up. Secondary outcomes included the visual analog scale of the EuroQol, the Short-Form Health Survey (SF-12), the Positive and Negative Affect Schedule (PANAS), and the Pemberton Happiness Index (PHI). We conducted regression models to estimate outcome differences along study stages. A moderate decrease was detected in PHQ-9 scores from HLP (β=-3.05; P=.01) and MP (β=-3.00; P=.01) compared with iTAU at posttreatment. There were significant differences between all intervention groups and iTAU in physical SF-12 scores at 6 months after treatment. Regarding well-being, MP and PAPP reported better PHI results than iTAU at 6 months post treatment. PAPP intervention significantly decreased PANAS negative affect scores compared with iTAU 12 months after treatment. The low-intensity, internet-based psychological interventions (HLP and MP) for the treatment of depression in primary care are more effective than iTAU at posttreatment. Moreover, all low-intensity psychological interventions are also effective in improving medium- and long-term quality of life. PAPP is effective for improving health-related quality of life, negative affect, and well-being in patients with depression. Nevertheless, it is important to examine possible reasons that could be implicated for PAPP not being effective in reducing depressive symptomatology; in addition, more research is still needed to assess the cost-effectiveness analysis of these interventions. ISRCTN Registry ISRCTN82388279; http://www.isrctn.com/ISRCTN82388279. RR2-10.1186/s12888-015-0475-0.


Elastosis perforans serpiginosa in a patient with renal disease.
We encountered a case of elastosis perforans serpiginosa in a patient with coexisting renal disease, the first such reported association of which we are aware. The perforating disorders tend to have atypical clinical features when associated with renal disease. The exact pathogenic mechanism by which renal disease predisposes to a perforating disease remains to be elucidated but is likely to be related to minor trauma, which occurs in renal disease.


Acoustic source localization in an anisotropic plate without knowing its material properties - A new approach.
Acoustic source localization (ASL) in a highly anisotropic plate is a challenging task. The basic assumption in many of the currently available techniques is that the wave propagates along a straight line from the source to the receiving sensor. However, waves in anisotropic solids propagate along curved lines and form non-circular wave fronts. As a result, for a highly anisotropic solid the acoustic source localization techniques that assume straight line propagation of waves from the source to the receiver are bound to produce a significant error. In this paper a new technique is introduced for acoustic source localization in an anisotropic plate by dealing with non-circular shape of wave fronts. Direction vectors of the wave fronts are computed from the Time-Difference-Of-Arrivals (TDOA) at three sensors placed in a cluster, then they are cast into a geometric vector analysis or an optimization process to accurately obtain the acoustic source location. Two common wave front shapes in highly anisotropic plates, rhombus and ellipse, are analyzed. Following this analysis, the acoustic source could be successfully localized without knowing the material properties of the plate.


Stereology: methods for quantitative light and electron microscopy.
There are available to the biologist sophisticated methods for the quantitative determination of many structural parameters of tissues; the methds are covered by the term stereology and are based on statistical sampling techniques introduced by geologists and materials scientists. Methods for determining the volume fractions of various compartments within a cell or tissue are presented, together with methods for determination of surface area, surface-to-volume ratio, and particle size and size distribution. The problems involved in applying these methods to tissue sections are discussed, together with the problems arising from anisotropy within the tissues. Sampling methods and test systems in common use are described and discussed in relation to available counting and recording systems, and the potentialities of automatic image analysing equipment in this field are assessed. A discussion of shape recognition follows, with a survey of recent stereological work.


Genome-Wide Analysis of Cation/Proton Antiporter Family in Soybean (Glycine max) and Functional Analysis of GmCHX20a on Salt Response.
Monovalent cation proton antiporters (CPAs) play crucial roles in ion and pH homeostasis, which is essential for plant development and environmental adaptation, including salt tolerance. Here, 68 CPA genes were identified in soybean, phylogenetically dividing into 11 Na+/H+ exchangers (NHXs), 12 K+ efflux antiporters (KEAs), and 45 cation/H+ exchangers (CHXs). The GmCPA genes are unevenly distributed across the 20 chromosomes and might expand largely due to segmental duplication in soybean. The GmCPA family underwent purifying selection rather than neutral or positive selections. The cis-element analysis and the publicly available transcriptome data indicated that GmCPAs are involved in development and various environmental adaptations, especially for salt tolerance. Based on the RNA-seq data, twelve of the chosen GmCPA genes were confirmed for their differentially expression under salt or osmotic stresses using qRT-PCR. Among them, GmCHX20a was selected due to its high induction under salt stress for the exploration of its biological function on salt responses by ectopic expressing in Arabidopsis. The results suggest that the overexpression of GmCHX20a increases the sensitivity to salt stress by altering the redox system. Overall, this study provides comprehensive insights into the CPA family in soybean and has the potential to supply new candidate genes to develop salt-tolerant soybean varieties.


Random number generation in neglect patients reveals enhanced response stereotypy, but no neglect in number space.
Based on interactions between number and space apparent from healthy subjects' randomization attempts we expected random number generation (RNG) to be sensitive for the monitoring of unilateral spatial deficits. Specifically, we predicted patients with left-sided hemineglect to evidence "neglect in number space", i.e. to produce a deficiency in the generation of small, "left-sided" numbers. In RNG of digits from 1 to 6, 19 patients with left-sided neglect generated sequences with a higher redundancy, but as many small numbers as did a matched control group. We discuss possible reasons for the absence of a small-number neglect and emphasize that the observed redundancy was not due to a counting bias, as known from other neurological patients, but to an unspecific imbalance in the use of response alternatives. We speculate that this may be the consequence of disrupted fronto-parietal functions normally serving in the sequential organization and manipulation of items in working memory.


Mice learn to avoid regret.
Regret can be defined as the subjective experience of recognizing that one has made a mistake and that a better alternative could have been selected. The experience of regret is thought to carry negative utility. This typically takes two distinct forms: augmenting immediate postregret valuations to make up for losses, and augmenting long-term changes in decision-making strategies to avoid future instances of regret altogether. While the short-term changes in valuation have been studied in human psychology, economics, neuroscience, and even recently in nonhuman-primate and rodent neurophysiology, the latter long-term process has received far less attention, with no reports of regret avoidance in nonhuman decision-making paradigms. We trained 31 mice in a novel variant of the Restaurant Row economic decision-making task, in which mice make decisions of whether to spend time from a limited budget to achieve food rewards of varying costs (delays). Importantly, we tested mice longitudinally for 70 consecutive days, during which the task provided their only source of food. Thus, decision strategies were interdependent across both trials and days. We separated principal commitment decisions from secondary reevaluation decisions across space and time and found evidence for regret-like behaviors following change-of-mind decisions that corrected prior economically disadvantageous choices. Immediately following change-of-mind events, subsequent decisions appeared to make up for lost effort by altering willingness to wait, decision speed, and pellet consumption speed, consistent with past reports of regret in rodents. As mice were exposed to an increasingly reward-scarce environment, we found they adapted and refined distinct economic decision-making strategies over the course of weeks to maximize reinforcement rate. However, we also found that even without changes in reinforcement rate, mice transitioned from an early strategy rooted in foraging to a strategy rooted in deliberation and planning that prevented future regret-inducing change-of-mind episodes from occurring. These data suggest that mice are learning to avoid future regret, independent of and separate from reinforcement rate maximization.


Parameter estimation of in silico biological pathways with particle filtering towards a petascale computing.
The aim of this paper is to demonstrate the potential power of large-scale particle filtering for the parameter estimations of in silico biological pathways where time course measurements of biochemical reactions are observable. The method of particle filtering has been a popular technique in the field of statistical science, which approximates posterior distributions of model parameters of dynamic system by using sequentially-generated Monte Carlo samples. In order to apply the particle filtering to system identifications of biological pathways, it is often needed to explore the posterior distributions which are defined over an exceedingly high-dimensional parameter space. It is then essential to use a fairly large amount of Monte Carlo samples to obtain an approximation with a high-degree of accuracy. In this paper, we address some implementation issues on large-scale particle filtering, and then, indicate the importance of large-scale computing for parameter learning of in silico biological pathways. We have tested the ability of the particle filtering with 10(8) Monte Carlo samples on the transcription circuit of circadian clock that contains 45 unknown kinetic parameters. The proposed approach could reveal clearly the shape of the posterior distributions over the 45 dimensional parameter space.


Associations between Depression and Self-Reported COVID-19 Symptoms among Adults: Results from Two Population-Based Seroprevalence Studies in Switzerland.
(1) Mental health may modulate the perceived risk of SARS-CoV-2 infection. However, it is unclear how psychological symptoms may distort symptom perception of COVID-19 and SARS-CoV-2 infection. We assessed whether depressive symptoms predicted self-reported COVID-19 symptoms, independently of serologically confirmed SARS-CoV-2 infection. (2) Participants (aged 20-64) in the Geneva (N = 576) and Ticino (N = 581) Swiss regions completed the Patient Health Questionnaire before being tested for anti-SARS-CoV-2 IgG antibodies and recalled COVID-19-compatible symptoms on two occasions: April-July 2020 (baseline), and January-February 2021 (follow-up). We estimated prevalence ratios for COVID-19 symptoms by depression scores in interaction with serological status. (3) At baseline, in Geneva, higher depression predicted higher probability of reporting systemic, upper airways, and gastro-intestinal symptoms, and fever and/or cough; in Ticino, higher depression predicted systemic, upper airways, and gastro-intestinal symptoms, fever and/or cough, dyspnea, and headache. At follow-up, in Geneva, higher depression predicted higher probability of reporting systemic symptoms and dyspnea; in Ticino, higher depression predicted higher probability of reporting systemic and upper airways symptoms, dyspnea and headache (all p values < 0.05). (4) We found positive associations between depressive symptoms and COVID-19-compatible symptoms, independently of seropositivity. Mental wellbeing has relevant public health implications because it modulates self-reported infection symptoms that inform testing, self-medication, and containment measures, including quarantine and isolation.


Association of Technetium(99m) MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies.
Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies. Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium(99m) MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy. Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V(25)) and 40 Gy (V(40)) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively). Decline in split renal function using Technetium(99m) MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.


Mass spectrometry analysis of proteome-wide proteolytic post-translational degradation of proteins.
Protein proteolytic degradation is an essential component to proper cell function and its life cycle. Here, we study the protein degradation in yeast Saccharomyces cerevisiae cells on a proteome-wide scale by detection of the intermediate peptides produced from the intracellular degradation of proteins using sequencing-based tandem mass spectrometry. By tracing the detected approximately 1100 peptides and their approximately 200 protein-substrate origins we obtain evidence for new insights into the proteome-wide protein-selective degradation in yeast cells. This evidence shows that the yeast cytoplasm is the largest pool for the degradation of proteins with both biochemical and geometric specificities, whereas the yeast nucleus seems to be a proteolysis-inert organelle under the condition studied. Yeast V-ATPase subunits appear to be degraded during their disassembly, and yeast mitochondrial proteins functioning as precursors, transport carriers, and gates are preferentially degraded. Ubiquitylation may be unnecessary for the proteasomal degradation of yeast cytoplasmic regulatory and enzyme proteins according to our observations. This study shows that the intracellular peptides are informational targets for directly probing the protein degradation-involved molecular mechanisms and cell biology processes.


Increased fatty acid synthase is a therapeutic target in mesothelioma.
Many common human cancer tissues express high levels of fatty acid synthase (FAS), the primary enzyme for the synthesis of fatty acids, and the differential expression of FAS between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS for the treatment of pleural mesothelioma, we first determined whether FAS is overexpressed in human mesothelioma. By immunohistochemistry, we found 22 of 30 human mesothelioma tissue samples tested to express significantly increased levels of FAS compared with normal tissues, including mesothelium. To further explore FAS as a therapeutic target in mesothelioma, we established a nude mouse xenograft model for human mesothelioma using the H-Meso cell line. The i.p. xenografts of this cell line have high levels of FAS expression and fatty acid synthesis pathway activity and grow along mesothelial surfaces in a manner similar to the growth pattern of human mesothelioma. Growth of these tumor xenografts was essentially abolished in mice treated with weekly i.p. injections of C75, a synthetic, small molecule inhibitor of FAS, at levels that resulted in no significant systemic toxicity except for reversible weight loss. These results suggest that FAS may be an effective target for pharmacological therapy in a high proportion of human mesotheliomas.


Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women's health across the nation 1999-2018.
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.


Socially disadvantaged city districts show a higher incidence of acute ST-elevation myocardial infarctions with elevated cardiovascular risk factors and worse prognosis.
The importance of socioeconomic status (SES) for coronary heart disease (CHD)-morbidity is subject of ongoing scientific investigations. This study was to explore the association between SES in different city-districts of Bremen/Germany and incidence, severity, treatment modalities and prognosis for patients with ST-elevation myocardial infarctions (STEMI). Since 2006 all STEMI-patients from the metropolitan area of Bremen are documented in the Bremen STEMI-registry. Utilizing postal codes of their home address they were assigned to four groups in accordance to the Bremen social deprivation-index (G1: high, G2: intermediate high, G3: intermediate low, G4: low socioeconomic status). Three thousand four hundred sixty-two consecutive patients with STEMI admitted between 2006 and 2015 entered analysis. City areas with low SES showed higher adjusted STEMI-incidence-rates (IR-ratio 1.56, G4 vs. G1). This elevation could be observed in both sexes (women IRR 1.63, men IRR 1.54) and was most prominent in inhabitants <50 yrs. of age (women IRR 2.18, men IRR 2.17). Smoking (OR 1.7, 95%CI 1.3-2.4) and obesity (1.6, 95%CI 1.1-2.2) was more prevalent in pts. from low SES city-areas. While treatment-modalities did not differ, low SES was associated with more extensive STEMIs (creatine kinase > 3000 U/l, OR 1.95, 95% CI 1.4-2.8) and severe impairment of LV-function post-STEMI (OR 2.0, 95% CI 1.2-3.4). Long term follow-up revealed that lower SES was associated with higher major adverse cardiac or cerebrovascular event (MACCE)-rates after 5 years: G1 30.8%, G2 35.7%, G3 36.0%, G4 41.1%, p (for trend) = 0.02. This worse prognosis could especially be shown for young STEMI-patients (<50 yrs. of age) 5-yr. mortality-rates(G4 vs. G1) 18.4 vs. 3.1%, p = 0.03 and 5-year-MACCE-rates (G4 vs. G1) 32 vs. 6.3%, p = 0.02. This registry-data confirms the negative association of low socioeconomic status and STEMI-incidence, with higher rates of smoking and obesity, more extensive infarctions and worse prognosis for the socio-economically deprived.


Parent-child relationships of boys in different offending trajectories: a developmental perspective.
This study tested the theoretical assumption that transformations of parent-child relationships in late childhood and adolescence would differ for boys following different offending trajectories. Using longitudinal multiinformant data of 503 boys (ages 7-19), we conducted Growth Mixture Modeling to extract offending trajectories. Developmental changes in child reports of parent-child joint activities and relationship quality were examined using Latent Growth Curves. Five offending trajectories were found: non-offenders, moderate childhood offenders, adolescent-limited offenders, serious childhood offenders, and serious persistent offenders. Non-offenders reported high and stable levels of relationship quality between age 10 and 16. Adolescent-limited offenders reported a similarly high relationship quality as non-offenders at ages 7 and 10, but a lower and decreasing relationship quality in adolescence. Compared with non-offenders, serious persistent offenders reported poorer parent-child relationship quality at all ages, and a decreasing relationship quality in adolescence. Serious persistent offenders and adolescent-limited offenders reported similar levels and changes in parent-child relationship quality in adolescence. Although serious persistent offenders reported fewer joint activities at age 10 and 13 than non-offenders, a similar linear decrease in joint activities in early to middle adolescence was found for boys in each trajectory. Developmental changes in parent-child relationship quality differ for different types of offenders. This finding has scientific and practical implications.


Arthroscopic tennis elbow release.
Lateral epicondylitis, originally referred to as "tennis elbow," affects between 1% and 3% of the population and is usually noted in patients aged between 35 and 50 years old. Although it was first thought lateral epicondylitis was caused by an inflammatory process, most microscopic studies of excised tissue demonstrate a failure of reparative response in the extensor carpi radialis brevis tendon in any of these associated structures. Most cases of lateral epicondylitis respond to appropriate nonoperative treatment protocols. Nonoperative management includes medication, bracing, physical therapy, corticosteroid injections, shock wave therapy, platelet-rich plasma, and low-dose thermal ablation devices. When these are unsuccessful, however, surgical measures may be performed with a high rate of success. Satisfactory results of the arthroscopic surgical procedures have been documented, with reported improvement rates of 91% to 97.7%. The recent advances in arthroscopic repair and plication of these lesions, along with the recognition of the presence and repair of coexisting lesions, have allowed arthroscopic techniques to provide results superior to other measures.


Associations of physical activity with quality of life and functional ability in breast cancer patients during active adjuvant treatment: the Pathways Study.
Physical activity can improve quality of life (QOL) in breast cancer survivors but little is known about associations of physical activity and QOL during active cancer therapy. We examine associations between activity levels and QOL in a large cohort of breast cancer patients. Women with invasive, non-metastatic breast cancer (n=2,279) were enrolled between 2006 and 2009 from a managed care organization; assessment were done during active therapy. A physical activity frequency questionnaire was used to calculate the average weekly metabolic equivalent task (MET) hours spent in moderate and vigorous activity during active treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Breast Cancer. Linear regression models tested cross-sectional associations of QOL and functional well-being with physical activity and covariates [socio-demographics, comorbidity, body mass index (BMI), clinical variables, social support, and assessment timing]. Physical activity had a significant positive unadjusted association with all QOL sub-scales (except emotional well-being) (all P values < 0.01). Overall QOL was 4.6 points higher for women in the highest quartile of moderate and vigorous activity versus women in the lowest quartile (P<0.001). In regression models, higher activity was associated with better overall QOL and functional well-being, controlling for covariates (P<0.05). Increasing BMI was also independently but inversely associated with overall QOL (P<0.001) but did not explain the relationship of activity and QOL. White women reported the higher levels of activity than minority women and activity was associated with QOL for Whites but not for minority women. Greater physical activity is associated with small but clinically meaningful increases in QOL during active breast cancer care therapy for Whites but this effect is not seen for minority women. If confirmed in longitudinal analyses, these differences may have implications for disparities research.


[The wave-like character of the defence conditioned reflex acquisition in rats].
The dynamic peculiarities of formation of conditioned avoidance in rats were studied during 15-day sessions using different experimental paradigms (massed and spaced training). In all the experimental situations, the acquisition curves were wave-like (independently of the paradigm). Regression curves of the 6th or 7th order most perfectly fit the experimental data, which suggests that the acquisition dynamics in both paradigms is non-linear.


Recent developments of the PET imaging agents for metabotropic glutamate receptor subtype 5.
Glutamate is a major excitatory neurotransmitter in central nervous system (CNS) acting through ionotropic and G-protein coupled metabotropic glutamate receptors. Metabotropic glutamate receptor 5 (mGluR5), a subtype in the group I mGluRs, presents in high density in many brain regions (hippocampus, cortex and olfactory system). Stimulation of mGluR5 leads to the release of calcium from intracellular supplies and protein kinase C activation. Excessive activation of mGluR5 has been associated with psychiatric, neurological and neurodegenerative diseases, including Parkinson's disease, anxiety, depression, schizophrenia, pain, epilepsy, focal and global ischemia diseases. 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 2-methyl-4-(pyridin-3-ylethynyl)thiazole (MTEP) are the first generation of non-competitive mGluR5 antagonists with potent, selective and systemically active properties. They have therapeutic functions in varied diseases. Investigation of mGluR5 physiological functions under pathologic conditions in patients will be critically important in mGluR5 antagonist's therapy using noninvasive positron emission tomography (PET) imaging technique. There are eleven mGluR5 imaging PET tracers have been tested in animal studies. This article highlights efforts on the design and development of novel PET tracers for mGluR5 in vivo imaging.


Temperature dependence of charge separation and recombination in porphyrin oligomer-fullerene donor-acceptor systems.
Electron-transfer reactions are fundamental to many practical devices, but because of their complexity, it is often very difficult to interpret measurements done on the complete device. Therefore, studies of model systems are crucial. Here the rates of charge separation and recombination in donor-acceptor systems consisting of a series of butadiyne-linked porphyrin oligomers (n = 1-4, 6) appended to C(60) were investigated. At room temperature, excitation of the porphyrin oligomer led to fast (5-25 ps) electron transfer to C(60) followed by slower (200-650 ps) recombination. The temperature dependence of the charge-separation reaction revealed a complex process for the longer oligomers, in which a combination of (i) direct charge separation and (ii) migration of excitation energy along the oligomer followed by charge separation explained the observed fluorescence decay kinetics. The energy migration is controlled by the temperature-dependent conformational dynamics of the longer oligomers and thereby limits the quantum yield for charge separation. Charge recombination was also studied as a function of temperature through measurements of femtosecond transient absorption. The temperature dependence of the electron-transfer reactions could be successfully modeled using the Marcus equation through optimization of the electronic coupling (V) and the reorganization energy (λ). For the charge-separation rate, all of the donor-acceptor systems could be successfully described by a common electronic coupling, supporting a model in which energy migration is followed by charge separation. In this respect, the C(60)-appended porphyrin oligomers are suitable model systems for practical charge-separation devices such as bulk-heterojunction solar cells, where conformational disorder strongly influences the electron-transfer reactions and performance of the device.


Involvement of calcium and cytoskeleton in gallbladder epithelial cell volume regulation.
The importance of calcium and cellular cytoskeletal elements in the activation or control of volume regulation by epithelial cells was explored in Necturus gallbladder. Gallbladder cells have been previously shown to rapidly readjust their volumes to control size after osmotic perturbation of the mucosal bathing solution. Removal of calcium from the perfusates caused dramatic morphological changes that prevented assessment of the role of extracellular calcium in volume regulation. The regulatory volume increase (RVI) that follows shrinkage of the cell due to perfusion of a hypertonic mannitol solution is insensitive to agents that interfere with cell calcium- or calmodulin-mediated events (quinidine, trifluoperazine) and is not blocked by agents that cause changes in the cytoskeleton (colchicine, cytochalasin B). Osmotically induced cell swelling is followed by regulatory volume decrease (RVD), which is inhibited by agents that interfere with calcium-dependent processes (quinidine, trifluoperazine) and by the microfilament inhibitor, cytochalasin B. These results indicate that RVD depends on calcium, calmodulin, and an intact microfilament network, whereas RVI is independent of these factors.


Body composition and amino acid concentrations of select birds and mammals consumed by cats in northern and central California.
The diet of the feral domestic cat consists of primarily birds and small mammals, but the nutritional composition is relatively unknown. Because of the increasing popularity of natural diets for cats and other wild captive carnivores, the purpose of this study was to describe the body composition and AA concentrations of select birds and small mammals in northern and central California: wild-caught mice (n = 7), Norway rats (n = 2), roof rats (n = 2), voles (n = 4), moles (n = 2), gophers (n = 3), and birds (n = 4). Body water, crude fat (CFa), CP, ash, and AA composition for each specimen were determined. Results are reported as mean ± SD. All results are reported on a DM basis except body water (as-is basis) and AA (g/16 g N). Combined, carcasses had this mean composition: 67.35 ± 3.19% water, 11.72 ± 6.17% CFa, 62.19 ± 7.28% CP, and 14.83 ± 2.66% ash. Concentrations of Arg, Tau, Cys, and Met were 5.63 ± 0.46, 0.92 ± 0.33, 1.91 ± 0.89, and 1.82 ± 0.19 g/16 g N, respectively. Using NRC physiologic fuel values for CP, CFa, and carbohydrate by difference, the combined average energy content of the carcasses was 3,929 kcal/kg DM, but the fiber content was not determined. With the exception of mice and rats, little historical data exist regarding the body and AA composition of many of the species analyzed in this study. Wild-caught mice and rats were composed of less fat but more ash compared with previously reported data in their purpose-bred counterparts. The CP content of mice in this study was similar to previous reports in purpose-bred mice. The CP content of rats was similar or slightly greater compared with historical findings in purpose-bred rats. The N content of rats and AA concentrations on a per-N basis for both rats and mice were similar to previously published data on purpose-bred rodents. The discrepancies in nutrient composition, especially fat concentration, indicate that using purpose-bred animals to represent the diet of the feral domestic cat may not be valid in many instances. When consumed to meet energy needs, the nutrient content of the species reported in the present study exceed the NRC (2006) recommended allowances (RA) for total fat, CP, and essential AA for felines at all life stages.


Vasa nervorum of epicardial nerves and valves of small veins investigated in porcine heart by two types of vascular injections.
The morphology of the vascular supply of peripheral branches of cardiac nerves has not been systematically described until now. The aim of this study was to describe the architectonics of the vasa nervorum of epicardial nerves in porcine hearts by using two injection techniques. Twenty-three hearts from young healthy pigs were used. In 10 hearts India ink solution was injected into the origin of the anterior interventricular branch. In another 10 hearts India ink solution was injected retrogradely through the coronary sinus. The hearts were then analyzed using a magnifying glass and light microscopy. The arterial injection showed the entirety of the rich venous components of the vasa nervorum, which often consisted of paired veins accompanying the epicardial nerves. The thickness of the nerves ranged from 50 to 815 μm. The vasa nervorum drained into larger subepicardial veins. In seven of the hearts prepared with venous injections the vasa nervorum of epicardial nerves were visualized in the same detail as in the arterial preparations and India ink solution filled the right ventricle via the smallest cardiac veins. The histological analysis of these seven hearts showed complete dehiscence and functional insufficiency of small and larger veins valves. In the other three hearts prepared with venous injections the valves were competent, which prevented retrograde filling of larger and smaller veins. The results obtained expand the current knowledge on epicardial nerves vasa nervorum and provide anatomical evidence behind the mechanism of retrograde application of cardioplegic solutions in cardiac surgery.


Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease.
Cigarette smoking is the main risk factor for developing the inflammatory lung disease chronic obstructive pulmonary disease (COPD). Differences in susceptibility among smokers have been attributed to a genetic predisposition. A recent publication on the Framingham Heart Study found a strong association of the Asn142Asp SNP in Glutatthione-S-transferase Omega (GSTO) 2 with forced expiratory volume in the first second (FEV(1)) and forced vital capacity (FVC). FEV(1) is the main parameter reflecting the degree of airflow limitation in patients with COPD. Therefore the present study was undertaken to investigate whether the Asn142Asp polymorphism in GSTO2 occurs more frequently in patients with COPD than healthy subjects and to replicate the finding that it strongly correlates with FEV(1). Furthermore, the Ala140Asp substitution in GSTO1 was examined. Genotyping was carried out in 195 healthy controls and 355 patients with COPD. The results demonstrate that the Asn142Asp polymorphism in GSTO2 and the GSTO1140Asp/GSTO2142Asp haplotype were associated with increased risk of COPD. However, single-marker and haplotype-based analyses failed to reveal an association between lung function parameters and investigated non-synonymous coding SNPs in the GSTO genes. In conclusion, GSTO2 is a candidate gene for COPD, but is not associated with FEV(1).


Post-exposure vaccine effectiveness and contact management in the mpox outbreak, Madrid, Spain, May to August 2022.
BackgroundAppropriate vaccination strategies have been key to controlling the outbreak of mpox outside endemic areas in 2022, yet few studies have provided information on mpox vaccine effectiveness (VE).AimTo assess VE after one dose of a third-generation smallpox vaccine against mpox when given as post-exposure prophylaxis (PEP) within 14 days.MethodsA survival analysis in a prospective cohort of close contacts of laboratory-confirmed mpox cases was conducted from the beginning of the outbreak in the region of Madrid in May 2022. The study included contacts of cases in this region diagnosed between 17 May and 15 August 2022. Follow up was up to 49 days. A multivariate proportional hazard model was used to evaluate VE in the presence of confounding and interaction.ResultsInformation was obtained from 484 close contacts, of which 230 were vaccinated within 14 days of exposure. Of the close contacts, 57 became ill during follow-up, eight vaccinated and 49 unvaccinated. The adjusted effectiveness of the vaccine was 88.8% (95% CI: 76.0-94.7). Among sexual contacts, VE was 93.6% (95% CI: 72.1-98.5) for non-cohabitants and 88.6% (95% CI: 66.1-96.2) for cohabitants.ConclusionPost-exposure prophylaxis of close contacts of mpox cases is an effective measure that can contribute to reducing the number of cases and eventually the symptoms of breakthrough infections. The continued use of PEP together with pre-exposure prophylaxis by vaccination and other population-targeted prevention measures are key factors in controlling an mpox outbreak.


VgrG-5 is a Burkholderia type VI secretion system-exported protein required for multinucleated giant cell formation and virulence.
The type VI secretion system (T6SS) has emerged as a critical virulence factor for the group of closely related Burkholderia spp. that includes Burkholderia pseudomallei, B. mallei, and B. thailandensis. While the genomes of these bacteria, referred to as the Bptm group, appear to encode several T6SSs, we and others have shown that one of these, type VI secretion system 5 (T6SS-5), is required for virulence in mammalian infection models. Despite its pivotal role in the pathogenesis of the Bptm group, the effector repertoire of T6SS-5 has remained elusive. Here we used quantitative mass spectrometry to compare the secretome of wild-type B. thailandensis to that of a mutant harboring a nonfunctional T6SS-5. This analysis identified VgrG-5 as a novel secreted protein whose export depends on T6SS-5 function. Bioinformatics analysis revealed that VgrG-5 is a specialized VgrG protein that harbors a C-terminal domain (CTD) conserved among Bptm group species. We found that a vgrG-5 ΔCTD mutant is avirulent in mice and is unable to stimulate the fusion of host cells, a hallmark of the Bptm group previously shown to require T6SS-5 function. The singularity of VgrG-5 as a detected T6SS-5 substrate, taken together with the essentiality of its CTD for virulence, suggests that the protein is critical for the effector activity of T6SS-5. Intriguingly, we show that unlike the bacterial-cell-targeting T6SSs characterized so far, T6SS-5 localizes to the bacterial cell pole. We propose a model whereby the CTD of VgrG-5-, propelled by T6SS-5-, plays a key role in inducing membrane fusion, either by the recruitment of other factors or by direct participation.


[Osteosynthesis with Kirschner wires in the treatment of dislocated supracondylar humeral fractures in children].
Elbow fractures account for 7-9% of all fractures in childhood, while the supracondylar type is the most common (up to 70%). 84% of all supracondylar elbow fractures occur under the age of 10 years (most often between the age of 5 and 8). The aim of this study was to present the technique and results of treatment of supracondylar fractures with grade III fragment dislocation in pediatric population. Treatment included orthopedic repositioning and percutaneous pin fixation. Over the period 1991-2000, 255 patients were hospitalized due to supracondylar fracture of the humerus with grade III fragment dislocation at the Pediatric Surgery Clinic in Novi Sad. All patients were aged 3-15 years. Orthopedic repositioning and percutaneous pin fixation under X-ray control was performed in 243 patients (95.29%). This study included 167 (65.5%) patients with full documentation. Extensor type of fracture was verified in 151 patients (90.42%). Male patients predominated over female patients--119:48. The average follow-up period was 4, 5 months. On the basis of clinical examination, and after completed rehabilitation, satisfactory results were obtained in 158 patients (94.6%), while in 9 patients the final outcome was unsatisfactory. Literature analysis points to advantages of orthopedic repositioning and percutaneous pin fixation, with certain modifications in the treatment of supracondylar elbow fractures with grade III dislocation. Obtained results of treatment, advantages of this procedure, and our experience, suggest that orthopedic repositioning and percutaneous pin fixation is a procedure of choice in treatment of supracondylar elbow fractures with third III dislocation in children.


[YUAN Qing's experience of Tiaoshen acupuncture in treating autism spectrum disorder].
YUAN Qing's clinical experience in treating autism spectrum disorder using Tiaoshen (regulating the spirit) acupuncture is summarized. YUAN Qing believes that the basic pathogenesis of children with autism spectrum disorder is due to the impairment of brain essence and heart mind. Thus regulating the spirit, especially adjusting brain essence and heart mind is essential during clinical treatment. The main acupoints on the head (brain tri-points, four-spirit points, spirit setting points, mental tri-points, spirit waking-up points and foot mental points) are used to adjust brain essence, and hand mental tri-points (Shenmen[HT 7], Neiguan[PC 6] and Laogong[PC 8]) are used for adjusting heart mind, and emphasizing the importance of the spirit of the doctor and the children's parents.


MRI in the diagnosis and management of epileptomas.
High-resolution magnetic resonance imaging (MRI) is invaluable for identifying cerebral tumors that cause epilepsy. Serial voxel-based automated quantitative analyses are more sensitive than visual reading for detecting change in a lesion. Eloquent cortex can be identified with functional MRI (fMRI), with cautions about the precise location and extent of critical cortex. Tractography is useful for delineating critical white matter tracks as are MR venography and computerized tomography (CT) angiography for displaying veins and arteries. These data may be combined into a three-dimensional (3D) multimodal MR data presentation and displayed interoperatively to increase the precision and minimize the risk of neurosurgical treatment, and for the illustrations.


Chromium (VI) inhibits mouse metallothionein-I gene transcription by modifying the transcription potential of the co-activator p300.
The production of the heavy metal-binding proteins, the metallothioneins (MTs), is induced by heavy metals such as Zn, Cd, and Hg. MTs maintain Zn homeostasis and attenuate heavy metal-induced cytotoxicity by sequestering these metals and lowering their intracellular concentrations. Previously, we had reported that Zn induced the formation of a co-activator complex containing metal response element-binding transcription factor-1 (MTF-1) and the histone acetyltransferase (HAT), p300, which plays an essential role in the activation of MT-1 transcription. In addition, we had shown that Cr(VI) inhibits Zn-induced MT-1 transcription by preventing the Zn-dependent formation of the MTF-1-p300 complex. In the current study, we have shown that the inhibition by Cr(VI) was partially overcome by the overexpression of p300 or MTF-1 in an MT-I promoter-driven luciferase reporter assay system and have used real-time RT-PCR to determine MT-I mRNA levels. It has been reported that Cr(VI) inhibits CYP1A1 transcription by crosslinking histone deacetylase (HDAC) to the promoter. The crosslink inhibits the recruitment of p300 to the MT-1 promoter and blocks HAT-dependent transactivation by p300. However, our results demonstrate that trichostatin A, an HDAC inhibitor, could not block the inhibitory effects of Cr(VI) on MT-1 transcription and that there were no significant differences in the in vitro inhibitory effects of Cr(VI), Cr(III), and Zn on p300 HAT activity. This suggests that the inhibitory effects of Cr(VI) on MT-I transcription may be due to its effects on the HAT-independent transactivation ability rather than the HAT-dependent, HDAC release-related transactivation ability of p300.


The Centrality of the Response Process in Construct Validity: An Illustration via the Rorschach Space Response.
Recently, psychologists have emphasized the response process-that is, the psychological operations and behaviors that lead to test scores-when designing psychological tests, interpreting their results, and refining their validity. To illustrate the centrality of the response process in construct validity and test interpretation, we provide a historical, conceptual, and empirical review of the main uses of the background white space of the Rorschach cards, called space reversal (SR) and space integration (SI) in the Rorschach Performance Assessment System. We show how SR and SI's unique response processes result in different interpretations, and that reviewing their literatures with these distinct interpretations in mind produces the expected patterns of convergent and discriminant validity. That is, SR was uniquely related to measures of oppositionality; SI was uniquely related to measures of cognitive complexity; and both SR and SI were related to measures of creativity. Our review further suggests that the Comprehensive System use of a single space code for all uses of white space likely led to its lack of meta-analytic support as a measure of oppositionality (Mihura, Meyer, Dumitrascu, & Bombel, 2013 ). We close by discussing the use of the response process to improve test interpretation, develop better measures, and advance the design of research.


Opportunities and Challenges for a Histology-Agnostic Utilization of Trastuzumab Deruxtecan.
This review delves into the prospects and challenges offered by a potential pan-histological utilization of trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors. The HER2-targeted antibody-drug conjugate (ADC) T-DXd has shown broad activity across cancer types, with current indications for patients with biomarker-selected breast, gastric, and non-small-cell lung cancer and relevant activity observed in multiple histology-specific trials. Moreover, two recently reported phase 2 trials (DESTINY-Pantumor02 and HERALD) have supported the potential for a pan-cancer utilization of this ADC in patients with advanced cancers expressing HER2 or with HER2 amplifications. By improving the delivery of cytotoxic chemotherapy, ADCs have allowed for meaningful clinical advantages in broad populations of cancer patients, often leading to survival advantages over conventional chemotherapy. Notably, the broad spectrum of activity of certain ADCs has led to the hypothesis of a histology-agnostic utilization based on detecting specific biomarkers, similar to what is already established for certain targeted treatments and immunotherapy. To date, T-DXd has shown the broadest activity across cancer types, with current approvals in breast, gastric, and lung cancer, and relevant antitumor activity observed in a multiplicity of additional cancer types. The optimization of the drug dose, identification of predictive biomarkers, and clarification of mechanisms of resistance will be critical steps in view of a pan-histological expansion in the use of T-DXd.


Identification of differential aberrations in multiple-sample array CGH studies.
Most existing methods for identifying aberrant regions with array CGH data are confined to a single target sample. Focusing on the comparison of multiple samples from two different groups, we develop a new penalized regression approach with a fused adaptive lasso penalty to accommodate the spatial dependence of the clones. The nonrandom aberrant genomic segments are determined by assessing the significance of the differences between neighboring clones and neighboring segments. The algorithm proposed in this article is a first attempt to simultaneously detect the common aberrant regions within each group, and the regions where the two groups differ in copy number changes. The simulation study suggests that the proposed procedure outperforms the commonly used single-sample aberration detection methods for segmentation in terms of both false positives and false negatives. To further assess the value of the proposed method, we analyze a data set from a study that identified the aberrant genomic regions associated with grade subgroups of breast cancer tumors.


Selection of patients with hepatocellular cancer: a difficult balancing between equity, utility, and benefit.
Although liver transplantation (LT) represents the gold-standard strategy for hepatocellular cancer (HCC), its use is circumscribed by several factors like donor shortage, perioperative complications, or competition with other candidates without HCC. Moreover, different alternative approaches like resection or loco-regional therapies may be attempted in selected cases. The best option for the treatment of an HCC patient is a complex decision, involving several ethical principles including: equity (horizontal equity and vertical equity or urgency), and utility. These principles influence the different phases of the patient selection process for LT: inscription in the waiting list (WL), deciding upon patient priority and drop-out before LT, allocating the liver donor to the best matched recipient. The best end-point for describing the principle of utility is the "transplant benefit" (TB). This concept expresses the survival gain obtained comparing LT with the best alternative therapies (i.e., difference between life years obtained with and without LT). The TB used with a mid-term time horizon (post-transplant 5-10 years), has the intrinsic potential to reach the dignity of an independent LT selection principle. Thus, the present review investigates the role of organ allocation using a TB model with the intent to introduce equity among patients transplanted having HCC or non-tumoral diseases.


Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake.
Biological effects of dietary isoflavones, such as daidzein and genistein are of interest in preventive medicine. We estimated the dietary intake of isoflavones from dietary records and compared the values with the plasma concentrations and urinary excretions in Japanese middle-aged women. The dietary intake of daidzein and genistein was 64.6 and 111.6 mumol /day/capita (16.4 and 30.1 mg/day/capita), respectively. The isoflavones intake was mostly attributable to tofu, natto and miso. The median of plasma daidzein and genistein concentration was 72.46 and 206.09 nmol/L, respectively. The median of urinary excretion was 20.54 mumol /day for daidzein, 10.79 for genistein, 15.74 for equol and 1.64 for O-desmethylangolensin (O-DMA). Equol and O-DMA were excreted by 50% and 84% of all participants, respectively. Equol metabolizers were significantly lower the plasma and urinary daidzein and urinary O-DMA. The dietary intake of daidzein and genistein after the adjustment for total energy intake was significantly correlated with the urinary excretion (r = 0.365 for daidzein and r = 0.346 for genistein) and plasma concentration (r = 0.335 for daidzein and r = 0.429 for genistein). The plasma concentration of isoflavones was also significantly correlated with the urinary excretion. We conclude that in epidemiological studies measurements of plasma concentration or urinary excretion of these isoflavones are useful biomarkers of dietary intake and important for studies on their relation to human health.


Characterization of cytoplasmic and chloroplast 5S ribosomal ribonucleic acid from broad-bean leaves.
Green leaves of the broad bean (Vicia faba) contain two 5S RNA components that can be separated from each other by polyacrylamide-gel electrophoresis. The major component is located in the larger subunit of cytoplasmic ribosomes, whereas the minor component occurs in the larger subunit of chloroplast ribosomes. Their electrophoretic mobilities relative to those of Escherichia coli 5S RNA (120 nucleotides) and plant 4S RNA (78 nucleotides) suggest that they consist of 118 and 122 nucleotide residues respectively. Thermal ;melting' profiles of plant cytoplasmic and chloroplast 5S RNA species at 260nm indicate the similarity of their secondary structures, not only to each other, but also to those of E. coli and mammalian 5S RNA species. The base compositions of the two plant 5S RNA species have more in common with each other than with the corresponding molecules from either E. coli or mammalian cells.


Reuse of CLO test in the diagnosis of helicobacter pylori infection.
Negative CLO test pellets can be reused repeatedly in diagnostic endoscopy within a short period of time. However, the duration that these pellets can be stored at room temperature before second use remains unclear. A total of 360 patients, 190 males and 170 females, who required a CLO test during endoscopy, were enrolled in this study. Two biopsies were taken from the gastric antrum of each patient, one for testing with a new pellet and the other for testing with a reused pellet. The reused pellets were used randomly and were divided into five groups according to the time interval between their initial and second usages (1, 2, 3, 6, and > 6 mo). When a positive result was found, the time to color change was recorded. Good correlation was noted for nearly all the paired CLO tests in all groups with either both positive or both negative. Only four pairs produced discrepant results. There was no significant difference when the results of both new and reused CLO tests were compared using McNemar's test (p > 0.05). In positive pairs, there was no significant difference in the color change time of both tests in all five groups by two-tailed t-test (p > 0.05); Pearson's correlation and linear regression showed a strong correlation between the color time change in the five groups (p < 0.0001). Only 54 of the 427 negative pellets stored for more than 6 months could be reused because most were dried out or no longer yellow in color. In conclusion, negative CLO test pellets may be reused within 6 months after initial usage provided they are stored at room temperature.


Diversity and Biogeography of Bathyal and Abyssal Seafloor Bacteria and Archaea Along a Mediterranean-Atlantic Gradient.
Seafloor sediments cover the majority of planet Earth and microorganisms inhabiting these environments play a central role in marine biogeochemical cycles. Yet, description of the biogeography and distribution of sedimentary microbial life is still too sparse to evaluate the relative contribution of processes driving this distribution, such as the levels of drift, connectivity, and specialization. To address this question, we analyzed 210 archaeal and bacterial metabarcoding libraries from a standardized and horizon-resolved collection of sediment samples from 18 stations along a longitudinal gradient from the eastern Mediterranean to the western Atlantic. Overall, we found that biogeographic patterns depended on the scale considered: while at local scale the selective influence of contemporary environmental conditions appeared strongest, the heritage of historic processes through dispersal limitation and drift became more apparent at regional scale, and ended up superseding contemporary influences at inter-regional scale. When looking at environmental factors, the structure of microbial communities was correlated primarily with water depth, with a clear transition between 800 and 1,200 meters below sea level. Oceanic basin, water temperature, and sediment depth were other important explanatory parameters of community structure. Finally, we propose increasing dispersal limitation and ecological drift with sediment depth as a probable factor for the enhanced divergence of deeper horizons communities.


Surface ultrastructure after excimer laser ablation. Expanding vs contracting apertures.
Excimer laser corneal ablation (photorefractive keratectomy) for myopia using a diaphragm delivery system was performed on eye bank and animal eyes by either progressively expanding or contracting the iris aperture. Use of an expanding aperture, in which the final ablations cover the entire treatment zone, produced a pseudomembrane over the zone that had few discontinuities. Ultrastructural examination of the corneas ablated using a progressively contracting aperture, however, revealed numerous discontinuities in the surface pseudomembrane. Use of an expanding iris aperture to perform ablations to correct myopia may be preferable as it produces a pseudomembrane with few discontinuities. Clinical studies of surface healing in humans are necessary to determine the clinical relevance of improved continuity of the surface pseudomembrane.


[Effect of reserpine on the ultrastructure and electrical instability of the heart].
The time course of ultrastructural and electrophysiological disorders and their role in sudden death of ventricular fibrillation at various intervals of desympathization caused by reserpine administration were studied. Early in the effect of reserpine (up to 30 min), glycogen granules were found to accumulate in the sarcoplasm of cardiomyocytes. At later intervals (1-24 hours), along with glycogen accumulation destructive lesions of organoids were observed in the form of myofibrillar recontraction, destruction of mitochondria, degeneration of sarcolemma. These changes are morphologic reflections of metabolic disorders developing in the myocardium under conditions of acute desympathization of the patient, and may be one of the causes of increased vulnerability of the heart in fibrillation.


Different timing and spatial separation of parental chromosomes in intergeneric somatic hybrids between Brassica napus and Orychophragmus violaceus.
Experimental and newly formed hybrids and polyploids generated by wide crosses usually show varying degrees of cytological instability. The spatial separation of parental genomes and uniparental chromosome elimination in hybrid cells has been reported in many hybrids from plants and animals. Herein, the behavior of parental genomes in intergeneric somatic hybrids between Brassica napus and Orychophragmus violaceus was analyzed using genomic in situ hybridization (GISH). In mitotic and meiotic cells, the chromosomes from O. violaceus were distinguished from B. napus by their larger size and staining patterns. In interphase nuclei of the hybrid, O. violaceus-labeled chromatin appeared as large heterochromatic blocks that were nonrandomly distributed at prophase, typically distributed toward one side of the nucleus. In pollen mother cells at prophase I of meiosis, O. violaceus chromosomes appeared as one or two deeply stained chromatin blocks that resolved into bivalents at a late stage, after bivalents from B. napus were visible. Thereafter, bivalents of O. violaceus congressed to the equatorial plate and segregated at anaphase I after those from B. napus. The different behavior of O. violaceus chromosomes in the hybrids indicates that they have differential condensation states at interphase and progress later through the cell cycle and meiosis than B. napus chromosomes. This difference in behavior may restrict or prevent the formation of bivalents of mixed genome origin. Differential gene expression of parental alleles including rDNA loci may contribute to their distinct cytological behavior and to the phenotype of hybrids.


Association between Continuity of Care and the Onset of Thyroid Disorder among Diabetes Patients in Korea.
Objectives: As the relationship between diabetes mellitus and thyroid dysfunction is well known, it is important to investigate the factors influencing this association. Continuity of care is associated with better quality of care and outcomes, such as reduced complications, among diabetes patients. Therefore, the purpose of this study was to investigate the association between continuity of care and the onset of thyroid dysfunction among diabetes patients. Methods: We used Korean National Health Insurance Service National Sample Cohort data from 2002 to 2013. Our final study population included 16,806 newly diagnosed diabetes patients who were older than 45 years of age. Continuity of care was measured using the Continuity of Care index. The dependent variable was the onset of thyroid disorder. Cox proportional hazard regression models were used for statistical analyses. Results: Diabetes patients with low continuity of care were at increased risk of the onset of thyroid disorder compared with those with high continuity of care (hazard ratio (HR): 1.28, 95% confidence interval (CI): 1.07⁻1.54). Subgroup analyses showed that this association was significant within patients with type 2 diabetes (HR: 1.24, 95% CI: 1.01⁻1.52) or whose main attending site was a local clinic (HR: 1.32, 95% CI: 1.07⁻1.64). Conclusions: Our results show that diabetes patients with low continuity of care are more likely to experience the onset of thyroid disorder. Therefore, improving continuity of care could be a reasonable method of preventing complications or comorbidities, including thyroid disorder, among diabetes patients.


Spatial updating and the maintenance of visual constancy.
Spatial updating is the means by which we keep track of the locations of objects in space even as we move. Four decades of research have shown that humans and non-human primates can take the amplitude and direction of intervening movements into account, including saccades (both head-fixed and head-free), pursuit, whole-body rotations and translations. At the neuronal level, spatial updating is thought to be maintained by receptive field locations that shift with changes in gaze, and evidence for such shifts has been shown in several cortical areas. These regions receive information about the intervening movement from several sources including motor efference copies when a voluntary movement is made and vestibular/somatosensory signals when the body is in motion. Many of these updating signals arise from brainstem regions that monitor our ongoing movements and subsequently transmit this information to the cortex via pathways that likely include the thalamus. Several issues of debate include (1) the relative contribution of extra-retinal sensory and efference copy signals to spatial updating, (2) the source of an updating signal for real life, three-dimensional motion that cannot arise from brain areas encoding only two-dimensional commands, and (3) the reference frames used by the brain to integrate updating signals from various sources. This review highlights the relevant spatial updating studies and provides a summary of the field today. We find that spatial constancy is maintained by a highly evolved neural mechanism that keeps track of our movements, transmits this information to relevant brain regions, and then uses this information to change the way in which single neurons respond. In this way, we are able to keep track of relevant objects in the outside world and interact with them in meaningful ways.


Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR.
HP1-type chromodomain proteins self-associate as well as interact with the inner nuclear membrane protein LBR (lamin B receptor) and transcriptional coactivators TIF1alpha and TIF1beta. The domains of these proteins that mediate their various interactions have not been entirely defined. HP1-type proteins are predicted by hydrophobic cluster analysis to consist of two homologous but distinct globular domains, corresponding to the chromodomain and chromo shadow domain, separated by a hinge region. We show here that the chromo shadow domain mediates the self-associations of HP1-type proteins and is also necessary for binding to LBR both in vitro and in the yeast two-hybrid assay. Hydrophobic cluster analysis also predicts that the nucleoplasmic amino-terminal portion of LBR contains two globular domains separated by a hinge region. The interactions of the LBR domains with an HP1-type protein were also analyzed by the yeast two-hybrid and in vitro binding assays, which showed that a portion of the second globular domain is necessary for binding. The modular domain organization of HP1-type proteins and LBR can explain some of the diverse protein-protein interactions at the chromatin-lamina-membrane interface of the nuclear envelope.


Multicellular magnetotactic bacterial consortia are metabolically differentiated and not clonal.
Consortia of multicellular magnetotactic bacteria (MMB) are currently the only known example of bacteria without a unicellular stage in their life cycle. Because of their recalcitrance to cultivation, most previous studies of MMB have been limited to microscopic observations. To study the biology of these unique organisms in more detail, we use multiple culture-independent approaches to analyze the genomics and physiology of MMB consortia at single cell resolution. We separately sequenced the metagenomes of 22 individual MMB consortia, representing eight new species, and quantified the genetic diversity within each MMB consortium. This revealed that, counter to conventional views, cells within MMB consortia are not clonal. Single consortia metagenomes were then used to reconstruct the species-specific metabolic potential and infer the physiological capabilities of MMB. To validate genomic predictions, we performed stable isotope probing (SIP) experiments and interrogated MMB consortia using fluorescence in situ hybridization (FISH) combined with nano-scale secondary ion mass spectrometry (NanoSIMS). By coupling FISH with bioorthogonal non-canonical amino acid tagging (BONCAT) we explored their in situ activity as well as variation of protein synthesis within cells. We demonstrate that MMB consortia are mixotrophic sulfate reducers and that they exhibit metabolic differentiation between individual cells, suggesting that MMB consortia are more complex than previously thought. These findings expand our understanding of MMB diversity, ecology, genomics, and physiology, as well as offer insights into the mechanisms underpinning the multicellular nature of their unique lifestyle. The emergence of multicellular lifeforms represents a pivotal milestone in Earth's history, ushering in a new era of biological complexity. Because of the relative scarcity of multicellularity in the domains Bacteria and Archaea , research on the evolution of multicellularity has predominantly focused on eukaryotic model organisms. In this study, we explored the complexity of the only known bacteria without a unicellular stage in their life cycle, consortia of multicellular magnetotactic bacteria (MMB). Genomic and physiological analyses revealed that cells within individual MMB consortia are not clonal and exhibit metabolic differentiation. This implies a higher level of complexity than previously assumed for MMB consortia, prompting a reevaluation of the evolutionary factors that have led to the emergence of multicellularity. Because of their unique biology MMB consortia are ideally suited to become a model system to explore the underpinnings of bacterial multicellularity.