Hip instability: anatomic and clinical considerations of traumatic and atraumatic instability.
Hip instability is uncommon because of the substantial conformity of the osseous femoral head and acetabulum. It can be defined as extraphysiologic hip motion that causes pain with or without the symptom of hip joint unsteadiness. The cause can be traumatic or atraumatic, and is related to both bony and soft tissue abnormality. Gross instability caused by trauma or iatrogenic injury has been shown to improve with surgical correction of the underlying deficiency. Subtle microinstability, particularly from microtraumatic or atraumatic causes, is an evolving concept with early surgical treatment results that are promising.


Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme that catalyzes the sixth step of glycolysis and thus, serves to break down glucose for energy production. Beyond the traditional aerobic metabolism of glucose, recent studies have highlighted additional roles played by GAPDH in non-metabolic processes, such as control of gene expression and redox post-translational modifications. Neuroproteomics have revealed high affinity interactions between GAPDH and Alzheimer's disease-associated proteins, including the β-amyloid, β-amyloid precursor protein and tau. This neuronal protein interaction may lead to impairment of the GAPDH glycolytic function in Alzheimer's disease and may be a forerunner of its participation in apoptosis. The present review examines the crucial implication of GAPDH in neurodegenerative processes and clarifies its role in apoptotic cell death.


CD45-CD14 +CD34 + murine bone marrow low-adherent mesenchymal primitive cells preserve multilineage differentiation potential in long-term in vitro culture.
Bone marrow-derived cells have been postulated as a source of multipotent mesenchymal stem cells (MSC). However, the whole fraction of MSC remains heterogeneous and the expansion of primitive subset of these cells is still not well established. Here, we optimized the protocol for propagating the low-adherent subfraction of MSC which results in long-term expansion of population characterized by CD45(-)CD14(+)CD34(+) phenotype along with expression of common MSC markers. We established that the expanded MSC are capable of differentiating into endothelial cells highly expressing angiogenic markers and exhibiting functional properties of endothelium. Moreover, we found these cells to be multipotent and capable of giving rise into cells from neuronal lineages. Interestingly, the expanded MSC form characteristic cellular spheres in vitro indicating primitive features of these cells. In sum, we isolated the novel multipotent subpopulation of CD45(-)CD14(+) CD34(+) bone marrow-derived cells that could be maintained in long-term culture without losing this potential.


[A rare cause of obstruction of mitral valve prosthesis: periannular fibrosis. Diagnostic by transesophageal echocardiography].
The authors report a case of dysfunction of a double hemi-disc mitral valve prosthesis due to peri-annular fibrous overgrowth on the atrial side of the prosthesis. Conventional transthoracic Doppler echocardiography showed signs of thrombosis of the prosthesis. Transoesophageal echocardiography allowed a precise diagnosis of the lesions, resulting in immediate surgical referral.


Competition for sucrose-pellets in triads of male Wistar rats: effects of acute and subchronic chlordiazepoxide.
Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose pellets (so-called poor-performing rats), whereas other rats consistently win the competition (so-called high-performing rats). Subchronic (5 mg/kg; 5 consecutive days), but not acute (0.1-20 mg/kg), treatment with chlordiazepoxide temporarily helped poor-performing rats to behave more competitively. This finding, considered together with parallel studies (using high-performing rats), suggested that chlordiazepoxide's beneficial effect was only demonstrable when the poor-performing rats had become tolerant to the drug's initial sedative effect.


Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis.
The objective of this study was to evaluate our experience using cyclosporine A (CyA) in the treatment of Hunner lesion interstitial cystitis (HLIC). Retrospective chart review was performed on patients with HLIC treated with CyA from August 2012 to September 2019. Demographic and clinical variables, number of interstitial cystitis therapies, frequency, nocturia, and bladder pain visual analog scores before and after CyA treatment were collected, as well as the Global Response Assessment (GRA) and the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index. CyA responders were defined as those with moderately or markedly improved GRA scores. A total of 51 patients with HLIC treated with CyA were identified. Mean follow-up was 3 years (0.36-6.8 years). Seventy-six percent (28 of 37) were female; mean age was 68 years (51-84 years). Before CyA treatment, an average of 8 previous therapies were tried and patients reported an average of 8 of 10 bladder pain. Daytime frequency was 11-20 times per day, and nocturia was 7 times per night. Per the GRA, 84% (31 of 37) were considered CyA responders. Posttherapy Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were lower in responders compared with nonresponders (8.9 ± 5.7 vs 21.3 ± 7.0, P = 0.001). Bladder pain, number of hydrodistentions/fulgurations, nocturia, and daytime frequency improved significantly after CyA treatment. The cyclosporine A response rate was 84%, with most of these patients reporting marked improvement. Bladder pain, daytime frequency, and nocturia were significantly improved after CyA treatment, and the number of interventions after CyA treatment decreased. Cyclosporine A should be considered earlier than fifth-line therapy in HLIC.


Jacaranda flower (Jacaranda mimosifolia) as an alternative for antioxidant and antimicrobial use.
Antimicrobial resistance to antibiotics is a serious health problem worldwide, for this reason, the search for natural agents with antimicrobial power against pathogenic microorganisms is of current importance. The objective of this work was to evaluate the antioxidant capacity (ABTS+ and DPPH), antimicrobial activity, and polyphenol compounds of methanolic and aqueous extracts of Jacaranda mimosifolia flowers. The antimicrobial activity against Bacillus cereus ATCC 10876, Bacillus subtilis ATCC 6633, Enterococcus faecalis ATCC 51299, Escherichia coli ATCC 25922, Listeria monocytogenes ATCC 19115, Pseudomonas aeruginosa ATCC 27853, Salmonella typhimurium ATCC 14028, Staphylococcus aureus ATCC 25923, and Streptococcus mutans ATCC 25175, was determined using the Kirby Bauer technique. The results of polyphenolic compounds showed a high amount of total flavonoids in the methanolic and aqueous extracts (503.3 ± 86.5 and 245. 7 ± 27.8 mg Rutin Equivalents/g DW, respectively). Quercetin, gallic acid, caffeic acid, and rutin were identified by the HPLC-DAD technique, while in the GC-MS analysis, esters, fatty acids, organic compounds, as well as monosaccharides were identified. Higher antioxidant capacity was detected by the ABTS technique (94.9% and 62.6%) compared to DPPH values (52.5% and 52.7 %) for methanolic and aqueous extracts, respectively. The methanolic extract showed a greater inhibitory effect on gram-positive bacteria, with a predominant higher inhibition percentage on Listeria monocytogenes and Streptococcus mutans (86% for both). In conclusion, Jacaranda flower extracts could be a natural antimicrobial and antioxidant alternative due to the considerable amount of polyphenolic compounds, and serve as a sustainable alternative for the isolation of active ingredients that could help in agriculture, aquaculture, livestock, pharmaceutics, and other industrial sectors, to remediate problems such as oxidative stress and antimicrobial abuse.


Osteoprotegerin serum levels in women: correlation with age, bone mass, bone turnover and fracture status.
Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast function and therefore plays an important role in bone remodelling. This study aimed to evaluate the clinical value of serum OPG. Do higher OPG serum levels reflect decreased bone resorption and perhaps higher bone mass in women? Serum OPG levels were measured in 177 healthy women (aged 17-85 years) and in 48 untreated patients (mean age 71 +/- 5) with established osteoporosis, and related to age, bone mass, markers of bone turnover and, in the case of patients with osteoporosis, to pre-existing vertebral fractures. In healthy women OPG levels showed a positive correlation with age (r = 0.25, p < 0.001) but not to bone mass or markers of bone turnover. In women with osteoporosis, however, there was a strong relationship between serum OPG and markers of bone turnover (serum c-terminal crosslinked telopeptides of thpe I collagen (sCTX): r = +0.82, p < 0.0001; osteocalcin (OC): r = +0.69, p < 0.0001), with patients who had higher levels of bone-turnover markers showing higher serum levels of OPG. After adjustment for bone mass and bone markers, patients with pre-existing vertebral fractures had significantly lower serum OPG levels than patients without fractures (57 +/- 8 vs. 97 +/- 10 pg/ml, [mean +/- SE], p < 0.01). The age-dependent increase of OPG as an antiresorptive factor may reflect an insufficient paracrine mechanism of bone cells to compensate for bone loss in older age. In patients with osteoporosis, however, OPG correlated strongly with markers of bone turnover; this may point toward a higher level of RANKL/OPG expression in these patients. Finally, low OPG serum levels seem to be associated with vertebral fractures. We hypothesise that low OPG levels in preset conditions of bone turnover may indicate a higher risk of fracture in patients with osteoporosis.


Mind the gap: The mediating role of emotion mechanisms in social bonding through musical activities.
I support the music and social bonding (MSB) framework, but submit that the authors' predictions lack discriminative power, and that they do not engage sufficiently with the emotion mechanisms that mediate between musical features and social bonding. I elaborate on how various mechanisms may contribute, in unique ways, to social bonding at various levels to help account for the socio-emotional effects of music.


Development of IgM-ELISA for diagnosis of recent infection of Japanese encephalitis virus in equines.
Japanese encephalitis (JE) is a re-emerging mosquito borne disease, for which equines are most susceptible amongst all animals. Detection of specific immunoglobulin 'M' (IgM) is considered as an ideal way to diagnose recent JE virus infection in equines due to low virus load and short-term viremia. The present study was undertaken to develop a sensitive and specific recombinant NS1 protein based indirect IgM-ELISA and IgM capture (MAC) ELISA to diagnose recent infection of JEV in equines. Indirect IgM ELISA was standardized with relative diagnostic sensitivity and specificity of 100% and 88.5%, respectively. The validation of indirect IgM-ELISA in different laboratories revealed excellent reproducibility with Cohen's kappa value ranging between 0.84 and 1. The standardization of MAC ELISA was attempted using checker board titration method and non-specific binding of polyclonal anti-equine IgM capture antibody with anti-porcine IgG conjugate and with hyperimmune serum raised in swine against the antigen was observed. Hence, the MAC ELISA was standardized with monoclonal capture antibody; however, its diagnostic performance could not meet the satisfactory limit. Due to better sensitivity and less turnaround time, indirect IgM-ELISA was employed to screen 821 equine serum samples revealing 33.73% positivity of IgM antibodies against JEV in equine population of India. The high JEV sero-positivity warrants the need for vaccination in Indian equine population along with the demand for research focused towards anti-viral therapy. The indirect IgM-ELISA developed in the present study could be useful to diagnose acute or recent infection of JEV in equines as well as in sero-epidemiological studies.


Catabolite regulation of two Escherichia coli operons encoding nitrite reductases: role of the Cra protein.
The Escherichia coli nir and nrf operons, which encode alternative nitrite reductases expressed during anaerobic growth, are subject to catabolite regulation. Transcription from the nir promoter is maximal when bacteria are grown in rich media such as Lennox broth supplemented with glucose. Conversely, expression of the nrf operon is suppressed by rich media, but stimulated during growth in minimal medium with glycerol and fumarate. The role of the catabolite repressor-activator (Cra) protein in catabolite regulation of the nir and nrf promoters was investigated. Transcription from the nir promoter was repressed by Cra when cells were grown in minimal medium with glycerol and fumarate. Crude protein extracts from a strain overproducing Cra encoded on a multicopy plasmid retarded a nir promoter fragment in a mobility shift assay, confirming that the observed Cra-dependent repression was due to the direct interaction of Cra with the regulatory region of the nir operon. Furthermore, the inclusion of fructose 1-phosphate, an effector of Cra DNA-binding activity, in the assay decreased the ability of Cra to retard the nir promoter fragment. In contrast, transcription from the nrf promoter was not regulated by Cra under any of the growth conditions tested.


Vaspin (but not neuropeptide B or neuropeptide W) as a possible predictor of body weight normalization in anorexia nervosa.
The aim of the study was to evaluate the correlation between the nutritional status of patients with anorexia nervosa (AN) and levels of vaspin (VASP), neuropeptide B (NPB), neuropeptide W (NPW) and total antioxidant status (TAS). Ninety serum samples collected from 30 teenage female patients during the acute stage of AN and 30 healthy persons (CONTR) were subjected to biochemical analysis; patients with AN were examined at the beginning of the study (AN-I) and after hospitalization (AN-II), as a result of which partial stabilization of anthropometric measurements was achieved (an increase of body mass index (BMI) by 3.5 kg/m2). Vaspin levels dropped at the end of the hospitalization (compared to AN-I, p < 0.05), achieving values comparable to the CONTR; moreover there was a positive correlation between VASP level and the achieved body weight in AN-II (p < 0.05). Positive correlations were also noted with regard to VASP vs. NPB in AN-I (p < 0.02) (and AN-II, p < 0.013), as well as in the case of VASP vs. NPW in the same groups (p < 0.02 and p < 0.015, respectively). NPB concentration was higher in AN-I (p < 0.05) and AN-II (p < 0.018) than in CONTR, whereas there were no differences (p > 0.05) with regard to levels of VASP, NPW, or TAS. The high level of NPB despite treatment and normalization of VASP level may suggest that there are chronic neuroendocrine disorders at play in anorexia nervosa.


Impact of regular additional endobiliary radiofrequency ablation on survival of patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.
Prognosis of patients with advanced extrahepatic cholangiocarcinoma (eCCA) is poor. The current standard first-line treatment is systemic chemotherapy (CT) with gemcitabine and a platinum derivate. Additionally, endobiliary radiofrequency ablation (eRFA) can be applied to treat biliary obstructions. This study aimed to evaluate the additional benefit of scheduled regular eRFA in a real-life patient cohort with advanced extrahepatic cholangiocarcinoma under standard systemic CT. All patients with irresectable eCCA treated at University Hospital Bonn between 2010 and 2020 were eligible for inclusion. Patients were stratified according to treatment: standard CT (n = 26) vs. combination of eRFA with standard CT (n = 40). Overall survival (OS), progression free survival (PFS), feasibility and toxicity were retrospectively analyzed using univariate and multivariate approaches. Combined eRFA and CT resulted in significantly longer median OS (17.3 vs. 8.6 months, p = 0.004) and PFS (12.9 vs. 5.7 months, p = 0.045) compared to the CT only group. While groups did not differ regarding age, sex, tumor stage and chemotherapy treatment regimen, mean MELD was even higher (10.1 vs. 6.7, p = 0.015) in the eRFA + CT group. The survival benefit of concomitant eRFA was more evident in the subgroup with locally advanced tumors. Severe hematological toxicities (CTCAE grades 3 - 5) did not differ significantly between the groups. However, therapy-related cholangitis occurred more often in the combined treatment group (p = 0.031). Combination of eRFA and systemic CT was feasible, well-tolerated and could significantly prolong survival compared to standard CT alone. Thus, eRFA should be considered during therapeutic decision making in advanced eCCA.


The transmission of health across 7 generations in China, 1789-1906.
We study the intergenerational transmission of health using registered data from China between 1789 and 1906. We first document the intergenerational correlations in lifespans, and we find much higher correlations for mothers, compared to fathers. We then compare children born from brother and twin fathers, and the intergenerational transmission from fathers becomes weaker and is likely to be mostly driven by genetic factors. On the contrary, our results suggest a strong role of women in affecting their children's health outcomes across generations in developing countries.


Thermosensitization, heat shock protein synthesis and development of thermotolerance in M-14 human tumor cells subjected to step-down heating.
M-14 human tumor cells have been subjected to two regimens of step-down heating (SDH) consisting of a conditioning treatment at 42 degrees C for 1 h or at 44.5 degrees C for 20 min, immediately followed by heating at 40 degrees C. Both conditioning treatments thermosensitize the cells towards the subsequent heating at 40 degrees C; the thermosensitization ratio is 6.4 for cells conditioned at 42 degrees C for 1 h and 32.3 for cells conditioned at 44.5 degrees C for 20 min. The overall protein synthetic activity is reduced to 32.7% or 18.4% of control values following 1 h at 42 degrees C and 20 min at 44.5 degrees C, respectively; this inhibition is followed by a full recovery of the synthetic activity during the subsequent exposure at 40 degrees C. SDH-treated cells synthetize four heat shock proteins, with approximate molecular weights of 28, 64, 70 and 90 kDa. The pattern of HSPs induction observed in SDH-treated cells is similar to that found in cells subjected to single hyperthermic exposures. Cells subjected to the SDH sequence 42 degrees C/1 h-->40 degrees C/4 h develop thermotolerance, as indicated by a reduced sensitivity to further hyperthermic challenges.


The measurement of internal carotid artery stenosis: comparison of duplex with digital subtraction angiography.
To compare the subjective (eyeballed) method for measuring internal carotid artery (ICA) stenosis by non-selective intra-arterial digital subtraction angiography (IA-DSA) with objective and duplex methods. Retrospective study. Fifty-three consecutive patients underwent IA-DSA prior to carotid endarterectomy providing 103 carotid angiograms. Objective assessment of ICA stenosis was by the North American Symptomatic Carotid Endarteectomy Trial (NASCET) criterion and the Carotid Stenosis Index (CSI). Duplex estimation of stenosis was derived from peak systolic and diastolic velocities in the ICA and common carotid artery (CCA). The coefficient of repeatability was poorest for NASCET stenosis estimates (40%), whilst the improved values for CSI (20%) were consistent with the lower variability recorded for measuring the CCA diameter. Correlation and agreement levels between subjective (r = 0.80, -41% to +33%) or objective assessments and duplex (NASCET: r = 0.76; -52 to +28%; CSI: r = 0.72; -27 to +39%) showed similar values. We conclude that the inter-observer variability for assessing angiograms obtained by arch injection is considerable and precludes high agreement when IA-DSA is compared with other methods. As the agreement of duplex ultrasound with IA-DSA is similar to the agreement between DSA methods, duplex can be offered as the first stage assessment of ICA stenosis, with the proviso that the duplex assessment is performed consistently by an experienced operator.


Prediction of placenta accreta spectrum in patients with placenta previa using clinical risk factors, ultrasound and magnetic resonance imaging findings.
To predict placental accreta spectrum (PAS) in patients with placenta previa (PP) evaluating clinical risk factors (CRF), ultrasound (US) and magnetic resonance imaging (MRI) findings. Seventy patients with PP were retrospectively selected. CRF were retrieved from medical records. US and MRI images were evaluated to detect imaging signs suggestive of PAS. Univariable analysis was performed to identify CRF, US and MRI signs associated with PAS considering histology as standard of reference. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) was calculated. Multivariable analysis was also performed. At univariable analysis, the number of previous cesarean section, smoking, loss of the retroplacental clear space, myometrial thinning < 1 mm, placental lacunae, intraplacental dark bands (IDB), focal interruption of myometrial border (FIMB) and abnormal vascularity were statistically significant. The AUC in predicting PAS progressively increased using CRF, US and MRI signs (0.69, 0.79 and 0.94, respectively; p < 0.05); the accuracy of MRI alone was similar to that obtained combining CRF, US and MRI variables (AUC = 0.97) and was significantly higher (p < 0.05) than that combining CRF and US (AUC = 0.83). Multivariable analysis showed that only IDB (p = 0.012) and FIMB (p = 0.029) were independently associated with PAS. MRI is the best modality to predict PAS in patients with PP independently from CRF and/or US finding. It is reasonable to propose the combined assessment of CRF and US as the first diagnostic level to predict PAS, sparing MRI for selected cases in which US findings are uncertain for PAS.


Classical swine fever virus Npro antagonises IRF3 to prevent IFN-independent TLR3 and RIG-I-mediated apoptosis.
Classical swine fever virus (CSFV) is the causative agent of classical swine fever, a notifiable disease of economic importance that causes severe leukopenia, fever and haemorrhagic disease in domesticated pigs and wild boar across the globe. CSFV has been shown to antagonise the induction of type I IFN, partly through a function of its N-terminal protease (Npro) which binds IRF3 and targets it for proteasomal degradation. Additionally, Npro has been shown to antagonise apoptosis triggered by the dsRNA-homolog poly(I:C), however the exact mechanism by which this is achieved has not been fully elucidated. In this study we confirm the ability of Npro to inhibit dsRNA-mediated apoptosis and show that Npro is also able to antagonise Sendai virus-mediated apoptosis in PK-15 cells. Gene edited PK-15 cell lines were used to show the dsRNA-sensing pathogen recognition receptors (PRRs) TLR3 and RIG-I specifically respond to poly(I:C) and SeV respectively, subsequently triggering apoptosis through pathways that converge on IRF3 and culminate in the cleavage of caspase-3. Importantly, this IRF3-mediated apoptosis was found to be dependent on transcription-independent functions of IRF3 and also on Bax, a pro-apoptotic Bcl-2 family protein, through a direct interaction between the two proteins. Deletion of IRF3, stable expression of Npro and infection with wild-type CSFV were found to antagonise the mitochondrial localisation of Bax, a key hallmark of the intrinsic, mitochondrial pathway of apoptosis. Together, these findings show that Npro's putative interaction with IRF3 is involved not only in its antagonism of type I IFN, but also dsRNA-mediated mitochondrial apoptosis.Importance Responsible for severe haemorrhagic disease in domestic pigs and wild boar, classical swine fever is recognised by the World Organisation for Animal Health (OIE) and European Union as a notifiable disease of economic importance. Persistent infection, immunotolerance and early dissemination of the virus at local sites of infection have been linked to the antagonism of type I IFN induction by Npro This protein may further contribute to these phenomena by antagonising the induction of dsRNA-mediated apoptosis. Ultimately, apoptosis is an important innate mechanism by which cells counter viruses at local sites of infection, thus preventing wider spread and dissemination within the host, potentially also contributing to the onset of persistence. Elucidation of the mechanism by which Npro antagonises the apoptotic response will help inform the development of rationally-designed live-attenuated vaccines and antivirals for control of outbreaks in typically CSFV-free countries.


Breast Cancer Treatment Delays at an Urban Safety Net Hospital Among Women Experiencing Homelessness.
Disparities in outcomes for vulnerable women is an ongoing problem. Homelessness and breast cancer treatment outcomes is understudied. This is a descriptive study exploring types of homelessness and treatment delays at an urban safety net hospital providing care to a vulnerable patient population.This study is a retrospective chart review of homeless female patients diagnosed with breast cancer between January 1, 2000 and December 31, 2014. Data for this study were acquired from the hospital cancer registry and electronic medical record. All demographic characteristics, time to treatment and factors related to delays to treatment were analyzed descriptively, reporting frequencies and proportions. The total number of individuals analyzed was 24. All except two subjects were delayed to treatment (≥ 30 days from diagnosis to treatment). Most women in this cohort were categorized as chronically homeless (46%) with the rest categorized as transitionally (29%) or episodically (12%) homeless. The majority of subjects (70%) were Black, non-Hispanic. All except one subject were publicly insured (71% Medicaid; 12% Medicare) or uninsured (8%). Regardless of type of homelessness, most subjects were either 30-60 or 60-90 days delayed. Those who were chronically homeless experienced significantly more delays to first treatment (56% of those who were delayed 30-60 days and 57% of those who were delayed 60-90 days; p value 0.006) than those who were episodically or transitionally homeless. Significant delays and barriers to breast cancer treatment exist among women experiencing homelessness. Further studies to improve breast cancer care for homeless women are warranted.


Is Forensic Entomology Lost in Space?
Spatial and scale effects have barely been considered in forensic entomology, despite their pervasive influence on most of the parameters affecting the development of insect larval stages and the progression of insect succession on cadavers. Here, we used smoothing/interpolation techniques and semivariograms to document the spatial dynamics of sarcosaprophageous Calliphoridae, an important forensic taxon, in the Greater Moncton area in New Brunswick, Canada. Results indicated that the spatial dynamics of Calliphoridae differed between species, some species showing strong patterns of regional aggregation while others did not. Multivariate spatial correlations indicated that interspecific relationships in space varied widely, ranging from local and large-scale aggregation to spatial anticorrelation between species. Overall, this study suggested that even within a restricted timescale, the spatial dynamics of Calliphoridae can operate at many scales, manifest in different patterns, and be attributed to multiple different causes. We stress that forensic entomology has much to benefit from the use of spatial analysis because many important forensic questions, both at the fundamental and practical levels, require a spatial solution.


Analysis on the Meiosis-Related Gene (Dmc1, Ph1) Expression in Autotriploid Carassius auratus.
Triploid is usually considered to be unable to perform normal meiosis due to the abnormal behavior of the three sets of chromosomes. But autotriploid Carassius auratus in the Dongting water system (3n = 150, abbreviated as 3nCC) can perform normal meiosis. In artificial autotriploid Carassius auratus (3n = 150, abbreviated as 3nRR), female individuals undergo normal meiosis and produce mature gametes, while male individuals cannot. To better understand the effects of triploidization on meiosis in fish, we study the structure, methylation level, and expression level of meiosis-related genes (Dmc1, Ph1) in diploid Carassius auratus (2n = 100, abbreviated as 2nCC), Carassius auratus red var.(2n = 100, abbreviated as RCC), 3nCC and 3nRR. The results show that, compared with their diploid ancestors (2nCC and RCC), Dmc1 and Ph1 genes are hypomethylated in all 3nCC and female 3nRR, while are hypermethylated in male 3nRR. Correspondingly, Dmc1 and Ph1 genes are highly expressed in all 3nCC and female 3nRR, while are lowly expressed in male 3nRR. These results indicate that high expression of meiosis-related genes can contribute to restoration of bivalent pairing during meiosis in autotriploid Carassius auratus. This study provides new insights into the effect of DNA methylation on the fertility in triploid fish.


Bioavailability and cellular effects of metals on Lumbricus terrestris inhabiting volcanic soils.
Whether the radial thickness (RT) of the chloragogenous tissue and intestinal epithelium of earthworms (Lumbricus terrestris) reflects the bioavailability of metals in soils was investigated in two areas, one with active volcanism (Furnas) and another with no volcanic activity since 3 million years ago (Santa Maria), in the Azores. Metal contents in soil samples and earthworms from the two areas were analyzed. Autometallography and measurements of the RT were performed in the chloragogenous tissue and intestinal epithelium. Earthworms from the active volcanic area demonstrated lower RT of chloragogenous tissue and intestinal epithelium as well as higher levels of bioavailable metals, especially Zn and Cd. Comparison of bioavailable metal contents between both areas suggests a higher risk for uptake of potentially toxic metals in the active volcanic area than in the non-active volcanic area, which is reflected by the lower RT of the chloragogenous tissue and intestinal epithelium in the former.


(2,2'-Bipyridyl-κN,N')chlorido(dl-threoninato-κN,O)copper(II) monohydrate.
In the title compound, [Cu(C(4)H(8)NO(3))Cl(C(10)H(8)N(2))]·H(2)O, the Cu(II) atom is in a slightly distorted square-pyramidal coordination geometry with the basal plane defined by the two N atoms of the bipyridine ligand and the N and O atoms from the threoninate ion and the apical site occupied by the Cl atom. In the crystal, inter-molecular O-H⋯O, N-H⋯O, O-H⋯Cl, C-H⋯O and C-H⋯Cl inter-actions link the mol-ecules into a three-dimensional network. A π-π inter-action with a centroid-centroid distance of 3.461 (1) Å is also present.


Purification of protein fatty acyltransferase and determination of its distribution and topology.
Studies reported from this laboratory have demonstrated that O-glycosidic glycoproteins of salivary, pulmonary, and gastrointestinal origin are acylated by fatty acyltransferase residing in Golgi and microsome-enriched fraction (Slomiany, A., Liau, Y.H., Takagi, A., Laszewicz, W., and Slomiany, B.L. (1984) J. Biol. Chem. 259, 13304-13308). Here we report on the successful purification of this enzyme from rough microsomal membranes of rat gastric mucosa and its identification in a number of diverse tissues and organs, such as heart, liver, pancreas, lung, kidney, salivary glands, and lymphoblasts. The enzymatic activity has been released from the stripped and salt-extracted microsomes with 0.5% Triton X-100 and recovered from 100,000 x g supernatant by affinity chromatography on Cibacron blue F3GA column. The retained fatty acyltransferase protein was selectively displaced from the column with 50 microM palmitoyl-CoA. On nonreducing polyacrylamide gel electrophoresis, the enzymatic activity was associated with a 234-kDa complex, and on sodium dodecyl sulfate polyacrylamide gel electrophoresis, the complex afforded 65- and 67-kDa protein bands. Incubation of microsomes with trypsin prior to enzyme extraction resulted in a 50% inactivation of the fatty acyltransferase and generation of 53- and 55-kDa protein bands, which also had affinity to Cibacron blue F3GA and were displaced from the column together with the active (intact) enzyme. We suggest that the fatty acyltransferase is an integral rough microsomal protein partially exposed to cytosol, which catalyzes the fatty acyl-CoA-protein reaction on the cytosolic site of the rough endoplasmic reticulum and that this enzyme is responsible for processing of the group of protein which are entering rough endoplasmic reticulum-Golgi secretory pathway.


[The dynamics of the urinary glycosaminoglycan indices in the pathogenetic therapy of glomerulonephritis].
A positive dynamics of the course of glomerulonephritis under the effect of pathogenetic therapy evaluated in 140 patients was accompanied by a statistically valid reduction of glycoseaminoglycanes in the urine. This allows to use these indices as adjunctive criteria of treatment efficiency, especially in patients with chronic forms of the disease.


Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization.
After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP-)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. The extent of M1CL reorganization was related to greater lesion volume in the MEP- group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP- but not MEP+ participants. Absence of an MEP (MEP-), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence.ClinicalTrials.gov Identifier: NCT02544503.


AAFP and ISFM Guidelines for diagnosing and solving house-soiling behavior in cats.
These Guidelines have been developed by the American Association of Feline Practitioners (AAFP) and the International Society of Feline Medicine (ISFM) as a resource for veterinary practitioners who want to better understand and manage the important clinical condition of house-soiling in their feline patients. The Guidelines offer straightforward, practical solutions that, in most cases, will help veterinarians and cat owners prevent, manage or entirely remediate feline house-soiling behavior. The Guidelines include scientifically documented information when it is available. However, because research is often lacking, some recommendations reflect the accumulated clinical experience of the authors.


Development of a novel stall design for dairy cattle: Part II. The effect of minimal stall partitioning on lying behavior, rumination, stall cleanliness, and preference.
Free-stalls for dairy cows promote cleanliness, provide cows with a defined space to lie down, and decrease labor and bedding required for maintenance. However, current stall features can restrict behavior and reduce stall use. The objective of this study was to assess the short-term effect of a novel free-stall design (flexible single-bar partition, no neck rail, increased slope) on stall cleanliness and the lying behavior, rumination, milk production, and preferences of dairy cows in comparison to standard free-stalls (metal loop partitions, neck rail). In the first experiment, 60 Holstein cows were randomly divided into two groups and switched between standard and novel stalls in a replicated crossover design with four 7-day periods. Lying behavior and rumination were recorded continuously. Milk yields were recorded 2x/day, and stall cleanliness scores were collected on the last four days of weeks 3 and 4. The second experiment was a 6-day preference test where 14 cows from experiment 1 were given free access to 16 standard and 16 novel stalls. Lying behavior was recorded continuously. On day 6, standing, perching, and intention, lying, and rising movements were recorded. In experiment 1, cows spent 12 min less time lying down (14.1 vs 14.3 ± 0.48 h/d), had one fewer lying bouts (8.8 vs 9.8 ± 0.23 bouts/d), and had longer lying bouts by 6 min (1.4 vs 1.5 ± 0.05 h/bout) in novel stalls. Rumination time (547.3 vs 548.9 ± 4.66 min/d) and milk yield (35.0 vs 35.2 ± 0.51 kg/d) did not differ between stall types. However, novel stalls were more than twice as soiled as standard stalls (32.8 vs 14.2 ± 1.38% of rear half soiled). In experiment 2, the cows most recently housed in the novel stalls showed a clear preference for lying down in those stalls, whereas cows most recently housed in standard stalls showed no preference. Intention and lying down movements were longer in standard stalls when other cows were present in diagonally opposite stalls, but were similar between stall types when not occupied. All cows preferred standing in novel stalls. Novel stalls may have improved stall use compared to standard free-stalls, and the design requires further development to address cleanliness concerns. Future work is required to provide comfortable stalls without sacrificing cleanliness.


Underestimation of snakebite mortality by hospital statistics in the Monaragala District of Sri Lanka.
Estimates of snakebite mortality are mostly based on hospital data, although these may considerably underestimate the problem. In order to determine the accuracy of hospital-based statistics, data on snakebite mortality in all hospitals in the Monaragala District of Sri Lanka were compared to data on snakebite as the certified cause of death for the district, for the 5-year period between 1999 and 2003. Data were cross-checked in a sample of hospitals and divisional secretariats within the district. Hospital statistics did not report 45 (62.5%) of the true number of snakebite deaths in the Monaragala District. Twenty-six (36.1%) of the victims either did not seek, or had no access to, a hospital. Another 19 (26.4%) had arrived at hospital, but had done so too late to receive treatment. Our study confirms the limitations of official hospital-based mortality data on snakebite.


Sleep pattern and bone mineral density: a cross-sectional study of National Health and Nutrition Examination Survey (NHANES) 2017-2018.
This research is a cross-sectional study based on the participants aged 50 years and older from National Health and Nutrition Examination Survey (NHANES) database. Poor sleep patterns were associated with lower bone mineral density (BMD) and a higher risk of osteoporosis, especially among older individuals or females. Accumulated evidence demonstrates that sleep duration, which is one aspect of sleep pattern, is associated with the risk of osteoporosis. However, the related studies on the association between sleep patterns and the risk of osteoporosis were limited. Therefore, this research aims to investigate the association of sleep patterns with BMD and the risk of osteoporosis among individuals aged 50 years and older. Participants aged ≥ 50 years from the NHANES database were included in the present study. The diagnosis of osteoporosis was based on the results of BMD testing. Moreover, all the participants were divided into different sleep pattern groups according to nocturnal sleep duration and bedtime. In addition, this study used multivariate linear regression models to evaluate the association between sleep patterns and BMD and exploited multiple logistic regression models to investigate the odds ratios (ORs) for osteoporosis. Finally, 1,865 individuals (non-osteoporosis: N = 1,713; osteoporosis: N = 152) aged over 50 years old with complete data were analyzed. The results of multivariate linear regression models showed that individuals with normal sleep duration/later bedtime or long sleep duration/later bedtime had lower femoral BMD than those with normal sleep duration/usual bedtime. Moreover, subjects with long sleep duration/later bedtime had a higher risk of osteoporosis compared with those with normal sleep duration/usual bedtime. In addition, subgroup analyses revealed the association of sleep patterns with BMD and the risk of osteoporosis appeared to be more pronounced among individuals aged ≥ 65 years or females. This study demonstrated that sleep patterns are associated with BMD and the risk of osteoporosis. Poor sleep patterns contribute to decreased bone mass and the increased risk of osteoporosis. Therefore, a healthy sleep pattern is favorable for the prevention of osteoporosis.


Hydrogen peroxide and reoxygenation cause prostaglandin-mediated contraction of human placental arteries and veins.
Because our previous studies in several vascular preparations suggest that posthypoxic reoxygenation elicits tone responses by generation of hydrogen peroxide we compared the actions of reoxygenation and hydrogen peroxide on isolated human placental arteries and veins. Endothelium-intact and denuded arteries and veins (1 to 2 mm diameter, from normal term deliveries), incubated under 95% oxygen/5% carbon dioxide or 5% oxygen/5% carbon dioxide (balance nitrogen) and precontracted with 1 to 10 nmol/L U46619, were exposed to hypoxia (95% nitrogen/5% carbon dioxide, PO2 8 to 10 torr) followed by reoxygenation and to 1 to 100 mumol/L hydrogen peroxide in the presence and absence of the inhibitor of prostaglandin biosynthesis, 10 mumol/L indomethacin. In both arteries and veins posthypoxic reoxygenation or exposure to hydrogen peroxide produced vascular contraction that was eliminated or reversed to a modest relaxation by indomethacin, consistent with mediation by prostaglandins. Hypoxia after incubation with 5% oxygen, but not 95% oxygen, caused a modest prostaglandin-independent relaxation. Removal of the endothelium did not alter any of these responses. Placental arteries and veins show a similar prostaglandin-mediated contraction to hydrogen peroxide and posthypoxic reoxygenation, consistent with a possible involvement of hydrogen peroxide in the response to reoxygenation.


Effect of environmental enrichment on behavioral and morphological outcomes following neonatal hypoxia-ischemia in rodent models: A systematic review and meta-analysis.
Neonatal hypoxia-ischemia (HI) is a major cause of mortality and morbidity in newborns and, despite recent advances in neonatal intensive care, there is no definitive treatment for this pathology. Once preclinical studies have shown that environmental enrichment (EE) seems to be a promising therapy for children with HI, the present study conducts a systematic review and meta-analysis of articles with EE in HI rodent models focusing on neurodevelopmental reflexes, motor and cognitive function as well as brain damage. The protocol was registered a priori at PROSPERO. The search was conducted in PubMed, Embase and PsycINFO databases, resulting in the inclusion of 22 articles. Interestingly, EE showed a beneficial impact on neurodevelopmental reflexes (SMD= -0.73, CI= [-0.98; -0.47], p< 0.001, I2= 0.0%), motor function (SMD= -0.55, CI= [-0.81; -0.28], p< 0.001, I2= 62.6%), cognitive function (SMD= -0.93, CI= [-1.14; -0.72], p< 0.001, I2= 27.8%) and brain damage (SMD= -0.80, CI= [-1.03; -0.58], p< 0.001, I2= 10.7%). The main factors that potentiate EE positive effects were enhanced study quality, earlier age at injury as well as earlier start and longer duration of EE exposure. Overall, EE was able to counteract the behavioral and histological damage induced by the lesion, being a promising therapeutic strategy for HI.


Combined Treatment of Cinobufotalin and Gefitinib Exhibits Potent Efficacy against Lung Cancer.
This study aimed to evaluate the efficacy of cinobufotalin combined with gefitinib in the treatment of lung cancer. A549 cells were treated with gefitinib, cinobufotalin, or cinobufotalin plus gefitinib. MTT assay, annexin-V/PI staining and flow cytometry, TUNEL staining, DCFH-DA staining, Western blot, and real-time RT-PCR were performed to investigate the synergistic inhibitory effect of cinobufotalin combined with gefitinib on the growth of A549 cells. Results showed that cinobufotalin synergized with gefitinib displayed inhibited cell viability and enhanced apoptosis in the combination group. Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Besides, cinobufotalin plus gefitinib downregulated the levels of HGF and c-Met. In summary, cinobufotalin combined with gefitinib impedes viability and facilitates apoptosis of A549 cells, indicating that the combined therapy might be a new promising treatment for lung cancer patients who are resistant to gefitinib.


Pitfalls and progress in the diagnosis and management of canine inflammatory bowel disease.
Inflammatory bowel disease (IBD) is the collective term for a group of chronic enteropathies characterized by persistent or recurrent gastrointestinal (GI) signs and inflammation of the GI tract. The specific steps that lead to IBD and the basis for phenotypic variation and unpredictable responses to treatment are not known. This article examines IBD in dogs, focusing on the interaction between genetic susceptibility and the enteric microenvironment (bacteria, diet), the utility of recently developed histologic criteria, the prognostic indicators, and the standardized approaches to treatment.


Activation of naturally occurring lung CD4(+)CD25(+) regulatory T cells requires CD8 and MHC I interaction.
Naturally occurring Foxp3(+)CD4(+)CD25(+) T cells (nTregs) isolated from lungs of naive mice regulate allergic airway hyperresponsiveness (AHR) and inflammation. Here, we demonstrate the critical requirement for engagement of MHC class I on CD4(+)CD25(+) T cells by CD8 for the functional activation of these nTregs. Suppression of allergen-induced AHR and inflammation by nTregs was abolished in mice treated with anti-CD8. Correspondingly, decreased levels of IL-10 and TGF-beta and increased levels of Th2 cytokines in bronchoalveolar lavage were detected in these treated mice. Similarly, nTregs isolated from beta2m(-/-) mice or from mice treated with anti-MHC I antibody in vitro before intratracheal transfer failed to modulate AHR or inflammation. Coculture of nTregs with CD8(+) T cells increased IL-10 and TGF-beta. Addition of anti-MHC I or anti-CD8 reduced IL-10 and TGF-beta. These results demonstrate that functional activation of nTregs requires the interaction between MHC I on CD4(+)CD25(+) T cells and CD8.


Human tumor-lymphocyte interaction in vitro. III. T lymphocytes in autologous tumor stimulation (ATS).
The T-cell nature of the responding cells in autologous tumor stimulation (ATS) was proven by (1) E-rosette formation of lymphocytes attached to tumor cells during the early period of co-cultivation; (2) blast-transformed E-rosetting cells detectable at the end of the test period (day 6) and (3) the reactivity of T-enriched lymphocyte subset and unresponsiveness of T-depleted fractions. Preparation of tumor suspensions devoid of lymphocytes made it possible to carry out cross-tests between patients. Blastogenesis with allogeneic tumors was rare. The restricted autologous nature of the reaction is a strong indication for genuine tumor-relatedness.


Corrigendum: A Dietary Assessment Training Course Path: The Italian IV SCAI Study on Children Food Consumption.
[This corrects the article DOI: 10.3389/fpubh.2021.590315.].


Normal human epidermal keratinocytes express in vitro specific molecular forms of (pro)filaggrin recognized by rheumatoid arthritis-associated antifilaggrin autoantibodies.
The so-called antikeratin antibodies and the antiperinuclear factor are the most specific serological markers of rheumatoid arthritis (RA). They were recently shown to be largely the same autoantibodies and to recognize human epidermal filaggrins and profilaggrin-related proteins of buccal epithelial cells (collectively referred to as (pro)filaggrin). To further characterize the target antigens, we investigated their expression by normal human epidermal keratinocytes cultured in differentiating conditions, using immunofluorescence and immunoblotting with RA sera and three different monoclonal antibodies to (pro)filaggrin. On the cornified, stratified epithelial sheets obtained in vitro, RA sera with anti(pro)filaggrin autoantibodies (AFA) produced granular staining of the stratum granulosum and diffuse staining of the stratum corneum. The antigens recognized by RA sera strictly colocalized with (pro)filaggrin in keratohyalin granules. Following sequential extraction of the proteins from the epithelial sheets, the RA sera and the three monoclonal antibodies to (pro)filaggrin, recognized a series of low-salt-soluble molecules, including a neutral/acidic isoform of filaggrin and several proteins with sizes and pI intermediates between this isoform and profilaggrin. They also recognized urea-soluble high-molecular-weight profilaggrin-related molecules. These results show that in vitro epidermal keratinocytes express various molecular forms of (pro) filaggrin that bear epitopes targeted by AFA of RA sera, and that some of these are absent from epidermis. Moreover, these epitopes, which are present on the keratohyalin granules of buccal epithelial cells but not on those of epidermal cells, are present on the granules of the cultured keratinocytes. This work completes the molecular characterization of the proteins targeted by AFA.


Interatrial distance predicts the necessity of additional carina ablation to isolate the right-sided pulmonary veins.
Ablation of the pulmonary vein (PV) carina is occasionally required for PV isolation (PVI). Marshall bundle and epicardial connections between the right-sided PV (RtPV) carina and right atrium (RA) may be one of the mechanisms that necessitates carina ablation. We sought to clarify anatomical characteristics predictive of the necessity of carina ablation. Forty-five consecutive patients undergoing radiofrequency catheter ablation of atrial fibrillation were prospectively included in this study. Left atrial (LA) and PV size and morphology, and interatrial distance in the posterior aspect, were measured on cardiac computed tomography (CT) images. For right-sided PVI, the patients were divided into 2 groups based on the necessity of RtPV carina ablation, Carina-ABL group (n = 21) and Non-Carina-ABL group (n = 24). The distance between the anterior portion of the RtPV carina and RA was shorter in the Carina-ABL group vs in the Non-Carina-ABL group (7.7 ± 1.7 mm/m2 vs 9.5 ± 2.3 mm/m2; P = .005), whereas other anatomical parameters (LA and RA volumes, right inferior PV angle, and ostial diameters of the RtPVs) did not differ between the groups. For left-sided PVI, the ostial diameter and circumference of the left superior PV were smaller in the Carina-ABL group (n = 13) vs the Non-Carina-ABL group (n = 32) (8.6 ± 2.1 mm/m2 vs 7.3 ± 1.5 mm/m2; P = .044, and 34.9 ± 6.0 mm/m2 vs 30.1 ± 5.1 mm/m2; P = .017, respectively). A shorter interatrial distance for right-sided PVI and a smaller PV ostium for left-sided PVI were associated with the necessity of additional carina ablation. The presence and location of the epicardial fibers may be affected by the atrial and PV geometry.


A model of anuran retina relating interneurons to ganglion cell responses.
A model is presented which accounts for many characteristic response properties used to classify anuran ganglion cell types while being consistent with data concerning interneurons. In the model color is ignored and input stimuli are assumed to be only black and white at high contrast. We show that accurate ganglion cell responses are obtained even with simplified receptors and horizontal cells: Receptors are modeled as responding with a step change, while horizontal cells respond only to global changes in intensity brought about by full field illumination changes. A hyperpolarizing and depolarizing bipolar cell are generated by subtracting local receptor and horizontal potentials. Two transient amacrine cells (On and Off) are generated using a high-pass filter like mechanism with a thresholded output which responds to positive going changes in the corresponding bipolar cell potentials. The model shows how a selective combination of bipolar and amacrine channels can account for many of the response properties used to classify the anuran ganglion cell types (class-0 through 4) and makes several experimental predictions.


Initial Asian experience in hysteroscopic sterilisation using the Essure permanent birth control device.
To present our initial experience in the use of the Essure permanent birth control device in a predominately Asian population. A retrospective study. Minimally Invasive Surgery Unit, KK Women's and Children's Hospital, Singapore. Eighty women seeking permanent birth control. From 22 June 2001, women who sought sterilisation were counselled with regards to the various options of permanent birth control. Informed consent for hysteroscopic sterilisation was obtained only after the woman met the criteria for Essure permanent birth control. The sterilisation procedure was carried out without the need for general anaesthesia in a day surgery centre using the Essure permanent birth control device. The surgical details and post procedure follow up were analysed. Feasibility and safety of the Essure permanent birth control device in Asians and its non-placement rate. No serious adverse events or complications were encountered in using the Essure device. No pregnancies have been reported in our series to date. A significant reduction in the Essure device non-placement rate (20.0%vs 4.0%, P= 0.021) and mean operation time (27.3 vs 19.6 minutes, P= 0.006) were seen when patients were pre-medicated with spasmolytic agent and analgesia. The Essure permanent birth control device is safe and suitable for Asians. Its non-placement rate may be improved with pre-medication of spasmolytic agent and analgesia.


Wideband frequency-swept excitation in pulsed EPR spectroscopy.
Excitation of electron spins with monochromatic rectangular pulses is limited to bandwidths that are smaller than the spectral widths of most organic radicals and much smaller than the spectral widths of transition and rare earth metal ions. With frequency-swept pulses, bandwidths of up to 800MHz have previously been attained for excitation and detection of spin packets at frequencies of about 9.6GHz and bandwidths of up to 2.5GHz in a polarization transfer experiment at frequencies of about 34GHz. The remaining limitations, mainly due to resonator bandwidth and due to pulse length restrictions are discussed. Flip angles for state-space rotations on passage of a transition can generally be computed from the critical adiabaticity by the Landau-Zener-Stückelberg-Majorana expression. For hyperbolic secant pulses, the Demkov-Kunike model describes excitation for spin packets within and outside the sweep range. Well within the sweep range, the Bloch-Siegert phase shift is proportional to critical adiabaticity to a very good approximation. Because of the dependence of both flip angle and coherence phase on critical adiabaticity, it is advantageous to use pairs of amplitude and frequency modulation functions that provide such offset-independent adiabaticity. Compensation for the resonator response function should restore offset-independent adiabaticity. Whereas resonance offsets and Bloch-Siegert phase can be refocused at certain pulse length ratios, phase dispersion in coupled spin systems cannot generally be refocused. Based on the bandwidth limitations that arise from spin dynamics, requirements are derived for a spectrometer that achieves precise spin control over wide bands. The design of such a spectrometer and hardware characterization by EPR experiments are discussed.


Community as laboratory: reflections from Rochester, New York, in celebration of the dedication of the Robert J. Haggerty child health services research laboratories.
The dedication of the Robert J. Haggerty Child Health Services Research Laboratories at the University of Rochester (New York) Medical Center in October 2004 provided an opportunity to reflect on the current state of child health services research. Dr Haggerty had a grand vision for using the community in which children live as a laboratory for studying the varied medical, psychosocial, and behavioral morbidities that affect them. He believed that the diverse problems faced by children were best studied by a multidisciplinary team, including both academic and community pediatricians, epidemiologists, sociologists, policy makers, and community leaders. Research done in the community involving front-line providers allows investigation into the most challenging and relevant problems faced by children. To this end, Dr Haggerty made collaboration and cooperation between the community and the academic medical center a priority during his tenure at Rochester. His vision of community as laboratory continues through the child health services research emanating from the Haggerty Laboratories. Nevertheless, many barriers remain that need to be overcome for the sake of improving the lives of children in the United States and throughout the world.


Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program.
Our intent was to investigate systematically the overlap between conduct disorder (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the two disorders would have correlates of both. Results from a series of programmatic studies examining phenotypic features of bipolar and conduct disorder alone or combined in probands and relatives were evaluated within and without the context of ADHD. Examination of the clinical features, patterns of psychiatric comorbidity, functioning in multiple domains, and familiality showed that children with CD and BPD had similar features of each disorder irrespective of the comorbidity with the other disorder. Our data suggest that when BPD and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to BPD, and manic symptoms should not be viewed as secondary to CD.


Increased expression of co-stimulatory molecules and enhancement of the IgG response in rats orally administered with a polyherbal formulation.
Link Samahan® (LS) is a standardized modern formulation of a polyherbal preparation used in the indigenous system of medicine in Sri Lanka. Evaluation of the immunostimulatory activity of LS and the molecular mechanisms that modulate the humoral immune response. Immunostimulatory activity of LS was tested in rats following oral administration on days 1-5 and 15-19 and immunization with bovine serum albumin (BSA) on day 1 and 15. Anti-BSA IgM and IgG response in rats treated with LS, water and sugar (as controls) were compared on days 0-35, using ELISA. The expression of co-stimulatory molecules on lymphocytes was assessed on days 0-8 and days 14-22 using RT-qPCR. IgM and IgG levels of LS-treated rats were increased significantly by day 7 and 21 respectively compared to controls (p < 0.05). IgG response of LS-treated group reached a higher magnitude compared to its IgM response. Gene expression of CD28 and CD40L on T cells (4.9-5.1 fold) and CD80, CD86 and CD40 on APCs (2.4-3.1 fold) were induced significantly by day 2 compared to their expression on day 0 (p < 0.05). The expression levels of CD28 and CD40L on day 2-4 and 16-18 were similar while the expression of CD80, CD86 and CD40 on day 16-18 was higher (3.7-5.1 folds) compared to their levels on day 2-4 (2.4-3.2). These findings support an adjuvant effect of LS contributing to its immunostimulatory activity and increased expression of co-stimulatory molecules that contribute to boosting immune response.


Role of breast cancer screening in the overdiagnosis of thyroid cancer: results from a cross-sectional nationwide survey.
South Korea has the highest incidence of thyroid cancer worldwide, raising questions regarding the possibility of overdiagnosis. Examining the factors affecting thyroid cancer screening is crucial in elucidating the reasons for this unusually high incidence of thyroid cancer. Therefore, in the present study, we investigated the association between breast cancer screening and thyroid cancer screening to determine the potential role of breast cancer screening in the overdiagnosis of thyroid cancer in South Korea. We analyzed the data of women aged > 30 years who were enrolled in the 2014 Korean National Cancer Screening Survey. Self-reported breast cancer screening behavior was categorized as follows: no screening, mammography only, ultrasonography only, and both ultrasonography and mammography. Thyroid cancer screening behavior was categorized as follows: those who had or had not undergone ultrasonography screening. Logistic regression analysis was used to examine the associations between breast and thyroid cancer screening behaviors. Of the 2270 participants, a total of 569 (25.1%) were screened for thyroid cancer. Those who underwent only mammography, only ultrasonography, or both mammography and ultrasonography were more likely to be screened for thyroid cancer than those who did not undergo breast cancer screening (odds ratio [OR]: 1.47, 95% confidence interval [CI] 1.06-2.04; OR 2.71, 95% CI 1.83-4.02; OR 2.75, 95% CI 1.99-3.80, respectively). Our findings indicate that thyroid cancer screening in Korea is likely to be performed on an opportunistic basis. Therefore, a nationwide public health and medical initiative is needed to curb the unnecessary use of thyroid screening in the asymptomatic general population.


[Retroperitoneal laparoscopic treatment of symptomatic caliceal diverticular calculi].
Treatment of urinary calculi in caliceal diverticular is indicated when they are symptomatic. Minimally invasive techniques, in particularly laparoscopic approach, occupy an increasingly important place in the urological therapeutic armamentarium and have changed from an open surgical approach to endoscopic treatment for the management of symptomatic caliceal diverticular calculi. Herein, we report the case of a woman with symptomatic calculi in an upper caliceal diverticular managed by retroperitoneal laparoscopic approach.


Chemopreventive action of mace (Myristica fragrans, Houtt) on methylcholanthrene-induced carcinogenesis in the uterine cervix in mice.
The present paper reports the chemopreventive action of mace (aril covering the testa of the seed of Myristica fragrans) on 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin, young adult, Swiss albino mice. Placement of cotton-thread impregnated with beeswax containing MCA (approximately 600 micrograms) inside the canal of the uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experiment using the cervical carcinogenesis model system, if mace was administered orally at the dose level of 10 mg/mouse per day for 7 days before and 90 days following carcinogen thread insertion, the cervical carcinoma incidence, as compared with that of the control (73.9%), was 21.4%. This decline in the incidence of carcinoma was highly significant (P less than 0.001). The incidence of precancerous lesions did not display any definite association with different treatments.


Driving the Emission Towards Blue by Controlling the HOMO-LUMO Energy Gap in BF2 -Functionalized 2-(Imidazo[1,5-a]pyridin-3-yl)phenols.
Several boron compounds with 2-(imidazo[1,5-a]pyridin-3-yl)phenols, differentiated by the nature of the substituent (R) in the para position of the hydroxy group, have been synthesized and thoroughly characterized both in solution (1 H, 13 C, 11 B, 19 F NMR) and in the solid state (X-ray). All derivatives displayed attractive photophysical properties like very high Stokes shift, high fluorescence quantum yields and a good photostability in solution. Time-Dependent Density Functional Theory (TD-DFT) calculations allowed to define the main electronic transitions as intra ligand transitions (1 ILT), which was corroborated by the Natural Transition Orbitals (NTOs) shapes. The HOMO-LUMO energy gap was correlated to the electronic properties of the substituent R on the phenolic ring, as quantified by its σp Hammett constant.


Parathyroid hormone-related protein (PTHrP) and malignancy.
PTHrP (parathyroid hormone related protein) is an important mediator of malignancy-related tumor progression and hypercalcemia that shares considerable homology and functionality with parathyroid hormone. In this chapter, we review what has been elucidated to date regarding PTHrP's role in malignancies. Starting with a review of calcium metabolism and regulation, we then summarize the discovery and structure of PTHrP and development of sensitive immunoassays for specific measurement. Subsequently, we explore its role in tumor progression, with emphasis on the primary tumor as well as skeletal and non-osseus metastases. We then consider the clinical implications of PTHrP in cancer before concluding with a discussion of both established and potential treatments for malignancy associated hypercalcemia and bone metastases.


Urethral stricture after pancreas-kidney transplantation due to polypoid urethritis.
Urologic complications are common after pancreas-kidney transplantation using bladder drainage. We report a case of urethral stricture caused by polypoid urethritis occurring 4 years after simultaneous pancreas-kidney transplantation. Endoscopic exploration revealed irregular, ragged-appearing urethral mucosa. The diagnosis of polypoid urethritis was confirmed histopathologically.


Differential IgE binding to isoallergens from Asian seabass (Lates calcarifer) in children and adults.
Fish allergy is a common food allergy, with prevalence rates in the general population ranging between 0.2% and 2.3%. In both adults and children fish ranks in the top eight foods known to cause IgE mediated food allergy. Fish allergy is rarely outgrown and individuals with fish allergy may be allergic to some but not all species of fish. Whilst fish allergy occurs around the world, the characterization of allergenic components of individual species of fish has been largely confined to Northern hemisphere and European fish species. To date allergy to commonly consumed fish in the Asian-Pacific region including barramundi (Asian seabass; Lates calcarifer) have been less well investigated. The aim of this study was to identify and characterize allergenic proteins from barramundi in both fish allergic adult and pediatric patients. Serum from 17 fish allergic adults and children from Australia were characterized by immunoblotting and enzyme linked immunosorbent assays (ELISA) against raw and heated barramundi. Molecular analysis of identified allergens included genetic sequencing and generation of recombinant isoallergens. Two novel parvalbumin isoforms of the β-type were identified as the only allergens in barramundi and subsequently designated as Lat c 1.0101 and Lat c 1.0201 by the International Union of Immunological Societies. These two isoallergens do not differ in their ability to bind IgE antibodies, but are differentially expressed in barramundi tissue. This study characterized two novel heat stable parvalbumin allergens from barramundi, with differential IgE binding capacity between adults and pediatric patients.


Evolutionary algorithm-based generation of optimum peptide sequences with dengue virus inhibitory activity.
Background: There is currently no effective dengue virus (DENV) therapeutic. We aim to develop a genetic algorithm-based framework for the design of peptides with possible DENV inhibitory activity. Methods & results: A Python-based tool (denominated AutoPepGEN) based on a DENV support vector machine classifier as the objective function was implemented. AutoPepGEN was applied to the design of three- to seven-amino acid sequences and ten peptides were selected. Peptide-protease (DENV) docking and Molecular Mechanics-Generalized Born Surface Area calculations were performed for the selected sequences and favorable binding energies were observed. Conclusion: It is hoped that AutoPepGEN will serve as an in silico alternative to the experimental design of positional scanning combinatorial libraries, known to be prone to a combinatorial explosion. AutoPepGEN is available at: https://github.com/sjbarigye/AutoPepGEN.


Consumer survey on the final consumer behavior concerning the disposal of WEEE in Germany.
The evaluation of the waste of electric and electronic equipment (WEEE) collection masses in relation to the amounts placed on the market shows comparably low rates of about 43 to 45% in Germany for the last years. Since a minimum collection rate of 65% has to be achieved from 2019 onward, it is important to ask how the current low rates can be explained. In light of these low rates, the disposal behavior of consumers might play a significant role which is examined in this study. A survey was conducted at the end of February 2018 to assess the consumers' behavior concerning the individual disposal of WEEE. The residents' knowledge about the known return possibilities and the collection systems for WEEE were investigated and if disposal routes differ for large and for small devices. On top of that regional differences in disposal behavior within Germany were considered to explain in all the existing deficits in the collection rate. The consumer survey showed that predominantly regular routes for the disposal of WEEE are used and relevant quantities are not only physically "lost," but that there are also significant deficits in the monitoring itself.


Linear-lumped-parameter modeling of pulmonary impedance in monkeys.
Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linear-lumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr approximately 19%). Networks consisting of two series RIC pathways in parallel resulted in a lower Dr (approximately 14%), but parameter values were difficult to interpret. Despite not modeling the decrease in RL with frequency below 8 Hz, an airway wall compliance, Caw, network in which the airways were separated into central and peripheral components resulted in an even lower Dr (approximately 11%). In addition, parameter values were easy to interpret, consistent among our "normal" monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that networks containing both parallel pathways and Caw are necessary to model ZL over the entire frequency range (2-32 Hz), the effect of Caw is an important determinant of ZL above 8 Hz, and a six-parameter Caw network with the ratio of Caw to parenchymal compliance, Cp, fixed may prove useful in interpreting changes in ZL induced by alterations in lung mechanics in monkeys.


In situ immunoassays for gene translation products in phage plaques and bacterial colonies.
A series of simple, in situ immunoassays have been developed which can be used in screening for translation products of genes cloned in vitro recombination experiments with either phage or plasmid vectors. Antigen-antibody complex formation occurring within a vector-phage plaque can be used to detect the production of a specific protein from an amplified gene. Immunoassays of colonies lysed in situ either by lambda prophage induction or by biochemical means afford a much higher level of sensitivity than the plaque assay probably adequate to detect the production of a few molecules of protein per cell.


Preparation and characterization of core-shell nanoparticles hardened by gamma-ray.
Core-shell nanoparticles have been prepared by irradiation of gamma-ray on block copolymer micelles consisting of hydrophilic polyacrylic acid and hydrophobic polyisoprene with each 40 monomer units. The structure was determined by means of dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and atomic force microscopy (AFM). The size distribution of the core-shell nanoparticles determined by DLS and AFM was very narrow. The average diameter of the particles decreased from 48 nm for the original micelles to 26 nm by the irradiation of 30 kGy. The core size determined by SAXS combined with DLS was roughly constant of 10 nm, irrespective of irradiation dose, whereas the shell thickness of the micelles was twice as large as the core size, and decreased with increasing irradiation dose.


Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice.
We tested the effect of Lactobacillus casei strain Shirota (LcS) on the murine model of ulcerative colitis induced by dextran sodium sulphate. The effect of LcS was tested either as a prophylactic 10 days before the onset of the disease, simultaneously with ulcerative colitis induction or continued 10 days after the disease was induced. LcS was not able to prevent the disease induction in any of the experiments. However, important clinical parameters including blood anemia indicators, body weight, and organ weight were improved in the animals receiving LcS as compared with the ulcerative colitis-induced controls. Increased colonic epithelial regeneration in the LcS treated animals was observed in the chronic stage. The results seemed better for the simultaneous short LcS treatment where some parameters remained similar to the PBS controls, including disease activity scores measured in the acute stage. We can conclude that although LcS alone cannot prevent the induction of ulcerative colitis by dextran sodium sulphate, it can improve the clinical condition of the mice. This could imply important biological consequences for the human situation. Further studies including LcS or other probiotic bacteria together with the available treatment are encouraged.


Utility of food allergy thresholds.
Food allergy is a prevalent disease worldwide that is a significant quality-of-life burden and accidental exposures to food allergens may elicit severe, life-threatening reactions such as anaphylaxis. The threshold level, or the dose that triggers an allergic reaction determined by oral food challenges, varies considerably among individuals suffering from food allergies. IgE concentration, diversity, or function can only partially explain this variation in threshold; pathogenic effector Th2 cells (peTh2) have also been shown to contribute to the eliciting dose. Though very sensitive to co-factors such as physical activity/stress, threshold is a stable and reproducible feature of an individual's allergy over periods of many months, made clear in the past several years from treatment studies in which repeated threshold determination has been used as a treatment outcome however, there also appear to be age-related changes at a population level. More routine determination of food allergy thresholds may help patients stratify risk to improve management of their food allergy. Precautionary allergen labeling, such as "may contain" labels, often cause confusion as they are inconsistent and regularly contain little to trace allergen residues, so food products with such labeling may be unnecessarily avoided. Population-based eliciting dose levels have been determined in the literature lower risk patients with higher thresholds may be more confident with introducing foods with precautionary allergen labels. Understanding of a patient's threshold level could aid in shared decision-making to determine the most suitable treatment options for patients, including the starting dose for oral immunotherapy and/or use of biologics.


Inadvertent cystotomy at laparoscopic hysterectomy--Sydney West Advanced Pelvic Surgery (SWAPS) Unit January 2001 to June 2009.
To review the rate of inadvertent cystotomy during laparoscopic hysterectomy performed by the Sydney West Advanced Pelvic Surgery Unit (SWAPS). To compare this rate with other published data. To identify the risk factors for bladder injury at laparoscopic hysterectomy and to review the management and outcome following such injury. This was a retrospective observational study. All hysterectomies where the SWAPS clinical fellow was involved were included. The study period was from January 2001 to June 2009. Simple statistical formulae were used to analyse data in this study. There were 1223 hysterectomies performed during this period. Eighty-one percent of these were performed laparoscopically. There were 14 (1.1%) bladder injuries reported during this period. All bladder injuries occurred in the laparoscopic group. The majority were managed by laparoscopic repair or conservative management (86%). Two cases (14%) were converted to laparotomy. There were no short- or long-term sequelae. With increasing experience, a fall in the incidence of inadvertent cystotomy was noted during the study period. Inadvertent cystotomy is a recognised complication at hysterectomy. The rate in the SWAPS unit is comparable to that of other published series. Overall, there has been a decline in the rate of bladder injury, which appears attributable to more experience gained with an acquisition of increased skill levels and improved techniques.


Increased plasma levels of ED1+ cellular fibronectin precede the clinical signs of preeclampsia.
To evaluate alterations in fibronectin homeostasis in preeclampsia we measured the plasma concentrations of fibronectin bearing an extra type III domain in 33 preeclamptic and 36 control patients at varying gestational ages. This fibronectin variant is concentrated in the endothelium of blood vessels and has been shown to be released at sites of vascular injury. In addition, total circulating fibronectin levels, composed primarily of hepatic-derived fibronectin lacking the extra type III domain, were also determined. Significant elevations in the average circulating concentrations of fibronectin with an extra type III domain (5.5 micrograms/ml [95% confidence interval, 4.7,6.2] versus 3.2 micrograms/ml [95% confidence interval, 2.9,3.5]; p = 0.0001) as well as total fibronectin (387 micrograms/ml [95% confidence interval, 357,417] versus 327 micrograms/ml [95% confidence interval, 305,348]; p = 0.036) were observed in preeclamptic versus control patients. Significant elevations in fibronectin levels with an extra type III domain occurred in the first trimester before clinical evidence of preeclampsia. In addition, multivariate logistic regression demonstrated a 5.4-fold increase in the risk of preeclampsia with each 1 microgram/ml elevation in concentration of fibronectin with an extra type III domain. These findings lend support to the hypothesis that endothelial-vascular injury is a primary event in the genesis of preeclampsia.


[Current views on pathology and new therapeutic perspective. I: Immunological aspects of the neoplasm (author's transl)].
Several experimental data support the evidence that Osteogenic Sarcoma is a virus-originated neoplasm. Cytogenetic and immunological aspects of this neoplasm are examined by the Authors on the basis of the latest advances in this field, and in view of possible therapeutic applications.


The anticonvulsant and behavioral effects of phencyclidine and ketamine following chronic treatment in rats.
The effects of chronic phencyclidine (PCP) or ketamine (KET) on their respective acute behavioral and anticonvulsant actions were investigated. Female rats were treated for 15 days with twice daily i.p. injections of saline, 20 mg/kg PCP or 40 mg/kg KET. Subjects treated chronically with PCP were challenged with either 10 mg/kg or 20 mg/kg i.p. PCP, while subjects treated chronically with KET were challenged with 40 mg/kg i.p. KET only. Neither chronic drug treatment induced tolerance to the acute anticonvulsant effect, nor to hyperlocomotion and stereotypy as measured by automated activity monitors. However, evidence of tolerance to the stereotypy induced by acute KET was obtained when an observer-based rating scale was employed. In addition, tolerance occurred to the ataxia induced by KET and the 10 mg/kg, but not 20 mg/kg, dose of PCP. Thus, tolerance occurs to some of the acute behavioral effects of PCP and KET while the anticonvulsant action of these compounds remains unaffected.


Neuropathic pain: is it an underestimated symptom in systemic sclerosis?
Pain is one of the most common symptoms in systemic sclerosis (SSc) patients, yet not considered in the assessment of disease severity. This study aimed to investigate the frequency of neuropathic pain (NP) and to evaluate its interference with the quality of life (QoL) in SSc patients. Diffuse and Limited SSc patients diagnosed by American College of Rheumatology 2013 criteria were included in the study. Pain was evaluated with Visual Analogue Scale (VAS); presence of NP was screened with The Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) questionnaire; disease activity was evaluated with modified Medsger Severity Scale (MSS) and QoL with short-form 36 (SF-36). One hundred twenty patients were included in the study (mean age 53.64 ± 11.44 years, female/male 83.3-16.7%). Total pain frequency was found 69.2% and NP was 35.9% in the entire patient group. Pain was most frequently seen in wrist-hand (50.6%) and ankle-foot (43.4%) regions; albeit, NP rates were highest in face (94.4%), lower leg (87.5%), and hip-thigh (78.6%) regions. SF-36 scores were significantly lower in patients with NP than the patients without NP (P < 0.05). The most associated factors with NP were MSS score for muscle involvement and drug consumption of the patient. According to our results, high frequency of NP is seen in SSc patients, and NP is associated with low QoL. Differential diagnosis of NP is important to consider right treatment options and accurate management of pain in all rheumatologic diseases including SSc.


Effect of anisotropy on deformation and crack formation under the brittle removal of 6H-SiC during SPDT process.
Monocrystal SiC is representative of the third generation semiconductor materials, the efficient process technology of 6H-SiC wafer have always been a hot topic. Developing a SPDT processing method based on brittle removal mode with controllable surface/subsurface damage is an important approach to solve the processing difficulties of 6H-SiC. This work aims to analyze the brittle removal process and fully explain the brittle separation behavior and deformation mechanism of 6H-SiC. The micro-scale crack propagation and the effect of anisotropy on crack distribution during machining process are investigated. Large-scale molecular dynamics simulation was used in this work. Under the condition of brittle removal, shear fracture occurs in the front area of tool tip. Shear plane is high-index surface, independent of slip system. The location of tensile fracture is the cleavage plane of hexagonal system, and the fracture surface is composed of step-like joint planes or perfect plane structures. Cracks with self-healing capability appear in the area behind the tool when the surface to be machined is basal plane. When the surface to be machined is not basal plane, a large number of dislocations or cracks remain in subsurface region. Under brittle removal mode, a large amount of plastic deformation appears as well, and deformation mode is related to processing scheme. The brittle removal behavior of 6H-SiC under SPDT process has obvious anisotropy. Basal plane is more suitable for brittle removal of 6H-SiC without residual damage such as sub-surface cracks. The crack behind the tool generated by cleavage fracture can be repaired by itself. Fracture behavior is not related to dislocation. The processing method parallel to the c-axis can cause the generation of a large number of surface cracks. The (011¯0)/[21¯1¯0] and (112¯0)/[11¯00] mode is the best way to achieve plastic removal of 6H-SiC during SPDT process.


Vascular Endothelial Growth Factor Isoform-B Stimulates Neurovascular Repair After Ischemic Stroke by Promoting the Function of Pericytes via Vascular Endothelial Growth Factor Receptor-1.
Ischemic stroke triggers endogenous angiogenic mechanisms, which correlates with longer survival in patients. As such, promoting angiogenesis appears to be a promising approach. Experimental studies investigated mostly the potent angiogenic factor vascular endothelial growth factor isoform-A (VEGF-A). However, VEGF-A increases the risk of destabilizing the brain microvasculature, thus hindering the translation of its usage in clinics. An attractive alternative VEGF isoform-B (VEGF-B) was recently reported to act as a survival factor rather than a potent angiogenic factor. In this study, we investigated the therapeutic potential of VEGF-B in ischemic stroke using different in vivo and in vitro approaches. We showed that the delayed intranasal administration of VEGF-B reduced neuronal damage and inflammation. Unexpectedly, VEGF-B stimulated the formation of stable brain microvasculature within the injured region by promoting the interaction between endothelial cells and pericytes. Our data indicate that the effects of VEGF-B were mediated via its specific receptor VEGF receptor-1 (VEGFR-1) that is predominately expressed in brain pericytes. Importantly, VEGF-B promoted the survival of pericytes, and not brain endothelial cells, by inducing expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and the main protein involved in energy homeostasis AMP-activated protein kinase α (AMPKα). Moreover, we showed that VEGF-B stimulated the pericytic release of factors stimulating a "reparative angiogenesis" that does not compromise microvasculature stability. Our study unraveled hitherto unknown role of VEGF-B/VEGFR-1 signaling in regulating the function of pericytes. Furthermore, our findings suggest that brain microvasculature stabilization via VEGF-B constitutes a safe therapeutic approach for ischemic stroke.


Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes.
In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.


Molecular mechanism of mulberry response to drought stress revealed by complementary transcriptomic and iTRAQ analyses.
The use of mulberry leaves has long been limited to raising silkworms, but with the continuous improvement of mulberry (Morus alba) resource development and utilization, various mulberry leaf extension products have emerged. However, the fresh leaves of mulberry trees have a specific window of time for picking and are susceptible to adverse factors, such as drought stress. Therefore, exploring the molecular mechanism by which mulberry trees resist drought stress and clarifying the regulatory network of the mulberry drought response is the focus of the current work. In this study, natural and drought-treated mulberry grafted seedlings were used for transcriptomic and proteomic analyses (CK vs. DS9), aiming to clarify the molecular mechanism of the mulberry drought stress response. Through transcriptome and proteome sequencing, we identified 9889 DEGs and 1893 DEPs enriched in stress-responsive GO functional categories, such as signal transducer activity, antioxidant activity, and transcription regulator activity. KEGG enrichment analysis showed that a large number of codifferentially expressed genes were enriched in flavonoid biosynthesis pathways, hormone signalling pathways, lignin metabolism and other pathways. Through subsequent cooperation analysis, we identified 818 codifferentially expressed genes in the CK vs. DS9 comparison group, including peroxidase (POD), superoxide dismutase (SOD), aldehyde dehydrogenase (ALDHs), glutathione s-transferase (GST) and other genes closely related to the stress response. In addition, we determined that the mulberry gene MaWRKYIII8 (XP_010104968.1) underwent drought- and abscisic acid (ABA)-induced expression, indicating that it may play an important role in the mulberry response to drought stress. Our research shows that mulberry can activate proline and ABA biosynthesis pathways and produce a large amount of proline and ABA, which improves the drought resistance of mulberry. MaWRKYIII8 was up-regulated and induced by drought and exogenous ABA, indicating that MaWRKYIII8 may be involved in the mulberry response to drought stress. These studies will help us to analyse the molecular mechanism underlying mulberry drought tolerance and provide important gene information and a theoretical basis for improving mulberry drought tolerance through molecular breeding in the future.


Visuospatial and other "right-hemispheric" functions after long recovery periods in left-hemispherectomized subjects.
Two subjects who had infantile brain damage and left hemispherectomies at the ages of 17 and 18 yr are assessed after 28 and 16 yr recovery periods. Both have intact language and verbal memory abilities. However, on functions normally mediated predominantly by the right hemisphere, including nonverbal memory, higher cognitive visuospatial skills, and complex extrapersonal orientation ability, they are severely impaired. Simple visuospatial perceptual and orientation abilities, emotional expression, and face recognition, also "right-hemispheric" functions, are normal. It is postulated that the right hemisphere, if isolated in infancy, has the potential to take over most cognitive functions. The pattern of intact and impaired abilities shown by these subjects allows a hierarchy of functionally important abilities to be constructed. The functions mediated by the solitary right hemisphere are those most essential for independent survival, and functions that are not represented are those least required.


[Connection of perforating and intramuscular veins of the crus in varicosity].
This study was undertaken to investigate the clinical anatomy of indirect perforating veins and their connection to the intramuscular venous collector of the crus by means of MSCT phlebography. From 2015 till now, MSCT phlebography was used to examine a total of 400 patients with chronic diseases of lower limb veins. According to the CEAP classification, clinical class C0-C1 was present in 108 (27%) subjects, C2-C3 - in 173 (43.3%) patients, and C4-C6 - in 119 (29.7%) patients. All examinations were performed using a 128-slice multispiral CT scanner Philips Ingenuity, followed by 3D reconstruction with the help of the IntelliSpace Portal Image Editing Software package. In the 400 extremities examined, we identified a total of 11 655 indirect perforating veins of the calf. Studying the anatomical localization of perforating veins demonstrated that 3248 veins belonged to the posterior tibial group, 1830 veins - to the lateral group, 873 veins - to the paraachillary group, 276 veins - to the intergemellary group, 4451 veins - to the medial group, and 997 perforating veins - to the lateral group. 3D imaging made it possible to trace the entire course of the perforating veins originating from the posterior arched, intersaphenous, oblique veins or other communicating branches to the subfascial and intramuscular portions to the connection with the gastrocnemius and soleus veins which as the disease progresses undergo ectasia with the formation therein of pathological segmental hypervolemia. Studying the ratio of the revealed indirect perforating veins of the determined groups and the presence of gradually developing ectasia of the intramuscular venous collectors in patients of various clinical classes from C0-C1 to C4-C6 made it possible to draw a conclusion on the involvement of perforating veins and intramuscular veins of the crus into the common pathohaemodynamic circle of the development and progression of chronic venous insufficiency in patients with varicose veins.


Electrophysiologic and imaging evidence for an occult myopathic substrate in patients with idiopathic ventricular arrhythmias.
Idiopathic VA are traditionally considered benign, although occasional patients develop an ectopy-mediated cardiomyopathy (EMC). It is unclear whether patients with idiopathic VA in the absence of left ventricular (LV) dysfunction harbor a subclinical cardiomyopathy. We aim to assess for cardiomyopathic substrate in patients with idiopathic ventricular arrhythmias (VA) using imaging and electrophysiologic markers of early fibrosis. Cardiac magnetic resonance (CMR) imaging and ventricular electroanatomic mapping was performed in 3 groups: patients undergoing ablation for idiopathic VA without (Group 1, n = 17) and with LV dysfunction (Group 2 [presumed EMC], n = 12) plus a control group undergoing ablation of supraventricular tachycardia (Group 3, n = 16). Global LV strain, T1 mapping and extended electrogram (EGM) characteristics were compared. Global strain was impaired in patients with presumed EMC (Group 2, p < 0.001). Native T1 times did not differ between groups, however patients in both idiopathic VA groups (Groups 1 and 2) had shorter post-contrast T1 times at 8 min compared to SVT controls (Group 3, p = 0.04). Similarly, the duration of the bipolar EGM was subtly prolonged in both Group 1 and 2 compared to Group 3 (p = 0.002). There were no between group differences in unipolar or bipolar voltage, the no. of bipolar EGM deflections or the maximal unipolar EGM dV/dt. Patients with idiopathic VAs and apparently structurally normal hearts may have subtle CMR and electrophysiologic changes similar in magnitude to that seen in frank presumed EMC, possibly suggestive of an occult cardiomyopathic process.


Analysis of inducible costimulatory molecule participation during the induction and elicitation of granulomatous responses to mycobacterial and schistosomal antigens.
The contribution of inducible costimulatory molecule (ICOS) to Th1 and Th2 cell-mediated immune responses was examined in well-defined pathogen antigen-elicited models of cell-mediated granuloma formation. Th1 and Th2 granulomas were respectively induced by intravenous challenge of CBA/J mice with Mycobacteria bovis purified protein derivative (PPD) or Schistosoma mansoni egg (SEA) antigen-coated beads. Effects of anti-ICOS blocking antibody on granulomas and lymphoid responses were assessed during elicitation and sensitization. Anti-ICOS treatment during the elicitation abrogated Th1- but not Th2-cell-mediated granuloma formation. Treatment during sensitization augmented SEA-bead granulomas and Th2 cytokines in lymphoid tissue. Anti-ICOS reduced the primary inflammatory response to PPD- but not to SEA-beads, despite comparable induction of ICOS-ligand and ICOS+ T cells. Treatment did not prevent early development of IFNgamma producing cells. Thus, post-activation effector Th1 activity was subject to ICOS blockade and chronic treatment caused diversion to Th2 dominance likely by eroding Th1 effector function or survival.