Ca2+ binding protein-1 inhibits Ca2+ currents and exocytosis in bovine chromaffin cells.
Calcium binding protein-1 (CaBP1) is a calmodulin like protein shown to modulate Ca2+ channel activities. Here, we explored the functions of long and short spliced CaBP1 variants (L- and S-CaBP1) in modulating stimulus-secretion coupling in primary cultured bovine chromaffin cells. L- and S-CaBP1 were cloned from rat brain and fused with yellow fluorescent protein at the C-terminal. When expressed in chromaffin cells, wild-type L- and S-CaBP1s could be found in the cytosol, plasma membrane and a perinuclear region; in contrast, the myristoylation-deficient mutants were not found in the membrane. More than 20 and 70% of Na+ and Ca2+ currents, respectively, were inhibited by wild-type isoforms but not myristoylation-deficient mutants. The [Ca2+]( i ) response evoked by high K+ buffer and the exocytosis elicited by membrane depolarizations were inhibited only by wild-type isoforms. Neuronal Ca2+ sensor-1 and CaBP5, both are calmodulin-like proteins, did not affect N(+, Ca2+ currents, and exocytosis. When expressed in cultured cortical neurons, the [Ca2+]( i ) responses elicited by high-K+ depolarization were inhibited by CaBP1 isoforms. In HEK293T cells cotransfected with N-type Ca2+ channel and L-CaBP1, the current was reduced and activation curve was shifted positively. These results demonstrate the importance of CaBP1s in modulating the stimulus-secretion coupling in excitable cells.


Neuroimmune interplay during type 2 inflammation: Symptoms, mechanisms, and therapeutic targets in atopic diseases.
Type 2 inflammation is characterized by overexpression and heightened activity of type 2 cytokines, mediators, and cells that drive neuroimmune activation and sensitization to previously subthreshold stimuli. The consequences of altered neuroimmune activity differ by tissue type and disease; they include skin inflammation, sensitization to pruritogens, and itch amplification in atopic dermatitis and prurigo nodularis; airway inflammation and/or hyperresponsiveness, loss of expiratory volume, airflow obstruction and increased mucus production in asthma; loss of sense of smell in chronic rhinosinusitis with nasal polyps; and dysphagia in eosinophilic esophagitis. We describe the neuroimmune interactions that underlie the various sensory and autonomic pathologies in type 2 inflammatory diseases and present recent advances in targeted treatment approaches to reduce type 2 inflammation and its associated symptoms in these diseases. Further research is needed to better understand the neuroimmune mechanisms that underlie chronic, sustained inflammation and its related sensory pathologies in diseases associated with type 2 inflammation.


The euro area's pandemic recession: A DSGE-based interpretation.
This paper augments the European Commission's open-economy DSGE model (GM) with COVID-specific shocks ('forced savings', labour hoarding) and financially-constrained investors to account for the extreme volatility of private domestic demand and hours worked during COVID-19, and it estimates the model on euro area data for the period 1998q4-2021q4. It takes a pragmatic approach of adapting the workhorse model of a policy institution to COVID-19 data. 'Forced savings' are central to explain quarterly real GDP growth during the pandemic, complemented by contributions from foreign demand and trade, and the negative impact of persistently higher savings after the first wave. We provide extensive model validation, including a comparison to off-model evidence for COVID-related restrictions, and a comparison of different model specifications.


How and why phosphotyrosine-containing peptides bind to the SH2 and PTB domains.
Specific recognition of phosphotyrosine-containing protein segments by Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains plays an important role in intracellular signal transduction. Although many SH2/PTB-domain-containing receptor-peptide complex structures have been solved, little has been done to study the problem computationally. Prediction of the binding geometry and the binding constant of any peptide-protein pair is an extremely important problem. A procedure to predict binding energies of phosphotyrosine-containing peptides with SH2/PTB domains was developed. The average deviation between experimentally measured binding energies and theoretical evaluations was 1.8 kcal/mol. Binding states of unphosphorylated peptides were also predicted reasonably well. Ab initio predictions of binding geometry of fully flexible peptides correctly identified conformations of two pentapeptides and a hexapeptide complexed with a v-Src SH2 domain receptor with root mean square deviations (rmsds) of 0.3 A, 1.2 A and 1.5 A, respectively. The binding energies of phosphotyrosine-containing complexes can be effectively predicted using the procedure developed here. It was also possible to predict the bound conformations of flexible short peptides correctly from random starting conformations.


Consultation and supervision in cases of non-accidental injury to children.
Consultation and supervision play an essential role in the management of the anxieties, conflicts and demands experienced by those working long-term with cases of non-accidental injury. In our setting we employ our own external staff consultant and in turn our workers offer a consultative service to workers from other agencies. It seems to us that consultation and supervision are inter-related but distinct processes: consultation is essentially experiential and non-directive; supervision is didactic and directive. A consultant may give advice from his own area of expertise (which may be different from that of the consultor), but he may also be called upon to interpret or comment on other areas, such as the conflicts between workers and their clients or workers and their organizations. A consultant may also be called on to offer a model of supervision to supervisor and worker. A supervisor, by definition, is expert in the area of work of the worker and in a position within the organization to give direction. He at times, however, will be called upon for non-directive discussion and comment--in effect consultation. He may also have to fill the role of manager and resource provider. Our experience shows it is essential to clarify this inter-relationship as a first step to exploring the skills necessary for supervisor and consultant to help workers fulfil their task.


Isolated right ventricular dysfunction in patients with human immunodeficiency virus.
HIV-infected individuals are at increased risk for pulmonary hypertension and cardiomyopathy, portending a poor prognosis. Right ventricular (RV) dysfunction is associated with worse outcomes in these conditions, yet its prevalence is poorly defined in HIV. We sought to determine the prevalence of RV dysfunction in an outpatient HIV cohort. Echocardiograms were evaluated from 104 HIV-infected adults. Measurements included estimated pulmonary arterial systolic pressure (PASP) and several measures of RV function, including tricuspid annular plane systolic excursion (TAPSE), RV longitudinal myocardial strain (RVLMS), RV fractional area change (RVFAC), and myocardial performance index (MPI). Sixteen subjects (15%) had PASP >35 mm Hg, yet RV function did not differ significantly from those with normal estimated PASP. RV dysfunction defined by RVFAC <35% occurred in 11%. RVLMS had a median value of -27.3%, and individuals below the median had lower TAPSE but no differences in left ventricular ejection fraction (LVEF), PASP, or other measures. Dyspnea was associated with the lowest quintile of RVLMS (≥-21.05%). There were 6 subjects with LVEF <50%, and these individuals had lower TAPSE but no differences in PASP or other RV functional measures. RV dysfunction was common as estimated PASP >35 mm Hg and LV dysfunction, but these findings did not cosegregate. RV dysfunction in HIV-infected individuals may be a separate entity from LV/global cardiomyopathy or pulmonary hypertension and deserves further study.


Phenotypic and genotypic variability in Alpers syndrome.
Alpers syndrome is one of the most common phenotypes of mitochondrial disorders in early childhood and has been associated with pathogenic mutations in POLG1. To investigate the phenotypic-genotypic correlations in Alpers syndrome and to identify potential differences among patients with Alpers syndrome with or without pathogenic POLG1 mutations. Patients with the phenotype of Alpers syndrome who were referred to our pediatric hospital during 1984-2007 and were diagnosed with mitochondrial encephalomyopathy underwent further biochemical, morphological and genetic investigations. A total of 19 patients were included in the study, of whom six had pathogenic POLG1 mutations including a novel mutation (c.907 G>A, p.Gly303Arg). Complete mtDNA sequencing in the subgroup without POLG1 mutations showed 5 novel and 5 very rare mtDNA variants considered as rare polymorphisms. Compared to POLG1(-) patients, the POLG1(+) patients more frequently had seizures at onset, which often became refractory. Ataxia and stroke-like episodes were much more common, while microcephaly and spasticity were encountered almost solely in the POLG1(-) group. Hepatic and ophthalmological involvement developed in 79% and 88% of patients, respectively. Most of the patients in both groups had predominant deficiency of complex I. In addition to the major degenerative changes in the cerebral cortex, the basal ganglia, thalamus and white matter were also involved to variable extent. Alpers syndrome is a heterogeneous syndrome that should be considered in patients with early-onset progressive cortical encephalopathy regardless of liver involvement. The phenotype is different depending on the presence or absence of POLG1 mutations.


Neoadjuvant Chemotherapy and Nodal Response Rates in Luminal Breast Cancer: Effects of Age and Tumor Ki67.
Neoadjuvant chemotherapy (NAC) is standard for most triple-negative and human epidermal growth factor receptor 2 (HER2)+ breast cancers, and frequently downstages node-positive (cN+) disease, permitting omission of axillary dissection. In estrogen receptor (ER)+/HER2- disease, response rates are lower. Whether Ki67 is associated with axillary downstaging in ER+/HER2- disease is unknown. With institutional review board approval, we queried our institutional database to identify all patients with primary ER+/HER2- biopsy-proven cN+ breast cancer treated with NAC followed by surgery from January 2012 to December 2021. Nodal pathologic complete response (pCR) rates were evaluated by pretreatment Ki67 and patient age. 315 patients (median age 50 years) were included. Nodal pCR rate was 24.8% (78/315) and was higher in patients aged < 50 years than ≥ 50 years (31.8% versus 17.7%, p = 0.004). Ki67 was available on 236 patients (74.9%). Median Ki67 was 29.0% (range 1-98%) and did not differ by age category (p = 0.23). Patients with nodal pCR had higher Ki67 (median 40.3% versus 25.0%, p < 0.001). Nodal pCR rates were 28.4% (Ki67 ≥ 20%) versus 8.1% (Ki67 < 20%) (p < 0.001). On multivariable analysis, Ki67 and age category were predictive of nodal pCR. Combining these two parameters together, nodal pCR rates in age < 50 years were 35.8% when Ki67 ≥ 20% versus 14.3% with Ki67 < 20% (p = 0.02). In contrast, for age ≥ 50 years, nodal pCR was 21.0% for Ki67 ≥ 20% versus 2.6% with Ki67 < 20% (p = 0.008). In ER+/HER2- breast cancer, nodal downstaging with NAC is associated with age (< 50 years) and Ki67 (≥ 20%). Age and Ki67 should be considered for NAC decision-making and can identify patients with high rates of nodal downstaging (36%) who would benefit from NAC to enable axillary preservation.


The therapeutic effect of hypertonic solutions on the changes in the effective circulating plasma volume in acute necrotizing pancreatitis in rats.
While hypovolemia or hypovolemic shock is dominant in the early stage of severe acute pancreatitis, there have been few studies on the effects of hypertonic solutions in the management of this disease. We conducted this study to evaluate the therapeutic effects of hypertonic saline solutions (HS) on the course of severe acute pancreatitis in rats. Pancreatitis was induced in male Wistar rats by injecting a 5% solution of sodium taurocholate into the biliopancreatic duct. The effective circulating plasma volume (ECPV) was measured using radioiodinated [125I]bovine serum albumin. Samples of blood and of ascitic fluid were obtained 3, 6, and 12 h after the onset of pancreatitis. Lactated Ringer's solution (LR) and HS were administered consecutively for 3 h beginning 3 h after the induction of pancreatitis. ECPV was measured 6 h after the onset of pancreatitis. The survival rates were investigated for up to 10 days. The mean ECPV decreased significantly from 24.9 +/- 1.1 ml/kg before disease onset to 11.5 +/- 1.3 ml/kg 6 h postoperatively. LR failed to achieve a normal value for ECPV even following a 150 ml/kg infusion. HS200 and HS300 restored the ECPV to the normal level, and with smaller volumes infused. All rats in the untreated group died within 3 days. LR and HS improved the survival rates, with the infusion of HS200, 100 ml/kg, thus attaining a 45% survival at 10 days.


Bovine theileriosis--an emerging problem in south-eastern Australia?
Bovine theileriosis is an arthropod-borne disease caused by one or more haemoprotozoan parasites of the genus Theileria. Traditionally, Theileria infection in cattle in Australia was largely asymptomatic and recognized to be associated with Theileria buffeli, now assigned to the Theileria orientalis-group. There have been some recent outbreaks of theileriosis in dairy and beef cattle, mainly in subtropical climatic zone (New South Wales) of Australia. Here, we provide the first published evidence of an outbreak of bovine theileriosis in the south-eastern Australia (state of Victoria) linked to the ikeda and chitose genotypes of T. orientalis. Future investigations should focus sharply on the elucidating the epidemiology and ecology of Theileria in this region to subvert the possible impact on the cattle industry.


Hepatotoxicity and cholestasis in rats induced by the sesquiterpene, 9-oxo-10,11-dehydroageraphorone, isolated from Eupatorium adenophorum.
Eupatorium adenophorum leaves cause hepatotoxicity and cholestasis in rats. The hepatotoxicant has been characterized as 9-oxo-10,11-dehydroageraphorone (ODA), a cadinene sesquiterpene. Oral administration of ODA, mixed in feed to rats, caused jaundice in 24 h. The liver of the intoxicated animals had focal areas of hepatocellular necrosis, proliferation, and dilation of bile ducts with degenerative changes in the lining epithelium. There was marked increase in the conjugated form of plasma bilirubin and in the activities of the enzymes glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, glutamate dehydrogenase, and 5'-nucleotidase. The histopathological lesions in liver and biochemical profile of marker enzymes show that ODA induced hepatotoxicity and cholestasis in rats. This is the first report on the toxicity of a cadinene sesquiterpene in rats.


A Pyrene-Poly(acrylic acid)-Polyrotaxane Supramolecular Binder Network for High-Performance Silicon Negative Electrodes.
Although being incorporated in commercial lithium-ion batteries for a while, the weight portion of silicon monoxide (SiOx , x ≈ 1) is only less than 10 wt% due to the insufficient cycle life. Along this line, polymeric binders that can assist in maintaining the mechanical integrity and interfacial stability of SiOx electrodes are desired to realize higher contents of SiOx . Herein, a pyrene-poly(acrylic acid) (PAA)-polyrotaxane (PR) supramolecular network is reported as a polymeric binder for SiOx with 100 wt%. The noncovalent functionalization of a carbon coating layer on the SiOx is achieved by using a hydroxylated pyrene derivative via the π-π stacking interaction, which simultaneously enables hydrogen bonding interactions with the PR-PAA network through its hydroxyl moiety. Moreover, the PR's ring sliding while being crosslinked to PAA endows a high elasticity to the entire polymer network, effectively buffering the volume expansion of SiOx and largely mitigating the electrode swelling. Based on these extraordinary physicochemical properties of the pyrene-PAA-PR supramolecular binder, the robust cycling of SiOx electrodes is demonstrated at commercial levels of areal loading in both half-cell and full-cell configurations.


Hemichorea, an unusual complication of ventriculoperitoneal shunt.
We report an unusual case of left hemichorea in a 24-year-old male patient that followed the insertion of a right ventriculoperitoneal shunt. This completely resolved after removal of the shunt. A review of the available literature and the possible aetiopathogenesis is discussed.


Comparison of clinicopathological characteristics and prognoses between bilateral and unilateral breast cancer.
The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer. Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3 months) or metachronous (diagnosed after 3 months of first cancer). SPSS was used for data analysis. 106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T > 5 cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P = 0.000 for both). Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2 years after the first cancer was significantly worse than synchronous bilateral cancer.


Patients' perception of safety climate in Irish general practice: a cross-sectional study.
Although patients have the potential to provide important information on patient safety, considerably fewer patient-report measures of safety climate (SC) have been applied in the primary care setting as compared to secondary care. Our aim was to examine the application of a patient-report measure of safety climate in an Irish population to understand patient perceptions of safety in general practice and identify potential areas for improvement. Specifically, our research questions were: 1. What are patients' perceptions of SC in Irish general practice? 2. Do patient risk factors impact perceptions of SC? 3. Do patient responses to an open-ended question about safety enhance our understanding of patient safety beyond that obtained from a quantitative measure of SC? The Patient Perspective of Safety in General Practice (PPS-GP) survey was distributed to primary care patients in Ireland. The survey consisted of both Likert-response items, and free-text entry questions in relation to the safety of care. A series of five separate hierarchical regressions were used to examine the relationship between a range of patient-related variables and each of the survey subscales. A deductive content analysis approach was used to code the free-text responses. A total of 584 completed online and paper surveys were received. Respondents generally had positive perceptions of safety across all five SC subscales of the PPS-GP. Regarding patient risk factors, younger age and being of non-Irish nationality were consistently associated with more negative SC perceptions. Analysis of the free-text responses revealed considerably poorer patient perceptions (n = 85, 65.4%) of the safety experience in primary care. Our findings indicate that despite being under-utilised, patients' perceptions are a valuable source of information for measuring SC, with promising implications for safety improvement in general practice. Further consideration should be given to how best to utilise this data in order to improve safety in primary care.


Conducting osteochondral injury model in rabbit knee: Pearls and pitfalls.
Osteochondral damage is a commonly encountered issue in the daily orthopedic practice and has been extensively researched across various areas, including tissue transplantations, tissue engineering products, stem cell applications, and cell culture studies. The absence of a universally accepted treatment as the gold standard for osteochondral damage indicates the necessity for further studies in this field in the future. Although the biomechanical characteristics of the rabbit knee do not perfectly mimic those of the human knee, experimental studies conducted on rabbit knees are considered the most practical experimental model for testing a well-constructed experimental hypothesis. Our article endeavors to impart our practical insights and experiences to researchers without experience whom seeking to design studies utilizing this model. We aim to offer valuable guidance for preoperative, operative, and postoperative considerations. •Rabbits used in osteochondral healing models should be at least 4 months old or older. Inducing damage in the trochlea is a well-established technique and relatively easy to apply.•Do not use pointy ended drills as it might create uneven damage. Do not place applied treatment agent in inappropriate level in relation to the surrounding cartilage surface.


Evolutionary constraint on low elevation range expansion: Defense-abiotic stress-tolerance trade-off in crosses of the ecological model Boechera stricta.
Most transplant experiments across species geographic range boundaries indicate that adaptation to stressful environments outside the range is often constrained. However, the mechanisms of these constraints remain poorly understood. We used extended generation crosses from diverged high and low elevation populations. In experiments across low elevation range boundaries, there was selection on the parental lines for abiotic stress-tolerance and resistance to herbivores. However, in support of a defense-tolerance trade-off, extended generation crosses showed nonindependent segregation of these traits in the laboratory across a drought-stress gradient and in the field across the low elevation range boundary. Genotypic variation in a marker from a region of the genome containing a candidate gene (MYC2) was associated with change in the genetic trade-off. Thus, using crosses and forward genetics, we found experimental genetic and molecular evidence for a pleiotropic trade-off that could constrain the evolution of range expansion.


Food insecurity and unmet healthcare needs in South Korea.
Food insecurity is a significant risk factor for chronic and infectious diseases. It is also a barrier to accessing healthcare because food insecurity tends to co-occur with other socioeconomic disadvantages. The objective of this study is to examine whether food insecure individuals in South Korea can access desired level of healthcare when needed. This repeated cross-sectional study used data from the 2013-2015 and 2019-2021 waves of the Korean National Health and Nutrition Examination Survey. Multivariable logistic regression models were used to examine the association between household food insecurity and two indicators of unmet healthcare needs - any experience of forgoing medical service and the reasons for unmet needs (problems with availability, acceptability, and accessibility). Covariates indicating predisposing, enabling, and need factors were included in the regression analyses. Of the 19,394 participants aged 19-64 years, 4.5% were moderately food insecure, 0.9% were severely food insecure, and 9.3% reported unmet healthcare needs. In the adjusted model, moderate food insecurity (OR, 1.47; 95% CI, 1.19-1.82) and severe food insecurity (OR, 3.32; 95% CI, 2.27-4.85) were associated with higher odds of unmet healthcare needs in a dose-graded manner. These associations were largely due to the increased odds of accessibility-related unmet needs among participants with moderate (OR, 2.31; 95% CI, 1.68-3.19) and severe food insecurity (OR, 6.15; 95% CI, 3.91-9.68). Food insecurity was associated with higher odds of unmet healthcare needs among Korean adults. Competing life demands may have a cumulative impact on health over the short and long term. Efforts to address trade-offs between healthcare needs and food insecurity may improve the health and well-being of marginalized populations.


Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis.
I briefly review the discovery and characterization of the first human retrovirus, human T-cell leukemia virus type 1, focusing on contributions from Japanese researchers. The unique regulatory mechanisms for the viral regulation with Tax and Rex, etiology of ATL and possible leukemogenic mechanism with Tax are also discussed briefly.


Residue 134 determines the dimer-tetramer assembly of nucleoside diphosphate kinase from moderately halophilic bacteria.
Halomonas nucleoside diphosphate kinase (HaNDK) forms a dimeric assembly and Pseudomonas NDK (PaNDK) forms a tetrameric assembly. The mutation of Glu134 to Ala in HaNDK resulted in the conversion of the native dimeric structure to the tetramer assembly. Conversely, the mutation of Ala134 to Glu in PaNDK lead to the conversion from the tetramer to the dimer assembly, indicating that a single amino acid substitution at position 134 results in an alteration of the oligomeric structure of NDK. By modeling the structure of HaNDK and PaNDK based on the crystal structure of Myxococcus NDK, we showed that Glu134 exerts sufficient repulsive forces to disrupt the dimer-dimer interaction and prevent the formation of the tetramer.


Toxicity of Certain Penta-Coordinated Organotin(IV) and Tetra-Coordinated Tin(II) Complexes of Heterocyclic beta-Diketones Against the Larvae of Aedes Aegypti (Liston).
Some organotin(IV) and tin(II) complexes of composition R(3)Sn[R'COC:CON(C(6)H(5))N:CCH(3)] (where R=C(4)H(9), R'=CH(3), C(3)H(5), p-ClC(6)H(4); R=C(6)H(5), R'=C(6)H(5) and p-ClC(6)H(4)) and Sn[p-ClC(6)H(4)COC:CON(C(6)H(5))N:CCH(3)](2) were screened for their toxicity against Aedes aegypti larvae. Organotin(IV) complexes were more active than tin(II) complexes.


The development of empathy in the healthcare setting: a qualitative approach.
Healthcare professionals' empathetic behaviors have been known to lead to higher satisfaction levels and produce better health outcomes for patients. However, empathy could decrease over time especially during training and clinical practice. This study explored factors that contributed to the development of empathy in the healthcare setting. Findings could be used to improve the effectiveness and sustainability of empathy training. A qualitative approach, informed by aspects of grounded theory, was utilized to identify factors that enabled the development of empathy from the perspectives of doctors, nurses, allied healthcare workers and students. Twelve sessions of focus group discussions were conducted with 60 participants from two hospitals, a medical school, and a nursing school. Data was analyzed independently by three investigators who later corroborated to refine the codes, subthemes, and themes. Factors which influence the development of empathy were identified and categorized. This formed the basis of the creation of a tentative theory of empathy development for the healthcare setting. The authors identified various personal (e.g. inherent characteristics, physiological and mental states, professional identity) and external (e.g. work environment, life experience, situational stressors) factors that affected the development of empathy. These could be further categorized into three groups based on the stability of their impact on the individuals' empathy state, contributed by high, medium, or low stability factors. Findings suggest empathy is more trait-like and stable in nature but is also susceptible to fluctuation depending on the circumstances faced by healthcare professionals. Interventions targeting medium and low stability factors could potentially promote the development of empathy in the clinical setting. Understanding factors that impact the development of empathy allows us to develop measures that could be implemented during training or at the workplace leading to improve the quality of care and higher clinical work satisfaction.


The influence of bone substitute materials on the bone volume after maxillary sinus augmentation: a microcomputerized tomography study.
This study aims to evaluate the effect of adding bone substitute materials (BSM) to particulated autogenous bone (PAB) on the volume fraction (Vf) of newly formed bone after maxillary sinus augmentation. Thirty healthy patients undergoing maxillary sinus augmentation were included. PAB (N = 10), mixtures of PAB and beta-tricalciumphosphate (PAB/β-TCP) (N = 10), as well as PAB and β-TCP and hydroxyapatite (PAB/HA/β-TCP) (N = 10) were randomly used for sinus augmentation. A sample of the graft material was maintained from each patient at time of maxillary sinus augmentation, and Vfs of the PAB and/or BSM in the samples were determined by means of microcomputerized tomography (μ-CT). Five months later, samples of the grafted areas were harvested during implantation using a trephine bur. μ-CT analysis of these samples was performed, and the Vf of bone and BSM were compared with the data obtained 5 months earlier from the original material. The mean Vf of the bone showed a statistically significant increase (p < 0.05) in all groups after a healing period of 5 months without statistically significant difference between the groups. With regard to the increase of bone volume, it is not relevant if PAB is used alone or combined with β-TCP or HA/β-TCP. The amount of PAB and associated donor site morbidity may be reduced by adding BSM for maxillary sinus augmentation.


DeepCIP: A multimodal deep learning method for the prediction of internal ribosome entry sites of circRNAs.
Circular RNAs (circRNAs) have been found to have the ability to encode proteins through internal ribosome entry sites (IRESs), which are essential RNA regulatory elements for cap-independent translation. Identification of IRES elements in circRNA is crucial for understanding its function. Previous studies have presented IRES predictors based on machine learning techniques, but they were mainly designed for linear RNA IRES. In this study, we proposed DeepCIP (Deep learning method for CircRNA IRES Prediction), a multimodal deep learning approach that employs both sequence and structural information for circRNA IRES prediction. Our results demonstrate the effectiveness of the sequence and structure models used by DeepCIP in feature extraction and suggest that integrating sequence and structural information efficiently improves the accuracy of prediction. The comparison studies indicate that DeepCIP outperforms other comparative methods on the test set and real circRNA IRES dataset. Furthermore, through the integration of an interpretable analysis mechanism, we elucidate the sequence patterns learned by our model, which align with the previous discovery of motifs that facilitate circRNA translation. Thus, DeepCIP has the potential to enhance the study of the coding potential of circRNAs and contribute to the design of circRNA-based drugs. DeepCIP as a standalone program is freely available at https://github.org/zjupgx/DeepCIP.


Neuroimaging Patterns of Intracranial Infections: Meningitis, Cerebritis, and Their Complications.
Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic imaging patterns help radiologists distinguish different types of intracranial infections including meningitis and cerebritis from a variety of bacterial, viral, fungal, and/or parasitic causes. Here, we describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis. We discuss various imaging modalities and recent diagnostic advances such as deep learning through a survey of intracranial pathogens and their radiographic findings. Moreover, we explore critical complications and differential diagnoses of intracranial infections.


Green bonds and other assets: Evidence from extreme risk transmission.
Green bonds (GB) are gaining a prominent role in sustainable development because of their ability to fund environment-friendly projects. This study aims to investigate if investors can benefit from the risk diversification properties of including GB with other assets, particularly within the context of the ongoing COVID-19 pandemic. To do so, we utilize a quantile-connectedness approach to examine a set of GB and traditional assets, i.e., commodities, stocks, and bonds, from 2008 to 2020. We find higher total time-varying risk spillovers during extreme high volatility periods than those with average and low volatility. For pairwise risk spillovers, GB offers more diversification opportunities when volatility is very low. Nevertheless, the diversification benefits increase during the COVID period. The strong bidirectional risk spillovers between GB and conventional bonds imply that GB can be considered a good alternative to traditional bonds while benefiting from their diversification potential, particularly with energy and agriculture. Our findings are useful for investors wishing to implement green diversification portfolio strategies in extreme volatility periods and act as an encouragement to policymakers to establish efficient policies to promote green finance.


Psychiatric symptoms in a patient with isolated adrenocorticotropin deficiency: case report and literature review.
We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency.


Do people reason rationally about causally related events? Markov violations, weak inferences, and failures of explaining away.
Making judgments by relying on beliefs about the causal relationships between events is a fundamental capacity of everyday cognition. In the last decade, Causal Bayesian Networks have been proposed as a framework for modeling causal reasoning. Two experiments were conducted to provide comprehensive data sets with which to evaluate a variety of different types of judgments in comparison to the standard Bayesian networks calculations. Participants were introduced to a fictional system of three events and observed a set of learning trials that instantiated the multivariate distribution relating the three variables. We tested inferences on chains X1→Y→X2, common cause structures X1←Y→X2, and common effect structures X1→Y←X2, on binary and numerical variables, and with high and intermediate causal strengths. We tested transitive inferences, inferences when one variable is irrelevant because it is blocked by an intervening variable (Markov Assumption), inferences from two variables to a middle variable, and inferences about the presence of one cause when the alternative cause was known to have occurred (the normative "explaining away" pattern). Compared to the normative account, in general, when the judgments should change, they change in the normative direction. However, we also discuss a few persistent violations of the standard normative model. In addition, we evaluate the relative success of 12 theoretical explanations for these deviations.


Alcohol Use Predicts 10-Year Depressive Symptom Trajectories in the Health and Retirement Study.
To determine effects of late-middle-aged adults' baseline drinking behavior on their subsequent 10-year depressive symptom trajectories. Health and Retirement Study participants (N = 7,939) were assessed on baseline demographic, health, and drinking characteristics, and biennially assessed for the next 10 years on their depressive symptoms. Growth mixture modeling generated four classes of depressive symptom trajectories: Consistently low (72%), consistently elevated (6%), increasing (12%), and decreasing (10%). Baseline abstinence from alcohol, possibly enforced by poorer health and a history of drinking problems, and heavier drinking, "binge" drinking, and having a history of drinking problems, raised risk of membership in the "consistently elevated" class. Abstinence by participants without history of drinking problems-and light, moderate, and heavier drinking-protected against membership in the "increasing" class. Abstinence by participants without history of drinking problems elevated-and moderate drinking reduced-likelihood of membership in the "decreasing" class. Late-middle-aged adults' alcohol use is associated with the subsequent long-term course of their depressive symptoms.


Serum immunoglobulin levels in N. brasiliensis infection.
We have measured the levels of IgG1, IgG2a, IgG2c, IgA and IgM in the serum of normal rats, and at various times after infection or re-infection with Nippostrongylus brasiliensis, in order to compare these responses with previously measured IgE levels. The results we have to report are that while the levels of the various immunoglobulin classes or subclasses are elevated to a greater or lesser extent, the increments are modest by comparison with the great elevation of total IgE.


The ABCA1 Q597R mutant undergoes trafficking from the ER upon ER stress.
Mutations in ATP binding cassette transporter 1 (ABCA1), a membrane protein associated with cellular cholesterol efflux, cause Tangier disease (TD). Previously, we showed that an ABCA1 Q597R mutant (QR) identified in TD is retained in the endoplasmic reticulum. Here, we report that QR trafficking to the plasma membrane was rapidly induced by thapsigargin or DTT, indicating that ER stress-induced QR trafficking. However, pharmacological rescue of ABCA1 activity was not observed. The trafficking was dependent on COPII components and occurred via the ER-Golgi intermediate compartments. Furthermore, we found that QR was more sensitive to ER stress than ATF6, a transcription factor associated with the ER stress response. These results suggest that thapsigargin can be effective in correcting trafficking defects, and raise the possibility that ER stress-induced trafficking is involved in ER quality control.


Targeting oestrogen to kill the cancer but not the patient.
The link between sex steroids and the development and growth of breast cancer has proved to be an invaluable clue for advances in the prevention and treatment of breast cancer. The identification of the oestrogen receptor (ER) not only allowed advances in the molecular endocrinology of oestrogen action, but also provided a target for antioestrogenic therapeutic agents. However, the application of long-term or indefinite treatment regimens has consequences for the breast cancer. New forms of resistance, based upon enhanced cellular survival networks independent of ER and the suppression of apoptotic mechanisms, develop and then evolve. Remarkably, low concentrations of oestrogen collapse survival pathways and induce apoptosis in completely antihormonally refractory breast cancer. However, recurrent oestrogen-stimulated disease is again sensitive to antihormonal therapy. The novel reapplication of the ER as a therapeutic target for apoptosis is emerging as a new strategy for the long-term targeted maintenance treatment of breast cancer, and in formulating a targeted strategy for endocrine independent cancer.


Help2care: ehealth strategies for self care of users and caregivers based on Nightingale's work.
To report the experience of design and implementation of the Help2Care (an ehealth program that aims to support informal caregivers of dependent people); and to identify its structure and functionality. This is a Portuguese experience report about Help2Care, a practice-based action research project carried out between 2017 and 2019, having as a guiding axis Florence Nightingale's concepts about the relevance of the home-care environment. The Help2Care program revealed itself to be a valuable support tool for providing better healthcare learning, counselling, and assistance of the informal caregivers of dependent people. Different ehealth strategies were used to empower caregivers in self-care in order to have a safe transition between contexts of care at the time of patient discharge. Help2Care allows to inspire other ways of providing care, as well as a reduction in the readmission rate in health organizations for patients who reveal poor care support in home environments.


Mobilisation of HLA-F on the surface of bronchial epithelial cells and platelets in asthmatic patients.
Uncontrolled inflammation of the airways in chronic obstructive lung diseases leads to exacerbation, accelerated lung dysfunction and respiratory insufficiency. Among these diseases, asthma affects 358 million people worldwide. Human bronchial epithelium cells (HBEC) express both anti-inflammatory and activating molecules, and their deregulated expression contribute to immune cell recruitment and activation, especially platelets (PLT) particularly involved in lung tissue inflammation in asthma context. Previous results supported that HLA-G dysregulation in lung tissue is associated with immune cell activation. We investigated here HLA-F expression, reported to be mobilised on immune cell surface upon activation and displaying its highest affinity for the KIR3DS1-activating NK receptor. We explored HLA-F transcriptional expression in HBEC; HLA-F total expression in PBMC and HBEC collected from healthy individuals at rest and upon chemical activation and HLA-F membrane expression in PBMC, HBEC and PLT collected from healthy individuals at rest and upon chemical activation. We compared HLA-F transcriptional expression in HBEC from healthy individuals and asthmatic patients and its surface expression in HBEC and PLT from healthy individuals and asthmatic patients. Our results support that HLA-F is expressed by HBEC and PLT under healthy physiological conditions and is retained in cytoplasm, barely expressed on the surface, as previously reported in immune cells. In both cell types, HLA-F reaches the surface in the inflammatory asthma context whereas no effect is observed at the transcriptional level. Our study suggests that HLA-F surface expression is a ubiquitous post-transcriptional process in activated cells. It may be of therapeutic interest in controlling lung inflammation.


Postoperative irradiation in malignant epithelial tumors of the parotid.
From 1954 through 1979, 77 patients with malignant tumors of the parotid gland were referred from the Department of Head and Neck Surgery for postoperative irradiation. The analysis has been made by grouping the patients according to the estimated amount of disease left after the surgical procedure and by the histological types. There were no local failures in the low-grade tumors, and there were 6 in the 63 patients with high-grade tumors. With gross residual disease or potential residual disease the patients received slightly higher doses than those without. Although there were only 6 failures in the various histological types, there was perhaps a trend to more failures in the adenocarcinomas. There was no difference in the failure rates in patients having had a total resection of the facial nerve or partial resection or no resection. The preferred treatment has been a combination of 20 MeV photons and 18 MeV electrons. Five neck failures were essentially a result of lack of elective irradiation of the neck. Severe complications appeared only in the patients irradiated either for gross residual disease or excision of a recurrence with a high risk of widespread microscopic residual disease.


Evaluating the conformation of recombinant domain I of β(2)-glycoprotein I and its interaction with human monoclonal antibodies.
Pathogenic antiphospholipid antibodies (aPL) cause the antiphospholipid syndrome (APS) by interacting with domain I (DI) of beta-2-glycoprotein I (β(2)GPI). The aPL/β(2)GPI complex then exerts pathogenic effects on target cells. We previously described periplasmic bacterial expression of native and mutated variants of DI, and reported the presence of immunodominant epitopes at positions 8-9 (D8/D9) and position 39 (R39). Mutations at these positions strongly influenced the ability of recombinant DI to bind patient-derived IgG aPL and to inhibit pathogenic effects of these aPL in a mouse model of APS. We now describe an improved cytoplasmic bacterial expression system allowing higher yield of DI. We demonstrate that the nuclear magnetic resonance (NMR) spectra of a (15)N,(13)C-isotope-labelled sample of the recombinant DI protein exhibit properties consistent with the structure of DI in crystal structure of intact β(2)GPI. Mutations at D8/D9 and R39 had limited impact on the NMR spectrum of DI indicating maintenance of the overall fold of the DI domain. We investigated interactions between five variants of DI and ten monoclonal human IgG antibodies, all derived from the IgG aPL antibody IS4 by sequence manipulation and in vitro expression. Arginine residues at positions 100 and 100g in IS4V(H) CDR3 play a particularly important role in binding to DI, but this is unlikely to be due to electrostatic interactions with negatively charged amino acids on DI. Both the strength of binding to DI and the ability to discriminate different DI variants varies between the different IgG antibodies tested. There was no simple relationship between these binding properties and antibody pathogenicity.


Right hemisphere and metaphor comprehension: A connectionist perspective.
Metaphor comprehension is a cognitively complex task, with evidence pointing to the engagement of multiple cerebral areas. In addition, the involvement of the right hemisphere appears to vary with cognitive effort. Therefore, the interconnecting pathways of such distributed cortical centers should be taken into account when studying this topic. Despite this, the potential contribution of white matter fasciculi has received very little attention in the literature to date and is not mentioned in most metaphor comprehension studies. To highlight the probable implications of the right inferior fronto-occipital fasciculus, right superior longitudinal system, and callosal radiations, we bring together findings from different research fields. The aim is to describe important insights enabled by the cross-fertilization of functional neuroimaging, clinical findings, and structural connectivity.


Surgically managed idiopathic intracranial hypertension in adults: a single centre experience.
Idiopathic intracranial hypertension (IIH) is a rare condition that is often managed conservatively. In patients with aggressive progression of the disease surgical options are considered. There are few data on the outcomes of these patients when surgically managed. We describe our experience of surgically managed IIH and the outcomes of these patients, in particular the surgical revision rate and interventions required for resolution of symptoms. A retrospective review of all patient files coded with benign intracranial hypertension, idiopathic intracranial hypertension or pseudotumour cerebri was undertaken. Files were searched with the date of diagnosis and the date these patients were referred for surgical intervention. The surgical interventions and complications were then documented and note was made of the number of inpatient admissions and days spent in hospital. From 2000-2013, 79 patients were identified as patients with IIH that had required surgical intervention; 52 % required further surgical intervention. The average number of surgical interventions was 5.6. For patients requiring further intervention the average number of surgical interventions was 8.6. On average patients with IIH also spent 42 inpatient days in neurosurgical beds, whilst those patients who required further intervention spent 63 days on average in neurosurgical beds. The length of the average individual admission was longer for patients requiring repeated surgical interventions. Based on our experience, patients that require surgical management of IIH frequently require further surgical interventions to control symptoms and manage complications of CSF diversion surgery. Those that require such further intervention on average will have six further operations and spend significantly longer in hospital. Lumboperitoneal (LP) shunting is an effective first line surgical intervention for 52 % of our patient cohort. This sub-group of patients therefore requires specialist neurosurgical input for this long-term and challenging pathological process.


Getting to the Heart of the Matter in Later Life: The Central Role of Affect in Health Message Framing.
Adopting healthy behaviors is often influenced by message framing; gain-framed messages emphasize the benefits of engaging in a behavior, whereas loss-framed messages highlight the consequences of not engaging in a behavior. Research has begun to uncover the underlying affective pathways involved in message framing. In the current study, we examined the role of affect in message framing to encourage exercise program enrollment among older adults. We mailed flyers to 126 volunteers assigned to a gain- or loss-framed condition and measured their affective reactions to the flyer and enrollment intentions. After the call, participants had the opportunity to contact us to enroll. Gain versus loss framing led to more positive affect toward the flyer, which predicted intentions and enrollment effort. In indirect effect analyses, frame indirectly influenced intentions and enrollment effort via positive affect. Although message framing plays an indirect role in influencing behavior, affect plays a central role.


Eating quality of the longissimus thoracis muscle in beef cattle - Contributing factors to the underlying variability and associations with performance traits.
The objective was to determine the factors associated with meat tenderness, juiciness, flavour and chewiness in 4791 growing crossbred cattle. Meat quality of bulls was inferior to that of both steers and heifers with little difference between the latter two genders. Angus, Hereford and Belgian Blues had the most tender meat with the Simmental being the toughest albeit the difference was, on average, only 5%. Moderate to strong correlations (r ≥ |0.43|) existed among tenderness, juiciness and flavour although some of the correlations differed by animal gender. Correlations between chewiness and tenderness in the different genders varied from -0.81 to -0.74 while the correlations between chewiness and the other sensory traits varied from -0.54 to -0.09. The (partial) correlations between each of the four sensory metrics and all of carcass weight, carcass conformation and carcass fat score were ≤|0.09| with most not being different from zero. Correlations between the sensory traits with growth rate, muscle depth, feed intake and efficiency were all ≤|0.08| and mostly not different from zero.


Campomanesia adamantium (Myrtaceae) fruits protect HEPG2 cells against carbon tetrachloride-induced toxicity.
Campomanesia adamantium (Myrtaceae) is an antioxidant compounds-rich Brazilian fruit popularly known as gabiroba. In view of this, it was evaluated the hepatoprotective effects of pulp (GPE) or peel/seed (GPSE) hydroalcoholic extracts of gabiroba on injured liver-derived HepG2 cells by CCl4 (4 mM). The results showed the presence of total phenolic in GPSE was (60%) higher when compared to GPE, associated with interesting antioxidant activity using DPPH• assay. Additionally, HPLC chromatograms and thin layer chromatography of GPE and GPSE showed the presence of flavonoids. Pretreatment of HepG2 cells with GPE or GPSE (both at 800-1000 μg/mL) significantly (p < 0.0001) protected against cytotoxicity induced by CCl4. Additionally, the cells treated with both extracts (both at 1000 μg/mL) showed normal morphology (general and nuclear) contrasting with apoptotic characteristics in the cells only exposed to CCl4. In these experiments, GPSE also was more effective than GPE. In addition, CCl4 induced a marked increase in AST (p < 0.05) and ALT (p < 0.0001) levels, while GPE or GPSE significantly (p < 0.0001) reduced these levels, reaching values found in the control group. In conclusion, the results suggest that gabiroba fruits exert hepatoprotective effects on HepG2 cells against the CCl4-induced toxicity, probably, at least in part, associated with the presence of antioxidant compounds, especially flavonoids.


Localized imaging using stimulated echoes.
Stimulated-echo localized spectroscopy was combined with phase- and frequency-encoding gradients to obtain "zoom" or magnified images of specific organs in situ. The technique requires neither surface coils nor an imaging coil arrangement that exclusively isolates the target organ. This technique can be readily applied to conventional spectrometer imagers that have limited computational capabilities.


Appendicitis in infancy.
One percent (40 infants) of all the children treated for acute appendicitis at Our Lady's Hospital for Sick Children presented during the first 2 yr of life. Nineteen of the 40 children had an appendix mass at the time of the diagnosis. Conservative management of the appendix mass followed by delayed elective appendectomy is a safe and effective method of treatment.


Involvement of insulin-like growth factors-I and -II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas.
The role of the insulin-like growth factors (IGFs) system was investigated in hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. IGF-II protein and message showed a three- to four-fold increase in HD lines growing in MPA-treated mice, as compared with HD tumors growing in untreated mice. Progression to a hormone-independent phenotype in all these lines was accompanied by a high constitutive expression of IGF-II. Similar IGF-I mRNA levels were detected in HD and HI lines. Both IGF-I and -II messages arose from the malignant epithelial cells, as shown by in situ hybridization studies. A significant decrease in Man-6P/type II IGF-R content was detected in HD tumors growing in MPA-treated mice as compared with HD lines growing in untreated mice. On the other hand, in HI tumors, notwithstanding high IGF-II synthesis, the levels of Man-6P/type II IGF-R remain high. Competitive inhibition and affinity labeling studies showed an almost exclusive binding of IGF-II to Man-6P/type II IGF-R on tumor membranes. The involvement of IGFs in the growth of epithelial primary cultures of the C4-HD line was evaluated. Exogenous IGF-I potentiated MPA stimulatory effect at concentrations of 50-100 ng/ml. Treatment of C4-HD cells with antisense oligodeoxynucleotides (ASODNs) to type I IGF-R and to IGF-II RNA resulted in a dose-dependent inhibition of MPA-mediated cell proliferation. The inhibition caused by IGF-II ASODNs could not be overcome by the addition of IGF-II up to 150 ng/ml. ASODNs to type I IGF-R at 40 microg/ml reduced by 75% the number of type I IGF-R; ASODNs to IGF-II at 1 microM decreased by 83% the levels of IGF-II protein. Our results provide support for the involvement of IGF-I and -II in MPA-induced mammary tumor growth by autocrine pathways.


Renal prothrombin: quantification of mRNA using reverse transcription-polymerase chain reaction in a rat model.
Attempts to quantify renal prothrombin (PT) have failed due to interference of its hepatic counterpart. In order to gauge PT synthesized by the kidney, the expression of PT mRNA was compared in renal and hepatic tissues of rats. PT mRNAs were quantified, using quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR), from RNA extracts of kidneys and livers of ten hooded Wistar rats. To control variations in sample preparation, the amount of PT transcript in each sample was normalized to the amount of its beta-actin transcript. The median ratio of PT to beta-actin transcript of 0.0011 (with a mean +/- standard deviation (SD) of 0.0010 +/- 0.0002, range 0.0007-0.0014) in the renal tissues was significantly (p < or = 0.001) lower than its corresponding value of 0.3669 (with a mean +/- SD of 0.3729 +/- 0.0716, range 0.2718-0.4675) in the hepatic tissues. Thus, expression of PT mRNA in the rat kidney was almost 300-fold less as compared with its expression in hepatic tissue.


Mutational removal of the Thr669 and Ser671 phosphorylation sites alters substrate specificity and ligand-induced internalization of the epidermal growth factor receptor.
The epidermal growth factor (EGF) receptor contains multiple sites of phosphorylation on serine, threonine, and tyrosine residues. Because the biological responsiveness of the EGF receptor is regulated by phosphorylation at several of these sites, we studied the functional consequences of removal of the Thr669 and Ser671 phosphorylation sites using site-directed mutagenesis. The mutant EGF receptor expressed in mouse B82 cells displayed normal EGF binding and in vivo autophosphorylation and was fully active in biological signal transduction as measured by EGF-stimulated gene transcription. However, the EGF-dependent phosphorylation of an 85-kDa cellular substrate by the mutant receptor was impaired relative to the wild type receptor, indicating that the mutated region may specifically interact with this substrate. Endocytosis of the mutant receptor was also impaired as measured by both receptor down-regulation and ligand internalization studies. This was due to impaired uptake of the mutant receptor by the saturable, high affinity endocytic system. Several aspects of mutant receptor function were regulated normally by TPA, indicating a lack of interaction between the mutated phosphorylation sites and the nearby protein kinase C phosphorylation site Thr654. These results suggest that phosphorylation of the EGF receptor at Thr669 and Ser671 mediates interaction of the receptor with a specific tyrosine kinase substrate and is required for efficient ligand-induced receptor internalization.


Bacterial and Respiratory Viral Interactions in the Etiology of Acute Otitis Media in HIV-infected and HIV-uninfected South African Children.
Bacteria and respiratory viruses are implicated in the pathogenesis of acute otitis media (AOM); however, data from low-middle income countries are sparse. We investigated the etiology of AOM in HIV-infected (HIV+), HIV-uninfected (HIV-) and HIV-exposed clinically asymptomatic for HIV-infection (HEU) South African children. Children ≥3 months to <5 years of age with AOM were enrolled between May 2009 and April 2010 (NCT01031082). Middle ear fluid samples were cultured for bacteria; antibacterial susceptibility was done and serotyping undertaken for Streptococcus pneumoniae and Haemophilus influenzae. Nasopharyngeal aspirates were analyzed for respiratory viruses using immunofluorescence assay and polymerase chain reaction. Of 260 AOM episodes (HIV+:15; HIV-:182; HEU:63), bacteria were found in 54.6%, including Haemophilus influenzae (30.8%), 98.8% of which were nontypeable, and Streptococcus pneumoniae (20.4%), Staphylococcus aureus (15.8%), Moraxella catarrhalis (5.0%) and Streptococcus pyogenes (1.5%). Nonsusceptibility of Streptococcus pneumoniae to penicillin was 64.2%. Respiratory viruses were detected in 74.2% of cases. Human rhinovirus was most frequently detected (37.7%), followed by adenovirus (14.2%) and human bocavirus (11.5%) overall and irrespective of HIV status. Respiratory viruses were identified concurrently with S. pneumoniae, H. influenzae, M. catarrhalis (76.9-78.8%) and Staphylococcus aureus (63.4%) cultured from middle ear fluid, as well as in 72.0% of episodes negative for any bacteria. The study suggests that respiratory viruses and pathogenic bacteria play an important role in the development of AOM in children. A similar spectrum of pathogens was observed independently of HIV status. Vaccines targeting both nontypeable Haemophilus influenzae and S. pneumoniae may have a broad impact on AOM in South Africa.


Outstanding fluoride removal from aqueous solution by a La-based adsorbent.
A La-based adsorbent was prepared with La(NO3)3·6H2O, 2-methylimidazole and DMF via amide-hydrolysis and used for fluoride decontamination from aqueous water. The obtained adsorbent was lanthanum methanoate (La(COOH)3). The effects of pH value, initial F- concentration and interfering ions on defluoridation properties of as-prepared La(COOH)3 were assessed through batch adsorption tests. The adsorption kinetics, isotherm models and thermodynamics were employed to verify the order, nature and feasibility of La(COOH)3 towards fluoride removal. The results imply that La(COOH)3 is preferable for defluoridation over a wide pH range of 2 to 9 without interference. Simultaneously, the defluoridation process of La(HCOO)3 accords to the pseudo-second order model and Langmuir isotherm, revealing chemical adsorption is the main control step. The maximum fluoride capture capacities of La(COOH)3 at 30, 40 and 50 °C are 245.02, 260.40 and 268.99 mg g-1, respectively. The mechanism for defluoridation by La(COOH)3 was revealed by PXRD and XPS. To summarize, the as-synthesized La based adsorbent could serve as a promising adsorbent for defluoridation from complex fluoride-rich water.


Repair of a tear at the base of a blister-like aneurysm with suturing and an encircling clip: technical note.
An aneurysm can produce large defects in the parent vessel if the aneurysm tears at the neck of the vessel. The authors present a technique to repair a tear at the base of a blister-like aneurysm encountered during microsurgical clipping of an anterior wall aneurysm of the internal carotid artery. The repair technique involved suturing and covering the aneurysm with an encircling aneurysm clip. A large tear had destroyed the vessel's tubular structure, and repair was not sufficient using an encircling clip alone. Two microsuture stitches were placed on the tear, so that a split artery re-formed a tubular structure. The lesion was then covered with Surgicel (Ethicon, Inc., Somerville, NJ) and fibrin glue. When the Surgicel and fibrin glue were applied, the temporary clip on the distal internal carotid artery was removed for a moment, allowing retrograde blood flow to provide the counterforce necessary to maintain the vessel's tubular structure. An encircling clip was then applied to cover the entire circumference of the lesion. This method required only a short occlusion time for arterial repair, thus helping avoid ischemic complications. The patient awoke with transient hemiparesis, but recovery was prompt. This technique is useful for repairing an aneurysmal tear at its base, especially if the tear is large.


Uptake of adenosine in a marine bacterium is not an active transport process.
The uptake and intracellular interconversions of [8-14C]adenosine in a marine bacterium Vibrio harveyi were investigated under varying physiological conditions. The results indicated that in contrast with the current views, translocation of adenosine across the cytoplasmic membrane in Vibrio harveyi was not driven by respiration. The uptake of adenosine was dependent upon its intracellular utilization and was inhibited under conditions preventing its metabolic conversions.


Inflammatory response of TLR4 deficient spleen macrophages (CRL 2471) to Brucella abortus S19 and an isogenic ΔmglA deletion mutant.
Brucellosis is a worldwide distributed zoonosis caused by members of the genus Brucella. One of them, Brucella abortus, is the etiological agent of bovine brucellosis. With the attenuated strain B. abortus S19 a vaccine is available. However, both, virulence (safety) and the ability to induce a protective B and T cell response (efficacy) have to be tested in suitable assays before successful use in the field. For this purpose, several macrophage cell lines of various origins have been used while splenic macrophages are the preferred host cells in vivo. We here characterized the in vitro response of the murine splenic macrophage cell line CRL 2471(I-13.35) to B. abortus. This cell line still depends on the presence of colony-stimulating factor 1 (CSF1) and is derived from LPS resistant (TLR4 deficient) C3H/HeJ mice. For infection the vaccine strain B. abortus S19A as well as the formerly described isogenic deletion mutant B. abortus S19A ΔmglA 3.14 were used. While numbers of viable bacteria did not differ significantly between the vaccine strain and the deletion mutant at 6h post infection, a higher bacterial load was measured in case of the mutant at 24h and 48h after infection. This was also true, when IFNγ was used for macrophage activation. A comprehensive gene expression profile of macrophages was analysed 6 and 24h after infection by means of an RT-PCR based gene expression array. The mutant strain B. abortus S19A ΔmglA 3.14 elicited a stronger cellular response of the splenic macrophages as compared to the parental vaccine strain. This was most prominent for the pro-inflammatory cytokines IL-1α, IL-1β, TNF-α and IL6 as well as for the chemokine ligands CXCL1, CXCL2, CXCL10, CCL2, CCL5, CCL7, CCL17 and the co-stimulatory molecules CD40 and ICAM1. While these differences were also present in IFNγ-stimulated macrophages, an addition of IFNγ after infection not only resulted in a dramatic increase of the translation of the afore mentioned genes but also resulted in the translation of IFNß1, IL12ß, MIP1α and β (CCL3, CCL4), NOS2 (and SOD2) and FAS. The TLR4 deficient murine splenic macrophage cell line CRL 2471 was used for the first time for the characterization of macrophage-Brucella interaction to investigate the pre-immune phase of brucellosis in vitro. Typical pro-inflammatory cytokines and certain surface receptors were differentially induced by B. abortus S19 A and an isogenic ΔmglA deletion mutant in vitro. This model may be useful for further studies to characterize the inflammatory response of splenic macrophages to intracellular gram-negative bacteria avoiding cell responses to soluble LPS.


The application of QAE-Sephadex for the purification of two staphylococcal enterotoxins. I. Purification of enterotoxin C2.
A new method developed for purification of enterotoxin C2 from Staphylococcus aureus strain 361 consisted of four steps: batchwise adsorption from culture supernatant on QAE-Sephadex; gel filtration on Sephadex G-100; chromatography on QAE-Sephadex using a buffer of constant pH and molarity; and gel filtration using a volatile buffer of constant pH and molarity; and gel filtration using a volatile buffer as the eluting solvent. The purified enterotoxin appeared homogeneous by gel immunodiffusion, gel chromatography and in the analytical ultracentrifuge, although an apparent heterogeneity was noted on QAE-Sephadex chromatography and polyacrylamide disc electrophoresis at pH 4.5. The emetic dose, ED50, by intravenous route in cynomolgus monkeys was 0.04 mug/kg of animal weight. Upon treatment with sodium dodecylsulfate, beta-mercaptoethanol and urea, enterotoxin C2 separated into 3 bands in sodium dodecylsulfate-electrophoresis. One band mol. wt 29000, and two bands of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight were so close that they moved as a single zone. After elution from gels, the zone of lower molecular weight oligopeptides emerged as a single peak at the same position as untreated enterotoxin C2 during gel filtration with buffer lacking thiol and denaturant, and gave a reaction of complete identify to enterotoxin C2 in Ouchterlony immunodiffusion. The results suggest that enterotoxin C2 is a mixture composed of intact polypeptide chains, mol. wt 29000, and two fragments cleaved in the disulfide region of molecular weight of approx. 15400 and 12800 linked by the single disulfide bond in the toxin molecule. Amino acid analysis indicates that enterotoxin C2 consists of 255 amino acid residues.


Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants.
The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.


Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.
Language deficits frequently occur during the prodromal stages of Alzheimer's disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.


Enantioselective separation of biologically active basic compounds in ultra-performance supercritical fluid chromatography.
The enantioseparation of basic compounds represent a challenging task in modern SFC. Therefore this work is focused on development and optimization of fast SFC methods suitable for enantioseparation of 27 biologically active basic compounds of various structures. The influences of the co-solvent type as well as different mobile phase additives on retention, enantioselectivity and enantioresolution were investigated. Obtained results confirmed that the mobile phase additives, especially bases (or the mixture of base and acid), improve peak shape and enhance enantioresolution. The best results were achieved with isopropylamine or the mixture of isopropylamine and trifluoroacetic acid as additives. In addition, the effect of temperature and back pressure were evaluated to optimize the enantioseparation process. The immobilized amylose-based chiral stationary phase, i.e. tris(3,5-dimethylphenylcarbamate) derivative of amylose proved to be useful tool for the enantioseparation of a broad spectrum of chiral bases. The chromatographic conditions that yielded baseline enantioseparations of all tested compounds were discovered. The presented work can serve as a guide for simplifying the method development for enantioseparation of basic racemates in SFC.


The role of short-term visuo-spatial memory in control of rapid multi-joint prehensive movements.
How memorized visuo-spatial information influences motor control and whether this information is able to replace the feedback processing in cases of visual deprivation was studied using an unrestrained finger- and hand-movement paradigm. Nineteen right-handed subjects were asked to grasp and lift a small block with the index finger and thumb of the right hand, as quickly as possible. The efficiency of motor performance was analysed by measuring the grasping time derived from tangential velocity profiles of the fingertips. The data revealed significantly shorter grasping times under continuous visual guidance than during blind grasping. Grasping times increased under conditions with stepwise prolongation of visual deprivation time prior to the movement onset. The results support the general concept that within the first seconds of visual deprivation, stored visuo-spatial information can partly compensate for the lack of continuous visual feedback.


Mesothelial Stem Cells and Stromal Vascular Fraction for Skin Rejuvenation.
The use of stem cells in regenerative medicine and specifically facial rejuvenation is thought provoking and controversial. Today there is increased emphasis on tissue engineering and regenerative medicine, which translates into a need for a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue is currently recognized as an accessible and abundant source for adult stem cells. Cellular therapies and tissue engineering are still in their infancy, and additional basic science and preclinical studies are needed before cosmetic and reconstructive surgical applications can be routinely undertaken and satisfactory levels of patient safety achieved.


Association between intraoperative plantar regional oxygen saturation and acute kidney injury after cardiac surgery.
Acute kidney injury (AKI) is one of the most common complications after cardiac surgery, associated with increased mortality and morbidity. Near-infrared spectroscopy (NIRS) continuously measures regional oxygen saturation(rSO2) in real-time. This exploratory retrospective study aimed to investigate the association between intraoperative plantar rSO2 and postoperative AKI in cardiac surgery patients. Between August 2019 and March 2021, 394 patients were included. Plantar and cerebral rSO2 were monitored using NIRS intraoperatively. The primary outcome was AKI within 7 postoperative days. The nonlinear association between plantar rSO2, cerebral rSO2, and mean arterial blood pressure (MBP) and AKI was assessed, and plantar rSO2<45% was related to an increased risk of AKI. Multivariable logistic regression analyses revealed that longer duration and higher area under the curve below plantar rSO2<45% and MBP<65 mmHg were more likely to be associated with increased odds of AKI. In additional multivariable regression analyses, association between plantar rSO2<45% and AKI was still maintained after adjusting the duration or AUC of MBP<65 mmHg as a covariate. Cerebral rSO2 levels were not associated with AKI. Independent of MAP, intraoperative plantar rSO2 was associated with AKI after cardiac surgery. However, intraoperative cerebral rSO2 was not associated with AKI. Intraoperative plantar rSO2 monitoring may be helpful in preventing AKI.


WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation.
WNT signaling controls many biological processes including cell differentiation in metazoans. However, how WNT reprograms cell identity is not well understood. We have investigated the potential role of cellular metabolism in WNT-induced osteoblast differentiation. WNT3A induces aerobic glycolysis known as Warburg effect by increasing the level of key glycolytic enzymes. The metabolic regulation requires LRP5 but not β-catenin and is mediated by mTORC2-AKT signaling downstream of RAC1. Suppressing WNT3A-induced metabolic enzymes impairs osteoblast differentiation in vitro. Deletion of Lrp5 in the mouse, which decreases postnatal bone mass, reduces mTORC2 activity and glycolytic enzymes in bone cells and lowers serum lactate levels. Conversely, mice expressing a mutant Lrp5 that causes high bone mass exhibit increased glycolysis in bone. Thus, WNT-LRP5 signaling promotes bone formation in part through direct reprogramming of glucose metabolism. Moreover, regulation of cellular metabolism may represent a general mechanism contributing to the wide-ranging functions of WNT proteins.


Purification of a protein associated with human bronchogenic squamous-cell carcinoma.
A heteroantiserum raised in rabbits to extracts of human squamous-cell carcinoma of the lung which exhibited marked tumour specificity was used to monitor the fractionation and isolation of a tumour-associated component of the extract. KC1 extracts of pools of both normal lung and bronchogenic squamous-cell carcinoma were subjected to a series of purification steps involving acid precipitation, salting out, DEAE chromatography and preparative polyacrylamide-gel electrophoresis. At each stage, fractions were tested for their ability to react in the complement-fixation assay with the antiserum. A protein was ultimately isolated which did not appear to be present at detectable levels in an equivalent fraction of normal lung extract, reacted with the heteroantiserum, and appeared to be present in all extracts of squamous-cell carcinoma.


Multi-modality imaging findings of splenic hamartoma: a report of nine cases and review of the literature.
To investigate the presentation of splenic hamartomas (SHs) on ultrasonography (US), CT and MRI. Nine patients (5 males and 4 females, mean age, 52.8 years) with pathologically proven SHs were included in this study. US, CT and MRI images were analyzed retrospectively, and imaging features were correlated with pathological findings. SHs appeared solitary lesion (n = 8) and multiple lesions (n = 1) in the present study. (1) In 8 cases of solitary lesion, the lesions appeared as solid nodules or masses with well-defined margins and varying echogenicity (hyperecho = 5, hypoecho = 2, strong echo = 1) on ultrasound. The lesions showed iso-attenuation (n = 3) or slightly hypo-attenuation (n = 4) on unenhanced CT, and calcification were revealed in 3 lesions. MRI showed isointensity (n = 3) or hypointensity (n = 2) on the T1-weighted image, and heterogeneous hypointensity (n = 2), slightly hyperintensity (n = 2) and hyperintensity (n = 1) on the T2-weighted image. The enhanced patterns of SHs showed mild diffuse heterogeneous enhancement (n = 6) and prominent enhancement (n = 1) during arterial phase and above 7 lesions were demonstrated progressive enhancement at delayed phase on enhanced CT. One lesion without any enhancement was revealed in another patient. (2) One case of multiple lesions included 1 cystic lesion with irregular calcification and 7 solid lesions with progressive enhancement on CT images. Combination of a variety of imaging modalities could more fully reflect the pathological characteristics and contribute to the diagnosis of SH.


Pain Relief for Acute Urolithiasis: The Case for Non-Steroidal Anti-Inflammatory Drugs.
Pain from renal colic is often severe and incapacitating. Many patients require emergent hospitalization and aggressive analgesia to relieve such discomfort. For many years, the optimal analgesic strategy has been sought to manage such severe pain. One of the mainstays of therapy for acute renal colic is with non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the mechanism by which NSAIDs allow pain relief in renal colic, the evidence for their use in this condition, and the use of NSAIDs combined with other agents in renal colic.


Significance of the distribution of 57Co-vitamin B12 in Spirometra mansonoides (Cestoidea) during growth and differentiation in mammalian intermediate and definitive hosts.
The distribution of labeled cyanocobalamin (CN-[57Co]Cbl = [57Co]-vitamin B12) in pleurocercoids and adult tapeworms of Spirometra mansonoides was studied during development in mice 22 days days PI, respectively. Plerocercoid scolices, obtained by cutting away their bodies or by in vitro enzymatic dissolution of the bodies, were pulsed with CN- magnitude of 57Co Cbl for 1h at 37 degrees C and reimplanted subcutaneously into mice or given per os to cats. In regenerated plerocercoids, the highest concentration of magnitude of 57Co Cbl occurred in the scolex and then decreased posteriorly in the newly-formed tissues of the body. Approximately 60% of the total magnitude of 57Co Cbl present remained concentrated in the scolex following body regeneration plerocercoids and adult tapeworms of Spirometra mansonoides was studied during development in mice 22 days post-infection (PI) and in cats 16 days PI, respectively. Plerocercoid scolices, obtained by cutting away their bodies or by in vitro enzymatic dissolution of the bodies, were pulsed with CN-[57Co]Cbl for 1 h at 37 degrees C and reimplanted subcutaneously into mice or given per os to cats. In regenerated plerocercoids, the highest concentration of [57Co]Cbl occurred in the scolex and then decreased posteriorly in the newly-formed tissues of the body. Approximately 60% of the total [57Co]Cbl present remained concentrated in the scolex following body regeneration for up to 109 days PI. This high [57Co]Cbl concentration in the plerocercoid scolex was bound to protein and appears to be maintained by a complex homeostatic mechanism in association with directional transport of [57Co]Cbl to the scolex with ultimate depletion along the length of the body.(ABSTRACT TRUNCATED AT 250 WORDS)


Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells.
Intact mycobacteria and mycobacterial cell wall extracts have been shown to inhibit the growth of human and murine bladder cancer. Their mechanism of action is, however, poorly understood. Mycobacterium phlei mycobacterial cell complex (MCC) is a cell wall preparation that has mycobacterial DNA in the form of short oligonucleotides complexed on the cell wall surface. In this study, we have investigated the possibility that MCC has anti-cancer activity that is mediated by two different mechanisms--a direct effect on cancer cell proliferation and viability and an indirect effect mediated by the production of interleukin 12 (IL-12), a cytokine known to possess anti-cancer activity. We have found that, although MCC is a potent inducer of IL-12 and IL-6 synthesis in monocytes and macrophages either in vitro or in vivo, it is unable to induce the synthesis of either IL-12, IL-6 or granulocyte-macrophage colony-stimulating factor (GM-CSF) by the human transitional bladder cancer cell lines HT-1197 and HT-1376. MCC is not directly cytotoxic towards these cancer cells, but induces apoptosis as determined by nuclear DNA fragmentation and by the release of nuclear mitotic apparatus protein. Mycobacterium phlei DNA associated with MCC is responsible for the induction of apoptosis. Our results indicate that MCC directly effects bladder cancer cells by inhibiting cellular proliferation through the induction of apoptosis, and has the potential for an indirect anti-cancer activity by stimulating cancer-infiltrating monocytes/macrophages to synthesize IL-12.


Impact of postoperative weight gain on complications after liver surgery.
Recent data has suggested that excessive perioperative weight gain may be associated with adverse outcomes after abdominal surgery, but this observation remains unexplored following liver surgery. The present study aimed to investigate the predictive value of perioperative weight fluctuation in predicting complications after liver surgery. Retrospective monocentric analysis of consecutive patients undergoing liver surgery between 2010 and 2016. Patients without available perioperative weight were excluded. Test variable was postoperative weight change (ΔWeight) measured on day 2 (POD2). Primary outcome was postoperative major morbidity according to Clavien classification (grades III-IV). Secondary outcomes were overall complications, Comprehensive Complication Index (CCI) and length of hospital stay (LoS). Area under the receiver operating characteristic curve (AUROC) and logistic regression with multivariable analysis were performed. A total of 181 patients met the inclusion criteria. Major and overall postoperative complications were reported in 25 (14%) and 87 (48%) patients, respectively. On POD2, median ΔWeight was 2.6 Kg (IQR: 1.1-4.0). Patients with major complications showed increased ΔWeight of 4.2 Kg (IQR: 2.7-5.7), compared to 2.3 Kg (IQR: 0.9-3.7) in patients without major complications (p < 0.001). AUROC of ΔWeight for major complications was 0.74, determining an optimal cut-off of 3.5 Kg, which yielded a negative predictive value of 94%. Multivariable analysis identified ΔWeight ≥3.5 Kg as independent predictor of major complications (OR, 4.73; 95% CI, 1.51-14.80; p = 0.008). ΔWeight ≥3.5 Kg was independently associated with major complications after liver surgery. Perioperative fluctuation of weight appears as an important predictor of adverse outcomes after liver surgery.


Diurnal Regulation of the Orexin/Hypocretin System in Mice.
A prominent feature of the hypothalamic neuropeptides orexins/hypocretins is their role in the regulation of sleep-wake behavior. While there is strong evidence for a diurnal (i.e. 24-h) rhythmicity of the expression of prepro-orexin (PPO) and its cleavage products, orexin A and B, it is not known whether orexin receptors are also subject to diurnal regulation. Here we ask whether besides the regulation of PPO the expression of the orexin receptor subtypes OX1R and OX2R varies over 24 hours in the mouse brain. The mRNA levels of PPO, OX1R, and OX2R as well as of various clock genes were analyzed over 24 hours in the hypothalamus, cortex, and adrenal glands of male mice using qPCR. We found a significant diurnal regulation of the mRNA levels of PPO as well as both orexin receptor subtypes in the brain, while no regulation was observed in adrenal glands. While in the cortex the mRNA levels of both OX1R and OX2R showed a significant diurnal regulation, in the hypothalamus, only the OX2R mRNA expression was subject to a diurnal rhythm. The expression of both orexin receptor subtypes significantly correlated with that of clock genes. Remarkably, the expression pattern of OX2R showed a strong and highly significant correlation with that of the clock gene Bmal1 in the cortex and hypothalamus. These results suggest that the rhythmic expression of orexin receptors is linked to clock gene expression and that OX2R may potentially play a role in the timing of sleep-wake behavior.


Some biochemical changes in the ageing heart of the male garden lizard.
The SDH activity of cardiac muscle homogenates reached a peak level in the middle-aged lizards followed by a decline in the old. The inhibition of enzyme activity by oxaloacetate, a competitive inhibitor, declined with advancing age. Both salt and acid solubilities of cardiac muscle collagen declined with advancing age of the lizard. An age-related accumulation of total collagen was evident per organ basis but a reverse trend prevailed on the basis of relative value. Quantitative estimations revealed a loss of DNA in ageing heart; per organ basis the DNA content increased till the lizards were middle-aged showing no further change thereafter. On the other hand the RNA content and the RNA/DNA ratio of cardiac muscle declined between young and middle-aged followed by a rise in the old lizards. The protein content increased with rise in fresh weight of heart during ageing.


Integrating a community-based continuous mass dog vaccination delivery strategy into the veterinary system of Tanzania: A process evaluation using normalization process theory.
Sustained vaccination coverage of domestic dog populations can interrupt rabies transmission. However, challenges remain including low dog owner participation, high operational costs associated with current (centralized and annually delivered (pulse)) approaches and high dog population turnover. To address these challenges an alternative (community-based continuous mass dog vaccination (CBC-MDV)) approach was designed. We investigated the potential for successful normalization of CBC-MDV into routine practice within the context of local communities and the veterinary system of Tanzania. In a process evaluation of a pilot implementation of CBC-MDV, we conducted in-depth interviews with implementers and community leaders (n = 24), focus group discussion with implementers and community members (n = 12), and non-participant observation (n = 157 h) of delivery of the intervention components. We analyzed these data thematically drawing on the normalization process theory, to assess factors affecting implementation and integration. Implementers and community members clearly understood the values and benefits of the CBC-MDV, regarding it as an improvement over the pulse strategy. They had a clear understanding of what was required to enact CBC-MDV and considered their own involvement to be legitimate. The approach fitted well into routine schedules of implementers and the context (infrastructure, skill sets and policy). Implementers and community members positively appraised CBC-MDV in terms of its perceived impact on rabies and recommended its use across the country. Implementers and community members further believed that vaccinating dogs free of charge was critical and made community mobilization easier. However, providing feedback to communities and involving them in evaluating outcomes of vaccination campaigns were reported to have not been done. Local politics was cited as a barrier to collaboration between implementers and community leaders. This work suggests that CBC-MDV has the potential to be integrated and sustained in the context of Tanzania. Involving communities in design, delivery and monitoring of CBC-MDV activities could contribute to improving and sustaining its outcomes.


A case of severe ovarian hyperstimulation in a healthy oocyte donor.
To report an unexpected case of severe ovarian hyperstimulation syndrome (OHSS) and to compare E2 levels and number of follicles to other oocyte donors. Private assisted reproduction technology center. Healthy oocyte donors with normal menstrual cyclicity. Prophylactic and therapeutic use of human serum albumin infusions. The clinical development of signs and symptoms of severe OHSS. More than 60% of other oocyte donors had higher E2 levels and 12% had higher number of follicles without associated OHSS. The risk of developing severe OHSS cannot be predicted accurately to be low even in the absence of "risk factors."


A comparative analysis of complete mitochondrial genomes among Hexapoda.
With respect to bauplan radiation, species and taxa richness, hexapods have an unassailable lead. But still, the phylogenetic relationships among the orders and infraorders remain a matter of discussion. The rapidly increasing mitochondrial genome sequences from diverse insect species provide the opportunity to explore miscellaneous evolutionary questions in the superclass Hexapoda. A combined primary sequence analyses of the complete available data set has not yet been performed. Until now phylogenetic analyses of subsets of selected taxa resulted to strong supported topologies showing in some instances discrepancies between morphological and nuclear data. This circumstance started the discussion about the limits of complete mitochondrial genomes for inferring deep hexapod relationships. By using the hitherto densest taxon sampling of Hexapoda our analyses resulted in discrepancies to the current phylogenetic hypotheses based on morphological and nuclear data, e.g. monophyly of hexapods and some hexapods orders, e.g. Diptera, Hemiptera and Orthoptera. Nonetheless, compared to previously published studies that strongly support systematically erroneous groups using a sparse taxon sampling, our analyses had no support for theses discrepancies. Consequently, we highly recommend interpreting mt-genome based phylogenies with incomplete representation of major orders/taxa particularly for hexapods with cautions although the inferred relationships are highly supported.


Critical adsorption of multiple polyelectrolytes onto a nanosphere: splitting the adsorption-desorption transition boundary.
Employing extensive Monte Carlo computer simulations, we investigate in detail the properties of multichain adsorption of charged flexible polyelectrolytes (PEs) onto oppositely charged spherical nanoparticles (SNPs). We quantify the conditions of critical adsorption-the phase-separation curve between the adsorbed and desorbed states of the PEs-as a function of the SNP surface-charge density and the concentration of added salt. We study the degree of fluctuations of the PE-SNP electrostatic binding energy, which we use to quantify the emergence of the phase subtransitions, including a series of partially adsorbed PE configurations. We demonstrate how the phase-separation adsorption-desorption boundary shifts and splits into multiple subtransitions at low-salt conditions, thereby generalizing and extending the results for critical adsorption of a single PE onto the SNP. The current findings are relevant for finite concentrations of PEs around the attracting SNP, such as the conditions for PE adsorption onto globular proteins carrying opposite electric charges.


Stability of β-carotene during baking of orange-fleshed sweet potato-wheat composite bread and estimated contribution to vitamin A requirements.
Orange-fleshed sweet potato (OFSP) is known to be a rich source of β-carotene, a precursor of vitamin A and a potential tool for fighting vitamin A deficiency (VAD) in developing countries. OFSP flour was incorporated into wheat flour at 10, 20 and 30% (w/w) substitution levels. The stability of β-carotene during baking and the contribution of OFSP-wheat composite breads to vitamin A requirements were evaluated. The retention of all-trans-β-carotene in breads containing 10, 20 and 30% OFSP flour was 62.7, 71.4 and 83% respectively, after baking. Breads containing 20% and 30% OFSP flour could be used for the eradication of vitamin A deficiency as they were found to meet 29 and 89.2% (100g portion) respectively, of the recommended dietary allowance (RDA) of vitamin A amongst children aged 3-10years. The latter would meet nearly a half of the RDA of vitamin A for pregnant and lactating women.


Cardiac function during heat stress: impact of short-term passive heat acclimation.
A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 men/1 woman, 29 ± 6 yr old), pre and post 7 days of controlled hyperthermia. HR (P = 0.61), stroke volume (P = 0.99), and cardiac output (P = 0.99), were similar on days 1 and 7 of HA. Core (pre: 38.17 ± 0.42, post: 38.15 ± 0.27°C, P = 0.95) and mean skin (pre: 38.24 ± 0.41, post: 38.51 ± 0.29°C, P = 0.17) temperatures were similar during hyperthermic echocardiographic assessments. Cardiac systolic function was unaffected by HA (P ≥ 0.10). HA attenuated the decrease in end-diastolic volume (pre: -18 ± 18, post: -12 ± 19 mL, P = 0.05), accentuated the greater atrial contribution to diastolic filling (pre: +11 ± 5, post: +14 ± 5%, P = 0.02), and attenuated the increase in left atrial reservoir strain rate (pre: +1.5 ± 1.2, post: +0.8 ± 0.8 1/s, P = 0.02) during heating. Nonetheless, there were no differences in HR (pre: 106 ± 12, post: 104 ± 12 beats/min, P = 0.50), stroke volume (pre: 65 ± 15, post: 68 ± 13 mL, P = 0.55), or cardiac output (pre: 6.9 ± 2.0, post: 7.1 ± 1.7 L/min, P = 0.70) during passive heating. Short-term controlled hyperthermia HA results in limited adaptations of cardiac function during passive heating.NEW & NOTEWORTHY A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.