Differences in Obesity Prevalence by Demographic Characteristics and Urbanization Level Among Adults in the United States, 2013-2016.
Differences in obesity by sex, age group, race and Hispanic origin among US adults have been reported, but differences by urbanization level have been less studied. To provide estimates of obesity by demographic characteristics and urbanization level and to examine trends in obesity prevalence by urbanization level. Serial cross-sectional analysis of measured height and weight among adults aged 20 years or older in the 2001-2016 National Health and Nutrition Examination Survey, a nationally representative survey of the civilian, noninstitutionalized US population. Sex, age group, race and Hispanic origin, education level, smoking status, and urbanization level as assessed by metropolitan statistical areas (MSAs; large: ≥1 million population). Prevalence of obesity (body mass index [BMI] ≥30) and severe obesity (BMI ≥40) by subgroups in 2013-2016 and trends by urbanization level between 2001-2004 and 2013-2016. Complete data on weight, height, and urbanization level were available for 10 792 adults (mean age, 48 years; 51% female [weighted]). During 2013-2016, 38.9% (95% CI, 37.0% to 40.7%) of US adults had obesity and 7.6% (95% CI, 6.8% to 8.6%) had severe obesity. Men living in medium or small MSAs had a higher age-adjusted prevalence of obesity compared with men living in large MSAs (42.4% vs 31.8%, respectively; adjusted difference, 9.8 percentage points [95% CI, 5.1 to 14.5 percentage points]); however, the age-adjusted prevalence among men living in non-MSAs was not significantly different compared with men living in large MSAs (38.9% vs 31.8%, respectively; adjusted difference, 4.8 percentage points [95% CI, -2.9 to 12.6 percentage points]). The age-adjusted prevalence of obesity was higher among women living in medium or small MSAs compared with women living in large MSAs (42.5% vs 38.1%, respectively; adjusted difference, 4.3 percentage points [95% CI, 0.2 to 8.5 percentage points]) and among women living in non-MSAs compared with women living in large MSAs (47.2% vs 38.1%, respectively; adjusted difference, 4.7 percentage points [95% CI, 0.2 to 9.3 percentage points]). Similar patterns were seen for severe obesity except that the difference between men living in large MSAs compared with non-MSAs was significant. The age-adjusted prevalence of obesity and severe obesity also varied significantly by age group, race and Hispanic origin, and education level, and these patterns of variation were often different by sex. Between 2001-2004 and 2013-2016, the age-adjusted prevalence of obesity and severe obesity significantly increased among all adults at all urbanization levels. In this nationally representative survey of adults in the United States, the age-adjusted prevalence of obesity and severe obesity in 2013-2016 varied by level of urbanization, with significantly greater prevalence of obesity and severe obesity among adults living in nonmetropolitan statistical areas compared with adults living in large metropolitan statistical areas.


NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons.
Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS). Heterozygous loss-of-function mutations in NEK1 (NIMA-related kinase 1) have also been recently found to cause ALS. NEK1 codes for a multifunctional protein, crucially involved in mitotic checkpoint control and DDR. To resolve pathological alterations associated with NEK1 mutation, we compared hiPSC-derived motoneurons carrying a NEK1 mutation with mutant C9orf72 and wild type neurons at basal level and after DNA damage induction. Motoneurons carrying a C9orf72 mutation exhibited cell specific signs of increased DNA damage. This phenotype was even more severe in NEK1c.2434A>T neurons that showed significantly increased DNA damage at basal level and impaired DDR after induction of DNA damage in an maturation-dependent manner. Our results provide first mechanistic insight in pathophysiological alterations induced by NEK1 mutations and point to a converging pathomechanism of different gene mutations causative for ALS. Therefore, our study contributes to the development of novel therapeutic strategies to reduce DNA damage accumulation in neurodegenerative diseases and ALS.


Which thyroid cancer patients need periodic stimulation tests?
Recurrences are frequent in thyroid cancer patients and long-term follow-up is therefore necessary. We evaluated the yield of rhTSH stimulation in three groups of patients, classified according to the UICC/TNM risk stratification and the results of first follow-up testing. The study population comprised 129 patients referred for rhTSH testing. All had undergone first follow-up testing after thyroid hormone withdrawal (off-T4) within 1 year of 131I ablation. Negative first follow-up testing was defined as Tg <2 ng/ml and no neck uptake on 131I diagnostic whole-body scan. Seventy-five patients had stage I thyroid cancer and negative first follow-up testing (group A), 19 had stage I disease and positive first follow-up testing (group B), and 35 had stage II-IV disease (group C). RhTSH stimulation was performed an average of 6 years after first follow-up testing. 131I diagnostic scanning after rhTSH was negative in all 75 group A patients. Only one group A patient had detectable Tg after rhTSH injection (1.5 ng/ml), but Tg had also been detected at baseline in this patient (1.45 ng/ml). Given the absence of a response to stimulation, suggesting an interference, Tg was reassessed with a different technique and proved to be undetectable (<0.1 ng/ml). Stimulation with rhTSH in group B showed residual Tg in seven patients and residual 131I uptake in the thyroid bed in two patients, but none of these patients had signs of disease progression. Five group C patients (14%) had a positive rhTSH test result, and this was suggestive of disease progression in at least two cases. The first follow-up testing is essential for prognostic classification after 131I ablation of thyroid cancer. In stage I patients, undetectable Tg and negative 131I scan 1 year after ablation define a large population of subjects who have a very low risk of recurrence and who do not require further stimulation tests. In contrast, periodic rhTSH stimulation tests appear useful in higher-risk patients.


Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data.
The objective of this work was to substantially review all preclinical and clinical data on phytochemicals, such as genistein, lycopene, curcumin, epigallocatechin-gallate, and resveratrol, in terms of their effects as a potential treatment of prostate cancer. It is known, that prostate cancer patients increasingly use complementary and alternative medicines in the hope of preventing or curing cancer. The preclinical data for the phytochemicals presented in this review show a remarkable efficacy against prostate cancer cells in vitro, with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, well-conducted animal experiments support the belief that these substances might have a clinical activity on human cancer. However, it is impossible to make definite statements or conclusions on the clinical efficacy in cancer patients because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardised drug formulation. Although some results from these clinical studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. At present, there is no convincing clinical proof or evidence that the cited phythochemicals might be used in an attempt to cure cancer of the prostate.


Exposure of arc-furnace-plant workers to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs).
This study aimed to evaluate serum polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels in electric-arc-furnace workers according to their corresponding occupational exposure. In addition, the ambient PCDD/Fs of the work environment were measured to provide additional support for the exposure and accumulation inside the electric arc furnace. The ambient PCDD/F concentrations inside the electric arc furnace were 1.557-1.917 pg-TEQ/Nm(3), 5-24 folds higher than those outside (0.080-0.385 pg-TEQ/N m(3)). In addition, higher average serum levels were measured in the workers with high occupational dioxin exposure (24.0 pg WHO-TEQ/g lipid) than in those with lower occupational dioxin exposure (13.8 pg WHO-TEQ/g lipid). Higher PCDFs/PCDDs ratios were found in serum samples from high-exposure groups than in low-exposure groups. The higher ratio of PCDFs/PCDDs was also found in ambient samples consistent with other metallurgical processes reported previously. Our results suggest that PCDD/Fs exposure exits in the smelting process of electric arc furnace, and the occupational hygiene should be taken more seriously concern in that workplace.


A pilot study of chronomodulated infusional 5-fluorouracil chemoradiation for pancreatic cancer.
Dose limiting acute toxicity from chemoradiation for pancreatic cancer occurs in 15% -20% of patients treated with post-operative adjuvant therapy. Reported here is a pilot study using chronomodulated infusional 5-fluorouracil (5-FU) chemoradiation (CIC) for pancreatic cancer, a treatment designed to reduce normal tissue toxicity and maintain efficacy, with specific evaluation of acute and late morbidity, patterns of disease progression, and survival. Twenty-three patients with adenocarcinoma of the pancreas were treated with 5-FU CIC between January 1997 and September 1999. The median age was 64, and there were 9 males and 14 females. Six patients were considered unresectable and seventeen others were treated post-operatively. The median external beam irradiation dose was 50.4 Gy. 5-FU infusion was given five days per week (300 mg/m2/d) and the median total dose was 8.4 g/m2. The chronomodulated 5-FU infusion consists of a low basal infusion rate for 16 hours followed by an eight-hour escalating-deescalating infusion peaking at 10 p.m. All patients were followed from the time of initial diagnosis until last follow-up or death; the median follow-up was 16 months. No RTOG grade 3 or 4 hematologic toxicity occurred. Twelve of seventeen patients treated postoperatively have been controlled locally, and seven patients have no evidence of disease. The median survival is 28 months and one-year actuarial survival is 88% in the group of resected patients. The 6 patients treated for unresectable disease have a median survival of 13 months. Acute toxicity of 5-FU CIC appears to be less frequent and less severe than that reported with flat infusional or bolus 5-FU based chemoradiation used for adjuvant post-operative therapy for pancreatic cancer. This method may warrant further examination, as it may be attractive for the elderly or those who cannot tolerate the toxicity associated with standard post-operative treatment protocols.


Distinct subthalamic coupling in the ON state describes motor performance in Parkinson's disease.
Cross-frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross-frequency interactions across three consecutive cycles over unique 24-hour-long recordings. Identifying neurobiomarkers for PD can drive the development of novel personalized treatments by providing objective assessment of impairment. In particular, distinct frequency bands in LFP recordings and their interaction with one another have been shown to modulate with dopaminergic medication and thus, proposed as such biomarkers. We recorded local field potentials 3 weeks postoperatively from externalized leads in 9 patients and correlated the neural patterns with improvements in motor signs over three medication intake cycles. We used two modalities to assess symptoms in the unmedicated OFF and the l-dopa-induced motor ON state: a subsection of the UPDRS and a keyboard tapping score measuring bradykinesia. In the OFF state, the amplitude of high-frequency oscillations in the 200- to 300-Hz range was coupled with the phase of low-beta (13-22 Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high-beta (22-30 Hz) and high-frequency oscillations in the 300- to 400-Hz range had significantly greater improvement in bradykinesia, according to the keyboard scores. Observing diminished coupling in the ON state, previous studies have hypothesized that the sole existence of coupling in STN has an "impeding" effect on normal processes, and thus it was considered to be pathological. In contrast, our observation of ON state coupling at distinct frequencies associated with the improvements in motor features suggest that the underlying mechanism of coupling might have impeding or enhancing effects depending on the coupled frequencies. © 2019 International Parkinson and Movement Disorder Society.


Correlates of caregiver burden among family caregivers of older Korean Americans.
Despite the rapid growth of older ethnic minority populations, knowledge is limited about informal caregiving among these groups. Our aim was to identify correlates of caregiver burden among family caregivers of older Korean Americans (KAs). A cross-sectional survey collected data from 146 KA caregivers. Using a modified stress-appraisal model, we examined background and context characteristics (caregiver sex, relationship to care recipient, college education, English proficiency, time in caregiving role, family support network, friend support network), a primary stressor (care recipient functional dependency), a primary appraisal (caregiving hours), and resources (family agreement, care management self-efficacy, service use self-efficacy) as potential correlates of caregiver burden. Interactions between the primary stressor, primary appraisal, and resources were also tested. Being female and the care recipient's spouse were associated with higher burden. Conversely, a larger family support network, greater family agreement, and greater care management self-efficacy were associated with lower burden. A significant interaction was detected between functional dependency and family agreement; higher levels of family agreement moderated the association between care recipient functional dependency and caregiver burden. Interventions to reduce caregiver burden in KA caregivers may be more effective if they include approaches specifically designed to build family support, improve family agreement, and increase caregivers' self-efficacy.


Early postoperative seizures after posterior fossa surgery.
A review is reported of the seizure incidence in 726 patients who underwent 740 posterior fossa operations via a suboccipital craniectomy without prophylactic anticonvulsant agents. Thirteen patients (1.8%) experienced seizures within 2 weeks postoperatively. Five of these patients (0.7% of the series) had seizures within 24 hours after operation. The incidence was highest for patients with medulloblastoma (7.2%) followed by those with astrocytoma (2.3%). Also, a higher percentage was found in patients with preoperative ventriculoperitoneal shunt or intraoperative ventriculostomy (2.7%) than in those without (1%), but the difference was not statistically significant. Metabolic acidosis (80%) and hyponatremia (20%) were the major causes of the seizures that developed within 24 hours after operation. Follow-up computerized tomography showed no definite lesion in these patients. Hydrocephalus (75%) and supratentorial hemorrhage remote from the operative site (25%) were detected in the patients who developed seizures between the 2nd and 14th postoperative day. Two of these patients also had postoperative bacterial meningitis. This review suggests that seizures are a possible complication in the early postoperative period after suboccipital craniectomy for posterior fossa lesions.


Using a snowflake data model and autocompletion to support diagnostic coding in acute care hospitals.
Efficient and adequate coding is essential for all hospitals to optimize funding, follow activity, and perform epidemiological studies. We propose an autocompletion method for optimizing diagnostic coding in acute care hospitals. Using a terminology snowflake model integrating SNOMED 3.5 and ICD-10 codes, autocompletion algorithms generate a list of diagnostic expressions from partial input concepts. A general autocompletion component has been developed and tested on a set of inpatient summary reports. Concepts expressed as strings of three or four characters return a noisy list of diagnostic labels or codes. Concepts expressed as groups of strings return lists that are semantically close to the labels present in hospital reports. The most pertinent information lies in the length of the expressions entered. Autocompletion can be a complementary tool to existing coding support systems.


Making the Most of Mealtimes (M3): effect of eating occasions and other covariates on energy and protein intake among Canadian older adult residents in long-term care.
Food intake varies among long-term care (LTC) residents and, as a result, some residents are at risk for protein-energy malnutrition and its consequences, such as sarcopenia. The present study aimed to determine whether eating occasions, as well as other factors that may vary with eating occasions (e.g. family/volunteer presence), were associated with energy and protein intake at meals and snacks. The present study comprised a secondary analysis of the cross-sectional Making the Most of Mealtimes study, including 630 residents (median age 88.00 years, range 62-107 years; 197 males) from 32 Canadian LTC homes. An analysis of variance compared protein and energy intake at meals and snacks. Mixed repeated measures linear regression testing for meal and relevant covariates (e.g. family/volunteer presence) was also conducted. Energy and protein intake was significantly associated with eating occasions (F = 44.31, P < 0.001; F = 12.72, P < 0.001), with the greatest energy intake at breakfast, and the greatest protein intake at dinner. Regression analysis confirmed these findings when considering other factors. Covariates associated with higher intake included: being male (+79 kcal; +3.4 g protein), living on a dementia care unit (+39 kcal; +2.1 g protein) and family/volunteer presence at meals (+58 kcal; +2.5 g protein). Intake was lowest in the oldest age group (-59 kcal; -3.6 g protein) and for those sometimes requiring eating assistance (-36 kcal; -2.0 g protein). Energy and protein intake appears to be associated with eating occasions. Based on these exploratory findings, LTC homes may consider providing more protein-dense foods at breakfast. Protein and energy dense snacks could also be used more extensively to support intake.


Computational investigation of hysteresis and phase equilibria of n-alkanes in a metal-organic framework with both micropores and mesopores.
Adsorption hysteresis is a phenomenon related to phase transitions that can impact applications such as gas storage and separations in porous materials. Computational approaches can greatly facilitate the understanding of phase transitions and phase equilibria in porous materials. In this work, adsorption isotherms for methane, ethane, propane, and n-hexane were calculated from atomistic grand canonical Monte Carlo (GCMC) simulations in a metal-organic framework having both micropores and mesopores to better understand hysteresis and phase equilibria between connected pores of different size and the external bulk fluid. At low temperatures, the calculated isotherms exhibit sharp steps accompanied by hysteresis. As a complementary simulation method, canonical (NVT) ensemble simulations with Widom test particle insertions are demonstrated to provide additional information about these systems. The NVT+Widom simulations provide the full van der Waals loop associated with the sharp steps and hysteresis, including the locations of the spinodal points and points within the metastable and unstable regions that are inaccessible to GCMC simulations. The simulations provide molecular-level insight into pore filling and equilibria between high- and low-density states within individual pores. The effect of framework flexibility on adsorption hysteresis is also investigated for methane in IRMOF-1.


Neutrophil-to-lymphocyte ratio shows faster changing kinetics than C-reactive protein after total hip and knee arthroplasty.
Total hip arthroplasty (THA) and total knee arthroplasty (TKA) induce inflammatory reactions, which can be described by changes in the neuroendocrine, cellular, protein, and cytokine systems. The aim of this study was to document the normal distribution pattern of the neutrophil-to-lymphocyte ratio (NLR) after THA and TKA and to compare it with postoperative C-reactive protein (CRP) patterns. Changes in serum CRP levels, neutrophil count, and lymphocyte count were measured before and during the first 5 postoperative days in a prospective study performed on 387 patients undergoing total hip or knee arthroplasty. Mean CRP levels in patients undergoing THA were 7.7 mg/L, 184.8 mg/L, and 115.9 mg/L, respectively, at Days 0, 3 and 5. The mean NLR of patients undergoing THA was 2.9, 3.6, and 2.7, respectively, at Days 0, 3, and 5. Mean CRP levels in patients undergoing TKA were 7.8 mg/L, 192.6 mg/L, and 108.6 mg/L, respectively, at Days 0, 3 and 5. The mean NLR of patients undergoing TKA was 2.8, 3.4, and 2.6, respectively, at Days 0, 3, and 5. When comparing the preoperative value and the Day 3 value, CRP levels increased more than the NLR (almost a 24-fold increase in mean CRP values vs. a 1.2-fold increase in mean NLR values). In both groups, the NLR returned to preoperative values by the 5th postoperative day. The present study demonstrated a significant elevation in CRP levels and the NLR following THA and TKA. In both groups, the NLR showed a faster kinetics pattern than CRP levels in response to surgical trauma.The translational potential of this article: We describe results of the use of the NLR, as compared to a routinely used marker, CRP, as advantageous in clinical setting due to faster dynamics of change. Integrating the NLR in clinical practice seems easy and without extra cost.


Cloning of cDNA specifically involved in the thyroid cAMP mitogenic pathway.
The activation of the cyclic AMP cascade in dog and human thyroid cells in primary culture induces the expression of differentiated gene expression, hyperfunction and proliferation. These programs are developed simultaneously in quiescent dedifferentiated cells. In this paper the strategy followed by our group to define the genes involved in the cAMP mitogenic cascade is outlined.


Mapping the helix arrangement of the reconstituted ETR1 ethylene receptor transmembrane domain by EPR spectroscopy.
The plant ethylene receptor ETR1 is a key player in the perception of the phytohormone and subsequent downstream ethylene signal transmission, crucial for processes such as ripening, senescence and abscission. However, to date, there is sparse structural knowledge about the transmembrane sensor domain (TMD) of ETR1 that is responsible for the binding of the plant hormone and initiates the downstream signal transmission. Sequence information and ab initio modelling suggest that the TMD consists of three transmembrane helices. Here, we combined site-directed spin labelling with electron paramagnetic resonance spectroscopy and obtained distance restraints for liposome-reconstituted ETR1_TMD on the orientation and arrangement of the transmembrane helices. We used these data to scrutinize different computational structure predictions of the TMD.


[Kaposi's sarcoma: comparative immunohistochemical study and histogenic significance of endothelial markers].
The origin of spindle-shaped cells in Kaposi's sarcoma (KS) remains controversial. Non-specific histochemical reactions, electron microscopic examinations and immunostainings using antibody against factor VIII-related antigen (F VIII-RAG) and Ulex europaeus agglutinin I (UEAI) lectin as endothelial markers have given contradictory results. Immunohistochemical techniques were applied to 7 frozen skin biopsy specimen of KS from 5 elderly Mediterranean people and 1 renal allograft recipient, and a group of 27 other frozen cutaneous tumours including haemangio and lymphangiosarcomas, benign vascular lesions and various epithelial, melanocytic, fibrohistiocytic, fibrosarcomatous and muscular tumours. Using UEAI and antibodies against F VIII-RAG, HLA-DR and vimentin, a large proportion of positive KS spindle cells was found in all cases whereas cells were negative for keratin. Among the various immunoreactivity patterns observed in this study, a unique immunohistochemical profile was demonstrated for KS, angiosarcoma and endothelial cell, which strongly supports the endothelial origin of spindle cells in KS. Whereas F VIII-RAG, HLA-DR, vimentin and UEAI were sensitive endothelial markers, only F VIII-RAG appeared specific for endothelial cells since UEAI stained 2 squamous cell carcinomas and HLA-DR and vimentin were present in various mesenchymal and melanocytic tumours.


Synthesis, structures, and conformational characteristics of triptycene-derived calix[5]arenes.
A series of novel calix[5]arenes 5 containing one 1,8-dimethoxytriptycene moiety were synthesized through an efficient fragment coupling strategy. The subsequent demethylation of 5 with BBr(3) in dry dichloromethane gave the calix[5]arenes 6. Debutylation of both 5a-b and 6a-b with AlCl(3) resulted in the same products 7a-7b. The structural studies revealed that all of the macrocyclic compounds have well-defined structures with fixed cone conformations in both solution and solid state. Moreover, it was also found that the triptycene-derived calix[5]arenes could encapsulate small neutral molecules in the solid state.


Long Non-Coding RNA KCNQ1OT1 Regulates Protein Kinase CK2 Via miR-760 in Senescence and Calorie Restriction.
Long non-coding RNAs (lncRNAs) play important biological roles. Here, the roles of the lncRNA KCNQ1OT1 in cellular senescence and calorie restriction were determined. KCNQ1OT1 knockdown mediated various senescence markers (increased senescence-associated β-galactosidase staining, the p53-p21Cip1/WAF1 pathway, H3K9 trimethylation, and expression of the senescence-associated secretory phenotype) and reactive oxygen species generation via CK2α downregulation in human cancer HCT116 and MCF-7 cells. Additionally, KCNQ1OT1 was downregulated during replicative senescence, and its silencing induced senescence in human lung fibroblast IMR-90 cells. Additionally, an miR-760 mimic suppressed KCNQ1OT1-mediated CK2α upregulation, indicating that KCNQ1OT1 upregulated CK2α by sponging miR-760. Finally, the KCNQ1OT1-miR-760 axis was involved in both lipopolysaccharide-mediated CK2α reduction and calorie restriction (CR)-mediated CK2α induction in these cells. Therefore, for the first time, this study demonstrates that the KCNQ1OT1-miR-760-CK2α pathway plays essential roles in senescence and CR, thereby suggesting that KCNQ1OT1 is a novel therapeutic target for an alternative treatment that mimics the effects of anti-aging and CR.


The critical role of velocity storage in production of motion sickness.
We propose that motion sickness is mediated through the orientation properties of velocity storage in the vestibular system that tend to align eye velocity produced by the angular vestibulo-ocular reflex (aVOR) with gravito-inertial acceleration (GIA). (GIA is the sum of the linear accelerations acting on the head. In the absence of translational accelerations, gravity is the GIA.) We further postulate that motion sickness produced by cross-coupled vestibular stimulation can be characterized by a metric composed of the disparity between the axis of eye rotation and the GIA, the strength of the response to angular motion, and the response duration, as determined by the central vestibular time constant, that is, by the time constant of velocity storage. The nodulus and uvula of the vestibulocerebellum are likely to be the central sites where the disparity is sensed, where the vestibular time constants are habituated, and where links are made to the autonomic system to produce the symptoms and signs.


Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.
Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.


Targeting neuroblastoma by small-molecule inhibitors of human ALYREF protein: mechanistic insights using molecular dynamics simulations.
Neuroblastoma is a tumour of the sympathetic nervous system mainly prevalent in children. Many strategies have been employed to target several drug-targetable proteins for the clinical management of neuroblastoma. However, the heterogeneous nature of neuroblastoma presents serious challenges in drug development for its treatment. Albeit numerous medications have been developed to target various signalling pathways in neuroblastoma, the redundant nature of the tumour pathways makes its suppression unsuccessful. Recently, the quest for neuroblastoma therapy resulted in the identification of human ALYREF, a nuclear protein that plays an essential role in tumour growth and progression. Therefore, this study used the structure-based drug discovery method to identify the putative inhibitors targeting ALYREF for the Neuroblastoma treatment. Herein, a library of 119 blood-brain barrier crossing small molecules from the ChEMBL database was downloaded and docked against the predicted binding pocket of the human ALYREF protein. Based on docking scores, the top four compounds were considered for intermolecular interactions and molecular dynamics simulation analysis, which revealed CHEMBL3752986 and CHEMBL3753744 with substantial affinity and stability with the ALYREF. These results were further supported by binding free energies and essential dynamics analysis of the respective complexes. Hence, this study advocates the sorted compounds targeting ALYREF for further in vitro and in vivo assessment to develop a drug against neuroblastoma.Communicated by Ramaswamy H. Sarma.


Effect of surfactant architecture on the properties of polystyrene-montmorillonite nanocomposites.
A series of surfactants were designed and synthesized for use as clay modification reagents to investigate the impact of their chemical structure on the nanocomposites morphology obtained following polymerization. The behavior of the surfactant-modified clays at three different stages were investigated: after ion exchange, following dispersion in styrene monomer, and once polymerization was complete. The propensity of the styrene monomer to swell the surfactant-modified clay was observed to be a useful indicator of compatibility and predictor of the resultant polystyrene nanocomposite morphology which was directly observed using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (TEM). It was found that the key components of surfactant design driving exfoliated morphologies were (1) the position of the ammonium group, (2) the inclusion of a polymerizable group, (3) the solubility of the surfactant in the monomer, (4) the length of the alkyl chain, and (5) sufficient concentration of surfactant used to exchange the clay. This understanding should lead to better design of clay modifications for use in polymer nanocomposites.


Crosstalk between microwave ablation and ferroptosis: The next hot topic?
Microwave ablation has been one form of thermal ablation in treatments for many tumors, which can locally control unresectable tumors. Ferroptosis is iron-dependent cell death caused by the cumulative reactive oxygen species and lipid peroxidation products. Recently, increasing evidence has shown that ferroptosis might play a vital role in MWA-induced tumor suppression. In this article, we briefly illustrate the concept of ferroptosis, the related signal pathways and inducers, the basic principle of microwave ablation in killing tumors, and the key molecules released after microwave ablation. Then, we describe the cross-talking molecules between microwave ablation and ferroptosis, and discussed the potential mechanism of microwave ablation-induced ferroptosis. This review explores the therapeutic target of ferroptosis in enhancing the systemic antitumor effect after microwave ablation, providing theoretical support in combinational microwave ablation with pro-ferroptosis therapy.


Mental addition versus subtraction in counterfactual reasoning: on assessing the impact of personal actions and life events.
Assessing the consequences of actions and events often requires comparing a mental stimulation of the world in which the action is present to one in which the action is absent. We propose that people perceive more impact when asked to assess whether an action would increase the likelihood or degree of a potential outcome (mental addition) than when asked whether it would reduce the probability or extent of a potential consequence (mental subtraction). This judgmental asymmetry occurs because people (a) give more weight to features of the particular mental stimulation (the action or its absence) serving as the subject of comparison and (b) give more weight to factors that produce as opposed to inhibit the relevant outcome. In 4 studies, Ss assessed the impact of personal actions (e.g., studying for an exam). Ss perceived more impact when the assessment was placed in an additive frame (e.g., "how many more questions will you get right if you study?") as opposed to a subtractive one (e.g., "how many fewer will you get right if you do not study?"). This effect was not influenced by the hedonic value of the event or by whether the S had actually experienced it. Discussion centers on the relevance of these results for the undoing of scenarios and causal attribution.


Prevalence of hypertension in rural west Africa.
The prevalence of hypertension in rural African communities has been reported previously to be relatively low, with prevalence rates ranging between 2.5% and 10.9%. The authors obtained blood pressure recordings in 3,588 adult residents (age > 20 years) of the Liberian Agricultural Company rubber plantation, located in rural Liberia, West Africa. Blood pressures were obtained using automated digital blood pressure machines in a house-to-house survey. Individuals with a systolic blood pressure greater than 139 mm Hg or a diastolic blood pressure greater than 89 mm Hg were referred to a central site, where three subsequent blood pressure determinations were made, the mean of which was used to determine whether people were hypertensive. The overall prevalence of hypertension (blood pressure > 139/89 mm Hg) was 12.5%. Hypertension was most common in the older women (prevalence 5.7% in women age 20-24 years old, 50% in women older than 55). Using more stringent criteria for hypertension, systolic blood pressure greater than 159 mm Hg or diastolic blood pressure greater than 94 mm Hg, 20% of women between 50-54 had hypertension and 26% of the women older than 55 had hypertension. In some ethnic groups, the prevalence of hypertension was as high as 25%. Based on these results, the prevalence of hypertension in some rural African communities may be higher than reported previously, particularly in older women and among certain ethnic groups, possibly suggesting a strong hereditary component.


Time-resolved beam structure of an active Q-switched ruby laser.
Time-resolved observations show that the near field and far field patterns of an active Q-switched ruby laser remain almost constant for the duration of the output pulse. This is in marked contrast to the reported behavior of a passive Q-switched laser.


Salmonella in Captive Reptiles and Their Environment-Can We Tame the Dragon?
Reptiles are considered a reservoir of a variety of Salmonella (S.) serovars. Nevertheless, due to a lack of large-scale research, the importance of Reptilia as a Salmonella vector still remains not completely recognized. A total of 731 samples collected from reptiles and their environment were tested. The aim of the study was to assess the prevalence of Salmonella in exotic reptiles kept in Poland and to confirm Salmonella contamination of the environment after reptile exhibitions. The study included Salmonella isolation and identification, followed by epidemiological analysis of the antimicrobial resistance of the isolates. Implementation of a pathway additional to the standard Salmonella isolation protocol led to a 21% increase in the Salmonella serovars detection rate. The study showed a high occurrence of Salmonella, being the highest at 92.2% in snakes, followed by lizards (83.7%) and turtles (60.0%). The pathogen was also found in 81.2% of swabs taken from table and floor surfaces after reptile exhibitions and in two out of three egg samples. A total of 918 Salmonella strains belonging to 207 serovars and serological variants were obtained. We have noted the serovars considered important with respect to public health, i.e., S. Enteritidis, S. Typhimurium, and S. Kentucky. The study proves that exotic reptiles in Poland are a relevant reservoir of Salmonella.


Dental bleaching with violet LED: Effects on dentin color change, resin-dentin bond strength, hybrid layer nanohardness and dentinal collagen biostability.
The purpose of this study was to investigate the effect of a novel dental bleaching technique with Violet LED on enamel color change, bond strength and hybrid layer nanomechanical properties in resin-dentin restoration, and dentin biostability. A total of 125 bovine incisors were distributed into a control group, violet LED group (LED), and 35 % peroxide hydrogen bleaching gel (BLG) groups (n = 15). Three 45-minute sessions were performed for both bleaching procedures every week. Enamel color change (ΔE, ΔL, and Δb) was determined after every bleaching session. After color analysis, dentin was exposed for the resin-dentin bond strength analysis using microtensile test and evaluation of the nanomechanical properties at the hybrid layer (nanohardness). While half of the specimens were tested immediately, the remaining were evaluated after 10,000 thermal cycles (TC). Thirty additional teeth were used to investigate dentin ultimate tensile strength (UTS) after the bleaching treatments. UTS was evaluated before and after an enzymatic challenge. Two-way repeated measures ANOVA and Tukey's post-test were used for the statistical analysis (α = 0.05). Enamel bleaching effect was observed in the LED and BLG groups with significant alterations in the ΔE, ΔL, and Δb in the BLG group. No difference was observed in the resin-dentin bond strength among the groups (p > 0.05), however, TC negatively affected the bond strength values for all the groups. Nanomechanical properties remained unchanged when comparing immediate and after TC results (p > 0.05). Bleaching with BLG reduced significantly the dentin UTS, while all groups showed major decrease in UTS after the enzymatic challenge. Although violet LED was able to promote a bleaching effect, less color changes was observed when compared to BLG. None of the bleaching techniques effected the resin-bond strength or the nanomechanics of the hybrid layer. Violet LED did negatively effect dentin biostability as observed for BLG and it may promote less changes to the organic content of dentin.


The frequency of SMN gene variants lacking exon 7 and 8 is highly population dependent.
Spinal Muscular Atrophy (SMA) is a disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. In the majority of cases, SMA is caused by the homozygous absence of the SMN1 gene. The disease severity of SMA is strongly influenced by the copy number of the closely related SMN2 gene. In addition, an SMN variant lacking exons 7 and 8 has been reported in 8% and 23% of healthy Swedish and Spanish individuals respectively. We tested 1255 samples from the 1000 Genomes Project using a new version of the multiplex ligation-dependent probe amplification (MLPA) P021 probemix that covers each SMN exon. The SMN variant lacking exons 7 and 8 was present in up to 20% of individuals in several Caucasian populations, while being almost completely absent in various Asian and African populations. This SMN1/2Δ7-8 variant appears to be derived from an ancient deletion event as the deletion size is identical in 99% of samples tested. The average total copy number of SMN1, SMN2 and the SMN1/2Δ7-8 variant combined was remarkably comparable in all populations tested, ranging from 3.64 in Asian to 3.75 in African samples.


National Heart, Lung, and Blood Institute state of the science symposium in therapeutic apheresis-Therapeutic apheresis in cardiovascular disease.
The National Heart, Lung, and Blood Institute in collaboration with the American Society for Apheresis, convened a State of the Science Symposium in November of 2012 due to the expanding application of therapeutic apheresis despite the lack of well-designed research to address its efficacy. This article reviews the opportunities that were presented at this meeting in the area of cardiovascular disease (CVD), specifically the use of columns to adsorb autoantibodies in dilated cardiomyopathy or damaging lipids in peripheral vascular disease. Understanding how absorption of these pathologic substances alters the inflammatory response in these disorders is important for the application of these technologies to the treatment of CVD.


The use of a mobile application to track process workflow in perioperative services.
This article discusses the data collection tool developed to investigate how patient flow is affected by the delivery of different types of care within Perioperative Services. To better understand the Perioperative Services processes, this study tracked staff members as they perform their activities. A challenging aspect of documenting the processes observed while tracking the Perioperative Services staff is to record the specific times and order in which the activities took place. The Perioperative Services is a fast-paced, dynamic environment where the staff members often perform multiple tasks that may also be interrupted, and each staff member may perform these tasks in their own sequence. To meet the needs of accurate data gathering, an iPhone/iPod Touch application was developed. It provides several advantages over the traditional paper/pencil method: (1) time stamps are instantaneous and consistent among the data collectors, (2) activities are entered via swipe-and-click capability, (3) multiple active tasks and interruptions can be tracked, and (4) collected data can be output to Microsoft Excel or Access for analysis. The "app" has proven to be useful in capturing data for our study. This technology can be customized and applied to similar settings at other hospitals.


Are pregnancy-associated hypertensive disorders so sweet?
Worldwide, one in seven pregnancies is complicated by some form of diabetes, with a rising trend. Additionally, hypertension is one of the main causes of morbidity and mortality for both the pregnant woman and the fetus and also contributes to premature birth. In a cohort study of pregnant women with diabetes, which was recently published in this journal, at least 84.5% of the subjects had hypertension. This rate of hypertension might be among the highest reported thus far. In the medical literature, approximately 20% of women with diabetes during pregnancy have various pregnancy-associated hypertensive disorders. Racial/ethnic differences, apparently, were not implicated in this elevated rate of hypertension: Although black and Hispanic women have a twofold higher rate of hypertension in pregnancy compared to white women, 75% of the subjects in the study in question were white. Thus, the impressive finding delivered by this large study, merits additional clarifications.


Laparoscopic radiofrequency ablation of hepatic cavernous hemangioma. A preliminary experience with 27 patients.
Radiofrequency ablation (RFA), currently used extensively for liver tumors, also has been applied successfully to hepatic cavernous hemangioma (HCH) percutaneously. The aim of this study was to assess the feasibility, safety, and efficacy of laparoscopic RFA for patients with HCHs. Between March 2001 and March 2004, 27 patients with symptomatic and rapid-growth lesions were treated by laparoscopic RFA using the RF-2000 generator system. The treatment-related complications were observed. All the patients were followed up with helical computed tomography scans and ultrasonography at regular intervals to assess the therapeutic efficacy of laparoscopic RFA. This study assessed 9 men and 18 women with a mean age of 41.6 +/- 8.3 years. Three additional intrahepatic lesions missed preoperatively were found in three patients on intraoperative ultrasound. A total of 27 patients with 50 liver lesions were treated successfully with laparoscopic RFA. The mean maximum tumor diameter was 5.5 +/- 2.0 cm. The mean length of time for RFA per lesion was 20.7 +/- 11.9 min, and the mean blood loss was 134.4 +/- 88.9 ml. Laparoscopic cholecystectomy was performed simultaneously for gallstones in 13 patients and for abutting of gallbladder from hemangioma in 2 patients. In addition, 3 patients also had a laparoscopic deroofing of simple hepatic cysts. Although postoperative low-grade fever and transient elevation of serum transaminase levels were observed in 13 patients, there were no complications related to laparoscopic RFA. During a median follow-up period of 21 months (range, 12-42 months), complete lesion necrosis was achieved for all the patients. Laparoscopic RFA therapy is a safe, feasible, and effective treatment option for patients with symptomatic and rapid-growth HCHs located on the surface of the liver or adjacent to the gallbladder. Intraoperative ultrasonography is a useful adjunct for detecting additional liver lesions and offering more accurate targeting for RFA.


Differential involvement of reactive oxygen species in apoptosis caused by the inhibition of protein phosphatase 2A in Jurkat and CCRF-CEM human T-leukemia cells.
A better understanding of dysregulated signaling pathways in cancer cells may suggest novel strategies to prevent tumor development and/or progression. Here we show that Jurkat and CCRF-CEM human T-leukemia cell lines were more sensitive than normal human T cells to the cytotoxic effect of inhibiting protein phosphatase 2A (PP2A). Inhibition of PP2A by okadaic acid (OA) caused T-leukemia cells to die by apoptosis, as indicated by DNA fragmentation, caspase-3 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and changes in nuclear morphology that were consistent with apoptosis. PP2A might therefore be a useful intracellular target for the treatment of T cell-derived leukemias. We also observed that reactive oxygen species (ROS) were generated in response to PP2A inhibition in T-leukemia cells. However, loss of DeltaPsi(m) that resulted from PP2A inhibition was not prevented by exogenous antioxidants (glutathione and N-acetyl-cysteine), indicating that OA-induced changes in mitochondrial membrane permeability were not a consequence of ROS production. Moreover, exogenous antioxidants protected CCRF-CEM T-leukemia cells from apoptosis caused by PP2A inhibition but failed to prevent OA-induced apoptosis in Jurkat T-leukemia cells, indicating a differential role for ROS in apoptosis caused by PP2A inhibition in two different human T-leukemia cell lines.


Role of charge transfer configurations in LaMnO3, CaMnO3, and CaFeO3.
A simple scheme is proposed to analyze the N-electron wave function obtained in embedded cluster calculations in valence bond terms such as ligand-to-metal charge transfer and non-charge-transfer determinants. The analysis is based on a unitary transformation of pairs of natural orbitals to optimal atomiclike orbitals. The procedure is applied to compare the degree of ionicity in NiO and MnO and to explain the existence or absence of Jahn-Teller distortions in LaMnO3, CaMnO3, and CaFeO3. The authors find that the ground state of LaMnO3 is dominated by non-charge-transfer configurations, whereas the charge transfer configurations dominate the ground state wave function in the other two perovskites.


Advances in antiplatelet therapy.
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the western world. These disorders share a common pathophysiology -- atherosclerosis, which affects various arterial beds, leading to protean manifestations (coronary artery disease [CAD], stroke, peripheral arterial disease [PAD]). The platelet plays a pivotal role in the perpetuation and clinical expression of these disorders. The platelet, once believed to have a role confined to modulation of thrombosis and haemostasis, also plays an active role in vascular inflammation. Antiplatelet agents have become first-line therapy for CVD, and their unequivocal benefits are demonstrated in various basic and experimental models and supported by overwhelming evidence from clinical trials. Search is underway for more effective and safer antiplatelet therapy. Novel therapies are emerging to target the redundant pathways of platelet adhesion, activation and aggregation. Efforts are also ongoing to enhance implementation of existent therapy, target therapy selectively to high-risk patients and to those likely to respond (pharmacogenomics), and study the incremental benefits and safety of various antiplatelet combinations and their interaction with other medications in patients with CVD treated with polypharmacy.


Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis.
To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.


Collagen Peptide in a Combinatorial Treatment with Lactobacillus rhamnosus Inhibits the Cariogenic Properties of Streptococcus mutans: An In Vitro Study.
Dental caries is caused by the formation of cariogenic biofilm, leading to localized areas of enamel demineralization. Streptococcus mutans, a cariogenic pathogen, has long been considered as a microbial etiology of dental caries. We hypothesized that an antagonistic approach using a prebiotic collagen peptide in combination with probiotic Lactobacillus rhamnosus would modulate the virulence of this cariogenic biofilm. In vitro S. mutans biofilms were formed on saliva-coated hydroxyapatite discs, and the inhibitory effect of a combination of L. rhamnosus and collagen peptide on S. mutans biofilms were evaluated using microbiological, biochemical, confocal imaging, and transcriptomic analyses. The combination of L. rhamnosus with collagen peptide altered acid production by S. mutans, significantly increasing culture pH at an early stage of biofilm formation. Moreover, the 3D architecture of the S. mutans biofilm was greatly compromised when it was in the presence of L. rhamnosus with collagen peptide, resulting in a significant reduction in exopolysaccharide with unstructured and mixed bacterial organization. The presence of L. rhamnosus with collagen peptide modulated the virulence potential of S. mutans via down-regulation of eno, ldh, and atpD corresponding to acid production and proton transportation, whereas aguD associated with alkali production was up-regulated. Gly-Pro-Hyp, a common tripeptide unit of collagen, consistently modulated the cariogenic potential of S. mutans by inhibiting acid production, similar to the bioactivity of a collagen peptide. It also enhanced the relative abundance of commensal streptococci (S. oralis) in a mixed-species biofilm by inhibiting S. mutans colonization and dome-like microcolony formation. This work demonstrates that food-derived synbiotics may offer a useful means of disrupting cariogenic communities and maintaining microbial homeostasis.


[Use of PAR index to evaluate the treatment outcome for Class II division 1 malocclusion with different tooth extraction patterns].
To assess the outcome of orthodontic treatment for Class II division 1 malocclusion with different tooth extraction patterns using PAR index. PAR index was applied on pre- and post-orthodontic treatment cast for 64 Class II division 1 malocclusion patients with two different tooth extraction patterns: extraction of maxillary teeth only (Group 1), and extraction of maxillary and mandibular teeth(Group 2). SPSS 10.0 software package was used for Student's t test. The PAR index of group 1 and group 2 pre-orthodontic treatment was 36.21+/-6.82 and 38.34+/-7.51. There were no significant difference (P>0.05) between the two groups. The PAR index of group 1 and group 2 post-orthodontic treatment was 6.13+/-1.64 and 5.89+/-1.75. There were no significant difference (P>0.05) between the two groups. The decrement and the rate of reduction of group 1 was 30.05+/-7.43 and 85.33%+/-5.68%. The decrement and the rate of reduction of group 2 was 32.38+/-8.12 and 87.47%+/-5.21%. The occlusal relationship improved significantly in the two groups after treatment. Treatment for Class II division 1 malocclusion with different extraction patterns can both acquire satisfactory results.


Cell-cycle regulation of insulin-stimulated tyrosine aminotransferase activity in rat hepatoma cells.
Amongst the proteins that are subjected to variation during the cell division cycle few are under hormonal regulation. The variation in amount of tyrosine aminotransferase (TAT) in the hepatic tissue is under the control of glucagon, glucocorticoids and insulin. It has been reported that the inducibility of TAT activity by dexamethasone in rat hepatoma (HTC) is limited to the late G1 and the S portions of the cell cycle. Evidence is presented in this report that in the rat hepatoma Fao, insulin (which has the capability to promote both cell growth and hormonal effects via its own receptors) modulates the TAT activity during the cell cycle. The maximal insulin-stimulated induction of TAT activity was observed at the end of the G1 phase and then decreased as cells progressed through their mitotic cycle. The number of insulin binding sites per cell was decreased by only 30% during the same period of time. Furthermore, the extent of receptor autophosphorylation decreased in the same proportion, suggesting that insulin receptors remained functional through the whole cell cycle. In fact, another insulin-stimulated cellular function, neutral amino-acid transport, was not modified as cells progressed into the S phase. Hydroxyurea, which is known to prevent cell progression into the S phase, stabilized the insulin-induced TAT activity at its maximal level for several hours. Reciprocally, removal of hydroxyurea resulted in a concomitant decrease in TAT activity and reinitiation of DNA synthesis.


The Antecedents and Consequences of Health Literacy in an Ecological Perspective: Results from an Experimental Analysis.
This study analyses the relationship between the antecedents and consequences of health literacy (HL) at the ecological level among the nations involved in the European Health Literacy Survey (HLS-EU). The antecedents and consequences were investigated by means of proxy indicators. The HL was measured using the 47-item HLS-EU questionnaire (HLS-EUQ47) and the Newest Vital Sign (NVS). The two measures stood in significant correlation to the outcomes of the sub-discipline of the Euro Health Consumer Index (r = 0.790 for HLS-EUQ47; r = 0.789 for NVS). The HLS-EUQ47 also stood in correlation to the percentage of population with post-secondary education (r = 0.810), the reading performance for 15-year-old students (r = 0.905), the presence of a national screening program for breast (r = 0.732) or cervical cancer (r = 0.873). The NVS stood in correlation with the unemployment rate (r = −0.778), the Gross Domestic Product (r = 0.719), the Gini coefficient (r = −0.743), the rank of the Euro Patient Empowerment Index (r = −0.826), the expenditure on social protection (r = 0.814), the Consumer Empowerment Index (r = 0.898), the percentage of adults using the internet for seeking health information (r = 0.759), the prevalence of overweight individuals (r = −0.843), the health expenditure (r = 0.766), as well as the percentage of individuals using the internet for interacting with public authorities (r = 0.755). This study provides some preliminary considerations regarding alternative means by which to study HL and proposes new methods for experimentation. The methods and the results could offer a means by which the relationship between society and overall healthcare protection could be strengthened.


Insulin-releasing activity and successful transplantation of pancreatic islets preserved by tissue culture.
Preserving pancreatic islets for 7 days by a making use of the organ culture, we studied the insulin-releasing activity at the time of administration of glucose and various digestive tract hormones for the purpose of clarifying the function of preserved pancreatic islets. Furthermore, we transplanted pancreatic islets preserved for 3 to 5 days into the portal vein of rats with streptozotocin-induced diabetes and reached the following conclusions: (1). The islets of Langerhans of the pancreas responded well to glucose up to the seventh day of preservation and showed patterns similar to those of fresh pancreatic islets with respect to both the dose response and the time response. (2). Preserved pancreatic islets of the pancreas had insulin-releasing activity almost equal to that of fresh pancreatic islets against stimulation by glucagon, tolbutamide, and various digestive tract hormones. (3). Rats with streptozotocin-induced diabetes showed a marked improvement in blood glucose and urine glucose following transplantation of preserved pancreatic islets into the portal vein, and this effectiveness persisted for 6 to 8 weeks.


Depressed mothers as informants on child behavior: methodological issues.
Mothers with depressive symptoms more frequently report behavioral problems among their children than non-depressed mothers leading to a debate regarding the accuracy of depressed mothers as informants of children's behavior. The purpose of this integrative review was to identify methodological challenges in research related to the debate. Data were extracted from 43 articles (6 theoretical, 36 research reports, and 1 instrument scoring manual). The analysis focused on the methodologies considered when using depressed mothers as informants. Nine key themes were identified and I concluded that researchers should incorporate multiple informants, identify the characteristics of maternal depression, and incorporate advanced statistical methodology. The use of a conceptual framework to understand informant discrepancies within child behavior evaluations is suggested for future research.


Sound scattering from two concentric fluid spheres (L).
The solution to the problem of plane wave and point source scattering by two concentric fluid spheres is derived. The effect of differences in sound speed, density, and absorption coefficient is taken into account. The scattered field is then found in the limit as the outer sphere becomes an infinitely thin shell and compared to the solution for a single fluid sphere for verification. A simulation is then performed using the concentric fluid sphere solution as an approximation to the human head and compared to the solution of a single fluid sphere with the properties of either bone or water. The solutions were found to be similar outside of the spheres but differ significantly inside the spheres.


Methods for Detecting Processing Temperatures of Previously Cooked Meat and Poultry Products - A Review.
Title 9 of the Code of Federal Regulations establishes prescribed thermal treatment for a variety of meat and poultry products. These requirements are to ensure the destruction of harmful microorganisms and viruses that cause diseases in humans and livestock. The information presented in this review provides information relative to the current procedures used by the Food Safety and Inspection Service (FSIS) for monitoring the adequacy of heat treatment of meat and poultry products; and the research activities that have been and are currently being conducted to develop new and/or improved methods for determining the maximum internal temperature of meat and poultry products. Currently, FSIS is using a protein "Coagulation Test" for monitoring the maximum internal temperature (MIT) of both beef and pork products heat processed to temperatures lower than 65°C; a residual "Acid Phosphatase Activity Method" for determining the MIT of canned hams, canned picnics and canned luncheon meat, and a third method, known as the "Bovine Catalase Test", for the determination of catalase which gives a pass/fail indication at a cooking temperature of 62.8°C for rare roast beef and cooked beef. Since 1957, several attempts have been made to develop new and/or improved methods. These include an evaluation of the enzyme systems and various physical techniques. The lack of new and/or improved methods is not due to the lack of research efforts in this area, as evidenced by this review. The challenge is the development of a method which can accurately determine within ± 1.0°C the endpoint temperature in the temperature range (67.8 - 70.0°C) that is of most interest to FSIS.


Prevalence of neurological disorders in Udo, a rural community in southern Nigeria.
The residents of Udo, a rural community of Edo-speaking people (population 2,925) in Bendel State, Nigeria were screened in a door-to-door survey for neurological disorders by specially instructed primary health care workers (PHW). A standard protocol was followed by PHW in collecting census data, administering a screening questionnaire, and performing a simple neurological examination. A neurologist confirmed the presence of neurological disorders in 235 (47%) of 504 screen-positive subjects after further clinical evaluation. The point prevalence ratios, per 1,000 population, for the most common neurological disorders identified in Udo were: migraine 63.2, febrile convulsions in children under 7 years of age 10.7, epilepsy 6.2, peripheral neuropathy 2.1 and myelopathy 1.7.


Minimal Margin Surgery and Intraoperative Neuromonitoring in Benign Parotid Gland Tumors: Retrospective Clinical Study.
Extracapsular dissection (ECD) was introduced for the removal of superficial and small benign parotid tumors. According to a recent proposal, ECD is reserved for tumors that are 3 cm or less, mobile, and close to the parotid borders in cases of pleomorphic adenoma. The aim of the study is to evaluate the effectiveness of ECD for treatment of benign parotid tumors also in cases of tumors that were larger than 3 cm and deeper. All ECD for benign parotid neoplasms conducted between 2007 and 2017 were reviewed. The lesions included were limited to primary parotid tumors and categorized by Quer proposal. Facial nerve monitoring was used in all cases. Facial nerve palsy and local recurrences were assessed. The 88 ECD performed met inclusion criteria. The mean lesion size was 4.26 cm. Of the tumors, 68 were less than 3 cm in diameter and 20 were larger, 64 were superficial, and 24 were deep. The most common lesion types were pleomorphic adenoma (88.6%). There was no significant difference in complication rates between the size of tumor (p = 0.9) and location (p = 0.91). Our results suggest that extracapsular dissection could be considered an option for first-time diagnosed benign parotid tumors, even in cases of large dimensions and deep lobe involvement.


Reconciling biodiversity and carbon stock conservation in an Afrotropical forest landscape.
Protecting aboveground carbon stocks in tropical forests is essential for mitigating global climate change and is assumed to simultaneously conserve biodiversity. Although the relationship between tree diversity and carbon stocks is generally positive, the relationship remains unclear for consumers or decomposers. We assessed this relationship for multiple trophic levels across the tree of life (10 organismal groups, 3 kingdoms) in lowland rainforests of the Congo Basin. Comparisons across regrowth and old-growth forests evinced the expected positive relationship for trees, but not for other organismal groups. Moreover, differences in species composition between forests increased with difference in carbon stock. These variable associations across the tree of life contradict the implicit assumption that maximum co-benefits to biodiversity are associated with conservation of forests with the highest carbon storage. Initiatives targeting climate change mitigation and biodiversity conservation should include both old-growth and regenerating forests to optimally benefit biodiversity and carbon storage.


Gingival recession treatment: guided tissue regeneration with bioabsorbable membrane versus connective tissue graft.
Gingival recession represents a significant concern for patients and a therapeutic problem for clinicians. Several techniques have been proposed to achieve root coverage. The purpose of this randomized clinical trial was to evaluate the effect of a guided tissue regeneration (GTR) procedure in comparison to connective tissue graft (CTG) in the treatment of gingival recession defects. Twelve patients, each contributing a pair of Miller Class I or II buccal gingival recessions, were treated. In each patient one randomly chosen defect received a poly(lactic acid)-based bioabsorbable membrane, while the paired defect received a CTG. Clinical recordings included oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD statistically significantly decreased from 2.5 mm presurgery to 0.5 mm with GTR (81% root coverage), and from 2.5 mm to 0.1 mm with CTG (96% root coverage), at 6 months postsurgery. Prevalence of complete root coverage was 58% for the GTR group and 83% for the CTG group. Mean CAL gain was 2.0 mm for the GTR group and 2.2 mm for the CTG group. No statistically significant differences between treatment groups were observed for changes in RD, RW, PD, CAL, and KT. Treatment of human gingival recession defects by means of either GTR or CTG results in clinically and statistically significant improvement of the soft tissue conditions of the defect when pre- and post-treatment measurements were compared. Although differences between CTG and GTR in mean root coverage and prevalence of complete coverage consistently favored the CTG procedure, the differences in measurements were not statistically significant.


The role of retrieval practice in memory and analogical problem-solving.
Retrieval practice (e.g., testing) has been shown to facilitate long-term retention of information. In two experiments, we examine whether retrieval practice also facilitates use of the practised information when it is needed to solve analogous problems. When retrieval practice was not limited to the information most relevant to the problems (Experiment 1), it improved memory for the information a week later compared with copying or rereading the information, although we found no evidence that it improved participants' ability to apply the information to the problems. In contrast, when retrieval practice was limited to only the information most relevant to the problems (Experiment 2), we found that retrieval practice enhanced memory for the critical information, the ability to identify the schematic similarities between the two sources of information, and the ability to apply that information to solve an analogous problem after a hint was given to do so. These results suggest that retrieval practice, through its effect on memory, can facilitate application of information to solve novel problems but has minimal effects on spontaneous realisation that the information is relevant.


[Advances in the development of antifungal agents].
The present review paper deals with novel antifungal drugs. The lack of new antifungal drugs ascend proportionally to the increasing occurrence of serious infections caused by yeast and fungi mainly at immunocompromised or in other way sensitive patients. The topical state of pharmacotherapy is briefly drawn out; most attention is given to newly developed active entities. Established agents do not satisfy the medical need completely, azoles are fungistatic and vulnerable to resistance, whereas polyenes cause serious host toxicity. Drugs in clinical development include modified azoles and a new class of echinocandins and pneumocandins. Other promising novel agents in preclinical development include several inhibitors of fungal protein, lipid and cell wall syntheses.


Immunostimulatory bioactivity of algal polysaccharides from Chlorella pyrenoidosa activates macrophages via Toll-like receptor 4.
Much research suggests that a dietary supplement of Chlorella pyrenoidosa may be helpful to human health, but the molecular mechanism involved remains unclear. The aim of this research was to investigate the effects of certain hot-water-soluble polysaccharides from Chlorella pyrenoidosa (CWSP) on cytokine production, human leukocyte antigen (HLA) expression, and costimulatory molecule expression in macrophages. We demonstrated that CWSP induced IL-1beta secretion in macrophages via Toll-like receptor 4 (TLR4) mediated protein kinase signaling pathways. In addition, CWSP also stimulated the cell surface expression of HLA-DA, -DB, and -DC, and HLA-DR, -DP, and -DQ as well as the expression of costimulatory family molecules such as CD80 and CD86 in macrophages. Furthermore, we demonstrated that preinjection of C57BL/6J mice with CWSP increased lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha and IL-1beta secretion into serum in vivo. This outcome was consistent with the corresponding outcome for cells treated with CWSP in vitro. Our current results provide support for the possible use of CWSP as a modulation agent of immune responses in humans and certain animal species. Finally, in using GC-MS to analyze the polysaccharides, we found that the major monosaccharides of CWSP were rhamnose (31.8%), glucose (20.42%), galactose (10.28%), mannose (5.23%), and xylose (1.27%). This study is the first to report the molecular mechanism of immune-modulated signal transduction in vitro from the polysaccharides of Chlorella pyrenoidosa.


Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.
Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. Mutagen hypersensitivity increases the risk of developing second malignant tumors. Future research should focus on the molecular mechanisms underlying mutagen sensitivity.


Derivation of U.S. EPA's oral Reference Dose (RfD) for methylmercury.
Mercury (Hg) cycles in the environment through a series of complex chemical and physical transformations that occur in air, soils, and water bodies. One component of the environmental mercury cycle is the formation of methylmercury (MHg) primarily by aquatic and marine microorganisms and the accumulation of MHg in foodwebs, particularly in piscivorous species. Human consumption of piscivorous fish and other piscivorus animals is the most common pathway of exposure to MHg. For non-carcinogenic toxic endpoints, the U.S. EPA typically develops a Reference Dose (RfD). This is generally interpreted to be a concentration of a chemical which can be consumed on a daily basis over a lifetime without expectation of adverse effect. There is substantial evidence in both animal and humans that MHg is a neurotoxicant in the adult and the child as well as a developmental neurotoxicant for the fetus. Epidemics of MHg poisoning in Japan and Iraq have resulted from high-dose exposures to MHg. In these epidemics adults, children, nursing infants and fetuses were affected by MHg. The epidemics demonstrate that neurotoxicity is the health effect of greatest concern and that effects on the developing human nervous system apparently occur at lower exposures than those affecting the adult nervous system. We describe how the data from the Iraqi MHg epidemic were used to derive the current RfD of 0.1 microgram/Kgbw/day (U.S. EPA, 1995;).


Linear unbiased prediction of clock errors.
In this paper, we propose a new formula for linear unbiased prediction of the local clock timescales. To predict future errors over all the measurement data, a new gain is derived for the p-step ramp unbiased finite impulse response (FIR) predictor. We then show that this gain gives the best linear unbiased fit suitable for forming the prediction vector. The predictor proposed is consistent with linear regression and best linear unbiased estimator. Applications are given for a crystal clock and the USNO Master Clock.


[Principles of the use of anti-influenza drugs].
Long-term experience in the clinical and epidemiological testing of antiinfluenzal drugs made it possible to derive major principles of their practical application. A study of the therapeutic and prophylactic efficacy of antiinfluenzal drugs has demonstrated convincingly that success of testing depends on the onset of treatment and epidemiological substantiation of drug administration. The observance of these conditions provides a social, medical and economic effect. Practical implementation of the results obtained required the identification of risk groups of developing influenza and other ARVI, the expansion of a network of rapid diagnostic laboratories, early emergency prevention with maximum coverage of high risk groups, and early administration of antiinfluenzal drugs distributed free of charge.


Secondary hyperparathyroidism disease stabilization following calcimimetic therapy.
Standard therapy for secondary hyperparathyroidism (SHPT) includes dietary calcium supplementation, active vitamin D, and phosphate binders; however, these are often insufficient to allow patients to achieve their serum parathyroid hormone (PTH), calcium and calcium-phosphorus product (Ca × P) targets. Recent preclinical studies have demonstrated that treatment with type II calcimimetics that increase the sensitivity of the calcium-sensing receptor (CaR) to calcium can reverse the alterations in CaR and vitamin D receptor expression and parathyroid cell proliferation that are associated with SHPT. These data suggest that calcimimetic treatment could stabilize disease progression and improve maintenance of treatment goals. In clinical trials involving SHPT patients, the calcimimetic cinacalcet has been shown to decrease PTH, calcium, phosphorus and Ca × P. Significant improvements were seen regardless of initial disease severity, and benefits were maintained over the course of long-term therapy (up to 4 years), indicating effective disease stabilization. In conclusion, preclinical and clinical data provide both theoretical and empirical support for the use of calcimimetics in moderate and advanced SHPT to effectively stabilize disease.


Retrospective investigation of gingival invaginations: Part II: microbiological findings and genetic risk profile.
Gingival invaginations are a frequent finding during tooth extraction and following orthodontic space closure. Based on the interdental localization and sometimes pronounced depth, it has been suggested that a gingival invagination may impede oral hygiene. In Part I of this series, the time until active tooth movement and the localization of extraction were identified as potential risk factors for the development of gingival invagination. The aims of the present study were the analysis of the microbial spectrum of a gingival invagination in comparison with pool samples of the sulcus of Ramfjord teeth, on the one hand, and the importance of genetic variations of the pro-inflammatory mediator interleukin-1 (IL-1) and its receptor antagonist (IL-1-RN), on the other hand. In addition, a possible role of smoking as a risk factor was evaluated. A total of 30 patients with (n=16) and without (n=14) gingival invagination were examined for the presence of eleven periodontal pathogen bacterial species with a commercially available test (micro-IDent®Plus, Hain Lifescience, Nehren, Germany). The genetic evaluation was performed with the GenoType® IL-1 test (Hain Lifescience). The results of the microbiological analysis of gingival invaginations showed that the bacterial flora might differ or even be higher than the pool sample from sulcus regions. The genetic evaluation demonstrated that in the group without gingival invagination only 14% showed an IL-1 polymorphism, whereas this value was twice as high (35%) in the group with gingival invagination. In addition, a combination of both polymorphisms IL-1 and IL-1-RN was only found in patients with gingival invagination (25%). Interestingly, smoking patients showed a significant increase of the severity of the gingival invagination. This retrospective study demonstrated that gingival invagination might be accompanied with an altered microbiological bacterial spectrum and a genetic IL-1 polymorphism. In addition, smoking was identified as another potential risk factor for the severity of gingival invaginations.


Somatization or psychosomatic symptoms?
The author describes some problems emerging from the approach to and comprehension of somatization symptoms, discussing ambiguities regarding somatization seen in the current classification manuals (ICD-10 and DSM-IV). Then the author presents a case report of a man who presented with a bizarre symptom of feminization that was successfully treated with psychotherapy. The author ends with a discussion of the relationship between meaning and symptom.


Structure, magnetism and theory of a family of nonanuclear Cu(II)5Ln(III)4-triethanolamine clusters displaying single-molecule magnet behaviour.
Synthesis, crystal structures and magnetic studies are reported for four new heterometallic Cu(II)-Ln(III) clusters. The reaction of Cu(NO(3))(2)·3H(2)O with triethanolamine (teaH(3)), pivalic acid, triethylamine and Ln(NO(3))(3)·6H(2)O (Ln=Gd, Tb, Dy and Ho) results in the formation of four isostructural nonanuclear complexes of general formula [Cu(II)(5)Ln(III)(4)O(2)(teaH)(4){O(2)CC(CH(3))(3)}(2)(NO(3))(4)(OMe)(4)]·2MeOH·2Et(2)O [Ln=Gd (1), Tb (2), Dy (3) and Ho (4)]. The metal core of each cluster is made up of four face- and vertex-sharing tetrahedral units. Solid-state DC magnetic susceptibility studies reveal competing anti- and ferromagnetic interactions within each cluster leading to large-spin ground states for 1-4. Solid-state AC magnetic susceptibility studies show frequency-dependent out-of-phase (χ''(M)) signals for 2-4 below 4 K, suggestive of single-molecule magnet behaviour. Ab initio calculations on one of the anisotropic examples (3) provided a rare set of J values for Dy-Cu and Cu-Cu exchange interactions (Dy-Dy zero), some ferro- and some antiferromagnetic in character, that explain its magnetic behaviour.


Real-time studies of evaporation-induced colloidal self-assembly by optical microspectroscopy.
Real-time monitoring of the whole growth process of evaporation-induced colloidal self-assembly has been conducted using an optical microspectroscopy setup. Our observations suggest that the assembly process can be divided into three different growth stages as evidenced by the variations detected in the reflectance spectra. The thickness variation of the growing colloidal crystal was monitored by examining the Fabry-Perot fringes in the reflectance spectra. Furthermore, the scalar wave approximation was utilized to analyze the evolution of optical properties with growth. More detailed information, including the time dependence of number of layers and volume fraction of water, has been revealed by comparing the experimental and calculated reflectance spectra. The present work demonstrates that in situ real-time microspectroscopy is a promising technique for monitoring and investigating the dynamic process of colloidal self-assembly.


Amyloid β protein injection into medial septum impairs hippocampal long-term potentiation and cognitive behaviors in rats.
The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid β protein (Aβ) in AD has been investigated extensively, it is still unclear whether the Aβ aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aβ injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aβ25-35, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aβ25-35 and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aβ25-35, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aβ25-35 and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aβ could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aβ, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.


Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis.
Factors regulating the proliferation and apoptosis of intestinal stem cells (ISCs) remain incompletely understood. Because ISCs exist among microbial ligands, immune receptors such as toll-like receptor 4 (TLR4) could play a role. We now hypothesize that ISCs express TLR4 and that the activation of TLR4 directly on the intestinal stem cells regulates their ability to proliferate or to undergo apoptosis. Using flow cytometry and fluorescent in situ hybridization for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed on the Lgr5-positive intestinal stem cells. TLR4 activation reduced proliferation and increased apoptosis in ISCs both in vivo and in ISC organoids, a finding not observed in mice lacking TLR4 in the Lgr5-positive ISCs, confirming the in vivo significance of this effect. To define molecular mechanisms involved, TLR4 inhibited ISC proliferation and increased apoptosis via the p53-up-regulated modulator of apoptosis (PUMA), as TLR4 did not affect crypt proliferation or apoptosis in organoids or mice lacking PUMA. In vivo effects of TLR4 on ISCs required TIR-domain-containing adapter-inducing interferon-β (TRIF) but were independent of myeloid-differentiation primary response-gene 88 (MYD88) and TNFα. Physiological relevance was suggested, as TLR4 activation in necrotizing enterocolitis led to reduced proliferation and increased apoptosis of the intestinal crypts in a manner that could be reversed by inhibition of PUMA, both globally or restricted to the intestinal epithelium. These findings illustrate that TLR4 is expressed on ISCs where it regulates their proliferation and apoptosis through activation of PUMA and that TLR4 regulation of ISCs contributes to the pathogenesis of necrotizing enterocolitis.


Ocular biocompatibility of nitinol intraocular clips.
To evaluate the tolerance and biocompatibility of a preformed nitinol intraocular clip in an animal model after anterior segment surgery. Yucatan mini-pigs were used. A 30-gauge prototype injector was used to attach a shape memory nitinol clip to the iris of five pigs. Another five eyes received conventional polypropylene suture with a modified Seipser slip knot. The authors compared the surgical time of each technique. All eyes underwent standard full-field electroretinogram at baseline and 8 weeks after surgery. The animals were euthanized and eyes collected for histologic analysis after 70 days (10 weeks) postsurgery. The corneal thickness, corneal endothelial cell counts, specular microscopy parameters, retina cell counts, and electroretinogram parameters were compared between the groups. A two sample t-test for means and a P value of 0.05 were use for assessing statistical differences between measurements. The injection of the nitinol clip was 15 times faster than conventional suturing. There were no statistical differences between the groups for corneal thickness, endothelial cell counts, specular microscopy parameters, retina cell counts, and electroretinogram measurements. The nitinol clip prototype is well tolerated and showed no evidence of toxicity in the short-term. The injectable delivery system was faster and technically less challenging than conventional suture techniques.


The effect of an additional birth on low-income urban families.
Abstract The effects of the birth of an additional child to families living in poverty areas of New York City are studied in this paper. Surveys conducted by the National Opinion Research Center in 1965 and 1967 provided the data in a panel of parous or married women of childbearing age. Control ling for the number of children in the family in 1965, the non-occurrence of an additional birth in the following two years was found to have a significant effect on current income, savings, reliance on public assistance, general ability to plan and organize one's household, and wife's employment. No significant effects were found with respect to possession of consumer durables or attending a school or training course. While many claims have been made about the beneficial effects of family planning on family welfare, this study is among a very small number where such effects are empirically documented.


Success of Primary Trabeculectomy in Advanced Open Angle Glaucoma.
The study assesed trabeculectomy survival in advanced open angle glaucoma (OAG). This is a retrospective longitudinal study in advanced OAG undergoing primary trabeculectomy. Clinical and demographic parameters were recorded. Surgical survival (qualified/complete) was calculated by Kaplan-Meier analysis for multiple upper limits of intraocular pressure (IOP) with/without medication (≤21 mmHg, ≤18 mmHg, ≤15 mmHg, ≤12 mmHg); Cox hazard ratio analysis identified parameters influencing survival. We included 165 eyes from 165 OAG patients: primary forms (POAG) - 86 eyes and secondary (pseudoexfoliative, SOAG) - 79 eyes; mean follow-up interval was 36.21 ± 13.49 months. Clinical parameters were comparable between sub-groups at baseline, except a higher IOP in SOAG vs POAG (36.6 ± 13.2 vs 32.7 ± 11.1 mmHg, p = 0.04); IOP reduction was similar (SOAG vs POAG) 53.93% vs 56.19%, p = 0.45, yet longer hospitalization (8.47 ± 4.39 (SOAG) vs 6.69 ± 3.01 days (POAG), p=0.03) and more medications (0.65 ± 0.24 vs 0.36 ± 0.16, p = 0.05) were needed to achieve comparable final IOP (16.0 ± 9.1 vs 15.1 ± 7.8 mmHg, p = 0.45). Kaplan Meier survival analysis applied for IOP ≤21 mmHg, ≤18 mmHg, ≤15 mmHg and ≤12 mmHg, revealed complete success in 26.2%, 27.3%, 34.5% and 54.6% eyes, respectively; qualified success was found in 45.7%, 48.6%, 77% and 88.6% eyes, respectively. Multiple medications at baseline diminished survival in all tested models (hazard ratio HR > 1, p<0.05), while 5FU+needling improved survival, mostly if combined with lower IOP regime: HR = 0.15, 95% CI = [0.07 -1.12], p = 0.06, if IOP ≤15 mmHg and HR = 0.09, 95% CI = [0.02-1.25], p = 0.06, if IOP ≤12 mmHg. Trabeculectomy in advanced OAG reached very good survival rates (77% and 88.6%) at 36 months postoperative, if IOP could be maintained ≤15 mmHg, respectively ≤12 mmHg with medication and additional needling+5FU maneuvers. Specific factors influencing survival were identified for each success definition.


Altered immunoglobulins (A and G) in Ghanaian patients with type 2 diabetes.
Elevated immunoglobulin levels have been strongly linked to the development and progression of inflammatory disorders such as type 2 diabetes and obesity. This study aimed to evaluate circulating immunoglobulin levels and to identify other metabolic factors that influence humoral immune response among Ghanaian subjects with type 2 diabetes. A comparative cross-sectional study conducted at the National Diabetes Management and Research Center, Accra. Eighty persons with type 2 diabetes were age-matched with 78 controls. Immunoglobulin A, immunoglobulin G and immunoglobulin M; interleukin 6; fasting blood glucose; glycated hemoglobin; and lipid parameter concentrations were measured. Blood pressure, anthropometry and body composition indices were also assessed. Median immunoglobulin A and immunoglobulin G (g/L) levels were higher in the case group compared with controls (0.89 vs 0.74, p = 0.043; 7.58 vs 7.29, p < 0.001). Immunoglobulin G, immunoglobulin A and interleukin 6 levels in the case cohort, respectively, associated weakly with fasting blood glucose (r = 0.252, p = 0.001; r = 0.170, p = 0.031; r = 0.296, p = 0.001). There were positive correlations within the control group for immunoglobulin A versus interleukin 6 (r = 0.366, p = 0.001) and within the case group for glycated hemoglobin versus interleukin 6 (r = 0.190, p = 0.020). Our data suggest that humoral immune response is altered in subjects with type 2 diabetes and that serum immunoglobulin levels could serve as useful biomarkers in the investigation and management of diabetes mellitus.


Regulation of hepatic lanosterol 14 alpha-demethylase gene expression by dietary cholesterol and cholesterol-lowering agents.
Binding of sterol response element binding protein 1a to sterol response element-1 (SRE-1) in the promoter region of lanosterol 14 alpha-demethylase (14DM) has been demonstrated previously. Decreased 14DM activity has been shown to result in accumulation of the intermediate, 3 beta-hydroxy-lanost-8-en-32-al, a known translational downregulator of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Since it has also been demonstrated that feedback regulation of hepatic HMG-CoA reductase occurs primarily at the level of translation, the effects of dietary cholesterol and cholesterol lowering agents on levels of hepatic 14DM mRNA and immunoreactive protein were investigated. Addition of 1% cholesterol to a chow diet markedly decreased hepatic 14DM mRNA and protein levels in Sprague-Dawley rats. The extent and time course of this decrease in 14DM immunoreactive protein closely paralleled that of HMG-CoA reductase. Supplementation of the diet with the HMG-CoA reductase inhibitor, Lovastatin, to a level of 0.02%, raised 14DM mRNA and protein levels 2- to 3-fold. Addition of 2% Colestipol, a bile acid binding resin, to the chow diet caused smaller increases. The highest level of 14DM protein expression was observed in liver, the major site of feedback regulation of HMG-CoA reductase by cholesterol. Taken together, these observations suggest a critical role for 14DM in the feedback regulation of hepatic HMG-CoA reductase.


Impact of the Liquid Crystal Order of Poly(azomethine-sulfone)s on the Semiconducting Properties.
Organic semiconductors are an attractive class of materials with large application in various fields, from optoelectronics to biomedicine. Usually, organic semiconductors have low electrical conductivity, and different routes towards improving said conductivity are being investigated. One such method is to increase their ordering degree, which not only improves electrical conduction but promotes cell growth, adhesion, and proliferation at the polymer-tissue interface. The current paper proposes a mathematical model for understanding the influence of the ordering state on the electrical properties of the organic semiconductors. To this end, a series of aromatic poly(azomethine)s were prepared as thin films in both amorphous and ordered states, and their supramolecular and electrical properties were analyzed by polarized light microscopy and surface type cells, respectively. Furthermore, the film surface characteristics were investigated by atomic force microscopy. It was established that the manufacture of thin films from mesophase state induced an electrical conductivity improvement of one order of magnitude. A mathematical model was developed in the framework of a multifractal theory of motion in its Schrodinger representation. The model used the order degree of the thin films as a fractality measure of the physical system's representation in the multifractal space. It proposed two types of conductivity, which manifest at different ranges of fractalization degrees. The mathematical predictions were found to be in line with the empirical data.