Viral teratogenesis: brain developmental damage associated with maturation state at time of infection.
The rat brain continues to mature after birth and is particularly vulnerable to developmental damage following perinatal insult. Borna disease virus (BDV) infection of postnatal day one (PND-1) rat brain causes a non-encephalitic, persistent infection associated with developmental neuroanatomical and behavioral abnormalities. To test the hypothesis that BDV infection during different brain developmental stages yields variable pathological and clinical disease sequelae, rats were examined for BDV-induced neuroanatomical and behavioral abnormalities following inoculation with BDV on PND-15, and the findings were compared to those resulting from inoculation on PND-1. Similar to rats inoculated with BDV on PND-1, PND-15 inoculated rats developed a persistent infection associated with body weight stunting, abnormal salt taste preference and hippocampal neuron degeneration. However, unlike rats infected with BDV on PND-1, PND-15 inoculated rats did not show signs of cerebellar hypoplasia or hyperactivity. Thus, the risk of BDV-induced damage to specific brain regions, and their associated behaviors, appears, in part, dependent upon the brain's developmental stage at time of BDV-infection. These studies provide evidence of the selective vulnerability of specific neuroanatomic regions and behaviors in developing nervous system to virus-induced damage.


Interaction of colchicine analogues with purified tubulin.
Binding of two colchicine analogues, desacetamidocolchicine and 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone to purified tubulin have been studied. Both analogues bind to tubulin with a significant increase in fluorescence polarization of the drugs in solutions containing tubulin. The Kd for tubulin-drug complexes were found to be 1.25 X 10(-6) M and 1.08 X 10(-6) M for desacetamidocolchicine and 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone, respectively. Scatchard analysis of the fluorescence titration curve of drug tubulin interaction also gives the values of stoichiometry and affinity constant. These were 0.8 and 1.6 X 10(6) M-1 for desacetamidocolchicine, and 0.9 and 0.58 X 10(6) M-1 for 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone.


Necroptosis: an emerging form of programmed cell death.
Necrosis plays an important role in multiple physiological and pathological processes. Recently, a relatively new form of necrosis has been characterized as "necroptosis". Morphologically, necroptosis exhibits the features of necrosis; however, necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinase 1 and 3 (RIP1 and RIP3) and can be specifically inhibited by necrostatins. Necroptosis has been found to contribute to the regulation of immune system, cancer development as well as cellular responses to multiple stresses. In this review, we will summarize the signaling pathway, biological effects and pathological significance of this specific form of programmed cell death.


Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan.
The aim of present study was to investigate the cytoprotective effect of amifostine on salivary glands in 131I-treated differentiated thyroid cancer (DTC) patients using serial quantitative analysis of salivary gland scans. Serial quantitative salivary scintigraphies were performed in 80 newly diagnosed DTC patients (9 men, 71 women; mean age, 43.2 years old; range, 21-58 years old). Forty-two patients were assigned randomly to the amifostine treatment group, which received 300 mg/m2 amifostine intravenously before 131I administration. In both amifostine-treated and nontreated groups statistically significant declines of functional parameters after 131I treatment were revealed by quantitative salivary scintigraphy in DTC patients. Amifostine pretreatment did not prevent the parenchymal damage to major salivary gland function after 131I treatment (F = 1.37, p = 0.2461). However, the dose of 131I had significant effects on salivary gland function after 131I treatment (F = 9.72, p = 0.0002). The present study did not show cytoprotective effects of amifostine for DTC patients treated with 131I.


A national study on the prevalence of child abuse and neglect in Suriname.
The prevalence of child maltreatment in Suriname has never been subjected to a reliable assessment. The only data available include rough estimates of a range of internationally comparable indicators extrapolated from child protection and police corps statistics for offenses against children. This study aimed to provide a reliable estimate of the prevalence of all forms of child maltreatment in Suriname. One thousand three hundred and ninety-one (1,391) adolescents and young adults of different ethnicities completed a questionnaire about child maltreatment. The study sample, obtained by random probability sampling, consisted of students (ages 12 through 22) from five districts in Suriname. A significant proportion of Surinamese children experienced maltreatment. In total, 86.8% of adolescents and 95.8% of young adults reported having been exposed to at least one form of child maltreatment during their lives. Among the adolescents, 57.1% were exposed to child maltreatment in the past year. When the definition of the National Incidence Study was applied, 58.2% of adolescents and 68.8% of young adults had been exposed to at least one form of maltreatment. Among adolescents, 36.8% reported having experienced at least one form of maltreatment in the past year. The results indicate the (extremely) high lifetime and year prevalence of child maltreatment in Suriname. The serious and often lifelong consequences of such maltreatment indicate that a national approach to child abuse and neglect, including the development of a national strategic plan, a national surveillance system and changes to the state's programmatic and policy response, is urgently needed.


The primary structure of histone H4 from the nematode Caenorhabditis elegans.
1. The complete amino acid sequence of histone H4 from the nematode Caenorhabditis elegans has been established. 2. The polypeptide chain consists of 102 amino acids and has a completely alpha-N-blocked serine at residue 1. 3. The sequence differs from vertebrate H4 in position 73 by substitution of cysteine for threonine. 4. Lysine in position 20 is monomethylated.


Association between primary care practice characteristics and emergency department use in a medicaid managed care organization.
Many patients use emergency departments (EDs) for primary care. Previous studies have found that patient characteristics affect ED utilization. However, such studies have led to few policy changes. We sought to determine whether Medicaid patients' ED use is associated with characteristics of their primary care practices. This was a cohort study. A total of 57,850 patients, assigned to 353 primary care practices affiliated with a Medicaid HMO, were included. Predictor variables were characteristics of primary care practices, which were measured by visiting each practice. The outcome variable was ED use adjusted for patient characteristics. On average, patients made 0.80 ED visits/person/yr. Patients from practices with more than 12 evening hours/wk used the ED 20% less than patients from practices without evening hours. A higher ratio of the number of active patients per clinician-hour of practice time was associated with more ED use. When more Medicaid patients were in a practice, these patients used the ED more frequently. Other factors associated with ED use included equipment for the care of asthma and presence of nurse practitioners and physician assistants. Modifiable characteristics of primary care practices were associated with ED use. Because the observational design of this study does not allow definitive conclusions about causality, future studies should include intervention trials to determine whether changing practice characteristics can reduce ED use. Improving primary care access and scope of services may reduce ED use. Focusing on systems issues rather than patient characteristics may be a more productive strategy to improve appropriate use of emergency medical care.


Hfe Is Highly Expressed in Liver Sinusoidal Endothelial Cells But Is Not Needed to Maintain Systemic Iron Homeostasis In Vivo.
Supplemental Digital Content is available in the text.


An Efficient Method for Multi-Parameter Mapping in Quantitative MRI Using B-Spline Interpolation.
Quantitative MRI methods that estimate multiple physical parameters simultaneously often require the fitting of a computational complex signal model defined through the Bloch equations. Repeated Bloch simulations can be avoided by matching the measured signal with a precomputed signal dictionary on a discrete parameter grid (i.e. lookup table) as used in MR Fingerprinting. However, accurate estimation requires discretizing each parameter with a high resolution and consequently high computational and memory costs for dictionary generation, storage, and matching. Here, we reduce the required parameter resolution by approximating the signal between grid points through B-spline interpolation. The interpolant and its gradient are evaluated efficiently which enables a least-squares fitting method for parameter mapping. The resolution of each parameter was minimized while obtaining a user-specified interpolation accuracy. The method was evaluated by phantom and in-vivo experiments using fully-sampled and undersampled unbalanced (FISP) MR fingerprinting acquisitions. Bloch simulations incorporated relaxation effects (T1,T2) , proton density (PD ) , receiver phase ( φ0 ), transmit field inhomogeneity ( B1+ ), and slice profile. Parameter maps were compared with those obtained from dictionary matching, where the parameter resolution was chosen to obtain similar signal (interpolation) accuracy. For both the phantom and the in-vivo acquisition, the proposed method approximated the parameter maps obtained through dictionary matching while reducing the parameter resolution in each dimension ( T1,T2,B1+ ) by - on average - an order of magnitude. In effect, the applied dictionary was reduced from 1.47GB to 464KB . Furthermore, the proposed method was equally robust against undersampling artifacts as dictionary matching. Dictionary fitting with B-spline interpolation reduces the computational and memory costs of dictionary-based methods and is therefore a promising method for multi-parametric mapping.


The Effect of Face-to-Face and Phone Call Motivational Interviewing on Cervical Cancer Screening.
Having regular screening tests largely depends on motivational factors. Motivational interviewing (MI) facilitates the movement through the stages of the transtheoretical model of change. The aim of this study was to compare the effect of face-to-face and phone call MI on cervical cancer screening. This experimental study was conducted on 150 eligible women referred to health centers in Tabriz, Iran. The women were assigned into 3 groups (face-to-face MI, phone MI, or control) using blocked randomization. The face-to-face MI group participated in 3 weekly group counseling sessions, and the motivational phone call group received 3 weekly phone calls. The participants completed the demographic and obstetric questionnaire and stages of change checklist. Adherence to Pap smear was checked, according to the health profile, 6 months after the intervention. The data were analyzed using SPSS 24 software. Chi-square, homogeneity test, and sequential logistic regression by the generalized estimating equations were used. After the intervention, about 32% women from the face-to-face MI group, 22% from the motivational phone call group, and 4% from the control group underwent Pap smear screening ( P = .002). There was no significant difference between the 2 interventional groups in Pap smear frequency ( P = .36). The study results indicated that both face-to-face and phone call MI are effective in motivating women to have a Pap smear. Further studies are recommended to consider long-term follow-up (3-5 years). It is recommended that healthcare providers use motivational phone call to encourage cancer screening behaviors.


Sleep Subdomain of the Sinonasal Outcome Test as a Potential Screening Tool for Sleep Apnea in Chronic Rhinosinusitis.
Approximately 20% of patients with chronic rhinosinusitis (CRS) have comorbid obstructive sleep apnea (OSA). Patients with undiagnosed OSA are at high risk for perioperative complications. The Sinonasal Outcomes Test (SNOT-22) Questionnaire is commonly administered to CRS patients, whereas OSA screening tools are less routinely employed. This study compared SNOT-22 sleep subdomain (Sleep-SNOT) scores among non-OSA CRS versus OSA-CRS patients undergoing ESS, and assessed sensitivity, specificity, and diagnostic accuracy of the Sleep-SNOT for OSA screening. Retrospective review of patients that underwent endoscopic sinus surgery (ESS) for CRS from 2012 to 2021. Patients either carried a reported OSA diagnosis and completed the SNOT-22, or had undocumented OSA status and completed both STOP-BANG and SNOT-22. Demographics, questionnaire scores, and OSA status were collected. A receiver operating characteristic (ROC) curve assessed cutoff scores, sensitivity, and specificity of the Sleep-SNOT for OSA screening. Of 600 patients reviewed, 109 were included. 41% had comorbid OSA. OSA patients had a higher BMI (32.1 ± 7.7 vs. 28.35 ± 6.7 kg/m2 ; p = 0.02), Sleep-SNOT (21.96 ± 12.1 vs. 16.8 ± 11.2; p = 0.021) and STOP-BANG (3.1 ± 1.44 vs. 2.06 ± 1.27; p = 0.038) scores. A Sleep-SNOT score of 17.5 had a sensitivity of 68.9%, specificity of 55.7%, and diagnostic accuracy of 63% for OSA detection (p = 0.022). Sleep-SNOT scores are greater for CRS-OSA patients. The Sleep-SNOT ROC curve demonstrates a high sensitivity, specificity, and accuracy for OSA screening in CRS patients. A Sleep-SNOT score of ≥17.5 should prompt further OSA evaluation. The Sleep-SNOT may be considered as a surrogate OSA screening tool when other validated tools are not employed. Retrospective chart review, Level 3 Laryngoscope, 133:2029-2034, 2023.


Amyloid beta peptide causes chronic glial cell activation and neuro-degeneration after intravitreal injection.
We have previously demonstrated that amyloid beta (Abeta) peptide is acutely toxic to retinal neurones in vivo and that this toxicity is mediated by an indirect mechanism. We have now extended these studies to look at the chronic effect of intravitreal injection of Abeta peptides on retinal ganglion cells (RGC), the projection neurones of the retina and the glial cell response. 5 months after injection of Abeta1-42 or Abeta42-1 there was no significant reduction in RGC densities but there was a significant reduction in the retinal surface area after both peptides. Phosphate-buffered saline (PBS) injection had no effect on retinal size or RGC density. There was a pronounced reduction in the number of large RGCs with a concomitant significant increase in medium and small RGCs. There was no change in cell sizes 5 months after injection with PBS. At 5 months after injection of both peptides, there was marked activation of Muller glial cells and microglia. There was also expression of the major histocompatibility complex (MHC) class II molecule on some of the microglial cells but we saw no evidence of T-cell infiltration into the injected retinas. In order to elucidate potential toxic mechanisms, we have looked at levels of glutamine synthetase and nitric oxide synthase. As early as 2 days after injection we noted that activation of Muller glia was associated with a decrease in glutamine synthetase immuno-reactivity but there was no detectable expression of inducible nitric oxide synthase in any retinal cells. These results suggest that chronic activation of glial cells induced by Abeta peptides may result in chronic atrophy of projection neurones in the rat retina.


An enteric duplication cyst of the pancreas causing abdominal pain and pancreatitis in a child.
A rare case of a gastric duplication in the tail of the pancreas in a child presenting with recurrent abdominal pain and evidence of pancreatic calcification suggesting pancreatitis was cured by excision of the cyst and adjacent pancreas. Congenital causes of pancreatitis are rare, but are curable with surgery. These lesions are often misdiagnosed, and patients may be subjected to inappropriate surgery. Imaging is sensitive in the detection of such lesions, but the lack of specific features necessitates an index of suspicion. Similar cases have been described previously, but the pancreatic tail is rarely involved.


Pulmonary artery sling in identical twins--report of two cases.
Pulmonary artery sling was successfully treated by division and reimplantation of the left pulmonary artery in identical twins. Long-term patency of the reimplanted pulmonary artery in both twins as well as in 4 other operated children was confirmed by lung perfusion scan. Early operative treatment of pulmonary artery sling is advocated.


Leveraging HFRS to assess how frailty affects healthcare resource utilization after elective ACDF for CSM.
Frailty is a common comorbidity associated with worsening outcomes in various medical and surgical fields. The Hospital Frailty Risk Score (HFRS) is a recently developed tool which assesses frailty using 109 International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) comorbidity codes to assess severity of frailty. However, there is a paucity of studies utilizing the HFRS with patients undergoing anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). The aim of this study was to investigate the impact of HFRS on health care resource utilization following ACDF for CSM. A retrospective cohort study was performed using the Nationwide Inpatient Sample (NIS) database from 2016-2019. All adult (≥18 years old) patients undergoing primary, ACDF for CSM were identified using the ICD-10 CM codes. Weighted patient demographics, comorbidities, perioperative complications, LOS, discharge disposition, and total admission costs were assessed. The 109 ICD-10 codes with pre-assigned values from 0.1 to 7.1 pertaining to frailty were queried in each patient, with a cumulative HFRS ≥5 indicating a frail patient. Patients were then categorized as either Low HFRS (HFRS<5) or Moderate to High HFRS (HFRS≥5). A multivariate stepwise logistic regression was used to determine the odds ratio for risk-adjusted extended LOS, non-routine discharge disposition, and increased hospital cost. A total of 29,305 patients were identified, of which 3,135 (10.7%) had a Moderate to High HFRS. Patients with a Moderate to High HFRS had higher rates of 1 or more postoperative complications (Low HFRS: 9.5% vs. Moderate-High HFRS: 38.6%, p≤.001), significantly longer hospital stays (Low HFRS: 1.8±1.7 days vs. Moderate-High HFRS: 4.4 ± 6.0, p≤.001), higher rates of non-routine discharge (Low HFRS: 5.8% vs. Moderate-High HFRS: 28.2%, p≤.001), and increased total cost of admission (Low HFRS: $19,691±9,740 vs. Moderate-High HFRS: $26,935±22,824, p≤.001) than patients in the Low HFRS cohort. On multivariate analysis, Moderate to High HFRS was found to be a significant independent predictor for extended LOS [OR: 3.19, 95% CI: (2.60, 3.91), p≤.001] and non-routine discharge disposition [OR: 3.88, 95% CI: (3.05, 4.95), p≤.001] but not increased cost [OR: 1.10, 95% CI: (0.87, 1.40), p=.418]. Our study suggests that patients with a higher HFRS have increased total hospital costs, a longer LOS, higher complication rates, and more frequent nonroutine discharge compared with patients with a low HFRS following elective ACDF for CSM. Although frail patients should not be precluded from surgical management of cervical spine pathology, these findings highlight the need for peri-operative protocols to medically optimize patients to improve health care quality and decrease costs.


The small-scale spatial distribution of male and female plants.
There are many reports of dioecious flowering plants with positive spatial association of gender, such that males and females tend to occur at different sites. This pattern has been interpreted as demonstrating environmenal heterogeneity, the two sexes having different habitat preferences. However, it is not clear: (a) to what extent the literature reflects the greater likelihood of publishing striking positive results; and (b) whether the association of stems of like gender within habitats is caused by differences in microhabitat preference rather than by vegetative ramification. We surveyed natural populations of ten sexually heteromorphic species in southern Quebec, and found that five showed positive association and four showed no association between the genders. With one exception (Silene cucubalus) these results appeared to reflect the presence or absence of vegetative ramification. We conclude that the demonstration of spatial association cannot be used to infer the existence of microenvironmental heterogeneity except in species with no capacity for vegetative ramification. The tenth species, Silene alba, showed negative association, with an excess of neighbouring pairs of unlike gender, but we were unable to reproduce this phenomenon experimentally.


Long-term outcomes of balloon dilation of esophageal strictures in children.
The purpose of this study was to determine the long-term success of the use of angioplasty balloons for dilation of esophageal strictures in children. The authors studied 24 children who had undergone fluoroscopically guided angioplasty balloon dilation of esophageal strictures. Ten children had stricture of the anastomosis after surgical repair of esophageal atresia; five had achalasia; three had strictures due to gastroesophageal reflux; three had corrosive strictures; two had congenital stenosis; and one had stricture after radiation therapy. Success was defined as resolution of the dysphagia a year after dilation. A year after the last dilation, 15 of the 24 children had no dysphagia. Patients in whom treatment was successful included eight children with strictures after surgery for esophageal atresia, one with achalasia, three with strictures caused by gastroesophageal reflux, one with a corrosive stricture, one with congenital stenosis, and one with a stricture resulting from radiation therapy. The long-term results of balloon catheter dilation are highly successful in patients with stricture after surgical repair of esophageal atresia and stricture due to gastroesophageal reflux. Dilation is not as valuable in the treatment of esophageal strictures resulting from other causes.


Postoperative prolonged mechanical ventilation in patients with surgically treated pyogenic spondylodiscitis: a surrogate endpoint for early postoperative mortality.
Surgical procedures with spinal instrumentation constitute a prevalent and occasionally highly indicated treatment modality in patients with pyogenic spondylodiscitis (PSD). However, surgical therapy might be associated with the need of prolonged postoperative intensive care medicine which in turn might impair intended operative benefit. Therefore, we analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential correlations with mortality in this vulnerable patient cohort. Between 2012 and 2018, 177 consecutive patients received stabilization surgery for PSD at the authors' neurosurgical department. PMV was defined as postoperative mechanical ventilation of more than 24 h. A multivariable analysis was performed to identify independent predictors for 30-day mortality. Twenty-three out of 177 patients (13%) with PSD suffered from postoperative PMV. Thirty-day mortality rate was 5%. Multivariable analysis identified "spinal empyema" (p = 0.02, odds ratio (OR) 6.2, 95% confidence interval (CI) 1.3-30.2), "Charlson comorbidity index (CCI) > 2" (p = 0.04, OR 4.0, 95% CI 1.0-15.5), "early postoperative complications (PSIs)" (p = 0.001, OR 17.1, 95% CI 3.1-96.0) and "PMV > 24 hrs" (p = 0.002, OR 13.0, 95% CI 2.7-63.8) as significant and independent predictors for early postoperative mortality. The present study indicates PMV to significantly correlate to elevated early postoperative mortality rates following stabilization surgery for PSD. These results might entail further scientific efforts to investigate PMV as a so far underestimated negative prognostic factor in the surgical treatment of PSD.


Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears.
We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione peroxidase activity) and thyroid status (concentrations and ratios of thyroxine, T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among cohorts, and relationships to circulating concentrations of contaminants. Concentrations of total mercury (Hg) in whole blood were similar among cohorts (prime aged males and females, older animals, ages≥16 years, and young animals, ages 1-5 years; 48.44±35. 81; p=0.253). Concentrations of sum of seven polychlorinated biphenyls (∑PCB7) in whole blood were greater in females (with and without cubs, 26.44±25.82 ng/g ww) and young (26.81±10.67 ng/g ww) compared to males (8.88±5.76 ng/g ww, p<0.001), and significantly related to reduced body condition scores (p<0.001). Concentrations of Se and albumin were significantly greater in males than females (whole blood Se, males, 42.34 pmol/g ww, females, 36.25±6.27 pmol/g ww, p=0.019; albumin, males, 4.34±0.34 g/dl, females, 4.10±0.29 g/dL, p=0.018). Glutathione peroxidase activity ranged from 109.1 to 207.8 mU/mg hemoglobin, but did not differ significantly by sex or age (p>0.08). Thyroid hormones were greater in females (solitary females and females with cubs) compared to males (p<0.001). Biomarkers of Se status and concentrations of T3 were significantly positively related to Hg in all prime aged polar bears (p<0.03). Albumin concentrations were significantly positively related to total TT4, and significantly negatively related to concentrations of ∑PCB7 (p<0.003). Total thyroxine (TT4) was significantly negatively associated with blood concentrations of ∑PCB7 in solitary females (p=0.045). These data suggest that female polar bears were more susceptible to changes in blood-based biomarkers of selenium and thyroid status than males. Further classifications of the physiologic states of polar bears and repeated measures of individuals over time are needed to accurately assess the biological impact of combined toxicant exposures.


Income-related inequalities in health and health services use in Israel.
Income-related inequalities in health and in health services use pose a disturbing and challenging issue in health systems, which are based on social health insurance such as Israel. To explore income-related inequalities in health and in health services use in Israel in 2009-2010. We used the Central Bureau of Statistics file, which linked information on 7,175 households (24,595 persons) from the 2009 Health Survey and the 2010 Incomes Survey. Raw and adjusted concentration curves and indices were calculated for ten chronic conditions (adjusting for age), visits to physicians and hospitalizations (adjusting for health and location). There is no income-related inequality in asthma and in cancer. The income-related inequality in the remaining eight conditions is 'pro-poor', namely, they are more prevalent among poor households. The order of the level of inequality is (from the least unequally distributed): any condition, hypertension, heart diseases, diabetes, depression, respiratory diseases, digestive diseases, and the condition with the highest income-related inequality is activities of daily living (ADL) limitations. The income-related inequality in secondary physicians' services is 'pro-rich'. The income-related inequality in primary care is 'pro- poor'. Hospitalization days are significantly more unequally - 'pro-poor' - distributed in the population. International findings are basically similar to the ones found in this paper. Three reasons are believed to have caused these income-related inequalities: the use of preventive services, health behavior and compliance with the doctors' directions; they might constitute a useful framework for strategizing interventions. The efforts of the Ministry of Health and of the sickness funds launched in 2010 to reduce inequalities should be evaluated by repeating the present analysis with newer data.


Synchronous diagnosis of prostatic adenocarcinoma and sarcoidosis.
Sarcoidosis and prostatic carcinoma in the same patient is a rare clinical entity. This is the third reported case of such pathology. Immunodeficiency caused by sarcoidosis may induce immunity disorientation resulting in the presence of prostatic carcinoma. Sarcoidosis in relation with malignancy may give some answers for the etiopathology of cancer.


PTH regulates osteogenesis and suppresses adipogenesis through Zfp467 in a feed-forward, PTH1R-cyclic AMP-dependent manner.
Conditional deletion of the PTH1R in mesenchymal progenitors reduces osteoblast differentiation, enhances marrow adipogenesis, and increases zinc finger protein 467 (Zfp467) expression. In contrast, genetic loss of Zfp467 increased Pth1r expression and shifts mesenchymal progenitor cell fate toward osteogenesis and higher bone mass. PTH1R and ZFP467 could constitute a feedback loop that facilitates PTH-induced osteogenesis and that conditional deletion of Zfp467 in osteogenic precursors would lead to high bone mass in mice. Prrx1Cre; Zfp467fl/fl but not AdipoqCre; Zfp467fl/fl mice exhibit high bone mass and greater osteogenic differentiation similar to the Zfp467-/- mice. qPCR results revealed that PTH suppressed Zfp467 expression primarily via the cyclic AMP/PKA pathway. Not surprisingly, PKA activation inhibited the expression of Zfp467 and gene silencing of Pth1r caused an increase in Zfp467 mRNA transcription. Dual fluorescence reporter assays and confocal immunofluorescence demonstrated that genetic deletion of Zfp467 resulted in higher nuclear translocation of NFκB1 that binds to the P2 promoter of the Pth1r and increased its transcription. As expected, Zfp467-/- cells had enhanced production of cyclic AMP and increased glycolysis in response to exogenous PTH. Additionally, the osteogenic response to PTH was also enhanced in Zfp467-/- COBs, and the pro-osteogenic effect of Zfp467 deletion was blocked by gene silencing of Pth1r or a PKA inhibitor. In conclusion, our findings suggest that loss or PTH1R-mediated repression of Zfp467 results in a pathway that increases Pth1r transcription via NFκB1 and thus cellular responsiveness to PTH/PTHrP, ultimately leading to enhanced bone formation.


Activation and increased production of interleukin-17 and tumour necrosis factor-α of mucosal-associated invariant T cells in patients with periodontitis.
Mucosal-associated invariant T (MAIT) cells are known to be resident in oral mucosal tissue, but their roles in periodontitis are unknown. This study aimed to examine the level and function of MAIT cells in periodontitis patients. Frequency, activation, and function of MAIT cells from 28 periodontitis patients and 28 healthy controls (HCs) were measured by flow cytometry. Circulating MAIT cells were numerically reduced in periodontitis patients. Moreover, they exhibited higher expression of CD69 and annexin V, together with more increased production of interleukin (IL)-17 and tumour necrosis factor (TNF)-α, in periodontitis patients than in HCs. Interestingly, periodontitis patients had higher frequencies of MAIT cells in gingival tissue than in peripheral blood. In addition, circulating MAIT cells had elevated expression of tissue-homing chemokine receptors such as CCR6 and CXCR6, and the corresponding chemokines (i.e., CCL20 and CXCL16) were more strongly expressed in inflamed gingiva than in healthy gingiva. This study demonstrates that circulating MAIT cells are numerically deficient with an activated profile toward the production of IL-17 and TNF-α in periodontitis patients. Furthermore, circulating MAIT cells have the potential to migrate to inflamed gingival tissues.


Therapeutic Strategies Targeting Urokinase and Its Receptor in Cancer.
Several studies have ascertained that uPA and uPAR do participate in tumor progression and metastasis and are involved in cell adhesion, migration, invasion and survival, as well as angiogenesis. Increased levels of uPA and uPAR in tumor tissues, stroma and biological fluids correlate with adverse clinic-pathologic features and poor patient outcomes. After binding to uPAR, uPA activates plasminogen to plasmin, a broad-spectrum matrix- and fibrin-degrading enzyme able to facilitate tumor cell invasion and dissemination to distant sites. Moreover, uPAR activated by uPA regulates most cancer cell activities by interacting with a broad range of cell membrane receptors. These findings make uPA and uPAR not only promising diagnostic and prognostic markers but also attractive targets for developing anticancer therapies. In this review, we debate the uPA/uPAR structure-function relationship as well as give an update on the molecules that interfere with or inhibit uPA/uPAR functions. Additionally, the possible clinical development of these compounds is discussed.


Time from trophectoderm biopsy to vitrification affects the developmental competence of biopsied blastocysts.
The present study aimed to examine the correlations of the time interval from trophectoderm (TE) biopsy to vitrification with the blastocyst survival rate and blastocyst outgrowth ability. A total of 1,202 mouse blastocysts were randomly divided into control (non-biopsy) and TE biopsy groups. The biopsied blastocysts were vitrified at various time points. The survival rate after warming, blastocyst adhesion rate, and outgrowth area was investigated. Several biopsied blastocysts were cultured in a time-lapse incubator, and the time required for re-expansion was measured. Blastocyst survival rates after warming and blastocyst adhesion rates were comparable between the control and biopsy groups. The area of trophoblast outgrowth in the 1-h biopsy group was significantly smaller than that in the control, 0-h biopsy, and 4-h biopsy groups (p = 0.0304, p = 0.0058, and p = 0.0029, respectively). Re-expansion of blastocysts was observed at a high incidence 1-2 h after TE biopsy. The vitrification of biopsied blastocysts in the process of re-expansion impairs outgrowth competence; therefore, blastocyst vitrification should be performed immediately after TE biopsy and before initiation of re-expansion.


Psychosocial functioning of spouses in the chronic phase after stroke: improvement or deterioration between 1 and 3 years after stroke?
To describe the psychosocial functioning of spouses of stroke patients at 1 and 3 years after stroke and identify predictors of substantial negative change in psychosocial functioning. Prospective study (N=119). Five domains of psychosocial functioning were assessed: burden, life satisfaction, depression, harmony in the relationship and social support. We used paired t-tests to describe changes and identified substantial changes using an Effect Size of 0.5 as the cut-off point. Fifty-one percent reported significant burden, 46% were dissatisfied with life and 51% reported depressive symptoms 1 year after the stroke. Changes in psychosocial functioning between 1 and 3 years post stroke were reported by 27%-57% of the spouses. Although burden improved, life satisfaction, social support and harmony in the relationship deteriorated significantly. The percentage of spouses with depressive symptoms remained stable. Spouses with young children were at risk of deteriorating psychosocial functioning. A large proportion of spouses experience serious caregiver burden, depression and decreased life satisfaction, 1 year as well as 3 years after the stroke, and harmony in the relationship, social support and life satisfaction decline over time. Rehabilitation programmes should give more attention to the relationship with the patient's partner, family life and the maintenance of a support network.


Silver staining of proteins in polyacrylamide gels: increased sensitivity by a blue toning.
An image amplification of silver-stained proteins in polyacrylamide gels by a blue toning has been developed. Following the silver staining, this technique is fast, simple, requires only stable and inexpensive reagents, and its sensitivity is three- to sevenfold higher than the silver staining alone, and 300- to 700-fold higher than the Coomassie blue. When combined with a silver staining utilizing dithiothreitol (J. H. Morrissey, (1981) Anal. Biochem. 117, 307-310) this method is shown to be uniform in sensitivity for five standard proteins. The blue toning does not affect the linearity of the staining and allows the quantitation of proteins by densitometric evaluation.


The impact of the Safe Delivery Application on knowledge and skills managing postpartum haemorrhage in a low resource setting: a cluster randomized controlled trial in West Wollega region, Ethiopia.
Postpartum haemorrhage is one of the leading causes of maternal mortality in low-income countries. Improving health workers' competencies in obstetric emergencies in low-income settings, has been recognized as an important factor in preventing maternal mortality and morbidity. mHealth interventions in maternal and newborn health care has shown the potential to improve health service delivery. Strong study designs such as randomized controlled trials are missing to estimate the effectiveness of the mHealth interventions. Between August 2013 and August 2014, 70 health facilities in West Wollega Region, Ethiopia were included and randomized to intervention or control in a cluster randomized controlled trial. At intervention facilities birth attendants were provided with a smartphone with the SDA installed. Of 176 midwives and "health extension workers," 130 completed at 12 months follow-up. At baseline and after 6- and 12-months participants were assessed. Knowledge was tested by a Key Feature Questionnaire, skills by an Objective Structured Assessment of Technical Skills in a structured role-play scenario. Baseline skills scores were low and comparable with a median of 12/100 in the intervention and the control group. After 6 months skills had doubled in the intervention group (adjusted mean difference 29.6; 95% CI 24.2-35.1 compared to 1·8; 95% CI - 2.7 to 6.3 in the control group). At 12 months skills had further improved in the intervention group (adjusted mean difference 13.3; 95% CI 8.3-18.3 compared to 3.1; 95% CI - 1.0 to 7.3 in the control group). Knowledge scores also significantly improved in the intervention group compared to the control (adjusted mean difference after 12 months 8.5; 95% CI 2.0-15.0). The Safe Delivery App more than doubled clinical skills for managing postpartum haemorrhage among birth attendants making it an attractive tool to reduce maternal mortality. Clinicaltrial.gov Identifier NCT01945931. September 5, 2013.


Productivity of key informants for identifying blind children: evidence from a pilot study in Malawi.
To determine the productivity of village-based 'key informants' (KIs) in identifying blind children. Ngabu subdistrict (population 101,000) of Chikwawa district was divided into KI catchment areas. KIs, selected by local village leaders, were trained to register children reported to be blind or with severe visual impairment. These children were clinically assessed at designated centres. In total, 44 KIs were selected and trained to cover 196 villages in Ngabu. They identified and referred 151 children, 37 of whom were blind (presenting vision <3/60 best eye). Overall, village leaders tended to choose female KIs (80%) compared to male KIs (20%); however, male KIs tended to be more productive, identifying 4.22 children each (compared to 3.23 for female KIs). Male KIs were 2.7 times more likely to identify blind children compared to female KIs. Only 25% of all identified blind children of school going age were in school. KIs may be effective in identifying blind children in the community; however, additional work is needed to determine who will be the most effective KI in a community and whether gender roles will limit interpretation of findings from KIs activities.


Anti-BCMA Immuno-NanoPET Radiotracers for Improved Detection of Multiple Myeloma.
Current clinical imaging modalities for the sensitive and specific detection of multiple myeloma (MM) rely on nonspecific imaging contrast agents based on gadolinium chelates for magnetic resonance imaging (MRI) or for 18 F-FDG-directed and combined positron emission tomography (PET) and computed tomography (CT) scans. These tracers are not, however, able to detect minute plasma cell populations in the tumor niche, leading to false negative results. Here, a novel PET-based anti-BCMA nanoplatform labeled with 64 Cu is developed to improve the monitoring of these cells in both the spine and femur and to compare its sensitivity and specificity to more conventional immunoPET (64 Cu labeled anti-BCMA antibody) and passively targeted PET radiotracers (64 CuCl2 and 18 F-FDG). This proof-of-concept preclinical study confirmed that by conjugating up to four times more radioisotopes per antibody with the immuno-nanoPET platform, an improvement in the sensitivity and in the specificity of PET to detect tumor cells in an orthotopic model of MM is observed when compared to the traditional immunoPET approach. It is anticipated that when combined with tumor biopsy, this immuno-nanoPET platform may improve the management of patients with MM.


Enhancing the role of the social network in activity (re)engagement post-stroke: a focus group study with rehabilitation professionals.
People post-stroke are at risk of not being able to participate in valued activities. It is important that rehabilitation professionals prepare people post-stroke for the transition home and provide needed support when they live at home. Several authors have suggested that members of the broad social network should play an active role in rehabilitation. This includes informing them about the importance of activity (re)engagement post-stroke and learning strategies to provide support. It is not clear when and how the broad social network can best be equipped to provide adequate activity support. This study aimed to explore stroke professionals' perspectives on strategies that establish a social network that supports activity (re)engagement of people post-stroke, when strategies are best implemented, and the factors that influence the implementation of these strategies. Two focus groups were executed. Content analysis was used to analyze the transcripts of the recorded conversations. Eighteen professionals with various professional backgrounds and roles in treating people post-stroke participated. Strategies to establish a supportive social network included identifying, expanding, informing, and actively engaging network members. Working with the network in the immediate post-stroke phase was regarded as important for improving long-term activity outcomes. Participants expressed that most strategies to equip the social network to support people post-stroke need to take place within community care. However, the participants experienced difficulties in implementing network strategies. Perceived barriers included interprofessional collaboration, professional knowledge, self-efficacy, and financial structures. Strategies to involve the social network of people post-stroke are not fully implemented. Although identifying members of a social network should begin during inpatient rehabilitation, the main part of actively engaging the network will have to take place when the people post-stroke return home. Implementing social network strategies requires a systematic process focusing on collaboration, knowledge, attitude, and skill development.


Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives.
Chemotaxis is an essential mechanism that enables bacteria to move toward favorable ecological niches. Escherichia coli, the historical model organism for studying chemotaxis, has five well-studied chemoreceptors. However, many bacteria with different lifestyle have more chemoreceptors, most of unknown function. Using a high throughput screening approach, we identified a chemoreceptor from Pseudomonas putida KT2440, named McpH, which specifically recognizes purine and its derivatives, adenine, guanine, xanthine, hypoxanthine and uric acid. The latter five compounds form part of the purine degradation pathway, permitting their use as sole nitrogen sources. Isothermal titration calorimetry studies show that these six compounds bind McpH-Ligand Binding Domain (LBD) with very similar affinity. In contrast, non-metabolizable purine derivatives (caffeine, theophylline, theobromine), nucleotides, nucleosides or pyrimidines are unable to bind McpH-LBD. Mutation of mcpH abolished chemotaxis toward the McpH ligands identified - a phenotype that is restored by complementation. This is the first report on bacterial chemotaxis to purine derivatives and McpH the first chemoreceptor described that responds exclusively to intermediates of a catabolic pathway, illustrating a clear link between metabolism and chemotaxis. The evolution of McpH may reflect a saprophytic lifestyle, which would have exposed the studied bacterium to high concentrations of purines produced by nucleic acid degradation.


Why has plasma exchange failed in TRACK syndrome? Lessons from a new variant of the atypical hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening form of thrombotic microangiopathy, associated with high mortality and morbidity. Most cases present with hemolytic anemia, thrombocytopenia, and renal insufficiency. However, it can have unusual multiple end-organ injuries including extrarenal organ and system involvements such as neurologic, cardiac, gastrointestinal, and respiratory systems. We describe a 4-year-old girl who developed aHUS due to the TSEN2 mutation and had cardiac involvement. She did not benefit from plasma exchange, as stated in previous cases. It should be kept in mind that therapeutic plasma exchange may not be beneficial in some cases of aHUS, especially due to genetic mutations.


Deucravacitinib, a selective tyrosine kinase 2 inhibitor, for the treatment of moderate-to-severe plaque psoriasis.
Protein kinases play a crucial role in intracellular signaling pathways that lead to inflammation and cell proliferation. New understandings of the involvement of these metabolic pathways in the pathogenesis of psoriasis allowed the development of a new class of drugs. Unlike biologics, these compounds work by blocking intracellular targets involved in the immune response. Deucravacitinib is an oral small-molecule inhibitor of TYK2 that binds the pseudokinase domain and locks the kinase in an inactive state by an allosteric mechanism, arresting TYK2-mediated signaling cascades and disabling the upregulation of proinflammatory genes implicated in psoriasis. The authors present the results of phase I-III clinical trials of deucravacitinib for the treatment of psoriasis. At week 16 about 56% of the patients treated with deucravacitinib achieved PASI75. No serious infections were reported, nor were thromboembolic events or laboratory abnormalities. Efficacy was reported to be persistent and safety profiles were shown to be consistent for up to 2 years. Deucravacitinib can potentially become a safe, effective, well-tolerated treatment for patients suffering from moderate-to-severe disease. Future studies and real-life experiences will be important to determine the exact role of this drug in the treatment of psoriasis.


Biological activities of chemically synthesized N-acetylneuraminic acid-(alpha 2----6)-monosaccharide analogs of lipid A.
The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate linked to tetraacetyl-N-acetylneuraminic acid (compound A-207) or to N-acetylneuraminic acid (compound A-307), were examined. Although the mitogenic activity of the synthetic compounds was weaker than that of bacterial LPS, doses of 10-50 micrograms/ml of A-207 and 5-10 micrograms/ml of A-307 were capable of increasing incorporation of [3H]thymidine into cultured spleen cells of C57BL/6 mice. Lethal toxicity of A-207 was observed at 10 micrograms/mouse in C57BL/6 mice sensitized with D-galactosamine hydrochloride. However, the attachment of tetraacetyl-N-acetylneuraminic acid or N-acetylneuraminic acid does not appear to enhance the biological activity of acyloxyacylglucosamine-4-phosphate.


Preventing/Reversing Adverse Effects of Endocrine Disruption on Mouse Testes by Normalizing Tissue Resident VSELs.
Reproductive health of men is declining in today's world due to increased developmental exposure to endocrine-disrupting chemicals (EDCs). We earlier reported that neonatal exposure to endocrine disruption resulted in reduced numbers of seminiferous tubules in Stage VIII, decreased sperm count, and infertility along with testicular tumors in 65% of diethylstilbestrol (DES) treated mice. Epigenetic changes due to EDCs, pushed the VSELs out of a quiescent state to enter cell cycle and undergo excessive self-renewal while transition of c-KIT- stem cells into c-KIT + germ cells was blocked due to altered MMR axis (Np95, Pcna, Dnmts), global hypomethylation (reduced expression of 5-methylcytosine) and loss of imprinting at Igf2-H19 and Dlk1-Meg3 loci. The present study was undertaken to firstly show similar defects in FACS sorted VSELs from DES treated testis and to further explore the reversal of these testicular pathologies by (i) oral administration of XAR (a nano-formulation of resveratrol) or (ii) inter-tubular transplantation of mesenchymal stromal cells (MSCs). Similar defects as reported earlier in the testes were evident, based on RNAseq data, on FACS sorted VSELs from DES treated mice. Both strategies were found effective, improved spermatogenesis, increased number of tubules in Stage VIII, normalized numbers of VSELs and c-KIT + cells, improved epigenetic status of VSELs to restore quiescent state, and reduced cancer incidence from 65% after DES to 13.33% and 20% after XAR treatment or MSCs transplantation respectively. Results provide a basis for initiating clinical studies and the study falls under the umbrella of United Nations Sustainable Development Goal 3 to ensure healthy lives and well-being for all of all ages.


Stepwise regulation of TH1 responses in autoimmunity: IL-12-related cytokines and their receptors.
Interleukin (IL)-12 is a key cytokine of cell-mediated immune responses. Until recently, IL-12 was believed to be unique in its ability to induce the differentiation of naive T cells toward the TH1 phenotype and in its pathogenic activity, as shown in various disease models including inflammatory bowel disease. However, recently, 2 additional cytokines closely related to IL-12, IL-23 and IL-27, were discovered. Until then, the role of IL-12 was overestimated because it was believed that the p40 subunit was unique to IL-12. The discovery that IL-12 shares p40 with IL-23 and that IL-23 but not IL-12 is essential in models of chronic inflammation and autoimmunity led to a model in which IL-12 is essential to induce interferon-gamma-producing TH1 cells, whereas IL-23 mediates effector functions. The latest cytokine added to this cytokine family is IL-27. IL-27 has the unique feature to act on naive T cells, rendering them susceptible to IL-12 signaling. Thus, IL-27 may be essential for the early events of a cell-mediated immune response. This review focuses on these novel cytokines and their role in cell-mediated immune responses and discusses differences and common features within the family of IL-12-related cytokines.


Metamorphic protein IscU alternates conformations in the course of its role as the scaffold protein for iron-sulfur cluster biosynthesis and delivery.
IscU from Escherichia coli, the scaffold protein for iron-sulfur cluster biosynthesis and delivery, populates a complex energy landscape. IscU exists as two slowly interconverting species: one (S) is largely structured with all four peptidyl-prolyl bonds trans; the other (D) is partly disordered but contains an ordered domain that stabilizes two cis peptidyl-prolyl peptide bonds. At pH 8.0, the S-state is maximally populated at 25 °C, but its population decreases at higher or lower temperatures or at lower pH. The D-state binds preferentially to the cysteine desulfurase (IscS), which generates and transfers sulfur to IscU cysteine residues to form persulfides. The S-state is stabilized by Fe-S cluster binding and interacts preferentially with the DnaJ-type co-chaperone (HscB), which targets the holo-IscU:HscB complex to the DnaK-type chaperone (HscA) in its ATP-bound from. HscA is involved in delivery of Fe-S clusters to acceptor proteins by a mechanism dependent on ATP hydrolysis. Upon conversion of ATP to ADP, HscA binds the D-state of IscU ensuring release of the cluster and HscB. These findings have led to a more complete model for cluster biosynthesis and delivery.


Leg extension power asymmetry and mobility limitation in healthy older women.
To investigate the association of asymmetry in leg extension power (LEP) with walking and standing balance. Cross-sectional analysis. Research laboratory. Healthy female twins (N=419), ages 63 to 75 years. Not applicable. The LEP difference between the stronger and the weaker leg, measured with the Nottingham power rig, was calculated. Ten-meter maximal walking velocity was assessed in a laboratory corridor on a wide (170 cm) and narrow (35 cm) track, and the ability to maintain tandem stance for 20 seconds was recorded. The mean LEP difference +/- standard deviation between the legs was 15%+/-9% (P<.001). Those with large LEP difference had lower walking velocity and poorer standing balance than those with small LEP difference, in particular when the LEP of the stronger leg was below the median. Even in healthy older women, substantial LEP asymmetry between the lower limbs was present, encumbering walking and standing balance. Lower-limb muscle power asymmetry warrants further study in order to develop well-targeted strategies for preventing mobility limitation in older people.


An acute increase in water temperature can decrease the swimming performance and energy utilization efficiency in rainbow trout (Oncorhynchus mykiss).
In order to evaluate the effects of acute temperature exposure on the swimming performance of rainbow trout (Oncorhynchus mykiss), the critical swimming speed (Ucrit) and oxygen consumption rates (MO2) were determined at different temperatures (13.2, 18.4, and 22.5 °C). The Ucrit and MO2 of different body mass (109.44, 175.74, and 249.42 g) fish were also obtained at 13.4 °C. The Ucrit first increased as the temperature increased from 13.2 to 15.2 °C, which was calculated to be the optimal temperature for the Ucrit, and then decreased with increasing temperature. The optimal swimming speed (Uopt) showed a similar trend to the Ucrit. At a given swimming speed, the MO2 and cost of transport (COT) were significantly higher at 22.5 than at 13.2 °C, suggesting the energy utilization efficiency decreased with increasing temperature. The absolute values of Ucrit and Uopt increased as the body mass increased from 109.44 to 249.42 g, whereas the relative values decreased. Although not statistically significant, the maximum metabolic rate (MMR) tended to increase with temperature but decrease with body mass. Results can be of value in understanding the behavioral and physiological response of rainbow trout to acute temperature change.


In vivo self-assembled drug nanocrystals for metastatic breast cancer all-stage targeted therapy.
Chemotherapy is still the mainstay treatment for metastatic triple-negative breast cancers (TNBC) currently in clinical practice. The unmet needs of chemotherapy for metastatic TNBC are mainly from the insufficient drug delivery and unavailable targeting strategy that thwart the whole progression of metastatic TNBC. The in vivo ligands-mediated active targeting efficiency is usually affected by protein corona. While, the protein corona-bridged natural targeting, in turn, provides a new way for specific drug delivery. Herein, we develop a novel metastatic progression-oriented in vivo self-assembled Cabazitaxel nanocrystals (CNC) delivery system (PC/CNC) through the CNC automatically absorbing functional plasma proteins (transferrin, apolipoprotein A-IV and apolipoprotein E) in vivo, aiming to achieve the simultaneously targeted delivery to primary tumors, circulating tumor cells and metastatic lesions. With the unique advantages of superhigh drug-loading and protein corona empowered active targeting properties to tumor cells, HUVECs, active-platelets and blood-brain barrier/blood-tumor barrier, the PC/CNC exhibits a significantly improved therapeutic effect in metastatic TNBC therapy compared with free drug and CNC-loaded liposomes.


First experiences with high-density silicone oil (Densiron) as an intraocular tamponade in complex retinal detachment.
In this study, we evaluated the anatomic and functional outcome and intraocular adverse effects after a 3-month endotamponade with Densiron 68, a mixture of F(6)H(8) with silicone oil, in complex inferior re-detachments. Forty-eight eyes of 48 patients aged 27-82 years with retinal re-detachment due to proliferative vitreoretinopathy (PVR) grades CP1 to CA7 were included. Mean duration of the Densiron endotamponade was 108.7+/-66.9 days, with a mean follow-up after removal of 102.8+/-31.9 days. Twenty-two patients (45.8%) showed stable retinal reattachment after Densiron removal. Fourteen patients (29.2%) developed retinal re-detachment after removal, generally within 1 month and in the upper circumference (n=8). In 11 patients (22.9%) recurrent re-detachment (inferior n=8) appeared during Densiron endotamponade. In one eye (2.1%) treatment was primarily unsuccessful. Visual acuity improved from mean logMAR 1.66+/-1.03 to 1.47+/-0.97 (not statistically significant, P=0.257). Side effects included temporary inflammatory reaction (n=10), fibrin accumulation (n=6), sterile hypopyon (n=2), vitreous hemorrhage (n=6), elevated IOP (n=5), emulsification (n=4) and chronic hypotony (n=4). The anatomical success rate without further interventions of 45.8% (22 of 48 patients) seems unsatisfactory. However, in evaluating the potential of Densiron, it should be considered that all patients in this study had previous surgery with standard procedures, including silicone oil, which had already failed. Intraoperative laser photocoagulation of the periphery of the upper quadrants might reduce the risk of retinal re-detachments.


Evidence that glutaric acid reduces glutamate uptake by cerebral cortex of infant rats.
The role of excitotoxicity in the cerebral damage of glutaryl-CoA dehydrogenase deficiency (GDD) is under intense debate. We therefore investigated the in vitro effect of glutaric (GA) and 3-hydroxyglutaric (3-OHGA) acids, which accumulate in GDD, on [(3)H]glutamate uptake by slices and synaptosomal preparations from cerebral cortex and striatum of rats aged 7, 15 and 30 days. Glutamate uptake was significantly decreased by high concentrations of GA in cortical slices of 7-day-old rats, but not in cerebral cortex from 15- and 30-day-old rats and in striatum from all studied ages. Furthermore, this effect was not due to cellular death and was prevented by N-acetylcysteine preadministration, suggesting the involvement of oxidative damage. In contrast, glutamate uptake by brain slices was not affected by 3-OHGA exposure. Immunoblot analysis revealed that GLAST transporters were more abundant in the cerebral cortex compared to the striatum of 7-day-old rats. Moreover, the simultaneous addition of GA and dihydrokainate (DHK), a specific inhibitor of GLT1, resulted in a significantly higher inhibition of [(3)H]glutamate uptake by cortical slices of 7-day-old rats than that induced by the sole presence of DHK. We also observed that both GA and 3-OHGA exposure did not alter the incorporation of glutamate into synaptosomal preparations from cerebral cortex and striatum of rats aged 7, 15 and 30 days. Finally, GA in vivo administration did not alter glutamate uptake into cortical slices from 7-day-old rats. Our findings may explain at least in part why cortical neurons are more vulnerable to damage at birth as evidenced by the frontotemporal cortical atrophy observed in newborns affected by GDD.


[The pharmacological modulation of group behavior and biorhythms in the dynamics of a chronic experiment].
Cyclic daily experiments were conducted using the standard method of free behavior of animals in an "open field" (Opto-Varimex, USA) with by the hour recording of locomotor parameters. The neuromodulating activity of 124 pharmacological agents was compared according to the size and duration of their stimulating or depressant effect.


Structure of the biological repeating unit of the O-antigen of Pseudomonas aeruginosa immunotype 4 containing both 2-acetamido-2,6-dideoxy-D-glucose and 2-acetamido-2,6-dideoxy-D-galactose.
A phosphorylated core-lipid A backbone oligosaccharide that carries a disaccharide remainder of the first O-antigen repeating unit was derived by strong alkaline degradation following mild hydrazinolysis of the lipopolysaccharide of Pseudomonas aeruginosa immunotype 4 (serogroup O-1). The structure of the oligosaccharide was determined using ESI MS and NMR spectroscopy and it was demonstrated that 2-acetamido-2,6-dideoxy-D-glucose is the first monosaccharide of the O-polysaccharide that is linked to the LPS core. These data define the structure of the biological repeating unit of the O-antigen.


Commonly used mouse models of osteosarcoma.
Osteosarcoma is the commonest primary tumour of bone and the second highest cause of cancer-related death in the paediatric age group. Little is known of the aetiology of human osteosarcoma and lesser still of the various interactions that occur between host and tumour cells that govern growth and progression of osteosarcoma in vivo. Although numerous osteosarcoma cell lines have been established and characterized in vitro, some as far back as in the 1960s, there is a scarcity of reliable and reproducible in vivo animal models that mimics all aspects of the human condition at the temporal, physiological and histopathological level, hence, making the accurate testing of therapeutic strategies difficult. Given that osteosarcoma is a disease that affects young people and better disease management strategies are essential, development of a robust human osteosarcoma model is long overdue.


Rate of progression of idiopathic full-thickness macular holes before surgery.
To evaluate the spontaneous change in size over the time of idiopathic full-thickness macular holes (IFTMHs) using optical coherence tomography (OCT). This retrospective observational study included 24 eyes of 24 consecutive patients waiting for IFTMH surgery. On OCT horizontal B-scan passing through the center of the fovea, the minimum linear diameter (MLD), the basal diameter (BD), and the presence of vitreomacular adhesion (VMA) were evaluated. The mean total and daily MLD and BD variations were calculated as both absolute and percentage values. The MLD and BD size increase was statistically significant (P < 0.0001). The MLD size increase was significantly greater for small (<250 μm) versus both medium (≥250 to ≤400 μm) and large (>400 μm) IFTMHs in all analysis: the total absolute (P = 0.0248), the daily absolute (P = 0.0186), the total percentage (P = 0.0020), and the daily percentage (P = 0.0008) variations. For the BD, the significance between the same groups was achieved only in the daily percentage change (P = 0.0220). The presence of VMA did not influence the amount of MLD and BD increase. The rate of increase was dependent on the size of hole at presentation (MLD: small: 1.67 microns per day; medium: 0.61 microns per day; large: 0.44 microns per day). Both MLD and BD increase over the time in IFTMHs. There is a significantly greater rate of increase in hole size in smaller holes compared with larger. Therefore, prioritisation for small IFTMH may be justified.


Flow cytometric analysis of DNA content in children with neuroblastoma.
Flow cytometric DNA content analyses were performed in a retrospective study of archival tumor specimens of 15 patients with diagnosed neuroblastoma treated at a single institution. Survival statistics were positively influenced by the presence of aneuploidy. Kaplan-Meier analysis indicated a significant survival advantage for patients with aneuploid tumors (P = .036). Survivors were significantly younger at the time of diagnosis than nonsurvivors, but age at diagnosis did not correlate with DNA content. We conclude that DNA content analysis may be of value in determining the prognosis for children with neuroblastoma.


Organocatalytic asymmetric total synthesis of (R)-rolipram and formal synthesis of (3S,4R)-paroxetine.
An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.


Efficacy of applied behavioral intervention in preschool children with autism for improving cognitive, language, and adaptive behavior: a systematic review and meta-analysis.
To review the effectiveness of applied behavior intervention (ABI) programs for preschool children with autism spectrum disorder (ASD) in their cognitive, adaptive behavior, and language development. Systematic reviews, randomized or quasirandomized controlled trials (RCT) of ABI delivered to preschool children with ASD were reviewed. Quantitative data on cognitive, language, and behavior outcomes were extracted and pooled for meta-analysis (RevMan 4.2). Thirteen studies met the inclusion criteria. Six of these were randomized comparison trials with adequate methodologic quality (PEDro >or= 6). Meta-analysis of 4 studies concluded that, compared with standard care, ABI programs did not significantly improve the cognitive outcomes of children in the experimental group who scored a standardized mean difference (SMD) of 0.38 (95%CI -0.09 to 0.84; P = .1). There was no additional benefit over standard care for expressive language; SMD of 0.37 (95%CI -0.09 to 0.84; P = .11), for receptive language; SMD of 0.29 (95%CI -0.17 to 0.74; P = .22) or adaptive behavior; SMD of 0.30 (95%CI -0.16 to 0.77; P = .20). Currently there is inadequate evidence that ABI has better outcomes than standard care for children with autism. Appropriately powered clinical trials with broader outcomes are required.


Reliability of Vocal Self-assessment Tools in Individuals With Vocal Complaints Applied Using a Digital Platform and In-person.
To verify the reliability of vocal self-assessment tools in individuals with vocal complaints using a digital platform and in-person. Data from 50 Brazilian adults with vocal complaints were collected. The participants answered the Voice Symptoms Scale (VoiSS), the Voice Handicap Index - 10 (VHI-10), and questions regarding personal information and their general health. The data collection occurred in two moments, within a period of 2-14 days, with time variation between participants, and always in the same collection order: 1. using a digital platform (Google Forms); 2. In-person. The data were analyzed descriptively and inferentially using the SPSS 25.0 software and the Wilcoxon Test. The self-perception of vocal symptoms in the Emotional factors for women presented a statistical difference between the digital platform and the in-person response (P = 0.029); higher scores were observed when answers were given in-person compared to using a digital platform. Overall, the participants perceived their voice symptoms and voice handicap similarly when answers were given using a digital platform and in-person. The Emotion voice symptoms in women were the only exception, although remaining deviated; however, the perception of the symptoms may have been attenuated during the in-person care.


Estrogen metabolism in normal and neoplastic endometrium.
Studies on normal endometrium at different phases of the menstrual cycle have shown that progesterone and synthetic progestins reduce the levels of estradiol receptors in the tissue and increase the activity of estradiol-17beta-dehydrogenase, an enzyme that converts estradiol to estrone. These effects may account for the antiestrogenic characteristics of the progestins. Similar effects were obtained in some postmenopausal patients with endometrial adenocarcinoma treated for two to 10 days with oral medroxyprogesterone acetate. These results point to the potential usefulness of a short-term, in vivo biochemical test which, combined with histologic observations, may identify patients who are likely to respond to treatment with progestins.


Quantification of Cadmium in Rice by Surface-enhanced Raman Spectroscopy Based on a Ratiometric Indicator and Conical Holed Enhancing Substrates.
A surface-enhanced Raman spectroscopy (SERS) based method was developed for the quantification of Cd2+ in rice. Gold nano-particles (AuNPs) modified with trimercaptotriazine served as a ratiometric SERS probe for the detection of Cd2+. A conical holed substrate was used to further enhance SERS signals, and hence to improve the sensitivity. A calibration model based on the spectral shape deformation quantitative theory was employed to mitigate the influence of variations in the number and distribution of "hot spots". The proposed SERS method was applied to quantitative analysis of Cd2+ in three types of rice, and achieved satisfactory quantitative results with accuracy comparable to that of the reference method-inductively coupled plasma mass spectrometry. The limit of detection of the proposed method was estimated to be 8 μg kg-1. The proposed SERS method has the potential to become a fast screening method for the detection of Cd2+ in rice.


The immature stages of Eurymerus eburioides Audinet-Serville, 1833 (Coleoptera: Cerambycidae: Ectenessini).
Last instar larva and pupa of Eurymerus eburioides Audinet-Serville, 1833, are described and illustrated based on specimens reared from neonate larvae on Eucalyptus globulus globulus logs in the laboratory. Characters of possible diagnostic value are presented in this work.


Release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126: a comparative study.
Nitrilases constitute an important class of hydrolases, however, cheap and ready availability of enzyme sources limit their practical synthetic applications. The present investigation was directed to compare the applicability of various physical cell disintegration methods namely, solid shear, liquid shear and sonication, for the release of an enantioselective nitrilase from Alcaligenes faecalis MTCC 126. Different parameters associated with each method were optimized in order to ensure maximal release of active nitrilase. The methods were also compared under optimal conditions for their efficiency of nitrilase release and extent of cell disruption, and enzyme release were visualized under a differential interference contrast microscope (DIC) and SDS-PAGE, respectively. Maximum release of the enzyme protein from the cells was observed in case of liquid shear method employing high-pressure homogenization, however, the specific activity of nitrilase was highest in cell-free extract (CFE) generated by sonication. Both the solid shear and liquid shear proved to be equally effective for maximum release of intracellular enzymes, however, from the specific activity point of view, sonication was found to be a better one compared to other two methodologies. The generated cell-free extract can be further employed for the production of enantiopure chiral carboxylic acids, which are important chiral building blocks.


Localization of 4S RNA genes on the chloroplast genome of Chlamydomonas reinhardii.
The genes coding for 4S RNA have been localized on the physical map of the chloroplast genome of Chlamydomonas reinhardii by hybridizing 32P-labelled 4S RNA to EcoRI, BamHI, Bg1II and Hind III chloroplast DNA digests and to hybrid plasmids containing EcoRI and Bam HI chloroplast DNA fragments. At least 10 EcoRI and 7 Bam HI fragments carry sequences coding for 4S RNA. These genes are interspersed throughout the genome. The spacer between the 16S and 23S ribosomal RNA genes, which is repeated twice per chloroplast DNA molecule, codes for at least one 4S RNA, shown to be transcribed from the same strand as the ribosomal RNAs.


A case series and literature review on 98 pediatric patients of germ cell tumor developing growing teratoma syndrome.
Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.


Impact of nitrogen loading rates on treatment performance of domestic wastewater and fouling propensity in submerged membrane bioreactor (MBR).
In this study, performance of laboratory-scale membrane bioreactor (MBR) was evaluated in treating high strength domestic wastewater under two nitrogen loading rates (NLR) i.e., 0.15 and 0.30 kg/m(3)/d in condition 1 and 2, respectively, while organic loading rate (OLR) was constant at 3 kg/m(3)/d in both conditions. Removal efficiencies of COD were above 95.0% under both NLR conditions. Average removal efficiencies of ammonium nitrogen (NH₄(+)-N), total nitrogen (TN) and total phosphorus (TP) were found to be higher in condition 1 (90.5%, 74.0%, and 38.0%, respectively) as compared to that in Condition 2 (89.3%, 35.0%, and 14.0%, respectively). With increasing NLR, particle size distribution shifted from narrow (67-133 μm) towards broader distribution (3-300 μm) inferring lower cake layer porosity over membrane fibers. Soluble extracellular polymer substance (sEPS) concentration increased at higher NLR due to biopolymers released from broken flocs. Higher cake layer resistance (Rc) contributed towards shorter filtration runs during condition 2.


Retracted: Optimization of Artistic Image Segmentation Algorithm Based on Feed Forward Neural Network under Complex Background Environment.
[This retracts the article DOI: 10.1155/2022/9454344.].


Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis.
Bone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment. We analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment. Here, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy. Taken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.


Organizational insight for physician leaders: a critical perspective.
Learn how to develop and institute the organizational awareness that leadership teams require to run healthy medical care systems.


On the autonomic innervation of the human vas deferens.
The autonomic innervation of the human vas deferens was studied histochemically. In the well-developed smooth muscle layers there were a small number of delicate adrenergic nerve terminals. Varicose nerve terminals able to take up and bind quinacrine were also found. These nerves may represent a specific nerve population previously denoted as "purinergic" nerves. In contrast, nerves displaying acetylcholine esterase (AchE) activity and/or immunoreactivity specific for vasoactive intestinal polypeptide (VIP) were mainly found subepithelially in the connective tissue of the mucosa.


Sequential implementation of DSC-MR perfusion and dynamic [18F]FET PET allows efficient differentiation of glioma progression from treatment-related changes.
Perfusion-weighted MRI (PWI) and O-(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and [18F]FET PET. We evaluated 104 patients with WHO grade II-IV glioma and suspected TP on conventional MRI using PWI and dynamic [18F]FET PET. Leakage corrected maximum relative cerebral blood volumes (rCBVmax) were obtained from dynamic susceptibility contrast PWI. Furthermore, we calculated static (i.e., maximum tumor to brain ratios; TBRmax) and dynamic [18F]FET PET parameters (i.e., Slope). Definitive diagnoses were based on histopathology (n = 42) or clinico-radiological follow-up (n = 62). The diagnostic performance of PWI and [18F]FET PET parameters to differentiate TP from TRC was evaluated by analyzing receiver operating characteristic and area under the curve (AUC). Across all patients, the differentiation of TP from TRC using rCBVmax or [18F]FET PET parameters was moderate (AUC = 0.69-0.75; p < 0.01). A rCBVmax cutoff > 2.85 had a positive predictive value for TP of 100%, enabling a correct TP diagnosis in 44 patients. In the remaining 60 patients, combined static and dynamic [18F]FET PET parameters (TBRmax, Slope) correctly discriminated TP and TRC in a significant 78% of patients, increasing the overall accuracy to 87%. A subgroup analysis of isocitrate dehydrogenase (IDH) mutant tumors indicated a superior performance of PWI to [18F]FET PET (AUC = 0.8/< 0.62, p < 0.01/≥ 0.3). While marked hyperperfusion on PWI indicated TP, [18F]FET PET proved beneficial to discriminate TP from TRC when PWI remained inconclusive. Thus, our results highlight the clinical value of sequential use of PWI and [18F]FET PET, allowing an economical use of diagnostic methods. The impact of an IDH mutation needs further investigation.


Relation between sleep disorders and post-stroke cognitive impairment.
To investigate the effects of sleep disorders on post-stroke cognitive impairment (PSCI) and other factors affecting post-stroke cognitive impairment. A total of 1,542 first-ever stroke inpatients in department of neurology of Tianjin Huanhu Hospital from 2015.6.1 to 2016.12.31. We recorded the personal history of patients. The MMSE (mini-mental state examination), MoCA (Montreal Cognitive Assessment), HAMD (Hamilton Depression Scale), BI (Barthel index), mRS (Modified Rankin Scale), PSQI (Pittsburgh Sleep Quality Index), ESS (Epworth Sleepiness Scale), Berlin questionnaire, nocturnal TST (total sleep time) were assessed before discharge. All patients were followed up at 3 months, 6 months, and 4 years (2019-2020) after stroke. During follow-up, the above scales should be evaluated again to assess the sleep status and cognitive function of patients at that time. Nocturnal TST (>8 h) (OR 3.540, 95% CI 1.692-7.406, P = 0.001) was a risk factor for cognitive impairment 3 months after stroke. Nocturnal TST (<7 h) (OR 6.504, 95% CI 3.404-12.427, P < 0.001) was a risk factor for cognitive impairment 6 months after stroke. Low sleep quality (OR 2.079, 95% CI 1.177-3.672, P = 0.012), sleepiness (OR 3.988, 95% CI 1.804-8.818, P = 0.001), nocturnal TST (<7 h) (OR 11.334, 95% CI 6.365-20.183, P < 0.001), nocturnal TST (>8 h) (OR 4.096, 95% CI 1.682-9.975, P = 0.002) were risk factors for cognitive impairment 4 years after stroke. The prevalence of cognitive impairment with TIA were 79.3% at admission, 68.1% at 3-months follow-up, 62.1% at 6-months follow-up and 52.2% at 4-year follow-up. Long or short nocturnal TST (<7 h or >8 h) was a risk factor for cognitive impairment after stroke (3 months, 6 months and 4 years). Poor sleep quality and sleepiness were shown to be risk factors for cognitive impairment at 4-year follow-up. Cognitive impairment was very common in patients with TIA.


Serial assessment of knee joint moments in posterior cruciate ligament and posterolateral corner reconstructed patients during a turn running task.
During post-operative rehabilitation for posterior cruciate ligament (PCL) reconstruction, flexion is limited to 90° for the first 6 weeks, and hamstring strengthening is initiated at 3 months because of static stability. The posterolateral corner sling (PLCS) procedure is frequently performed with PCL reconstruction to help alleviate posterolateral rotator instability, and it is possible, during this procedure, to damage the dynamic motion and to over-constrain the knee. For the patients group, PCL and PLCS reconstructions were performed simultaneously, and all reconstructed patients had stable knees and showed no complications. A motion analysis system was used to measure and calculate kinematic and kinetic data for seven patients after PCL and PLCS reconstruction (patients group) and seven normal subjects (control group) during a turn running task. The study was conducted on two groups at both 3 months (return to daily activity) and 6 months (return to light sports) post-operation. At 6 months after surgery, the dial test was also performed to observe the static rotational stability. Compared to the control group, the patients group showed a decreased extension moment (-1.15 ± 0.46 vs. -3.51 ± 0.69 Nm/kg, p = 0.000), a decreased valgus moment (-1.36 ± 0.72 vs. -2.15 ± 0.54 Nm/kg, p = 0.041) and a decreased external rotational moment (-0.15 ± 0.11 vs. -0.37 ± 0.10 Nm/kg, p = 0.002) 3 months post-operatively. However, these results approximated to the normal control, and the patients group showed an improved extension moment (-2.95 ± 0.67 Nm/kg, p = 0.188), valgus moment (-1.73 ± 0.58 Nm/kg, p = 0.359) and external rotational moment (-0.30 ± 0.09 Nm/kg, p = 0.325) at 6 months post-operatively. A static rotational stability revealed a similar or over-constrained state compared with the contralateral knee, and no patient showed rotational instability. PCL-PLCS reconstructed patients were reluctant to engage in, or lacked strength for, daily rotational activities. Therefore, we must consider more active and systematic co-contraction exercise of the hamstring and quadriceps and rehabilitation program about rotation that is not adverse to the static stability in PCL-PLCS reconstructed patients for early return to daily activities.


The use of the spanning suspension suture in facial reconstruction.
The closure of large cutaneous defects of the upper face can be challenging, often requiring the use of large rotation, advancement, or transposition flaps or skin grafts. To describe the use of the spanning suspension suture, a technique we have adapted to facilitate closure of large cutaneous defects of the upper face. Report of an illustrated case. A large full-thickness defect of the temple was successfully reconstructed using the spanning suspension suture. Use of the spanning suspension suture permits recruitment of skin from the lower cheek and neck in the closure of large wounds of the upper face, avoiding the need for transposition or rotation flaps and grafts.


Antimicrobial dispersions and films from positively charged styrene and acrylic copolymers.
Antimicrobial properties of methyl methacrylate - ethyl acrylate and styrene - ethyl acrylate copolymers, both as latexes and after film formation were tested. The polymers were synthesized using a cationic surfactant, cetytrimethylammonium bromide (CTAB) as an emulsifier, in presence of either a cationic or an anionic initiator. The resulting latex particles showed sizes between 50 and 320 nm (larger for the anionic initiator), and ζ-potential between +30 and +70 mV (more positive for the cationic initiator). Dialysis did not change significantly the size distribution and ζ-potential of the latexes, and most of them inhibited growth of Gram-negative (E. coli), Gram-positive (S. aureus, B. subtilis) and yeast (C. albicans). On the other hand, only few compositions were effective against Gram-negative P. aeruginosa. Both completely ("dry") and incompletely ("wet") formed films produced from the respective latexes showed similar, although less pronounced antimicrobial activity pattern. The analysis of streaming potential for the films confirmed that part of the positive surface charge brought by non-covalent binding of CTAB to the polymer chains, is lost during dialysis of the latexes and during rinsing, especially under high-shear flow. From the practical point of view, films with the best mechanical and antimicrobial properties can be achieved using polymers with high proportion of ethyl acrylate, while nature of the co-monomer and initiator do not play crucial roles.


Increased synthesis of α-tocopherol, paramylon and tyrosine by Euglena gracilis under conditions of high biomass production.
To analyse the production of different metabolites by dark-grown Euglena gracilis under conditions found to render high cell growth. The combination of glutamate (5 g l(-1) ), malate (2 g l(-1) ) and ethanol (10 ml l(-1) ) (GM + EtOH); glutamate (7·15 g l(-1) ) and ethanol (10 ml l(-1) ); or malate (8·16 g l(-1) ), glucose (10·6 g l(-1) ) and NH(4) Cl (1·8 g l(-1) ) as carbon and nitrogen sources, promoted an increase of 5·6, 3·7 and 2·6-fold, respectively, in biomass concentration in comparison with glutamate and malate (GM). In turn, the production of α-tocopherol after 120 h identified by LC-MS was 3·7 ± 0·2, 2·4 ± 0·1 and 2 ± 0·1 mg [g dry weight (DW)](-1) , respectively, while in the control medium (GM) it was 0·72 ± 0·1 mg (g DW)(-1) . For paramylon synthesis, the addition of EtOH or glucose induced a higher production. Amino acids were assayed by RP-HPLC; Tyr a tocopherol precursor and Ala an amino acid with antioxidant activity were the amino acids synthesized at higher concentration. Dark-grown E. gracilis Z is a suitable source for the generation of the biotechnologically relevant metabolites tyrosine, α-tocopherol and paramylon. By combining different carbon and nitrogen sources and inducing a tolerable stress to the cell by adding ethanol, it was possible to increase the production of biomass, paramylon, α-tocopherol and some amino acids. The concentrations of α-tocopherol achieved in this study are higher than others reported previously for Euglena, plant and algal systems. This work helps to understand the effect of different carbon sources on the synthesis of bio-molecules by E. gracilis and can be used as a basis for future works to improve the production of different metabolites of biotechnological importance by this organism.


What explains the reductions in /s/-clusters: sonority or [continuant]?
This study is a cross-linguistic examination of the patterns of reduction of two-member /s/-clusters. Data from six languages (English, Dutch, Norwegian, Croatian, Hebrew, and Polish) gathered from the productions of typically developing children and from children with phonological disorders are analyzed. While the languages belong to three different families, the results point to a universal tendency. Specifically, in the reductions of "s+stop" and "s+nasal" targets, the preference is the retention of C2, whereas in /sl/ and /sw/ targets, the clear pattern is in favor of the retention of C1. These patterns suggest that the continuancy of C2, not sonority, is the determining factor; C2 prevailed in "/s/+[-continuant]" targets, whereas C1 is retained in "/s/+[+continuant]" targets.


The effect of orally administered triprolidine and pseudoephedrine singly and combined on histamine-induced skin reactions.
The effect of a single oral dose of triprolidine and pseudoephedrine, singly and combined, on histamine-induced wheal and flare reactions, was assessed in a fully randomised, placebo-controlled, double-blind crossover study. Triprolidine alone and the combination had a significantly greater effect of (p less than 0.05) in reducing skin reactions than pseudoephedrine alone or placebo, but there was no significant difference between triprolidine ane the combination (p less than 0.05).


Genomic alteration is not associated with fatty and clear cell change in hepatocellular carcinomas and its precursor nodular lesions in cirrhotic liver.
The aim of this study was to investigate whether fatty and clear cell areas in large regenerative nodules (LRN), dysplastic nodules (DN), and hepatocellular carcinoma (HCC) show higher degree of genomic mutation compared to non-fatty/clear cell area in the same nodule or non-lesional tissue. We examined 22 nodular lesions (9 HCC, 5 DN and 8 LRN) from seven cirrhotic livers removed at transplantation. Frozen sections were used for manual microdissection of areas with fatty/clear cell change. DNA from microdissected tissue was amplified using arbitrarily primed polymerase chain reaction (AP-PCR), and PCR products were run on polyacrilamide gel generating a "fingerprint" band pattern. Autoradiographs were analysed using Adobe Photoshop version 6.0. Fingerprints from lesional tissue were compared to reference tissue and the total number of bands in excess or defect was calculated and divided by the total number of bands identified, obtaining the genomic damage fraction (GDF). Increasing GDF average values were seen from cirrhotic liver (0.13+/-0.04), to LRN (0.16+/-0.1), DN (0.28+/-0.08) and HCC (0.30+/-0.07). A statistically significant difference in GDF values was documented between cirrhotic liver and DN (p=0.008) and HCC (p=0.005) and between HCC and LRN (p=0.02). No significant difference was documented between DN and HCC, and between LRN and cirrhotic liver. Eleven nodules containing fat/clear cell areas were compared to the other 11 nodules without fat/clear cell areas. The GDF was not different between the two groups: 0.29+/-0.11 versus 0.25+/-0.12; p=0.5. The average value of genomic damage fraction between fat/clear cell areas (0.29+/-0.11) and no fat/clear cell areas (0.25+/-0.1) within the same nodules were not significantly different (p=0.11). Fatty and clear cell change in nodular lesions in cirrhotic liver may be an epigenetic phenotypic modification caused by microenvironmental factors such as ischaemia rather than indicating areas of increased malignant potential per se.


Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities.
Trypanothione reductase (TR) is an essential enzyme of trypanosomatids and therefore a promising target for the development of new drugs against African sleeping sickness and Chagas' disease. Diaryl sulfides with a central anilino moiety, decorated with a flexible N-alkyl side chain bearing a terminal ammonium ion, are a known class of inhibitors. Using computer modelling, we revised the binding model for this class of TR inhibitors predicting simultaneous interactions of the ammonium ion-terminated N-alkyl chain with Glu18 as well as Glu465'/Glu466' of the second subunit of the homodimer, whereas the hydrophobic substituent of the aniline ring occupies the "mepacrine binding site" near Trp21 and Met113. Systematic alteration of the carboxylate-binding fragments and the diaryl sulfide core of the inhibitor scaffold provided evidence for the proposed binding mode. In vitro studies showed IC(50) values in the low micromolar to submicromolar range against Trypanosoma brucei rhodesiense as well as the malaria parasite Plasmodium falciparum.


Pharmacotherapy of bipolar II disorder: a critical review of current evidence.
There is much controversy surrounding the diagnosis and treatment of patients with bipolar II disorder (BP II). To address the growing need to find effective treatment strategies for patients with BP II, this article identifies and summarizes available published evidence specific to the pharmacotherapy of BP II. Using the keywords, 'bipolar disorder', 'type II' or 'type 2', 'bipolar II', 'hypomania', and 'bipolar spectrum', a search of the databases Medline (via PubMed), the Cochrane Central Register of Controlled Trials (via Ovid), and PsychInfo was conducted for the period January 1994 to January 2003. Articles deemed directly relevant to the treatment of BP II were selected. Studies that included both BP I and II patients were excluded if results for BP II patients were not analyzed and reported separately. Fourteen articles were selected for the review period. There are no double blind, randomized controlled trials (RCT) involving only BP II patients. Most studies investigating the pharmacotherapy of BP II are methodologically limited, having observational or retrospective designs and small samples. For long-term treatment, lamotrigine has the strongest quality of evidence (double blind RCT), while lithium is the best studied. With regard to short-term treatment, there is some limited support for the use of risperidone in hypomania, and for divalproex, fluoxetine and venlafaxine in treating depression. There is a paucity of sound evidence to help guide clinicians treating BP II patients. Decisions about pharmacotherapy should be made on a case-by-case basis; overall, broad recommendations that are based on available evidence cannot be adequately made. More quality research is needed to delineate effective treatment strategies.