Ethical issues in tissue banking for research: the prospects and pitfalls of setting international standards.
Bauer, Taub, and Parsi's review of an international sample of standards on informed consent, confidentiality, commercialization, and quality of research in tissue banking reveals that no clear national or international consensus exists for these issues. The authors' response to the lack of uniformity in the meaning, scope, and ethical significance of the policies they examined is to call for the creation of uniform ethical guidelines. This raises questions about whether harmonization should consist of voluntary international standards or international regulations that include an official oversight mechanism and sanctions for noncompliance, and about who should participate in the harmonization process. Moreover, the normative assumptions and political dynamics that shape global policymaking need to be addressed. This commentary explores the policy implications and normative questions raised by the idea of international ethical guidelines for the use of biotechnologies and biotechnological resources such as stored samples of human tissue.


Rare cause of dyspnoea.
Although primary amyloidosis is the most common systemic form of amyloidosis, its diagnosis remains notoriously difficult. Unless included in the differential diagnosis, the condition may be missed as a cause of severe and ultimately fatal clinical syndromes. We describe two patients with primary amyloidosis who presented with dyspnoea/orthopnoea and oedema due to cardiac and renal involvement. Both had a fatal outcome.


Androstadienone, a putative chemosignal of dominance, increases gaze avoidance among men with high social anxiety.
Socially anxious individuals show increased sensitivity toward social threat signals, including cues of dominance. This sensitivity may account for the hypervigilance and gaze avoidance commonly reported in individuals with social anxiety. This study examines visual scanning behavior in response to androstadienone (androsta-4,16,-dien-3-one), a putative chemosignal of dominance. We tested whether exposure to androstadienone would increase hypervigilance and gaze avoidance among individuals with high social anxiety. In a double-blind, placebo-controlled, within-subject design, 26 participants with high social anxiety and 26 with low social anxiety were exposed to androstadienone and a control solution on two separate days. On each day, an eye-tracker recorded their spontaneous scanning behavior while they viewed facial images of men depicting dominant and neutral poses. The results indicate that among participants with high social anxiety, androstadienone increased gaze avoidance by reducing the percentage of fixations made to the eye-region and the total amount of time spent gazing at the eye-region of the faces. Participants with low social anxiety did not show this effect. These findings indicate that androstadienone serves as a threatening chemosignal of dominance, further supporting the link between hypersensitivity toward social threat cues and the perpetuation of social anxiety.


Ultrasound-assisted neuroendoscopic lavage for intraventricular hemorrhage in a newborn: illustrative case.
The optimal treatment for posthemorrhagic hydrocephalus in newborns has not been established yet. Moreover, despite many valid therapeutic alternatives, unfavorable neurodevelopmental outcomes are frequent. According to recent literature, these discouraging results could be related to secondary inflammatory damage of the white matter due to the gradual dissolution of the intraventricular hematoma, which should be removed. Neuroendoscopic lavage (NEL) has proven to be a safe and reliable procedure, able to adequately remove the intraventricular clots and the products of blood degradation. To increase surgical control of the entire ventricular system, the authors illustrated a case in which they associated real-time transfontanellar ultrasound monitoring with NEL. Coupling these two techniques, the authors performed a rapid ventricular wash and obtained intraoperative confirmation of complete and accurate clot removal.


Validity of proxy data obtained by different psychological autopsy information reconstruction techniques.
Two informants were interviewed for each of 416 living controls (individuals sampled from the normal population) interviewed in a Chinese case-control psychological autopsy study. The validity of proxy data, obtained using seven psychological autopsy information reconstruction techniques (types 1, 2 and A - E), was evaluated, with living controls' self reports used as the gold-standard. Proxy data for reconstruction technique types 1, 2 and D on the Impulsivity Inventory Scale (total impulsivity score) were no different from the living controls' self report gold standard, whereas data for types A and E were smaller than data from living controls. On the 'acceptance or resignation' sub-scale of the avoidance coping dimension of the Moos Coping Response Inventory, information obtained by reconstruction technique types 1 and D was not significantly different from the living controls' self reports, whereas proxy data from types 2, A and E were smaller than those from the living controls. No statistically significant differences were identified for other proxy data obtained by reconstruction technique types 1, 2, A, D and E. These results indicate that using a second informant does not significantly enhance information reconstruction for the target.


Has Psychoanalysis Reached Its Limits in the Question of the Trans Child and Adolescent?
New medical advances and options for transitioning along with an array of gender representations have provided gender diverse children and adolescents liberating possibilities. The transitioning youth's demands for recognition and/or support for initiation of medical intervention pushes against the analyst's theories of gender and challenges conservative understanding of sexual identity, moving it closer to the multidetermined nature of dreamwork. In this article, the author traces recurrent metaphors in discussions about gender transitioning with a focus on selected articles recently published in the International Journal of Psychoanalysis, particularly an essay authored by David Bell (2020) entitled "First Do No Harm." The author focuses on three images-contagion, the naturality of gender, and amputation-to ask, what do these apparently disparate signifiers reveal about the anxieties in the field?


Fetal chemoreception: a developing story.
The central and peripheral chemoreceptors are critical to the efficient uptake and delivery of oxygen and the removal of carbon dioxide after birth. However, the importance and activity of fetal chemoreception has been questioned, since oxygen uptake and carbon dioxide removal are not regulated in the lungs in the fetus. Early studies suggested that chemotransduction-the conversion of a chemical stimulus to cardiovascular and ventilatory responses via the integration of chemoreceptor stimulation, neural afferent activity and neurohormonal effector mechanisms-was immature in its individual components or their interaction. However, it now appears that the chemoreceptor cascade is structurally and functionally intact in the late-term fetus, and responds actively to normal and other chemical stimuli. The differences between fetal and postnatal chemotransduction appear to be primarily dependent on the central inhibition of the ventilatory response, the inhibitory area being localized to the lateral pons. It appears to be mediated in part by a placental factor which is removed at birth, allowing for the expression of the ventilatory response. The suppression of this response is also responsible for the difference in the heart rate response: the postnatal tachycardia is caused by the lung inflation reflex; when abolished, bradycardia is seen, just as in the fetus. Despite the suppression of the ventilatory component of chemoreception, the fetal carotid chemoreceptor is more important than the aortic, even though it has been considered to be more important to ventilatory than to cardiovascular stability. This review discusses current knowledge of the various components of the mature chemoreceptor cascade, and presents the fetal story within that framework.


Disclosure of funding sources and conflicts of interest in evidence underpinning vitamin D and calcium recommendations in bone health guidelines.
The present study aims to examine the relationship between study funding sources, author conflicts of interest (COI) and conclusions in studies supporting vitamin D and Ca intake cited in bone health guideline recommendations. Cross-sectional. Forty-seven global bone health guidelines with vitamin D and/or Ca recommendations for adults aged 40 years and above. The evidence cited to support the recommendations was extracted by two independent reviewers and classified by type of recommendation, article characteristics, study design, types of funding sources and conflict of interest (COI) disclosure and direction of study conclusions. Of 156 articles cited to support the bone health recommendations, 120 (77 %) disclosed a funding source, and 43 (28 %) declared that at least one author had a COI. Compared with articles with non-commercial or no funding source, those funded by commercial sponsors tended to have a study conclusion favourable towards vitamin D/Ca (relative risk (95 % CI): 1·32 (0·94, 1·87), P = 0·16), but the association was not statistically significant (Fisher's exact test). Compared to those with a COI disclosure statement, articles with missing or unclear COI disclosure were more likely to have favourable conclusions (1·56 (1·05, 2·31), P = 0·017) (Fisher's exact test). In the evidence underpinning a sample of global bone health guidelines, COI disclosure was low and studies with missing or unclear COI disclosures were more likely to have favourable study conclusions than those with disclosures, suggesting a need for greater transparency of COI in bone health guidelines.


[Cocaine-induced myocardial infarction (clinical case report)].
Cocaine abuse has been associated with various cardiovascular complications, including angina pectoris, myocardial infarction, and sudden cardiac death. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. This article discusses the possible pathological mechanisms underlying the pathogenesis of myocardial ischemia and infarction secondary to cocaine abuse, and current ideas on the management of cocaine-induced myocardial infarction. We report a case of acute myocardial ischemia in a young healthy male patient and his 5-year follow-up.


Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia.
Plasma membrane Ca(2+)-ATPases (PMCAs) participate in epithelial Ca(2+) transport and intracellular Ca(2+) signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca(2+) channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca(2+) flux and investigated the localization and regulation of Pmca4 in Ca(2+)-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca(2+) channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na(+)-Cl(-) cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca(2+) balance, pointing to a housekeeping function of the pump in Ca(2+)-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca(2+)-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca(2+) transport.


Extended phase-space dynamics for the generalized nonextensive thermostatistics.
We apply a variant of the Nosé thermostat to derive the Hamiltonian of a nonextensive system that is compatible with the canonical ensemble of the generalized thermostatistics of Tsallis. This microdynamical approach provides a deterministic connection between the generalized nonextensive entropy and power-law behavior. For the case of a simple one-dimensional harmonic oscillator, we confirm by numerical simulation of the dynamics that the distribution of energy H follows precisely the canonical q statistics for different values of the parameter q. The approach is further tested for classical many-particle systems by means of molecular dynamics simulations. The results indicate that the intrinsic nonlinear features of the nonextensive formalism are capable of generating energy fluctuations that obey anomalous probability laws. For q<1 a broad distribution of energy is observed, while for q>1 the resulting distribution is confined to a compact support.


Ductal Carcinoma in Situ: Current Concepts in Biology, Imaging, and Treatment.
Ductal carcinoma in situ (DCIS) of the breast is a group of heterogeneous epithelial proliferations confined to the milk ducts that nearly always present in asymptomatic women on breast cancer screening. A stage 0, preinvasive breast cancer, increased detection of DCIS was initially hailed as a means to prevent invasive breast cancer through surgical treatment with adjuvant radiation and/or endocrine therapies. However, controversy in the medical community has emerged in the past two decades that a fraction of DCIS represents overdiagnosis, leading to unnecessary treatments and resulting morbidity. The imaging hallmarks of DCIS include linearly or segmentally distributed calcifications on mammography or nonmass enhancement on breast MRI. Imaging features have been shown to reflect the biological heterogeneity of DCIS lesions, with recent studies indicating MRI may identify a greater fraction of higher-grade lesions than mammography does. There is strong interest in the surgical, imaging, and oncology communities to better align DCIS management with biology, which has resulted in trials of active surveillance and therapy that is less aggressive. However, risk stratification of DCIS remains imperfect, which has limited the development of precision therapy approaches matched to DCIS aggressiveness. Accordingly, there are opportunities for breast imaging radiologists to assist the oncology community by leveraging advanced imaging techniques to identify appropriate patients for the less aggressive DCIS treatments.


Some observations on the response of ring-necked pheasants to inoculation with various strains of cell-culture-propagated type II avian adenovirus.
The response of ring-necked pheasants to inoculation with three strains of cell-culture-propagated type II avian adenovirus was examined. Marble spleen disease (MSD) virus of pheasants and both avirulent and virulent strains of hemorrhagic enteritis virus (HEV) of turkeys all induced typical gross and microscopic splenic lesions of MSD; neither MSD-associated lung lesions nor mortality were noted in inoculated pheasants, regardless of strain of virus used. Pheasants inoculated with a cell-culture-propagated avirulent strain of HEV were properly immunized against challenge with virulent HEV, as indicated by seroconversion and by protection against virus-induced splenic lesions. We conclude that these strains of type II avian adenovirus are comparable in pathogenicity for pheasants and cannot be distinguished. Further, absence of MSD-associated lung lesions and mortality in pheasants maintained under controlled laboratory conditions suggest that other environmental factors are probably involved in induction of such lesions and mortality in field cases of MSD.


Epicardial adipose tissue thickness correlates with the presence and severity of angiographic coronary artery disease in stable patients with chest pain.
Epicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD). We measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis. Of 970 patients (age 60.9 years, 71% male), 75% (n = 731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; p = 0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was OR = 1.46 [1.03-2.08], p = 0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (p = 0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76. Although left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.


Amniotic fluid C-peptide and phosphatidyl glycerol in diabetic pregnancy.
The concentrations of C-peptide and phosphatidylglycerol in the amniotic fluid were determined in 36 pregnant diabetic women. Twenty-one patients who were being treated with insulin for gestational diabetes as well as 15 patients who were insulin dependent were studied. All patients were subjected to a program of strict metabolic control, and amniocentesis was performed at gestational week 36-37. Phosphatidyl glycerol was present in the amniotic fluid in 15 cases and absent in 21. The mean concentration of C-peptide did not differ whether phosphatidyl glycerol was present or absent. (C-peptide: 0.56 +/- 0.06 and 0.43 +/- 0.05 nmol/l respectively). Although the mean value for amniotic fluid C-peptide in both groups was close to that in diabetic pregnancies with an uneventful neonatal outcome, it was significantly higher than that in non-diabetic pregnancies, indicating minor fetal hyperinsulinemia. The level of C-peptide in the amniotic fluid showed a correlation to the subsequent birthweight of the infant (r = 0.50; p less than 0.01). It is concluded that with rigorous metabolic control of the pregnant diabetic patient, the presence or absence of phosphatidyl glycerol, as an index of fetal lung maturity, is apparently not related to the level of C-peptide in the amniotic fluid.


Trapped Flexible Ureteroscope in Ureteral Access Sheath During Retrograde Intrarenal Surgery: An Unexpected Problem.
Background: Instrument-related complications occur occasionally with the use of flexible ureteroscopes. In this study, we present a unique problem related to instrument malfunction of flexible ureteroscope during retrograde intrarenal surgery. Case Presentation: A 60-year-old male patient with a 1.2 cm left upper ureteral stone initially underwent semirigid ureteroscopic laser lithotripsy and during the procedure the stone got retropulsed into middle calix of the kidney. Subsequently, a 9.5F (internal diameter) ureteral access sheath was placed and using URF P6R flexible ureteroscope (Olympus) the stone was completely dusted with holmium laser. At the end of the procedure, the operating surgeon was unable to remove the ureteroscope out of the ureteral access sheath as it was getting stuck inside. On careful inspection under fluoroscopy, it was noticed that there was a partial break in the outer surface of the flexible ureteroscope at the level of the junction of the distal flexible part of the ureteroscope with the shaft. Since multiple attempts to retrieve the ureteroscope into the access sheath failed, a decision was made to pull the ureteroscope and ureteral access sheath as a whole over a 0.035″ terumo guidewire. Gentle traction was applied on the entire assembly and the instrument was withdrawn out of ureter over the guidewire under fluoroscopic guidance. A lateral angulation of the distal flexible portion with the shaft of the flexible ureteroscope caused by breakage of the fiber-optic cables led to this problem intraoperatively. Conclusion: Breakage of fiber-optic cables caused by excessive manipulation of flexible ureteroscope during retrograde intrarenal surgery can lead to entrapment of the ureteroscope within the ureteral access sheath. This problem might be solved by gently withdrawing the whole assembly out of the ureter over a guidewire.


Colony size optimisation in colony-based laser imaging for microbial source tracking.
The colony-based laser scatter imaging provides a convincing solution to microbial source tracking. The optical scattering patterns of bacterial colonies are tightly correlated to the corresponding growth patterns. This relationship is manifested as the development of optical scattering patterns with the increment of colony size. An investigation was conducted into this relationship and the optimal range of colony size for improving the accuracy of microbial source tracking technique. All the bacterial samples from five host species were cultivated under the same conditions. The optical scattering patterns were recorded for the average colony diameter from 0.1 mm to 1.5 mm, using a bench top laser imaging system. Gabor wavelet was utilised to encode image signatures. Fuzzy-C-means was employed to cluster the colony patterns from the same host species. The experimental results demonstrate that the optimal range of the colony diameters is 0.8-1.0 mm. The corresponding identification rate of microbial source tracking is >80%.


4E-BP1 degradation and eIF4E truncation occur spatially distinctly in the porcine uterine epithelia and are features of noninvasive implantation in the pig.
The implantation of the blastocyst into the endometrium is an indispensable premise for successful embryonic development. This process is regulated by maternal and embryonic signals that influence gene expression at the translational level, among other processes. Recently, we have shown that proteolytical cleavage of the prototypical 25-kDa, mRNA cap-binding protein eIF4E produces a stable variant with a molecular mass of approximately 23 kDa exclusively in the porcine endometrium during implantation. This is accompanied by dephosphorylation and reduction of the abundant repressor 4E-BP1. Here, we investigate the distribution of the truncated eIF4E and of 4E-BP1 in the porcine uterine tissue, their binding in native samples, and we analyzed eIF4E-, eIF4G-, and 4E-BP1-specific proteolytic activities. Our results show that in pigs, the truncated eIF4E is located in the endometrial luminal epithelium during implantation. Neither glandulary tissue nor stroma expressed any truncated eIF4E. The reduced abundance of 4E-BP1 during implantation is mainly the result of decay in the glandular epithelia. Moreover, steroid replacements, in vitro protease assays, and cell lysate fractionation showed that eIF4E cleavage and 4E-BP1 decay both depended on the ovarian steroid hormones estradiol and progestrone, but these effects are the result of different proteolytic activities. Although eIF4G cleavage also depends on calcium, stimulation by these steroids could not be established. We propose that the translation initiation process in the endometrium is differently regulated by the truncated eIF4E, utilizing different abundances of 4E-BP1 and binding dynamic of eIF4E/4E-BP1 in distinct forms of implantation.


[Contraception, abortion, and infanticide before modern vital registration].
"The author [investigated]...conscious limitations of fertility in the Czech Lands [during] the period before modern vital registration. She used three main...sources of data: the ecclesiastic literature..., medical literature and juridical literature." The data show that people did practice birth control, abortion, and infanticide despite laws and church teachings to the contrary. (SUMMARY IN ENG)


Burning through the pain: treatments for diabetic neuropathy.
The rise in the global burden of diabetes is spurring an increase in the prevalence of its complications. Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, with multiple clinical manifestations. The most common is a symmetrical length-dependent dysfunction and damage of peripheral nerves. The management of DPN rests on three tenets: intensive glycaemic control, even though the evidence of benefit is questionable in people with type 2 diabetes; pathogenetic therapies; and symptomatic treatment. A number of pathogenetic treatments have been evaluated in phase III clinical trials, including α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage) and aldose-reductase inhibitors (reduce flux through the polyol pathway), protein kinase C inhibitors (prevent hyperglycaemia-induced activation of protein kinase C), nerve growth factors (stimulate nerve regeneration) and Actovegin® (improves tissue glucose and oxygen uptake). However, none have gained US Food and Drug Administration or European Medicines Agency (EMA) approval, questioning the validity of current trial designs and the endpoints deployed to define efficacy. For painful diabetic neuropathy, clinical guidelines recommend: atypical analgesics for pain relief, including duloxetine and amitriptyline; the γ-aminobutyric acid analogues gabapentin and pregabalin; opioids, including Tapentadol; and topical agents such as lidocaine and capsaicin. No single effective treatment exists for painful DPN, highlighting a growing need for studies to evaluate more potent and targeted drugs, as well as combinations. A number of novel potential candidates, including erythropoietin analogues and angiotensin II type 2 receptor anatagonists are currently being evaluated in phase II clinical trials.


Eco-friendly Water-Based λ-Cyhalothrin Polydopamine Microcapsule Suspension with High Adhesion on Leaf for Reducing Pesticides Loss.
Recently, innovations of nano/microcarrier formulations have been focused on improving application efficiencies and retention time. In this study, a water-based 2.5% λ-cyhalothrin (LC) microcapsule suspension (CS) was developed by orthogonal test with biodegradable and adhesive polydopamine (PDA) microcapsules (MCs) as carriers. The obtained LC-PDA CS had good suspension properties, flow behavior, storage stability, and rheological properties. LC-PDA CS had higher retention, wettability, and decreased rainwater washing out on the leaves than commercial CS. LC-PDA CS displayed higher insecticidal activity against Lipaphis erysimi compared to commercial CS. LC-PDA CS reduced the toxicity of LC to the aquatic organism Danio rerio compared to LC. The above results demonstrated that LC-PDA CS would be eco-friendly water-based pesticides carrier system for prolonging the retention time on target leaf and reducing toxicity to aquatic organisms.


Permanent occlusion of bilateral internal carotid arteries produces cognitive deficits in two learning behavior tasks.
We investigated the effects of permanent bilateral occlusion of the internal carotid arteries (2ICAO) on the learning and memory performances in rats to evaluate the permanent 2ICAO rats as a model for vascular dementia. The learning and memory performance was tested by a step-through passive avoidance task and an 8-arm radial maze task. Permanent 2ICAO decreased cerebral blood flows in the cortex and hippocampus by 46.3 +/- 3.3 and 21.1 +/- 4.6%, respectively, when measured at 15 min after occlusion. In the passive avoidance task, the 2ICAO rats showed no impairment of learning or of memory retention when tested 1 h after learning trial, while they showed a shorter latency than sham-operated rats when tested 24 h after learning trial. In the radial maze learning task, the non-pretrained 2ICAO rats showed impairment. The pretrained 2ICAO rats had no deficit in the radial maze retention task but they showed impaired performance when a 3-min delay was interposed in the task. These results suggest that permanent 2ICAO is a useful animal model for studying vascular dementia.


Psychometric properties of the Children's Response Styles Questionnaire in a Hong Kong Chinese community sample.
The Children's Response Styles Questionnaire (CRSQ) is a widely-adopted inventory that assesses response styles in youths. It is useful in examining how coping styles (particularly rumination) may relate to depressive vulnerability in youths. Despite its utility, little is known about its applicability in non-Western cultures and CRSQ has not been evaluated using current psychometric methods including item response theory (IRT). The present study assessed the properties using IRT methods in a Chinese youth sample. Students in Grades 4-6 were recruited from seven public primary schools in Hong Kong, and a total of 581 children (280 boys and 301 girls) between 8 and 14 years of age participated in the study. A Chinese version of CRSQ was administered to them in groups at school after receiving written parental consent as well as students' assent. Confirmatory factor analysis revealed a two-factor structure that was comparable to that identified in Western samples, namely, the rumination and distraction/problem-solving subscales. IRT analysis suggested that items varied in levels of item discrimination and item severity, and in precision/usefulness for assessing the underlying latent trait levels. Test information analysis indicated that rumination subscale was more useful than the distraction and problem-solving subscale in assessing the latent trait over a broader range of levels. For gender-based Differential Item Functioning (DIF) analysis, item 1 "When I am sad, I think about how alone I feel" was found to exhibit higher discriminating power for girls than boys. The study presents the first attempt to examine CRSQ item properties using IRT analysis and supports its validity beyond the Western cultures. The factor structure of CRSQ was found to be comparable to the West in our Chinese sample. Differential Item Functioning (DIF) evaluation suggested all but one item in the rumination subscale of the CRSQ apply equally well to both boys and girls.


Alcohol consumption and ischemic heart disease mortality in Sweden.
Most previous studies on the relationship between alcohol consumption and mortality from ischemic heart disease (IHD) have been conducted in countries with an alcohol consumption pattern different from that in Sweden (and other countries in the "Vodka Belt"), where irregular binge drinking of distilled spirits is common. Therefore, we carried out an ecological study in Sweden where cross-sectional, longitudinal, and time series analyses (1973-1986) were performed on consumption of spirits, wine and beer in relation to age-standardized mortality in IHD for males and females. There was a negative correlation in both cross-sectional and longitudinal analyses between wine consumption and mortality from IHD, especially strong for women, but no consistent relationship between the consumption of total ethanol, spirits and beer versus the mortality from IHD. In the time series analysis, only wine was negatively correlated with IHD mortality for women. We conclude that, on a population level, consumption of spirits and beer in a Swedish drinking pattern does not imply any protection against death from IHD. On the other hand, wine consumption in Sweden could be associated with a reduced risk of IHD death among women.


No evidence of vertical transmission of HTLV-I in bottle-fed children.
The most frequent pathway of vertical transmission of HTLV-I is breast-feeding, however bottle fed children may also become infected in a frequency varying from 4 to 14%. In these children the most probable routes of infection are transplacental or contamination in the birth canal. Forty-one bottle-fed children of HTLV-I seropositive mothers in ages varying from three to 39 months (average age of 11 months) were submitted to nested polymerase chain reaction analysis (pol and tax genes). 81.5% of the children were born by an elective cesarean section. No case of infection was detected. The absence of HTLV-I infection in these cases indicates that transmission by transplacental route may be very infrequent.


Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for canine transitional cell carcinoma.
As a prelude to photodynamic therapy, 5-aminolevulinic acid (ALA) was given orally to healthy dogs. ALA-induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose-dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA-based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA-based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA-based PDT resulted in tumour progression-free intervals from 4 to 34 weeks in five dogs; one dog with pre-existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.


Atmospheric emission of PCDD/Fs, PCBs, hexachlorobenzene, and pentachlorobenzene from the coking industry.
The coking process is considered to be a potential source of unintentionally produced persistent organic pollutants (UP-POPs). However, intensive studies on the emission of UP-POPs from the coking industry are still very scarce. Emission of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), hexachlorobenzene (HxCBz), and pentachlorobenzene (PeCBz) covered under the Stockholm Convention were investigated for the coking process in this study. Stack gases from some typical coke plants in China were collected and analyzed to estimate the emission of UP-POPs from the coking industry. Emission factors of 28.9 ng WHO-TEQ tonne(-1) for PCDD/Fs, 1.7 ng WHO-TEQ tonne(-1) for dl-PCBs, 596 ng tonne(-1) for HxCBz, and 680 ng tonne(-1) for PeCBz were derived based on the investigated data. The annual emissions from the global coking industry were estimated to be 15.8 g WHO-TEQ for PCDD/Fs, 0.93 g WHO-TEQ for dl-PCBs, 333 g for HxCBz, and 379 g for PeCBz, respectively (reference year 2007). According to the distribution of PCDD/Fs, we argued for the de novo synthesis to be the major pathway of PCDD/F formation. With regard to the characteristics of dl-PCBs, the most abundant congener was CB-118, and the most dominant contributor to the total WHO-TEQ of dl-PCBs was CB-126.


Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and phosphate ingredients in the treatment of dental hypersensitivity. Part II: comparison with a professional treatment for tooth hypersensitivity.
Tooth hypersensitivity can occur when gum recession causes exposure of dentin. Tiny tubules, which permeate dentin, provide open passageways from the mouth to the intradental nerve in the pulpal cavity. Under such circumstances, stimuli in the mouth can cause pressure on the intradental nerve, leading to pain. Sealing the outside of the tubules with an impermeable substance can effectively treat hypersensitivity. One such clinically proven composition is a professionally applied tooth desensitizer, which has been shown to initially produce a layer of amorphous calcium phosphate (ACP) on the surface of dentin. Under the influence of fluoride, ACP reforms as hydroxyapatite (HAP), which has essentially the same composition as tooth mineral. Three fluoride toothpastes that deliver calcium and phosphate salts to the teeth also have been demonstrated in clinical trials to relieve hypersensitivity. This study compared the mechanism of action of these toothpastes to that of the professional desensitizer. A single application of the professional desensitizer or multiple applications of any of the three toothpastes was shown to reduce dentin permeability. A conventional fluoride toothpaste also was found to inhibit fluid flow through the dentin but to a lesser degree than the other toothpastes. The desensitizer and the three toothpastes were found to occlude the dentinal tubules with a layer of calcium phosphate that had a calcium-to-phosphate ratio consistent with the formation of ACP or HAP. The morphology of the coherent mineral layer formed by Arm & Hammer Enamel Care Sensitive was similar, especially to that produced by the desensitizer. In contrast, the conventional toothpaste left localized areas of surface residue composed of silica particles. The mechanism of action of the three toothpastes that deliver calcium and phosphate salts is the same as that of the professional desensitizer.


Development of a novel phantom using polyethylene glycol for the visualization of restricted diffusion in diffusion kurtosis imaging and apparent diffusion coefficient subtraction method.
The present study aimed to investigate whether polyethylene glycol (PEG) phantoms have the potential to be used as standard phantoms for magnetic resonance imaging (MRI) in order to visualize restricted diffusion in diffusion kurtosis imaging (DKI), the ADC subtraction method (ASM) and the apparent diffusion coefficient (ADC). Diffusion-weighted images of 0-120 mM PEG phantoms were captured to create ADC, DKI and ASM images with post-processing. ASM is a recently developed method for restricted diffusion imaging using the readout segmentation of long variable echo-train sequences. As the PEG concentration increases, the ADC value decreases. Conversely, an increase in DKI and ASM values is associated with increasing PEG concentration. Formulae were constructed to represent the association between PEG concentrations and ADC, DKI and ASM values. These formulae can be used to determine the required PEG concentrations to mimic arbitrary ADC, DKI and ASM values of certain diseases, including tumors and infarctions. Validation experiments were conducted using bio-phantoms and clarified that the PEG phantoms cover the range of ADC and DKI values reported in previous clinical research using 3T MRI. PEG phantoms may be useful for future MRI research involving restricted diffusion.


Intracellular milieu changes associated with hypoxia impair sarcoplasmic reticulum Ca2+ transport in cardiac muscle.
The effects on sarcoplasmic reticulum (SR) Ca2+ transport of solutions mimicking the important intracellular milieu changes associated with short-term hypoxia (hypoxic solutions, as described by Kammermeier et al. J. Mol. Cell. Cardiol. 14: 267, 1982) were examined. SR Ca2+ content was estimated by measuring the magnitude of the caffeine-induced contracture in saponin-skinned rat papillary muscle. SR Ca2+ uptake was inhibited by hypoxic solutions only at loading times less than or equal to 30 s. This inhibition was primarily due to the increase in Pi. The hypoxic solutions had no effect on Ca(2+)-induced Ca2+ release from the SR. We also tested the effects of ATP-free (rigor) solutions that mimic the intracellular environment during late hypoxia and ischemia. Elevating Pi or ADP alone in rigor solution had no effect on SR Ca2+ content. However, elevating Pi and ADP (+/-Mg2+) produced a 44-48% reduction in SR Ca2+ content. This reduction is most likely due to reversal of the SR Ca2+ pump. We conclude that the changes in milieu with short-term hypoxia can depress contractility in intact cardiac muscle by inhibiting SR Ca2+ uptake. During long-term hypoxia or ischemia, these milieu changes can elevate intracellular Ca2+ by reversing the SR Ca2+ pump.


Cocaine-associated chest pain: one-year follow-up.
To determine the one-year mortality and incidence of myocardial infarction (MI) post-hospital discharge or ED release for patients with cocaine-associated chest pain. A prospective, observational study of an inception cohort of consecutive patients who presented to one of four municipal hospital EDs with cocaine-associated chest pain. Patients were followed for one year from the end of the enrollment period. Main outcome parameters were the one-year actuarial survival and the frequency of nonfatal MI. Mortality data were available for all 203 patients at a mean of 408 days. Additional clinical information was available for 185 patients (91%). There were six deaths (one-year actuarial survival 98%; 95% CI, 95-100%); none from MI. Nonfatal MI occurred in two patients (1%; 95% CI, 0-2%). Continued cocaine use was common (60%; 95% CI, 52-68%) and was associated with recurrent chest pain (75% vs 31%, p < 0.0001). No MI or death was reported for patients who claimed to have ceased cocaine use. Patients who presented with cocaine-associated chest pain commonly continued to use cocaine after discharge. Urgent evaluation of coronary anatomy or cardiac stress tests may not be necessary for patients for whom MI is ruled out and who do not have recurrent potentially ischemic pain. The subsequent risk for MI and death in this group appears to be low. Intervention strategies should emphasize cessation of cocaine use.


[Prolonged abdominal aortic aneurysm rupture penetrating the lumbar spine].
The prevalence of prolonged rupture of aortic aneurysm was estimated in a group of 65 patients operated for ruptured abdominal aortic aneurysm (AAA). Patients with chronically contained rupture AAA were hemodynamically stable. Contained rupture of an AAA should be considered in patients presenting unexplained back pain and when radiograms suggest the degenerative changes within spine.


Human histocompatibility complex (HLA). The distribution of HLA-ABC antigens and structure of exclusions in investigations on disputable paternity in population of north-eastern Poland.
In the present study 80 cases of disputable paternity analysed at the Department of Forensic Medicine in Bialystok in years 1990-1993 were reviewed. Gene frequencies of HLA antigens calculated for the north-eastern population of Poland are not significantly different from those reported for all-Polish population. Similarly, the most frequent HLA haplotypes calculated per 10,000 individuals for the studied population corresponded to those reported by others for central European population. In 13 cases (16.3%) paternity of a defendant was excluded. One case (7.7%) represented exclusions based on three antigens (of loci A, B and C), four cases (30.8%)-exclusions based on two antigens (of loci A and B) and eight cases (61.5%) exclusions based on one antigen (three of locus A and five of locus B).


Regulation of PDGFR-β gene expression by targeting the G-vacancy bearing G-quadruplex in promoter.
G-quadruplex is an essential element in gene transcription that serves as a promising drug target. Guanine-vacancy-bearing G-quadruplex (GVBQ) is a newly identified G-quadruplex that has distinct structural features from the canonical G-quadruplex. Potential GVBQ-forming motifs are widely distributed in gene promoter regions. However, whether GVBQ can form in genomic DNA and be an effective target for manipulating gene expression is unknown. Using photo-crosslinking, dimethyl sulfate footprinting, exonuclease digestion and in vitro transcription, we demonstrated the formation of a GVBQ in the G-rich nuclease hypersensitivity element within the human PDGFR-β gene promoter region in both single-stranded and double-stranded DNA. The formation of GVBQ in dsDNA could be induced by negative supercoiling created by downstream transcription. We also found that the PDGFR-β GVBQ was specifically recognized and stabilized by a new synthetic porphyrin guanine conjugate (mPG). Targeting the PDGFR-β GVBQ in human cancer cells using the mPG could specifically alter PDGFR-β gene expression. Our work illustrates that targeting GVBQ with mPG in human cells can regulate the expression level of a specific gene, thus indicating a novel strategy for drug development.


Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin.
Dysregulated microglia and astrocytes have been associated with progressive neurodegeneration in multiple sclerosis (MS), highlighting the need for strategies that additionally target intrinsic inflammation in the central nervous system (CNS). The objective of the present study was to investigate the glial response in experimental autoimmune encephalomyelitis (EAE)-induced mice treated with a combination of dimethyl fumarate (DMF) and pregabalin (PGB). For that, 28 C57BL/6J mice were randomly assigned to the five experimental groups: naïve, EAE, EAE-DMF, EAE-PGB, and EAE-DMF + PGB. Pharmacological treatments were initiated with the beginning of clinical signs, and all animals were euthanized at 28 dpi for the lumbar spinal cord evaluation. The results demonstrated a stronger attenuation of the clinical presentation by the combined approach. DMF alone promoted the downregulation of Iba-1 (microglia/macrophages marker) in the ventral horn compared with the non-treated EAE animals (P < 0.05). PGB treatment was associated with reduced Iba-1 immunofluorescence in both the dorsal (P < 0.05) and ventral horn (P < 0.05) compared to EAE vehicle-treated counterparts. However, the combined approach reduced the Iba-1 marker in the dorsal (P < 0.05) and ventral (P < 0.01) horns compared to non-treated EAE animals and further reduced Iba-1 in the ventral horn compared to each drug-alone approach (P < 0.05). In addition, the combination of DMF and PGB reduced activated astrocytes (GFAP) in both the dorsal and ventral horns of the spinal cord to a naïve-like level and upregulated Nrf-2 expression. Taken together, the data herein suggest robust attenuation of the glial response in EAE mice treated with DMF and PGB.


Dynamic Manugraphy as a Promising Tool to Assess the Outcome of Limited Aponeurectomy in Patients With Dupuytren's Contracture.
Background: Dupuytren's contractures interfere with physiological gripping. While limited aponeurectomy is an accepted treatment modality to restore finger mobility, methods to objectify functional outcome beyond determination of the range of motion are scarce. Methods: Patients with Dupuytren's contracture being scheduled for unilateral limited aponeurectomy were invited to participate. Clinical data were gathered prospectively by chart review and interview. The DASH-score and flexion contracture for fingers were registered prior to surgery, 3 and 6 months afterwards. At the same time, dynamic manugraphy for simultaneous recording of the grip pattern and forces generated by the affected hand and anatomic areas (i.e., thumb, index finger, middle finger, ring finger, little finger and palm) were performed. All findings obtained during the follow-up period were compared to the situation at baseline. Comparison between paired samples was done using Wilcoxon rank test. All p-values are two-sided and p < 0.05 was considered to be significant. Results: Out of 23 consecutively enrolled patients, 19 (15 men, 4 women) completed follow-up examinations. Manugraphy confirmed the impairment of physiological gripping with concomitant pathological load distribution at base line. Limited aponeurectomy significantly reduced flexion contractures. However, the DASH-score remained at an excellent level in one patient, indicated improvement in 11 and worsening in seven patients. Six patients had lower grip force at t6 compared to the preoperative condition, although the preoperative flexion contracture (≥110°) was considerably improved in all of them. In four of those, the DASH-score improved while it turned worse in two of them. The force of surgically treated fingers remained unchanged in three patients while it was improved and worsened in half of the remaining patients, respectively. Manugraphy revealed physiological gripping by enlargement of contact area and higher force transmission by the fingertips in 10 of 12 patients with constant or even improved DASH-score and in three of seven patients with a worsened DASH-score. Conclusions: Assessing the reduction of flexion contracture and grip force alone is not sufficient to comprehensively reflect the functional outcome of aponeurectomy for Dupuytren's disease. Visualizing physiological grip pattern provides an additional tool to objectify the success of surgical treatment.


Total thyroidectomy performed with the Starion vessel sealing system versus the conventional technique: a prospective randomized trial.
Meticulous dissection and accurate hemostasis are required in thyroid surgery. The authors recently performed a number of thyroidectomies using a new device that combines heat and pressure for sealing and cutting tissue. A prospective randomized trial was conducted on 98 patients subjected to total thyroidectomy for benign disease: 49 patients (group A) with the Starion tissue welding system and 49 (group B) with the clamp-and-tie technique. The 2 groups were comparable in mean age, gender, thyroidal volume (20-60 mL), incision length (<35 mm), and pathology. The authors evaluated operative time, postoperative serum calcemia, dosage and length of postoperative calcium and vitamin D treatment, drainage volume, hospital stay, and complications. Student's t test was used for quantitative variables; for categorical variables, the chi(2) test or Fisher's exact test, as appropriate, was used. The mean operative time was 53.8 +/- 6.1 minutes in group A and 63.2 +/- 8 minutes in group B (P < .0001). The difference in terms of postoperative calcemia was significant (group A: 8.35 +/- 0.39 mg/dL; group B: 8.08 +/- 0.39 mg/dL; P < .001). The duration of postoperative treatment with calcium and vitamin D was significantly different (group A: 4 days; group B: 5 days; P < .039). No significant difference in terms of postoperative complications was found. The new system reduced operative time and the duration of postoperative hypocalcemia, and there was minimal tissue necrosis and thermal spread. The reduction in duration of postoperative calcium and vitamin D treatment is also an indication of improvement in quality of the treatment.


Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene promoter by the DNA-binding protein Finb/RREB-1.
The basic helix-loop-helix protein BETA2/NeuroD activates transcription of the secretin gene and is essential for terminal differentiation of secretin-producing enteroendocrine cells. However, in heterodimeric complexes with its partner basic helix-loop-helix proteins, BETA2 does not appear to be a strong activator of transcription by itself. Mutational analysis of a proximal enhancer in the secretin gene identified several cis-acting elements in addition to the E-box binding site for BETA2. We identified by expression cloning the zinc finger protein RREB-1, also known to exist as a longer form, Finb, as the protein binding to one of the mutationally sensitive elements. Finb/RREB-1 lacks an intrinsic activation domain and by itself did not activate secretin gene transcription. Here we show that Finb/RREB-1 can associate with BETA2 to enhance its transcription-activating function. Both DNA binding and physical interaction of Finb/RREB-1 with BETA2 are required to potentiate transcription. Thus, Finb/RREB-1 does not function as a classical activator of transcription that recruits an activation domain to a DNA-protein complex. Finb/RREB-1 may be distinguished from coactivators, which increase transcription without sequence-specific DNA binding. We suggest that Finb/RREB-1 should be considered a potentiator of transcription, representing a distinct category of transcription-regulating proteins.


Relational and Spiritual Coping Among Emerging and Young Adult Cancer Survivors.
Cancer presents uncertainties for individuals of any age; however, emerging and young adults (EYA) are challenged to cope with developmental tasks in addition to cancer-related stressors. Guided by the double ABC-X model and biopsychosocial-spiritual framework, the current study investigates coping strategies used by this population and the role of psychological resources (perception of parental care/control and spirituality) on their coping ability. Recruited from online social media, 210 EYA cancer survivors self-reported demographic, medical information, and completed the Brief Cope scale. In addition, spirituality reliance, perceived parental care, and parental control were measured and examined in relation to coping ability. While nearly half of participants experienced positive adaptation in relation to multiple stressors, hierarchical multiple regression revealed the developmental nature of coping and indicated that higher spirituality reliance and higher degree of parental care were predictive of adaptive coping among EYA cancer survivors. Content analyses of the open-ended questions confirmed these results. In order to facilitate adaptive coping, attention must be paid to the unique biopsychosocial-spiritual and developmental needs of young cancer survivors while encouraging family support and spirituality reliance as significant tools in coping. Practical recommendations for nursing support and healthcare teams are discussed.


Total proximal ureter substitution using buccal mucosa.
The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.


Urine concentrations of fentanyl and norfentanyl during application of Duragesic transdermal patches.
A study of the urinary concentration of fentanyl (F) and its major metabolite norfentanyl (NF) in chronic pain patients treated with the Duragesic continuous release transdermal patches is presented. These patches are available in 10, 20, 30, and 40 cm(2) sizes releasing 25, 50, 75, and 100 microg/h F, respectively. F is rapidly and extensively metabolized, with NF as the major metabolite. Five hundred-forty six random urine specimens were collected from chronic pain patients wearing 25, 50, 75, or 100 ug F transdermal patches. Urine specimens were collected from hours after application to several days later after continuous F release. Each specimen was analyzed for F, NF, creatinine, and pH. Additionally, each was screened by enzyme immunoassay for the following: amphetamines, barbiturates, benzodiazepines, cocaine metabolite, methadone, phencyclidine, d-propoxyphene, opiates, and marijuana metabolites. All positive screening results were confirmed by gas chromatography-mass spectrometry (GC-MS). F and NF were isolated from urine by solid-phase extraction then identified and quantified by GC-MS in SIM mode. The LODs and LOQs for F and NF were 3 ng/mL, respectively. The results of F and NF analysis of urine form those wearing 25-microg patches (N = 142) was mean F, 47 ng/mL with a range of 0 to 983 ng/mL, and 97% of the specimens contained < 200 ng/mL and mean NF, 175 ng/mL with a range of 0-980 ng/mL, while 95% of the specimens contained < 400 ng/mL. The results of F and NF analysis of urine form those wearing 50 microg patches (N = 184) was: mean F, 74 ng/mL with a range of 0 to 589 ng/mL, and 92% of the specimens contained < 200 ng/mL and mean NF, 257 ng/mL with a range of 0-2200 ng/mL, and 98% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 75 microg patches (N = 85) was mean F, 107 ng/mL with a range of 0 to 1280 ng/mL, and 98% of the specimens contained < 400 ng/mL and mean NF, 328 ng/mL with a range of 0-5630 ng/mL, and 99% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 100 ug patches (N = 135) was mean F, 100 ng/mL with a range of 0 to 1080 ng/mL, while 96% of the specimens contained < 400 ng/mL and mean NF, 373 ng/mL with a range of 0-5730 ng/mL, and 95% of the specimens contained < 1000 ng/mL. The incidence of other drugs detected as a percentage the specimens was opiates, 48%, benzodiazepines, 43%; barbiturates, 3%; methadone, 4%; marijuana metabolite, 3%; and cocaine metabolite, 1%. With the exception of F and/or NF, no other drugs were detected in 25% of the specimens. These data demonstrate the wide variation in concentrations of F and NF in random urine specimens following application of Duragesic patches. However, these values obtained during therapeutic use far exceed concentrations previously reported in fatal poisoning. In general, one may expect to find urine NF concentrations 3-4 times higher than those of F.


Phytochemical profile, antimicrobial and antioxidant activities of essential oil extracted from Ecuadorian species Piper ecuadorense sodiro.
In the present research, the essential oil from Piper ecuadorense was analysed by GC/MS and GC/FID techniques. A total of forty-four chemical compounds were identified which represent 98.65% of the essential oil composition. The main compounds were bicyclogermacrene (12.98%), 3-thujopsanone (11.59%), α-phellandrene (6.89%), (E)-nerolidol (6.88%), δ-elemene (6.83%) and shyobunol (5.79%). The essential oil from P. ecuadorense exerted a strong activity against Gram-positive bacterium Staphylococcus aureus (ATCC 25923) with an MIC of 250 μg/mL, and a very strong activity against Trichophyton rubrum (ATCC 28188) and Trichophyton mentagrophytes (ATCC 28185) with an MIC of 62.5 μg/mL in both cases. The antioxidant activity of essential oil was explored using DPPH and ABTS method, through ABTS assay. The oils showed an IC50 of 1.81 ± 0.09 mg/mL. This is the first report on the chemical composition and biological activity of essential oil from this species.


Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked by symptoms that symbolized death in a patient with terminal stage stomach cancer: case report and review of the literature.
We report here a terminally ill patient with stomach cancer who developed a brief psychotic disorder mimicking cerebrovascular attack after a short episode of nasal bleeding. Close examination of the patient revealed that nasal bleeding was an event that symbolized deterioration of the general condition leading to death for the patient. A 77-year-old male, who was diagnosed as having stomach cancer and was receiving palliative care, presented with tremor and insomnia just after a short episode of nasal bleeding and showed reduced response to stimuli mimicking cerebrovascular attack. Laboratory data were unremarkable. The next day, catatonic behavior developed. He had no history of psychiatric illness or drug or alcohol abuse. After receiving haloperidol, psychiatric symptoms disappeared and he returned to the previous level of functioning within 3 days. The patient explained that he had seen a patient whose general condition deteriorated after nasal bleeding and regarded nasal bleeding as a symptom of deteriorating general condition leading to death and thereafter became afraid of the nasal bleeding. Although, nasal bleeding is common and usually not severe in medical settings, for the patient, it was an event that symbolized deterioration of the general condition leading to death. Brief psychotic disorder in cancer patients is rare in the literature, although patients receiving terminal care share various kinds of psychological burden. Medical staff in the palliative care unit should be aware of the psychological distress experienced by each patient and consider brief psychotic disorder as part of the differential diagnosis when patients show unexplained neurological-like and/or psychiatric symptoms.


Transition from positive to neutral in mutation fixation along with continuing rising fitness in thermal adaptive evolution.
It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution.


Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression.
We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL11A1 expression levels, as well as resistance to cisplatin or paclitaxel. SC66 inhibited phosphorylation of Akt and its downstream effectors 4EBP1 and p70S6 kinase. SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. SC66-sensitized chemoresistant cells to cisplatin and paclitaxel treatment, and promoted apoptosis. In addition, SC66 inhibited COL11A1 expression via decreased binding of CCAAT/enhancer-binding protein beta (c/EBPβ), reducing chemoresistance and decreasing binding of nuclear transcription factor Y (NF-YA) to COL11A1. A mouse xenograft experiment demonstrated that SC66 treatment caused a reduction in tumor formation and enhanced the therapeutic efficacy of cisplatin. This study demonstrates the role of Akt in ovarian tumor progression and chemoresistance, and supports the application of SC66 as a therapy for ovarian cancer.


Human papillomavirus type 16 and 18 variants: race-related distribution and persistence.
Analogous to the geographic distribution of variants of human papillomavirus (HPV) types, the distribution and persistence of these variants among infected individuals may be related to the racial composition of a population living in one geographic region. We studied 1114 women in the United States participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 and/or HPV18 at enrollment. Race was self-reported. HPV samples were characterized by sequencing the E6 gene and part of the long control region and classified as variants according to established lineages. Subjects were examined for HPV every 6 months for 2 years. All statistical tests were two-sided. HPV18 African variants were predominant in the 97 HPV18-infected African American women (i.e., 62 women or 63.9%, 95% confidence interval [CI] = 53.5% to 73.4%), and European variants were common in the 168 HPV18-infected white women (i.e., 91 women or 54.2%, 95% CI = 46.3% to 61.9%). HPV16 African variants accounted for 43 (26.5%, 95% CI = 19.9% to 34.0%) of the infections in the 162 HPV16-infected African American women but for only 25 (4.3%, 95% CI = 2.8% to 6.3%) in the 584 HPV16-infected white women. The likelihood of remaining HPV18 positive was statistically significantly higher in white women infected with European than in white women infected with African variants (P = .04); the reverse was observed in African American women (P = .03). A similar pattern was observed for persistence of HPV16 variants, with the likelihood of remaining positive being higher for white women, but lower for African American women, infected with an European variant than with an African variant (P = .03 and P = .16, respectively). Variants of HPV16 and HPV18 appear to persist longer in a host whose race indicates an ancestral geographic distribution that was once shared with that of the variant-i.e., European variants persist longer in white women, and African variants persist longer in African American women.


Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds.
Combination immunotherapy is promising to overcome the limited objective response rates of immune checkpoint blockade (ICB) therapy. Here, a tumor immunological phenotype (TIP) gene signature and high-throughput sequencing-based high-throughput screening (HTS2) were combined to identify combination immunotherapy compounds. We firstly defined a TIP gene signature distinguishing "cold" tumors from "hot" tumors. After screening thousands of compounds, we identified that aurora kinase inhibitors (AKIs) could reprogram the expression pattern of TIP genes in triple-negative breast cancer (TNBC) cells. AKIs treatments up-regulate expression of chemokine genes CXCL10 and CXCL11 through inhibiting aurora kinase A (AURKA)-signal transducer and activator of transcription 3 (STAT3) signaling pathway, which promotes effective T cells infiltrating into tumor microenvironment and improves anti-programmed cell death 1 (PD-1) efficacy in preclinical models. Our study established a novel strategy to discover combination immunotherapy compounds and suggested the therapeutic potential of combining AKIs with ICB for the treatment of TNBC.


Microstructure Development and Its Influence on the Properties of Styrene-Ethylene-Butylene-Styrene/Polystyrene Blends.
The present work is a novel attempt to understand the microstructure of styrene-ethylene-butylene-styrene (SEBS)/polystyrene (PS) blends not only through morphological studies, but also thermal, mechanical and rheological characterizations. SEBS/PS blends containing 10, 30 and 50 wt % PS were processed in a micro-compounder and characterized. Scanning electron microscopy (SEM) studies, with selective staining of the PS phase, revealed the presence of PS as nanometer-sized domains, as well as phase-separated micrometer-sized aggregates. Blends with 30 and 50 wt % PS exhibited a fibrillar microstructure, obeying Hirsch's model of short fiber composites. A remarkable increase in glass transition temperature indicated a strong interaction of the fibrils with SEBS. All blends showed two modes of relaxation corresponding to the two phases. A single mode of relaxation of the PS phase has been attributed to combined effects of the partial miscibility of the added PS, along with the interaction of the fibrils with SEBS. The long relaxation time of the elastomeric phase indicated the tendency of these materials to undergo time-dependent shrinkage in secondary processing operations. An increase in PS content resulted in the lowering of the shear viscosity and energy requirement for mixing, indicating the ease of processing.


Changes in afferent activity after spinal cord injury.
To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Adelta) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord.


Gliclazide decreases vascular smooth muscle cell dysfunction induced by cell-mediated oxidized low-density lipoprotein.
Accumulating evidence indicates that oxidative modification of low-density lipoprotein (LDL) plays an important role in vascular dysfunction associated with diabetes mellitus. The aim of the present study was to investigate the effect of gliclazide, a second-generation sulfonylurea with free-radical-scavenging activity, on human aortic smooth muscle cell (HASMC)-mediated LDL oxidation and HASMC dysfunction induced by oxidatively modified LDL. Incubation of HASMCs with native human LDL (100 microg/mL) in the presence of increasing concentrations of gliclazide (1 to 10 microg/mL) resulted in a dose-dependent decrease in HASMC-mediated LDL oxidation. Exposure of HASMCs to gliclazide (1 to 10 microg/mL) and native LDL (100 microg/mL) also led to a dose-dependent decrease in oxidized LDL-induced human monocyte adhesion to HASMCs. In addition, incubation of HASMCs with gliclazide dramatically reduced the ability of oxidized LDL to stimulate the proliferation of these cells. Finally, treatment of HASMCs with gliclazide resulted in a marked decrease in oxidatively modified LDL-induced monocyte chemoattractant protein (MCP)-1 and human heat shock protein 70 (hsp 70) expression, both at the gene and protein levels. These results show that gliclazide, at concentrations in the therapeutic range (5 to 10 microg/mL), is effective in vitro in reducing vascular smooth muscle cell (VSMC) dysfunction induced by oxidatively modified LDL. These observations suggest that administration of gliclazide to type 2 diabetic patients could form part of the strategy for the prevention and management of diabetic cardiovascular diseases.


The prevalence of dental anomalies in orthodontic patients at the State University of New York at Buffalo.
To determine the prevalence of permanent tooth anomalies in patients attending the graduate orthodontic clinic at the State University of New York at Buffalo. Charts of 496 subjects (310 females and 186 males) met the inclusion criteria for this study. The mean ages were 16 years and 3 months for the combined gender sample that received orthodontic treatment in the graduate orthodontic clinic between 2007 and 2010. Full pretreatment records (intraoral photographs, digital study models, lateral cephalograms and panoramic radiographs) were used for the assessment. Charts were examined for these anomalies: agenesis, supernumerary, impaction and delayed tooth eruption. Subjects were categorized by gender and ethnicity. The percentages of the anomalies were assessed according to type of malocclusion, gender, race, location, tooth class and region in the dental arches. Sixty-four subjects (12.9%) had at least one occurrence of delayed eruption and impaction (DEI), followed by 47 subjects (9.5%) who had at least one occurrence of agenesis, and seven (1.4%) had a supernumerary condition. Approximately 80% of the subjects had no dental anomalies. The presence of more than one anomaly was observed in 61 subjects. Twelve subjects (2.4%) had both agenesis and DEI. Agenesis tended to be more common in class II malocclusions (p=0.012). The prevalence of permanent tooth anomalies was (20.4%). The percentage occurrence of DEI was the highest (12.9%) followed by dental agenesis (9.5%) and supernumerary teeth (1.4%) in the orthodontic patients at the State University of New York at Buffalo.


Microstructure-Dependent Charge/Discharge Behaviors of Hollow Carbon Spheres and its Implication for Sodium Storage Mechanism on Hard Carbon Anodes.
Hard carbons are actively developed as a promising anode material for sodium ion batteries (SIBs). However, their sodium storage mechanism is poorly understood, leading to difficulties in design and development of high-performance hard carbon anode materials. In this work, hollow carbon spheres (HCSs) with different shell thickness as a model material to investigate the correlation between the microstructural change and resulting Na+ storage behavior during charge/discharge cycles are designed and synthesized. Ex situ X-ray diffraction and Raman evidences reveal that an interlayer spacing change of the graphitic nanodomains occurs in HCS electrode, leading to a shift of the reversible capacity from the high-potential sloping (HPS) region to the low-potential plateau (LPP) region. This unusual capacity shift suggests a microstructure-dependent Na+ storage reaction on the HCS electrode and can be well explained by "adsorption-intercalation" mechanism for these HCS materials. This work strengthens the understanding of the sodium storage behavior and provides a new perspective for the morphological and structural design of hard carbon anode materials for high-performance SIBs.


Platelet-derived growth factor is a principal inductive factormodulating mannose 6-phosphate/insulin-like growth factor-II receptorgene expression via a distal E-box in activated hepatic stellate cells.
Hepatic stellate cells (HSCs) become activated during the earlystages of hepatic injury associated with fibrogenesis. The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGFIIR) plays animportant role in early fibrogenesis by participating in the activationof latent transforming growth factor-beta, a potent inducer of thematrix proteins in activated stellate cells that produce the hepaticnodule. Platelet-derived growth factor (PDGF), a potent HSC mitogen, isreleased early in hepatic injury and activates several signallingpathways in HSCs. In this study we examined the role of PDGF-BB in HSCregulation of M6P/IGFIIR gene expression. Several promoter elementswere found and characterized that modulate M6P/IGFIIR expression inactivated stellate cells. The presence of a distal CACGTG E-box at-2695 was required for M6P/IGFIIR expression in transfectedstellate cells. When the distal E-box was removed there was no significant M6P/IGFIIR promoter activity. The distal E-box-binding protein responded specifically to PDGF-BB with increased binding. This coincided with PDGF-BB up-regulation of M6P/IGFIIR mRNA transcript levels. Downstream elements include two proximal (-2 to-48) CACGTG E-boxes that bind a different protein to the distal(-2695) E-box. The proximal E-boxes respond moderately to PDGF-BB. The promoter segment encompassing -144 to +109 is able to respond dramatically to serum but is refractory to PDGF-BB. However, a constitutively bound protein binding to the -611/-716 fragment appears to be a repressor that suppresses inductive changes in protein binding occurring downstream of -611. These results indicate that the M6P/IGFIIR promoter responds primarily and specifically to PDGF-BB through a distal E-box element and possibly through two proximal E-box elements.


Steroids in villous atrophy: opening a can of worms?
A 60 year old man presented to the emergency department with septic shock and respiratory distress. He noted significant weight loss over the last 6 months with associated postprandial bloating. Endoscopy demonstrated partial villous atrophy. He had been on a gluten free diet, received empirical treatment for giardiasis and was receiving treatment with high dose systemic steroids for retroperitoneal fibrosis. This case discusses histology findings, differentials and reason for this acute presentation.


Systematic Isolation of Key Parameters for Estimating Skeletal Maturity on Knee Radiographs.
The ability to estimate skeletal maturity using a knee radiograph would be useful in anterior cruciate ligament (ACL) injuries and limb-length discrepancy in immature patients. Currently, a quick, accurate, and reproducible method is lacking. Serial knee radiographs made 3 years before to 2 years following the chronologic age associated with 90% of final height (an enhanced skeletal maturity gold standard compared with peak height velocity) were analyzed in 78 children. The Pyle and Hoerr (PH) knee method was simplified by developing discrete stages for the distal part of the femur, the proximal part of the tibia, the proximal part of the fibula, and the patella. The Roche-Wainer-Thissen (RWT) knee method was simplified from the 36 original parameters to 14 parameters by removing parameters that were poorly defined, were not relevant to the peripubertal age range, were poorly correlated with 90% final height, or were poorly reliable on a 20-radiograph pilot analysis. We also compared the recently described central peak value (CPV) of the distal part of the femur. The Greulich and Pyle (GP) left-hand bone age was included for comparison. In this study, 326 left knee radiographs from 41 girls (age range, 7 to 15 years) and 37 boys (age range, 9 to 17 years) were included. Stepwise linear regression showed higher correlation in predicting years from 90% final height using the modified RWT and demographic characteristics (R2 = 0.921) compared with demographic characteristics alone (R2 = 0.840), CPV and demographic characteristics (R2 = 0.866), GP and demographic characteristics (R2 = 0.899), and PH and demographic characteristics (R2 = 0.902). Seven parameters were excluded from the RWT and demographic characteristics model using stepwise linear regression and generalized estimating equations analysis, leaving 7 parameters (2 femoral, 4 tibial, and 1 fibular) in the final model. Compared with RWT and demographic characteristics (R2 = 0.921), there were minimal incremental increases by adding CPV (R2 = 0.921), GP (R2 = 0.925), or PH (R2 = 0.931). This large analysis of knee skeletal maturity systems isolated 7 discrete radiographic knee parameters that theoretically outperform the GP bone age in estimating skeletal maturity. We present a modified knee skeletal maturity system that can potentially preclude the need for additional imaging of the hand and wrist in reliably estimating skeletal maturity.


The complete mitochondrial genome of Oocatochus rufodorsatus (Reptilia, Serpentes, Colubridae).
The complete mitochondrial genome from the red-backed ratsnake Oocatochus rufodorsatus was determined. The following four distinctive features are observed: duplicate control regions that have nearly identical sequences at two different locations of mitogenome, translocation of tRNA-Leu (UUR), a pseudogene for tRNA-Pro and truncations of TΨC arm for most tRNA genes.


The nitrate transporter OsNPF7.9 mediates nitrate allocation and the divergent nitrate use efficiency between indica and japonica rice.
Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica-japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding.


Synthesis and Characterization of Ferrierite-Type Zeolite in the Presence of Nonionic Surfactants.
Pure-phase ferrierite (FER) zeolite has been synthesized in the presence of small amounts of nonionic surfactants, Tween 20 and Tween 80. The input SiO(2)/Al(2)O(3) molar ratio has been varied over a range of 25 to 150. The results confirm that a small amount of pyrrolidine acts as a template and is necessary. The effects of varying concentration of surfactant on ferrierite crystallization and output SiO(2)/Al(2)O(3) molar ratio are reported. The results also show that in the absence of pyrrolidine, ZSM-5 cocrystallized with FER, whereas in the absence of a nonionic surfactant the yield and crystallization of FER are very poor. The XRF analysis shows the changes in SiO(2)/Al(2)O(3) output molar ratios as the surfactant concentration changes. The XRD data show that the samples are fully crystalline and pure. The TG/DTA of the sample shows its structural stability. The scanning electron microscopy results show changes in particle size with varying concentration of nonionic surfactant. Copyright 2001 Academic Press.


Adenosine and sleep homeostasis in the Basal forebrain.
It is currently hypothesized that the drive to sleep is determined by the activity of the basal forebrain (BF) cholinergic neurons, which release adenosine (AD), perhaps because of increased metabolic activity associated with the neuronal discharge during waking, and the accumulating AD begins to inhibit these neurons so that sleep-active neurons can become active. This hypothesis grew from the observation that AD induces sleep and AD levels increase with wake in the basal forebrain, but surprisingly it still remains untested. Here we directly test whether the basal forebrain cholinergic neurons are central to the AD regulation of sleep drive by administering 192-IgG-saporin to lesion the BF cholinergic neurons and then measuring AD levels in the BF. In rats with 95% lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6 h of prolonged waking. However, the lesioned rats had intact sleep drive after 6 and 12 h of prolonged waking, indicating that the AD accumulation in the BF is not necessary for sleep drive. Next we determined that, in the absence of the BF cholinergic neurons, the selective adenosine A1 receptor agonist N6-cyclohexyladenosine, administered to the BF, continued to be effective in inducing sleep, indicating that the BF cholinergic neurons are not essential to sleep induction. Thus, neither the activity of the BF cholinergic neurons nor the accumulation of AD in the BF during wake is necessary for sleep drive.


Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.
Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.


Cooling for cerebral protection during brain surgery.
The brain is at risk of ischaemia during a variety of neurosurgical procedures, and this can lead to devastating results. Induced hypothermia is the controlled lowering of core body temperature for therapeutic purposes. This remains the current practice during neurosurgery for the prevention or minimization of ischaemic brain injury. Brain surgery may lead to severe complications due to factors such as requirement for brain retraction, vessel occlusion, and intraoperative haemorrhage. Many anaesthesiologists believe that induced hypothermia is indicated to protect the central nervous system during surgery. Although hypothermia is often used during brain surgery, clinical efficacy has not yet been established. To evaluate the effectiveness and safety of induced hypothermia versus normothermia for neuroprotection in patients undergoing brain surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE, LILACS, EMBASE and Current Controlled Trials (from inception to November 2010), reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. There were no language restrictions. We included randomized controlled trials and quasi-randomized controlled trials of induced hypothermia versus normothermia for neuroprotection in patients undergoing brain surgery. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We included four trials of cooling for cerebral protection during brain surgery, involving a total of 1219 patients. We did not find any evidence that hypothermia for neuroprotection in patients undergoing brain surgery is either effective or unsafe when compared to normothermia. Although there is some evidence that mild hypothermia is safe, its effectiveness is not clear when compared with normothermia. We need to perform more clinical trials in order to establish the benefit, if any, of hypothermia for cerebral protection during brain surgery before making firm recommendations for the routine use of this intervention.


An abbreviated history of the ear: from Renaissance to present.
In this article we discuss important discoveries in relation to the anatomy and physiology of the ear from Renaissance to present. Before the Renaissance, there was a paucity of knowledge of the anatomy of the ear, because of the relative inaccessibility of the temporal bone and the general perception that human dissections should not be conducted. It was not until the sixteenth century that the middle ear was described with detail. Further progress would be made between the sixteenth and eighteenth century in describing the inner ear. In the nineteenth century, technological advancement permitted a description of the cells and structures that constitute the cochlea. Von Helmholtz made further progress in hearing physiology when he postulated his resonance theory and later von Békésy when he observed a traveling wave in human cadavers within the cochlea. Brownell later made a major advance when he discovered that the ear has a mechanism for sound amplification, via outer hair cell electromotility.


Mesenchymal and Phosphatase of Regenerating Liver-3 Status in Circulating Tumor Cells May Serve as a Crucial Prognostic Marker for Assessing Relapse or Metastasis in Postoperative Patients With Colorectal Cancer.
Circulating tumor cells (CTCs) and phosphatase of regenerating liver-3 (PRL-3) have been considered to be significant prognostic indicators in metastatic colorectal cancer (CRC). This study discusses the prognostic significance of mesenchymal CTCs with PRL-3 (M+ PRL-3+ CTCs) in postoperative patients with CRC. We detected CTC subtypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) and PRL-3 in CTCs from the peripheral blood samples of 156 patients. Receiver operating characteristic curve analysis, Kaplan-Meier analysis, and Cox proportional hazards regression analysis were performed to identify the prognostic value of mesenchymal CTCs with PRL-3+. Immunohistochemistry was used to detect the expression of PRL-3 in tumor tissues from some of the patients to explore the connection between CTCs and tissues. All CTCs were positive in all samples, both mesenchymal CTCs and PRL-3-positive cells. The count of mesenchymal and PRL-3+ CTCs was significantly associated with recurrence, and the optimal cutoff value was 2 (area under the curve = 0.690, P < 0.001). In addition, these patients had a significantly shorter median disease-free survival than those who did not fulfill the criteria (8.5 vs 24 months, P < 0.001) according to multivariable and multinomial logistic regression. Immunohistochemistry was applied to explore the associations between PRL-3 expression and significant prognostic risk factors, including recurrence (R = 0.566; P < 0.001), and M+ PRL-3+ status in CTCs (R = 0.452; P = 0.001). The status of M+ PRL-3+ in CTCs may serve as a crucial prognostic marker for assessing clinical outcomes in CRC.


Effects of body condition on measures of intramuscular and rump fat, endocrine factors, and calving rate of beef cows grazing common bermudagrass or endophyte-infected tall fescue.
Multiparous beef cows were managed to achieve marginal (BCS = 4.7 ± 0.07; n = 106) or good (BCS = 6.6 ± 0.06; n = 121) body condition (BC) to determine the influence of forage environment on BW and BC changes, intramuscular fat percentage (IMF), rump fat (RF), and serum hormones during 2 yr. Cows within each BC were randomly assigned to graze either common bermudagrass (CB; n = 3 pastures/yr) or toxic endophyte-infected tall fescue (EI; n = 3 pastures/yr) during a 60-d breeding season. Blood samples were collected at d 0, 30, and 60 of the breeding season, and serum concentrations of prolactin (PRL), IGF-I, and cortisol (CORT) were quantified; PRL and progesterone (P(4)) also were quantified 10 d before the breeding season (d -10). Body weight and BCS were recorded during the breeding season (d 0, 30, and 60). Cow IMF and RF were measured via ultrasonography at the start and end of the breeding season. Cows with increased (>1 ng/mL) P(4) at the beginning of the breeding season (cyclic) had greater (P < 0.02) concentrations of PRL on d 30 and 60 compared with anestrous cows. A forage environment × BC interaction tended (P = 0.07) to influence PRL. Cows grazing CB independent of BC had increased PRL compared with cows grazing EI. Prolactin was decreased in good-BC cows grazing EI compared with cows grazing CB, and cows in marginal BC grazing EI had the least concentrations of PRL. Concentrations of IGF-I were similar (P > 0.10) among good- and marginal-BC cows grazing CB, as well as good-BC cows grazing EI; however, marginal-BC cows grazing EI had reduced (P < 0.04) concentrations of IGF-I compared with all other groups. Cows in marginal BC grazing CB gained (P = 0.02) the most BW during the breeding season, whereas good-BC cows grazing EI gained the least amount of BW. Marginal-BC cows grazing CB tended (P = 0.06) to increase BC during the breeding season, whereas good-BC cows grazing either CB or EI lost BC. Rump fat tended (P = 0.07) to increase during the breeding season in marginal-BC cows compared with cows in good BC. Calving rates were similar (P > 0.10) among good- (82%) and marginal- (84%) BC cows grazing CB, and good-BC cows grazing EI (79%); however, marginal-BC cows grazing EI had a reduced (P = 0.04) calving rate (61%). Cattle grazing EI during the breeding season lost BC. That reduction in BC may be communicated to the pituitary via hormones that include IGF-I or PRL or both, resulting in decreased calving rates.


The social, cosmopolitanism and beyond.
First, this article will outline the metaphysics of "the social" that implicitly and explicitly connects the work of classical and contemporary cosmopolitan sociologists as different as Durkheim, Weber, Beck and Luhmann. In a second step, I will show that the cosmopolitan outlook of classical sociology is driven by exclusive differences. In understanding human affairs, both classical sociology and contemporary cosmopolitan sociology reflect a very modernist outlook of epistemological, conceptual, methodological and disciplinary rigour that separates the cultural sphere from the natural objects of concern. I will suggest that classical sociology -- in order to be cosmopolitan -- is forced (1) to exclude "non-social and non-human objects" as part of its conceptual and methodological rigour, and (2) consequently and methodologically to rule out the non-social and the non-human. Cosmopolitan sociology imagines "the social" as a global, universal "explanatory device" to conceive and describe the non-social and non-human. In a third and final step the article draws upon the work of the French sociologist Gabriel Tarde and offers a possible alternative to the modernist social and cultural other-logics of social sciences. It argues for a inclusive conception of "the social" that gives the non-social and non-human a cosmopolitan voice as well.


Plant-Based Alternative Products: Are They Healthy Alternatives? Micro- and Macronutrients and Nutritional Scoring.
In recent decades, the demand, supply, and consumption of plant-based (pb) alternative products have increased worldwide. The objective of this study was to characterize pb meat and cheese products and compare them with their respective animal-based products. Data were collected in online market analyses (2019/2021). Nutritional data, Nutri-Score, and analysis of micronutrients are presented in this article. The number of products has grown in all categories, with the largest increase of 110% in pb cheese. The main protein sources in pb meat were soy and wheat, followed by an increasing use of peas. Pb meat generally contained less energy and total and saturated fat, but more carbohydrates and sugars than meat. In pb cheese, the protein content was lower than that of cheese. In 3 of 17 food groups, the salt content of pb alternatives was lower than in animal products. The daily requirement for iron could be covered better by pb alternatives than previously anticipated as well as the need for the vitamins E and K. The calculated Nutri-Score was generally lower for pb meat and higher for pb cheese than for the respective animal products. The trend towards consumption of pb alternative products is increasing, but the high level of processing, wide range of nutrients, and high salt content indicate the need for nutritional guidelines for these products.


Fluorescence-based Western blotting for quantitation of protein biomarkers in clinical samples.
Since most high throughput techniques used in biomarker discovery are very time and cost intensive, highly specific and quantitative analytical alternative application methods are needed for the routine analysis. Conventional Western blotting allows detection of specific proteins to the level of single isotypes while its quantitative accuracy is rather limited. We report a novel and improved quantitative Western blotting method. The use of fluorescently labelled secondary antibodies strongly extends the dynamic range of the quantitation and improves the correlation with the protein amount (r=0.997). By an additional fluorescent staining of all proteins immediately after their transfer to the blot membrane, it is possible to visualise simultaneously the antibody binding and the total protein profile. This allows for an accurate correction for protein load. Applying this normalisation it could be demonstrated that fluorescence-based Western blotting is able to reproduce a quantitative analysis of two specific proteins in blood platelet samples from 44 subjects with different diseases as initially conducted by 2D-DIGE. These results show that the proposed fluorescence-based Western blotting is an adequate application technique for biomarker quantitation and suggest possibilities of employment that go far beyond.