Codependence with hypersexual and gambling disorder.
Background The risks of behavioral addictions are well documented. There are biological, medical, social, spiritual, psychological, and safety risks to the individual as well as risks, like ripple effects, to the family and friends with whom the individual with behavioral addictions lives. The phenomenon of collateral damage from addictions, especially alcoholism and substance dependence, is well documented. Aims and methods A selected review of the literature reveals little regarding the risks of collateral damage, in particular codependence, from behavioral addictions on non-addicted family and friends. Results This article theoretically posits the existence of codependence to those with two well documented and researched behavioral addictions, hypersexual and gambling disorder, using the biopsychosocial lens. Conclusions Addictions professionals are encouraged to revisit the literature on codependence and consider its influence on family and friends of those with behavioral addictions when providing services.


The crosslinking and antimicrobial properties of tunichrome.
Tunichromes are small peptides containing one or more dehydrodopa derived units that have been identified in the blood cells of at least eleven species of tunicates. Incubation of tunichromes isolated from Ascidia nigra hemocytes (or model dopa-containing compounds) under oxidative conditions with either lysozyme, cytochrome c or ovalbumin resulted in a time-dependent polymerization of these test proteins to dimers, trimers, tetramers and potentially to other oligomers. These results indicate that the oxidation products of tunichromes possess inherent crosslinking properties. Hence it is possible that tunichromes participate in tunic production by forming adducts and crosslinks with structural proteins and/or carbohydrate polymers, similar to the well-understood process of insect cuticle hardening. Since such crosslinking potentials could also be beneficial for defense reactions against invading microorganisms, antibacterial activity of tunichromes was tested using both a radial diffusion assay and the Microtox(R) test. Tunichromes exhibited antimicrobial activity against gram-negative bacteria Escherichia coli and Photobacterium phosphorium. However, they did not show any antimicrobial activity against the gram-positive bacteria Staphylococcus aureus at the concentrations tested. We propose that the crosslinking and antimicrobial functions are both based on the reactivity of dehydrodopa units present in the tunichromes, and their subsequent ability to form highly reactive quinone methides.


Trigeminocardiac reflex preceding development of postoperative superior orbital fissure syndrome.
The superior orbital fissure syndrome (SOFS) is a rare condition presenting as painful unilateral opthalmoplegia, ptosis, pupillary dilatation and anesthesia of the upper eyelid and forehead. It has been described after facial trauma. Other etiologies include infections, tumors or spontaneous hemorrhages in the retro-orbital space. Occurrence of SOFS after surgery in the skull base has not been described before. We recently encountered a case where a young female developed SOFS following surgery for cerebrospinal fluid (CSF) rhinorrhea. The occurrence of SOFS was preceded by episodes of trigemino-cardiac reflex (TCR) during the surgery. This is the first case report associating TCR with SOFS. We managed the case report with megadose methylprednisolone and the patient showed improvement in the deficit over time.


Impact of perioperative blood transfusion on oncologic outcomes in patients with nonmetastatic renal cell carcinoma treated with curative nephrectomy: A retrospective analysis of a large, single-institutional cohort.
To evaluate the impact of perioperative blood transfusion (PBT) on oncologic outcomes after surgery in patients with nonmetastatic renal cell carcinoma (RCC). This retrospective review included 2,329 patients who underwent partial or radical nephrectomy for localized RCC in a single institution from 2000 to 2014. PBT was defined as transfusion of allogeneic packed red blood cells (pRBCs) during nephrectomy or within the preoperative or postoperative hospitalization period. Oncologic outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). PBT was performed in 275 patients (11.8%). In the multivariable logistic regression analysis, symptomatic presentation, advanced age at surgery, higher preoperative serum creatinine, and lower preoperative hemoglobin were independent preoperative risk factors for PBT (all p<0.05). Kaplan-Meier plots revealed that transfused patients showed poorer 5-year RFS (65.1% vs. 91.2%, p<0.001), OS (71.4% vs. 92.8%, p<0.001), and CSS (74.0% vs. 95.5%, p<0.001) than nontransfused patients. However, in the multivariable Cox regression analyses, PBT was not significantly associated with RFS, OS, or CSS. In multivariable analyses involving transfused patients only (n=275), an higher number of pRBC units was an independent predictor of worse OS (hazard ratio [HR], 1.043; 95% confidence interval [CI], 1.008-1.078; p=0.016) and CSS (HR, 1.066; 95% CI, 1.033-1.100; p<0.001). The results of this study are inconclusive in that the influence of PBT on survival outcomes could not be determined in the multivariate analysis. However, increasing pRBC units in transfused patients might be a concern in light of worse OS and CSS. Therefore, efforts to limit PBT overuse seem necessary to improve postoperative survival in patients with RCC.


[The role of neuroprotection in complex rehabilitation of patients with ischemic stroke].
In this review we considered some questions of early rehabilitation in ischemic stroke. Rehabilitation tactics such patients provides non-medical (treatment status, developmental kinesitherapy, early vertical integration and activation of the patient), and medications (antiplatelet, nootropic, antioxidant and vascular therapy) methods. It was examined the data on the pathogenesis of acute ischemia and the role of neuroprotection in early rehabilitation. We analyzed the rationale for the use of citicoline in the most acute period of stroke.


Protection of a restriction enzyme from heat inactivation by [alpha]-crystallin.
To determine whether the chaperone activity of human alpha-crystallin can protect a restriction enzyme from heat inactivation. The restriction enzyme Nde I was heated in the presence or absence of purified bovine alpha-crystallin. Following heat treatment, the enzymatic activity of the heat treated samples was assayed by cleavage of plasmid DNA. The extent of digestion was monitored by agarose gel electrophoresis and visualization of DNA fragments by ethidium bromide staining. Heating of Nde I in the absence of alpha-crystallin resulted in inactivation. However, Nde I heated in the presence of alpha-crystallin remained active. Furthermore, an increased amount of alpha-crystallin provided a longer period of thermal protection. The chaperone activity and thermo-protective effect of alpha-crystallin extend to protection of enzymatic activity, not merely the protection from thermally induced aggregation/denaturation. In addition, inclusion of alpha-crystallin during some enzymatic reactions may be beneficial.


Non-heartbeating donation of kidneys for transplantation.
There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation.


Transpyloric Feeding Tube Placement Using Electromagnetic Placement Device in Children.
Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube placement, however, can be difficult, be time-consuming, and incur multiple radiation exposures. An electromagnetic device (EMD) is available for confirmation of successful placement of TPTs. We conducted a retrospective cohort study to evaluate the efficacy of an EMD for TPT placement in children and determine its impact on placement success, radiation exposure, confirmation time, and cost for tube placement compared with traditional blind TPT placement. Retrospective data were collected in patients receiving a TPT before (pre-EMD group) and after implementation of an EMD (EMD group). Need for radiographic exposure decreased significantly in the EMD group (n = 40) compared with the pre-EMD group (n = 38) (0.6 vs 1.6 x-rays, P < .001). TPTs were placed and confirmed without abdominal x-ray in 21 of 40 patients in the EMD group. There were no serious adverse events such as misplacement into the lung or pneumothorax or perforation injury of the stomach. Successful tube confirmation took a significantly shorter time in the EMD group than in the pre-EMD group (1.45 vs 4.59 hours, P < .0001). There was an estimated cost savings of $245.10 per placement associated with decreased x-ray and fluoroscopy. The use of an EMD in children significantly decreased radiation exposure and confirmation time while maintaining TPT placement success. The use of an EMD can potentially offer large cost savings. Elimination of abdominal x-ray with EMD during TPT placement was achieved without any serious complications in approximately half of the children.


A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain.
Zinc (Zn) deficiency during early development can result in multiple brain abnormalities and altered neuronal functions. In rats, a gestational deficit of Zn can affect the fetal brain cytoskeleton and signaling cascades involved in cellular processes that are central to brain development. In this paper, we tested the hypothesis that oxidative stress is involved in Zn deficiency-induced altered tubulin dynamics and the associated dysregulation of transcription factor NF-κB. For this purpose, we used two cell culture models (rat cortical neurons, human IMR-32 neuroblastoma cells) and an animal model of Zn deficiency. A low rate of in vitro tubulin polymerization, an increase in tubulin oligomers, and a higher protein cysteine oxidation were observed in the Zn-deficient neuronal cells and in gestation day 19 fetal brains obtained from dams fed marginal-Zn diets throughout pregnancy. These alterations could be prevented by treating the Zn-deficient cells with the reducing agent tris(2-carboxyethyl)phosphine or by the presence of N-acetylcysteine (NAC) and α-lipoic acid (LA). Consistent with the above, Zn deficiency-induced tubulin-mediated alterations in transcription factor NF-κB nuclear translocation were prevented by treating IMR-32 cells with LA and NAC. Binding of the NF-κB protein p50, dynein, and karyopherin α (components of the NF-κB transport complex) to β-tubulin as well as the expression of NF-κB-dependent genes (Bcl-2, cyclin D1, and c-myc) was also restored by the addition of LA and NAC to Zn-deficient cells. In conclusion, a deficit in Zn viability could affect early brain development through: (1) an induction of oxidative stress, (2) tubulin oxidation, (3) altered tubulin dynamics, and (4) deregulation of signals (e.g., NF-κB) involved in critical developmental events.


Introducing Porosity in Colloidal Biocoatings to Increase Bacterial Viability.
A biocoating confines nongrowing, metabolically active bacteria within a synthetic colloidal polymer (i.e., latex) film. Bacteria encapsulated inside biocoatings can perform useful functions, such as a biocatalyst in wastewater treatment. A biocoating needs to have a high permeability to allow a high rate of mass transfer for rehydration and the transport of both nutrients and metabolic products. It therefore requires an interconnected porous structure. Tuning the porosity architecture is a challenge. Here, we exploited rigid tubular nanoclays (halloysite) and nontoxic latex particles (with a relatively high glass transition temperature) as the colloidal "building blocks" to tailor the porosity inside biocoatings containing Escherichia coli bacteria as a model organism. Electron microscope images revealed inefficient packing of the rigid nanotubes and proved the existence of nanovoids along the halloysite/polymer interfaces. Single-cell observations using confocal laser scanning microscopy provided evidence for metabolic activity of the E. coli within the biocoatings through the expression of a yellow fluorescent protein. A custom-built apparatus was used to measure the permeability of a fluorescein sodium salt in the biocoatings. Whereas there was no measurable permeability in a coating made from only latex particles, the permeability coefficient of the composite biocoatings increased with increasing halloysite content up to a value of 1 × 10-4 m h-1. The effects of this increase in permeability was demonstrated through a specially developed resazurin reduction assay. Bacteria encapsulated in halloysite composite biocoatings had statistically significant higher metabolic activities in comparison to bacteria encapsulated in a nonoptimized coating made from latex particles alone.


Reversal of negative pressure ventilation-induced lower esophageal sphincter dysfunction with metoclopramide.
We have previously demonstrated that lower esophageal sphincter (LES) dysfunction is induced in healthy volunteers placed in negative pressure body ventilators. This is important, because regurgitation of gastric contents and peptic esophagitis are frequent complications of the use of such ventilators. The present study was conducted to determine whether LES dysfunction during the use of these ventilators also occurs in patients with chronic respiratory failure, and whether this dysfunction can be pharmacologically reversed. Seven patients with documented chronic respiratory failure due to COPD were studied. After an overnight fast, esophageal, LES, and gastric pressures were simultaneously recorded in the unassisted state and during mechanically assisted ventilation, after which 10 mg iv metoclopramide were administered to each patient, and pressure recordings were continued for 1 h more. In all seven patients, baseline LES pressures were in the normal range. During the inspiratory cycle of mechanical ventilation, five of the seven patients demonstrated a significant reduction in LES pressure, whereas it was unchanged in the other two. Within 15 min of metoclopramide administration, there was an increase in LES pressure to baseline levels in the five patients in which a significant decrease in LES pressure had occurred. Metoclopramide did not have any effect on the LES pressure of the other two patients. Thus, we conclude that in patients with chronic respiratory failure, as in normals, there is a subset of individuals in whom negative pressure mechanical ventilatory assistance induces dysfunction of the LES, and that this dysfunction is reversible with metoclopramide.


[Thoughts on long-term estrogen substitution--should gynecologists change their mind?].
Public opinion and a large proportion of physicians believe that very often women must necessarily experience a restricted quality of life as a result of menopause, postmenopause and the senium, and that even a possible early death from the sequels of osteoporosis is quite natural and hence inevitable. However, the present state of the art rules out such fatalism, since it has been established beyond doubt that early initiation of oestrogen and progestagen substitution after the menopause is of high prophylactic value both from the viewpoint of social medicine and also in each individual case. Calculations of cost and effect in elderly women have shown that treatment results in reduced morbidity and mortality caused by carcinoma of the breast and of the endometrium, and also by cardiovascular disease, quite apart from an enhanced quality of life. Hence, all women who would like to receive such prophylactic treatment--in particular, also risk patients likely to suffer from osteoporosis-should definitely not be deprived of regular long-term administration of oestrogen that should continue until old age. The only basic condition is the sequential administration of oestrogen and progestagen at low dosage levels.


[Estimating ability of dihydroquercetin to inhibit oxidation of fibrinogen by ozone].
The ability of dihydroquercetin to inhibit the oxidation of fibrinogen has been evaluated. It is established that dihydroquercetin inhibits oxidation of fibrinogen by ozone, thus preventing oxidative modification of fibrinogen and preserving its functional activity.


[Hospital mortality in acute myocardial infarction: is it possible to predict using admission data?].
To identify clinical variables on admission that are related to hospital mortality in acute myocardial infarction (AMI) and to generate a mathematic model to predict accurately this mortality. Prospective study with 347 consecutive patients with AMI in which clinical variables related to mortality were identified by univariate and multivariate analysis. The mathematic model generated by multivariate logistic regression analysis was applied in each patient to determine his/her probability (P) of hospital death. Model's accuracy was validated by reliability and discrimination tests. Admission variables directly and independently related to hospital mortality: female gender, age, absence of history of hypertension, history of previous infarction, non-inferior AMI and Killip class. These six variables, when present cumulatively, showed increasing mortality rates. Mean P value for non-survivors was significantly greater than for survivors (43.2 +/- 31.4% vs 9.1 +/- 12.5%, p < 0.00001). Reliability of the model to predict death, assessed by stratifying patients in three risk groups (low, medium and high) or continuously (by linear regression analysis) showed excellent predictive performance. Discrimination between survivors and non-survivors, assessed by C-index (concordance probability), disclosed 85% rate of success. Risk variables can be used in a mathematic model that is capable of predicting accurately in-hospital mortality of each patient with AMI. Mortality prediction can allow physicians to be more efficient in assessing risk-benefit ratios in these patients when faced with therapeutic decisions.


HIGHLIGHTS OF HYPERTENSIVE AND NORMOTENSIVE GLAUCOMA.
The paper presents the up-to-date overview of pathogenesis, functional and structural changes in normotensive glaucoma (NTG) and its differences from hypertensive glaucoma (HTG). The autors point out new facts that distinguish both diagnostic groups. In the first place are the results of OCT angiography, which verify the pathology of NTG to the anterior part of optic nerve. Our findings confirmed that vascular component (VD) is more involved in changes of visual field than in perfusion parameters, especially in arteria ophtalmica (AO). Perfusion in arteria centralis retinae (ACR) does not play a significant role in NTG changes in the visual field. VD has very little effect on changes in visual field in HTG. Similarly, the retinal nerve fiber layer (RNFL) for changes in the visual field. Howerver, VD is moderately influenced by changes in RNFL. It should be emphasized that we compared the sum of sensitivity in the central part of the visual field (0-22 degrees) with RNFL and VD. In NTG, the anterior part of the optic nerve is altered. Mainly VD contributes to visual filed changes in NTG. It is also important to note that when the intraocular pressure (IOP) increased above 20 mm Hg, the macular and papillary VD was significantly reduced. Antiglaucomatous treatment with prostaglandins and beta-blockers is essential for the reduction of IOP in HTG. This reduction shoud be bellow 20 mm Hg, in eyes with thinner cornea the decrease in IOP should be more pronounced. It does not matter which antiglaucoma treatment was used. However, it should be noted that prostaglandins have a greater effect on disease progression, but the greater protective effect on the visual field have beta-blockers. Neuroprotectives should be recommended systemically in patients with HTG. When treating NTG, it is important to maintain blood flow of the posterior pole of the eye, but mainly of the anterior part of the optic nerve. Prostaglandins are not suitable in NTG patients, although their effect on IOL reduction is high. Beta-blockers (betaxolol and carteol) and brimonidine are most suitable. Corneal thickness has no effect on disease progression.


[Quantification of the differential diagnosis of Cushing's syndrome using computers].
The possibility to separate 11 patients with anatomically and histologically proven Cushing's syndrome from those 23 with Cushing's syndrome imitating obesity on the basis of 2 anamnestical, 10 physical and 8 basic laboratory and instrumental examinations was studied with the aid of a pattern recognition procedure by computer. Both groups were well distinguished one from another. The sensitivity of Cushing's diagnosis was 73%, its specificity 100% and effectivity 91%. The most important sign appeared the muscle hypotrophy of the proximal limb girdle.


What's in a Name? Correlates of Ecstasy Users Knowing or Agreeing that Molly is Ecstasy/MDMA.
Ecstasy (MDMA) has regained popularity in powder and crystalline form, known as Molly. However, it is unknown whether all Molly users are aware that Molly is ecstasy. A total of 1045 nightclub/festival-attending adults in New York City were surveyed about ecstasy/MDMA/Molly use in 2016. Users were asked if they agreed that "Molly is (or is supposed to be) ecstasy/MDMA." Of the 43.5% reporting lifetime use, 84.6% agreed that Molly is ecstasy, 9.5% disagreed, and 5.9% reported not knowing that Molly is ecstasy. Prevalence of use of other drugs (e.g., ketamine, opioids, methamphetamine, NBOMe, 2C series) was lowest among those not knowing that Molly is ecstasy, and highest among those not agreeing that Molly is ecstasy. Those not knowing that Molly is ecstasy were less likely to have used powder or crystal MDMA and less likely to have used in the past 12 months or to report intention to use again. Those disagreeing or not knowing that Molly is ecstasy were at over six times the odds of obtaining ecstasy from an unknown dealer, and those disagreeing were at four times higher odds of having suspected or found out that their ecstasy was adulterated. Results suggest that knowing or agreeing that Molly is ecstasy/MDMA can help indicate ecstasy-related risk.


A review of potential bluetongue virus vaccine strategies.
Bluetongue (BT) is an economically important, non-zoonotic arboviral disease of certain wild and domestic species of cloven-hooved ungulates. Bluetongue virus (BTV) is the causative agent and the occurrence of BTV infection is distinctly seasonal in temperate regions of the world, and dependent on the presence of vector biting midges (e.g. Culicoides sonorensis in much of North America). In recent years, severe outbreaks have occurred throughout Europe and BTV is endemic in most tropical and temperate regions of the world. Several vaccines have been licensed for commercial use, including modified live (live-attenuated) and inactivated products, and this review summarizes recent strategies developed for BTV vaccines with emphasis on technologies suitable for differentiating naturally infected from vaccinated animals. The goal of this review is to evaluate realistic vaccine strategies that might be utilized to control or prevent future outbreaks of BT.


New type of matrix support for bone marrow cell cultures: in vitro culture and in vivo transplantation experiments.
A new type of bone marrow cell culture system was developed by using a highly porous substrate matrix, i.e., porous polyvinyl formal (PVF) resin. Murine bone marrow (BM) cells were cultured without the use of exogenous growth factors in a three-dimensional matrix support made of collagen coated porous PVF resin. To examine the optimal conditions for highest stromal cell density, short-term and long-term in vitro culture experiments using PVF were performed. In the short-term culture experiments, it was found that cubes of PVF (10 x 10 x 2 mm and 130 microm in pore size) coated with type I collagen with a seeding density of 2x10(7) BM cells offered the most appropriate culture conditions. In the long-term cultures, BM cells in PVF maintained their viability for up to 6 weeks. In another series of re-inoculation experiments, freshly isolated BM cells were inoculated onto the already developed stromal layer. In this study, a higher cell density of the stromal layer was obtained in the PVF culture compared with those in the control dish culture. Based upon the results of in vitro experiments, in vivo transplantation studies were also performed. Histologic examinations of the subcutaneously transplanted PVF with stroma revealed host derived hematopoiesis inside the PVF matrix. Moreover, survival of approximately 15% of the transplanted BM cells that were cultured in PVF were confirmed in X-ray irradiated recipients. From these results, it is suggested that PVF resin is a promising three-dimensional substrate for BM cell culture and that it can maintain hematopoietic stem cells or progenitor cells after transplantation.


Morphological and mechanical properties of flexible resilin joints on damselfly wings (Rhinocypha spp.).
Resilin functions as an elastic spring that demonstrates extraordinary extensibility and elasticity. Here we use combined techniques, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM) to illuminate the structure and study the function of wing flexibility in damselflies, focusing on the genus Rhinocypha. Morphological studies using LSCM and SEM revealed that resilin patches and cuticular spikes were widespread along the longitudinal veins on both dorsal and ventral wing surfaces. Nanoindentation was performed by using atomic force microscopy (AFM), where the wing samples were divided into three sections (membrane of the wing, mobile and immobile joints). The resulting topographic images revealed the presence of various sizes of nanostructures for all sample sections. The elasticity range values were: membrane (0.04 to 0.16 GPa), mobile joint (1.1 to 2.0 GPa) and immobile joint (1.8 to 6.0 GPa). The elastomeric and glycine-rich biopolymer, resilin was shown to be an important protein responsible for the elasticity and wing flexibility.


Sapphire-fiber thermometer ranging from 20 to 1800 degrees C.
A novel, to our knowledge, sapphire-fiber thermometer ranging from 20 degrees to 1800 degrees C is presented that combines the radiance detection and the fluorescent lifetime detection schemes into one system. The thermal probe is a sapphire fiber grown from the laser-heated pedestal growth method. Its end part is doped with Cr(3+) ion and coated with some radiance material to constitute a minifiber cavity. The sapphire fiber is coupled with a Y-shaped silica fiber bundle for signal transmission. Radiance and fluorescence signal processing schemes are also set up within one thermometer system. A sandwich two-band p-i-n detector is used that may respond to both the radiation and the fluorescence. Preliminary experimental results show that the thermometer is suitable for practical application with potential long-term stability and a high-temperature resolution.


Incidence and prognostic implications of stable angina pectoris among women and men.
Stable angina pectoris in women has often been considered a "soft" diagnosis, with less-severe prognostic implications than in men, but large-scale population studies are lacking. To determine sex differences in the incidence and prognosis of stable angina in a large ambulatory population. Prospective cohort study using linked national registers. All municipal primary health care centers, hospital outpatient clinics, occupational health care services, and the private sector in Finland. Among ambulatory patients aged 45 to 89 years who had no history of coronary disease, we defined new cases of "nitrate angina" based on nitrate prescription (56,441 women and 34,885 men) or "test-positive angina" based on abnormal invasive or noninvasive test results (11,391 women and 15,806 men). Potentially eligible patients were evaluated between January 1, 1996, and December 31, 1998. Follow-up ended in December 2001. Coronary mortality at 4 years (n = 7906 deaths) and fatal and nonfatal myocardial infarction at 1 year (n = 3129 events). The age-standardized annual incidence per 100 population of all cases of angina was 2.03 in men and 1.89 in women, with a sex ratio of 1.07 (95% confidence interval [CI], 1.06-1.09). At every age, nitrate angina in women and men was associated with a similar increase in risk of coronary mortality relative to the general population. Women with test-positive angina who were younger than 75 years had higher coronary-standardized mortality ratios than men; for example, among those aged 55 to 64 years, it was 4.69 (95% CI, 3.60-6.11) in women compared with 2.40 (95% CI, 2.11-2.73) in men (P<.001 for interaction). There was a strong, graded relationship between amount of nitrates used and event rates; women using higher doses of nitrates had prognoses comparable with those of men. Among patients with diabetes and test-positive angina, age-standardized coronary event rates were 9.9 per 100 person-years in women vs 9.3 in men (P = .69), and the fully adjusted male-female sex ratio was 1.07 (95% CI, 0.81-1.41). Women have a similarly high incidence of stable angina compared with men. Furthermore, stable angina in women is associated with increased coronary mortality relative to women in the general population and, among easily identifiable clinical subgroups, has similarly high absolute rates of prognostic outcomes compared with men.


Struggling for confirmation--patients' experiences of dissatisfaction with hospital care.
The aim of the study was to illuminate patients' experiences of dissatisfaction with hospital care. During the last decade, interest in measuring patient satisfaction has become an important indicator of the quality of care. Researchers have, however, criticized the concept theoretically and methodologically. Subsequently, researchers have increasingly argued that the focus of attention should shift to explore patient dissatisfaction. A qualitative approach. Narrative interviews were conducted with six people who had experienced dissatisfaction during a hospital care episode. The interview text was analysed using qualitative content analysis. The results show the patients' struggle for confirmation, the feeling of distrust in health care and what they have been forced to sacrifice because of lack of treatment. A feeling of being a troublesome patient is also apparent. At the same time a positive encounter is described, as well as situations of confirmation from caregivers. The results also show hope and a will to get on with life. Dissatisfaction relating to aspects of encounter is a common problem in health care and conceivable causes and possible solutions are discussed from different perspectives. RELEVANCE TO CLINICAL: Caregivers as well as patients are in need of confirmation. If management were to take notice of and confirm caregivers this could consequently help them to gain the strength and energy necessary to provide care permeated with confirmation. A veritable, trustworthy care can be established through personal presence. To take notice of, confirm and listen to patients, creates opportunities for providing them with a positive experience of human encounter, which in the long run is rewarding from all perspectives.


Ergodicity of random-matrix theories: the unitary case
We prove ergodicity of unitary random-matrix theories by showing that the autocorrelation function with respect to energy or magnetic field strength of any observable vanishes asymptotically. We do so using Efetov's supersymmetry method, a polar decomposition of the saddle-point manifold, and an asymptotic evaluation of the boundary terms generated in this fashion.


Effect of leptin on LH and FSH release in ovariectomized rats.
We compared the estradiol/progesterone-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release between normally fed and leptin-supplemented starved ovariectomized female rats and studied also the effect of hyper-leptinaemia on the steroid-induced hormonal release in normally fed ovariectomized rats. Three days' starvation completely abolished steroid-induced LH and FSH release. Significant recovery of the hormonal release was shown in the leptin-supplemented starved group. The magnitudes of LH and FSH release in the normally fed animals with a higher dose of leptin were statistically the same as those in the normally fed group without leptin. These observations indicate that physiological concentrations of circulating leptin exert a stimulatory effect on steroid-induced LH and FSH release.


A new class of cyclin dependent kinase in Chlamydomonas is required for coupling cell size to cell division.
Proliferating cells actively control their size by mechanisms that are poorly understood. The unicellular green alga Chlamydomonas reinhardtii divides by multiple fission, wherein a 'counting' mechanism couples mother cell-size to cell division number allowing production of uniform-sized daughters. We identified a sizer protein, CDKG1, that acts through the retinoblastoma (RB) tumor suppressor pathway as a D-cyclin-dependent RB kinase to regulate mitotic counting. Loss of CDKG1 leads to fewer mitotic divisions and large daughters, while mis-expression of CDKG1 causes supernumerous mitotic divisions and small daughters. The concentration of nuclear-localized CDKG1 in pre-mitotic cells is set by mother cell size, and its progressive dilution and degradation with each round of cell division may provide a link between mother cell-size and mitotic division number. Cell-size-dependent accumulation of limiting cell cycle regulators such as CDKG1 is a potentially general mechanism for size control.


Temporal trends in sudden cardiac death in Ontario, Canada.
Although the prevention and treatment of cardiovascular conditions have significantly improved over the past decade, whether they have reduced the incidence of sudden cardiac death (SCD) is not known. We sought to evaluate the temporal trends of SCD in a large unselected population. We conducted a population-based cohort study using multiple linked longitudinal data in Ontario Canada. We included patients aged 35-74 years who had SCD from April 1st 2003 to March 31st 2014. SCD was defined as those who died of cardiac causes outside of the hospital or the emergency department, and had no recent hospitalization, no serious illness, and who were not residing in long-term care facilities. We identified 36,334 patients who fulfilled criteria for SCD. The overall age and sex-standardized rate of SCD declined from 57.9/100,000 in fiscal year 2003 to 42.4/100,000 in 2013. Men and women had similar declining trends in SCD incidence. Larger reductions were seen among the older age groups. Patients who had prior heart failure experienced the largest decline in SCD incidence from 829/100,000 to 533/100,000 from 2003 to 2013. Patients who had prior myocardial infarction also had significant reduction from 484/100,000 to 381/100,000. In contrast, individuals with cardiac risk factors without disease had much smaller declines in SCD incidence. Although significant progress to reduce SCD among patients with cardiac conditions was made in the past decade, additional effort should focus on the prevention of SCD in individuals without heart disease.


Flight psychology at Sheppard Air Force Base.
Flight psychology is the application of psychological principles to the unique environment of the aviator in order to enhance training, flight safety, and mission accomplishment. At Sheppard Air Force Base, TX, flight psychology is a cooperative effort between a clinical psychologist and the aeromedical services, with the former acting as a consultant to the latter. The primary focus of the flight psychology program is stress management, including managing the stress response of airsickness, for students in the Euro-NATO Joint Jet Pilot Training (ENJJPT) program. Psychological assessments of flying personnel, air traffic controllers, and individuals being considered for special duties constitute a valuable contribution to aeromedical services. We present clinical vignettes to illustrate the interaction of the flight psychologist and aeromedical services, and the effect on flying training and flight safety.


The Upregulation of Genomic Imprinted DLK1-Dio3 miRNAs in Murine Lupus Is Associated with Global DNA Hypomethylation.
Epigenetic factors such as DNA methylation and microRNAs (miRNAs) are now increasingly recognized as vital contributors to lupus etiology. In this study, we investigated the potential interaction of these two epigenetic factors in lupus-prone MRL-lpr mice. We recently reported dysregulated expression of miRNAs in splenocytes of MRL-lpr mice. Here, we report that a majority of the upregulated miRNAs in MRL-lpr mice is located at the genomic imprinted DLK1-Dio3 domain. Further, we show a differential magnitude of upregulation of DLK1-Dio3 miRNA cluster in purified splenic CD4+ T, CD19+ B, and splenic CD4-CD19- cells from MRL-lpr lupus mice when compared to control MRL mice. MRL-lpr splenocytes (especially CD19+ and CD4-CD19- subsets) were hypomethylated compared to cells from control, MRL mice. We further show that deliberate demethylation of splenocytes from control MRL mice, but not from MRL-lpr lupus mice, with specific DNA methylation inhibitor 5-Aza-2'-deoxycytidine significantly augmented DLK1-Dio3 miRNAs expression. These findings strongly indicate that the upregulation of DLK1-Dio3 miRNAs in lupus splenic cell subsets is associated with reduced global DNA methylation levels in lupus cells. There was a differential upregulation of DLK-Dio3 miRNAs among various demethylated splenic cell subsets, which implies varied sensitivity of DLK1-Dio3 miRNA cluster in these cell subsets to DNA hypomethylation. Finally, inhibition of select DLK1-Dio3 miRNA such as miR-154, miR-379 and miR-300 with specific antagomirs significantly reduced the production of lupus-relevant IFNγ, IL-1β, IL-6, and IL-10 in lipopolysaccharide (LPS) activated splenocytes from MRL-lpr mice. Our study is the first to show that DNA methylation regulates genomic imprinted DLK1-Dio3 miRNAs in autoimmune lupus, which suggests a connection of DNA methylation, miRNA and genomic imprinting in lupus pathogenesis.


Menopausal hormone therapy: a better and safer future.
Major advances in menopause hormone therapy (MHT) hold promise in the future of better and safer care for women at and after the menopause. The principal advances are: (1) the critical window or 'window of opportunity' in the 10 years or so after the menopause, during which the benefits of MHT in healthy women exceed any risks; (2) use of transdermal instead of oral administration of estrogen to reduce the risk of venous thromboembolism; (c) investigation of the use of oral micronized progesterone (MP) and vaginal MP to prevent endometrial hyperplasia and carcinoma without any increased risk of breast cancer and venous thromboembolism in postmenopausal women receiving estrogens; vaginal MP prevents endometrial proliferation in the short term but the long-term effects in MHT remain to be established; (4) investigation into the use of intrauterine levonorgestrel-releasing devices (LNG-IUDs), which are an attractive form of MHT in perimenopausal women, providing contraception and reducing uterine bleeding, although the risk of breast cancer with LNG-IUDs requires clarification. Women in the future can look forward to a symptom-free menopause and to safer and more beneficial MHT.


Explosion Seismology: Capabilities and limitations of long-range methods for detecting and recognizing explosions are discussed.
I have tried to describe some current research trends in seismology which are specifically directed toward solving the problem of detecting, locating, and identifying underground nuclear explosions. Attention has been directed specifically toward problems which arise in efforts to obtain information at distances in excess of 2500 kilometers. The main scientific advantage which accrues from working at such distances is that the seismic signals suffer minimal distortion by the geological complexities of the earth. Extrapolation of the data to the question of an international test ban is not within the scope of this article. Suffice it to note that all of the parameters must, in the final resort, be resolved in terms of probabilities. In some cases the seismological probabilities can be estimated with reasonable degrees of accuracy, but the future of the test ban question depends not only on seismology but on such questions as inspection and what probabilities are acceptable.


Antimicrobial activity of a chlorhexidine intravascular catheter site gel dressing.
The antimicrobial efficacy of a chlorhexidine gluconate (CHG) intravascular catheter gel dressing was evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and an extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Chlorhexidine deposition on the skin surface and release from the gel were determined. The antimicrobial efficacy was evaluated in in vitro studies following microbial inoculation of the dressing and application of the dressing on the inoculated surface of a silicone membrane and donor skin [with and without a catheter segment and/or 10% (v/v) serum] on diffusion cells. Antimicrobial activity was evaluated for up to 7 days. Chlorhexidine skin surface deposition and release were also determined. MRSA and E. coli were not detectable within 5 min following direct inoculation onto the CHG gel dressing. On the silicone membrane, 3 log and 6 log inocula of MRSA were eradicated within 5 min and 1 h, respectively. Time to kill was prolonged in the presence of serum and a catheter segment. Following inoculation of donor skin with 6 log cfu of MRSA, none was detected after 24 h. Chlorhexidine was released from the gel after a lag time of 30 min and increasing amounts were detected on the donor skin surface over the 48 h test period. The CHG gel dressing retained its antimicrobial activity on the artificial skin for 7 days. The CHG intravascular catheter site gel dressing had detectable antimicrobial activity for up to 7 days, which should suppress bacterial growth on the skin at the catheter insertion site, thereby reducing the risk of infection.


The Effects of Tryptophan on Everyday Interpersonal Encounters and Social Cognitions in Individuals with a Family History of Depression.
Individuals with a family history of depression show subtle abnormalities in the processing of social stimuli. This could negatively affect their interpersonal functioning and contribute to their depression risk. Repeated administration of the serotonin precursor tryptophan has previously been shown to increase agreeable behavior and reduce quarrelsome behavior in irritable people, who are also considered at risk for depression. To examine the effects of tryptophan on social functioning in individuals with a family history of depression, 40 men and women with at least one first-degree relative with depression received tryptophan (1g three times a day) and placebo for 14 days each in a double-blind crossover design and recorded their social behavior and mood during everyday interpersonal encounters. Participants also provided daily ratings of their positive and negative cognitions concerning their social functioning. Tryptophan improved mood. Unexpectedly, tryptophan increased quarrelsome behavior and reduced agreeable behavior, specifically during interactions at home. The behavioral effects of tryptophan were not moderated by mood or by the interaction partner. Negative social cognitions were lower when tryptophan was given second and lower during placebo when placebo was given second. Overall, tryptophan may not alter social behavior in individuals with a family history of depression as it does in irritable people. However, the behavioral effects of tryptophan at home might be seen as a way for individuals with a family history of depression to achieve more control. Over time, this may positively influence the way they feel and think about themselves in a social context.


OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes.
OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by a meta-analysis of four orthology-prediction methods, has been a popular tool for identifying conserved genes for research into biological and disease mechanisms. However, the efficacy of orthology prediction depends on the accuracy of gene-model predictions, an ongoing process, and orthology-prediction algorithms have also been updated over time. Here we present OrthoList 2 (OL2), a new comparative genomic analysis between C. elegans and humans, and the first assessment of how changes over time affect the landscape of predicted orthologs between two species. Although we find that updates to the orthology-prediction methods significantly changed the landscape of C. elegans-human orthologs predicted by individual programs and-unexpectedly-reduced agreement among them, we also show that our meta-analysis approach "buffered" against changes in gene content. We show that adding results from more programs did not lead to many additions to the list and discuss reasons to avoid assigning "scores" based on support by individual orthology-prediction programs; the treatment of "legacy" genes no longer predicted by these programs; and the practical difficulties of updating due to encountering deprecated, changed, or retired gene identifiers. In addition, we consider what other criteria may support claims of orthology and alternative approaches to find potential orthologs that elude identification by these programs. Finally, we created a new web-based tool that allows for rapid searches of OL2 by gene identifiers, protein domains [InterPro and SMART (Simple Modular Architecture Research Tool], or human disease associations ([OMIM (Online Mendelian Inheritence in Man], and also includes available RNA-interference resources to facilitate potential translational cross-species studies.


Dynamic Association between HIV-1 Gag and Membrane Domains.
HIV-1 particle assembly is driven by the structural protein Gag. Gag binds to and multimerizes on the inner leaflet of the plasma membrane, eventually resulting in formation of spherical particles. During virus spread among T cells, Gag accumulates to the plasma membrane domain that, together with target cell membrane, forms a cell junction known as the virological synapse. While Gag association with plasma membrane microdomains has been implicated in virus assembly and cell-to-cell transmission, recent studies suggest that, rather than merely accumulating to pre-existing microdomains, Gag plays an active role in reorganizing the microdomains via its multimerization activity. In this paper, we will discuss this emerging view of Gag microdomain interactions. Relationships between Gag multimerization and microdomain association will be further discussed in the context of Gag localization to T-cell uropods and virological synapses.


GDF-15 prevents platelet integrin activation and thrombus formation.
Integrin-mediated platelet function plays an important role in primary hemostasis. Growth-differentiation factor 15 (GDF-15) has been shown to inhibit β(2) -integrin activation in leukocytes. We investigated the effect of GDF-15 on platelet integrin activation in vitro and in different in vivo models of thrombus formation. GDF-15(-/-) mice showed an accelerated thrombus formation and a reduced survival rate after collagen-induced pulmonary thromboembolism. In reconstitution experiments, recombinant GDF-15 decelerated thrombus formation and prolonged the bleeding time. In vitro experiments demonstrated that GDF-15 pretreated, agonist-stimulated platelets showed decreased binding to fibrinogen in flow chamber assays and reduced activation of β(1) - and β(3) -integrins in flow cytometry experiments. Pretreating human and mouse platelets with GDF-15 reduced platelet aggregation. Mechanistically, GDF-15 prevents agonist-induced Rap1- dependent α(II) (b) β(3) activation by activating PKA. Platelet P-selectin expression and dense granule secretion after stimulation were unaffected by GDF-15, indicating a specific effect of GDF-15 on integrin activation. GDF-15 specifically inhibits platelet integrin activation. These findings may have profound clinical implications for the treatment of hemostatic conditions involving platelets.


Regio- and stereo-selective [4+4] photodimerization of angular-shaped dialkyltetracenedithiophene.
Angular-shaped dialkyltetracenedithiophenes (aTDTs) undergo [4+4] photodimerization in solution to form a butterfly-shaped skeleton. This reaction proceeds in a regio- and stereo-selective manner, forming only a single planosymmetric syn-[2,2]-daTDT out of six possible products. The photocycloaddition of aTDTs can take place topochemically in the thin-film state while maintaining regio- and stereo-selectivity. Stronger aliphatic dispersion forces and π-π interactions play important roles in forming the eclipsed dimeric complex that leads to the syn-[2,2]-daTDT isomer.


Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial.
Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare the effect of delivering early with delaying birth for as long as possible. 548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726. Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1.1 (0.7-1.8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen. The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development.


Plasma glial fibrillary acidic protein levels in children with sickle cell disease.
To determine if glial fibrillary acidic protein (GFAP) is associated with brain injury in children with sickle cell disease (SCD), we measured plasma GFAP among cross-sectional groups of unselected children with SCD, subsets of children with SCD and normal brain MRI or MRI evidence of cerebral infarct, healthy pediatric controls, and adults with brain injury. Children with SCD had higher plasma GFAP than healthy pediatric controls (mean concentrations 0.14 ± 0.37 vs. 0.07 ± 0.08 ng/mL; P 5 0.003); also, 16.0% (16/100) of children with SCD and cerebral infarct had GFAP elevations above the 95th percentile of healthy pediatric controls (P 5 0.04). Although not statistically significant, children with SCD and cerebral infarct had more elevated GFAP levels than with SCD and no infarct (16/100, 16.0% vs. 14/168, 8.3%; P 5 0.07). Children with SCD and acute brain ischemia had a higher proportion of elevated GFAP than SCD children with normal MRI (3/6, 50% vs.8.3%; P 5 0.01). GFAP was associated with elevated systolic blood pressure in the preceding year and correlated positively with white blood cell count and negatively with age and performance IQ. Plasma GFAP is elevated among children with SCD and may be associated with subclinical brain injury.


Enhanced cooperative interactions at the nanoscale in spin-crossover materials with a first-order phase transition.
We analyzed the size effect on a first-order spin transition governed by elastic interactions. This study was performed in the framework of a nonextensive thermodynamic core-shell model. When decreasing the particle size, differences in surface energies between the two phases lead to the shrinking of the thermal hysteresis width, the lowering of the transition temperature, and the increase of residual fractions at low temperature, in good agreement with recent experimental observations on spin transition nanomaterials. On the other hand, a modification of the particle-matrix interface may allow for the existence of the hysteresis loop even at very low sizes. In addition, an unexpected reopening of the hysteresis, when the size decreases, is also possible due to the hardening of the nanoparticles at very small sizes, which we deduced from the size dependence of the Debye temperature of a series of coordination nanoparticles.


The specificity of the passive hemagglutination methods used in serology of tuberculosis.
The Middlebrook-Dubos hemagglutination test with normal red cells and the Boyden hemagglutination test with red cells tanned with tannic acid were shown to be strictly specific, for tubercle polysaccharide and for the protein antigens. The former test detects polysaccharide antibodies and the latter protein antibodies. Convincing evidence is given that polysaccharide does not adhere to the surface of tanned red cells nor protein to the normal red cell surface. Hemosensitizing ability and in vitro antigenicity were found to be two distinct properties of tubercle polysaccharide and protein antigens. The phosphatide hemagglutination test with normal red cells sensitized with tubercle phosphatide is also specific; it detects only phosphatide antibodies. The three different kinds of antibodies, antipolysaccharide, antiprotein, and antiphosphatide, were shown to be completely distinct from each other in tuberculous serum. Each of them can be completely removed from serum by absorption with red cells or kaolin particles coated with its corresponding antigen. The reliability of the cross-inhibition test is discussed.


Glutamate involvement in calcium-dependent migration of astrocytoma cells.
Astrocytoma are known to have altered glutamate machinery that results in the release of large amounts of glutamate into the extracellular space but the precise role of glutamate in favoring cancer processes has not yet been fully established. Several studies suggested that glutamate might provoke active killing of neurons thereby producing space for cancer cells to proliferate and migrate. Previously, we observed that calcium promotes disassembly of integrin-containing focal adhesions in astrocytoma, thus providing a link between calcium signaling and cell migration. The aim of this study was to determine how calcium signaling and glutamate transmission cooperate to promote enhanced astrocytoma migration. The wound-healing model was used to assay migration of human U87MG astrocytoma cells and allowed to monitor calcium signaling during the migration process. The effect of glutamate on calcium signaling was evaluated together with the amount of glutamate released by astrocytoma during cell migration. We observed that glutamate stimulates motility in serum-starved cells, whereas in the presence of serum, inhibitors of glutamate receptors reduce migration. Migration speed was also reduced in presence of an intracellular calcium chelator. During migration, cells displayed spontaneous Ca(2+) transients. L-THA, an inhibitor of glutamate re-uptake increased the frequency of Ca(2+) oscillations in oscillating cells and induced Ca(2+) oscillations in quiescent cells. The frequency of migration-associated Ca(2+) oscillations was reduced by prior incubation with glutamate receptor antagonists or with an anti-β1 integrin antibody. Application of glutamate induced increases in internal free Ca(2+) concentration ([Ca(2+)]i). Finally we found that compounds known to increase [Ca(2+)]i in astrocytomas such as thapsigagin, ionomycin or the metabotropic glutamate receptor agonist t-ACPD, are able to induce glutamate release. Our data demonstrate that glutamate increases migration speed in astrocytoma cells via enhancement of migration-associated Ca(2+) oscillations that in turn induce glutamate secretion via an autocrine mechanism. Thus, glutamate receptors are further validated as potential targets for astrocytoma cancer therapy.


The NDR/LATS family kinase Cbk1 directly controls transcriptional asymmetry.
Cell fate can be determined by asymmetric segregation of gene expression regulators. In the budding yeast Saccharomyces cerevisiae, the transcription factor Ace2 accumulates specifically in the daughter cell nucleus, where it drives transcription of genes that are not expressed in the mother cell. The NDR/LATS family protein kinase Cbk1 is required for Ace2 segregation and function. Using peptide scanning arrays, we determined Cbk1's phosphorylation consensus motif, the first such unbiased approach for an enzyme of this family, showing that it is a basophilic kinase with an unusual preference for histidine -5 to the phosphorylation site. We found that Cbk1 phosphorylates such sites in Ace2, and that these modifications are critical for Ace2's partitioning and function. Using proteins marked with GFP variants, we found that Ace2 moves from isotropic distribution to the daughter cell nuclear localization, well before cytokinesis, and that the nucleus must enter the daughter cell for Ace2 accumulation to occur. We found that Cbk1, unlike Ace2, is restricted to the daughter cell. Using both in vivo and in vitro assays, we found that two critical Cbk1 phosphorylations block Ace2's interaction with nuclear export machinery, while a third distal modification most likely acts to increase the transcription factor's activity. Our findings show that Cbk1 directly controls Ace2, regulating the transcription factor's activity and interaction with nuclear export machinery through three phosphorylation sites. Furthermore, Cbk1 exhibits a novel specificity that is likely conserved among related kinases from yeast to metazoans. Cbk1 is functionally restricted to the daughter cell, and cannot diffuse from the daughter to the mother. In addition to providing a mechanism for Ace2 segregation, these findings show that an isotropically distributed cell fate determinant can be asymmetrically partitioned in cytoplasmically contiguous cells through spatial segregation of a regulating protein kinase.


The impact of cerebrovascular disease in Panama.
In Latin America, the cerebrovascular disease is considered a catastrophic public health problem. The objective of this publication is to describe the demographic characteristics and risk factors of cerebrovascular disease in Panama. A hospital-based stroke registry was carried out between 2005 and 2006 to record all patients with cerebrovascular disease admitted to the two major teaching public hospital in Panama City. A comparative analysis was realized of the risk factor of two regional survey studies in Panamá and Colón province on 2007 and 2010. Sixty-three percent of the stroke was ischemic, and high blood pressure was the most common risk factor with 73%; the intrahospital mortality was 28·4%. In a National Health and Quality of Life Survey carried out in 2007, the crude prevalence of cerebrovascular disease was 0·7%. High blood pressure (22%), smoking (9·1%), alcoholism (10·8%), dyslipidemia (8·7%), and diabetes mellitus (5·4%) were the most common risk factors. In 2010, a survey to find out the Prevalence of Risk Factor Associated to Cardiovascular disease in the province of Panama and Colon found that crude prevalence of cerebrovascular disease was 1·6%. High blood pressure (28·4%), dyslipidemia (20·8%), and alcoholism (17·0%) were the most common risk factors. Since 2013, both hospitals' intravenous thrombolytic therapy program has been successfully applied as public health policy. A successful campaign on healthy lifestyle must be strengthened through a comprehensive approach with other public sectors in order to have an impact on the population, particularly in children and adolescents.


[Study on the association between gene polymorphism of ENPP1 and left ventricular hypertrophy: a Guangzhou Biobank Cohort Study-CVD].
To examine the association between genetic polymorphism of rs1409181 in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and left ventricular hypertrophy (LVH) among older Chinese in Guangzhou. 390 subjects aged ≥ 50 years were randomly selected from the Guangzhou Biobank Cohort Study-CVD. Information on personal history, blood pressure, fasting plasma glucose and lipids were collected. Color Doppler ultrasound was used to measure the indicators of LVH, including left ventricular internal diastolic diameter (LVIDD), thickness of the interventricular septum diastolic wall (IVSD) and the posterior wall diastolic diameter (LVPWD). LVIDD was calculated using Devereux ventricular mass (LVM) equation while the Left ventricular mass index (LVMI) equation was used to estimate LVH. The genotype of rs1409181 was determined by Taqman SNP genotyping kits using the ABI 7900HT real time PCR system. In the GG, CG and CC genotype groups, the proportions of LVH were 21.5%, 28.2% and 37.5% respectively. Compared with GG, the adjusted odds ratios (95% confidence interval) for the LVH were 1.39 (0.78 - 2.50) and 2.36 (1.21 - 4.60) for CG genotype and CC genotype of ENPP1 respectively (P for trend = 0.01). Polymorphism of ENPP1 gene rs1409181 was associated with LVH in the older Chinese people in Guangzhou.


Carbohydrate stabilization extends the kinetic limits of chemical polysaccharide depolymerization.
Polysaccharide depolymerization is an essential step for valorizing lignocellulosic biomass. In inexpensive systems such as pure water or dilute acid mixtures, carbohydrate monomer degradation rates exceed hemicellulose-and especially cellulose-depolymerization rates at most easily accessible temperatures, limiting sugar yields. Here, we use a reversible stabilization of xylose and glucose by acetal formation with formaldehyde to alter this kinetic paradigm, preventing sugar dehydration to furans and their subsequent degradation. During a harsh organosolv pretreatment in the presence of formaldehyde, over 90% of xylan in beech wood was recovered as diformylxylose (compared to 16% xylose recovery without formaldehyde). The subsequent depolymerization of cellulose led to carbohydrate yields over 70% and a final concentration of ~5 wt%, whereas the same conditions without formaldehyde gave a yield of 28%. This stabilization strategy pushes back the longstanding kinetic limits of polysaccharide depolymerization and enables the recovery of biomass-derived carbohydrates in high yields and concentrations.


Protein digestion and absorption in young chicks and turkeys.
The site of digestion and absorption of protein was examined in chicks fed soybean meal and casein and in turkeys fed soybean meal, using 91YCl3 as a non-absorbed reference substance. In soy-fed chicks, peptides with molecular weight (MW) between 8,000 to 15,000 accumulated in the proximal small intestine, and low MW peptides accumulated distally. A similar pattern was observed in soy-fed turkeys, although with events occurring proximally to those in the chick. In casein-fed chicks, a gradual reduction in the peptide MW was observed with increasing distance from the pylorus. The rates of formation and absorption of peptides with MW below 500 were similar throughout the small intestine in soy-fed chicks; whereas, the rate of their formation exceeded absorption rate in casein-fed chicks. Net secretion of nitrogen into the duodenum was observed in soybean-fed chicks, no net secretion in casein-fed chicks and 50% absorption in soybean-fed turkeys with net secretion in the gizzard. From the sequence of digestive and absorptive events, apparently solubilization and breakdown of intermediate peptides are rate-limiting in protein absorption from soybean meal diets. But when casein is fed, the rate of uptake of low MW peptides appears to be limiting.


The Relationship between Adult Attachment and Mental Health Care Utilization: A Systematic Review.
Several studies have shown a relationship between individual attachment and various aspects of treatment utilization in individuals with medical problems as well as mental health disorders. This review systematically evaluates existing literature targeting the relationship between attachment and all aspects of treatment utilization, such as engagement, participation, and completion, in adults with mental health problems. A computerized search of PsycINFO, Medline, Embase, PubMed, and Healthstar and a manual search were employed. Of 5733 titles, 105 abstracts were selected. Of these, 18 studies met full inclusion criteria. The quality of studies was evaluated and scored according to 9 characteristics. Most studies supported an association between attachment and treatment engagement and participation. In general, attachment anxiety was associated with higher engagement and participation in services while attachment avoidance was associated with less. Data regarding attachment dimensions and treatment completion were less conclusive. The review suggests a clear relationship between attachment and stages of treatment engagement and participation in a variety of psychiatric populations and treatments. The 2 attachment dimensions appear to have opposite effects, with possible risks for either treatment over- or underutilization. Clinical implications are discussed.


Risk factors for lactation mastitis in China: A systematic review and meta-analysis.
Lactation mastitis (LM) affects approximately 3% to 33% of postpartum women and the risk factors of LM have been extensively studied. However, some results in the literature reports are still not conclusive due to the complexity of LM etiology and variation in the populations. To provide nationally representative evidence of the well-accepted risk factors for LM in China, this study was aimed to systematically summary the risk factors for LM among Chinese women and to determine the effect size of individual risk factor. Six major Chinses and English electronic literature databases (PubMed, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan fang Database and China Science Technology Journal Database) were searched from their inception to December 5st, 2020. Two authors extracted data and assessed the quality of included trials, independently. The strength of the association was summarized using the odds ratio (OR) with 95% confidence intervals (CI). The population attributable risk (PAR) percent was calculated for significant risk factors. Fourteen studies involving 8032 participants were included. A total of 18 potential risk factors were eventually evaluated. Significant risk factors for LM included improper milking method (OR 6.79, 95%CI 3.45-13.34; PAR 59.14%), repeated milk stasis (OR 6.23, 95%CI 4.17-9.30; PAR 49.75%), the first six months postpartum (OR 5.11, 95%CI 2.66-9.82; PAR 65.93%), postpartum rest time less than 3 months (OR 4.71, 95%CI 3.92-5.65; PAR 56.95%), abnormal nipple or crater nipple (OR 3.94, 95%CI 2.34-6.63; PAR 42.05%), breast trauma (OR 3.07, 95%CI 2.17-4.33; PAR 15.98%), improper breastfeeding posture (OR 2.47, 95%CI 2.09-2.92; PAR 26.52%), postpartum prone sleeping position (OR 2.46, 95%CI 1.58-3.84; PAR 17.42%), little or no nipple cleaning (OR 2.05, 95%CI 1.58-2.65; PAR 24.73%), primipara (OR 1.73, 95%CI 1.25-2.41; PAR 32.62%), low education level (OR 1.63, 95%CI 1.09-2.43; PAR 23.29%), cesarean section (OR 1.51, 95%CI 1.26-1.81; PAR 18.61%), breast massage experience of non-medical staff (OR 1.51, 95%CI 1.25-1.82; PAR 15.31%) and postpartum mood disorders (OR 1.47, 95%CI 1.06-2.02; PAR 21.27%). This review specified several important risk factors for LM in China. In particular, the incidence of LM can be reduced by controlling some of the modifiable risk factors such as improper breastfeeding posture, improper milking method, repeated milk stasis, nipple cleaning, breast massage experience of non-medical staff and postpartum sleeping posture.


Musculoskeletal injuries among overweight army trainees: incidence and health care utilization.
Musculoskeletal injuries are a major cause of morbidity in military training. They are more common among overweight/obese individuals, and the prevalence of overweight/obesity in the military has increased. During strong economic periods, the military can be challenged to recruit enough qualified personnel, and physical standards are sometimes relaxed. This study was conducted to compare the incidence of and outpatient utilization for training-related overuse injuries among men who were over body fat (OBF) standards compared with those who were weight qualified (WQ). All study subjects were men ≥18 years old, who were classified as OBF or WQ and were followed for 90 days. During this period, everyone entering through the study sites was required to take a physical fitness test (5 min step test). Only individuals passing the fitness test were included in these analyses. There were 812 OBF and 6511 WQ study participants. OBF were 47% more likely to experience a musculoskeletal injury and had 49% higher health care utilization. Other significant factors included age >19 and a history of smoking. Among this population who had passed a fitness test, those who were OBF had a substantially higher risk of injury and higher utilization for these injuries. Because the recruiting environment is much better, military entrance standards have been tightened, but should the economy improve substantially the military may again be challenged to recruit adequate numbers of personnel, and the lessons learned in this project may prove valuable.


99mTc-glucoheptonate for quantitation of differential renal function.
Differential renal function was calculated by using 99mTc-glucoheptonate (Tc-GH) in 51 patients. Computer-acquired background-corrected individual renal function was calculated by using both the 1-3-min uptake counts and the 2-4-hr delayed static counts. The degree of correlation between the two was high (r = .96). An equally high correlation was noted in 16 children who were 12 years old or younger, in 15 patients with renal size disparity greater than 60/40%, and in six patients with abnormal creatinine clearances. Ten patients had a 30-min dynamic 99mTc-DTPA study followed immediately by the injection of Tc-GH and acquisition of delayed static images 2-4 hr later. A high degree of correlation (r = .99) was seen between the 1-3-min differential function obtained by using Tc-DTPA and the 2-4-hr delayed differential function obtained by using Tc-GH. This study shows that Tc-GH is a clinically useful and valid tool for calculation of differential renal function and that Tc-GH combines many of the best aspects of Tc-DTPA and Tc-DMSA.


The context of care matters: Older people's existential loneliness from the perspective of healthcare professionals-A multiple case study.
To explore existential loneliness among older people in different healthcare contexts from the perspective of healthcare professionals. Professionals meet and care for older people in most care contexts and need to be prepared to address physical, psychological, social and existential needs. Addressing existential loneliness can be both challenging and meaningful for professionals and is often not prioritised in times of austerity. A multiple case study design was used. Focus group interviews were conducted with healthcare professionals (n = 52) in home, residential, hospital and palliative care settings. The analysis was performed in two steps: firstly, a within-case analysis of each context was conducted, followed by a cross-case analysis. Differences and similarities were observed among the care contexts, including for the origin of existential loneliness. In home care and residential care, the focus was on life, the present and the past, compared to hospital and palliative care, in which existential loneliness mainly related to the forthcoming death. The older person's home, as the place where home care or palliative care was received, helped preserve the older person's identity. In hospital and palliative care, as in institutional care, the place offered security, while in residential care, the place could make older people feel like strangers. Creating relationships was considered an important part of the professionals' role in all four care contexts, although this had different meanings, purposes and conditions. The context of care matters and influences how professionals view existential loneliness among older people and the opportunities they have to address existential loneliness. Support for professionals must be tailored to their needs, their education levels and the context of care. Professionals need training and appropriate qualifications to address existential loneliness related to existential aspects of ageing and care.


CD83 is locally regulated and differentially expressed in disturbed murine pregnancy.
Alterations in the immunologic balance during pregnancy have been associated with poor pregnancy outcomes. The underlying mechanisms are complex and mouse models delivered valuable information on inflammatory imbalance in disturbed pregnancies and served as model to test potential anti-inflammatory therapies. CD83 is a transmembrane protein (mCD83) with a soluble form (sCD83) which possesses strong anti-inflammatory properties. During murine pregnancy, upregulated mCD83 expression induces sCD83 release after in vitro stimulation with LPS, phorbol myristate acetate (PMA) and ionomycin. The release mechanism of sCD83 and its control are yet to be elucidated. In this study, the expression of mCD83 and sCD83 has been extensively studied in the CBA/J × DBA/2J mouse model of pro-inflammatory-mediated pregnancy disturbances. mCD83 was higher expressed on splenic B cells, uterus-draining lymph nodes T cells and dendritic cells from mice with poor pregnancy outcome (PPOM) compared to mice with good pregnancy outcome (GPOM). PPOM, however, was accompanied by lower sCD83 serum levels. In vitro treatment of splenic B cells with progesterone led to a reduction of TIMP1 expression, mCD83 expression and sCD83 release, while TIMP1 treatment had a positive effect on sCD83 availability. These results suggest that tissue and matrix components are involved in the regulation of CD83 in murine pro-inflammatory pregnancies.


Analysis of cohort studies with multivariate and partially observed disease classification data.
Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.


Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults.
The majority of intramedullary spinal cord tumors (IMSCT) in children and young adults are low-grade gliomas. Radical resection of similar tumors in the cerebral hemisphere or cerebellum is usually curative; however, the conventional management for IMSCTs remains partial resection followed by radiotherapy because of the concern for surgical morbidity. Nevertheless, radical resection of IMSCTs without routine adjuvant treatment has been the rule at our institution since 1980. In an attempt to resolve this controversy, the long-term morbidity and survival in a large series of children have been retrospectively reviewed. The database records and current status of 164 patients 21 years of age and younger in whom an IMSCT was resected were reviewed. A gross-total resection (>95%) was achieved in 76.8% of the surgical procedures. Subtotal resections (80-95%) were performed in 20. 1%. The majority of patients (79.3%) had histologically low-grade lesions. There were no deaths due to surgery. When comparing the preoperative and 3-month postoperative functional grades, 60.4% stayed the same, 15.8% improved, and 23.8% deteriorated. Only 13 patients deteriorated by more than one functional grade. Patients with either no deficits or only mild deficits before surgery were rarely injured by the procedure, reinforcing the importance of early diagnosis and treatment. The major determinant of long-term patient survival was histological composition of the tumor. The 5-year progression-free survival rate was 78% for patients with low-grade gliomas and 30% for those with high-grade gliomas. Patients in whom an IMSCT was only partially resected (<80%) fared significantly worse. The long-term survival and quality of life for patients with low-grade gliomas treated by radical resection alone is comparable or superior to minimal resection and radiotherapy. The optimum therapy for patients with high-grade gliomas is yet to be determined.


Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa.
In the Neurospora Genome Project at the University of New Mexico, expressed sequence tags (ESTs) corresponding to three stages of the life cycle of the filamentous fungus Neurospora crassa are being analyzed. The results of a pilot project to identify expressed genes and determine their patterns of expression are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones were determined using single-pass sequencing. Contig analysis allowed the identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones. For about 34% of the sequences, highly or moderately significant matches to sequences (of known and unknown function) in the NCBI database were detected. Approximately 56% of the ESTs showed no similarity to previously identified genes. Among genes with assigned function, about 43.3% were involved in metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell division (2.6%).


Consensus Recommendations on the Use of Hyaluronic Acid-Based Fillers for Nonsurgical Nasal Augmentation in Asian Patients.
Nonsurgical nasal augmentation using dermal fillers such as hyaluronic acid is increasing in popularity because of its less invasive nature and shorter downtime compared with traditional surgery. However, the complexity of the nasal vasculature makes it a high-risk procedure without proper training. Appropriate patient and product selection and safer standardized injection techniques are warranted to minimize complications and to achieve reproducible aesthetic results. In this article, recommendations for nonsurgical nasal augmentation using hyaluronic acid fillers are outlined, with focus on the dorsum, tip, and columella. A consensus meeting was conducted to develop recommendations on nonsurgical nasal augmentation in Asian patients using hyaluronic acid-based fillers. Literature review was performed using PubMed and Google Scholar. Relevant studies were included to formulate recommendations. Consensus statements were graded using the criteria outlined by the Grading of Recommendations Assessment, Development and Evaluation Working Group. Nonsurgical nasal augmentation is an advanced procedure that warrants in-depth knowledge of the nasal anatomy. The panel recommends thorough preinjection assessment and counseling to fully align the patient's expectations with aesthetic goals. Injections must be deep and at the level of the periosteum or perichondrium to minimize risk of intravascular injection. Aliquots of hyaluronic acid must be introduced using slow, low-pressure, and low-volume injections. Optimal aesthetic effect is achieved with hyaluronic acid dermal fillers that are highly elastic, cohesive, and with good adaptability to their environment. Hyaluronic acid injections are safe and effective in nonsurgical nasal augmentation. In-depth knowledge of vascular anatomy and proper injection techniques using suitable products are necessary to achieve aesthetic goals safely. Therapeutic, V.


Progestin-Primed Ovarian Stimulation with Dydrogesterone versus Medroxyprogesterone Acetate in Women with Polycystic Ovarian Syndrome for in vitro Fertilization: A Retrospective Cohort Study.
Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear. This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle. A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9-11 and trigger day (all P<0.001), and the dose of hMG was significantly lower (1710.7±431.6 vs 1891.3±402.2 IU, P<0.001). No significant between-group differences were found in the number of viable embryos (5.3±3.1 vs 5.0±4.1, P=0.139) and live birth rate per FET cycle (43.5% vs 47.7%, P=0.383). None of the participants experienced moderate-to-severe ovarian hyperstimulation syndrome in either group. Our results showed that the application of DYG in PPOS protocol could achieve comparable oocyte retrieval and pregnancy outcomes to MPA, but significantly reduce the consumption of gonadotropins in PCOS women for IVF treatment.


Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting Aβ Accumulation.
Notoginsenoside R1 (NTR1) is the main active ingredient of the well-known traditional Chinese herbal medicine Panax notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen. Studies demonstrated that NTR1 may have some neuronal protective effects. Alzheimer's disease (AD) is a neurodegenerative disease characterized by β -amyloid protein (Aβ) deposition, neurofibrillary tangle formation and neuronal loss. This study was designed to explore the protective effect of NTR1 on an APP/PS1 double-transgenic mouse model of AD and investigate the possible mechanism. The 3-month-old mice were fed with 5 mg/(kg•d), 25 mg/(kg•d) NTR1 or vehicle via oral gavage for 3 months and changes in behavior, neuropathology, and amyloid pathology were investigated. The mice with NTR1 treatment showed significant amelioration in the cognitive function and increased choline acetyl transferase expression, as compared to the vehicle treated mice. NTR1 treatment inhibited Aβ accumulation and increased insulin degrading enzyme expression in both APP/PS1 mice and N2a-APP695sw cells, suggesting that of NTR1 may exert its protective effects through the enhancement of the Aβ degradation. Furthermore, our data showed that the increased level of peroxisome proliferator-activated receptor γ (PPARγ) and the up-regulation of insulin degrading enzyme induced by NTR1 were inhibited by administration of GW9662 (a PPARγ antagonist), indicating that the effect of NTR1 was mediated, at least in part, by PPARγ. Thus, our findings provide the evidences that NTR1 has protective effect on AD mouse model and NTR1 may be a potential candidate for AD treatment.


Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and breast cancer risk.
The ratio of urinary 6beta-hydroxycortisol:cortisol is a measure of the activity of cytochrome p450 3A4 (CYP3A4). CYP3A4 catalyzes the formation of the genotoxic estrogen, 16alpha-hydroxyestrone. It is also involved in the activation of many other mammary carcinogens, such as the polycyclic aromatic hydrocarbons and heterocyclic amines. We evaluated the association between urinary cortisol ratios and breast cancer risk in a subgroup of women who participated in a population-based case-control study in Shanghai. Overnight urine samples from 246 case-control pairs were assayed for 6beta-hydroxycortisol (6beta-OHC) to cortisol. The urine samples from all of the breast cancer patients were collected before any chemotherapy or radiotherapy. In-person interviews were conducted to obtain comprehensive information on dietary habits, reproductive history, and other lifestyle factors. The median levels of 6beta-OHC:cortisol ratios were 2.61 in cases and 2.16 in controls, a 20.8% difference (P < 0.001). The case-control difference was larger in women over 45 years of age (31.3% difference; P < 0.001) than younger women (6.0%; P = 0.45). After adjusting for confounding variables, the risks of breast cancer were increased from 1.0 (reference) to 1.6 [95% confidence interval (CI), 0.9-3.1], 2.2 (95% CI, 1.1-4.2), and 3.7 (95% CI, 1.9-7.4; P for trend, <0.001) with increasing levels of 6beta-OHC:cortisol ratios. The positive association was more pronounced among older women (>45 years) than among younger women (< or = 45 years). The adjusted odds ratios associated with the highest cortisol ratio were 6.0 (95%CI, 2.2-16.1) among older women and 2.2 (95%CI, 0.8-6.1) among younger women. The association of the 6beta-OHC:cortisol ratio was stronger among older women who had a high body mass index, late age at menopause, and early age at menarche (factors related to high endogenous estrogen exposure) than those who did not have these factors. These findings are consistent with the role of CYP3A4 in estrogen and carcinogen metabolism and suggest that high CYP3A4 activity may be a risk factor for breast cancer risk.


[The characteristics of erythropoiesis in extremely premature neonates in the 1st 2 months of life].
Based on studies of morphometric indices for red blood and morphometric characteristics of erythrocytes, an evaluation was carried out of the condition of erythropoiesis in 109 extremely premature newborn babies (gestational age 26 to 32 weeks, body mass at birth 800-1600 gr). Noted in the above babies were markedly decreased values for the red blood during the first 1 to 1.5 mo of life and apparent relatedness of the rate of decrement to gestational age and concurrent pathology (infections, intraventricular hemorrhage, grave breathing disorders, hypotrophy). Besides, a low reticulocytic response was recordable to the developing anemia and high degree heterogeneity of the cellular (erythroid) population. The data secured suggest failure of erythropoiesis in extremely premature neonates, the reason for which phenomenon might be too little production of erythropoietins, which fact prompts us to look at the pathogenesis of early anemia and potentialities of correcting thereof from a new angle.


Medical Education in Decentralized Settings: How Medical Students Contribute to Health Care in 10 Sub-Saharan African Countries.
African medical schools are expanding, straining resources at tertiary health facilities. Decentralizing clinical training can alleviate this tension. This study assessed the impact of decentralized training and contribution of undergraduate medical students at health facilities. Participants were from 11 Medical Education Partnership Initiative-funded medical schools in 10 African countries. Each school identified two clinical training sites-one rural and the other either peri-urban or urban. Qualitative and quantitative data collection tools were used to gather information about the sites, student activities, and staff perspectives between March 2015 and February 2016. Interviews with site staff were analyzed using a collaborative directed approach to content analysis, and frequencies were generated to describe site characteristics and student experiences. The clinical sites varied in level of care but were similar in scope of clinical services and types of clinical and nonclinical student activities. Staff indicated that students have a positive effect on job satisfaction and workload. Respondents reported that students improved the work environment, institutional reputation, and introduced evidence-based approaches. Students also contributed to perceived improvements in quality of care, patient experience, and community outreach. Staff highlighted the need for resources to support students. Students were seen as valuable resources for health facilities. They strengthened health care quality by supporting overburdened staff and by bringing rigor and accountability into the work environment. As medical schools expand, especially in low-resource settings, mobilizing new and existing resources for decentralized clinical training could transform health facilities into vibrant service and learning environments.


Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells.
The delicately orchestrated process of bone fracture healing is not always successful and long term non union of fractured bone occurs in 5-20% of all cases. Atrophic fracture non unions have been described as the most difficult to treat and this is thought to arise through a cellular and local failure of osteogenesis. However, little is known about the presence and osteogenic proficiency of cells in the local area of non union tissue. We have examined the growth and differentiation potential of cells isolated from human non union tissues compared with normal human bone marrow mesenchymal stromal cells (BMSC). We report the isolation and culture expansion of a population of non union stromal cells (NUSC) which have a CD profile similar to that of BMSC, i.e. CD34-ve, CD45-ve and CD105+ve. The NUSC demonstrated multipotentiality and differentiated to some extent along chondrogenic, adipogenic and osteogenic lineages. However, and importantly, the NUSC showed significantly reduced osteogenic differentiation and mineralization in vitro compared to BMSC. We also found increased levels of cell senescence in NUSC compared to BMSC based on culture growth kinetics and cell positivity for senescence associated beta galactosidase (SA-beta-Gal) activity. The reduced capacity of NUSC to form osteoblasts was associated with significantly elevated secretion of Dickkopf-1 (Dkk-1) which is an important inhibitor of Wnt signalling during osteogenesis, compared to BMSC. Conversely, treating BMSC with levels of rhDkk-1 that were equivalent to those levels secreted by NUSC inhibited the capacity of BMSC to undergo osteogenesis. Treating BMSC with NUSC conditioned medium also inhibited the capacity of the BMSC to undergo osteogenic differentiation when compared to their treatment with BMSC conditioned medium. Our results suggest that the development of fracture non union is linked with a localised reduced capacity of cells to undergo osteogenesis, which in turn is associated with increased cell senescence and Dkk-1 secretion.


[Antibodies to the antigenic markers of viral hepatitis in biologically active fluids of the human reproductive system].
This research has been carried out with the aim of studying the factors of immunity to viral hepatitis in biologically active fluids of the human reproductive system. As a result, the human reproductive system has been found to contain the complete set of antibodies to the antigenic markers of viral hepatitis. No specific protective mechanisms have been detected in cervical mucus, which permits the penetration of the virus into the upper sections of the female reproductive system with the possibility of ensuing lesions.


In vitro polymyxin activity against clinical multidrug-resistant fungi.
Although antifungals are available and usually used against fungal infections, multidrug-resistant (MDR) fungal pathogens are a growing problem for public health. Moreover, fungal infections have become more prevalent nowadays due to the increasing number of people living with immunodeficiency. Thus, previously rarely-isolated and/or unidentified fungal species including MDR yeast and moulds have emerged around the world. Recent works indicate that polymyxin antibiotics (polymyxin B and colistin) have potential antifungal proprieties. Therefore, investigating the in vitro activity of these molecules against clinical multidrug-resistant yeast and moulds could be very useful. In this study, a total of 11 MDR yeast and filamentous fungal strains commonly reported in clinical settings were tested against polymyxin antibiotics. These include strains belonging to the Candida, Cryptococcus and Rhodotorula yeast genera, along with others belonging to the Aspergillus, Fusarium, Scedosporium, Lichtheimia and Rhizopus mould genera. The fungicidal or fungistatic action of colistin against clinical yeast strains was determined by the time-kill study. Further, a checkerboard assay for its combination with antifungal agents, usually used in clinical practices (amphotericin B, itraconazole, voriconazole), was carried out against multi-drug resistant fungal strains. Polymyxin B and colistin exhibited an antifungal activity against all MDR fungal strains tested with MICs ranging from 16 to 128 μg/ml, except for the Aspergillus species. In addition, colistin has a fungicidal action against yeast species, with minimum fungicidal concentrations ranging from 2 to 4 times MICs. It induces damage to the MDR Candida albicans membrane. A synergistic activity of colistin-amphotericin B and colistin-itraconazole associations against Candida albicans and Lichtheimia corymbifera strains, respectively, and colistin-fluconazole association against Rhodotorula mucilaginosa, was demonstrated using a checkerboard microdilution assay. colistin could be proposed, in clinical practice, in association with other antifungals, to treat life-threatening fungal infections caused by MDR yeasts or moulds.