Relationships Between Vasomotor Symptoms and Mood in Midlife Urban Chinese Women: Observations in a Prospective Study.
During the menopausal transition, there is a greater likelihood of the prevalence of various bothersome symptoms, including vasomotor symptoms (VMS) and mood symptoms. To investigate the association among bothersome VMS and symptoms of anxiety and depression in Chinese women during perimenopause and early in menopause. This study included 430 midlife Chinese women who had experienced natural menopause and were followed up for 10 years. A structured questionnaire was provided annually, comprising the VMS Bother Score (range 1-8) from the Menopause-Specific Quality of Life questionnaire, the Hospital Anxiety and Depression Scale, and other physical and behavioral factors. Among the 430 women evaluated, 78.8% had experienced VMS during long-term follow-up. The overall level of VMS bother score was relatively low (1.92 ± 1.32). Both anxiety and depressive symptoms were significantly associated with VMS bother. After adjusting for potential covariates, the association between anxiety or depression symptoms and VMS bother remained highly significant. Menopausal stage, body mass index, general health, follicle-stimulating hormone, and estradiol were independent contributors to VMS. In time-lagged (1-year) models, VMS bother scores significantly predicted the risk of symptoms of both anxiety and depression the following year. In contrast, anxiety symptoms, rather than depressive symptoms, could predict VMS bother the following year. The prevalence of VMS in our cohort was higher than has been previously reported; however, the overall level of bother was relatively low. This study demonstrated a strong relationship between VMS bother and mood symptoms in Chinese women progressing from perimenopause through natural menopause.


Reverse pharmacogenetic modulation of the nucleus accumbens reduces ethanol consumption in a limited access paradigm.
Bilateral stereotactic lesioning of the nucleus accumbens (NAc) core reduces relapse rates in alcohol-dependent patients but may cause irreversible cognitive deficits. Deep brain stimulation has similar effects but requires costly implanted hardware and regular surgical maintenance. Therefore, there is considerable interest in refining these approaches to develop reversible, minimally invasive treatments for alcohol dependence. Toward this end, we evaluated the feasibility of a reverse pharmacogenetic approach in a preclinical mouse model. We first assessed the predictive validity of a limited access ethanol consumption paradigm by confirming that electrolytic lesions of the NAc core decreased ethanol consumption, recapitulating the effects of similar lesions in humans. We then used this paradigm to test the effect of modulating activity in the NAc using the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM3Dq and hM4Di. We found that increasing activity with hM3Dq had no effect, but suppressing activity with hM4Di reduced alcohol consumption to a similar extent as lesioning without affecting consumption of water or sucrose. These results may represent early steps toward a novel neurosurgical treatment modality for alcohol dependence that is reversible and externally titratable, yet highly targetable and less invasive than current approaches such as lesioning or deep brain stimulation.


Rupture of the Extensor Hallucis Longus Muscle Secondary to Repetitive Overuse in a Taekwondo AthleteA Case Report.
Closed rupture of the extensor hallucis longus (EHL) tendon is rare, with most cases caused by either direct penetrating trauma or predisposing factors such as corticosteroid injection and iatrogenic trauma incidences. Almost all of the previous case reports have reported on rupture of the EHL tendon rather than the EHL muscle. In this report, we highlight an unusual clinical presentation of a rupture of the EHL muscle and discuss its predisposing factors. This patient was a taekwondo athlete with EHL muscle rupture secondary to repetitive overuse without any underlying systemic or local predisposing factors or direct trauma. Fifteen months after successful surgical treatment, he became fully functional again as an elite taekwondo athlete.


Graphic strategies for analyzing and interpreting curricular mapping data.
To describe curricular mapping strategies used in analyzing and interpreting curricular mapping data and present findings on how these strategies were used to facilitate curricular development. Nova Southeastern University's doctor of pharmacy curriculum was mapped to the college's educational outcomes. The mapping process included development of educational outcomes followed by analysis of course material and semi-structured interviews with course faculty members. Data collected per course outcome included learning opportunities and assessment measures used. Nearly 1,000 variables and 10,000 discrete rows of curricular data were collected. Graphic representations of curricular data were created using bar charts and stacked area graphs relating the learning opportunities to the educational outcomes. Graphs were used in the curricular evaluation and development processes to facilitate the identification of curricular holes, sequencing misalignments, learning opportunities, and assessment measures. Mapping strategies that use graphic representations of curricular data serve as effective diagnostic and curricular development tools.


The membrane-bound respiratory chain of Pseudomonas pseudoalcaligenes KF707 cells grown in the presence or absence of potassium tellurite.
The respiratory chain of Pseudomonas pseudoalcaligenes KF707 in membranes isolated from cells grown in the presence or absence of the toxic oxyanion tellurite (TeO3(2-)) was examined. Aerobic growth in the absence of tellurite shows an NADH-dependent respiration which is 80% catalysed by the cytochrome (cyt) bc1-containing pathway leading to two terminal membrane-bound cyt c oxidases inhibited by different concentrations of KCN (IC50 0.2 and 1 microM). A third oxidase, catalysing the remaining 20% of the cyanide-resistant respiration and fully inhibited by 2-3 mM KCN, is also present; this latter pathway accounts for 60-70% of the total NADH-dependent respiration in membranes from cells grown in LB medium supplemented with potassium tellurite (35 microg x ml(-1)). Two high-potential b-type haems (E(m,7) +395 and 318 mV) are redox centres of a membrane-bound cyt c oxidase (possibly of the cbb3 type) which shows a 50% decrease of its activity in parallel with a similar decrease of the c-type haem content (mostly soluble cyt c) in membranes from tellurite-grown cells; the latter type of cells specifically contain a cyt b type at +203 mV (pH 9.0) which is likely to be involved in cyanide-resistant respiration. Comparison of the growth curve of KF707 cells in parallel with tellurite uptake showed that intracellular accumulation of tellurium (Te(0)) crystallites starts from the mid-exponential growth phase, whereas tellurite-induced changes of the respiratory chain are already evident during the early stages of growth. These data were interpreted as showing that reduction of tellurite to tellurium and tellurite-dependent modifications of the respiratory chain are unrelated processes in P. pseudoalcaligenes KF707.


Sexual agreements among gay male couples.
Many gay male couples make agreements about whether or not to permit sex with outside partners, yet little is known about the development and maintenance of these agreements, their impact on relationships, and whether they are an effective HIV prevention strategy. Using semi-structured, qualitative interviews, 39 gay male couples were asked about their sexual agreements and about other relationship dynamics that might affect their agreements. Analysis revealed a wide range of agreement types, all of which are presented along a continuum rather than as discrete categories. For couples with open agreements, most placed rules or conditions limiting when, where, how often, and with whom outside sex was permitted. Although motivations for having agreements varied, HIV prevention did not rank as a primary factor for any couple. Most couples had congruous agreements; however, a small number reported discrepancies which may increase HIV transmission risk. How couples handled breaks in their agreements also varied, depending on what condition was broken, whether it was disclosed, and the partner's reaction. Additional results include differences in agreement type and motivations for having an agreement based on couple serostatus. Overall, agreements benefited couples by providing boundaries for the relationship, supporting a non-heteronormative identity, and fulfilling the sexual needs of the couple. Future prevention efforts involving gay couples must address the range of agreement types and the meanings couples ascribe to them, in addition to tempering safety messages with the relationship issues that are important to and faced by gay couples.


The association between metabolic syndrome and successful aging- using an extended definition of successful aging.
To examine the association between metabolic syndrome (MetS) and successful aging among community-dwelling older adults. Adults aged ≥ 65 years who participated in the senior health checkup program at National Taiwan University Hospital during 2011-2013 were recruited (N = 467 at baseline). The participants were followed after 4 years and 6 years. MetS was assessed at baseline. Successful aging was evaluated at baseline, 4-year follow-up, and 6-year follow-up. We adopted an extended definition of successful aging, which was defined as three major domains: physiological, psychological, and sociological and economic domains. Generalized linear mixed models were used to assess the association between MetS and successful aging adjusting for time (follow-up years), age, sex, years of education, alcohol consumption and MetS×time interaction term. The mean age of the study population was 72.9 (SD 5.5) years. The absence of baseline MetS had a positive effect on the probability of successful aging over six years. The absences of abdominal obesity, hyperglycemia, reduced high-density lipoprotein cholesterol, and hypertension were associated with the physiological successful aging. The absence of hypertension was the most significant predictor of physiological successful aging [aOR (95% CI) = 2.76 (1.67-4.58), p<0.001]. Significant increased trend was found in the overall and physiological successful aging across MetS status (No MetS, pre MetS, MetS; Ptrend <0.001). We found that MetS is a risk factor of successful aging among community-dwelling older adults. Public health policy should aim at avoidance of MetS in order to facilitate successful aging in older population.


AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.
Drugs that selectively activate estrogen receptor β (ERβ) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERβ and ERα. The selective ERβ agonist AC-186 was evaluated in a rat model of Parkinson's disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186. Hence, in addition to a beneficial safety profile for use in both males and females, a selective ERβ agonist has a differentiated pharmacological profile compared to 17β-estradiol in males.


Automated contrast injectors for angiography: devices, methodology, and safety.
Automated contrast injectors (ACIs) are widely employed in interventional cardiology, radiology and neurology. Information regarding the specifications of advanced ACIs and the appropriate injection settings of these devices is limited in the medical literature. This review describes the specifications of the most widely used ACIs and provides appropriate recommendations for injection settings for the various angiographic studies. These recommendations are based on expert consensus and commercial experience regarding characteristics of devices, catheters and contrast. The suggested settings were not subject to rigorous comparative clinical assessment. This review should increase the familiarity, comfort and appreciation of safety among ACI users.


The nutritional modulation of the evolving intestine.
Nutrition plays a major role in the modulation of the evolving human gut influencing all the main components of the intestinal ecosystem. The regulatory role of nutrition is particularly crucial in the early postnatal period but it continues also in subsequent ages when the development of the gastrointestinal tract is completed. Recent data support the hypothesis that nutrition can affect some inherited disorders of gastrointestinal tract. These "epigenetic" mechanisms are involved in the development of intestinal enzymes, hormones, transporters, and immunity. This is an expanding research area related to the possible nutritional intervention in selected clinical condition. This paper is focused on the main components and mechanisms of action of the nutritional modulation on intestinal development.


Membrane Trafficking Modulation during Entamoeba Encystation.
Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Lectins and chitin are secreted to form the cyst wall, although little is known about the underlying membrane trafficking processes supporting encystation. As E. histolytica does not readily form cysts in vitro, we assessed membrane trafficking gene expression during encystation in the closely related model Entamoeba invadens. Genes involved in secretion are up-regulated during cyst formation, as are some trans-Golgi network-to-endosome trafficking genes. Furthermore, endocytic and general trafficking genes are up-regulated in the mature cyst, potentially preserved as mRNA in preparation for excystation. Two divergent dynamin-related proteins found in Entamoeba are predominantly expressed during cyst formation. Phylogenetic analyses indicate that they are paralogous to, but quite distinct from, classical dynamins found in human, suggesting that they may be potential drug targets to block encystation. The membrane-trafficking machinery is clearly regulated during encystation, providing an additional facet to understanding this crucial parasitic process.


Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo.
In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nucleic acid precursors and by flow cytometrical measurement of accumulation of rhodamine 123. Furthermore, we treated mice bearing resistant L1210 ascites cells with doxorubicin and hycanthone or chlorophenoxamine. Hycanthone in combination with doxorubicin significantly inhibited tumor growth. We also found an improved therapeutic effect of doxorubicin plus chlorophenoxamine. Our results in vitro and in vivo indicate that hycanthone and chlorophenoxamine might be appropriate tools for the circumvention of MDR in human tumors.


THERAPEUTIC OUTCOMES AFTER ENDORESECTION OF COMPLEX RETINAL CAPILLARY HEMANGIOBLASTOMA.
To evaluate the anatomical and functional outcomes after endoresection of complex retinal capillary hemangioblastoma (RCH). Retrospective case series of 12 patients (13 eyes), all treated with pars plana vitrectomy, endodiathermy of feeding and draining vessels, endoresection of RCH and silicone oil injection. The mean age at the time of surgery was 32.5 ± 15.9 years. The mean follow-up duration after initial surgery was 50.5 ± 49.4 months. Indications for surgery included RCH with associated complications such as tractional retinal detachment in five eyes (38%), exudative retinal detachment in four eyes (31%), and combination of tractional retinal detachment and exudative retinal detachment in four eyes (31%). The dimensions of the resected RCHs were as follows: >3.0 mm in seven eyes (54%), >3.5 mm in three eyes (23%), and >4.0 mm in three eyes (23%). No tumor was located closer than 10 mm to the optic nerve or fovea. Anatomical success after initial surgery was 92%. One eye had a second vitreoretinal procedure owing to recurrent RD. The mean preoperative Snellen visual acuity was 20/303. The mean Snellen visual acuity at the final visit was 20/73. At the final visit, visual acuity had improved in seven eyes (54%), and six eyes (46%) were stable. Short-term complications included recurrent proliferative vitreoretinopathy in one eye (8%), transient ocular hypertension requiring topical antiglaucoma treatment in four eyes (31%), and long-term complications included progression of cataract in seven eyes (54%). Combined pars plana vitrectomy, endodiathermy of feeding and draining vessels, endoresection of RCH, and silicone oil injection may be an effective treatment option for complex RCH, achieving high anatomical success and stable or even improved visual acuity, acceptable rates of disease- and treatment-related complications, and minimal need for retreatment.


Introduction.
The pace of technological advancement of Optical Coherence Tomography (OCT) over the last several years has been extremely rapid. The field has progressed from one-dimensional low-coherence ranging to full three-dimensional imaging with individual two-dimensional images aquired at near video rate in a span of less than eight years. Imaging applications have included polymers and advanced composites, Ophthalmology, Developmental Biology, Gastroenterology, Urology, Cardiology, Neurology, and Gynecology. These preliminary studies indicate the great potential for OCT to make a significant impact, especially in clinical medicine.


Effects of combined treatment of rats with cadmium and ionizing radiation on nucleic acids in the kidneys, liver and haemopoietic organs.
The influence of Cd (1 mg/rat CdCl2 i.p.) and/or gamma radiation (6 Gy) on RNA and DNA content and/or concentration in the intact kidney and hypertrophic kidney (on the 44th hour after UN) and in other slowly and quickly proliferating organs was studied. The period between administration of Cd and Ir in the group with combined treatment was 30 min; between treatment (administration of Cd, Ir and combination of both treatments--Cd + Ir) and UN it was 1, 7, 14 and 21 days. The total extent of damage caused by the treatments in the investigated organs was following: intact kidney < liver < hypertrophic kidney and bone marrow < spleen < thymus. In the intact and hypertrophic kidney and liver, the administration of Cd caused more extensive changes in comparison with gamma irradiation, and the effects of combination of the treatments were similar to those of Cd alone. In the bone marrow, spleen and thymus, more profound changes were observed after Ir in comparison with Cd administration, and the effects of combined treatment were similar to the effects of Ir alone. The changes in the hypertrophic kidney after administration of Cd and/or Ir were more extensive than in the intact kidney, which suggests latent injury induction in the rat kidney by these noxa. The higher effectiveness of the treatments in the hypertrophic kidney than in the intact one was manifested mostly by the decrease in the RNA and DNA content, which was mainly due to inhibition of growth induced by UN and not by a real decrease in DNA and RNA contents caused by loss of damaged cells.


Scanning noise microscopy.
The paper describes a simple scheme enabling the real-time characterization of fluctuations, e.g., of the conductance in scanning tunneling microscopy. The technique can be used in parallel to other data acquisition, evaluating the rate, the amplitude, and the duty cycle of telegraphic noise in the tunneling current. This kind of scanning probe microscopy allows to evaluate the noise parameters as a function of the average tunneling current, the electron energy, and the lateral position. Images of the noise with Ångstrom spatial resolution are acquired simultaneously to the topographic information providing a direct correlation between the structural information and the noise. The method can be applied to a large variety of systems to monitor dynamics on the nanoscale, e.g., the localization of tunneling current induced switching within a single molecule. Noise spectroscopy may reveal the involved molecular orbitals, even if they cannot be resolved in standard scanning tunneling spectroscopy. As an example we present experimental data of the organic molecule copper phthalocyanine on a Cu(111) surface [J. Schaffert, M. C. Cottin, A. Sonntag, H. Karacuban, C. A. Bobisch, N. Lorente, J.-P. Gauyacq, and R. Möller, Nature Mater. 12, 223-227 (2013)].


Co-Existence of Iron Oxide Nanoparticles and Manganese Oxide Nanorods as Decoration of Hollow Carbon Spheres for Boosting Electrochemical Performance of Li-Ion Battery.
Here, we report that mesoporous hollow carbon spheres (HCS) can be simultaneously functionalized: (i) endohedrally by iron oxide nanoparticle and (ii) egzohedrally by manganese oxide nanorods (FexOy/MnO2/HCS). Detailed analysis reveals a high degree of graphitization of HCS structures. The mesoporous nature of carbon is further confirmed by N2 sorption/desorption and transmission electron microscopy (TEM) studies. The fabricated molecular heterostructure was tested as the anode material of a lithium-ion battery (LIB). For both metal oxides under study, their mixture stored in HCS yielded a significant increase in electrochemical performance. Its electrochemical response was compared to the HCS decorated with a single component of the respective metal oxide applied as a LIB electrode. The discharge capacity of FexOy/MnO2/HCS is 1091 mAhg-1 at 5 Ag-1, and the corresponding coulombic efficiency (CE) is as high as 98%. Therefore, the addition of MnO2 in the form of nanorods allows for boosting the nanocomposite electrochemical performance with respect to the spherical nanoparticles due to better reversible capacity and cycling performance. Thus, the structure has great potential application in the LIB field.


A clinical rationale for assessing rapid automatized naming in children with language disorders.
Three continuous rapid naming tasks (Semel, Wiig, & Secord, 1995) were administered to 2,450 American, English-speaking, academically achieving individuals with typical language development and intellectual ability (ages 6 to 21 years) and 136 individuals with primary language disorders (LD; ages 6, 7, 9, 11, 12, 15-16). Naming time in seconds differed significantly (p < .01) between the groups for color naming (Task 1) at age 12, shape naming (Task 2) at age 6, and color-shape naming (Task 3) at ages 6, 7, 9, and 12. Naming accuracy did not differ significantly (p > .01) between groups at the majority of the age levels compared. In the normative group, naming speed increased with age in a monotonic progression. The developmental trajectory in the LD group was essentially parallel, but elevated. The percentages of individuals who failed the naming-time criteria for Task 3 (color-shape naming) differed significantly in the two groups at all ages compared (p < .05). These findings indicate that the requirements for two-dimensional, continuous naming (Task 3 color-shape naming) resulted in reduced naming speed (longer total times) and interference with fluency in language production in about half of the clinical sample.


Psychodynamic psychotherapy is associated with sustained reduction in health care utilization and cost.
Our objective was to examine the effectiveness and efficiency of psychodynamic psychotherapy on the reduction in health care utilization and cost while controlling for age, gender, and year. Health care utilization and cost were examined yearly in 1,675 patients from 2 years before outpatient psychotherapy (i.e., baseline) to three consecutive years after psychotherapy in a naturalistic longitudinal design. A multilevel analytic approach (LMLM) was applied to account for repeated measures effect and missing data. In the year prior to psychotherapy, there was a significant increase in total cost compared with baseline (14.8%) and in use of health care services (primary and specialist doctors' visits and outsourced referrals). In the first year following therapy, there was a significant decrease in total cost (10%) and in use of health care services (all doctors' visits, imaging, and outsourced referrals). The decrease was to baseline levels or lower and was maintained for two additional years. Psychiatric medication usage increased significantly after psychotherapy and remained so. The overall cumulative decrease in total cost per patient over 3 years after therapy was 3,665.92 NIS, equalling a 69% average cost of psychotherapy. Further cost saving can be expected due to the reduction in sick leave, disability, and psychiatric hospitalization. These findings support the notion that providing outpatient psychodynamic psychotherapy can be financially beneficial to health care systems, although further research is required for causal inferences. Also, an increase in health care utilization along with scarce physical findings may indicate unaddressed psychological distress and warrant referral for mental assessment and possible psychotherapy.


Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions.
Excessive activation of N-methyl-d-aspartic acid (NMDA) receptors after cerebral ischemia is a key cause of ischemic injury. For a long time, it was generally accepted that calcium influx is a necessary condition for ischemic injury mediated by NMDA receptors. However, recent studies have shown that NMDA receptor signaling, independent of ion flow, plays an important role in the regulation of ischemic brain injury. The purpose of this review is to better understand the roles of metabotropic NMDA receptor signaling in cerebral ischemia and to discuss the research and development directions of NMDA receptor antagonists against cerebral ischemia. This mini review provides a discussion on how metabotropic transduction is mediated by the NMDA receptor, related signaling molecules, and roles of metabotropic NMDA receptor signaling in cerebral ischemia. In view of the important roles of metabotropic signaling in cerebral ischemia, NMDA receptor antagonists, such as GluN2B-selective antagonists, which can effectively block both pro-death metabotropic and pro-death ionotropic signaling, may have better application prospects.


[KL-6 in patients with interstitial pneumonitis].
Levels of KL-6 are high in serum and in bronchoalveolar lavage fluid (BALF) from patients with interstitial pneumonitis. To examine the usefulness of the KL-6 level as a marker of disease activity in interstitial pneumonitis, KL-6 was measured in serum and in BALF from patients with this disease. Correlations between KL-6 levels and the number of cells in BALF and between KL-6 levels and pulmonary function were computed. Serum KL-6 levels were abnormally high and correlated with the number of lymphocytes in BALF in patients with interstitial pneumonitis. Furthermore, changes in serum KL-levels reflected clinical coursed in these patients. KL-6 levels in BALF were very high and correlated with the total number of cells, and with the numbers of lymphocytes, neutrophils, and eosinophils in BALF. KL-6 levels in serum and in BALF correlated significantly with %VC, %DLco, and %DLco/VA. These results suggest that KL-6 levels in serum and in BALF reflect the degree of alveolitis and of deterioration of pulmonary function in these patients, and that KL-6 is a useful indicator of disease activity in interstitial pneumonitis.


[Risk groups of newborn infants of diabetic mothers in relation to their somatic outcome and maternal diabetic metabolic status in pregnancy].
In a prospective study, neonatal morbidity of newborn children of diabetic mothers and its association with the maternal metabolism was determined. Particular attention was directed on the somatic outcome of the children and their frequent metabolic imbalances. In addition, we determined the influence of maternal biological and somatometrical variables on the somatic outcome of newborns. Dependent upon the mothers' and children' variables, risk groups of newborns (fetopathy groups) were defined to optimize clinical care and surveillance of newborns. A total of 810 children were included born to mothers with primary insulin dependent diabetes mellitus (IDDM), non insulin dependent diabetes (NIDDM), or gestational diabetes (GDM). Among the study population, 41.7% of children had macrosomia, 27.2% had a weight-length index > 1.2, 17.9% developed hypoglycemia and 19.5% hyperbilirubinemia within the initial 72 hours after birth. The somatic outcome of the children was significantly associated with pregnancy duration, maternal age, weight, height, and HbA1. Increasing maternal HbA1 prior to delivery (categorized in < 8.5%, 8.6-10%, > 10%) was associated with increased relative risk of incidence of neonatal morbidity. Finally, risk groups (fetopathy groups I-III) were defined according to maternal HbA1 value and somatic outcome of the newborns. The importance of these fetopathy groups for criteria of neonatal morbidity is demonstrated. Based upon categorization of newborn children into fetopathy groups, children should be allocated to specific concepts of appropriate surveillance and clinical care. The fetopathy classification may also serve as an independent tool for retrospective quality control of diabetic pregnancy.


Unexpected events during mandibular distraction osteogenesis.
Various unexpected events during mandibular distraction osteogenesis are described in 16 syndromic children with severely retrognathic or asymmetric lower jaws who were treated with unilateral or bilateral extraoral distraction. The mean total time with the distraction devices attached was 14 weeks (range 10-19). Although improvement in facial aesthetics and the desired occlusion was achieved in all but one case, there were unexpected events associated with mandibular distraction. These included pain not related to the operation, functional disturbance in movement of the jaw, dietary problems, weight loss, unfulfilled expectations of decannulation, temporary unilateral facial nerve palsy, and transient unilateral hypoaesthesia of the inferior alveolar nerve. Reoperation was required in 5 of the 16. In addition to these events, psychosocial problems within one family complicated the procedure. Patients and their families should be informed of the lesser-known aspects of distraction osteogenesis before the procedure is used.


Colonic gallstone ileus.
Gallstone ileus is a rare aetiology of bowel obstruction and very infrequently occurs in the colon. Typically, colonic gallstone ileus carries a high morbidity and mortality and requires surgery. This case report describes a cholecystocolonic fistula in a patient with ulcerative colitis with resulting colonic gallstone ileus, which was successfully intervened on via an endoscopic approach.


[Modifying cutoff values of the UF 1000i(®) automated urine analyzer to predict urinary tract infection].
The fundamental advantage of using automated urine analyzers lies in the current grouping of laboratories as technical divisions. The UF1000i(®) Biomérieux is a 2(nd) generation automated urine analyzer which uses fluorescence flow cytometry to count the particles and bacteria present in urine. It also provides a prediction indicator for the urinary tract infection, based on the leukocyte and bacteria count. The indicator is an alarm (UTI) which triggers according to the cut off values set by the supplier (bacteria count (B): 100000 arbitrary units (AU)/mL, and leukocyte count (L): 25000/mL). Different cut off values of bacteria and leukocytes were evaluated to give the best discrimination, compared with conventional cytobacteriological examination based on the REMIC recommendations of 2010. Our study highlighted two cut off pairs with distinctive performances: L = 15000/mL and B = 100000 AU/mL ; L = 15000/mL and B = 150000 AU/mL. For these cut off values, the negative predictive values is respectively 1 and 0.99. Thus, UF 1000i gives a fairly good indicator for the probable absence of urinary tract infection.


In vitro propagation from axillary buds of the endangered tree Dalbergia congestiflora Pittier (Fabaceae).
Dalbergia congestiflora Pittier is a woody plant species grown in Mexico and Central America and widely used as timber wood and medicinal material. Since D. congestiflora is an endangered species, an in-vitro micropropagation technique is needed for mass propagation of D. congestiflora plantlets. Nodal segments of D. congestiflora stem cuttings grown in greenhouse conditions were disinfected with an appropriate protocol and in vitro established on Murashige and Skoog medium (MS) supplemented with 0.05 mg l-1 benzylaminopurine (BA). The explants showed 10% contamination with 90% survival, and the initial shoot was regenerated in 90% of them. Axillary buds of 45-day-old initial shoots were cultured on MS containing BA (0, 0.05, 0.1, 0.5, 1, 1.5 and 2 mg l-1) singly or in combination with α-naphthaleneacetic acid (NAA) (0, 0.1, 0.5 and 1 mg l-1). A higher shoot number (9.6 shoots/explant) was obtained on MS with 1 mg l-1 BA and 0.1 mg l-1 NAA. Rooting was investigated using half-strength MS, 2% sucrose and different concentrations of indole butyric acid (IBA) (0, 0.1, 0.5 and 1 mg l-1). After 30 days of culture, developing shoots were elongated and rooted in culture medium without IBA, with production of 3.2 roots/shoot. Micropropagated plantlets of D. congestiflora were successfully transplanted and acclimatized to a mixture of peat moss and perlite (2 : 1) with 100% relative humidity in greenhouse conditions with 80% survival at 30 days of culture. This micropropagation protocol will contribute to the conservation of D. congestiflora, and assure the mass propagation for sustainable usage of this species.


Cholinergic modulation of N-methyl-D-aspartate-evoked [3H]norepinephrine release from rat cortical slices.
Previous work has shown that N-methyl-D-aspartate (NMDA) receptor activation inhibits muscarinic receptor-mediated phosphoinositide hydrolysis in brain slices. To further explore the potential interactions between NMDA receptors and cholinergic receptors, the effects of cholinergic agonists and NMDA on [3H]norepinephrine (NE) release from rat cortical slices were determined. Slices were labeled with [3H]NE, washed and treated with various agonists by transferring the slices through a series of vials at 1-min intervals. Radioactivity remaining in the medium was then quantitated to determine the fractional release of [3H]NE from the slices. Carbachol (30-3000 microM) slightly stimulated [3H]NE release from a basal level of 0.10 to approximately 0.35 fractional release by itself and significantly enhanced the effect of 250 microM NMDA (3.6 fractional release for NMDA and 5.3 for carbachol + NMDA) in a concentration-dependent manner. Carbachol (1 mM) increased the maximal response but had no effect on the EC50 of NMDA. Atropine (1 microM) significantly attenuated the effect of carbachol alone and the potentiation of NMDA-evoked [3H]NE release by carbachol, whereas d-tubocurarine (10 microM) inhibited the effect of carbachol alone but had no effect on the enhancement of the NMDA response by carbachol. Mecamylamine (100 microM) inhibited the effect of carbachol alone, but also inhibited the NMDA-evoked response with an IC50 of 16 microM. The nicotinic agonist, dimethylphenylpiperazinium (DMPP) stimulated [3H]NE release (approximately 0.4 fractional release at 30 microM) and also potentiated NMDA-stimulated [3H]NE release (2.0 above NMDA alone). d-Tubocurarine, but not atropine, partially inhibited DMPP-stimulated [3H]NE release, but neither antagonist altered the enhancement of NMDA-stimulated [3H]NE release by DMPP.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of an animal model for prostate cancer cell metastasis to adult human bone.
Prostate cancer metastases to bone are associated with significant morbidity and mortality. Presently, there is little known about the biological interaction between prostate cancer cells and bone. Development of an animal model using adult human bone will enhance our ability to study the biology of prostate cancer metastasis to bone. Bone was harvested from patients undergoing total joint arthroplasty and implanted in the hindlimbs of pre-treated SCID mice. Two months after bone implantation 4 x 104 prostate cancer cells (PC-3 or LAPC-4) were injected near the bone implantation site. The animals were sacrificed approximately 8 to 12 weeks after the injections of the cells. Complete histological analysis including immunostaining was performed. Both the PC-3 and LAPC-4 prostate cancer cells homed to the human bone implant, specifically the reconstituted bone marrow cavity. Analysis of the bone-tumor interaction after injection of PC-3 cells revealed strong labeling for PTHrP, TNF alpha and IL-6, consistent with osteoclast recruitment and osteoclast activity. These cells also were positively stained for CK18. After cellular injection of LAPC-4 cells, there was strong labeling for TNF alpha, IL-6, and IL-1 (osteoclast recruitment and osteolytic activity). PTHrP staining was also noted. The bone cells were strongly stained for osteocalcin, and the tumor cells for PSA. These data suggest that the tumor cells may induce an osteolytic response to enhance their ability to metastasize to bone. This animal model allows us to study the biologic interaction between prostate cancer cells and human bone and may enhance our understanding of the events associated with prostate cancer metastasis to bone.


Course and characteristics of depression over a 12-month period among Ghanaians living with HIV: the EVERLAST study.
Individuals with HIV are predisposed to depression but there is limited data on its dynamics and correlates. We aimed to assess course and characteristics of depression among Ghanaian HIV patients over a 12-month period. We interrogated a longitudinal study dataset of patients at a tertiary hospital and assessed depression at month 0 and 12 using the Patient Health Questionnaire-9 (PHQ-9). Association between clinical, sociodemographic factors and changes in PHQ-9 scores were evaluated. Among 320 study participants, 171 (53.4%) and 55 (17.2%) had depression at month 0 and 12 respectively. Persistent depression was detected in 41 (24.0%) of the 171 patients with depression at month 0, whilst 135 (42.2%) of them never experienced depression. Patients' CD4 count was associated with depression at month 0 and 12 (p<0.05). Predictors of change in depression scores were urban dwelling [-1.98, 95%CI: -3.86 to -0.06, p=0.039], not knowing one's monthly income [2.10, 95%CI: 0.58 to 3.61, p=0.007], participant being single [-1.62 95%CI: -2.45 to -0.78, p<0.001] and being on antiretroviral therapy at recruitment [-1.5, 95%CI: -2.55 to -0.45, p<0.001]. There was a significant decrease in depression scores over a 12-month period and persistent depression is rife among this cohort of Ghanaians with HIV.


Effectiveness of home single-channel nasal pressure for sleep apnea diagnosis.
Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis, but no cost studies have yet been carried out. Automatic scoring is simpler but generally less effective than manual scoring. To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis several apnea-hypopnea index (AHI) cutoff points. We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed receiver operating characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cutoff points, and costs were calculated for equally effective alternatives. Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI < 15; similar curves were obtained for AHI ≥ 15. A valid HNP with manual scoring would determine the presence of OSA (or otherwise) in 90% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 74% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 61% of patients with a polysomnographic AHI ≥ 15 cutoff point. In the same way, a valid HNP with automatic scoring would determine the presence of OSA (or otherwise) in 73% of patients with a polysomnographic AHI ≥ 5 cutoff point, in 64% of patients with a polysomnographic AHI ≥ 10 cutoff point, and in 57% of patients with a polysomnographic AHI ≥ 15 cutoff point. The costs of either HNP approaches were 40% to 70% lower than those of PSG at the same level of diagnostic efficacy. Manual HNP had the lowest cost for low polysomnographic AHI levels (≥ 5 and ≥ 10), and manual and automatic scorings had similar costs for higher polysomnographic cutoff points (AHI ≥ 15) of diagnosis. Home single-channel nasal pressure (HNP) is a cheaper alternative than polysomnography for obstructive sleep apnea diagnosis. HNP with manual scoring seems to have better diagnostic accuracy and a lower cost than automatic scoring for patients with low apnea-hypopnea index (AHI) levels, although automatic scoring has similar diagnostic accuracy and cost as manual scoring for intermediate and high AHI levels. Therefore, automatic scoring can be appropriately used, although diagnostic efficacy could improve if we carried out manual scoring on patients with AHI < 15. Clinicaltrials.gov identifier: NCT01347398.


Single-molecule observation of long jumps in polymer adsorption.
Single-molecule fluorescence imaging of adsorption onto initially bare surfaces shows that polymer chains need not localize immediately after arrival. In a system optimized to present limited adsorption sites (quartz surface to which polyethylene glycol (PEG) chains adsorb from aqueous solution at pH 8.2), we find that some chains diffuse back into bulk solution and readsorb at some distance away, sometimes multiple times before they either localize at a stable position or diffuse away into bulk solution. This mechanism of surface diffusion is considerably more rapid than the classical model in which adsorbed polymers crawl on surfaces while the entire molecule remains adsorbed, suggesting the conceptual generality of a recent report ( Phys. Rev. Lett. 2013 , 110 , 256101 ) but in a new experimental system and with comparison of different chain lengths. We find the trajectories with jumps to follow a truncated Lévy distribution of step size with limiting slope -2.5, consistent with a well-defined, rapid surface diffusion coefficient over the times we observe. The broad waiting time distribution appears to reflect that polymer chains possess a broad distribution of bound fraction: the smaller the bound fraction of a given chain, the shorter the surface residence time before executing the next surface jump.


[Quality assurance measures in surgical gynecology. Program development and routine introduction in Hessia].
Frequently, quality assurance measures fail during application in routine practice despite showing very promising results in the developmental stage. Using the project 'Quality assurance in gynecological surgery' as an example which has made the leap into routine practice, we describe the development of a successful quality assurance measure. We name some of the elements which have proved to be crucial for the assumption of a new quality assurance measure. First of all, decisive was the development of the measure by renowned experts of the scientific medical society together with methodologists. All current professional and legal demands on medical quality assurance were included as were methodological knowledge for the optimal formation of such a measure. The evaluation of the measure on approximately 50,000 gynecological surgical procedures showed that the new quality assurance measure is suitable in gynecological surgery as an instrument both for making transparent the quality of health care delivery as well as for supporting comprehensive internal and external assessments of performance, outcomes, and processes of care and comparisons with the "best" care provider ("benchmarking"). Secondly, a favorable point in time--here the introduction of a diagnosis related payment system--and the early and close cooperation on the part of the program developers with political decision-makers helped to ensure that the newly developed quality assurance measure in gynecological surgery was accepted for routine practice.


Temperature evolution of structure and bonding of formic acid and formate on fully oxidized and highly reduced CeO2(111).
Adsorption of formate on oxide surfaces plays a role in water-gas shift (WGS) and other reactions related to H(2) production and CO(2) utilization. CeO(2) is of particular interest because its reducibility affects the redox of organic molecules. In this work, the adsorption and thermal evolution of formic acid and formate on highly ordered films of fully oxidized CeO(2)(111) and highly reduced CeO(x)(111) surfaces have been studied using reflection absorption infrared spectroscopy (RAIRS) under ultra-high vacuum conditions, and the experimental results are combined with density functional theory (DFT) calculations to probe the identity, symmetry, and bonding of the surface intermediates. Disordered ice, ordered alpha-polymorph and molecular formic acid bonded through the carbonyl are observed at low temperatures. By 250 K, desorption and deprotonation lead to formate coexisting with hydroxyl on CeO(2)(111), identified to be a bridging bidentate formate species that is coordinated to Ce cations in nearly C(2v) symmetry and interacting strongly with neighboring H. Changes in the spectra at higher temperatures are consistent with additional tilting of the formate, resulting in C(s)(2) or lower symmetry. This change in bonding is caused primarily by interaction with oxygen vacancies introduced by water desorption at 300 K. On reduced CeO(x), multiple low-symmetry formate states exist likewise due to interactions with oxygen vacancies. Isotopic studies demonstrate that the formyl hydrogen does not contribute to H incorporated in hydroxyl on the surface, and that both formate oxygen atoms may exchange with lattice oxygen at 400 K. The combined experimental and theoretical results thus provide important insights on the surface reaction pathways of formic acid on ceria.


Inositol Trisphosphate Metabolism in Carrot (Daucus carota L.) Cells.
The metabolism of exogenously added d-myo-[1-(3)H]inositol 1,4,5-trisphosphate (IP(3)) has been examined in microsomal membrane and soluble fractions of carrot (Daucus carota L.) cells grown in suspension culture. When [(3)H]IP(3) was added to a microsomal membrane fraction, [(3)H]IP(2) was the primary metabolite consisting of approximately 83% of the total recovered [(3)H] by paper electrophoresis. [(3)H]IP was only 6% of the [(3)H] recovered, and 10% of the [(3)H]IP(3) was not further metabolized. In contrast, when [(3)H]IP(3) was added to the soluble fraction, approximately equal amounts of [(3)H]IP(2) and [(3)H]IP were recovered. Ca(2+) (100 micromolar) tended to enhance IP(3) dephosphorylation but inhibited the IP(2) dephosphorylation in the soluble fraction by about 20%. MoO(4) (2-) (1 millimolar) inhibited the dephosphorylation of IP(3) by the microsomal fraction and the dephosphorylation of IP(2) by the soluble fraction. MoO(4) (2-), however, did not inhibit the dephosphorylation of IP(3) by the soluble fraction. Li(+) (10 and 50 millimolar) had no effect on IP(3) metabolism in either the soluble or membrane fraction; however, Li(+) (50 millimolar) inhibited IP(2) dephosphorylation in the soluble fraction about 25%.


Acute effect of air pollutants' peak-hour concentrations on ischemic stroke hospital admissions among hypertension patients in Beijing, China, from 2014 to 2018.
Air pollutants' effect on ischemic stroke (IS) has been widely reported. But the effect of high-level concentrations during people's outdoor periods among hypertension patients was unknown. Peak-hour concentrations were defined considering air pollutants' high concentrations as well as people's outdoor periods. We conducted a time-series study and used the generalized additive model to analyze peak-hour concentrations' acute effect. A total of 315,499 IS patients comorbid with hypertension were admitted to secondary and above hospitals in Beijing from 2014 to 2018. A 10 µg/m3 (CO: 1 mg/m3) increase of the peak-hour concentrations was positively associated with IS hospital admissions among hypertension patients. The maximum effect sizes were as follows: for PM2.5, 0.17% (95% confidence interval [CI]: 0.10-0.24%) at Lag0 and 0.22% (95% CI: 0.12-0.33%) at Lag0-5; for PM10, 0.09% (95% CI: 0.05-0.13%) at Lag5 and 0.17% (95% CI: 0.09-0.26%) at Lag0-5; for SO2, 0.87% (95% CI: 0.46-1.29%) at Lag5; for NO2, 0.83% (95% CI: 0.62-1.04%) at Lag0 and 0.86% (95% CI: 0.59-1.13%) at Lag0-1; for CO 1.23% (95% CI: 0.66-1.80%) at Lag0 and 1.33% (95% CI: 0.33-2.35%) at Lag0-5; for O3 0.23% (95% CI: 0.12-0.35%) at Lag0 and 0.20% (95% CI: 0.05-0.34%) at Lag0-1. The effect sizes of PM2.5, NO2, and O3 remained significant after adjusting daily mean. Larger effect sizes were observed for PM2.5 and PM10 in cool season and for O3 in warm season. As significant exposure indicators of air pollution, peak-hour concentrations exposure increased the risk of IS hospital admissions among hypertension patients and it is worthy of consideration in relative environmental standard. It is suggested for hypertension patients to avoid outdoor activity during peak hours. More relevant searches are required to further illustrate air pollutant's effect on chronic disease population.


Quantum communication beyond the localization length in disordered spin chains.
We study the effects of localization on quantum state transfer in spin chains. We show how to use quantum error correction and multiple parallel spin chains to send a qubit with high fidelity over arbitrary distances, in particular, distances much greater than the localization length of the chain.


Osteochondral Lesions of Major Joints.
This paper provides information about osteochondral lesions (OCL) and example cases of OCL occurring in major joints, some of which are rarely seen. This simple tutorial is presented in question and answer format.


The effect of early vs. delayed postpartum insertion of the LNG-IUS on breastfeeding continuation: a systematic review and meta-analysis of randomised controlled trials.
Objective: The aim of the study was to compare early vs. delayed postpartum insertion of the 52 mg levonorgestrel intrauterine system (LNG-IUS). Methods: The databases of PubMed, Scopus, Web of Science and CENTRAL were searched to February 2019. The search comprised randomised controlled trials (RCTs) comparing early vs. delayed postpartum insertion of the LNG-IUS. Data were extracted and combined in a meta-analysis. Pooled results were expressed as the relative risk (RR) with 95% confidence interval (CI). The main outcome measures were breastfeeding continuation, LNG-IUS expulsion, uterine perforation, LNG-IUS use, satisfaction and number of pregnancies. Results: Twelve RCTs were included, comprising 1006 women in total. Our analysis indicated no significant difference between early and delayed insertion of the LNG-IUS in terms of any breastfeeding continuation (RR 0.99; 95% CI 0.84, 1.16; p = 0.88). After removal of heterogeneity, there was a statistically significant superiority in LNG-IUS use at the endpoint in the early insertion group compared with the delayed insertion group (RR 1.27; 95% CI 1.07, 1.51; p = 0.006). LNG-IUS expulsion was significantly less in the delayed insertion group in comparison with the early insertion group (RR 5.32; 95% CI 2.68, 10.53; p = 0.00001). No significant differences were found between the groups in satisfaction, number of pregnancies and risk of uterine perforation. Conclusion: Early postpartum insertion of the LNG-IUS has no negative effects on breastfeeding continuation. Early postpartum insertion may be used as an alternative to delayed postpartum insertion.


A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.
Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.


Skp2 is required for incretin hormone-mediated β-cell proliferation.
The glucoincretin hormone glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (Ex-4) promote β-cell growth and expansion. Here we report an essential role for Skp2, a substrate recognition component of SCF (Skp, Cullin, F-box) ubiquitin ligase, in promoting glucoincretin-induced β-cell proliferation by regulating the cellular abundance of p27. In vitro, GLP-1 treatment increases Skp2 levels, which accelerates p27 degradation, whereas in vivo, loss of Skp2 prevents glucoincretin-induced β-cell proliferation. Using inhibitors of phosphatidylinositol 3-kinase and Irs2 silencing RNA, we also show that the effects of GLP-1 in facilitating Skp2-dependent p27 degradation are mediated via the Irs2-phosphatidylinositol-3 kinase pathway. Finally, we show that down-regulation of p27 occurs in islets from aged mice and humans, although in these islets, age-dependent accumulation of p16(Ink4a) prevent glucoincretin-induced β-cell proliferation; however, ductal cell proliferation is maintained. Taken together, these data highlight a critical role for Skp2 in glucoincretin-induced β-cell proliferation.


Accumulation and dietary risks of perfluoroalkyl substances in fish and shellfish: A market-based study in Barcelona.
Since the 1940s, per- and polyfluoroalkyl substances (PFAS) have been widely produced and used in various applications due to their unique properties. Consequently, the principal exposure routes of PFAS have been broadly studied, leading to the conclusion that dietary exposure (more specifically, the consumption of fish and seafood) was one of their main contributors. Thus, developing an analytical method that determines the level of PFAS in fish and seafood has become a relevant subject. In this work, a previous analytical method has been optimized to determine 12 PFAS in fish muscle from salmon, tuna, cod, hake, sardine, anchovy, and sole, as well as in seven different seafood species (i.e., cuttlefish, octopus, squid, shrimp, Norway lobster, prawn, and mussel) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Subsequently, the PFAS profile of the different species was studied to determine if it was consistent with that previously reviewed in the literature and to know the most relevant contribution of PFAS for each species. Finally, human exposure to PFAS through their consumption was estimated by the daily intake for seven different age/gender groups. PFAS were obtained from 0.014 to 0.818 ng g-1 wet weight in fish samples. Sardines, anchovies, and soles presented the highest PFAS levels. However, cod samples also showed some PFAS traces. Regarding seafood, PFAS levels range from 0.03 to 36.7 ng g-1 dry weight for the studied species. A higher concentration of PFAS has been found in the cephalopods' spleens and the crustaceans' heads. PFOS and PFBS were the predominant compounds in each seafood species, respectively. On the other hand, in the case of mussels, which are the less polluted species of the study, contamination by longer-chained PFAS was also observed. Finally, the total intake of PFAS due to fish and shellfish consumption for the Spanish adult population was estimated at 17.82 ng day-1. Nevertheless, none of the analyzed samples exceeded the European Food Safety Authority (EFSA) risk value for the supervised PFAS in any age/gender group reviewed.


Computer-Aided Design of Thrombin Inhibitors.
Computer-aided ligand design is an active, challenging, and multidisciplinary research field that blends knowledge of biochemistry, physics, and computer sciences. Whenever it is possible to experimentally determine or to model the three-dimensional structure of a pharmacologically relevant enzyme or receptor, computational approaches can be used to design specific high-affinity ligands. This article describes methods, applications, and perspectives of computer-assisted ligand design.


Age-related decline in deciduogenic ability of the rat uterus.
To study age-related changes in uterine responsiveness to deciduogenic stimuli, virgin female rats of the T strain were ovariectomized at 4, 8, 10, or 12 mo of age and given daily s.c. injections of 3 mg progesterone for 7 days, commencing on the day after operation, and a single s.c. injection of 0.1 microgram estradiol-17 beta on the third day of the period. Endometrial stimulation was effected by either endometrial traumatization or intraluminal instillation of sesame oil or prostaglandin E2 (PGE2), applied 16 h after the injection of estradiol. Decidual response began to decrease at 8 mo of age and completely disappeared between 8 and 12 mo, regardless of the type of induction stimulus. At 8 mo of age, females formed deciduomata in response to instillation of oil or PGE2, only when they had been cycling regularly at the time of ovariectomy. In 10-mo-old rats, instillation of oil or PGE2 invariably failed to elicit a positive response, regardless of the pattern of estrous cycles at surgery. However, if an ovary was transplanted s.c. 5 or 7 mo after ovariectomy at 4 mo of age, the uteri responded positively to oil instillation at 10 and 12 mo of age, after the ovarian grafts had been removed and steroid treatments had been administered. Moreover, a 2-mo interval between ovariectomy at 8 mo of age and the commencement of the standard treatment schedule restored or maintained the uterus's ability to form deciduomata by 10 mo of age.(ABSTRACT TRUNCATED AT 250 WORDS)


Variation in Hospitalization Rates Following Emergency Department Visits in Children with Medical Complexity.
To evaluate factors associated with admission from emergency department (ED) encounters for children with medical complexity (CMC) and to quantify the hospital admission rate as well as variation in adjusted hospital admission rates across EDs. Retrospective study of 271 806 visits to 37 EDs in freestanding children's hospitals from January 1, 2014, to June 30, 2017, for patients of all ages with a complex chronic condition. Associations between patient demographic, clinical, and health services characteristics and the likelihood of hospital admission were identified using generalized linear models, which were then used to calculate adjusted hospital admission rates. Hospital admission occurred with 25.7% of ED visits. Characteristics with the greatest aOR of hospitalization were ≥3 compared with 0 prior hospitalizations in 365 days (4.7; 95% CI, 4.5-4.9), ED arrival overnight compared with during workday 3.2 (95% CI, 3.1-3.3)], and ≥6 vs 0-1 chronic conditions (1.6; 95% CI, 1.5-1.6). Adjusted hospital admission rates varied significantly (P < .001) across EDs (21.1% [10th percentile]) and 30.0% [90th percentile]). Significant variation remained when excluding low-intensity ED visits, excluding hospitalizations requiring surgery and/or intensive care, or restricting the cohort to overnight ED arrival and to children with ≥3 prior hospitalizations. CMC are frequently admitted from the ED. Substantial variation in CMC hospital admission rates across EDs exists after case-mix adjustment.


Phytochrome activation of k channels and chloroplast rotation in mougeotia: action spectra.
The action spectra for K(+) channel activation and chloroplast rotation are shown to be similar. Both phenomena exhibit activation at 660 nanometers, inhibition at 740 nanometers, and partial activation at 460 to 500 nanometers. This confirms that K(+) channels in Mougeotia are regulated by phytochrome, and indicates that both phenomena share at least part of the same transduction pathway.


Predictors of maintained high-risk behaviors among impoverished women.
The researchers sought to explore and describe the demographic, cognitive, psychosocial, and behavioral factors associated with the continued risky behavior of a convenience sample of homeless and drug-addicted women two to four weeks after they had completed an AIDS education program. The sample included 942 crack users and 767 women who had multiple sex partners. Analyses revealed that impoverished women who maintained multiple sexual partners were less likely to be in drug recovery programs than in homeless shelters. They were more likely to share needles and be involved sexually with male injection drug users compared with impoverished women who did not maintain multiple sexual partners. Persistent crack users were older than those who reported cessation of crack use, were more often African American, and were more likely to have sex partners who were injecting drug users. Women who demonstrated less improvement in depression and distress scores, concerns, use of affective coping, appraisal of threat, and social support were more likely to maintain crack use and multiple partners. The study's implications for the design of intervention programs aimed at risk reduction based on ethnicity are discussed.


Time course of nitric oxide, peroxynitrite, and antioxidants in the endotoxemic heart.
To determine the time course for myocardial production of nitric oxide, peroxynitrite, and glutathione, to determine the activities of the myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and glutathione reductase throughout endotoxemia and into recovery, and to correlate the levels of these variables to left ventricular contractility in endotoxemia. Rats were treated with lipopolysaccharide. Endotoxemic hearts were examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time-control groups were treated identically. A pulmonary research laboratory of a university teaching hospital. Lipopolysaccharide administration resulted in decreased contractility at 16 hrs as assessed by the isolated papillary muscle technique. Contractility recovered by 24 hrs. Myocardial glutathione content initially increased, but it was decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both superoxide dismutase and glutathione reductase activities were increased early (4 hrs) and remained elevated throughout the course of the experiment. Myocardial nitric oxide content (assessed by the chemiluminescence technique) was increased by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite (assessed by measurement of 3-nitrotyrosine by high-pressure liquid chromatography) was elevated at 16 hrs and remained elevated despite normalization of contractility at 24 and 48 hrs. Myocardial dysfunction in endotoxemia correlates mainly with decreased glutathione content and glutathione peroxidase activity rather than nitric oxide or peroxynitrite formation. These data indicate that lipopolysaccharide-induced myocardial dysfunction is not solely caused by elevated myocardial nitric oxide levels but rather caused by the sum of complex interactions between various oxygen- and nitrogen-derived radicals.


Changes in distribution and numbers of CD4+ and CD8+ T-lymphocytes in lymphoid tissues and intestinal mucosa in the early phase of experimentally induced early onset mucosal disease in cattle.
Mucosal disease (MD), one sequelae of bovine virus diarrhoea virus (BVDV) infection, causes severe lesions in lymphoid tissues and mucosal surfaces. Lesions are associated with the presence of cytopathogenic (cp) BVDV and initially characterized by apoptotic cell death. The objective of this investigation was to determine if this cell death is mediated only by the cp BVDV, which is known to induce apoptosis in cell culture or if immune-mediated host reactions might also contribute. Early onset MD was experimentally induced in calves by inoculation of persistently viremic calves with a closely related cp BVDV. Calves were euthanized in the early phase of infection between days 5 and 13 post-inoculation and tissues from tonsils, lymph nodes, Peyer's patches, jejunum and colon were collected. Presence of cp BVDV antigen was correlated with distribution of lymphocyte subpopulations in consecutive cryostat sections. In the lymphoid tissues, cp BVDV antigen was predominantly found in the lymphoid follicles. The increase of infected cells with time post-inoculation was paralleled by a decrease of B-lymphocytes and an increase of CD4+ T-lymphocytes. An increased number of CD8+ T-lymphocytes was seen in progressed lesions only. In the intestinal mucosa, initially multifocal, later diffuse infection with cp BVDV was accompanied by a multifocal or diffuse increase of CD4+ T-lymphocytes, respectively. Numbers of IgA+ plasma cells and CD8+ T-lymphocytes were decreased. The common change observed in lymphoid tissues and mucosa was the increase of CD4+ T-lymphocytes in sites with lesions. This might indicate a cell-mediated immune response to the cp BVDV. Besides their helper function to other cells of the immune system, activated CD4+ T-lymphocytes might also exert cytotoxic activity, induce apoptosis in target cells via Fas/Fas ligand binding and thus contribute to the severity of tissue lesions in MD.


Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy.
Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).


Place of phenytoin in treatment of resistant epilepsy.
A retrospective therapeutical follow-up of 64 therapy-resistant epileptics treated by phenitoin (DPH) is made chronically. In the study 232 treatment periods of at least two years' duration were analyzed. Distribution of DPH therapeutic combinations was evaluated according to the type of epilepsy, seizure form, seizure frequency, elements of patient compliance, and results of serum level measurements. According to the author's opinions DPH is still one of the most effective agents in the treatment of resistant epilepsy, but in most cases as a constant component of antiepileptic bitherapy. Its pharmacokinetic features and optimal dosage show great individual variability, larger than that of other drugs and, in cases of combined drug regimens, interactions may more frequently be expected.


Surgical treatment of a parastomal hernia.
Parastomal hernia is a major complication of an intestinal stoma. This study was performed to compare the results of various operative methods to treat parastomal hernias. Results of surgical treatment for parastomal hernias (postoperative recurrence, complications and postoperative hospital stays) were surveyed in 39 patients over an 11-year period. The patients enrolled in this study underwent surgery by a single surgeon to exclude surgeon bias. Seventeen patients were male, and twenty-two patients were female. The mean age was 65.9 years (range, 36 to 86 years). The stomas were 35 sigmoid-end-colostomies (90%), 2 loop-colostomies (5%), and 2 double-barrel-colostomies. Over half of the hernias developed within two years after initial formation. Stoma relocation was performed in 8 patients, suture repair in 14 patients and mesh repair in 17 patients. Seven patients had recurrence of the hernia, and ten patients suffered from complications. Postoperative complications and recurrence were more frequent in stoma relocation than in suture repair and mesh repair. Emergency operations were performed in four patients (10.3%) with higher incidence of complications but not with increased risk of recurrence. Excluding emergency operations, complications of relocations were not higher than those of mesh repairs. Postoperative hospital stays were shortest in mesh repair patients. In this study, mesh repair showed low recurrence and a low complication rate with shorter hospital stay than relocation methods, though these differences were not statistically significant. Further studies, including randomized trials, are necessary if more reliable data on the surgical treatment of parastomal hernias are to be obtained.


Grand-parenting for healthy ageing in women: Fact or fiction?
Globally our populations are ageing and with this trend, there is a rise in chronic disease. We know that lifestyle and environment are significant contributors to risk for disease, quality of life and function. Despite this representing an opportunity to improve health and quality of life in ageing, there is a paucity of research in this field. The social aspects of this period of development which have been most researched include employment, function and disability. Grand-parenting is one of the most popular sources of childcare in the world and therefore research investigating this role is of vital significance.


Intravitreal Administration Effect of Adipose-Derived Mesenchymal Stromal Cells Combined with Anti-VEGF Nanocarriers, in a Pharmaceutically Induced Animal Model of Retinal Vein Occlusion.
Antiangiogenic therapeutic agents (anti-VEGF) have contributed to the treatment of retinal vein occlusion (RVO) while mesenchymal stromal cell- (MSCs-) mediated therapies limit eye degeneration. The aim of the present study is to determine the effect of adipose-derived MSCs (ASCs) combination with nanocarriers of anti-VEGF in a pharmaceutically induced animal model of RVO. Nanoparticles (NPs) of thiolated chitosan (ThioCHI) with encapsulated anti-VEGF antibody were prepared. ASCs were isolated and genetically modified to secrete the green fluorescence GFP. Twenty-four New Zealand rabbits were divided into the I-IV equal following groups: ASCs, ASCs + nanoThioCHI-anti-VEGF, RVO, and control. For the RVO induction, groups I-III received intravitreal (iv) injections of MEK kinase inhibitor, PD0325901. Twelve days later, therapeutic regiments were administered at groups I-II while groups III-IV received BSS. Two weeks later, the retinal damage evaluated via detailed ophthalmic examinations, histological analysis of fixed retinal sections, ELISA for secreted cytokines in peripheral blood or vitreous fluid, and Q-PCR for the expression of related to the occlusion and inflammatory genes. Mild retinal edema and hemorrhages, limited retinal detachment, and vasculature attenuation were observed in groups I and II compared with the pathological symptoms of group III which presented a totally disorganized retinal structure, following of positive immunostaining for neovascularization and related to RVO markers. Important reduction of the high secreted levels of inflammatory cytokines was quantified in groups I and II vitreous fluid, while the expression of the RVO-related and inflammatory genes has been significantly decreased especially in group II. GFP+ ASCs, capable of being differentiated towards neural progenitors, detected in dissociated retina tissues of group II presenting their attachment to damaged area. Conclusively, a stem cell-based therapy for RVO is proposed, accompanied by sustained release of anti-VEGF, in order to combine the paracrine action of ASCs and the progressive reduction of neovascularization.


Management of benign prostatic hyperplasia by the primary care physician in the 21st century: the new paradigm.
Benign prostatic hyperplasia (BPH) is one of the commonest causes of lower urinary tract symptoms (LUTS) in men over age 50. Fifty percent of men over age 50 will require some type of management for BPH/LUTS symptoms. Until about 15 years ago, the most common management for BPH was a transurethral resection of the prostate (TURP) operation. Initially, once a diagnosis of BPH has been made, most men are treated medically. One must first rule out other serious causes of these symptoms, such as prostate cancer, bladder cancer, and other obstructions. For men with an enlarged prostate, there is a good chance that therapy with a 5-alpha-reductase inhibitor (5-ARI) can prevent disease progression and the need for surgery. There has been a lot of recent work on different combination therapies for the treatment of BPH/LUTS. If a patient's serum prostate-specific antigen (PSA) level is greater than 1.5 ng/ml and his prostate volume is greater than 30 cc and he has significant LUTS, then combination medical therapy of an alpha blocker with a 5-ARI is the most effective therapy. After a careful workup, it is quite reasonable and appropriate for the primary care physician to initiate this therapy for a patient with BPH/LUTS.


Visfatin is involved in the cisplatin resistance of osteosarcoma cells via upregulation of Snail and Zeb1.
Understanding the mechanisms of chemoresistance in osteosarcoma (OS) cell is important for drug development. By establishment of cisplatin (CDDP) resistant OS cells, we found that the levels of visfatin in OS/CDDP cells were significantly greater than that in their parental cells. The CDDP resistant OS cells showed greater migration and invasion capability than that of parental cells. Knockdown of visfatin can rescue the CDDP sensitivity of resistant OS cells. Among the detected epithelial-mesenchymal transition-related transcription factors (EMT-TFs), visfatin can increase the expression of Snail and Zeb-1 in OS cells. Overexpression of Snail and Zeb1 can attenuate si-visfatin reduced CDDP resistance of OS cells. Mechanistical studies indicated that visfatin can increase the mRNA expression of Snail and therefore upregulate its expression via HIF-1α induced transcription. As to Zeb1, visfatin had no effect on its mRNA expression, while significantly increased its protein stability. Furthermore, the upregulation of ATM, which can phosphorylate and stabilize Zeb1, was involved in visfatin-induced Zeb1 expression in OS cells. Collectively, our revealed that visfatin was involved in CDDP resistance of OS cells via upregulation of Snail and Zeb1, suggesting that inhibition of visfatin might be a potential pathway for OS treatment.


Resident microglia, rather than blood-derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia-ischemia.
The mechanisms of neuronal injury after hypoxia-ischemia (HI) are different in the immature and the adult brain, but microglia activation has not been compared. The purpose of this study was to phenotype resident microglia and blood-derived macrophages in the hippocampus after HI in neonatal (postnatal day 9, P9) or adult (3 months of age, 3mo) mice. Unilateral brain injury after HI was induced in Cx3cr1(GFP/+) Ccr2(RFP/+) male mice on P9 (n = 34) or at 3mo (n = 53) using the Vannucci model. Resident microglia (Cx3cr1-GFP+) proliferated and were activated earlier after HI in the P9 (1-3 days) than that in the 3mo hippocampus, but remained longer in the adult brain (3-7 days). Blood-derived macrophages (Ccr2-RFP+) peaked 3 days after HI in both immature (P9) and adult (3mo) hippocampi but were twice as frequent in adult brains, 41% vs. 21% of all microglia/macrophages. CCL2 expression was three times higher in the P9 hippocampi, indicating that the proinflammatory response was more pronounced in the immature brain after HI. This corresponded well with the higher numbers of galectin-3-positive resident microglia in the P9 hippocampi, but did not correlate with CD16/32- or CD206-positive resident microglia or blood-derived macrophages. In conclusion, resident microglia, rather than infiltrating blood-derived macrophages, proliferate and are activated earlier in the immature than in the adult brain, but remain increased longer in the adult brain. The inflammatory response is more pronounced in the immature brain, and this correlate well with galectin-3 expression in resident microglia.


Screening of sex workers in Turkey for Chlamydia trachomatis.
Increasing migration of sex workers across East European borders into Turkey has resulted in increased arrests of unregistered sex workers. There is concern regarding the prevalence of sexually transmitted diseases (STD) such as C. trachomatis in this unregulated group. To measure the prevalence of C. trachomatis infection and selected related demographic and behavioral factors among registered and unregistered sex workers in Istanbul, Turkey. In a cross-sectional study, the prevalence of C. trachomatis infection was studied by direct fluorescent antibody testing in 248 sex workers: 158 presented for routine medical screening and 90 who were arrested for lack of registration. All subjects were interviewed regarding demographic factors, sexual activity, and antibiotic and drug use. The overall C. trachomatis prevalence was 12.9% (12.0% registered and 14.4% unregistered). There was a strong association between never using condoms and chlamydia positivity (odds ratio 8.9 [95% confidence interval 3.7 to 21.6]). The high rate of C. trachomatis among all tested sex workers and the lack of regular condom use, particularly among unregistered sex workers, indicate that there is an urgent need for safe sex education and continued STD screening of unregistered sex workers.


Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis.
Liver fibrosis is a common feature of chronic liver disease. Activated hepatic stellate cells (HSCs) are the main drivers of extracellular matrix accumulation in liver fibrosis. Hence, a strategy for regulating HSC activation is crucial in treating liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from various post-natal organs. Therapeutic approaches involving MSCs have been studied extensively in various diseases, including liver disease. MSCs modulate hepatic inflammation and fibrosis and/or differentiate into hepatocytes by interacting directly with immune cells, HSCs, and hepatocytes and secreting modulators, thereby contributing to reduced liver fibrosis. Cell-free therapy including MSC-released secretomes and extracellular vesicles has elicited extensive attention because they could overcome MSC transplantation limitations. Herein, we provide basic information on hepatic fibrogenesis and the therapeutic potential of MSCs. We also review findings presenting the effects of MSC itself and MSC-based cell-free treatments in liver fibrosis, focusing on HSC activation. Growing evidence supports the anti-fibrotic function of either MSC itself or MSC modulators, although the mechanism underpinning their effects on liver fibrosis has not been established. Further studies are required to investigate the detailed mechanism explaining their functions to expand MSC therapies using the cell itself and cell-free treatments for liver fibrosis.


Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system suppresses tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models.
Bladder cancer is considered as the fifth most common cancer in the whole world. This study aimed to investigate the anti-tumor effects of Nanoscale bubbles delivered yeast cytosine deaminase thymidine kinase/connexin 26 (YCD-TK/Cx26) on tumor cell proliferation and tumor growth. Nanoscale bubble was prepared using thin-film hydration-sonication method. Nanoscale bubble-LV5-YCD-TK+PCD-Cx26 was generated and transfected into BIU-87 cells. MTT assay was employed to detect cell viability. Apoptosis was determined using a flow cytometry assay. YCD-TK and Cx26 expressions were detected using Western blot and Real Time-PCR (RT-PCR). BIU-87 cells were transplanted into mice to establish Xenograft models. The tumor volume was recorded. HE staining was used to examine necrosis areas in tumor tissues. Nanoscale bubble (Nanoscale bubble-LV5-YCD-TK+PCD-Cx26) successfully mediated YCD-TK and Cx26 gene expression in BIU-87 cells. Nanoscale bubble delivered YCD-TK/Cx26 expression significantly inhibited cell viability and induced apoptosis compared to Nanoscale bubble-LV5-YCD-TK and Nanoscale bubble group (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression triggered significantly higher levels of bystander effect compared to single YCD-TK or single Cx26 gene (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced tumor volume in mouse Xenograft bladder cancer model compared to LV5-YCD-TK and 5-FC+GCV group (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced the necrosis of tumor tissues in mouse Xenograft bladder cancer model compared to LV5-YCD-TK group and 5-FC+GCV group (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system efficiently reduced BIU-87 cell proliferation in vitro, and suppressed tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models.


Host Egg Age and Supplementary Diet Influence the Parasitism Activity of Trichogramma zahiri (Hymenoptera: Trichogrammatidae).
Mass production of egg parasitoids mostly depends on the age of the host. Generally old eggs are less preferred by egg parasitoids, which can discriminate between eggs of different ages by using chemical cues. This study was designed to determine the preference, development, and arrestment of Trichogramma zahiri Polaszek (Hymenoptera: Trichogrammatidae) parasitizing eggs of its native host, the rice hispa, Dicladispa armigera (Olivier) (Coleoptera: Chrysomelidae). Eggs of different ages, in addition, with or without supplementary foods were evaluated. T. zahiri preferred to parasitize 1-d-old eggs rather than 2-, or 3-d-old eggs by no-choice assays. However, although the percentage emergence of parasitoids is significantly lower from 2- and 3-d-old eggs, the sex ratio is unaffected. Parasitoids lived longer when 25% honey solution was provided with the host food. Significantly higher fecundity (38.5 eggs per female) and parasitoid emergence (94.6%) occurred when 25% honey solution was provided in the diet with host food, followed by 25% sugar solution, as compared to the control (only water as food). An average of 7.9 eggs were parasitized when one parasitoid was released per 10 rice hispa eggs. Ability of T. zahiri to parasitize egg increased with an increase in the number of eggs offered. We also found that inclusion of a fresh host egg with the supplementary diet improves the mass rearing of T. zahiri for commercial purposes.


Fluorescent Nano-Biomass Dots: Ultrasonic-Assisted Extraction and Their Application as Nanoprobe for Fe3+ detection.
Biomass as sustainable and renewable resource has been one of the important energy sources for human life. Herein, luminescent nano-biomass dots (NBDs) have been extracted from soybean through ultrasonic method, which endows biomass with fluorescence property. The as-prepared NBDs are amorphous in structure with an average diameter of 2.4 nm and show bright blue fluorescence with a quantum yield of 16.7%. Benefiting from the edible raw materials and heating-free synthesis process, the cytotoxicity test shows that the cell viability still keeps 100% even if the concentration of the NBDs reaches 800 μg/ml, indicating the good biocompatibility of the NBDs. In addition, the fluorescence of the NBDs is very sensitive to Fe3+, which can be used for Fe3+ detection in terms of their health superiority. The limit of detection (LOD) of the proposed sensor was determined as 2.9 μM, which is lower than the maximum allowable level of Fe3+ (5.37 μM) in drinking water.


[A Case of Retroperitoneal Bronchogenic Cyst].
A 75-year-old male visited a clinic with the chief complaint of pollakiuria. A computed tomography scan revealed, a left adrenal mass, and the patient was then referred to our hospital. Since a malignant tumor could not be ruled out. We performed laparoscopic left adrenal resection. Postoperative histopathological findings revealed the mass to be a bronchogenic cyst, which had no continuity with the normal adrenal gland. The postoperative course was uneventful, and recurrence has not been observed. Retroperitoneal bronchogenic cysts are rare and often difficult to diagnose preoperatively using imaging studies.


Repair of anomalous aortic origin of a coronary artery in 113 patients: a Congenital Heart Surgeons' Society report.
Anomalous aortic origin of a coronary artery (AAOCA) encompasses a wide morphologic spectrum, which has impeded consensus regarding indications for the diverse repair strategies. We constructed a profile of current surgical techniques and explore their application to morphologic variants. Patients<30 years old (n=113) with isolated AAOCA who underwent operations at 29 Congenital Heart Surgeons Society (CHSS) institutions from 1998 to 2012 were identified from the CHSS AAOCA Registry. Operative findings were related to surgical techniques at index repairs by cross-tabulation. Anomalous origin of the left main or left anterior descending coronary artery was present in 33 (29%) patients and of the right coronary artery in 78 (69%) patients; 2 arteries originated directly above the commissure between the left and right sinuses. There were 101 (89%) interarterial and intramural (IA/IM) arteries, 10 (9%) were interarterial but not intramural (IA/NIM) and 2 (2%) were neither interarterial nor intramural. Intramural arteries were unroofed in 100 (88%) operations, usually with intimal tacking after incision (n=47) or excision (n=25) of the common wall. Coronary reimplantation (n=11), pulmonary artery relocation (n=7; 5 for IA/NIM), simple ostioplasty (without unroofing; n=3), coronary artery bypass grafting (n=2), and ostial window (n=1) were less common. In 37 (33%) operations, a valvar commissure was taken down; 33 were resuspended. Current surgical repair of AAOCA is individualized to morphology, particularly the presence of intramural and/or interarterial segments. This report is foundational for future planned CHSS studies that will examine interventional and noninterventional outcomes and ultimately guide management of AAOCA.


Static versus dynamic training programs for muscular strength using the knee-extensors in healthy young - men.
Nineteen young and healthy males (18-21 years) were subjected to two strength training programs (dynamic and static) by using each of the knee extensor (quadriceps) muscles in each subject for each program. The duration of the study was 10 weeks with a frequency of three sessions per week. Pre-training and posttraining strength measurements were made for each program. Weekly post-training measurements were also made. The difference between the pre- and post-training mean strength measurements for the two programs and the difference between the mean strength increases in the two programs were all found to be statistically significant (p c 0.05). This showed that muscular strength could be increased by either of the training programs. However, more positive effects seemed to have been achieved through the isometric or static strength training program of strength gains. J Orthop Sports Phys Ther 1986;8(5):243-247.


Mean platelet volume in children with systemic lupus erythematosus.
Platelets are heterogeneous in size, density, metabolic, functional, and biochemical properties. Mean platelet volume (MPV) is a measure of the average size of platelet in a blood sample. We aimed to evaluate the mean platelet volume as a marker for disease activity in children with systemic lupus erythematosus. This was a prospective case-control study, which included 50 patients with SLE and 50 age and sex, matched healthy controls. All subjects were subjected to history taking, physical examination and laboratory parameters in active and remission phases of the diseases. The MPV value in the SLE group was significantly higher than control group (9.6 ± 1.3 fL, 9.1 ± 0.57 fL, respectively, p = 0.04). There was a significant increase of weight, blood pressure, urea, creatinine, proteinuria, CRP, ESR, cholestrol, MPV values, SLEDAI-2K scores and significant decrease of HB, albumin, C3, mean platelet volume (MPC) in the active stage than in the remission stage. There was a significant negative correlation between MPV and MPC in active stage of the disease but the correlation was insignificant in remission stage. MPV increased in active phase of patients with SLE and can be an easy, rapid, inexpensive and simple method to assess disease activity in children with SLE.


Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka.
Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1-/-adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.


Movement-related brain macropotentials of persons with Down syndrome during skilled performance.
Motor performances and movement-related brain macropotentials of nine 23-year-old males with Down syndrome whose mean MA was 10.2 years were compared to those of two control groups whose members were matched to the experimental subjects on CA or MA. A self-paced, voluntary, goal-directed task, which consisted of calculating a time interval of 40 to 60 msec by pressing two buttons, was employed. Subjects with Down syndrome had great difficulty in organizing and timing a correct temporal sequence of ballistic movements. They were much slower, less accurate, and achieved a smaller number of target performances. These behavioral patterns were associated with movement-related brain macropotentials altered in amplitude and latency. The potentials related to programming movements and processing reafferent sensory information were absent, and those involved in the evaluation of the outcome of the performance were reduced.


Comparative in vitro activity of cefepime against nosocomial isolates.
Cefepime, a new parenteral cephalosporin, was evaluated for its in vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin. Cefepime was highly active against all species of Enterobacteriaceae with minimum inhibitory concentrations (MIC90S) ranging from 0.25-8 micrograms/ml. Cefepime showed moderate activity against Acinetobacter spp (MIC50 and MIC90, 16 micrograms/ml) but its activity was superior to that of any drug tested, except imipenem. Against Pseudomonas aeruginosa its activity was comparable to that of ceftazidime and was greater than that of cefotaxime, aztreonam, ciprofloxacin and aminoglycosides. Of all the agents tested, imipenem was the most active compound. Cefepime was active against Staphylococcus aureus and coagulase-negative methicillin-susceptible staphylococci but it had no activity against methicillin-resistant staphylococci and enterococci.


Pilot study of radical hysterectomy versus radical trachelectomy on sexual distress.
Radical trachelectomy, which leaves the uterus intact, has emerged as a desirable surgical option for eligible women with early-stage cervical cancer who wish to preserve fertility. The available data suggest excellent obstetrical outcomes with radical trachelectomy, and no differences in sexual responding between radical trachelectomy and radical hysterectomy. There is a need to examine the effect of radical hysterectomy on sexual distress given that it is distinct from sexual function. Participants were 34 women diagnosed with early-stage cervical cancer. The authors report 1-month postsurgery data for 29 women (radical hysterectomy group: n = 17, M age = 41.8 years; radical trachelectomy group: n = 12, M age = 31.8 years), and 6-month follow-up data on 26 women. Whereas both groups experienced an increase in sex-related distress immediately after surgery, distress continued to increase 6 months after surgery for the radical hysterectomy group but decreased in the radical trachelectomy group. There were no between-group differences in mood, anxiety, or general measures of health. The decrease in sex-related distress in the radical trachelectomy but not in the radical hysterectomy group suggests that the preservation of fertility may have attenuated sex-related distress. Care providers should counsel women exploring surgical options for cervical cancer about potential sex distress-related sequelae.


Multiple sclerosis: report on 200 cases from Curitiba, Southern Brazil and comparison with other Brazilian series.
We reviewed the clinical and laboratory findings of 200 patients in Curitiba, Southern Brazil (25 degrees 25'40" S; 49 degrees 16'23" W-GR), with multiple sclerosis (MS)according to Poser's criteria. The patients were classified as: clinically definite (A1 and A2) - 142 patients (71%); laboratory-supported definite - 42 patients (21%); and clinically probable - 16 patients (8%). Relapsing-remitting (RR) form was the most common clinical presentation, with 182 (91%), followed by primary progressive (PP)(16 cases, 8%), and only 2 cases with secondarily progressive form (SP). Nine women and 7 men totalized the 16 PP cases. The mean age of onset was 32.0+/-9.9 (median 32 years). The gender ratio was female 1.8:1 male. All patients, except 3 African-Brazilian, were white. Seven (3.5%) patients developed a clinical history of Devic's syndrome. The initial clinical picture included brainstem/cerebellar syndrome in 126 (63%) cases, sensorial findings in 106 (53%)patients, motor (pyramidal) syndrome in 102 (49.5%), and optic neuritis in 79 (39.5%) cases. 122 (61%) patients had a final EDSS score < 3.5; 45 (22.5%) a score between 3.5 and 5.5, and 33 (16.5%) a score > or = 6.0. There was no significant correlation between the number of relapses or duration of disease with EDSS scores (Spearman's test). Only 14 (7%) of the total number presented the benign form (EDSS< 3.5 after 10 years of disease). We observed a later age of onset and initial clinical findings with higher frequency of brainstem/cerebellar syndrome and optic neuritis, when compared to other Brazilian and Western series