Sources of intramammary infections from Staphylococcus aureus in dairy heifers at first parturition.
The study objective was to identify probable sources and modes of transmission of 91 Staphylococcus aureus isolates obtained from the colostrum of 76 heifers at parturition. Sources cultured were milk (including colostrum), heifer body sites (teats, muzzle, rectum, vagina, and lacteal secretions), and environmental sites (bedding, insects, housing, water, feedstuffs, humans, nonbovine animals, air, and equipment). Staphylococcus aureus isolates were characterized by 63 phenotypic traits. A similarity coefficient was calculated by herd to identify the S. aureus that most closely resembled the S. aureus obtained from heifer colostrum. Staphylococcus aureus from a heifer's colostrum was compared with all preexisting S. aureus isolates from that heifer's herd. Isolates that were > or = 90% similar were considered to be identical. Because 30 (of the 91) S. aureus isolates from heifer colostrum were collected prior to environmental sampling, only 61 S. aureus isolates from heifer colostrum were available for comparison among all three sources. Possible sources of S. aureus from heifer colostrum at parturition were milk (70%, 43 of 61 isolates), heifer body sites (39%, 24 of 61), environmental sites (28%, 17 of 61), or no identified source (16%, 10 of 61). Three heifers with intramammary infection (IMI) from S. aureus at parturition had the same S. aureus on their teats prior to parturition. Milk was the only source identified for 41% (25 of 61) of isolates from heifer colostrum. Isolates from heifer body sites were the only source identified for 5% (3 of 61) of heifer colostrum isolates. Staphylococcus aureus from the environment was never the sole possible source for S. aureus from heifer colostrum. Data suggest that the major sources of S. aureus IMI in heifers at parturition are milk and heifer body sites. Contact among heifers may be an important mode of transmission of S. aureus leading to IMI in heifers at parturition.


Interaction of sex, age, body mass index and race on hypertension risk in the American population: a cross-sectional study.
The joint effects of sex, age, body mass index (BMI) and race on hypertension have not been fully addressed. Herein, we carried out this study aiming to investigate the possible effects of the interaction of sex, age, BMI and race on risk of hypertension. By using the data of a sample-adjusted 2656 women and 2515 men in American National Health and Nutrition Examination Survey 2015-16, we analyzed the interaction of sex, age, BMI and race by logistic regression models, followed by strata-specific analyses. Hypertension was defined as a systolic blood pressure ≥130 mmHg/diastolic blood pressure ≥80 mmHg or taking anti-hypertensive medication. A total of 5171 participants were included in analysis, and the prevalence of hypertension was 53.68%. The interactive effect of sex and age, BMI and age, race and age were statistically significant on hypertension. Strata-specific analyses showed that female at 40 years and above were positively associated with hypertension than those at 20-39 years. The associations also persistence in male. The risk estimates for age ≥40 on hypertension were consistently positive across all overweight/obesity and race groups. The effect was most prominent among overweight populations aged 60-80 years and Other Hispanic aged 40 years and above. There exists interactive effect of sex and age, BMI and age, race and age on hypertension in American population. The effect of age on hypertension was more prominent in female, overweight populations and Other Hispanic populations. Differences in age, BMI and race should be considered when providing corresponding antihypertensive measures.


Connections between the facial, vestibular and cochlear nerve bundles within the internal auditory canal.
The vestibular, cochlear and facial nerves have a common course in the internal auditory canal (IAC). In this study we investigated the average number of nerve fibres, the average cross-sectional areas of the nerves and nerve fibres, and the apparent connections between the facial, cochlear and vestibular nerve bundles within the IAC, using light and scanning electron microscopy. The anatomical localization of the nerves within the IAC was not straightforward. The general course showed that the nerves rotated anticlockwise in the right ear from the inner ear end towards the brainstem end and vice versa for the left ear. The average number of fibres forming vestibular, cochlear, and facial nerves was not constant during their courses within the IAC. The superior and the inferior vestibular nerves showed an increase in the number of nerve fibres from the inner ear end towards the brainstem end of the IAC, whereas the facial and the cochlear nerves showed a reduction in the number of fibres. This suggests that some of the superior and inferior vestibular nerve bundles may receive fibres from the facial and/or cochlear nerves. Scanning electron microscopic evaluations showed superior vestibular-facial and inferior vestibular-cochlear connections within the IAC, but no facial-cochlear connections were observed. Connections between the nerves of the IAC can explain the unexpected vestibular disturbances in facial paralysis or persistence of tinnitus after cochlear neurectomy in intractable tinnitus cases. The present study offers morphometric and scanning electron microscopic data on the fibre connections of the nerves of the IAC.


Psychiatric diagnosis of patients requesting sex reassignment surgery.
This paper presents the psychiatric diagnostic findings on 51 patients who requested Sex Reassignment Surgery. The biologic females, as a group, were significantly healthier than the males. Ninety-two percent of the males and 58% of the females had psychiatric diagnoses, apart from gender dysphoria. Most of the abnormalities in both groups were character disorders; eight percent of the patients, however, were schizophrenic. Psychometric evaluation suggested that approximately one-half of the patients had more serious disorders than were indicated during clinical evaluation. The initial and ongoing diagnostic processes are helpful in the pre- and postoperative management of patients with gender dysphoria.


Hospital managers' attitude and commitment toward electronic medical records system in Isfahan hospitals 2014.
Electronic medical record system (EMRS) is a valuable system for safe access to the patient's data and increases health care quality. Manpower is one of the requirements for EMRS, among which manager is the most important person in any hospital. Taking into account manager's positive attitude and good commitments, EMRS will be implemented successfully. As such, we decided to assess manager's attitude and commitment toward EMRS in Isfahan hospitals in the year of 2014. This article aimed to determine the hospital managers' attitude and commitment toward the implementation of EMRS. The present article is an applied analytic study. Research society consisted of the managers of all the hospitals in Isfahan that include hospitals affiliated to Isfahan University of Medical Sciences, private, and social security hospitals. This study was done in 2014. Data collection tools included a questionnaire for which reliability and validity were determined. Data were analyzed by means of SPSS 20. Average score for the managers' attitude toward EMRS in the city of Isfahan was 77.5 out of 100 and their average score for commitment was 74.7. Manager's attitude in social security hospitals was more positive than the private and governmental ones (83.3%). In addition, the amount of commitment by the managers in social security hospitals was higher than the same in private and governmental hospitals (86.6%). At present, managers' attitude and commitment in Isfahan hospitals toward EMRS are very high and social security hospitals show more readiness in this respect.


Effects of dual modified resistant indica rice starch on azoxymethane-induced incipient colon cancer in mice.
In this study, the effects of different doses of dual modification-treated (DMT) indica rice resistant starch (IR-RS) on azoxymethane (AOM)-induced early colon cancer in mice were investigated. The investigated factors included body weight, gastrointestinal emptying rate, the number and morphology of aberrant crypt foci (ACFs) and the specific expressions of adenomatous polyposis coli (APC), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cytochrome c genes. The results demonstrated that DMT IR-RS controlled the increase in the body weights of the mice, increased the gastrointestinal emptying rates and reduced the numbers of ACFs and aberrant crypts. Reverse transcription-polymerase chain reaction revealed that DMT IR-RS promoted the expression of APC, Bax and cytochrome c and inhibited the expression of Bcl-2. These results demonstrate that a DMT IR-RS diet may induce apoptosis and has beneficial health effects in AOM-induced early colon cancer in mice.


Morphological changes in the skin and wool fibres of Merino sheep infused with mouse epidermal growth factor.
Intravenous infusion of 4.5-4.7 mg of mouse epidermal growth factor (mEGF) into nine castrated male Merino sheep for 26 h resulted in complete casting of the fleeces 6-8 days later. The morphological changes which occurred in the skin were studied in skin samples taken before infusion and at intervals between 1 h and 42 days after the infusion had begun. Wool fibres from the shed fleeces were examined with the scanning electron microscope. Increased cell proliferation occurred in the epidermis and sebaceous glands, whereas the wool follicles regressed. Transient dermal haemorrhages occurred during the first 3 h of infusion. The fibre and inner root sheath in the keratogenous zone of 30-40% of the follicles were partially disrupted within the first 6 h of mEGF infusion; catagen began in all follicle bulbs within 24 h. Fibre and inner root sheath production, although markedly reduced, continued in about 60% of follicles which had partially regressed, but production ceased in the remainder in which tapered ends formed on the fibres prior to shedding. Follicles began to regenerate asynchronously 4-8 days after the beginning of infusion and completed their development during the next 3 weeks. The follicle regression and fleece casting induced by mEGF infusion, and subsequent follicle regeneration were completed more rapidly than observed previously with other depilatory agents, and, except for prolonged epidermal thickening, there was no lasting cutaneous abnormality.


The epidemiology of hypertension-related renal disease.
An increasing number of population-based studies and clinical trials have examined the role of blood pressure in renal disease. Recent reports indicate that elevations of blood pressure, even within the normotensive range, may result in renal damage. The available evidence suggests that blood pressure reduction diminishes and may completely prevent the progressive deterioration of renal function in persons with established renal insufficiency. Blood pressure reduction with an angiotensin-converting enzyme inhibitor may provide the best means of achieving this goal, but other antihypertensive medications may be equally effective. Nonpharmacologic interventions can be used to lower blood pressure in hypertensive persons and prevent the development of hypertension in those with blood pressure in the high-normal range. Other recent studies examined the role of environmental nephrotoxins, unrecognized viral infections, lower socioeconomic status, access to health care, and genetic factors as determinants of renal disease and hypertension in the general population. Despite their overall importance, known risk factors for hypertension-related renal disease fail to explain the excess risk of this entity in blacks and other racial minorities.


Three detailed fluctuation theorems.
The total entropy production of a trajectory can be split into an adiabatic and a nonadiabatic contribution, deriving, respectively, from the breaking of detailed balance via nonequilibrium boundary conditions or by external driving. We show that each of them, the total, the adiabatic, and the nonadiabatic trajectory entropy, separately satisfies a detailed fluctuation theorem.


Anticoagulation management: an interdisciplinary curriculum for family medicine residents.
Anticoagulants are high-risk medications with the potential to cause significant patient harm if inappropriately managed. Medical trainees and practicing physicians often report inadequate education and uncertainty in decision-making related to anticoagulation therapy. To address this gap, an interdisciplinary Anticoagulation Management Training Program was developed for family medicine residents at the Toronto Western Family Health Team. Evaluation data demonstrated both improved knowledge and confidence in prescribing, monitoring, and adjusting anticoagulation therapy. This suggests that similar dedicated curricula be considered in other family medicine programs in order to optimize patient safety by enhancing the knowledge and self-efficacy of future practising physicians.


Induced acute non-lymphocytic leukemia following long-term chemotherapy: a study of 20 cases.
Twenty individuals developed acute non-lymphocytic leukemia (ANLL) following long-term chemotherapy for other disorders. The primary disorders included non-Hodgkin's lymphoma (five), Hodgkin's disease (five), carcinoma (four), multiple myeloma (three), chronic leukemia (two), and rheumatoid arthritis. Leukemia developed from 11-132 months (mean approximately 60 months) following institution of chemotherapy and all cases have occurred since 1974. Pre-leukemic cytopenias were present in 15 individuals. Fifteen of the 20 patients had chromosome analyses and 14 were abnormal. The leukemia was invariably refractory to chemotherapy with a median survival of only two months. Of the patients autopsied, only one individual had any evidence of the primary malignancy. This study illustrates the need for surveillance for secondary ANLL following long-term chemotherapy with/without radiotherapy. Duration of optimal chemotherapy for the primary disease must be determined by control trials and weighed against the risk of developing a secondary leukemia.


Effect of YHHJ on the expression of the hepatocellular bile acid transporters multidrug resistance-associated protein 2 and bile salt export pump in ethinylestradiol-induced cholestasis.
The herbal medicine Yin Huang Mixture (YHHJ; patent no. 200910031240.7) is an aqueous extract composed from various herbs, including Artemisia capillaries Thunb, Hypericum japonicum Thunb, Eucommia ulmoides Oliver, Rheum officinale Baill, Gardenia jasminoides Ellis, Poria cocos Wolf and Dictamnus dasycarpus Turcz. Previous studies have indicated that YHHJ treatment has a beneficial effect on ameliorating itching and reducing serum bile acid levels in patients with intrahepatic cholestasis of pregnancy (ICP). However, the molecular mechanisms of action of YHHJ in ICP have not been fully elucidated. Therefore, the present study investigated an experimental hepatocellular cholestasis model to explore the regulatory role of YHHJ on the expression of the bile acid carriers, multidrug resistance-associated protein 2 (MRP2) and the bile salt export pump (BSEP). Initially, 5 mg/kg/day 17-α ethinylestradiol (EE) was used to induce cholestasis in rats and primary isolated rat hepatocytes. Subsequently, 9 or 36 g/kg/day YHHJ water extract was administrated. Blood samples were collected and serum biochemical parameters of total bile acids (TBA), total bilirubin (TBil), alanine transaminase and aspartate aminotransferase levels were determined. Rat livers and primary isolated rat hepatocytes were obtained and the protein and mRNA expression levels of MRP2 and BSEP were analyzed by western blot analysis and reverse transcription-quantitative polymerase chain reaction, respectively. Results revealed that EE-induced hepatocellular cholestasis was associated with a significant increase in serum TBA and TBil levels, whereas, YHHJ treatment significantly reversed this effect (P<0.01). Further experiments on the molecular mechanism revealed that EE significantly decreased the expression of MRP2 and BSEP compared with the control group, whereas YHHJ treatment significantly upregulated MRP2 and BSEP expression in vivo and in vitro compared with no YHHJ treatment (P<0.01). In addition, to establish whether upregulation of MRP2 and BSEP protein expression levels resulted from increased expression of their respective mRNA, the mRNA expression levels were determined. Results indicated that YHHJ treatment significantly increased MRP2 and BSEP mRNA expression levels in EE-induced hepatocellular cholestasis compared with no YHHJ treatment (P<0.01). In conclusion, the present findings suggest that YHHJ effects EE-induced cholestasis and this process may be mediated through regulating hepatobiliary transporters, MRP2 and BSEP.


Paralytic ectropion: a complication of malar implant surgery.
The use of the malar implant to augment the malar-zygomatic eminence is rapidly becoming a popular aesthetic procedure; however, this surgery can lead to paralysis or paresis of the facial nerve. Paralytic ectropion may result from orbicularis oculi dysfunction. We report two cases of paralytic ectropion as a result of malar implant placement. Conservative management for mild orbicularis oculi dysfunction consisted of topical lubricants and observation, whereas persistent ectropion required surgical repair. Paralytic ectropion and secondary exposure keratopathy are possible complications of malar implant surgery.


C-Kit Promotes Growth and Migration of Human Cardiac Progenitor Cells via the PI3K-AKT and MEK-ERK Pathways.
A recent phase I clinical trial (SCIPIO) has shown that autologous c-kit+ cardiac progenitor cells (CPCs) improve cardiac function and quality of life when transplanted into patients with ischemic heart disease. Although c-kit is widely used as a marker of resident CPCs, its role in the regulation of the cellular characteristics of CPCs remains unknown. We hypothesized that c-kit plays a role in the survival, growth, and migration of CPCs. To test this hypothesis, human CPCs were grown under stress conditions in the presence or absence of SCF, and the effects of SCF-mediated activation of c-kit on CPC survival/growth and migration were measured. SCF treatment led to a significant increase in cell survival and a reduction in cell death under serum depletion conditions. In addition, SCF significantly promoted CPC migration in vitro. Furthermore, the pro-survival and pro-migratory effects of SCF were augmented by c-kit overexpression and abrogated by c-kit inhibition with imatinib. Mechanistically, c-kit activation in CPCs led to activation of the PI3K and the MAPK pathways. With the use of specific inhibitors, we confirmed that the SCF/c-kit-dependent survival and chemotaxis of CPCs are dependent on both pathways. Taken together, our findings suggest that c-kit promotes the survival/growth and migration of human CPCs cultured ex vivo via the activation of PI3K and MAPK pathways. These results imply that the efficiency of CPC homing to the injury site as well as their survival after transplantation may be improved by modulating the activity of c-kit.


How the shape of the NH2 group depends on the substituent effect and H-bond formation in derivatives of aniline.
The geometry and electronic structure of the amino group in aniline and its derivatives are very sensitive to both intramolecular interactions such as substituent effects and intermolecular ones such as H-bonding. An analysis of experimental geometries retrieved from the CSD base and computational modeling of aniline and its derivatives and their H-bonded complexes by use of B3LYP/6-311+G** and MP2/aug-cc-pVDZ showed that the degree of pyramidalization of the amino group depends on H-bonding, which exists in two forms, (i) NH...B (base) and (ii) N...HB (Brønsted acid), both of which affect the shape of the NH2 group. The effect may be significantly enhanced by a substituent through resonance interaction from electron-attracting substituents. The NH...B interactions lead to a substantial planarization of the group, whereas N...HB interactions do not. The natural bond orbital analysis allowed the authors to show that the changes in occupancy of the "lone pair" orbital and in geometry parameters describing pyramidalization of the group depend on the substituent constants.


Precise Spatially Selective Photothermolysis Using Modulated Femtosecond Lasers and Real-time Multimodal Microscopy Monitoring.
The successful application of lasers in the treatment of skin diseases and cosmetic surgery is largely based on the principle of conventional selective photothermolysis which relies strongly on the difference in the absorption between the therapeutic target and its surroundings. However, when the differentiation in absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To deal with such cases, we introduce a novel spatially selective photothermolysis method based on multiphoton absorption in which the radiant energy of a tightly focused near-infrared femtosecond laser beam can be directed spatially by aiming the laser focal point to the target of interest. We construct a multimodal optical microscope to perform and monitor the spatially selective photothermolysis. We demonstrate that precise alteration of the targeted tissue is achieved while leaving surrounding tissue intact by choosing appropriate femtosecond laser exposure with multimodal optical microscopy monitoring in real time.


A close look at fluorescence quenching of organic dyes by tryptophan.
Understanding fluorescence quenching processes of organic dyes by biomolecular compounds is of fundamental importance for in-vitro and in-vivo fluorescence studies. It has been reported that the excited singlet state of some oxazine and rhodamine derivatives is efficiently and almost exclusively quenched by the amino acid tryptophan (Trp) and the DNA base guanine via photoinduced electron transfer (PET). We present a detailed analysis of the quenching interactions between the oxazine dye MR121 and Trp in aqueous buffer. Steady-state and time-resolved fluorescence spectroscopy, together with fluorescence correlation spectroscopy (FCS), reveal three contributing quenching mechanisms: 1) diffusion-limited dynamic quenching with a bimolecular quenching rate constant k(d) of 4.0 x 10(9) s(-1) M(-1), 2) static quenching with a bimolecular association constant K(s) of 61 M(-1), and 3) a sphere-of-action contribution to static quenching described by an exponential factor with a quenching constant lambda of 22 M(-1). The latter two are characterized as nonfluorescent complexes, formed with approximately 30 % efficiency upon encounter, that are stable for tens of nanoseconds. The measured binding energy of 20-30 kJ mol(-1) is consistent with previous estimates from molecular dynamics simulations that proposed stacked complexes due to hydrophobic forces. We further evaluate the influence of glycerol and denaturant (guanidine hydrochloride) on the formation and stability of quenched complexes. Comparative measurements performed with two other dyes, ATTO 655 and Rhodamine 6G show similar results and thus demonstrate the general applicability of utilizing PET between organic dyes and Trp for the study of conformational dynamics of biopolymers on sub-nanometer length and nanosecond time-scales.


Subcortical hyperintensities are associated with cognitive decline in patients with mild cognitive impairment.
It has been suggested that subcortical lesions may influence cognitive performances at early stages of cognitive impairment but not in late stages of dementia. We aimed to test whether cognitive decline is associated with subcortical hyperintensities in patients with mild cognitive impairment (MCI). We included 170 consecutive MCI patients (mean follow-up, 3.8+/-1.6 years). We assessed subcortical hyperintensities on a baseline magnetic resonance imaging scan with a semiquantitative rating scale. The mean annual cognitive decline was calculated with the Mini-Mental State Examination and the Dementia Rating Scale at baseline and the end of follow-up. Compared with patients whose cognitive performances remained stable or improved during follow-up, patients whose cognitive performances declined often had a larger amount (greater than the median of the distribution) of periventricular (PVH) (P=0.0005) and white-matter (P=0.02) hyperintensities. The rate of cognitive decline was higher with increasing PVH: mean change in the Mini-Mental State Examination score=0.16 vs -0.66 points/year in patients with PVH in the first versus third tertile (P=0.0002). The rate of decline in executive functioning was also higher with increasing PVH: mean change in the Dementia Rating Scale initiation subscore=-0.05 vs -1.42 points/year in patients with PVH in the first versus third tertile (P=0.04). These associations were independent of vascular risk factors, temporal lobe atrophy, and MCI subtype and were stronger in patients with baseline executive dysfunction. White-matter hyperintensities and especially PVH were significantly associated with cognitive decline in MCI patients. This result was independent of the MCI subtype but stronger in cases of executive dysfunction at baseline.


Challenges in Quantifying Cytosine Methylation in the HIV Provirus.
DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in in vitro latency models, its correlation with HIV persistence and expression in vivo is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integration sites, functional proviral load, sampling bias, and stochastic PCR amplification. Recent studies into genomic features of cytosine methylation sites in mammalian genes offer potentially significant insights into this mechanism. Here, we discuss the importance of these factors in the context of the HIV.


[Neurotensin NT (8- 13) dipeptide analog dilept increases the pain threshold and decreases the severity of morphine withdrawal syndrome in rats].
The pain threshold effects of a neurotensin NT (8 - 13) dipeptide analog (dilept), morphine, and their combination have been studied using the tail flick test in rats. The animals of another experimental group were administered with morphine in increasing doses (10 - 20 mg/kg, i.p.) for 5 days in order to induce the state of dependence. The physical dependence on morphine was evaluated in the open-field test by monitoring 16 specific behavioral signs of withdrawal syndrome (WS) induced by the opioid receptor antagonist naloxone, after which the WS total index was calculated. It was established, that dilept (1.6 mg/kg, i.p.) produced a mild analgesic effect via increasing the pain threshold by 34% (p < 0.01), did not effect on the morphine analgesic effect, and decreased the expression of morphine WS by 29.1 and 37.5% (p < 0.01) after a single or subchronic administration, respectively. These behavioral effects of dilept were accompanied by normalization of dopamine and serotonin turnover in the hypothalamus, frontal cortex, and striatum of experimental animals.


Deep brain stimulation failure due to external cardioversion in a patient with Parkinson's disease.
We report a case of deep brain stimulation (DBS) hardware failure due to emergently performed subcutaneous coronary angioplasties complicated by cardioversion for rapid worsening of angina pectoris and some trouble shooting problems emerged after invasive cardiovascular procedures. The patient with prior implantation of permanent pacemaker due to vasovagal syndrome underwent successful left-sided unilateral electrode implantation into the subthalamic nucleus. During 21 months follow-up period the patient experienced 2 times episodes of aggravation of unstable angina pectoris 15 and 21 months respectively, which necessities emergent coronary angioplasties. After the first emergently performed coronary angioplasty with cardioversion the interrogation of DBS system revealed the depletion of an internal pulse generator (IPG). The secondly performed coronary angioplasty complicated by ventricular tachyarrhythmia with DBS system switched on during emergent cardioversion resulted in partial dysfunction of DBS electrode. Patients harboring cardiovascular implantable electronic devices (CIEDs) and DBS systems require special attention and good cooperation of neurosurgeons, interventional cardiologist, and neurologist. Some emergently performed invasive cardiovascular procedures which necessities cardioversion may cause DBS hardware failure with subsequent worsening of movement disorder symptoms.


On the possible role of focal cooling of the heart in the mechanism of repetitive ventricular extra beats.
The role of myocardial foci in the mechanism of ventricular arrhythmias was studied by local cooling of the intact dog heart. At normal heart rate conduction delay in the focus is not sufficient to account for re-entry of impulses. However, a premature stimulus applied near the refractory period caused sudden prolongation of conduction giving rise to nonstimulated extra beats, arising probably as a result of re-entry. The phenomenon is presumably due to the fact that at this time a large portion of the fibres has not yet recovered excitability. With increasing size of the focus, there is increased asynchrony of recovery of excitability and premature stimuli falling later in the cycle are able to produce reentry. A negative correlation exists between cycle length and conduction delay and a positive correlation between cycle length and the coupling interval, i.e. the time interval between a premature stimulus and the first nonstimulated extra beat.


Promoting the participation of low-risk pregnant women in the child birth process by developing a birth plan: The protocol of an action research study.
The birth plan reflects the preferences and expectations of women in the delivery process and can be designed with the participation of women and her partner and implement as a basis for midwifery care during childbirth. This research was designed to promote the participation of low-risk pregnant women in the child birth process by developing a birth plan. The present study is a participatory action research designed in a single specialized, main maternity hospital in Isfahan, Iran. This study was conducted in four stages proposed by the Kemmis, including planning, action, observation, and reflection with the participation of all midwives, gynecologists, and managers who involved in childbirth. Considering the importance of childbirth as an opportunity for participation and empowerment of women, it seems that designing a birth plan based on the preferences of these women and all people involved in this process can strengthen women's participation in child birth process.


Where are the polyps? Molecular identification, distribution and population differentiation of Aurelia aurita jellyfish polyps in the southern North Sea area.
For many species of metagenic jellyfish the location of the benthic polyps is unknown. To gain insight in the distribution, species composition and population structure of scyphozoan jellyfish polyps in the southern North Sea area, polyp samples were collected from natural and artificial substrates (settling plates, marina floats and wrecks) at ten inshore locations in the Netherlands, seven offshore locations in the North Sea and in the Gullmar Fjord in Sweden. Polyps were identified to species level by sequencing both a fragment of 18S rDNA and a fragment of mitochondrial COI, and comparing these sequences to reference sequences available in GenBank and to newly obtained sequences from medusae collected in the area. All polyps sequenced did belong to Aurelia aurita. For this species, molecular diversity in mitochondrial COI was high, with 50 haplotypes among 183 polyps. Population differentiation was detected between the Dogger Bank and other-more coastal-locations, indicating extremely low connectivity. No significant differences were found between coastal samples. The location of polyps of Cyanea capillata, Cyanea lamarckii, Chrysaora hysoscella and Rhizostoma octopus in the study area remains unresolved.


Revolutionizing Spinal Care: Current Applications and Future Directions of Artificial Intelligence and Machine Learning.
Artificial intelligence (AI) and machine learning (ML) are rapidly becoming integral components of modern healthcare, offering new avenues for diagnosis, treatment, and outcome prediction. This review explores their current applications and potential future in the field of spinal care. From enhancing imaging techniques to predicting patient outcomes, AI and ML are revolutionizing the way we approach spinal diseases. AI and ML have significantly improved spinal imaging by augmenting detection and classification capabilities, thereby boosting diagnostic accuracy. Predictive models have also been developed to guide treatment plans and foresee patient outcomes, driving a shift towards more personalized care. Looking towards the future, we envision AI and ML further ingraining themselves in spinal care with the development of algorithms capable of deciphering complex spinal pathologies to aid decision making. Despite the promise these technologies hold, their integration into clinical practice is not without challenges. Data quality, integration hurdles, data security, and ethical considerations are some of the key areas that need to be addressed for their successful and responsible implementation. In conclusion, AI and ML represent potent tools for transforming spinal care. Thoughtful and balanced integration of these technologies, guided by ethical considerations, can lead to significant advancements, ushering in an era of more personalized, effective, and efficient healthcare.


1-Acetyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one.
The two fused five- and six-membered rings in the mol-ecule of the title compound, C(8)H(6)BrN(3)O(2), are approximately coplanar, the largest deviation from the mean plane being 0.011 (3) Å at the NH atom. The acetyl group is slightly twisted with respect to the imidazo[4,5-b]pyridine system, making a dihedral angle of 2.7 (2)°. In the crystal, adjacent mol-ecules are linked by inter-molecular N-H⋯N and C-H⋯O hydrogen bonds, forming infinite chains.


Parathyroid crisis and acute viral hepatitis B infection.
The simultaneous development of acute hyperparathyroidism and viral hepatitis B infection in a 72 year old male is described. Resolution of the hepatitis was accompanied by improvement in the parathyroid hormone mediated hypercalcaemia. It is postulated that antibodies to the hepatitis B virus may have altered the calcium 'set point' allowing uncontrolled synthesis and release of parathyroid hormone during the acute illness.


Frequency of blood CX3CR1-positive natural killer cells correlates with disease activity in multiple sclerosis patients.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by enormous variability in its clinical presentation and course, and for which clear diagnostic parameters are lacking. Here we performed an RNA screen in peripheral mononuclear cells from relapsing-remitting (RR) and primary progressive (PP) MS patients compared with healthy donors (HD) that indicated, among other findings, a role for the chemokine receptor CX3CR1 as a diagnostic marker. Gene expression and flow cytometric analyses demonstrated a significantly lower expression of CX3CR1 in MS patients compared with healthy individuals. The subpopulation of cells responsible for causing this reduced expression of CX3CR1 consisted exclusively of natural killer (NK) cells. Importantly, we found a correlation between disease activity and frequency of CX3CR1-positive NK cells in RRMS patients. These findings emphasize the role of NK cells in the development and course of MS and provide evidence for CX3CR1 expression as a marker for MS patients and disease activity.


Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III.
A proteinase with high affinity for insulin has been proposed to play a role in the cellular processing of this hormone. A complementary DNA (cDNA) coding for this enzyme has been isolated and sequenced. The deduced amino acid sequence of the enzyme contained the sequences of 13 peptides derived from the isolated protein. The cDNA could be transcribed in vitro to yield a synthetic RNA that in cell-free translations produced a protein that coelectrophoresed with the native proteinase and could be immunoprecipitated with monoclonal antibodies to this enzyme. The deduced sequence of this proteinase did not contain the consensus sequences for any of the known classes of proteinases (that is, metallo, cysteine, aspartic, or serine), but it did show homology to an Escherichia coli proteinase (called protease III), which also cleaves insulin and is present in the periplasmic space. Thus, these two proteins may be members of a family of proteases that are involved in intercellular peptide signaling.


Remodeling of secretory compartments creates CUPS during nutrient starvation.
Upon starvation, Grh1, a peripheral membrane protein located at endoplasmic reticulum (ER) exit sites and early Golgi in Saccharomyces cerevisiae under growth conditions, relocates to a compartment called compartment for unconventional protein secretion (CUPS). Here we report that CUPS lack Golgi enzymes, but contain the coat protein complex II (COPII) vesicle tethering protein Uso1 and the Golgi t-SNARE Sed5. Interestingly, CUPS biogenesis is independent of COPII- and COPI-mediated membrane transport. Pik1- and Sec7-mediated membrane export from the late Golgi is required for complete assembly of CUPS, and Vps34 is needed for their maintenance. CUPS formation is triggered by glucose, but not nitrogen starvation. Moreover, upon return to growth conditions, CUPS are absorbed into the ER, and not the vacuole. Altogether our findings indicate that CUPS are not specialized autophagosomes as suggested previously. We suggest that starvation triggers relocation of secretory and endosomal membranes, but not their enzymes, to generate CUPS to sort and secrete proteins that do not enter, or are not processed by enzymes of the ER-Golgi pathway of secretion.


NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation.
Laminar shear stress (LSS) triggers signals that ultimately result in atheroprotection and vasodilatation. Early responses are related to the activation of specific signaling cascades. We investigated the participation of redox-mediated modifications and in particular the role of hydrogen peroxide (H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular endothelial cells to short periods of LSS (12 dyn/cm(2)) resulted in the generation of superoxide radical anion as detected by the formation of 2-hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was corroborated by the increase in the fluorescence of the specific peroxide sensor HyPer. By using biotinylated dimedone we detected increased total protein sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4 (NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to identify the phosphatase SHP2 as a protein susceptible to sulfenylation under LSS. Given the dependence of FAK activity on SHP2 function, we explored the role of FAK under LSS conditions. FAK activation and subsequent endothelial NO synthase (eNOS) phosphorylation were promoted by LSS and both processes were dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4-null mice. These results support the idea that LSS elicits redox-sensitive signal transduction responses involving NOX4-dependent generation of hydrogen peroxide, SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation.


Activation of Natural Products Biosynthetic Pathways via a Protein Modification Level Regulation.
Natural products are critical for drug discovery and development; however their discovery is challenged by the wide inactivation or silence of microbial biosynthetic pathways. Currently strategies targeting this problem are mainly concentrated on chromosome dissembling, transcription, and translation-stage regulations as well as chemical stimulation. In this study, we developed a novel approach to awake cryptic/silenced microbial biosynthetic pathways through augmentation of the conserved protein modification step-phosphopantetheinylation of carrier proteins. Overexpression of phosphopantetheinyl transferase (Pptase) genes into 33 Actinomycetes achieved a significantly high activation ratio at which 23 (70%) strains produced new metabolites. Genetic and biochemical studies on the mode-of-action revealed that exogenous PPtases triggered the activation of carrier proteins and subsequent production of metabolites. With this approach we successfully identified five oviedomycin and halichomycin-like compounds from two strains. This study provides a novel approach to efficiently activate cryptic/silenced biosynthetic pathways which will be useful for natural products discovery.


Trends in exploitation of packed red blood cells.
The following trends aim to a more efficient exploitation of packed red blood cells (PRBC): 1. Improvement of the operative distribution of PRBCs for transfusions before expiration. 2. Prolongation of the expiration time by monitoring the biochemical and physical processes during banking. Maintenance of native hemoglobin and restoration or substitution of substances involved in transport of energy and of oxygen are of utmost importance. Enzymic conversion of RBCs of blood group A, B to 0 is not supposed to leave laboratory scale soon. While cryo-conservation of RBCs with glycerine is known, freeze-drying of PRBCs remains a speculation. 3. Use of PRBCs after expiration as a raw material for products applicable in medicine and biochemistry. Stroma-free hemoglobin variants (SFH) are known as effective infusable oxygen carriers in experimental animal models. However, there is little convincing evidence on the metabolism and innocuity of SFH variants in human organism. Therefore, systemic infusion of SFH solutions is not yet acceptable to clinicians even in emergency situations. On the other hand, a broader use of SFH and its variants is anticipated and regarded as prospective in organ perfusion, cardioplegy and transplantation as well as in analytical biochemistry.


Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis.
Epsin is a key molecule in receptor-mediated endocytosis. Epsin is phosphorylated and ubiquitinated, and these post-translational modifications are necessary for the regulation of endocytosis. Since human Epsin (hEpsin) has two ubiquitin-interacting motifs (UIMs), we investigated the roles of these UIMs in endocytosis. hEpsin formed a complex with ubiquitinated proteins but did not bind to monoubiquitin. Neither of the two UIMs of hEpsin alone was sufficient to form a complex with ubiquitinated proteins: both UIMs were necessary. Mutations of Asp209 and Asp210 to Ala in UIM (hEpsinDA) abolished the binding activity of hEpsin to ubiquitinated proteins. However, hEpsinDA interacted with Eps15, POB1, and AP-2, which are involved in receptor-mediated endocytosis, as efficiently as wild-type hEpsin. Expression of hEpsinDA in CHO-IR cells affected neither the binding of insulin to nor insulin-dependent autophosphorylation of its receptor. Expression of wild-type hEpsin inhibited the internalization of insulin, whereas that of hEpsinDA did not. These results suggest that the UIM motifs of hEpsin interact with proteins modified with ubiquitin, and that the complex formation is involved in insulin-dependent receptor endocytosis.


A semimechanistic model of the time-course of release of PTH into plasma following administration of the calcilytic JTT-305/MK-5442 in humans.
JTT-305/MK-5442 is a calcium-sensing receptor (CaSR) allosteric antagonist being investigated for the treatment of osteoporosis. JTT-305/MK-5442 binds to CaSRs, thus preventing receptor activation by Ca(2+) . In the parathyroid gland, this results in the release of parathyroid hormone (PTH). Sharp spikes in PTH secretion followed by rapid returns to baseline are associated with bone formation, whereas sustained elevation in PTH is associated with bone resorption. We have developed a semimechanistic, nonpopulation model of the time-course relationship between JTT-305/MK-5442 and whole plasma PTH concentrations to describe both the secretion of PTH and the kinetics of its return to baseline levels. We obtained mean concentration data for JTT-305/MK-5442 and whole PTH from a multiple dose study in U.S. postmenopausal women at doses of 5, 10, 15, and 20 mg. We hypothesized that PTH is released from two separate sources: a reservoir that is released rapidly (within minutes) in response to reduction in Ca(2+) binding, and a second source released more slowly following hours of reduced Ca(2+) binding. We modeled the release rates of these reservoirs as maximum pharmacologic effect (Emax ) functions of JTT-305/MK-5442 concentration. Our model describes both the dose-dependence of PTH time of occurrence for maximum drug concentration (Tmax ) and maximum concentration of drug (Cmax ), and the extent and duration of the observed nonmonotonic return of PTH to baseline levels following JTT-305/MK-5442 administration.


Association of waist circumference with blood pressure and familial dietary habits in preschool children: a cross-sectional study in northeastern China.
Childhood obesity increases the risk of elevated blood pressure (BP) in children. Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) are traditional obesity indices, but the extent to which these indices are associated with elevated BP in childhood remains debatable. Moreover, the familial dietary environment plays an important role in obesity, so it is necessary to determine the most relevant dietary factors for childhood obesity to prevent elevated BP. Our study aimed to identify the obesity indices that are most closely associated with elevated BP and then to determine the independent familial dietary factors for those obesity indices. A total of 605 children aged 2 to 6 years, as well as their parents, were involved in this study. The weight, height, WC and BP of the children were measured. Information on familial environments was obtained by questionnaires completed by the parents. BMI, WC and WHtR were standardized into z scores, and categorical variables of these three obesity indices were defined as BMI Category, WC Category and WHtR Category. Logistic regression was used to analyse the associations between all obesity indices and elevated BP. Multivariate linear regression and logistic regression were used to determine the independent factors for obesity indices. The obesity indices that were most closely associated with elevated BP were WC and WC Category. Parental BMI, birth weight, eating wheat as a staple food, appetite, eating speed, snacking while watching TV, parental encouragement to eat a diverse assortment of foods and drinking milk were independently associated with WC in both males and females. The risk of abdominal obesity increased 1.375 times in males and 1.631 times in females if appetite increased one level. If eating speed increased one level, the risk of abdominal obesity increased 1.165 times in males and 0.905 times in females. Females who drank milk more than 6 times per week had a 0.546 times lower risk of abdominal obesity. WC was an anthropometric parameter more closely associated with elevated BP. In addition to genetics, some familial dietary factors involving eating preference, eating habits and parental feeding practice were independently associated with WC and abdominal obesity in preschool children.


Serum alpha-tocopherol and immune function in yearling ewes supplemented with zinc and vitamin E.
Yearling Targhee ewes (n = 24; not pregnant or lactating) were used in a 2 x 2 factorial arrangement of treatments to determine the effects of supplemental vitamin E (0 IU [0vitE] vs 330 IU vitamin E x ewe(-1) x d(-1) [+vitE]) and Zn (0 mg [0Zn] vs 140 mg Zn x ewe(-1) x d(-1) [+Zn]) on serum alpha-tocopherol concentrations, antibodies to parainfluenza type 3 (PI3), ewe BW, Zn liver concentrations, and serum alkaline phosphatase activity. Ewes were managed as one group, grazed native pasture, and had ad libitum access to white salt and water. Ewes that received supplemental vitamin E were orally dosed every other day with 660 IU of DL-alpha-tocopherol acetate in a gelatin capsule beginning on d 1 and continuing to d 63 of the study. Ewes that received Zn supplement were orally dosed every other day with 280 mg of Availa-Zn 100 (Zinpro Corp., Eden Prairie, MN, IFN 6-32-054) in gelatin capsules for 63 d. All ewes were vaccinated with killed PI3 on d 22 and 42. No interactions were detected (P > 0.35); however, serum alpha-tocopherol concentrations and PI3 antibody titer dilutions changed (P = 0.001) over the length of the study. Ewe BW change, serum alkaline phosphatase activity, and liver Zn concentrations did not differ (P > 0.22) between 0Zn and +Zn or 0vitE and +vitE ewes. Serum a-tocopherol tended to be higher (P = 0.08) in +vitE than 0vitE ewes and was numerically higher (P = 0.16) in +Zn than 0Zn ewes. Antibody titer dilutions were higher (P = 0.06) in 0Zn than +Zn ewes and did not differ (P = 0.83) between 0vitE and +vitE ewes. These results indicate that high levels of supplemental Zn may have a tendency to improve serum alpha-tocopherol concentrations but may have negative impacts on humoral immune function.


Nanostructure-based therapies for liver fibrosis.
Nanotechnology has led to the development of numerous new systems for drug delivery into the target tissue, as well as novel methods that may be useful in the treatment of liver fibrosis. Inorganic and organic nanoparticles (NPs) are currently used in medical investigations and in the treatment of liver diseases, with adverse reactions observed in some cases. A revised treatment procedure involving NPs is necessary to develop future drug delivery systems having minimal noxious effects on the hepatic cells that take up and metabolize these particles in a different manner, in order to find the medication that is capable of blocking and even reversing fibrosis in an inflamed liver. In addition, the administered medication should not induce systemic responses against the NPs used in the treatment.


Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein.
Prostate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary genistein on human prostate cancer grown in human bone environment. In this study, we investigated the effects of genistein on PC3 prostate cancer cells and experimental PC3 bone tumors created by injecting PC3 cells into human bone fragments previously implanted in severe combined immunodeficient (SCID) mice (SCID human model). We found that genistein significantly inhibited PC3 bone tumor growth using both prevention and intervention strategies. By using microarray and real-time polymerase chain reaction technology, we found that genistein regulated the expression of multiple genes involved in the control of cell growth, apoptosis, and metastasis both in vitro and in vivo. For example, the expression of various metalloproteinases (MMPs) in PC3 bone tumors was inhibited by genistein treatment, whereas osteoprotegerin was upregulated. MMP immunostaining and transfection experiments also demonstrated that MMP-9 expression was inhibited in PC3 cells in vitro and PC3 bone tumors in vivo after genistein treatment. These results, particularly the in vivo results, demonstrate that dietary genistein may inhibit prostate cancer bone metastasis by regulating metastasis-related genes. Genistein may thus be a promising agent for the prevention and/or treatment of prostate cancer.


Comparative study of diethyl phthalate degradation by UV/H2O2 and UV/TiO2: kinetics, mechanism, and effects of operational parameters.
The photodegradation of diethyl phthalate (DEP) by UV/H2O2 and UV/TiO2 is studied. The DEP degradation kinetics and multiple crucial factors effecting the clearance of DEP are investigated, including initial DEP concentration ([DEP]0), initial pH values (pH0), UV light intensity, anions (Cl(-), NO(3-), SO4 (2-), HCO3 (-), and CO3 (2-)), cations (Mg(2+), Ca(2+), Mn(2+), and Fe(3+)), and humic acid (HA). Total organic carbon (TOC) removal is tested by two treatments. And, cytotoxicity evolution of DEP degradation intermediates is detected. The relationship between molar ratio ([H2O2]/[DEP] or [TiO2]/[DEP]) and degradation kinetic constant (K) is also studied. And, the cytotoxicity tests of DEP and its degradation intermediates in UV/H2O2 and UV/TiO2 treatments are researched. The DEP removal efficiency of UV/H2O2 treatment is higher than UV/TiO2 treatment. The DEP degradation fitted a pseudo-first-order kinetic pattern under experimental conditions. The K linearly related with molar ratio in UV/H2O2 treatment while nature exponential relationship is observed in the case of UV/TiO2. However, K fitted corresponding trends better in H2O2 treatment than in TiO2 treatment. The Cl(-) is in favor of the DEP degradation in UV/H2O2 treatment; in contrast, it is disadvantageous to the DEP degradation in UV/TiO2 treatment. Other anions are all disadvantageous to the DEP degradation in two treatments. Fe(3+) promotes the degradation rates significantly. And, all other cations in question inhibit the degradation of DEP. HA hinders DEP degradation in two treatments. The intermediates of DEP degradation in UV/TiO2 treatment are less toxic to biological cell than that in UV/H2O2 treatment.


Knowledge and fears among Asian Americans chronically infected with hepatitis B.
Asian Americans are disproportionately affected by hepatitis B (HBV) infection. In the USA, one in ten Asian Americans is infected with HBV. The purpose of the study was to explore knowledge, fears and follow-up care among Asian Americans chronically infected with hepatitis B. A sample of 154 completed an online survey which included demographic information, follow-up treatment information, and HBV knowledge and fears/concerns. Our findings indicate that there are differences by ethnicity and birthplace among Asian Americans in terms of follow-up care and treatment. In addition, our study indicates that there were substantial knowledge gaps regarding contracting HBV, transmission, and prevention. We found that HBV-infected respondents had many fears about their infection. Three primary concerns were identified: (a) concerns related to liver cancer and overall health, (b) transmission to loved ones, and (c) stigma. Our findings indicate that Asian Americans chronically infected with HBV need more education to manage HBV including information on the importance of follow-up treatment and care and education on preventing transmission, risk for liver cancer, and HBV impact on overall health.


A silver impregnation technique for the study of steroid receptors in central nervous system tissue prepared for autoradiography.
The commonly used silver stains were found to be unsatisfactory for nervous tissue processed for autoradiography. A silver impregnation procedure for central nervous system tissues prepared for the autoradiographic study of steroid receptors is described. The procedure is a combination of several silver and reticular strains made up in solutions containing dimethylsulfoxide. The technique clearly distinguishes perikarya of neurons, brain nuclei and fiber tracts without substantial loss of silver grains, and thus greatly facilitates the identification of steroid receptor nuclei at all levels of the central nervous system.


Interaction of PALE CRESS with PAP2/pTAC2 and PAP3/pTAC10 affects the accumulation of plastid-encoded RNA polymerase complexes in Arabidopsis.
The transcription of photosynthesis genes in chloroplasts is largely mediated by the plastid-encoded RNA polymerase (PEP), which resembles prokaryotic-type RNA polymerases, but with plant-specific accessory subunits known as plastid transcriptionally active chromosome proteins (pTACs) or PEP-associated proteins (PAPs). However, whether additional factors are involved in the biogenesis of PEP complexes remains unknown. Here, we investigated the function of an essential gene, PALE CRESS (PAC), in the accumulation of PEP complexes in chloroplasts. We established that an Arabidopsis leaf variegation mutant, variegated 6-1 (var6-1), is a hypomorphic allele of PAC. Unexpectedly, we revealed that a fraction of VAR6/PAC is associated with thylakoid membranes, where it interacts with PEP complexes. The accumulation of PEP complexes is defective in both var6-1 and the null allele var6-2. Further protein interaction assays confirmed that VAR6/PAC interacts directly with the PAP2/pTAC2 and PAP3/pTAC10 subunits of PEP complexes. Moreover, we generated viable hypomorphic alleles of the essential gene PAP2/pTAC2, and revealed a genetic interaction between PAC and PAP2/pTAC2 in photosynthesis gene expression and PEP complex accumulation. Our findings establish that VAR6/PAC affects PEP complex accumulation through interactions with PAP2/pTAC2 and PAP3/pTAC10, and provide new insights into the accumulation of PEP and chloroplast development.


Acute inflammatory response to laser-induced micro- and nano-sized titanium surface features.
The inflammatory process induced by implant surfaces is an important component of the tissue response, where limited knowledge is available regarding the role of surface topography. With laser ablation, a combined micro- and nanoscale surface modification could be created, which have been shown to enhance bone growth and biomechanical stability in vivo. The aim of this article was to evaluate the early in vivo inflammatory response to laser-modified titanium disks, with machined titanium disks and sham operation sites serving as controls. Circular disks were installed in a subcutaneous rat model for 24 and 72 hours, where the cell number, cell types, and cytokine levels were evaluated. The results revealed that significantly fewer inflammatory cells (mononuclear and polymorphonuclear) were attracted to the sites with the laser-modified implants compared with the machined titanium implants. Similar concentrations of pro-inflammatory cytokines (TNF-a and MCP-1), together with slightly higher cell viability, were observed around the laser-modified surface compared with the machined surface. The results in the present study suggest that the combination of surface micro and nano features of the laser-treated surface contributes to the downregulation of early inflammatory events.


Association of Frailty Status with Risk of Fall among Hospitalized Elderly Patients: A Cross-Sectional Study in an Acute Geriatric Unit.
Introduction: The objective was to study the association of frailty status in hospitalized elderly patients with risk of fall in an acute geriatric unit and to characterize elderly "fallers" using a comprehensive gerontological assessment. Patients and Methods: A cross-sectional study was conducted in patients over 65 years of age and hospitalized in an acute geriatric unit. This work was carried out in the Acute Geriatric Medicine Unit, Saint-Julien Hospital, Center Hospitalier Universitaire de Rouen from 1 June 2016 to 15 August 2016. Results: 172 patients were included during the collection period, with a female predominance of 115 patients (66.9%). The average age of the sample was 79.37 years old (65−85). The average CHARLSON score was 6.93 (3−16). Patients came from home in 81.4% of cases (i.e., 140 patients), and from a nursing home in 18.6% of cases (i.e., 32 patients). The risk of falling, as assessed by the Monopodal Support Test, returned as abnormal for 127 patients. In our series, there was a statistically strong link between the risk of falling and the presence of a dementia pathology (p = 0.009), the presence of a vitamin D deficiency (p = 0.03), the presence of frailty, as assessed by the three scales (modified SEGA scale, Fried scale and CFS/7 (<0.001), a high comorbidity score (p = 0.04), and a disturbed autonomy assessment according to IADL (p = 1.02 × 10−5) and according to ADL (p = 6.4 × 10−8). There was a statistically strong link between the risk of falling and the occurrence of death (p = 0.01). Conclusion: The consequences of the fall in terms of morbidity and mortality and the frequency of this event with advancing age and its impact on the quality of life as well as on health expenditure justify a systematic identification of the risk of falling in the elderly population. It is therefore important to have sensitive, specific, and reproducible tools available for identifying elderly people at high risk of falling.


A beamline for photochemical processes at atmospheric pressure.
A beamline especially designed for atmospheric photochemical reactions has been constructed at the NTT synchrotron radiation facility. By inserting a buffer helium chamber with Be and Si(3)N(4) partition windows between the beamline and the reaction chamber, studies can be performed without the differential pumping systems normally used in existing photochemistry beamlines. The reaction chamber is equipped with a gas supply system and analysis systems to investigate gas-phase and surface reactions. Purging using dry purified gases in combination with water-bubbling gives effective control of water concentration in the reaction chamber.


Self-assembly of a Mn9 nanoscopic mixed-valent cluster: synthesis, crystal structure, and magnetic behavior.
A rare Mn9 micro3-oxo-centered mixed-valent cluster [Mn9O7(O2CPh)11(thmn)(py)2 (H2O)3] (1) is prepared by assembling an oxo-centered MnIIMnIII2 triangle, [Mn3O(O2CPh)6(py)2(H2O)].0.5MeCN, as the secondary building unit in the presence of a tripodal alcohol, 1,1,1-tris(hydroxymethyl)nitromethane (H3thmn), as the capping ligand. Complex 1 was formed along with a minor byproduct, [Mn6O2(O2CPh)10(MeCN)4] (2). Complex 1 was characterized by X-ray single-crystal structure analysis and was crystallized in a monoclinic system, space group P2(1)/n, a=16.214(6) A, b=25.874(10) A, c=26.497(10) A, and beta=94.214(7) degrees. The Manganese-oxo-carboxylate core in 1 looks like a funnel. Variable-temperature magnetic studies down to 2 K reveal the existence of dominant ferromagnetic interaction within the cluster. Alternating current susceptibility data of the cluster show strong frequency dependence of both the real and imaginary parts of susceptibility chi' and chi'' below 5 K. Moreover, the calculated relaxation time, tau0=1.2x10(-7) s, and the energy barrier, DeltaE=25 K, are consistent with the single-molecule magnetic behavior of 1.


A structured strategy for assessing chemical risks, suitable for small and medium-sized enterprises.
A previous study carried out in 20 Belgian companies, especially small and medium-sized enterprises (SMEs), showed that prevention advisors did not use any structured approaches to assess chemical risk. They used their personal judgement and the information contained in manufacturers' Safety Data Sheets to assess the risk. The purpose of the Regetox network is to provide companies with a global approach for assessing chemical health risks. The structured approach proposed consists of two successive steps of increasing complexity. For the first step, we chose a method developed by the INRS (France), the 'ranking of potential risk', which allows the safety officer or staff member to identify hazards and to set priorities among all the supplied products used in the workplace. For the second step, we applied the COSHH method and EASE model established by the UK Health & Safety Executive for assessing 'chemical risk by reference to occupational exposure limits'. The INRS and COSHH Essentials methods were chosen because they define hazards using R-phrases of the European classification system and assess the exposure by using simple information that is easy to collect in the workplace and toxicological databases. A feasibility study conducted in two enterprises shows the usefulness of this approach. In addition to the intrinsic limitations of the methods, the approach showed some limitations related to the inaccuracy of the manufactured safety data sheets and to the collection of the basic information needed for ranking potential risks. The use of the Regetox approach needs training of prevention advisors and a strategy involving employers, staff members and workers in collecting basic information and managing chemical risks. Under these conditions, Regetox seems to be a useful tool for chemical risk assessment in SMEs.


Intradiscal Autologous Platelet-Rich Plasma Injection for Discogenic Low Back Pain: A Clinical Trial.
Platelet-rich plasma (PRP) contains high concentrations of growth factors and cytokines and may promote healing and tissue formation and exert anti-inflammatory effects. PRP has been shown to improve intervertebral disc degeneration in vivo and in vitro. This study is aimed at evaluating the effectiveness of autologous PRP on discogenic low back pain (DLBP) at 48 weeks postinjection in patients who received a single intradiscal injection. All patients received a single intradiscal injection of PRP in a prospective trial. The pain scores, lumbar function, and adverse events were assessed at 1 week, 4 weeks, 8 weeks, 12 weeks, 24 weeks, and 48 weeks postinjection and compared to the preinjection values (0 weeks). Data were analysed from 31 patients with a 94% follow-up rate. Compared to preinjection, pain and lumbar function were significantly improved, and there were significant differences (P < 0.05) over the 48-week follow-up. Twenty-two (71%) patients were classified as successes after the intradiscal injection of PRP. One patient received surgery at two weeks postinjection due to intervertebral discitis. Intradiscal injection of PRP can significantly relieve pain sensation and improve lumbar function in patients with DLBP over a 48-week follow-up period. Further randomized controlled clinical trials are needed to assess the effects of this injection therapy.


Modification by sialic acid of Neisseria gonorrhoeae lipooligosaccharide epitope expression in human urethral exudates: an immunoelectron microscopic analysis.
Expression of lipooligosaccharide (LOS) antigenic determinants during human gonococcal infection was studied in secretions from seven men with gonococcal urethritis. Five monoclonal antibodies with distinct gonococcal LOS specificities and an H.8 lipoprotein monoclonal antibody were used in combination with immunogold electron microscopic analysis. The LOS epitope defined by antibody 6B7 was present on all seven strains in secretions and after in vitro growth. Gonococci from six of seven patients, when grown in vitro, expressed the 6B4 LOS epitope. The 6B4 epitope is a Gal beta 1-4-GlcNAc residue, which is immunochemically similar to the precursor of the human erythrocyte i antigen. This epitope was found unmodified on gonococcal LOS in urethral secretions from two patients. The unmodified epitope could not be demonstrated on organisms in five secretions. Neuraminidase digestion exposed the 6B4 epitope on organisms in these secretions and increased the 6B4 epitope density in the two secretions, which contained the unmodified epitope. These studies indicate that in vivo modification by sialylation of gonococcal LOS Gal beta 1-4-GlcNAc residue occurs during human infection.


Analysing clinical practice guidelines. A method of documentary analysis.
This paper will describe a method of documentary analysis used in a study examining the validity of clinical guidelines issued to health visitors to assist them in identifying families requiring increased health visitor support. This forms the preliminary work for a wider study examining how health visitors decide to increase support to vulnerable families. Although a number of published research texts discuss the value of records and documents as important data sources for health service researchers, there is relatively little information available about the processes of documentary analysis. This paper offers one method for analysing clinical practice guidelines, it describes the development of a critique and analysis tool and explores the strengths and weaknesses of this particular analysis instrument.


Perinatal and infant health outcomes among neonates born to aboriginal parents in Taiwan.
Poor health outcomes among neonates born to aborigines has been reported in many countries. This study was aimed to examine the nationwide characteristics of live births, adverse birth outcomes, and age-specific mortality among neonates born to non-aboriginal and aboriginal parents in Taiwan. All neonates born alive during the period of 2000 to 2003 in Taiwan were included. The adverse birth outcomes including low birth weight, preterm, and small-for-gestational-age births, and age-specific mortality were obtained. Logistic regression analysis was used to estimate odds ratios for parental ethnicity in relation to birth outcomes, while Cox's proportional hazards regression models were used to estimate hazard ratios for parental ethnicity in relation to age-specific infant deaths. A total of 947,317 live births were included that consisted of 9,381 born to aboriginal mothers, 6,429 born to aboriginal fathers, and 15,354 born to aboriginal parents. There was a gradual increase in the risk of having a baby with low birth weight, preterm, or small for gestational age born to the four parental aboriginal ethnicity groups: non-aboriginal parents, aboriginal mother only, aboriginal father only, and aboriginal parents. Similar trends were also found for early neonatal, neonatal, and infant mortalities after stratification of residential areas. The neonates born to both aboriginal parents with residence in rural or mountain areas were at highest risk of adverse birth outcomes and age-specific mortality. Our results demonstrated that aboriginality and residential area are important risk factors for adverse perinatal and infant outcomes.


Two cases of thyroid sarcoidosis presentation as painful, recurrent goiter in patients with Graves' disease.
Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high-resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found.


Seasonal and Daily Patterns in Activity of the Western Drywood Termite, Incisitermes minor (Hagen).
Activity of colonies of the western drywood termite, Incisitermes minor, was measured with acoustic emission (AE) technology in five loquat (Eriobotrya japonica) logs. Termite activity, whether it was feeding, excavation or movement, was monitored for 11 months under ambient conditions in a small wooden structure maintained at the University of California Richmond Field Station. AE, temperature, and humidity data were measured in 3-minute increments. Termite activity was greater during the warmer summer months compared to the cooler winter months. Termites in all five logs displayed a similar daily cycle of activity, peaking in the late afternoon. Seasonal and daily fluctuations in termite activity were significantly associated with temperature, whereas humidity did not appear to have a noticeable effect on termite activity. Possible mechanisms that drive the seasonal and daily cycles in termite activity, as measured by AE technology, and the possible implications for inspections and post-treatment analysis are discussed.


Telepsychiatry in Polish patients' and doctors' opinion.
Telepsychiatry is a new method of medical care, using modern communication technologies and electronic informations. It consists of web pages, containing data about diseases and their treatment in the form of multimedia libraries with video- and audiobooks. This research concerns verification of knowledge and attitude to telepsychiatry amongst patients and psychiatrists. An anonymous survey was conducted amongst 105 psychiatrists aged 26-74, including 74 women and 31 men and 102 patients aged 21-79, including 61 women and 41 men. Research reveals that majority of patients never met with the concept of 'telepsychiatry' and do not know what it means. However, more than 50% of respondents answered positively to every question considering the utility of telepsychiatry. Furthermore according to 18% it is possible to replace eye-to-eye conversation by videoconferencing. Only 15% of doctors claim to have an extensive knowledge on telepsychiatry, and 10% do not know what it means. The vast majority of physicians perceive positive aspects of this method of medical care, but 63% would not want general insertion of telepsychiatry. Doctors are apprehensive of losing personal data and medical confidentiality, and of the necessity of legal changes as well. The obtained results allow us to conclude that Polish patients and doctors, regardless of their knowledge, age, gender or disease, perceive advantages of telepsychiatry. In connection with this, implementing this method into the Polish medical market makes sense and is in accordance with both patients' and doctors' opinion. Based on our research, we confirmed that there is a necessity of wider popularization of telepsychiatry in Polish therapeutics.


S100A8 gene copy number and protein expression in breast cancer: associations with proliferation, histopathological grade and molecular subtypes.
Amplification of S100A8 occurs in 10-30% of all breast cancers and has been linked to poorer prognosis. Similarly, the protein S100A8 is overexpressed in a roughly comparable proportion of breast cancers and is also found in infiltrating myeloid-lineage cells, again linked to poorer prognosis. We explore the relationship between these findings. We examined S100A8 copy number (CN) alterations using fluorescence in situ hybridization in 475 primary breast cancers and 117 corresponding lymph nodes. In addition, we studied S100A8 protein expression using immunohistochemistry in 498 primary breast cancers from the same cohort. We found increased S100A8 CN (≥ 4) in tumor epithelial cells in 20% of the tumors, increased S100A8 protein expression in 15%, and ≥ 10 infiltrating S100A8 + polymorphonuclear cells in 19%. Both increased S100A8 CN and protein expression in cancer cells were associated with high Ki67 status, high mitotic count and high histopathological grade. We observed no association between increased S100A8 CN and S100A8 protein expression, and only a weak association (p = 0.09) between increased CN and number of infiltrating S100A8 + immune cells. Only S100A8 protein expression in cancer cells was associated with significantly worse prognosis. Amplification of S100A8 does not appear to be associated with S100A8 protein expression in breast cancer. S100A8 protein expression in tumor epithelial cells identifies a subgroup of predominantly non-luminal tumors with a high mean age at diagnosis and significantly worse prognosis. Finally, S100A8 alone is not a sufficient marker to identify infiltrating immune cells linked to worse prognosis.


Targeted gene silencing of CCL2 inhibits triple negative breast cancer progression by blocking cancer stem cell renewal and M2 macrophage recruitment.
Triple negative breast cancers are an aggressive subtype of breast cancer, characterized by the lack of estrogen receptor, progesterone receptor and Her2 expression. Triple negative breast cancers are non-responsive to conventional anti-hormonal and Her2 targeted therapies, making it necessary to identify new molecular targets for therapy. The chemokine CCL2 is overexpressed in invasive breast cancers, and regulates breast cancer progression through multiple mechanisms. With few approaches to target CCL2 activity, its value as a therapeutic target is unclear. In these studies, we developed a novel gene silencing approach that involves complexing siRNAs to TAT cell penetrating peptides (Ca-TAT) through non-covalent calcium cross-linking. Ca-TAT/siRNA complexes penetrated 3D collagen cultures of breast cancer cells and inhibited CCL2 expression more effectively than conventional antibody neutralization. Ca-TAT/siRNA complexes targeting CCL2 were delivered to mice bearing MDA-MB-231 breast tumor xenografts. In vivo CCL2 gene silencing inhibited primary tumor growth and metastasis, associated with a reduction in cancer stem cell renewal and recruitment of M2 macrophages. These studies are the first to demonstrate that targeting CCL2 expression in vivo may be a viable therapeutic approach to treating triple negative breast cancer.


[Cooperation between social-psychiatric services and psychiatric hospital--expectations and chances of improvement].
Expectations of social-psychiatric services regarding their cooperation with psychiatric hospitals should be examined by qualitative research. Based upon a content analysis of interviews with nine social-psychiatric services working in the catchment area of a psychiatric hospital, the statements were analysed quantitatively to assess their relative importance. Expectations on patient related communication between SpDi and hospital staff were expressed most frequently. Further aspects of an "ideal" cooperation from the SpDi's point of view are sympathy for each other, information of patients, community based psychiatric care, and quality of inpatient care. Social-psychiatric services' expectations represent important clues to improve the cooperation at the interface between outpatient and inpatient care and should be taken into consideration with respect to continuity of treatment of the chronically mentally ill.


A mouse model of the pathogenesis and postexposure prophylaxis of rabies.
A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine. Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine. Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection. IgM antibody did not protect the mice even when given 24 hr before infection. These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination. However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.


Designing Efficient Enzymes: Eight Predicted Mutations Convert a Hydroxynitrile Lyase into an Efficient Esterase.
Hydroxynitrile lyase from rubber tree (HbHNL) shares 45% identical amino acid residues with the homologous esterase from tobacco, SABP2, but the two enzymes catalyze different reactions. The x-ray structures reveal a serine-histidine-aspartate catalytic triad in both enzymes along with several differing amino acid residues within the active site. Previous exchange of three amino acid residues in the active site of HbHNL with the corresponding amino acid residue in SABP2 (T11G-E79H-K236M) created variant HNL3, which showed low esterase activity toward p-nitrophenyl acetate. Further structure comparison reveals additional differences surrounding the active site. HbHNL contains an improperly positioned oxyanion hole residue and differing solvation of the catalytic aspartate. We hypothesized that correcting these structural differences would impart good esterase activity on the corresponding HbHNL variant. To predict the amino acid substitutions needed to correct the structure, we calculated shortest path maps for both HbHNL and SABP2, which reveal correlated movements of amino acids in the two enzymes. Replacing four amino acid residues (C81L-N104T-V106F-G176S) whose movements are connected to the movements of the catalytic residues yielded variant HNL7TV (stabilizing substitution H103V was also added), which showed an esterase catalytic efficiency comparable to that of SABP2. The x-ray structure of an intermediate variant, HNL6V, showed an altered solvation of the catalytic aspartate and a partially corrected oxyanion hole. This dramatic increase in catalytic efficiency demonstrates the ability of shortest path maps to predict which residues outside the active site contribute to catalytic activity.


Exploring the role of basophil activation test in diagnosis of Dermatophagoides farinae sensitization and evaluation of therapeutic efficacy of subcutaneous immunotherapy in children.
It aims to detect basophil activation ratio (%CD63+ ) in peripheral blood of children with allergic asthma and rhinitis by using flow cytometry (FCM), so as to analyse the application values and clinical relevance of the basophil activation test (BAT) in diagnosis of Dermatophagoides farinae (Derf) sensitization and monitoring therapeutic efficacy of subcutaneous immunotherapy (SCIT). It was a prospective study. From the newly diagnosed children with asthma and rhinitis in our paediatric clinic, 39 patients diagnosed Derf sensitization and 15 patients not allergic to Derf were enrolled; another 4 healthy children were taken as control group. Using Derf extracts in concentration of 1, 10 μg/mL and 100 μg/mL as the stimulus, BAT results were expressed as %CD63+ in diagnosis of Derf sensitization and its correlation with skin prick tests (SPT), serum total IgE (tIgE), specific IgE (sIgE), sIgE/tIgE, specific IgG4 (sIgG4), FEV1%pred in pulmonary ventilation function, exhaled nitric oxide (FeNO), children asthma control test (C-ACT) and visual analogue scale (VAS) were observed. In sensitization group, %CD63+ , sIgG4 and clinical indicators were detected again from patients who had received SCIT to analyse their internal connections. The average levels of %CD63+ in 3 concentrations showed an increasing concentration-dependent trend overall. %CD63+ in sensitization group was significantly higher than that in the other 2 groups. The analysis of ROC for Derf sensitization showed the area under the curve (AUC) for BAT in 3 concentrations was higher than that for sIgE whose AUC is 0.893. %CD63+ was positively correlated with SPT grade, sIgE, sIgE/tIgE and VAS, and negatively correlated with C-ACT. In patients receiving SCIT, %CD63+ became lower and sIgG4 level became higher than pretreatment. There was no obvious change in sIgG4 in those who had not received SCIT. BAT is a reliable and non-invasive tool for diagnosis of Derf sensitization in children with asthma and rhinitis. CD63-based BAT has clinical value to monitor outcome of SCIT, and the change in basophil activation is inherently related to induction of sIgG4.


Serine protease inhibitor 6-deficient mice have increased neutrophil immunity to Pseudomonas aeruginosa.
Inflammation is a localized, protective response to trauma or microbial invasion that destroys the injurious agent and the injured tissue. Neutrophil elastase (NE), a serine protease stored in the azurophil granules of polymorphonuclear neutrophils, digests microbes after phagocytosis. NE can also digest microbes extracellularly but is associated with tissue damage and inflammatory disease. In this study, we show that polymorphonuclear neutrophils from mice deficient in serine protease inhibitor 6, a weak intracellular NE inhibitor, had increased susceptibility to self-inflicted lysis because of increased NE activity. The resulting transient increase in local extracellular NE activity was within a narrow range that resulted in the clearance of Pseudomonas aeruginosa but did not damage the lung. Therefore, deficiency in a weak intracellular inhibitor of NE results in an acute inflammatory response that protects from P. aeruginosa but does not cause lung disease.


Microfungal oasis in an oligotrophic desert: diversity patterns and community structure in three freshwater systems of Cuatro Ciénegas, Mexico.
The Cuatro Ciénegas Basin (CCB) comprises several oligotrophic aquatic ecosystems limited by phosphorus. These aquatic systems are dominated by a high prokaryotic diversity, shaped by the stress of low nutrient supplies and interspecific competition. Although fungi constitute a diverse and important component of microbial diversity, the microfungal diversity in the CCB remains to be unveiled. With the aim to explore microfungal diversity and ecological patterns in this area, we present the first investigation analyzing cultivable taxa from sediment and water, as well as lignocellulolytic taxa obtained from incubated submerged plant debris, and wood panels in three contrasting freshwater systems in the CCB: Churince, Becerra and Pozas Rojas. We chose a culture-based approach to analyze sediment and water samples in order to obtain fungal cultures, providing opportunities for a posteriori studies, and the possibility of ex situ preservation of the diversity. We evaluated sequence data from the nuclear ribosomal internal transcribed spacer including the 5.8 rDNA region for 126 isolates, revealing 37 OTUs. These OTUs were phylogenetically affiliated to several genera in the fungal phyla: Zygomycota, Basidiomycota, and Ascomycota. We recorded two OTUs with saline affinity, agreeing with previous findings on the prokaryotic communities with ancestral marine resemblances. All the studied systems showed moderate diversity levels, however discrepancies among the diversity indexes were observed, due to the occurrence of abundant taxa in the samples. Our results indicated that lignocellulolytic microfungal communities are dominated by transient fungal taxa, as resident species were not recorded perhaps as a result of the long-term strong competition with the highly adapted prokaryotic community. Moreover, the obtained microfungal taxa occurred mostly on the resident plant debris, rather than submerged wood panels, perhaps as a result of the high adaptation to specific environmental conditions. In conclusion, the CCB possess a moderate taxonomical diversity compared to other arid environments, probably as a result of high selective pressures. Nonetheless, due to high spatial and temporal heterogeneity, the functional fungal diversity was considerable as predicted by the intermediate disturbance hypothesis. Decisively, the assessment of microfungal diversity freshwater systems is relevant, since this ecological group of microorganisms represents an important indicator of trophic complexity and biotic interactions among microbial communities, having important implications for understanding eukaryotic survival at the oligotrophic limit for life.


Diethylphosphorus metabolites in serum and urine of persons poisoned by phosalone.
The presence and elimination rate of phosalone and its diethylphosphorus metabolites in blood serum and urine were studied in persons who had ingested a concentrated phosalone solution. Phosalone was detected only in serum samples. As it was rapidly hydrolysed and eliminated from the body, its diethylphosphorus metabolites were a more sensitive indicator of exposure. The concentration decrease of phosalone in serum and of total diethylphosphorus metabolites in serum and urine followed the kinetics of a biphasic reaction. The faster elimination half-times in serum, calculated for two persons, were 2.3 and 3.4 h for phosalone and 3.4 and 38.6 h for total diethylphosphorus metabolites. In the faster phase the average elimination half-time of total urinary metabolites in five persons was 25 +/- 17 h. The kinetic data for total urinary metabolites in a person occupationally exposed to phosalone indicated an early and very fast elimination phase (elimination half-time 1.3 h), which was overlooked in poisoned persons. The proportions of single metabolites in total urinary metabolites in poisoned persons depended on whether the total amount of diethylphosphorus metabolites was above 1000 or below 1000 nmol/mg creatinine. Diethylphosphorodithioate predominated at high and diethylphosphate at low concentrations of total metabolites. The correlation between the maximum concentrations of total metabolites, measured in urine of poisoned persons on the day of admission to hospital or a day later, and the initial depression of serum cholinesterase (EC 184.108.40.206) and erythrocyte acetylcholinesterase (EC 220.127.116.11) activities was poor (r = 0.6).


Results of non-operative treatment of fractures of the glenoid fossa.
Our aim was to investigate the outcomes of patients with a displaced fracture of the glenoid fossa who are treated conservatively. There is little information in the literature about the treatment of these rare injuries non-operatively. We reviewed 24 patients with a mean age of 52 years (19 to 81) at a mean of 5.6 years (11 months to 18 years) after the injury. At final follow-up, the mean Constant and Murley score was 79 points (18 to 98); the mean Western Ontario Shoulder Instability Index score (WOSI) was 77% (12 to 100) and the mean Rowe score was 93 points (50 to 100). Fractures with little intra-articular displacement (≤ 3 mm) had an uneventful outcome. Those with intra-articular displacement of ≤ 3 mm had a significant better mean Constant and Murley score than those with displacement of ≥ 5 mm and/or a fracture gap of ≥ 5 mm. Poor clinical results such as nonunion and post-traumatic osteoarthritis were associated with displaced or angulated glenoid fragments and significant intra-articular displacement. Glenoid fossa fractures with displacement of ≥ 5 mm should be treated surgically if the patient's condition allows. Displacement and angulation can lead to nonunion and a poor outcome if the degree of displacement results in a persistent fracture gap in the glenoid fossa or if the angulation of fragments leads to malunion. Cite this article: Bone Joint J 2016;98-B:1074-9.


Beta(Leu121-Lys122) segment of fibrinogen is in a region essential for plasminogen binding by fibrin fragment E.
It was shown previously that two sequentially nonidentical regions of human fibrin(ogen), present in fragments D and E, carry specific plasminogen-binding sites [V aradi , A., & Patthy , L. (1983) Biochemistry 22, 2440-2446]. Comparison of the affinity of a variety of fragment E species for immobilized Lys-plasminogen revealed that fragment E3e [(alpha 20/24-78, beta 54-122, gamma 1-53)2] possesses a strong plasminogen-binding site, whereas fragment E3t [(alpha 20/24-78, beta 54-120, gamma 1-53)2] has 30-fold lower affinity for the affinant . Since the two fragments differ only in the beta ( Leu121 - Lys122 ) segment, this suggests that residues beta ( Leu121 - Lys122 ), present in the triple-helical connector region of fibrin(ogen), are essential for plasminogen binding by fragment E. Reduction and alkylation of fragment E3e lead to the destruction of the plasminogen-binding site, indicating that none of the separated, alkylated polypeptide chains of the fragment are able to bind to plasminogen and probably the coiled-coil superstructure of the connector region is necessary for the maintenance of the plasminogen-binding site of fragment E.


Containment of herbicide resistance through genetic engineering of the chloroplast genome.
Glyphosate is a potent herbicide. It works by competitive inhibition of the enzyme 5-enol-pyruvyl shikimate-3-phosphate synthase (EPSPS), which catalyzes an essential step in the aromatic amino acid biosynthetic pathway. We report the genetic engineering of herbicide resistance by stable integration of the petunia EPSPS gene into the tobacco chloroplast genome using the tobacco or universal vector. Southern blot analysis confirms stable integration of the EPSPS gene into all of the chloroplast genomes (5000-10,000 copies per cell) of transgenic plants. Seeds obtained after the first self-cross of transgenic plants germinated and grew normally in the presence of the selectable marker, whereas the control seedlings were bleached. While control plants were extremely sensitive to glyphosate, transgenic plants survived sprays of high concentrations of glyphosate. Chloroplast transformation provides containment of foreign genes because plastid transgenes are not transmitted by pollen. The escape of foreign genes via pollen is a serious environmental concern in nuclear transgenic plants because of the high rates of gene flow from crops to wild weedy relatives.


Quality of Care for Patients With Multiple Sclerosis-A Review of Existing Quality Indicators.
Background: The care of patients with multiple sclerosis (MS) calls for a lifelong guidance and treatment and results in a high resource utilization. Therefore, strategies for the assessment and improvement of the care process are crucial. Quality indicators have become a widely used instrument to determine quality in many areas of the healthcare system. The currently available sets of indicators for the quality of MS care are summarized in this review. Methods: A literature search was conducted for reports that include statements on quality indicators for the care of people with MS. For the determination of the strength of the underlying evidence of the identified publications appropriate criteria of the PRISMA and AGREE-Statements were used. A further prioritization of the eligible indicators was based on the internal grading by the initial authors. Results: Of the 465 included records in the search, 6 sources were finally identified, 3 demonstrating a high and the others a medium strength of evidence. In total, these six reports described 226 quality indicators for the treatment of MS. Of them, 147 were further included in the assessment due to the scope of this article. Among the 101 indicators that originated from reports with a high strength of evidence, 6 also had a high initial internal grading. These six identified quality indicators describe five important characteristics of a high-quality care of MS. Conclusion: The search led to a scientifically evident set of six quality indicators for the assessment of care for patients with MS. These should be seen as starting points in the development of comprehensive sets of quality indicators in MS that addresses the individual objective of their use.


alpha Subunit of rat pituitary glycoprotein hormones. Primary structure of the precursor determined from the nucleotide sequence of cloned cDNAs.
Double-stranded complementary DNAs were constructed enzymatically from polyadenylated RNA extracted from pituitary glands of ovariectomized rats, were inserted into the Pst I site of plasmid pBR322 and were cloned in Escherichia coli chi 1776. Cloned cDNAs encoding the precursor to the alpha subunit (pre-alpha) of the glycoprotein hormones were identified by hybridization with a restriction fragment of a previously cloned and sequenced cDNA encoding the precursor to the alpha subunit of mouse thyrotropin (Chin, W. W., Kronenberg, H. M., Dee, P. C., Maloof, F., and Habener, J. F. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 5329-5333). The DNA sequences of the two largest rat cDNA inserts (591 and 554 base pairs) were determined and the amino acid sequence of the rat pre-alpha subunit was deduced from these sequences. The composite sequence determined from these cDNAs spans 610 base pairs, or almost the entire length of the messenger RNA (mRNA) of 800 bases, when account is taken of the 3' poly(A) tract. The rat alpha precursor consists of a 24 amino acid leader sequence and a 96 amino acid alpha subunit apoprotein. The amino acid homologies between the rat and mouse, and between the rat and human sequences are 95% and 74%, respectively. Nucleotide homologies between the rat and mouse cDNAs in the coding and untranslated regions are 94% and 80%, respectively. This cloned cDNA will be applied to analysis of the structure of the rat alpha subunit gene(s) and of the regulation of alpha subunit gene expression.