Performance of SCORE2 and SCORE2-OP risk algorithms in a Cypriot cohort.
SCORE2 and SCORE2-OP algorithms and associated online calculators provide a new and easy method of estimating the 10-year cardiovascular risk in apparently healthy Europeans. The aim of the study was to determine the performance of these algorithms in terms of discrimination and calibration in the cohort of the Cyprus Epidemiological Study on Atherosclerosis (CESA), not only for the 10-year risk for myocardial infarction (MI), stroke and cardiovascular death, but also for all types of atherosclerotic cardiovascular events (ASCVE). SCORE2 and SCORE2-OP for low-risk regions were calculated in a non-diabetic subset of CESA consisting of 908 people (mean age±SD: 57.8±10.5; range 40-89; 58.8% female) using baseline risk factors. Mean follow-up was 13.2±3.7 years (range 1-17) with 89 primary endpoints (MI, stroke and cardiovascular death) and 136 secondary endpoints (primary endpoints, angina, cardiac failure, coronary revascularization, transient ischemic attack, claudication and critical limb ischemia). The C-statistic for the prediction of the primary endpoint for all ages was 0.76 (95% CI 0.70 to 0.81) and the observed 10-year event rate was similar to the predicted one. However, the observed 10-year rate for secondary events was similar to the estimated one only when the algorithm for high-risk regions was used. SCORE2 and SCORE2-OP moderate risk algorithms perform well in the Cypriot population for predicting the 10-year risk for MI, stroke and fatal cardiovascular disease. However, an estimate of the 10-year risk for all ASCVD events is best calculated from the high-risk algorithm.


Hypoxia-inducible factor-2α promotes tumor progression and has crosstalk with Wnt/β-catenin signaling in pancreatic cancer.
Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function. Using several cell lines, mouse models, and human tissues, we obtained a general picture of hif-2α in pancreatic cancer progression. Functional assays revealed that hif-2α promotes epithelial-to-mesenchymal transition, enhances tumor proliferation and invasion, increases stemness, facilitates angiogenesis, and up-regulates aerobic glycolysis. We identified an interaction between hif-2α and β-catenin, and found that hif-2α/β-catenin complex formation increased the activity of β-catenin and the protein stability of hif-2α. In vivo study confirmed the pro-oncogenic role of hif-2α, whose expression correlated with those of E-cadherin, vimentin, Ki-67, and CD31, but not hif-1α. A human tissue study showed that hif-2α was associated with lymph node metastasis, pathological grade, stroma abundance, vascularization and patient survival. High expression of hif-2α was also identified as an independent indicator of poor prognosis in patients with pancreatic cancer. Our systematic study revealed the roles of hif-2α in pancreatic cancer, and may provide a novel target for this highly malignant disease.


FeO x Derived from an Iron-Containing Polyoxometalate Boosting the Photocatalytic Water Oxidation Activity of Ti3+-Doped TiO2.
The development of efficient and stable catalyst systems using low-cost, abundant, and nontoxic materials is the primary demand for photocatalytic water oxidation. Distinguishing the true active species in a heterogeneous catalytic system is important for construction of efficient catalytic systems. Herein, hydrothermally synthesized Ti3+ self-doped TiO2, labeled as Ti3+/TiO2, was first used as a light absorber in a powder visible light-driven photocatalytic water oxidation reaction. When an iron-containing polyoxometalate Na27[Fe11(H2O)14(OH)2(W3O10)2(α-SbW9O33)6] (Fe11) was used as a cocatalyst, an amorphous layer of active species was wrapped outside the initial Ti3+/TiO2 nanorod and the in situ formed composite was labeled as F/Ti3+/TiO2. When the composite F/Ti3+/TiO2 was tested as a photocatalytic water oxidation catalyst, dramatically improved oxygen evolution performance was achieved. The composite F/Ti3+/TiO2 showed an oxygen evolution rate of 410 μmol/g/h, which was about 11-fold higher than that of prism Ti3+/TiO2. After 24 h of illumination, an O2 yield of 36.4% was achieved. The contrast experiments, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy characterization demonstrated that FeO x is the true cocatalyst that enhanced the oxygen evolution activity of TiO2. A recycling experiment proved that the composite F/Ti3+/TiO2 has favorable stability in the oxygen production process.


Outcome of surgical management of developmental dysplasia of hip in children between 18 and 24 months.
Developmental dysplasia of hip (DDH) is a common condition presenting to a pediatric orthopedic surgeon. There is a consensus on the surgical treatment of children with ages ranged from 18 to 24 months where majority agree on open reduction and hip spica. Open reduction was done with an additional pelvic procedure wherever required to get better results and prevent residual acetabular dysplasia (RAD) and early osteoarthritis. 35 children with unilateral DDH were operated between 2002 and 2007 at our institute. Open reduction was performed in all using the standard anterior approach and peroperative test for hip stability was done. Nine children got an additional pelvic procedure in the form of Dega acetabuloplasty. All were followed up for a minimal period of 2 years (range 2-7 years). No hip got redislocated. At the end of 18 months, there were seven cases of RAD with acetabular index (AI) of 35° and above. These were all from the group where open reduction alone was done. We feel that a preoperative AI of >40° and a per-operative safe-zone <20° increases the need for supplementary pelvic osteotomy in age group of 18 to 24 months because in such cases, the remodeling capacity of the acetabulum is unable to overcome the dysplasia and to form a relatively normal acetabulum.


Atomic-scale interactions at the interface of biopolymer/hydroxyapatite.
Molecular dynamics (MD) simulation was used to study chitosan behaviors on different hydroxyapatite (HA) crystallographic planes at the atomic level. The interaction energy between the chitosan chain and different HA surfaces indicates that the interaction of the chitosan chain and HA(1 0 0) surfaces is stronger than that of HA(0 0 1) and HA(1 1 0) surfaces. The chemical interactions between chitosan and HA were analyzed through the concentration profile and pair correlation function of nitrogen and oxygen atoms in chitosan. The results show that there might be chemical interaction between nitrogen and calcium atoms, and hydrogen bonding between oxygen atoms and hydroxyl groups. This study provides useful information in understanding the interfacial interaction mechanism at the atomistic scale.


Retroperitoneoscopic left donor nephrectomy with duplicated IVC.
Vascular anomalies increase the difficulty during live donor nephrectomy. We herein report a left-sided retroperitoneoscopic living donor nephrectomy performed in a donor with a duplicated inferior vena cava (IVC). Computed tomography angiography provided accurate delineation of the venous anatomy and allowed preoperative planning. The duplicated IVC was clipped and divided just below its confluence with the left renal vein. The length of the left renal vein was sufficient for anastomosis in the recipient, and the recipient's serum creatinine was 1.21% on day 7. The donor made an uneventful recovery. Duplicated IVC is not a contraindication for left retroperitoneoscopic donor nephrectomy.


Robust measures of three-dimensional vascular tortuosity based on the minimum curvature of approximating polynomial spline fits to the vessel mid-line.
The clinical recognition of abnormal vascular tortuosity is important in the diagnosis of many diseases. This paper presents a novel approach to the quantification of vascular tortuosity, using robust metrics based on unit speed parameterizations of three-dimensional (3D) curvature. The use of approximating polynomial spline-fitting obviates the need for arbitrary filtering of mid-line data which is necessary with other tortuosity indices. The metrics were tested using both two-dimensional and three-dimensional synthesized images that mimicked clinically significant pathologies: two of the three metrics were scale invariant, additive, and produced tortuosity values tailored to be independent of the resolution of the imaging system. Our methodology is designed to explicitly handle the challenge of noisy data, and is largely tolerant of the inaccuracies in the mid-line extraction. While all the proposed metrics are sensitive to gently curved vessels, the rms curvature of the smoothest path was more effective in recognizing abnormalities involving high-frequency coiling such as occurs in malignant tumors. We have also indicated how values from two projection images, such as acquired in biplane angiography, can be combined to give an accurate approximation of the 3D value of this metric. Our proposed methodology is well-suited to automated detection and measurement, which are a prerequisite for clinical implementation.


Autotransplantation of Mandibular Third Molar with Buccal Cortical Plate to Replace Vertically Fractured Mandibular Second Molar: A Novel Technique.
Tooth replacement often leads to inadequate vertical volume in the recipient site bone when a tooth has been extracted because of a vertical root fracture (VRF). This case report presents the autotransplantation of a mandibular third molar (tooth #32) with the attached buccal cortical plate to replace a mandibular second molar (tooth #31) diagnosed with a VRF. After extraction of tooth #31, the recipient socket was prepared based on the size measured in advance with cone-beam computed tomographic imaging. The precise and calculated osteotomy of the cortical bone of tooth #32 allowed for the exact placement of the donor tooth in the position of tooth #31. The total extraoral time was only 25 minutes. The block was fixed to the recipient socket with an osteosynthesis screw and splinted with a double resin wire for 8 weeks. At the 6-month follow-up, the screw was removed, and the stability of the tooth and the regeneration obtained throughout the vestibular area were confirmed. At the 2-year follow-up, the transplanted tooth was asymptomatic and maintained a normal bone level. Advantages of autotransplantation over dental implants include maintenance of proprioception, possible orthodontic movements, and a relatively low cost. This case report demonstrates that an autotransplantation of a third molar attached to its buccal cortical plate is a viable option to replace teeth with a VRF.


UV Photodetectors Based on BiOCl Nanosheet Arrays: The Effects of Morphologies and Electrode Configurations.
A facile chemical bath method is adopted to grow bismuth oxychloride (BiOCl) nanosheet arrays on a piece of Cu foil (denoted as BiOCl-Cu) and isolated BiOCl nanosheets are collected by ultrasonication. A self-supporting BiOCl film is obtained by the removal of Cu foil. Photodetectors (PDs) based on these BiOCl materials are assembled and the effects of morphologies and electrode configurations on the photoelectric performance of these PDs are examined. The BiOCl nanosheet PD achieves high responsivities in the spectral range from 250 to 350 nm, while it presents quite a small photocurrent and slow response speed. The BiOCl film PD yields low photocurrents and near-unity on-off ratios, demonstrating poor photoelectric performance. The photocurrent of the BiOCl-Cu PD with both electrodes on the BiOCl film is much higher than those of these above-mentioned PDs, and the response times are fast. Meanwhile, the BiOCl-Cu PD with separate electrodes on the BiOCl film and Cu foil achieves even higher photocurrents and presents a self-powering characteristic, depicting the improved photodetecting performances induced by the specific morphology and distinct electrode configuration. These results would promote the applications of BiOCl nanostructures in the photoelectric devices.


Notification of infectious diseases by junior doctors in accident and emergency departments.
To assess the knowledge about notifiable infectious diseases by accident and emergency (A&E) senior house officers. A telephone questionnaire of senior house officers was carried out over a one week period at the end of their six month attachment in A&E departments in Northern Ireland. 81 (91%) of the senior house officers participated in the study; 23 (29%) realised that the doctor diagnosing the notifiable disease had a statutory duty to notify that disease; nine (11%) were aware there were three statutory lists in the United Kingdom. Knowledge about which infectious diseases require notification varied from 79/81 (98%) for meningococcal disease to 15/91 (19%) for methicillin resistant S aureus. Seventy nine (98%) of the doctors thought that a poster displayed in the A&E department would be helpful. There was no significant difference between duration of qualification and performance on the questionnaire (p = 0.2). Despite varying experience, junior doctors in A&E do not know which infectious diseases are notifiable by statute. They felt that it would be helpful to have a poster in the A&E department listing the notifiable diseases of that region. To encourage accurate reporting, interregional variation between the statutory lists should be abolished and replaced by one nationally agreed list.


In-vivo effects of flapless osteopuncture-facilitated tooth movement in the maxilla and the mandible.
This study aimed to investigate the effects of a minimally invasive, flapless procedure to enhance tooth movement in both jaws and to determine whether this triggers the acceleration when repeated monthly. The sample consisted of thirty-two individuals whose orthodontic treatment required canine retraction. They were divided into an experimental group and control group. Osteopunctures were performed using orthodontic mini-screws at the distal aspects of the canine teeth at the beginning and on the fourth week of distalization in the experimental group. The control group was treated with conventional mechanics. All canines were retracted. The rates of canine distalization, rotation, and tipping were measured on the first, fourth, and eighth weeks of distalization. First molar anchorage loss was also measured. Intergroup and intragroup analyses were performed. Flapless osteopuncture-facilitated tooth movement resulted in greater canine distalization and reduced molar movement in the maxilla in the experimental than in the control group during the first month of distalization. In addition, the extent of upper canine movement was significantly higher in the experimental group in the first month than in the second. No differences in canine and molar movement in the mandible were observed between the two groups. OP, as applied in this study, is an effective method for increasing the rate of tooth movement in the maxilla. Repeating the procedure monthly does not appear to show a major advance of tooth movement. Key words:Accelerated tooth movement, flapless osteopuncture.


Peridomestic natural breeding sites of Nyssomyia whitmani (Antunes and Coutinho) in an endemic area of tegumentary leishmaniasis in northeastern Argentina.
The scarce information about breeding sites of phlebotomines limits our understanding of the epidemiology of tegumentary leishmaniasis. Identifying the breeding sites and seasons of immature stages of these vectors is essential to propose prevention and control strategies different from those targeting the adult stage. Here we identified the rural breeding environments of immature stages of Ny. whitmani, vector species of Leishmania braziliensis in the north of Misiones province, Argentina; then we determined and compared the environmental and structural characteristics of those sites. We also identified the season of greatest emergence and its relationship with adult abundance. During a first collection period, between 28 and 48 emergence traps were set continuously for 16 months in six environments of the farm peridomicile and domicile: below house, chicken shed, experimental chicken shed, forest edge, pigsty and under fruit tree. Traps were checked and rotated every 40 nights. A total of 146 newly emerged individuals were collected (93.8% of them were Ny. whitmani), totaling an effort of 23,040 emergence trap-nights. The most productive environments were chicken shed and below house, and the greatest emergence was recorded in spring and summer. During a second collection period, emergence traps and light traps for adult capture were placed in the chicken shed and below house environments of eight farms. Emergence traps were active continuously during spring, summer, and early autumn. Environmental and structural characteristics of each environment were recorded. A total of 84 newly emerged phlebotomines (92.9% Ny. whitmani; 72,144 emergence trap-nights) and 13,993 adult phlebotomines (147 light trap-nights) were recorded in the chicken shed and below house environments. A positive correlation was also observed between trap success of newly emerged phlebotomines and of adults after 120 days. A high spatial variability was observed in the emergence of Ny. whitmani, with the number of newly emerged individuals being highest in soils of chicken sheds with the highest number of chickens and closest to forest edge. Moreover, below house was found to be as important as chicken sheds as breeding sites of Ny. whitmani. Management of the number of chickens in sheds, soil moisture and pH, and the decision of where to localize the chicken sheds in relation to the houses and the forest edge, might contribute to reduce the risk of human vector exposure and transmission of Leishmania.


Effect of short-term exposure to particulate air pollution on heart rate variability in normal-weight and obese adults.
The adverse effects of particulate air pollution on heart rate variability (HRV) have been reported. However, it remains unclear whether they differ by the weight status as well as between wake and sleep. A repeated-measure study was conducted in 97 young adults in Beijing, China, and they were classified by body mass index (BMI) as normal-weight (BMI, 18.5-24.0 kg/m2) and obese (BMI ≥ 28.0 kg/m2) groups. Personal exposures to fine particulate matter (PM2.5) and black carbon (BC) were measured with portable exposure monitors, and the ambient PM2.5/BC concentrations were obtained from the fixed monitoring sites near the subjects' residences. HRV and heart rate (HR) were monitored by 24-h Holter electrocardiography. The study period was divided into waking and sleeping hours according to time-activity diaries. Linear mixed-effects models were used to investigate the effects of PM2.5/BC on HRV and HR in both groups during wake and sleep. The effects of short-term exposure to PM2.5/BC on HRV were more pronounced among obese participants. In the normal-weight group, the positive association between personal PM2.5/BC exposure and high-frequency power (HF) as well as the ratio of low-frequency power to high-frequency power (LF/HF) was observed during wakefulness. In the obese group, personal PM2.5/BC exposure was negatively associated with HF but positively associated with LF/HF during wakefulness, whereas it was negatively correlated to total power and standard deviation of all NN intervals (SDNN) during sleep. An interquartile range (IQR) increase in BC at 2-h moving average was associated with 37.64% (95% confidence interval [CI]: 25.03, 51.51%) increases in LF/HF during wakefulness and associated with 6.28% (95% CI: - 17.26, 6.15%) decreases in SDNN during sleep in obese individuals, and the interaction terms between BC and obesity in LF/HF and SDNN were both statistically significant (p < 0.05). The results also suggested that the effects of PM2.5/BC exposure on several HRV indices and HR differed in magnitude or direction between wake and sleep. Short-term exposure to PM2.5/BC is associated with HRV and HR, especially in obese individuals. The circadian rhythm of HRV should be considered in future studies when HRV is applied.


Fine-scale transition to lower bacterial diversity and altered community composition precedes shell disease in laboratory-reared juvenile American lobster.
The American lobster Homarus americanus supports a valuable commercial fishery in the Northeastern USA and Maritime Canada; however, stocks in the southern portion of the lobster's range have shown declines, in part due to the emergence of shell disease. Epizootic shell disease is a bacterially induced cuticular erosion that renders even mildly affected lobsters unmarketable because of their appearance, and in more severe cases can cause mortality. Despite the importance of this disease, the associated bacterial communities have not yet been fully characterized. We sampled 2 yr old, laboratory-reared lobsters that displayed signs of shell disease at the site of disease as well as at 0.5, 1, and 1.5 cm away from the site of disease to determine how the bacterial community changed over this fine spatial scale. Illumina sequencing of the 16S rRNA gene revealed a distinct bacterial community at the site of disease, with significant reductions in bacterial diversity and richness compared to more distant sampling locations. The bacterial community composition 0.5 cm from the site of disease was also altered, and there was an observable decrease in bacterial diversity and richness, even though there were no signs of disease at that location. Given the distinctiveness of the bacterial community at the site of disease and 0.5 cm from the site of disease, we refer to these communities as affected and transitionary, and suggest that these bacteria, including the previously proposed causative agent, Aquimarina 'homaria', are important for the initiation and progression of this laboratory model of shell disease.


[Geographical distribution and time trends of suicide mortality in Catalonia and Spain [1986-2002]].
To analyze time trends in Catalonia (1986-2002) and Spain (1986-2001) in suicide mortality and its geographical variation by health areas in Catalonia. Standard annual mortality rates were calculated by the direct method for Catalonia (1986-2002) and Spain (1986-2001) (standard population of Catalonia 1991). The adjusted annual percent change was analyzed by means of a Poisson regression by gender and by age group for Catalonia and Spain. For the geographical variation in Catalonia, standardized mortality ratio using the indirect method (SMR) were calculated by gender and for the 46 health areas for the entire period and the comparative mortality figures and its confidence intervals at 95% were analyzed grouping the years in period 1(1986-1994) and period 2 (1995-2002). Men's mortality in Catalonia was lower than in Spain and an increase (not significant) was observed in both places during the period; for women, the evolution and rates were similar, with a small decrease (significant) for Catalonia and Spain. Differences in patterns and trends for age and sex were observed, showing a decrease in the elderly groups for both sexes and an increase for the young for Spain and Catalonia. In terms of geographic distribution, the health sectors of the Central, Northeast and South Catalonia zones show higher than average mortality. The time trends of mortality by suicide in Catalonia shows different patterns according to age and gender. A progressive homogenization in the territorial distribution by health areas was observed.


Dietary requirements and athletic performance of horses.
There is no clear evidence that the chronic requirement for any non-energy yielding nutrient rises in proportion as the energy requirement increases with hard work. The need for protein, and probably that for calcium, remain a function of bodyweight daily. Some proportionality with energy may exist for certain nutrients, although the evidence has not been adduced. For example, because of an increase in both the proportion and amount of propionic acid in the volatile fatty acids of caecal contents, the tissue requirement for vitamin B12 may rise with an increase in the rate of energy metabolism. Exercise influences appetite and therefore voluntary intake, and consequently the daily intake of nutrients. Although that intake is not just a function of dietary bulk and weight, it is necessary to increase energy concentration of diets to achieve an adequate chronic intake of energy where work intensity and energy expenditure are considerable. Acute nutrient requirements paint a different picture from chronic requirements. An increase in total feed intake, or the density of that feed, would neither satisfy these requirements nor be a desirable means of doing so. The acute needs of water, electrolytes and soluble carbohydrates should be met by dosing when the need arises. The timing of the consumption of energy yielding substrates relative to that of exercise may be critical to performance. An inevitable postprandial consequence of a meal of starch or protein by the resting horse, is an increase in the activity of plasma insulin. This increase decreases blood glucose, depriving muscles of a critical substrate, but the assertion has not been resolved by experiment in horses. Experiments are required to ascertain the optimum feeding regime during the 24 h preceding extreme exertion. Whereas exhaustion in sprint work is largely a function of elevated blood lactate concentration, that of extended work is a consequence of a decline in glycogen reserves and losses of body fluid and electrolytes. Glycogen loading is of benefit to many long distance human athletes, but no advantage has yet been established for this practice in horses, and without modification it could render them subject to laminitis and endotoxaemia. Nevertheless supplementation of horses with water, glucose and electrolytes during work may benefit their endurance. The provision of 5 litres water every 2 h with 30 g salt, or twice as much of mixed electrolytes, and 15 g sucrose or glucose, is recommended for a 500 kg horse during periods of extreme sweating.(ABSTRACT TRUNCATED AT 400 WORDS)


[The formation of the child in the womb reproduction and fetal development in medieval Arabic-Islamic medicine].
In the following survey of theories of reproduction and pre-natal development in medieval Arabic medicine, the first part outlines the historical and methodological premises, indicates the major Greek sources (Corpus Hippocraticum, Aristotle, Galen) and introduces the Arabic texts relevant to the subject. In the second part three examples taken from Ibn Sīnās' Canon medicinae are presented to substantiate the supposition that the particular contribution of medieval Islam in the field of reproduction (which continued into the Latin Middle Ages) lay in the merging and harmonisation of data of various origins and concepts developed in different explanatory contexts within the Greek tradition.


Non-invasive acquisition of fetal ECG from the maternal xyphoid process: a feasibility study in pregnant sheep and a call for open data sets.
The utility of fetal heart rate (FHR) monitoring can only be achieved with an acquisition sampling rate that preserves the underlying physiological information on the millisecond time scale (1000 Hz rather than 4 Hz). For such acquisition, fetal ECG (fECG) is required, rather than the ultrasound to derive FHR. We tested one recently developed algorithm, SAVER, and two widely applied algorithms to extract fECG from a single-channel maternal ECG signal recorded over the xyphoid process rather than the routine abdominal signal. At 126dG, ECG was attached to near-term ewe and fetal shoulders, manubrium and xyphoid processes (n = 12). fECG served as the ground-truth to which the fetal ECG signal extracted from the simultaneously-acquired maternal ECG was compared. All fetuses were in good health during surgery (pH 7.29 ± 0.03, pO2 33.2 ± 8.4, pCO2 56.0 ± 7.8, O2Sat 78.3 ± 7.6, lactate 2.8 ± 0.6, BE -0.3 ± 2.4). In all animals, single lead fECG extraction algorithm could not extract fECG from the maternal ECG signal over the xyphoid process with the F1 less than 50%. The applied fECG extraction algorithms might be unsuitable for the maternal ECG signal over the xyphoid process, or the latter does not contain strong enough fECG signal, although the lead is near the mother's abdomen. Fetal sheep model is widely used to mimic various fetal conditions, yet ECG recordings in a public data set form are not available to test the predictive ability of fECG and FHR. We are making this data set openly available to other researchers to foster non-invasive fECG acquisition in this animal model.


Treatment of open femur fractures in children: comparison between external fixator and intramedullary nailing.
Open femur fractures in children are uncommon and usually associated with other injuries. In adults, there is a current trend to treat open fractures with intramedullary (IM) devices. The goal of this study was to compare external fixator (EF) to IM devices in the treatment of open femur fractures in children. Diaphyseal femur fractures without growth plate involvement were included. Thirty-five patients (12 IM; 23 EF) were identified. Age, hospital stay, polytrauma, mechanism of injury, and Gustilo-Anderson grade were recorded. Follow-up was at least until the fracture was clinically and radiographically healed. Patients with EFs were 5.2 times more likely (95% confidence interval, 1.05-25.5) to have any complication. Excluding pin track infections, patients with EFs were 2.7 times as likely (95% confidence interval, 0.567-13.2) to have a complication. Refractures occurred only in the EF group (6/23, 26%) and not in the IM nailing group (P = 0.062, Fischer exact test). These were associated with varus malunions-all 3 of the EF group with more than 15 degrees of varus at fracture union suffered a refracture. Treatment of open femur fractures in children is a challenging problem. Treatment with IM devices had fewer complications than the EF. We think that whenever possible, the use of IM devices for the treatment of open femur fracture in children should be considered, especially grade 1 open injuries. If EFs are used, avoiding varus malunion may decrease the refracture rate, and secondary change to an IM device should be considered. Comparative cohort study. Grade 3 level of evidence.


Shall We Play the Same? Pedagogical Perspectives on Infants' and Children's Imitation of Musical Gestures.
Imitation, both gestural and vocal, has been acknowledged to be at the origin of human communication (Donald, 1991). Music is often considered to be the first means of communication of emotion via both vocal and gestural synchronization (Malloch, 1999; Malloch and Trevarthen, 2009). Instrumental music is part of the human heritage for more than 35,000 years before our era (Aimé et al., 2020). However, very little is known about the acquisition of gestures that produce sounds (i.e., musical gestures) and their role in the development of music and musicality. In the present paper, we propose that studying early synchronous imitation of musical gestures is essential both for investigating the development of the early action-perception system and for outlining early music interventions during infancy. We designed double musical objects which can be used in preschool music education for prompting synchronic imitation of musical gestures between adult and child, and between dyads of infants. We conclude by proposing a novel pedagogical perspective in music education for the early years which links the privileged orientation of infants and children towards sound discoveries with the development of perception-action coupling via imitation of musical gestures.


Expression of vascular endothelial growth factor by cultured endothelial cells from brain microvessels.
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells that may be involved in tumor angiogenesis. Cultured capillary endothelial cells from rat brain (BCEC) express transcripts for VEGF as assayed by Northern blots and polymerase chain reaction analysis. The three forms of VEGF (VEGF120, VEGF164 and VEGF188) are produced, VEGF188 being detected in lower amounts. The sequence of rat VEGF188 was determined. Rat and human exons 6 differ at only one position (human Tyr134-->rat Phe133). Transcripts for VEGF were observed in different clones of rat BCEC, in bovine BCEC but not in bovine aortic endothelial cells.


Modified Oxford technique of colpopexy for the treatment of uterine and vaginal vault prolapse: a retrospective pilot cohort study.
Pelvic organ prolapse is a common health issue that affects 30.8% of women. Laparoscopic sacrocolpopexy and colpopectopexy are two of the most common procedures to restore the pelvic anatomy. Mesh application on the other hand carries an increased complications risk over the short and long terms. The aim of this study is to provide a basis for meshless sacrocolpopexy and colpopectopexy. This study is a retrospective cohort pilot study that analyzed the data of patients with a pelvic organ prolapse according to the pelvic organ prolapse quantification system and underwent the modified technique for sacrocolpopexy and colpopectopexy. Descriptive statistics were used to express the different variables. A total of 36 patients met the inclusion criteria and provided consent for the participation in this study. The majority of patients were postmenopausal. 22 out of 36 patients received a previous prolapse surgery. All patients presented with reducible vaginal lump. Dyspareunia and sexual dysfunction were the most commonly reported symptoms. The intraoperative complications rate was 0%. Only one patient had a postoperative persistent urinary retention that was managed medically. Sacrocolpopexy and colpopectopexy seems to be a safe alternative to the mesh-based pelvic surgeries with a very low rate of intraoperative complications and favorable follow up outcomes.


Work-family conflict and sleep disturbance: the Malaysian working women study.
This study aimed at assessing effect of the four dimensions of work-family conflicts (strain and time-based work interference into family and family interference into work) on sleep disturbance in Malaysian working women. This cross-sectional study was conducted among 325 Malaysian married working women. Multiple-stage simple random sampling method was used to recruit women from public service departments of Malaysia. Self-administrated questionnaires were used to measure the study variables and data were analyzed using SPSS version 21. We found that high level of the four dimensions of work-family conflicts significantly increase sleep disturbance. Our analyses also revealed an age-dependent effect of the work-family conflict on sleep disturbance. Women in their 20 to 30 yr old suffer from sleep disturbance due to high level of time-based and strain-based work-interference into family. However, the quality of sleep among women aged 30-39 were affected by strain-based family-interference into work. Finally, women older than 40 yr had significantly disturbed sleep due to strain-based work-interference into family as well as time-based family interference into work. Our findings showed that sleep quality of working women might be disturbed by experiencing high level of work-family conflict. However, the effects of inter-role conflicts on sleep varied among different age groups.


Surgical treatment options for cartilage defects within the knee.
Injury to articular cartilage is increasingly diagnosed as a cause of knee pain. New surgical treatment options are now available to treat this clinical entity. Diagnosis is made easier by improved magnetic resonance imaging protocols that better visualize articular cartilage. On physical examination, patients at any age can have joint surface damage and primarily experience joint line tenderness and pain with activity. Treatment options include debridement of nonviable cartilage with abrasion or microfracture of the subchondral bone, transplantation of autologous osteochondral plugs, autologous chondrocyte transplantation, transplantation of cadaveric allogenic osteochondral grafts, and, for irreparable damage, total knee arthroplasty. These newer treatment options show promising early and intermediate results.


The pulmonary involvement in Theileria lestoquardi naturally infected sheep.
Malignant Ovine Theileriosis (MOT) caused by Theileria lestoquardi is considered a major constraint for sheep production in many areas of the world including Sudan. Pulmonary oedema is thought to be the main cause of animal death, but the mechanism, the cell types involved and/or the probable cause of this pneumonia has yet to be defined. The present study was carried out to investigate the pulmonary involvement post T. lestoquardi infection and to identify the cell types involved in pneumonia. Apparently healthy sheep were exposed to ticks challenge in T. lestoquardi endemic area. Lungs impression smears and tissue sections for histopathology were processed. At necropsy, fifteen infected sheep revealed severe pneumonia associated with oedema and accumulation of creamy-grayish frothy exudates. The microscopic findings of examined lungs showed emphysema, congestion, collapse and proliferation of immense amount of different kinds of cells. The current study indicates that T. lestoquardi infections are accompanied with remarkable pulmonary involvements and may lead to respiratory failure and death.


Immunoglobulin metabolism in disease.
Immunodeficiency and hypogammaglobulinemia are shown to occur by a variety of pathophysiologic mechanisms. Hypogammaglobulinemia may be caused by decreased synthesis of all classes of immunoglobulins, or may involve defective synthesis of selective classes of immunoglobulins. Alternatively, hypogammaglobulinemia may be due to a disorder of endogenous catabolic pathways of a single immunoglobulin class, or of all immunoglobulin classes. Finally, hypogammaglobulinemia may be caused by excessive loss of immunoglobulins into the urinary or gastrointestinal tracts.


Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH.
Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥ 3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation.


Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.
Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.


Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression.
Accumulating evidence shows that hallmarks of cancer include: "genetic and epigenetic alterations leading to inactivation of cancer suppressors, overexpression of oncogenes, deregulation of intracellular signaling cascades, alterations of cancer cell metabolism, failure to undergo cancer cell death, induction of epithelial to mesenchymal transition, invasiveness, metastasis, deregulation of immune response and changes in cancer microenvironment, which underpin cancer development". Natural compounds as bioactive ingredients isolated from natural sources (plants, fungi, marine life forms) have revolutionized the field of anticancer therapeutics and rapid developments in preclinical studies are encouraging. Natural compounds could affect the epigenetic molecular mechanisms that modulate gene expression, as well as DNA damage and repair mechanisms. The current review will describe the latest achievements in using naturally produced compounds targeting epigenetic regulators and modulators of gene transcription in vitro and in vivo to generate novel anticancer therapeutics.


Seasonal variations in vertical migration of glacier lanternfish, Benthosema glaciale.
The seasonal variations in glacier lanternfish (Benthosema glaciale) vertical distribution and diel vertical migration (DVM) were studied by use of a bottom-mounted upward-facing 38 kHz echo sounder deployed at 392 m depth and cabled to shore in Masfjorden (~60°52'N, ~5°24'E), Norway. Acoustic data from July 2007-October 2008 were analyzed, and scattering layers below ~220 m during daytime were attributed to glacier lanternfish based on net sampling in this, and previous studies, as well as from analysis of the acoustic data. At these depths, three different diel behavioral strategies were apparent: normal diel vertical migration (NDVM), inverse DVM (IDVM), and no DVM (NoDVM). NoDVM was present all year, while IDVM was present in autumn and winter, and NDVM was present during spring and summer. The seasonal differences in DVM behavior seem to correlate with previously established seasonal distribution of prey. We hypothesize that in regions with seasonally migrating zooplankton, such as where calanoid copepods overwinter at depth, similar plasticity in DVM behavior might occur in other populations of lanternfishes.


Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit.
Defects of peripheral nerves still represent a challenge for surgical nerve reconstruction. Recent studies concentrated on replacement by artificial nerve conduits from different synthetic or biological materials. In our study, we describe for the first time the use of spider silk fibres as a new material in nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk fibres. Cells adhered quickly on the fibres compared to polydioxanone monofilaments (PDS). SC survival and proliferation was normal in Live/Dead assays. The silk fibres were ensheathed completely with cells. We developed composite nerve grafts of acellularized veins, spider silk fibres and SC diluted in matrigel. These artificial nerve grafts could be cultivated in vitro for one week. Histological analysis showed that the cells were vital and formed distinct columns along the silk fibres. In conclusion, our results show that artificial nerve grafts can be constructed successfully from spider silk, acellularized veins and SC mixed with matrigel.


Production of microbial biosurfactants: Status quo of rhamnolipid and surfactin towards large-scale production.
Surfactants are an important class of industrial chemicals. Nowadays oleochemical surfactants such as alkyl polyglycosides (APGs) become increasingly important. This trend towards the utilization of renewable resources continues and consumers increasingly demand for environmentally friendly products. Consequently, research in microbial surfactants has drastically increased in the last years. While for mannosylerythritol lipids and sophorolipids established industrial processes exist, an implementation of other microbially derived surfactants has not yet been achieved. Amongst these biosurfactants, rhamnolipids synthesized by Pseudomonas aeruginosa and surfactin produced by Bacillus subtilis are so far the most analyzed biosurfactants due to their exceptional properties and the concomitant possible applications. In this review, a general overview is given regarding the current status of biosurfactants and benefits attributed to these molecules. Furthermore, the most recent research approaches for both rhamnolipids and surfactin are presented with respect to possible methods for industrial processes and the occurring drawbacks and limitations researchers have to address and overcome.


Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor.
Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m2. We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m2, in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy.


Sequential imaging of indium-111-labeled monoclonal antibody in human mammary tumors hosted in nude mice.
Using a bifunctional chelating agent, indium-111 was attached to a monoclonal antibody 10- 3D2 , specific for a 126-kilodalton phosphoglycoprotein antigen associated with human mammary carcinoma, and was then used to localize and visualize human mammary tumors hosted in nude mice. Simultaneous tumor concentration of In-111-10- 3D2 was eight times greater than that of control I-125-MOPC-21. Uptake of F(ab')2 and Fab of 10- 3D2 was also compared. the scintigrams demonstrated that intact antibody provided the best images. Control In-111-labeled MOPC-21 and plasma did not show specific localization in the tumor. Uptake of In-111-labeled 10- 3D2 was also compared in two lines of human mammary tumors, BT-20 and HS- 578T . Imaging with 10- 3D2 was better for BT-20 than for HS- 578T . These studies demonstrated that (a) In-111-10- 3D2 can be utilized to image human mammary tumors hosted in nude mice; (b) intact antibody provided the best tumor images, although F(ab')2 had optimal target-to-background ratios for earlier imaging; and (c) different mammary tumor lines with possibly different concentrations of tumor-associated antigen showed different rates of uptake and apparent saturation with 10- 3D2 .


Blood Flow Restriction Resistance Exercise Improves Muscle Strength and Hemodynamics, but Not Vascular Function in Coronary Artery Disease Patients: A Pilot Randomized Controlled Trial.
Resistance training may be associated with unfavorable cardiovascular responses (such as hemodynamic alterations, anginal symptoms or ventricular arrhythmias). In healthy adults, blood flow-restricted (BFR) resistance training improves muscle strength and hypertrophy improvements at lower loads with minimal systemic cardiovascular adverse responses. The aim of this study was to assess the safety and efficacy of BFR resistance training in patients with coronary artery disease (CAD) compared to usual care. Patients with stable CAD were randomized to either 8 weeks of supervised biweekly BFR resistance training (30-40% 1RM unilateral knee extension) or usual exercise routine. At baseline and after 8 weeks, patients underwent 1-RM knee extension tests, ultrasonographic appraisal of vastus lateralis (VL) muscle diameter and of systemic (brachial artery) flow-mediated dilation, and determination of markers of inflammation (CD40 ligand and tumor necrosis factor alfa), and fasting glucose and insulin levels for homeostatic model assessment (HOMA). A total of 24 patients [12 per group, mean age 60 ± 2 years, 6 (25%) women] were included. No training-related adverse events were recorded. At baseline groups significantly differ in age (mean difference: 8.7 years, p < 0.001), systolic blood pressure (mean difference: 12.17 mmHg, p = 0.024) and in metabolic control [insulin (p = 0.014) and HOMA IR (p = 0.014)]. BFR-resistance training significantly increased muscle strength (1-RM, +8.96 kg, p < 0.001), and decreased systolic blood pressure (-6.77 mmHg; p = 0.030), whereas VL diameter (+0.09 cm, p = 0.096), brachial artery flow-mediated vasodilation (+1.55%; p = 0.079) and insulin sensitivity (HOMA IR change of 1.15, p = 0.079) did not improve significantly. Blood flow restricted resistance training is safe and associated with significant improvements in muscle strength, and may be therefore provided as an additional exercise option to aerobic exercise to improve skeletal muscle functioning in patients with CAD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03087292.


Allulose in human diet: the knowns and the unknowns.
D-Allulose, also referred to as psicose, is a C3-epimer of D-fructose used as a sugar substitute in low energy products. It can be formed naturally during processing of food and drinks containing sucrose and fructose or is prepared by chemical synthesis or via enzymatic treatment with epimerases from fructose. Estimated intakes via Western style diets including sweetened beverages are below 500 mg per d but, when used as a sugar replacement, intake may reach 10 to 30 g per d depending on the food consumed. Due to its structural similarity with fructose, allulose uses the same transport and distribution pathways. But in contrast to fructose, the human genome does not encode for enzymes that are able to metabolise allulose leading to an almost complete renal excretion of the absorbed dose and near-to-zero energetic yield. However, in vitro studies have shown that certain bacteria such as Klebsiella pneumonia are able to utilise allulose as a substrate. This finding has been a subject of concern, since Klebsiella pneumoniae represents an opportunistic human pathogen. It therefore raised the question of whether a high dietary intake of allulose may cause an undesirable growth advantage for potentially harmful bacteria at mucosal sites such as the intestine or at systemic sites following invasive infection. In this brief review, we discuss the current state of science on these issues and define the research needs to better understand the fate of allulose and its metabolic and microbiological effects when ingested as a sugar substitute.


Idiopathic gross dilatation of the pancreatic duct with exocrine insufficiency in a patient with type 1 neurofibromatosis.
Pancreatic duct dilatation occurs in conditions including chronic pancreatitis, pancreatic carcinoma and intraductal papillary mucinous neoplasms. Although several pancreatic benign and malignant tumours have been reported in association with type 1 neurofibromatosis, an association with gross pancreatic duct dilatation or ectasia has not been previously published. We report on a patient with type 1 neurofibromatosis found to have idiopathic gross pancreatic duct dilatation and exocrine insufficiency. A 51-year-old female with type 1 neurofibromatosis presented with weight loss and steatorrhoea. Computed tomography and magnetic resonance cholangiopancreatography showed a possible cystic lesion in the head of the pancreas, a grossly dilated main pancreatic duct and minimal thinned out pancreatic parenchyma. Endosonography confirmed diffuse dilatation of the pancreatic duct with no evidence of a separate cystic neoplasm. Endosonography-guided aspiration revealed non-mucinous, clear fluid with high amylase and normal carcinoembryonic antigen levels. The patient was prescribed pancreatic enzyme supplementation and showed symptomatic improvement. Associations between type 1 neurofibromatosis and pancreatic duct ectasia or chronic pancreatitis have not been reported, and this finding may be coincidental. Clinical presentation in conjunction with multimodal imaging and biochemical and cytological fluid analysis did not reveal the aetiology of the ectatic duct system and attenuated glandular tissue in this patient which is most likely congenital.


Twenty-five years of hospital and community psychiatry: 1945-1970.
The author, the first medical director of the American Psychiatric Association and APA president in 1964-65, presents a historical review of the 25 years between 1945 and 1970, a period in which there was a reawakening of interest in the mentally ill and mentally retarded after years of neglect. He lists major landmarks in mental health care during those years, describes the first Mental Hospital Institiute held by the American Psychiatric Association in 1949, and presents an anecdotal footnote about the Joint Commission on Mental Illness and Health.


Structural and energetic characterizations of thin multi-walled carbon nanotubes using adsorption isotherms.
The structural and energetic heterogeneity of thin multi-walled carbon nanotubes (t-MWCNTs) was evaluated from the adsorption of nitrogen and aromatic compounds (benzene, toluene, and m-xylene). The t-MWCNTs was synthesized through the catalytic vapor deposition and characterized by using nitrogen adsorption-desorption isotherm and high-resolution transmission electron microscopy (HRTEM) analyses. The equilibrium adsorption data of aromatic compounds on t-MWCNTs were measured using gravimetric apparatus at three different temperatures (303.15, 313.15 and 323.15 K) and at pressures up to 4.0 kPa. The temperature dependent Toth isotherm model was employed to correlate the experimental adsorption isotherm data. The isosteric heat of adsorption was calculated from van't Hoff equation using the temperature dependent Toth isotherm parameters. The adsorption energy distributions (AEDs) were calculated from adsorption isotherms data of nitrogen and aromatic molecules to investigate the surface energetic heterogeneity of t-MWCNTs. The results of pore size distributions, isosteric heats of adsorption and AEDs revealed that t-MWCNTs have structurally and energetically heterogeneous surface.


A man in his sixties with acute chest pain.
Chest pain is a frequent symptom of acute myocardial infarction, but the cause is not always coronary atherothrombosis. We present a case where the patient himself had made a correct non-cardiac diagnosis, but this was initially overlooked by the doctor. A man with a history of cardiac infarction was admitted with acute chest pain and troponin elevation. Electrocardiogram suggested ST elevations, echocardiography showed a possible slight hypokinesia, and we primarily suspected an acute coronary syndrome. However, invasive coronary angiography was negative and a primary acute myocardial infarction was less likely. A renewed interview revealed that the patient had worked with a propane burner indoors without adequate ventilation. The patient himself suspected carbon monoxide poisoning. Arterial blood gas showed HbCO 27.4 %, which was unfortunately overlooked initially. The patient had carbon monoxide poisoning with symptoms of dizziness, hand ataxia and myocardial ischaemia. He received 100 % oxygen and HbCO was normalised. The imbalance between oxygen demand and supply resulted in a type 2 cardiac infarction. A thorough medical history is crucial for correct diagnosis but can unfortunately be missed on a busy shift. This case illustrates the importance of the patient's own diagnostic assumption.


A generalization of the membrane-plate analogy to non-homogeneous polygonal domains consisting of homogeneous subdomains.
The well-known membrane-plate analogy that relates the natural frequencies when dealing with polygonal homogeneous domains is herein extended to non-homogeneous systems comprised of homogeneous subdomains. The analogy is generalized and demonstrated and it is shown that certain restrictions among the frequency parameters of the membranes and plates arise. Several examples of membranes and plates with interfaces separating areas with different material properties are numerically solved with different approaches. The subdomains are separated by straight, curved, and closed line interfaces. It is shown that the analogy is verified provided that the restrictions are satisfied. The analogy is first demonstrated and presented as a practical methodology to find the natural frequencies of membranes knowing the corresponding ones of the plates or vice versa. Second, the plate and membrane vibration problems, governed by the bi-Laplacian and Laplacian differential operators, respectively, can be solved without distinction, though under certain conditions, i.e., solve one of them and deduce the other using the analogy. Various numerical examples validate the analogy.


Identification and analysis of Hic-5/ARA55 isoforms: Implications for integrin signaling and steroid hormone action.
Hic-5/ARA55 is a LIM-only member of the paxillin superfamily. Conflicting reports have suggested that Hic-5/ARA55 can both repress and enhance a number of biological processes, including myogenesis and tumorigenesis. With two Hic-5 isoforms documented, we hypothesized that multiple Hic-5 isoforms may exist that have both overlapping and isoform-specific functions. To test this hypothesis, we performed an extensive analysis of Hic-5 transcripts in both cell lines and mouse tissues and found 12 distinct isoforms that fall into two sub-families. These isoforms are derived from both alternative splicing and alternative transcriptional start sites (TSS). Hic-5 expression is regulated in a temporally and spatially controlled manner in vivo. The identification of numerous Hic-5 isoforms suggests that Hic-5 subsumes a number of distinct roles in cells and may explain the range of biological responses attributed to Hic-5.


"Nowadays it isn't easy to advise the young": Grandmothers and granddaughters among Abaluyia of Kenya.
Among Abaluyia of Kenya relative age (seniority) structures relationships hierarchically among co-wives, siblings and females of different generations. Ambiguous equality and affectionate informality in grandmother-granddaughter relationships mute the hierarchical implications of their different age and generation statuses. This facilitates grandmothers' educational roles although, as grandmothers say, "Nowadays it isn't easy to advise the young". Increased physical, cognitive and experiential distances between these generations resulted from radical changes in the female lifecourse associated with modernization and delocalization. Nevertheless, reciprocal exchanges continue. Granddaughters are also intermediaries in exchanges between older women and their adult daughters. Some grandmothers are denied the companionship and assistance of granddaughters caught in the middle of mother-in-law/daughter-in-law conflicts. Many grandmothers assume parental responsibilities as they deal with the modern problem of daughters' premarital pregnancies. All in all, these intergenerational relationships reveal both cultural persistence and the effects of social change, and continue to have instrumental and expressive value for both grandmothers and granddaughters.


The N-terminal rhodanese domain from Azotobacter vinelandii has a stable and folded structure independently of the C-terminal domain.
Sulfurtransferase are enzymes involved in the formation, conversion and transport of compounds containing sulfane-sulfur atoms. Although the three-dimensional structure of the rhodanese from the nitrogen-fixing bacterium Azotobacter vinelandii is known, the role of its two domains in the protein conformational stability is still obscure. We have evaluated the susceptibility to proteolytic degradation of the two domains of the enzyme. The two domains show different resistance to the endoproteinases and, in particular, the N-terminal domain shows to be more stable to digestion during time than the C-terminal one. Cloning and overexpression of the N-terminal domain of the protein was performed to better understand its functional and structural role. The recombinant N-terminal domain of rhodanese A. vinelandii is soluble in water solution and the spectroscopic studies by circular dichroism and heteronuclear NMR spectroscopy indicate a stable fold of the protein with the expected alpha/beta topology. The results indicate that this N-terminal domain has already got all the elements necessary for an C-terminal domain independent folding. Its solution structure by NMR, actually under course, will be a valid contribution to understand the role of this domain in the folding process of the sulfurtransferase.


Tacrolimus interaction with dexmedetomidine--a case report.
Drugs and xenobiotics that inhibit the CYP-450 isoenzyme 3A4 are associated with increased serum tacrolimus levels. We sought to determine whether there was a temporal association between initiation of dexmedetomidine and increased serum tacrolimus levels. An interaction has not been previously documented. We reviewed tacrolimus levels and dosing in a pediatric patient aged 8 months who had undergone deceased-donor liver transplantation for biliary atresia and later required sedation with dexmedetomidine continuous infusion during the POD (212-216). Serum tacrolimus trough levels increased 4-fold from 3.4 to 13.1 ng/mL (tacrolimus regimen: 1 mg every 12 h) within 21 h of initiating dexmedetomidine. During dexmedetomidine infusion, serum tacrolimus trough levels were maintained with doses that were 25% of baseline tacrolimus dose. Tacrolimus trough levels decreased to below goal range within 30-40 h of discontinuation of dexmedetomidine. Data submitted to the U.S. Food and Drug Administration demonstrate that dexmedetomidine inhibits CYP 3A4 and may produce adequate liver concentrations that could interfere with tacrolimus metabolism. We suggest that tacrolimus levels should be carefully monitored in children receiving prolonged infusions of dexmedetomidine to avoid adverse events associated with elevated tacrolimus levels.


LysM Proteins Regulate Fungal Development and Contribute to Hyphal Protection and Biocontrol Traits in Clonostachys rosea.
Lysin motif (LysM) modules are approximately 50 amino acids long and bind to peptidoglycan, chitin and its derivatives. Certain LysM proteins in plant pathogenic and entomopathogenic fungi are shown to scavenge chitin oligosaccharides and thereby dampen host defense reactions. Other LysM proteins can protect the fungal cell wall against hydrolytic enzymes. In this study, we investigated the biological function of LysM proteins in the mycoparasitic fungus Clonostachys rosea. The C. rosea genome contained three genes coding for LysM-containing proteins and gene expression analysis revealed that lysm1 and lysm2 were induced during mycoparasitic interaction with Fusarium graminearum and during colonization of wheat roots. Lysm1 was suppressed in germinating conidia, while lysm2 was induced during growth in chitin or peptidoglycan-containing medium. Deletion of lysm1 and lysm2 resulted in mutants with increased levels of conidiation and conidial germination, but reduced ability to control plant diseases caused by F. graminearum and Botrytis cinerea. The Δlysm2 strain showed a distinct, accelerated mycelial disintegration phenotype accompanied by reduced biomass production and hyphal protection against hydrolytic enzymes including chitinases, suggesting a role of LYSM2 in hyphal protection against chitinases. The Δlysm2 and Δlysm1Δlysm2 strains displayed reduced ability to colonize wheat roots, while only Δlysm1Δlysm2 failed to suppress expression of the wheat defense response genes PR1 and PR4. Based on our data, we propose a role of LYSM1 as a regulator of fungal development and of LYSM2 in cell wall protection against endogenous hydrolytic enzymes, while both are required to suppress plant defense responses. Our findings expand the understanding of the role of LysM proteins in fungal-fungal interactions and biocontrol.


Review of the epidemiological literature on antidepressant use and breast cancer risk.
Based on evidence that antidepressants increase levels of prolactin and may promote the growth of mammary tumor cells, there has been concern that the use of these drugs may increase the risk of breast cancer. This article reviews the epidemiological evidence on the relationship between breast cancer risk and the use of the selective serotonin reuptake inhibitors, the tricyclic antidepressants and other antidepressants. Overall, the evidence does not support the hypothesis that the use of antidepressants increases the risk of breast cancer. There is a dearth of data on long-term selective serotonin reuptake inhibitor use. Since these drugs are commonly used, it is prudent public health policy to monitor breast cancer incidence among women using this class of drug for long durations.


Comparison among various expressions of complex admittance for quantum systems in contact with a heat reservoir.
Relation among various expressions of the complex admittance for quantum systems in contact with heat reservoir is studied. Exact expressions of the complex admittance are derived in various types of formulations of equations of motion under contact with heat reservoir. Namely, the complex admittance is studied in the relaxation method and the external-field method. In the former method, the admittance is calculated using the Kubo formula for quantum systems in contact with heat reservoir in no external driving fields, while in the latter method the admittance is directly calculated from equations of motion with external driving terms. In each method, two types of equation of motions are considered, i.e., the time-convolution (TC) equation and time-convolutionless (TCL) equation. That is, the full of the four cases are studied. It is turned out that the expression of the complex admittance obtained by using the relaxation method with the TC equation exactly coincides with that obtained by using the external-field method with the TC equation, while other two methods give different forms. It is also explicitly demonstrated that all the expressions of the complex admittance coincide with each other in the lowest Born approximation for the system-reservoir interaction. The formulas necessary for the higher-order expansions in powers of the system-reservoir interaction are derived, and also the expressions of the admittance in the nth order approximation are given. By transforming inverse-temperature integrals into time integrals, the admittances are also given in the formulas with time-integrals alone. To characterize the TC and TCL methods, we study the expressions of the admittances of two exactly solvable models. Each exact form of admittance is compared with the results of the two methods in the lowest Born approximation. It is found that depending on the model, either of TC and TCL would be the better method.


Benign extraaxial tumors: contrast enhancement with Gd-DTPA.
Meningiomas, acoustic neuromas, and other benign extraaxial tumors have little contrast with adjacent brain tissue on conventional magnetic resonance (MR) images. The contrast enhancement produced by intravenous administration of 0.1 mmol/kg of gadolinium-DTPA in these tumors was measured on T1 MR images. Acoustic neuromas showed the greatest enhancement (average, 310%), meningiomas the next greatest (average, 180%), and neurofibromas, glomus tumors, and pituitary microadenomas the least enhancement. The degree of enhancement was almost always greater at 3 minutes than at 25 or 55 minutes. Contrast between the tumor and adjacent tissue resulted from tumor enhancement in neuromas, meningiomas, and neurofibromas and from enhancement of the surrounding tissue in pituitary microadenomas.


[The experience with the surgical treatment of glomus tumours].
glomus tumours of the temporal bones rank second after neurinomas of the VII-th pair of cranial nerves among the pathological conditions that are likely to cause hearing mpairment. Being extensively vascularized locally invasive neoplasms, glomus tumours constitute a serious challenge for the surgeon because of their localization in the vicinity of the vitally important vascular and neural structures of the lateral skull base. To characterize some peculiar features of the surgical interventions and postoperative management of the patients presenting with different types of glomus tumours. our experience is based on the surgical treatment of 15 patients with glomus tumours of the temporal bones of varying extent and localization. It is concluded that the magnitude and extent of the surgical intervention and of the follow-up examination depend on the spread of the neoplasm. The treatment of the B, S, D - type tumours implies the necessity of pre-operative embolization of the vessels feeding the neoplasm.


Cholescintigraphy in the critically ill.
Critical review of cholescintigraphy in critically ill patients suggests the examination will not conclusively prove or disprove the diagnosis of acute cholecystitis. Of 17 scans performed in critically ill patients with clinical evidence of acute cholecystitis, 7 were true-negative, 1 was false-negative, 6 were false-positive, and 3 were nondiagnostic. Cholestasis and hepatocyte dysfunction, common in the critically ill, result in abnormal clearance of hepatobiliary radionuclide imaging agents, decreasing the usefulness of cholescintigraphy in this patient population. Diagnosing acute cholecystitis in a critically ill patient remains difficult.


'Suppressed' double adenoma--a rare pitfall in minimally invasive parathyroidectomy.
Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.


Molecular Mechanism of Polysaccharide Acetylation by the Arabidopsis Xylan O-acetyltransferase XOAT1.
Xylans are a major component of plant cell walls. O-Acetyl moieties are the dominant backbone substituents of glucuronoxylan in dicots and play a major role in the polymer-polymer interactions that are crucial for wall architecture and normal plant development. Here, we describe the biochemical, structural, and mechanistic characterization of Arabidopsis (Arabidopsis thaliana) xylan O-acetyltransferase 1 (XOAT1), a member of the plant-specific Trichome Birefringence Like (TBL) family. Detailed characterization of XOAT1-catalyzed reactions by real-time NMR confirms that it exclusively catalyzes the 2-O-acetylation of xylan, followed by nonenzymatic acetyl migration to the O-3 position, resulting in products that are monoacetylated at both O-2 and O-3 positions. In addition, we report the crystal structure of the catalytic domain of XOAT1, which adopts a unique conformation that bears some similarities to the α/β/α topology of members of the GDSL-like lipase/acylhydrolase family. Finally, we use a combination of biochemical analyses, mutagenesis, and molecular simulations to show that XOAT1 catalyzes xylan acetylation through formation of an acyl-enzyme intermediate, Ac-Ser-216, by a double displacement bi-bi mechanism involving a Ser-His-Asp catalytic triad and unconventionally uses an Arg residue in the formation of an oxyanion hole.


A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: a case study for marker-assisted selection in grapevine.
Marker-assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next-generation sequencing and its derivative technologies have been used for genome-wide molecular marker discovery. To bridge the gap between marker development and MAS implementation, this study developed a novel practical strategy with a semi-automated pipeline that incorporates trait-associated single nucleotide polymorphism marker discovery, low-cost genotyping through amplicon sequencing (AmpSeq) and decision making. The results document the development of a MAS package derived from genotyping-by-sequencing using three traits (flower sex, disease resistance and acylated anthocyanins) in grapevine breeding. The vast majority of sequence reads (⩾99%) were from the targeted regions. Across 380 individuals and up to 31 amplicons sequenced in each lane of MiSeq data, most amplicons (83 to 87%) had <10% missing data, and read depth had a median of 220-244×. Several strengths of the AmpSeq platform that make this approach of broad interest in diverse crop species include accuracy, flexibility, speed, high-throughput, low-cost and easily automated analysis.


Persistent learning signals and working memory without continuous attractors.
Neural dynamical systems with stable attractor structures, such as point attractors and continuous attractors, are hypothesized to underlie meaningful temporal behavior that requires working memory. However, working memory may not support useful learning signals necessary to adapt to changes in the temporal structure of the environment. We show that in addition to the continuous attractors that are widely implicated, periodic and quasi-periodic attractors can also support learning arbitrarily long temporal relationships. Unlike the continuous attractors that suffer from the fine-tuning problem, the less explored quasi-periodic attractors are uniquely qualified for learning to produce temporally structured behavior. Our theory has broad implications for the design of artificial learning systems and makes predictions about observable signatures of biological neural dynamics that can support temporal dependence learning and working memory. Based on our theory, we developed a new initialization scheme for artificial recurrent neural networks that outperforms standard methods for tasks that require learning temporal dynamics. Moreover, we propose a robust recurrent memory mechanism for integrating and maintaining head direction without a ring attractor.


Comparative cost analysis of myringotomy with insertion of ventilation tubes in Ontario and British Columbia.
The purpose of this study was to conduct a comparative cost analysis of myringotomy with insertion of ventilation tube (MVT) for children performed at two regional paediatric centres: The Hospital for Sick Children, and the British Columbia Children's Hospital. Comparative cost analysis. The Hospital for Sick Children (HSC), Toronto, and the British Columbia Children's Hospital (BCCH), Vancouver. The cost analysis was performed from a health system perspective using a treatment protocol developed through a review of the literature and input from staff from each of the study hospitals. MVT cost estimates were derived, including direct treatment costs and overhead costs. Total costs per MVT case (in 1994 Canadian dollars: Cdn$ 1.00 approximately US$ 0.75) varied from $390.81 at BCCH to $455.63 at HSC. Regional variations in physician costs accounted for almost 70% of the difference in MVT case costs. The distribution of nonphysician MVT case costs were similar in each study hospital, with direct (nonphysician) surgical costs, preoperative assessment and recovery room costs, and administration accounting for 30%, 26%, and 44% of total nonphysician costs, respectively. This study identified the magnitude and determinants of regional variations in the cost of MVT surgery. Such cost estimates serve as an important (but not the sole) ingredient in service cost-effectiveness deliberations and in the formulation of evidence-based care when health care resources are scarce.


Brain single photon emission computed tomography in neonates.
This study was designed to rate the clinical value of [123I]iodoamphetamine (IMP) or [99mTc] hexamethyl propylene amine oxyme (HM-PAO) brain single photon emission computed tomography (SPECT) in neonates, especially in those likely to develop cerebral palsy. The results showed that SPECT abnormalities were congruent in most cases with structural lesions demonstrated by ultrasonography. However, mild bilateral ventricular dilatation and bilateral subependymal porencephalic cysts diagnosed by ultrasound were not associated with an abnormal SPECT finding. In contrast, some cortical periventricular and sylvian lesions and all the parasagittal lesions well visualized in SPECT studies were not diagnosed by ultrasound scans. In neonates with subependymal and/or intraventricular hemorrhage the existence of a parenchymal abnormality was only diagnosed by SPECT. These results indicate that [123I]IMP or [99mTc]HM-PAO brain SPECT shows a potential clinical value as the neurodevelopmental outcome is clearly related to the site, the extent, and the number of cerebral lesions. Long-term clinical follow-up is, however, mandatory in order to define which SPECT abnormality is associated with neurologic deficit.


The diagnostic standard of preclinical Cushing's syndrome: evaluation of the dexamethasone suppression test using various cortisol kits.
Incidental discovery of an adrenal mass, the so-called adrenal incidentaloma, has been increasing due to the advances in non-invasive diagnostic imaging tools. The criteria of diagnosis for preclinical Cushing's syndrome (preCS) in Japan were made by Nawata et al. supported by the Ministry of Health and Welfare in 1995. The results of suppression of cortisol by dexamethasone (DEX) (plasma cortisol above 3 microg/dl after 1 mg of DEX and above 1 microg/dl after 8 mg of DEX) are essential for the diagnosis of preCS due to an adrenal adenoma. However, plasma cortisol levels after the two doses of DEX suppression tests were found to be discrepant and repeated DEX suppression tests sometimes yielded different results. Therefore, we examined the cortisol values of DEX suppression tests in patients with preCS using four different cortisol assay kits: Amerlex cortisol kit (AMA), SPAC-S cortisol kit (SPA), ADVIA-Centaur cortisol assay (ADV) and ECLusys 2010 cortisol assay (ECL). The diagnosis for preCS was done using the AMA kit. Correlation between the kits was good. However, cortisol levels measured by SPA, ADV and ECL were lower than those measured by AMA. In the 1 mg DEX test, the cortisol levels measured with the SPA, ADV and ECL kits were suppressed in 2 patients with preCS. With 8 mg of DEX, cortisol levels measured with the SPA and ADV kits were suppressed in 2 patients with preCS. The diagnosis of preCS is decided by the cortisol kit used, but the cortisol levels differ among the kits. It is suggested that the lack of the standardization of cortisol measurement is one of the causes of confusion in the diagnosis of preCS.


Could Maternal Vitamin D Concentration Affect Cervical Length in Mid-Pregnancy? A Report From an Iranian Tertiary Center.
This descriptive-analytic cross-sectional study aimed to figure out whether maternal serum vitamin D concentration correlates with cervical length measurement in mid-gestation or not. During Jun-Jan 2021, 213 pregnant women at 18-22 weeks of gestation were investigated. First, demographic features were obtained then, maternal serum vitamin D concentration was measured by enzyme-linked immunoassay and cervical length was measured via transvaginal sonography according to fetal maternal foundation guideline and appropriate statistical test was used to analyze the correlation between maternal vitamin D level and cervical length in mid-pregnancy. It was shown that 29.6% and 25.4% of participants had vitamin D deficiency and insufficiency, respectively. Spearman's test found no significant correlation between maternal vitamin D level and cervical length in mid-pregnancy. Moreover, cervical length and maternal vitamin D level had no association with maternal BMI. Although maternal vitamin D level and its sufficiency status was not associated with cervical length in mid-pregnancy, as a trend toward decreased maternal serum vitamin D level by advancing gestational age was observed. It may be concluded that it is prolonged vitamin D deficiency during gestation that may lead to cervical length shortening and subsequent preterm delivery later in gestation.


Quantifying morphological variation in the Castilleja pilosa species complex (Orobanchaceae).
Robustly delimited species are of paramount importance, the identification of which relies on our ability to discern boundaries between one species and the next. This is not difficult to do when species are very distinct from one another. However, in recently evolved lineages where putative species may have relatively few diagnostic features (e.g., species complexes composed of very similar species, the boundaries between which are often unclear), defining species boundaries can be more challenging. Hence, the field of species delimitation has widely advocated the use of multiple lines of evidence to delimit species, particularly in species complexes. Excessive taxonomic confusion, often the result of species descriptions that shift through time (e.g., during revisionary work and regional treatments), can further complicate the search for diagnostic features in species complexes. Here, as a first step in robustly delimiting species boundaries, we quantify and describe morphological variation in the Castilleja pilosa species complex. We first infer the morphospace of the species complex and use fuzzy-clustering techniques to explore the morphological variation in the system. Next, we hypothesize the position of type specimens within that morphospace. In so doing, we aim to visualize the impact that regional treatments have had on the conceptualization of taxa through time. We find that there is limited morphological variation among members of this complex, and we determine that the morphological concept of these species have shifted through time and are no longer accurately represented by species descriptions.


Fluconazole for postpartum candidal mastitis and infant thrush.
This case report illustrates the difficulties inherent in treating candidal mastitis in lactating women and concurrent thrush in the breastfeeding baby. This mother's candidiasis vacillated from topical to ductal, depending on which medications were being used over the course of several months. Her baby's oral thrush was unique in that there were never any white plaques visible on his oral mucosa. Ultimately, both mother and child were treated simultaneously with oral fluconazole, with a relief of symptoms in both individuals.


Reducing devices for pressure sores with respect to nursing care procedures.
In a study that focused on patient comfort and ease of performing nursing care activities 10 common pressure-reducing devices were evaluated for cost, stability, dimensions, positioning, temperature, bounce, noise, cleaning, leakage, weight, mechanical reliability, linen displacement, transfers, bathing, feeding, and dressing. Thirteen subjects--six quadriplegic patients, five paraplegic patients, and two patients with cerebrovascular accidents--and three nurses evaluated each device according to a prearranged schedule of daily patient care activity. Each subject tested five devices at least four times during two separate 24-hour periods. The devices were ranked and rated by subjects and nurses. When Kendall rank correlation coefficients were compared, the tau for ranking by subjects and nurses was .82; for rating, .42; and for ranking and rating combined, .73. Subjective comments by subjects and nurses were examined for relevant factors.


Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children.
Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce the risk of graft-versus-host disease (GVHD) through reduced gastrointestinal (GI) permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 posttransplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days, P = .0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year, P = .03). Bloodstream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year, P = .03), supporting our hypothesis of increased intestinal permeability. The GI mucosal intestinal fatty acid-binding protein was decreased after transplant, confirming mucosal injury, but was not correlated with vitamin A levels, indicating that vitamin A did not protect against mucosal injury. Expression of the gut homing receptor CCR9 on T-effector memory cells 30 days after transplant was increased in children with vitamin A levels below the median (r = -0.34, P = .03). Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD and are not simply a marker of poor nutritional status or a sicker patient. Vitamin A supplementation might improve transplant outcomes.


Older people who smoke: why nurses should help them to stop.
Smoking is the greatest preventable cause of ill health and premature death in the UK. Although the prevalence of smoking is lower among adults over 65 years than in younger age groups, the actual number of older smokers is increasing steadily as the proportion of older adults in the population rises. If nurses are to function effectively in their role as health promoters it is important that they base their practice on appropriate research-based evidence. In this article we discuss the current evidence on the health consequences of smoking in later life and the benefits of cessation. We provide information on approaches that discuss some of the barriers to behavioural change. Our aim is to provide nurses with information that will help them to help older smokers make informed choices.


Alicycliphilus: current knowledge and potential for bioremediation of xenobiotics.
Alicycliphilus is a promising candidate for participating in the development of novel xenobiotics bioremediation processes. Members of the Alicycliphilus genus are environmental bacteria mostly found in polluted sites such as landfills and contaminated watercourses, and in sewage sludges from wastewater treatment plants. They exhibit a versatile metabolism and the ability to use oxygen, nitrate and chlorate as terminal electron acceptors, which allow them to biodegrade xenobiotics under oxic or anoxic conditions. Pure cultures of Alicycliphilus strains are able to biodegrade some pollutants such as industrial solvents (acetone, cyclohexanol and N-methylpyrrolidone), aromatic hydrocarbons (benzene, toluene and anthracene), as well as polyurethane varnishes and foams, and they can even transform Cr(VI) to Cr(III). In addition, Alicycliphilus has also been identified in bacterial communities involved in wastewater treatment plants for denitrification, and the degradation of emerging pollutants such as triclosan, nonylphenol, N-heterocyclic aromatic compounds (indole and quinoline), and antibiotics (tetracycline and oxytetracycline). This work summarizes the current knowledge on the Alicycliphilus genus, describing its different metabolic characteristics, focusing on its xenobiotic biodegradation abilities and examining the distinct pathways and molecular bases that sustain them. We also discuss the progress made in genetic manipulation and 'omics' analyses, as well as Alicycliphilus participation in novel bioremediation strategies.


Drug-induced weight gain in the last 10 years: a descriptive study.
Medication-induced weight gain can be frustrating to patients and health care providers. Drug-induced weight gain is a profound side effect of numerous commonly used medications. The present study aimed to investigate FAERS reports about drug-induced weight gain in the last ten years. Using the US FDA Adverse Event Reporting System (FAERS) between 2012 and 2021, a retrospective, descriptive analysis was conducted to analyze the major reported Adverse Events about weight gain. During the last ten years, 137370 reports were submitted to FAERS about drug-induced weight gain. The most common drugs that are reported by the patients and that are associated with weight gain were risperidone (11.55%), adalimumab (3.94%), pregabalin (3.86%), aripiprazole (3.1%), etanercept (2.72%), and prednisone (2.70%). In conclusion, the present study showed that drug-induced weight gain is a common side effect of several medications frequently used to treat chronic diseases. Healthcare providers should educate their patients about the medicines that may cause weight gain.


Structurally different alleles of the ath-MIR824 microRNA precursor are maintained at high frequency in Arabidopsis thaliana.
In plants and animals, gene expression can be down-regulated at the posttranscriptional level by microRNAs (miRNAs), a class of small endogenous RNA. Comparative analysis of miRNA content across species indicates continuous birth and death of these loci in the course of evolution. However, little is known about the microevolutionary dynamics of these genetic elements, especially in plants. In this article we examine polymorphism at two miRNA-encoding loci in Arabidopsis thaliana, miR856 and miR824, which are not found in rice or poplar. We compare their diversity to other miRNA-encoding loci conserved across distant taxa. We find that levels of variation vary significantly across loci and that the two recently derived loci harbor patterns of diversity deviating from neutrality. miRNA miR856 shows a weak signature of a selective sweep whereas miR824 displays signs of balancing selection. A detailed examination of structural variation among alleles found at the miR824-encoding locus suggests nonrandom evolution of a thermoresistant substructure in the precursor. Expression analysis of pre-miR824 and its target, AGL16, indicates that these structural differences likely impact the processing of mature miR824. Our work highlights the relevance of RNA structure in precursor sequence evolution, suggesting that the evolutionary dynamics of miRNA-encoding loci is more complex than suggested by the constraints exerted on the interaction between mature miRNA fragments and their target exon.


Na+:HCO3- cotransporters (NBC): expression and regulation in the kidney.
Recent molecular cloning experiments have identified the existence of four NBC isoforms (NBC1, 2, 3 and 4) and two NBC-related proteins AE4 and NCBE (Anion Exchanger 4 and Sodium-dependent Chloride-Bicarbonate Exchanger). Except for AE4 which does not transport Na, all are presumed to mediate the cotransport of Na+ and HCO3-. NBC1 is expressed on the basolateral membrane of proximal tubule, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. NBC1 is directly stimulated by carbonic anhydrase (CA) II, indicating that its inhibition by CA inhibitor acetazolamide is, in part, direct and due to the inhibition of CAII which in turn binds to the carboxy terminal tail of NBC1. NBC2 has two variants, NBCn1 and mNBC3, which are expressed in the kidney. NBCn1 is located on the basolateral membrane of the thick ascending limb of Henle whereas mNBC3 is expressed on the apical membrane of alpha intercalated cells. Both transporters are electroneutral. NBC3 or kNBC3 (also referred to as NDCBE), NBC4, AE4 and NCBE are all expressed in the kidney but their characterization is in early stages. The purpose of this article is to summarize recent functional and molecular advances on NBC isoforms and related proteins, examine the interaction of NBC1 and carbonic anhydrases, and discuss the role and regulation of NBC isoforms in renal bicarbonate transport in health and disease states.


Central modulation of parasympathetic outflow is impaired in de novo Parkinson's disease patients.
Task- and stimulus-based neuroimaging studies have begun to unveil the central autonomic network which modulates autonomic nervous system activity. In the present study, we aimed to evaluate the central autonomic network without the bias constituted by the use of a task. Additionally, we assessed whether this circuitry presents signs of dysregulation in the early stages of Parkinson's disease (PD), a condition which may be associated with dysautonomia. We combined heart-rate-variability based methods for time-varying assessments of the autonomic nervous system outflow with resting-state fMRI in 14 healthy controls and 14 de novo PD patients, evaluating the correlations between fMRI time-series and the instantaneous high-frequency component of the heart-rate-variability power spectrum, a marker of parasympathetic outflow. In control subjects, the high-frequency component of the heart-rate-variability power spectrum was significantly anti-correlated with fMRI time-series in several cortical, subcortical and brainstem regions. This complex central network was not detectable in PD patients. In between-group analysis, we found that in healthy controls the brain activation related to the high-frequency component of the heart-rate-variability power spectrum was significantly less than in PD patients in the mid and anterior cingulum, sensorimotor cortex and supplementary motor area, insula and temporal lobe, prefrontal cortex, hippocampus and in a region encompassing posterior cingulum, precuneus and parieto-occipital cortex. Our results indicate that the complex central network which modulates parasympathetic outflow in the resting state is impaired in the early clinical stages of PD.


Cardiac pathological conditions in young soldiers: case series.
We briefly review the disease processes for four young healthy soldiers who presented to our emergency department with serious cardiac pathological conditions. We present two unusual cases of myocardial infarction, a coronary artery aneurysm, and a case of smallpox vaccine-induced myocarditis/pericarditis. Our intent is to encourage others in military medicine to maintain a high index of suspicion for cardiac conditions even in a relatively young healthy population.