The determinants of dust mite allergen and its relationship to the prevalence of symptoms of asthma in the Asia-Pacific region.
The role that house dust mites play in the primary causation of asthma is controversial. Approximately thirty-six 10-yr-old children in each of 10 centres in the Asia-Pacific region participated. Researchers collected dust from mattresses and living room floors using standardized procedures. Der p1 and Der f1 were analysed using a double monoclonal antibody enzyme-linked immunosorbent assay. Geometric mean allergen levels were calculated for each centre. An ecological analysis was conducted to show the regression of the geometric mean allergen level, using the highest household level, against asthma symptom and severity prevalence data from the International Study of Asthma and Allergies in Childhood, Phase I. Among children aged 13-14 yr, the change in asthma symptom prevalence was associated with per unit change in Der p1 microg/g (1.08, 95% CI 0.10-2.06) and Der 1 microg/g (Der p1 + Der f1) (0.64, 95% CI 0.02-1.26). The change in having four or more attacks of asthma in the last 12 months was associated with per unit change in Der p 1 microg/g (0.29, 95% CI -0.02 to 0.60) and Der 1 microg/g (0.20, 95% CI 0.01-0.38). There was no effect for total Der p1 or Der f1 (total or microg/g). Among children aged 6-7 yr, neither allergen was related to symptoms or severity prevalence. While our findings suggest that Dermatophagoides pteronyssinus may have a role in the primary causation of asthma, the complexity of this association reinforces the need for prospective studies.


2-Chloro-2-phenylethylamine as a mechanistic probe and active site-directed inhibitor of monoamine oxidase from bovine liver mitochondria.
The reaction of 2-chloro-2-phenylethylamine with monoamine oxidase B was investigated to study the mechanism of this enzyme and its inactivation by this compound. 2-Chloro-2-phenylethylamine is a substrate with a Km of 30 microM and a turnover number of 80 min-1 at pH 6.5 at 30 degrees C. Incubation of 2-chloro-2-phenylethylamine with the enzyme led to the normal oxidation product, 2-chloro-2-phenylacetaldehyde, but only traces (0.25 mol%) of 2-phenylacetaldehyde, the product anticipated if the oxidation of substrate involved a stabilized carbanion at C-1 and elimination of chloride ion. These data suggest that a carbanion is not a likely intermediate in the oxidation of amines by monoamine oxidase. During the mechanistic studies we noted time-dependent inactivation of monoamine oxidase B by 2-chloro-2-phenylethylamine under both aerobic and anaerobic conditions. Inactivation was not reversible. Aerobically 2-chloro-2-phenylethylamine is oxidized to 2-chloro-2-phenylacetaldehyde which covalently modifies the enzyme (tau 1/2 = 40 min). Benzyl alcohol, a substrate analog, gives substantial protection against inactivation under aerobic conditions (tau 1/2 = 320 min), suggesting that an active site residue is modified. Anaerobic reaction of 2-chloro-2-phenylethylamine with monoamine oxidase B probably proceeds by direct alkylation of an enzyme residue (tau 1/2 = 140 min). Reduction with [3H]NaBH4 of the inactivated enzyme gave from 0 to 0.7 and from 4.5 to 5.6 mol of hydride incorporation for enzyme inactivated anaerobically and aerobically, respectively. The latter results are in agreement with inactivation by unmodified inhibitor and inactivation by oxidized inhibitor for the anaerobic and aerobic reactions, respectively. It is suggested that 2-chloro-2-phenylethylamine or its oxidation product 2-chloro-2-phenylacetaldehyde may serve as an active site affinity reagent for monoamine oxidase.


(-)-Epigallocatechin gallate suppresses adipocyte differentiation through the MEK/ERK and PI3K/Akt pathways.
EGCG [(-)-epigallocatechin gallate], tea catechin, is one of the compounds that has been reported to act against obesity and diabetes. To determine the effect of EGCG on adipocyte differentiation, we treated 3T3-L1 preadipocytes with different catechins. Oil Red O staining showed significantly reduced intracellular lipid accumulation, especially with EGCG. Cell cycle analysis showed that EGCG inhibited cell proliferation by disturbing the cell cycle during the clonal expansion of 3T3-L1. RT-PCR (real-time PCR) demonstrated that EGCG noticeably reduced mRNA expression of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer-binding protein α) and FoxO1 (forkhead box class O1). EGCG also caused a significant decrease in the transcription of FoxO1 - the forkhead transcription factor class O1 involved in adipocyte differentiation - via the PI3K (phosphoinositide 3-kinase)/Akt and MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] pathways. These results suggest that EGCG suppresses the clonal expansion of adipocytes by inactivating FoxO1 via insulin signalling and stress-dependent MAPK pathways.


Evaluation and Management of the Hair Loss Patient in the Primary Care Setting.
Alopecias represent a heterogeneous group of disorders with different etiologies, presentations, and treatment options. The evaluation of the hair loss patient includes a comprehensive clinical history and physical examination; appropriate laboratory testing; and if indicated, a scalp biopsy. Treatment methods vary depending on the type of alopecia, and include watchful waiting, topical and systemic formulations, surgery, and treatment of any underlying or associated conditions. Referral to a dermatologist is helpful in diagnostically challenging and difficult to treat cases. Alopecia can cause emotional, mental, and social distress to patients. Early diagnosis and timely institution of appropriate treatment are helpful and comforting to those affected by this disease.


An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots and Freckling. Part II. Other Skin Manifestations Characteristic of NF1. NF1 and Cancer.
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still based primarily on clinical observations. The 7 diagnostic criteria of the National Institutes of Health, which were established in 1988, include 3 skin manifestations (café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas). The age at which these diagnostic lesions appear is variable: onset can be late in some patients while others never develop certain symptoms. Definitive diagnosis may therefore be delayed by years. Although the appearance of the characteristic café-au-lait spots and freckling in the early years of childhood are very suggestive of the disease, these signs are not pathognomonic and, in isolation, do not constitute sufficient evidence to establish a definitive diagnosis. Thus, other diagnoses should be considered in patients whose only symptoms are café-au-lait spots and freckling. By contrast, the presence of multiple cutaneous neurofibromas or at least 1 plexiform neurofibroma is a very specific indication of NF1. Identification of the different types of neurofibroma allows us to confirm the diagnosis and initiate appropriate management.


Mental health and substance use of sexual minority college athletes.
Assess the mental health and substance use of sexual minority collegiate student-athletes in the United States, as compared with heterosexual college students and heterosexual student-athletes. Undergraduate students (N = 196,872) who completed the American College Health Association's National College Health Assessment (Fall 2008-Fall 2012 administrations). Written cross-sectional survey. Sexual minority student-athletes had a higher risk of experiencing mental health difficulties than their heterosexual athlete peers. There were no significant differences in mental health between sexual minority male athletes and nonathletes. Sexual minority female athletes appeared to fare better than nonathlete peers. Substance use was greater among sexual minority students (athlete and nonathlete) and was mediated by mental health. Participation in athletics does not appear to be associated with an elevated risk of negative mental health outcomes for sexual minority participants; however, there are disparities in mental health outcomes by sexual orientation regardless of athletics participation.


Hirsutism.
Many women have some facial hair, and most patients who seek advice will be at the far end of the normal distribution curve for hair. In a second group there is a slight excessive production of androgens with associated hirsutism, either idiopathic or associated with polycystic ovarian disease. An extremely small fraction of patients will have serious disorders of the adrenals or ovaries and significant elevations in androgen levels.


The evolution of DUX4 gene regulation and its implication for facioscapulohumeral muscular dystrophy.
Double homeobox 4 (DUX4) is an early embryonic transcription factor whose expression in the skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). Despite decades of research, our knowledge of FSHD and DUX4 biology is incomplete, and the disease has currently no cures or targeted therapies. The unusual evolutionary origin of DUX4, its extensive epigenetic and post-transcriptional gene regulation, and various feedback regulatory loops that control its expression and function all contribute to the highly complex nature of FSHD pathogenesis. In this minireview, I synthesize the current state of knowledge in DUX4 and FSHD biology to highlight key areas where further research is needed to better understand DUX4 regulation. I also emphasize post-transcriptional regulation of and by DUX4 via changes in RNA and protein stability that might underlie key features of FSHD pathophysiology. Finally, I discuss the various feedback loops involved in DUX4 regulation and the context-specific consequences of its expression, which could be key to developing novel therapeutic approaches to combat FSHD.


Three-dimensional cortical bone microstructure in a rat model of hypoxia-induced growth retardation.
Little is known about hypoxia-induced modification of the canal network in the cortical bone despite its involvement in intracortical vascularity and bone blood supply. In this study, we examined the effect of chronic hypoxia on the canal network in postnatal bone. Tibiae were harvested from 4- and 8-week-old rats (hyp-4 and -8, n = 8 each), whose growth was retarded owing to postnatal exposure to hypoxia (12-14% O₂), and from 3- and 4-week-old normoxic rats (cnt-4 and -5, n = 8 each), which were similar in tibial length and cortical cross-sectional area to hyp-4 and -8, respectively. The diaphyseal canals were detected by monochromatic synchrotron radiation CT with a 3.1-μm voxel resolution. The anatomical properties of the canal network were compared between age- or size-matched hypoxic and normoxic groups. The canals were larger in diameter, were more densely distributed and connected, and opened into the marrow cavity with a higher density in hyp-4 than in cnt-4. The canal density and connectivity were also higher in hyp-4 than in cnt-3. The canal diameter, density, and connectivity were smaller in hyp-8 than in cnt-4; however, the densities of endocortical and periosteal canal openings did not differ between hyp-8 and cnt-4. We concluded that chronic hypoxia enhanced the formation of cortical canal networks at the postnatal developmental stage, probably facilitating intra- and transcortical vascularization and bone perfusion accordingly.


Patient-assisted compression helps for image quality reduction dose and improves patient experience in mammography.
We evaluated the impact of patient-assisted compression (PAC) on image quality, dose, workflow and patient experience of mammography. Patients aged 40-90 years coming for bilateral mammography were included prospectively in the study. After positioning each breast, the technologist performed the compression and exposure of the first breast, initiated the compression of the other until 3 daN and then let the patient complete the compression using a remote control device. Image quality, compression force, breast thickness, average glandular dose and pain value for each breast were assessed for PAC and technologist compression (TC). The compression level was significantly higher with PAC than TC for both craniocaudal (CC; median difference 2.0 daN, p < 0.0001) and mediolateral oblique (MLO) views (median difference 1.5 daN, p < 0.0001). Breast thickness was reduced with PAC (CC, median difference -1.90 cm, p = 0.02), as well as glandular dose (CC, median difference -0.03, p = 0.02). The image quality was rated equivalent for both modes in 85% (85/100) of cases, superior for PAC in 10% (10/100) of cases and inferior in 5% (5/100) of cases. There was no significant difference in discomfort or pain felt between PAC and TC modes. Seventy-four percent of patients reported that the self-compressing device would facilitate their reattendance. PAC may be a suitable technique for mammography examinations, providing an equivalent image quality to TC. Moreover, as the breast compression level is increased, PAC may help reduce breast thickness, hence glandular dose. The fact that patients have control over the procedure may change their perception of mammography and improve uptake and compliance.


Functional dichotomy of dendritic cells following interaction with Leishmania braziliensis: infected cells produce high levels of TNF-alpha, whereas bystander dendritic cells are activated to promote T cell responses.
Leishmania braziliensis infections are often associated with exaggerated immune responses that can sometimes lead to severe disease associated with high levels of IFN-gamma and TNF-alpha. To explore the role played by dendritic cells (DCs) in these responses, we characterized DCs that were exposed to L. braziliensis. We found that DCs cultured with L. braziliensis parasites up-regulated DC activation markers and produced IL-12 and TNF-alpha. However, not all DCs in the culture became infected, and an analysis of infected and uninfected DCs demonstrated that the up-regulation of activation markers and IL-12 production was primarily confined to the uninfected (bystander) DCs. Further studies with Transwell chambers and parasite fractions indicated that the activation of bystander DCs was mediated by a soluble parasite product, in a type 1 IFN- and MyD88-independent, but TNF-alpha-dependent fashion, and that the activated DCs were more efficient at presenting Ag than control DCs. In contrast, L. braziliensis-infected DCs failed to up-regulate activation markers, but exhibited a dramatic enhancement in their ability to produce TNF-alpha in response to LPS as compared with uninfected DCs. These findings uncover a dual role for DCs in L. braziliensis infection: T cell activation by bystander DCs due to enhanced Ag-presenting capacity following exposure to soluble parasite products, and increased production of TNF-alpha by infected cells that may contribute to the local control of the parasites, but concomitantly induce immunopathology.


Combined microdialysis and Fos immunohistochemistry for the estimation of dopamine neurotransmission in the rat caudate-putamen.
Extracellular dopamine (DA) concentrations estimated by transcerebral dialysis and D1-dependent c-fos expression, as demonstrated by Fos immunohistochemistry, were studied after blockade of DA reuptake by GBR-12909. Rats implanted with dialysis probes in the dorsal caudate-putamen did not show any Fos-positive neuronal labeling in the implanted area or in the rest of the caudate-putamen. Administration of GBR-12909 dose-dependently increased DA output in dialysates and resulted in the appearance in the caudate-putamen of Fos-positive neurons whose density was related to the dose of GBR-12909 and to the increase in extracellular concentrations of DA. The D1 antagonist SCH-23390 blocked GBR-12909-induced activation of Fos while potentiating the stimulation of DA output. The results show that following blockade of DA reuptake by GBR-12909, the induction of Fos is related to stimulation of D1 receptors by extracellular DA. Combination of brain dialysis with Fos immunohistochemistry might provide a method for estimating the functional significance of extracellular DA as measured by brain microdialysis.


[Characteristics of the development of model psychosis in rats in intracerebral administration of lysergic acid diethylamide].
Chronic experiments on rats with a microcannula implanted into the brain were made to study the effect of diethylamide of lisergic acid (DLA) on spontaneous behavior, locomotion and emotional behavioral reactions. Administration of DLA into the lateral brain ventricles and mesencephalic reticular formation demonstrated that the action of DLA becomes manifest in extremely low doses and within the narrow dose range. The action of DLA is biphasic in nature: the first phase is noted for increased locomotion, while the second one for inhibition. The development of the first phase is linked with a direct effect of DLA on the mesencephalic reticular formation which appeared sensitive to the drug action. It is suggested that the effect of DLA on the central nervous system is realized with the aid of the triggering mechanism.


Estrogen therapy in the prevention and management of osteoporosis.
Many studies have shown that bone loss accelerates after oophorectomy or the menopause. If estrogen replacement therapy is instituted soon after the onset of these changes, much of this bone loss, and subsequent fractures, can be prevented. Most investigations have evaluated the effects of oral estrogens, but other routes of administration may be equally beneficial. The use of estrogens natural to the human also seems preferential. Several theories have been advanced regarding the mechanism of action of estrogen in this population. The most popular concept holds that estrogen stimulates calcitonin production, but other theories also must be considered since this is controversial and far from proven. A local action of estrogen on the skeleton cannot be ruled out. In addition to estrogen, calcium supplementation and exercise may have roles to play in the prevention and management of osteoporosis.


Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism.
Left ventricular assist devices (LVAD) are used to 'bridge' patients with end-stage heart failure to transplantation. After long-term LVAD support, ventricular function may partially recover, a process called 'reverse remodeling'. As several kinase-mediated signal transduction pathways have been implicated in the development of cardiac hypertrophy and failure, we examined the activities of the Erks, MEKs, Akt, GSK-3 beta, p70S6K, JNKs and p38 under LVAD support as well as during single myocyte strain and whole heart stretch. Western blotting and immunohistochemistry were performed using phospho-specific antibodies in matched samples from ten patients with end-stage heart failure before and after LVAD. Cyclic strain was performed in rat neonatal cardiac myocytes, and tensile stretch applied to Langendorff-perfused mouse hearts via a left ventricular balloon. The activity of Erks and Akt in failing hearts dramatically decreased after LVAD support, while that of GSK-3 beta increased. There was an endo/epicardial gradient for Erk activity which persisted after LVAD despite the reduction of total Erk activity. TUNEL-positivity and myocyte size decreased after LVAD, but independently of changes in kinase activity. In cardiomyocytes and Langendorff-perfused mouse hearts both strain/stretch and its relief regulated the activities of Erks, Akt, and GSK-3 beta. Erks and Akt/GSK-3 beta are highly responsive to myocyte stretch in vitro and in vivo, and may be sensitive molecular parameters of 'reverse remodeling' under LVAD support.


Vascular Imaging for the Primary Care Provider: Venous and Arterial Disease.
The vascular laboratory provides important contributions to the diagnosis, workup, and treatment of known or suspected vascular disease. Knowing what tests to order (and when to order them) allows for the best utilization of these resources. This article will focus on the appropriate use of the vascular lab for the primary care clinician regarding a variety of vascular presentations, including swollen leg, suspected peripheral artery disease, vasospastic disease, carotid artery stenosis, and abdominal aortic aneurysms. Patients with known vascular disease often require serial surveillance imaging to document the stability or progression of disease, and consensus guidelines regarding these strategies will be reviewed.


Human Venezuelan equine encephalitis virus infection and diabetes in Zulia State, Venezuela.
Venezuelan equine encephalitis (VEE) virus has been implicated as producing alterations in glucose metabolism in animals. We performed oral glucose tolerance tests and measured serum immunoreactive insulin responses in 13 patients who were infected by VEE virus during an epidemic in 1969, in Zulia State, Venezuela. No significant alterations in the glucose tolerance test were found. Sera of 86 diabetic outpatients and 98 control individuals with normal glycemia at a local hospital were tested for antibodies to VEE virus by hemagglutination inhibition. No statistically significant difference was found between the two groups; 10.4% of the diabetic patients had detectable antibodies against VEE virus, compared to 7.1% of controls. Seventy-three percent of the diabetics with antibodies were individuals over 40 yr old, whose diabetes could be catalogued as insulin independent. The results of these studies indicate no relationship of VEE virus infection to subsequent diabetes.


Spectrotypic analysis of antibodies to insulin A and B chains.
Antibodies produced by immunization with native insulin were analyzed by isoelectric focusing for binding to isolated A and B chains. Antibodies to isolated A chain of beef insulin were found to have restricted spectrotypes and were seen after immunization with either beef or human insulin. Hyperimmunization with beef insulin, but not human, increased the heterogeneity of anti-A chain antibodies. Antibodies to isolated B chains were also electrophoretically restricted but showed less heterogeneity after hyperimmunization than anti-A chain responses. When binding to chains was carried out in the presence of excess cold insulin, anti-B chain spectrotypes were inhibited by the native molecule. In contrast, only a portion of anti-A chain spectrotypes were inhibited by native insulin, suggesting that these clonotypes are directed at epitopes not present on the surface of the molecule. These data indicate that the anti-insulin repertoire includes antibodies that can bind isolated chains as well as the native molecule. Some of the determinants on isolated A chain are not available on intact insulin and may arise from antigen catabolism.


New technology, old standards: disparate activated clotting time measurements by the Hemochron Jr compared with the standard Hemochron.
Accurate control of the anticoagulation level is important for safe initiation of cardiopulmonary bypass. Using the Hemochron Jr., we consistently noted a higher than customary heparin dose required to achieve an activated clotting time (ACT) that, according to the literature and our quality standards, should be more than 480 seconds. This study was designed to determine whether there existed a significant difference in ACT values measured by the newer Hemochron Jr. and the older Hemochron 801 assay system. A total of 30 patients underwent cardiovascular surgical procedures requiring heparinization (300 U/kg). Multiple samples for measurement of the ACT were obtained from all patients before heparinization, after heparinization, during cardiopulmonary bypass, and after protamine administration. Arterial samples were collected, and ACT was determined simultaneously on the same sample using both Hemochron Jr. and Hemochron 801. Activated clotting time data were analyzed with a linear mixed model using an unstructured variance-covariance matrix. Descriptive statistics on all heparinized patients revealed that the Hemochron Jr. yielded ACT results that on average were 121.28 seconds lower than the determination by the standard Hemochron 801 on the same sample of blood. This difference was -139.04 in on-pump cases and -90.51 in off-pump cases, primarily a function of the fact that higher heparin doses and therefore longer ACTs were used in patients having operations using the heart-lung machine. From the linear mixed model, the estimated average paired difference between the Hemochron Jr. and Hemochron 801 was found to be -86.03, yielding a highly significant test statistic (t(28) = -6.18; p < 0.0001). Lower ACT values determined by Hemochron Jr. are consistent with higher, clinically acceptable ACT values as measured by the Hemochron 801. These findings would suggest that safe levels of anticoagulation are determined in part by the specific assay used.


Evidence for an amygdaloid projection to premotor cortex but not to motor cortex in the monkey.
Previous studies in the cat have demonstrated a direct projection from the amygdaloid complex to motor and premotor regions of the neocortex. In the present study both anterograde and retrograde tracer techniques have been used to determine whether a similar projection exists in the monkey brain. We have found that the dorsal, magnocellular division of the basal nucleus of the amygdaloid complex gives rise to a projection to the premotor cortex (Area 6), which terminates principally in layers I and II, and to a lesser extent in layer VI. No component of the amygdaloid complex has been found to project to the motor cortex (Area 4). The amygdaloid projection to Area 6 in the monkey appears to be substantially weaker than other rostrally directed projections from the basal amygdaloid nucleus to orbitofrontal and medial frontal areas, and also relatively weaker than the projection that has been described in the cat.


[The prosthodontic three-dimensional multimedia system developed for dental education and chairside communication].
To develop a three-dimensional multimedia system for enhancing the efficiency of dental education and chairside communication. A set of three-dimensional digital models of normal teeth and jaws related to dental education in prosthodontics were acquired or established under Microsoft Windows. The three-dimensional models were re-edited and rendered with texture attached, producing a large number of three-dimensional pictures and short animated pictures. A software platform was established for displaying all sorts of media, including the three-dimensional models. Finally, all media files produced or gathered before were integrated into the platform, similar to the textbook in chapter adopted in dental education at university. The prosthodontic three-dimensional multimedia system was successfully developed. The system covered basic information within the current textbook of prosthodontics, three-dimensional pictures, animated pictures, and virtual three-dimensional scenes. The system might serve as an assistant tool in dental education and chairside communication. It is technically feasible to establish the prosthodontic three-dimensional multimedia system, according to experiences in this study. The success also anticipates the possibility and feasibility of developing similar systems in other disciplines of dentistry.


Correlation between AV synchrony and device collected AM-VP sequence counter in atrioventricular synchronous leadless pacemakers: A real-world assessment.
Micra atrioventricular (AV) provides leadless atrioventricular synchronous pacing by sensing atrial contraction (A4 signal). Real-world operation and reliability of AV synchrony (AVS) assessment using device data have not been described. The purposes of this study were to (1) assess the correlation between AVS and atrial mechanical sensed-ventricular pacing (AM-VP) percentages in patients with permanent high-degree AV block and (2) report on the real-world effectiveness of Micra AV. The correlation between ECG-determined AVS in-clinic and device-collected %AM-VP was assessed using data from 40 patients with high-degree AV block enrolled in the Micra Atrial tRacking using a Ventricular AccELerometer (MARVEL) 2 study. A retrospective analysis to assess continuously-sampled %AM-VP since last session, device programming, and electrical parameters was performed using Micra AV transmissions from the Medtronic CareLink database. Patients with transmissions ≥180 days postimplant were included. Among the 40 MARVEL 2 AV block patients with a median %VP of 99.7%, AVS was highly correlated with AM-VP (median AVS 87.1%, median AM-VP 79.1%; R2 = 0.764, p < .001). The CareLink cohort included 4384 patients programmed to VDD mode. The mean A4 amplitude was 2.3 ± 1.8 m/s2 at implant and 2.3 ± 1.6 m/s2 at 28 weeks. In patients with %VP >90% (n = 1662), the median %AM-VP was 74.7%. For the full cohort, median %VP was 65.6% and median projected battery longevity was 10.5 years. In patients with a high pacing burden, %AM-VP provides a reasonable estimation of AVS. The first large real-world analysis of Micra AV patients with >90% VP showed stable atrial sensing over time with a median %AM-VP, a correlate of AVS, of 74.7%.


Potential of mobile intraoperative radiotherapy technology.
Mobile IORT units have the potential to change the way patients who have cancer are treated. The integration of IORT into cancer treatment programs, made possible by the new technologies of mobile linear accelerators that can be used in unshielded operating rooms, makes IORT significantly less time-consuming, less costly, and less risky to administer. It is now practical for IORT to be used in early-stage disease, in addition to advanced disease, and in sites for which patient transportation in the middle of surgery is considered too risky. Preliminary results of trials for early-stage breast and rectal cancer indicate benefits of IORT. Pediatric patients and patients who have lung cancer, previously underserved by IORT therapies, can be offered potential gains when patient transport issues do not limit IORT. Furthermore, because many of these mobile systems require no shielding, it is now practical for mobile units to be shared between hospitals, making this new mobile technology much more widely available.


[Safety in brachytherapy].
No technique can now be used without previously considering the safety of patients, staff and public and risk management. This is the case for brachytherapy. The various aspects of brachytherapy are discussed for both the patient and the staff. For all, the risks must be minimized while achieving a treatment of quality. It is therefore necessary to establish a list as comprehensive as possible regardless of the type of brachytherapy (low, high, pulsed dose-rate). Then, their importance must be assessed with the help of their criticality. Radiation protection of personnel and public must take into account the many existing regulation texts. Four axes have been defined for the risk management for patients: organization, preparation, planning and implementation of treatment. For each axis, a review of risks is presented, as well as administrative, technical and medical dispositions for staff and the public.


Sustained delivery of siRNA from dopamine-coated stainless steel surfaces.
Dopamine, an adhesive protein can be covalently deposited onto biomaterials. In this study, we evaluated the ability of dopamine-coated surfaces for small interfering RNA (siRNA) immobilization and release. Dopamine was deposited onto 316L stainless steel discs either as a monolayer at acidic pH or as polydopamine at alkaline pH, following which siRNA was immobilized onto these discs. To investigate the RNA interference ability of immobilized siRNA, reduction of luciferase expression in HeLa, and reduction of Egr-1 expression and cell proliferation in human aortic smooth muscle cells (HAoSMCs) were determined. Dopamine treatment of 316L stainless steel discs under both the acidic and alkaline conditions resulted in the deposition of amino (NH2) groups, which enabled electrostatic immobilization of siRNA. The immobilized siRNA was released from both types of coatings, and enhanced the percent suppression of firefly luciferase activity of HeLa significantly up to ~96.5% compared to HeLa on non-dopamine controls (18%). Both the release of siRNA and the percent suppression of firefly luciferase activity were sustained for at least 7 days. In another set of experiments, siRNA sequences targeting to inhibit the activity of the transcription factor Egr-1 were eluted from dopamine-coated surfaces to HAoSMCs. Egr-1 siRNA eluted from dopamine-coated surfaces, significantly reduced the proliferation of HAoSMCs and their protein expression of Egr-1. Therefore, this method of surface immobilization of siRNA onto dopamine-coated surfaces might be effective for nucleic acid delivery from stents.


Ultrasound-guided erector spinae plane block versus thoracic epidural analgesia: Postoperative pain management after Nuss repair for pectus excavatum.
Postoperative pain management is a significant challenge in patients undergoing Nuss repair for pectus excavatum chest wall deformity. Therapeutic anesthetic options primarily include patient-controlled intravenous analgesia, thoracic epidural analgesia (TEA), and cryoanalgesia. However, TEA is limited to inpatient use and both TEA and cryoanalgesia can result in neurologic injury. The novel technique of ultrasound-guided erector spinae plane regional analgesia has been used recently in our patients undergoing the Nuss repair and has shown impressive pain relief, but without the potential complications of other modalities. Erector spinae plane block (ESPB) postoperative pain management outcomes were studied as compared to TEA. Thirty consecutive patients with severe pectus excavatum undergoing Nuss repair and placement of ultrasound-guided ESPB were each paired to a historical cohort control patient with TEA postoperative pain management. The cohort patient match was defined by age (± 2 years), gender, and CT pectus index (± 15%). Study variables included hospital length of stay (LOS), pain scores, and pain medication usage. Pain scores as measured by area under the curve per hour (Day 1: 2.72 (SD = 1.37) vs. 3.90 (SD = 1.81), P = 0.006; Day 2: 2.83 (SD = 1.32) vs. 3.97 (SD = 1.82), P = 0.007) and oral morphine equivalent (OME) pain medication usage (Day 1: 11.9 (SD = 4.9) vs 56.0 (SD = 32.2), P < 0.001; Day 2: 14.7 (SD = 7.1) vs. 38.0 (SD = 21.7), P < 0.001) were higher for the first two postoperative days in the ESPB group. However, mean hospital LOS was nearly one day shorter for ESPB patients (3.78 (SD = 0.82) vs. 2.90 (SD = 0.87), P < 0.001) who were discharged home with the catheter in place until removal, typically at 5-7 days postoperatively. Ultrasound-guided ESPB is thus a feasible, safe, and effective alternative to TEA in postoperative pain management after Nuss repair and results in decreased hospital stay. III.


Parkinson's disease therapy: what lies ahead?
The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics. New formulations of approved drugs and treatment options of motor fluctuations in advanced stages accompanied by telehealth monitoring have improved PD patients care. In addition, continuous improvement in the understanding of PD disease mechanisms resulted in the identification of new pharmacological targets. Applying novel trial designs, targeting of pre-symptomatic disease stages, and the acknowledgment of PD heterogeneity raise hopes to overcome past failures in the development of drugs for disease modification. In this review, we address these recent developments and venture a glimpse into the future of PD therapy in the years to come.


Response to: J-E. Gjertsen, S. A. Lie, T. Vinje, et al. More re-operations after uncemented than cemented hemiarthroplasty used in the treatment of displaced fractures of the femoral neck: an observational study of 11,116 hemiarthroplasties from a national register. J Bone Joint Surg [Br] 2012;94-B:1113–1119.
We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.


Female patients with pseudomyxoma peritonei: a single-institution clinicopathologic study of 35 cases.
To explore clinicopathologic/prognostic aspects of pseudomyxoma peritonei (PMP). We reviewed records of 35 female patients with PMP treated at a single institution. Patients' median age was 57.0 years (range 35.0-71.0 years). Their median pre-surgery level of carbohydrate antigen 19-9 (CA-199) was 80.95 U/ml (range 0.00-1,562.10 U/ml); of carbohydrate antigen 12-5 (CA-125), 44.00 U/ml (range 0.90-231.20 U/ml); and of carcinoembryonic antigen (CEA), 17.20 ng/ml (range 2.04-211.60 ng/ml). Of the 35 patients, 23 (65.7 %) underwent cytoreductive surgery (CRS) by gynecological oncologists and 12 (34.3 %) underwent non-CRS surgeries by general gynecologists or surgeons, including one patient who refused surgical treatment beyond a diagnostic laparoscopy. After surgery, 18 patients (51.4 %) had residual lesions, 11 (31.4 %) had complete lesion removal and 6 (17.1 %)had insufficient information on residual lesion; 21 (60.0 %) had appendiceal-based tumors and 12 (34.3 %) had ovarian-based tumors. Median follow-up time was 37 months (range 1-148 months), during which 28 patients (80.0 %) had relapsed. By the end of the study, 12 patients (34.3 %) died of PMP, 16 (45.7 %) survived with disease, and 7 (20 %) survived without disease. Median progress-free survival (PFS) was 12 months (range 0.5-114.0 months). Median overall survival time was 42 months (range 5-150 months). Ovarian tumor origin, post-surgery residual lesions, preoperative CA199 > 258.9 U/ml and CA125 > 70.6 U/ml were independent predictors of PFS. PMP is rare in women, and has a poor long-term survival rate. Multi-center cooperation to gather more cases is needed to explore its behavior and proper treatment.


Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.
Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.


Shoot performance and population structure in pure stands of Mercurialis perennis L., a rhizomatous perennial herb.
Shoot populations of the rhizomatous perennial herb Mercurialis perennis were studied in pure stands throughout a developmental cycle in a mixed deciduous wood in eastern England. Shoot cohorts exhibited exponential decay between May and October, with half-lives ranging from 2.1 to 7.1 months, although three out of five populations decayed at virtually the same rate. Differences in decay rates were interpreted on environmental grounds. Fertile shoots exhibited higher percentage survival than sterile shoots throughout their growth, and fewer than 5% of them died until well after flowering had been completed. At all dates fertile shoots were significantly taller and heavier than sterile shoots. Shoot growth rates were rapid until tree canopy closure; after canopy closure little change in size occurred. Similarities exist between several aspects of the behaviour of shoot cohorts of M. perennis and Solidago canadensis, another rhizomatous herb.


Soil microbiota respond to green manure in organic vineyards.
The aim of this work was to investigate the effects of biodynamic management with and without the addition of green manure, in comparison with organic management, on the microbiota in vineyards soil. High throughput sequencing was used to compare the taxonomic structure of the soil bacterial and fungal communities from vineyards managed with different methods (organic, biodynamic or biodynamic with green manure). Our results showed that microbial communities associated with biodynamic and organic farming systems were very similar, while green manure was the greatest source of soil microbial biodiversity and significantly changed microbial richness and community composition compared with other soils. Green manure also significantly enriched bacterial taxa involved in the soil nitrogen cycle (e.g. Microvirga sp., Pontibacter sp. and Nitrospira sp.). Our results showed that the diversity and composition of the microbial communities associated with biodynamic and organic farming systems were similar, indicating that the use of biodynamic preparations 500 and 501 did not cause any significant detectable changes to the soil microbial community in the short term, while the effects of green manure were significant in soil microbiota. The microbiological richness and structure of soil are used as a sensitive indicator of soil quality. The extension of organic/biodynamic farming, associated with green manure application, could contribute to increase the abundance of functional groups of biological and agronomical relevance and maintaining microbial biodiversity in vineyard soils.


Peripherally inserted central catheter bloodstream infection surveillance rates in an acute care setting in Saudi Arabia.
Peripherally inserted central venous catheters (PICCs) are alternatives to short-term central venous catheters and provide intravenous access in the acute hospital setting. In this study, we describe the rate of PICC-associated bloodstream infections (BSI). Prospective cohort study using data on PICC lines reviewed from January to December 2009. The infection control team was responsible for prospective BSI case findings. The infection rate was calculated per 1000 device-days. During the study period, 92 PICC lines were inserted with a total of 3336 device-days of prospective surveillance. The most frequent reasons for the insertion of the PICC lines were chemotherapy (n=19, 20.7%), intravenous antimicrobial therapy (n=34, 37%), and for patients in the medical intensive care unit (ICU) (n=16, 17.4%). The overall BSI rate was 4.5/1000 PICC days. The PICC line-associated BSI rates for a specific indication were as follows: chemotherapy 6.6/1000 device-days, intravenous antimicrobial therapy 1.2/1000 device-days, medical ICU 7.3/1000 device-days, surgical ICU 4.6/1000 device-days, and total parental nutrition patients 2.4/1000 device-days (P<.001). The rates were not adjusted for patient severity of illness. Our data suggest that underlying conditions and indications for the PICC line use may play an important role in the development of BSI.


Flow-based solution-liquid-solid nanowire synthesis.
Discovered almost two decades ago, the solution-liquid-solid (SLS) method for semiconductor nanowire synthesis has proven to be an important route to high-quality, single-crystalline anisotropic nanomaterials. In execution, the SLS technique is similar to colloidal quantum-dot synthesis in that it entails the injection of chemical precursors into a hot surfactant solution, but mechanistically it is considered the solution-phase analogue to vapour-liquid-solid (VLS) growth. Both SLS and VLS methods make use of molten metal nanoparticles to catalyse the nucleation and elongation of single-crystalline nanowires. Significantly, however, the methods differ in how chemical precursors are introduced to the metal catalysts. In SLS, precursors are added in a one-off fashion in a flask, whereas in VLS they are carried by a flow of gas through the reaction chamber, and by-products are removed similarly. The ability to dynamically control the introduction of reactants and removal of by-products in VLS synthesis has enabled a degree of synthetic control not possible with SLS growth. We show here that SLS synthesis can be transformed into a continuous technique using a microfluidic reactor. The resulting flow-based SLS ('flow-SLS') platform allows us to slow down the synthesis of nanowires and capture mechanistic details concerning their growth in the solution phase, as well as synthesize technologically relevant axially heterostructured semiconductor nanowires, while maintaining the propensity of SLS for accessing ultrasmall diameters below 10 nm.


USF2 activates RhoB/ROCK pathway by transcriptional inhibition of miR-206 to promote pyroptosis in septic cardiomyocytes.
Septic cardiomyopathy (SCM) is one of the most serious complications of sepsis. The present study investigated the role and mechanism of upstream stimulatory factor 2 (USF2) in SCM. Serum samples were extracted from SCM patients and healthy individuals. A murine model of sepsis was induced by caecal ligation and puncture (CLP) surgery. Myocardial injury was examined by echocardiography and HE staining. ELISA assay evaluated myocardial markers (CK-MB, cTnI) and inflammatory cytokines (TNF-α, IL-1β, IL-18). Primary mouse cardiomyocytes were treated with lipopolysaccharide (LPS) to simulate sepsis in vitro. RT-qPCR and Western blot were used for analyzing gene and protein levels. CCK-8 assay assessed cell viability. NLRP3 was detected by immunofluorescence. ChIP, RIP and dual luciferase reporter assays were conducted to validate the molecular associations. USF2 was increased in serum from SCM patients, septic mice and primary cardiomyocytes. USF2 silencing improved the survival of septic mice and attenuated sepsis-induced myocardial pyroptosis and inflammation in vitro and in vivo. Mechanistically, USF2 could directly bind to the promoter of miR-206 to transcriptionally inhibit its expression. Moreover, RhoB was confirmed as a target of miR-206 and could promote ROCK activation and NLRP3 inflammasome formation. Moreover, overexpression of RhoB remarkably reversed the protection against LPS-induced inflammation and pyroptosis mediated by USF2 deletion or miR-206 overexpression in cardiomyocytes. The above findings elucidated that USF2 knockdown exerted a cardioprotective effect on sepsis by decreasing pyroptosis and inflammation via miR-206/RhoB/ROCK pathway, suggesting that USF2 may be a novel drug target in SCM.


Active syndromic surveillance of COVID-19 in Israel.
Syndromic surveillance systems monitor disease indicators to detect emergence of diseases and track their progression. Here, we report on a rapidly deployed active syndromic surveillance system for tracking COVID-19 in Israel. The system was a novel combination of active and passive components: Ads were shown to people searching for COVID-19 symptoms on the Google search engine. Those who clicked on the ads were referred to a chat bot which helped them decide whether they needed urgent medical care. Through its conversion optimization mechanism, the ad system was guided to focus on those people who required such care. Over 6 months, the ads were shown approximately 214,000 times and clicked on 12,000 times, and 722 people were informed they needed urgent care. Click rates on ads and the fraction of people deemed to require urgent care were correlated with the hospitalization rate ([Formula: see text] and [Formula: see text], respectively) with a lead time of 9 days. Males and younger people were more likely to use the system, and younger people were more likely to be determined to require urgent care (slope: [Formula: see text], [Formula: see text]). Thus, the system can assist in predicting case numbers and hospital load at a significant lead time and, simultaneously, help people determine if they need medical care.


Dynamic role of vision in the control of posture in man.
The influence of moving visual surround on the manitenance of upright posture has been studied in man during combined motion of a platform (cart) on which subjects were standing. The normal visual surround was either moving together with the cart, or with a velocity equal to cart velocity either in the same or in the opposite direction of car motion (cart acceleration was either 0.2 m/s2 or 0.05 m/s2). The changes in body pitch observed under these three conditions of visual surround motion were in the same direction as those observed when visual surround motion was given in isolation. However, their amplitude was greater, particularly when visual surround motion was in conflict with body motion.


High-grade spondylolisthesis: gradual reduction using Magerl's external fixator followed by circumferential fusion technique and long-term results.
To report the results of a cohort of patients treated with this technique high lighting radiological and functional outcomes, discussing also benefits arising from a gradual reduction procedure compared with other techniques. We evaluated nine patients who have undergone high-grade listhesis reduction and circumferential fusion at our institution from 1988 to 2006. Average length of follow-up was 11 years (5-19). Functional outcomes and radiological measurements were recorded and reported. Slip magnitude was reduced by an average of 2.9 grades (Meyerding classification). Slip angle improved by an average of 66% (p = 0.0001), lumbosacral angle by 47% (p = 0.0002), sacral rotation by 51% (p = 0.0068) and sacral inclination by 47% (p = 0.0055). At the latest follow-up 88.9% had achieved solid fusion. Post-operative 10-point Visual Analogue Score (VAS) for back pain had improved by 70% (p < 0.001) and that for leg pain by 76% (p < 0.001) compared with pre-operative score. Average postoperative Oswestry Disability Index for all patients was 8% (range 0-16%) and that for Low Back Outcome Scores was 56.6 (range 44-70). All components of Short Form 36 Health Survey were greater than 80%. Overall patients' expectations were met in 100%. This is an effective and safe technique which addresses the lumbosacral kyphosis and cosmetic deformity without the neurological complications which accompany other reduction and fusion techniques for high-grade spondylolisthesis.


Depression and anxiety in ovarian cancer: a systematic review and meta-analysis of prevalence rates.
To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. Systematic review and meta-analysis. 3623 patients with ovarian cancer from primary research investigations. The prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. We identified 24 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 3623 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 25.34% (CI 22.79% to 28.07%), 22.99% (CI 19.85% to 26.46%) and 12.71% (CI 10.14% to 15.79%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 19.12% (CI 17.11% to 21.30%), 26.23% (CI 22.30% to 30.56%) and 27.09% (CI 23.10% to 31.49%). Our findings suggest that the prevalence of depression and anxiety in women with ovarian cancer, across the treatment spectrum, is significantly greater than in the healthy female population. With the growing emphasis on improving the management of survivorship and quality of life, we conclude that further research is warranted to ensure psychological distress in ovarian cancer is not underdiagnosed and undertreated.


Metal-ligated amino acids and peptides as substrates for proteases.
Amino acids and peptides carrying a pentaamminecobalt(III) group at the carboxyl terminal have been prepared. It is shown that trypsin and papain accept such compounds as substrates provided the metal complex group is not too close to the enzyme-susceptible peptide bond. The possible applicability of this novel type of substrates in enzymatic peptide synthesis is discussed.


Suspension for the aging face.
Rejuvenation of the aging face involves modalities that refill, resurface, relax, and resuspend. As cosmetic rejuvenation procedures have become simpler and less aggressive, they have become safer, with less downtime and morbidity. Most facial rejuvenation involves a combination of these procedures, which can then be tailored to the needs of the patient.


Porcelain for veneers.
An ideal porcelain veneer placed on a non-discolored tooth requires the least amount of tooth preparation and the use of a translucent porcelain that interferes minimally with the transmission of light. In contrast, veneering a discolored tooth requires additional tooth preparation and the use of a chromatic or opacious porcelain. This article discusses several criteria for the selection of porcelain for porcelain veneers, including some steps to enhance the esthetic properties of these restorations.


An integrated open-cavity system for magnetic bead separation and manipulation.
Superparamagnetic beads are generally used in biomedical assays to manipulate, maneuver, separate, and transport bio-materials. We present a low-cost integrated system designed in bulk 0.5 μm process to automate the manipulation and separation process of magnetic beads. The system consists of an 8 × 8 coil-array suitable for a single bead manipulation, or collaborative manipulation using pseudoparallel executions. The size of a single coil is 30 μm × 30 μm and the driver DC current source supports 8 different levels up to 1.5 mA. The total power consumption of the entire system is 9 mW when running at full power and it occupies an area of 248 μm × 248 μm.


Robotic pullback technique of a precurved cochlear-implant electrode array using real-time impedance sensing feedback.
During traditional insertion of cochlear implant (CI) electrode arrays (EAs), surgeons rely on limited tactile feedback and visualization of the EA entering the cochlea to control the insertion. One insertion approach for precurved EAs involves slightly overinserting the EA and then retracting it slightly to achieve closer hugging of the modiolus. In this work, we investigate whether electrical impedance sensing could be a valuable real-time feedback tool to advise this pullback technique. Using a to-scale 3D-printed scala tympani model, a robotic insertion tool, and a custom impedance sensing system, we performed experiments to assess the bipolar insertion impedance profiles for a cochlear CI532/632 precurved EA. Four pairs of contacts from the 22 electrode contacts were chosen based on preliminary testing and monitored in real time to halt the robotic insertion once the closest modiolar position had been achieved but prior to when the angular insertion depth (AID) would be reduced. In this setting, the open-loop robotic insertion impedance profiles were very consistent between trials. The exit of each contact from the external stylet of this EA was clearly discernible on the impedance profile. In closed-loop experiments using the pullback technique, the average distance from the electrode contacts to the modiolus was reduced without greatly affecting the AID by using impedance feedback in real time to determine when to stop EA retraction. Impedance sensing, and specifically the access resistance component of impedance, could be a valuable real-time feedback tool in the operating room during CI EA insertion. Future work should more thoroughly analyze the effects of more realistic operating room conditions and inter-patient variability on this technique.


Zygoma implant under function: biomechanical principles clarified.
The purpose of this document is to clarify the biomechanical principles involved when zygoma implants are placed under functional loads. Two independent reviewers conducted electronic search of the literature from January 2000 to February 2023 describing the biomechanical principles involved using the zygoma implant for maxillary reconstruction. Articles describing the stresses within the zygoma implant, the maxillary bone and the zygoma bone under functional loads were included. The lack of maxillary boney support at the implant platform resulted in significant higher stress measured within the zygoma implant as well as the zygoma bone. The maxilla is the primary support when zygoma implants are placed under functional loads. Quad-cortical stabilization of the zygoma implants and their cross-arch stabilization are recommended to reduce the degree of stress whenever possible.


Nutritional assessment of drug addicts. Relation with HIV infection in early stages.
To assess the nutritional status of drug addicts without acute organic pathology, in order to determine the prevalence of malnutrition and to discern if early HIV infection is associated with a poor nutritional status in this group of patients. Prospective study. Detoxication unit of a university hospital. 140 drug addicts without acute organic pathology. 31 patients were HIV+. No one fulfilled the definition of AIDS. We found that drug addicts were undernourished: 92.4% weighed under the mean populational weight and 55.7% had a weight loss above 5%. The distribution of mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle area (MAMA) was lower than a reference normal population. Food intakes were poor; 66.4% of our patients complained of anorexia on admission. The mean caloric intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. The mean protein intakes were 39.3 +/- 3.3 g/day in females (0.76 +/- 0.07 g/kg/day) and 49.7 +/- 2.7 g/day in males (0.77 +/- 0.04 g/kg/day). When we compared nutritional parameters between HIV+ and HIV- patients we found no differences. Nutritional impairment in drugs abusers with early stages of HIV infection should be attributed to drug abuse rather than to HIV infection.


Moderating effects of cognitive reserve on the relationship between brain structure and cognitive abilities in middle-aged and older adults.
The cognitive reserve (CR) hypothesis is reinforced by negative moderating effects, suggesting that those with higher CR are less reliant on brain structure for cognitive function. Previous research on CR's moderating effects yielded inconsistent results, motivating our 3 studies using UK Biobank data. Study I examined five CR proxies' moderating effects on global, lobar, and regional brain-cognition models; study II extended study I by using a larger sample size; and study III investigated age-related moderating effects on the hippocampal regions. In study I, most moderating effects were negative and none survived the multiple comparison correction, but study II identified 13 global-level models with significant negative moderating effects that survived correction. Study III showed age influenced CR proxies' moderating effects in hippocampal regions. Our findings suggest that the effects of CR proxies on brain integrity and cognition varied depending on the proxy used, brain integrity indicators, cognitive domain, and age group. This study offers significant insights regarding the importance of CR for brain integrity and cognitive outcomes.


Cannibalism and virus production in Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) larvae fed with two leaf substrates inoculated with Baculovirus spodoptera.
Cannibalism in the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) (FAW), is a limiting factor in a baculovirus production system. To detect the impact of cannibalism, a two-step bioassay was conducted with different larval ages of FAW fed on two food sources (corn and castor bean leaves) contaminated with the S. frugiperda multiple-embedded nucleopolyhedrovirus. In a first bioassay, the food source affected the cannibalism, being higher for all larval ages tested (5-, 6- and 7-day-old larvae) in larvae fed on corn than on those fed on castor bean leaves. Larval mortality, weight equivalent and larval equivalents (LEs) per hectare decreased as the larval age increased. Larval weight, occlusion bodies (OBs)/larva and total OBs increased when the larval age increased. In a second bioassay, in which only 6- and 7-day-old larvae were used because of the performance in the first bioassay, the cannibalism rates were affected by the interaction between food sources and time of feeding (48 and 72 h), reaching the highest values for 6- and 7-day-old larvae fed on corn leaves for 72 h. Mortality of the FAW was affected by the interaction between food sources, larval age and time of feeding. The lowest mortalities were on 7-day-old larvae when they were fed on castor bean leaves for 48 and 72 h. Larval weight, OBs/larva, total OBs and LEs were affected by the interaction between food sources and larval age. A significant correlation was observed between larval weight and OBs/larva that fed on both food sources, suggesting that larval weight can be used to achieve a concentration to be sprayed in 1 ha.


Tolerability and effects of high doses acipimox as additional lipid-lowering therapy in familial hypercholesterolemia.
Acipimox, a derivative of nicotinic acid, lowers serum lipid levels by reducing the production of very-low-density and low-density lipoproteins (LDL). We studied the additional lipid-lowering effect of high doses of acipimox in 12 patients with severe familial hypercholesterolemia (FH) who were on treatment with an HMG CoA reductase inhibitor, in some cases in combination with a resin. There was a significant reduction in total serum cholesterol (-9%), LDL-cholesterol (-9%) and serum triglycerides (-21%) when the standard doses of acipimox (750 mg/day) was added to treatment with simvastatin (and a resin). However, higher doses had no further hypolipidemic effect. In concordance with the reduction of serum cholesterol and LDL-cholesterol there was a significant decrease in apolipoprotein (apo)-B (-11%). There was no change in HDL-cholesterol, apo-A1 and lipoprotein(a). Acipimox in high doses up to 2250 mg/d was well tolerated except for initial gastric complaints and of flushing; because of these side effects one patient dropped out of the study. Acipimox in high doses, which were well tolerated, has no additional lowering effect on LDL-levels compared to the standard dose in patients with severe FH who are already treated with simvastatin.


Molecular epidemiology and evolution of porcine parvoviruses.
Porcine parvovirus (PPV), recently named Ungulate protoparvovirus 1, is considered to be one of the most important causes of reproductive failure in swine. Fetal death, mummification, stillbirths and delayed return to estrus are predominant clinical signs commonly associated with PPV infection in a herd. It has recently been shown that certain parvoviruses exhibit a nucleotide substitution rate close to that commonly determined for RNA viruses. However, the PPV vaccines broadly used in the last 30 years have most likely reduced the genetic diversity of the virus and led to the predominance of strains with a capsid profile distinct from that of the original vaccine-based strains. Furthermore, a number of novel porcine parvovirus species with yet-unknown veterinary relevance and characteristics have been described during the last decade. In this review, an overview of PPV molecular evolution is presented, highlighting characteristics of the various genetic elements, their evolutionary rate and the discovery of new capsid profiles driven by the currently used vaccines.


Growth patterns of craniopharyngioma in children: role of the diaphragm sellae and its surgical implication.
Most craniopharyngiomas can be classified as either "prechiasmatic" or "retrochiasmatic" according to their growth patterns. The purpose of our study was to investigate the factors determining these growth patterns. The radiological, operative, and pathological findings of 25 consecutive cases were reviewed. In cases with prechiasmatic growth (n = 14), most tumors were easily separated from the undersurface of the third ventricular floor with the exception of a small area at the top of the tumor where tumor-glial interfaces occurred. Pathological examination of the tough tumor surface demonstrated well-organized collagen tissue, which is compatible with diaphragm sellae. All tumors of this type had intrasellar components, suggesting a subdiaphragmatic origin for this tumor type. On the other hand, tumors with retrochiasmatic growth (n = 11) demonstrated a prefixed chiasm, and most of the surface excluding areas exposed to ventricular cerebrospinal fluid showed tumor-glial interfaces. With the exception of three, all tumors of this type lacked intrasellar components, and the diaphragm sellae was depressed and free of tumor, suggestive of a supradiaphragmatic infundibular origin of the tumor. Growth pattern is closely correlated to the origin of the tumor, whether it is above or below the diaphragm sellae. In craniopharyngiomas with prechiasmatic growth, the major portion of the tumor could be resected by traction. These tumors are candidates for the transsphenoidal approach if the sphenoid sinus is pneumatized. Tumors with retrochiasmatic growth, which are not covered by diaphragm sellae and contact brain tissue directly, are easily torn by traction and the tumor-glial interface should be carefully dissected under direct vision.


The impact of emotional face stimuli on working memory performance among men and women with alcohol use disorder.
Individuals with alcohol use disorder (AUD) often display compromise in emotional processing and non-affective neurocognitive functions. However, relatively little empirical work explores their intersection. In this study, we examined working memory performance when attending to and ignoring facial stimuli among adults with and without AUD. We anticipated poorer performance in the AUD group, particularly when task demands involved ignoring facial stimuli. Whether this relationship was moderated by facial emotion or participant sex were explored as empirical questions. Fifty-six controls (30 women) and 56 treatment-seekers with AUD (14 women) completed task conditions in which performance was advantaged by either attending to or ignoring facial stimuli, including happy, neutral, or fearful faces. Group, sex, and their interaction were independent factors in all models. Efficiency (accuracy/response time) was the primary outcome of interest. An interaction between group and condition (F1,107 = 6.03, p < .02) was detected. Individual comparisons suggested this interaction was driven by AUD-associated performance deficits when ignoring faces, whereas performance was equivalent between groups when faces were attended. Secondary analyses suggested little influence of specific facial emotions on these effects. These data provide partial support for initial hypotheses, with the AUD group demonstrating poorer working memory performance conditioned on the inability to ignore irrelevant emotional face stimuli. The absence of group differences when scenes were to be ignored (faces remembered) suggests the AUD-associated inability to ignore irrelevance is influenced by specific stimulus qualities.


Monitoring antimicrobial resistance (AMR) using CUSUM control charts.
We evaluated the use of the Cumulative Summation (CUSUM) control chart methodology for detection of an excessive increase in antimicrobial-resistant (AMR) bacteria acquisition. We used administrative, clinical and bacteriological data from all 157,570 patients hospitalized for at least 48 h from January 1, 2010 to December 31, 2015 in a 654-bed university teaching hospital in Paris, France. Monthly computed CUSUM were evaluated for the detection of out-of-control situations, defined as incidence rates of acquired AMR bacterial colonization exceeding acceptable thresholds at the hospital and ward levels (based on six selected wards) for AMR bacteria overall and Extended-spectrum beta-lactamases Enterobacteriaceae (ESBL-E) and Methicillin-resistant Staphylococcus aureus (MRSA), specifically. During the study period, 1,403 samples of acquired AMR bacteria were identified including 1,129 ESBL-E and 151 MRSA. The incidence rate of acquired AMR bacteria was stable at the hospital and the wards level. When based on AMR bacteria overall, CUSUM alarms were triggered at the hospital level and at the ward level in four units. For ESBL-E, CUSUM tests generated alarms at the hospital level and for the same four wards, and for MRSA, CUSUM tests detected out-of-control situations in all the wards. The CUSUM approach appears complementary with hospital infection control strategies currently in practice and appears of interest in common practice as a simple tool for AMR surveillance.


Evolutionary characterization of the emerging porcine epidemic diarrhea virus worldwide and 2014 epidemic in Taiwan.
Since 2010, a new variant of PEDV belonging to Genogroup 2 has been transmitting in China and further spreading to the Unites States and other Asian countries including Taiwan. In order to characterize in detail the temporal and geographic relationships among PEDV strains, the present study systematically evaluated the evolutionary patterns and phylogenetic resolution in each gene of the whole PEDV genome in order to determine which regions provided the maximal interpretative power. The result was further applied to identify the origin of PEDV that caused the 2014 epidemic in Taiwan. Thirty-four full genome sequences were downloaded from GenBank and divided into three non-mutually exclusive groups, namely, worldwide, Genogroup 2 and China, to cover different ranges of secular and spatial trends. Each dataset was then divided into different alignments by different genes for likelihood mapping and phylogenetic analysis. Our study suggested that both nsp3 and S genes contained the highest phylogenetic signal with substitution rate and phylogenetic topology similar to those obtained from the complete genome. Furthermore, the proportion of nodes with high posterior support (posterior probability >0.8) was similar between nsp3 and S genes. The nsp3 gene sequences from three clinical samples of swine with PEDV infections were aligned with other strains available from GenBank and the results suggested that the virus responsible for the 2014 PEDV outbreak in Taiwan clustered together with Clade I from the US within Genogroup 2. In conclusion, the current study identified the nsp3 gene as an alternative marker for a rapid and unequivocal classification of the circulating PEDV strains which provides complementary information to the S gene in identifying the emergence of epidemic strain resulting from recombination.


Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts.
The differentiation of myoblasts is regulated by multiple extracellular and intracellular factors. Of the extracellular regulators, members of transforming growth factor-beta (TGF-beta) family play critical roles in the regulation of osteoblasts and myoblast differentiation. Little is known, however, about the regulation of Myostatin/TGF-beta signaling during myoblast differentiation. In this study, we examined the roles of Arkadia, an E3 ubiquitin ligase, in Myostatin/TGF-beta signaling and the regulation of myoblast differentiation. Knockdown of Arkadia reduced Myostatin/TGF-beta signaling and enhanced the differentiation of C2C12 myoblasts. In addition, exogenous overexpression of Arkadia enhanced Myostatin/TGF-beta signaling, preventing myoblast differentiation. In the absence of the activation of Myostatin/TGF-beta signaling, knockdown of Arkadia enhanced myoblast differentiation via upregulation of Ski protein, an intracellular enhancer of myoblast differentiation. Arkadia likely affected the differentiation of myoblasts in a Smad-independent fashion by inducing Ski degradation. Knockdown of Arkadia increased the Myostatin-induced phosphorylation of Smad2/3 in C2C12 cells. Arkadia bound Smad2/3 via Ski to induce the ubiquitination of Smad2/3. These results suggest that Arkadia targets Ski-bound, inactive phospho-Smad2/3 to regulate positively Myostatin/TGF-beta signaling. Taken together, this study indicates that Arkadia regulates myoblast differentiation through both Smad-dependent and Smad-independent pathways.


The Influence of Nucleus Mechanics in Modelling Adhesion-independent Cell Migration in Structured and Confined Environments.
Recent biological experiments (Lämmermann et al. in Nature 453(7191):51-55, 2008; Reversat et al. in Nature 7813:582-585, 2020; Balzer et al. in ASEB J Off Publ Fed Am Soc Exp Biol 26(10):4045-4056, 2012) have shown that certain types of cells are able to move in structured and confined environments even without the activation of focal adhesion. Focusing on this particular phenomenon and based on previous works (Jankowiak et al. in Math Models Methods Appl Sci 30(03):513-537, 2020), we derive a novel two-dimensional mechanical model, which relies on the following physical ingredients: the asymmetrical renewal of the actin cortex supporting the membrane, resulting in a backward flow of material; the mechanical description of the nuclear membrane and the inner nuclear material; the microtubule network guiding nucleus location; the contact interactions between the cell and the external environment. The resulting fourth order system of partial differential equations is then solved numerically to conduct a study of the qualitative effects of the model parameters, mainly those governing the mechanical properties of the nucleus and the geometry of the confining structure. Coherently with biological observations, we find that cells characterized by a stiff nucleus are unable to migrate in channels that can be crossed by cells with a softer nucleus. Regarding the geometry, cell velocity and ability to migrate are influenced by the width of the channel and the wavelength of the external structure. Even though still preliminary, these results may be potentially useful in determining the physical limit of cell migration in confined environments and in designing scaffolds for tissue engineering.


Craving of prescription opioids in patients with chronic pain: a longitudinal outcomes trial.
Little is known about whether patients with chronic pain treated with opioids experience craving for their medications, whether contextual cues may influence craving, or if there is a relationship between craving and medication compliance. We hypothesized that craving for prescription opioids would be significantly correlated with the urge for more medication, preoccupation with the next dose, and current mood symptoms. We studied craving in 62 patients with chronic pain who were at low or high risk for opioid misuse, while they were enrolled in an RCT to improve prescription opioid medication compliance. Using electronic diaries, patients completed ratings of craving at monthly clinic visits and daily during a 14-day take-home period. Both groups consistently endorsed craving, whose levels were highly correlated (P < .001) with urge, preoccupation, and mood. The intervention to improve opioid compliance in the high-risk group was significantly associated with a rate of decrease in craving over time in comparison to a high-risk control group (P < .05). These findings indicate that craving is a potentially important psychological construct in pain patients prescribed opioids, regardless of their level of risk to misuse opioids. Targeting craving may be an important intervention to decrease misuse and improve prescription opioid compliance. Patients with noncancer pain can crave their prescription opioids, regardless of their risk for opioid misuse. We found craving to be highly correlated with the urge to take more medication, fluctuations in mood, and preoccupation with the next dose, and to diminish with a behavioral intervention to improve opioid compliance.


Conductive, Acid-Doped Polyaniline Electrospun Nanofiber Gas Sensing Substrates Made Using a Facile Dissolution Method.
A novel dissolution method that allows for the total solvation of high-concentration, high-molecular-weight polyaniline (PANi) doped with (+)-camphor-10-sulfonic acid (CSA) is reported. Preparation of 12-16 wt % 65,000 Da PANi solutions in N,N-dimethylformamide is achievable using a simple one-pot method. Doped polyaniline solutions in common organic solvents were processed into nanofibers using a convenient single-nozzle electrospinning technique. The electrospinning of PANi-CSA into nanofibrous membranes generated substrates that were subsequently employed in colorimetric gas sensing. These substrates demonstrated linearity of response upon exposure to 50-5500 ppm ammonia at ambient (50 ± 10% RH) and high (80% RH) humidity.


Re-engineering cellular physiology by rewiring high-level global regulatory genes.
Knowledge of global regulatory networks has been exploited to rewire the gene control programmes of the model bacterium Salmonella enterica serovar Typhimurium. The product is an organism with competitive fitness that is superior to that of the wild type but tuneable under specific growth conditions. The paralogous hns and stpA global regulatory genes are located in distinct regions of the chromosome and control hundreds of target genes, many of which contribute to stress resistance. The locations of the hns and stpA open reading frames were exchanged reciprocally, each acquiring the transcription control signals of the other. The new strain had none of the compensatory mutations normally associated with alterations to hns expression in Salmonella; instead it displayed rescheduled expression of the stress and stationary phase sigma factor RpoS and its regulon. Thus the expression patterns of global regulators can be adjusted artificially to manipulate microbial physiology, creating a new and resilient organism.


Induction of vitellogenin mRNA in juvenile Chinese sturgeon (Acipenser sinensis Gray) treated with 17beta-estradiol and 4-nonylphenol.
It has been demonstrated that 4-nonylphenol (4-NP) exerts estrogenic effects in diverse fishes. The present study investigated the effects of 4-NP on Chinese sturgeon (Acipenser sinensis Gray) vitellogenin (VTG) gene expression. By reverse transcription-polymerase chain reaction (RT-PCR) using degenerate primers, a 462-base pair fragment of Chinese sturgeon VTG, corresponding to a 154-amino acid sequence, was amplified and sequenced. This sequence exhibited 152/154 identity to the amino acid sequence of white sturgeon (A. transmontano) VTG. Conventional RT-PCR and quantitative real-time RT-PCR were established and used to study the VTG and beta-actin gene expression in the liver of juvenile Chinese sturgeon injected three times with 17beta-estradiol (5 mg/kg body wt/week) or 4-NP (10 or 100 mg/kg/week) in the course of three weeks. Significant induction of VTG gene expression was detected in all treated groups, and no VTG mRNA was detected in the control group. The ratio of VTG to beta-actin analyzed from the results of quantitative real-time RT-PCR reached 0.041 +/- 0.024 (mean +/- SD) in the group receiving 10 mg/kg/week of 4-NP and 4.51 +/- 1.68 in the group receiving 100 mg/kg/week of 4-NP. Chemical analysis of 4-NP showed that the concentrations of 4-NP in the 10 mg/kg/week group and the 100 mg/kg/week group were 2.78 +/- 2.41 and 31.38 +/- 0.26 mcirog/ g wet weight, respectively. Compared with the 4-NP concentrations (0.8-1.92 microg/g wet wt) in fish from the Yangtze River, China, a potential hazard exists regarding 4-NP in Chinese sturgeon. These results represent the first indication of the risk of endocrine-disrupting chemicals for Chinese sturgeon.


Glutathione S-transferase is an in vitro substrate of Ca++-phospholipid-dependent protein kinase (protein kinase C).
Glutathione S-transferase was found to be a good substrate of Ca++-phospholipid-dependent protein kinase in vitro. Of 6 isozymes of glutathione transferase purified from rat liver cytosol (1-1, 1-2, 2-2, 3-3, 3-4, 4-4), only isozymes 1-1, 1-2 and 2-2 were significantly phosphorylated by the kinase purified from rabbit brain. Phosphorylation was more pronounced in subunit 1 than in subunit 2, and the degree of the phosphorylation was similar in all three homo- and heterodimers, where 1 mol of phosphoryl group per mol subunit was transferred to the subunit 1. The phosphorylated transferase 1-1 showed decreased affinity for bilirubin, suggesting that the phosphorylation affects the function of glutathione S-transferase in an isozyme-specific manner.


Prognostic significance of DNA content with special reference to age in gastric cancer.
The authors studied 93 patients who had undergone curative resection for advanced gastric cancer to assess the prognostic significance of DNA ploidy in relation to patient age. The cancers were classified as low and high-ploidy carcinomas and the patients were grouped by age (22-44 years, 45-64 years, 65-79 years). The incidence of high ploidy cancers increased with age. The 5-year survival rate increased with patient age in the low ploidy group whereas it decreased with patient age in the high ploidy group. There was a statistically significant difference (P less than 0.05) in the 5-year survival between our oldest patients with low (100%) and high ploidy (25.7%) gastric cancer. High ploidy cancers manifested a higher incidence of vessel invasion and lymph node metastasis. Our findings indicate that analysis of the DNA distribution pattern in gastric carcinoma is of prognostic value especially in older patients.


Androgens and estrogens stimulate ribosome biogenesis in prostate and breast cancer cells in receptor dependent manner.
Ribosome biogenesis is a fundamental cellular process intimately linked to cell growth and proliferation, which is upregulated in most of cancers especially in aggressive cancers. In breast and prostate cancers steroid hormone receptor signalling is the principal stimulus for cancer growth and progression. Here we investigated the link between estrogen and androgen receptor signalling and the initial stage of ribosome biogenesis - transcription of rRNA genes. We have discovered that oestrogen or androgen treatment can positively regulate rRNA synthesis in breast and prostate cancer cells respectively and that this effect is receptor dependent. This novel and interesting finding suggests a previously unidentified link between steroid hormone receptor signalling pathways and the regulation of ribosome biogenesis.


Current approaches for mitigating acid mine drainage.
AMD is one of the critical environmental problems that causes acidification and metal contamination of surface and ground water bodies when mine materials and/or over burden-containing metal sulfides are exposed to oxidizing conditions. The best option to limit AMD is early avoidance of sulfide oxidation. Several techniques are available to achieve this. In this paper, we review all of the major methods now used to limit sulfide oxidation. These fall into five categories: (1) physical barriers,(2) bacterial inhibition, (3) chemical passivation, ( 4) electrochemical, and (5) desulfurization.We describe the processes underlying each method by category and then address aspects relating to effectiveness, cost, and environmental impact. This paper may help researchers and environmental engineers to select suitable methods for addressing site-specific AMD problems.Irrespective of the mechanism by which each method works, all share one common feature, i.e., they delay or prevent oxidation. In addition, all have limitations.Physical barriers such as wet or dry cover have retarded sulfide oxidation in several studies; however, both wet and dry barriers exhibit only short-term effectiveness.Wet cover is suitable at specific sites where complete inundation is established, but this approach requires high maintenance costs. When employing dry cover, plastic liners are expensive and rarely used for large volumes of waste. Bactericides can suppress oxidation, but are only effective on fresh tailings and short-lived, and do not serve as a permanent solution to AMD. In addition, application of bactericides may be toxic to aquatic organisms.Encapsulation or passivation of sulfide surfaces (applying organic and/or inorganic coatings) is simple and effective in preventing AMD. Among inorganic coatings,silica is the most promising, stable, acid-resistant and long lasting, as compared to phosphate and other inorganic coatings. Permanganate passivation is also promising because it creates an inert coating on the sulfide surface, but the mechanism by which this method works is still unclear, especially the role of pH. Coatings of Fe-oxyhydroxide, which can be obtained from locally available fly ash are receiving attention because of its low cost, self-healing character, and high cementation capacity. Among organic coatings, lipids and natural compounds such as humic acid appear to be encouraging because they are effective, and have a low environmental impact and cost. Common advantages of organic vs. inorganic coatings are that they work best at low pH and can prevent both chemical and biological oxidation.However, organic coatings are more expensive than inorganic coatings. Furthermore,while organic coatings are effective under laboratory conditions, they often fail under field conditions or require large amounts of reagents to insure effectiveness.Electrochemical cover technology may become a suitable technique to prevent AMD, but the mechanism by which this technique operates is still under investigation.Limitations of this method include the initial capital cost and ongoing costs of anodes and cathodes.Desulfurization is an alternative process for managing large-scale sulfide wastes/tailings. This process can separate sulfide minerals into a low-volume stream, leaving mainly waste with low sulfur content that will be non-acid-generating. The attractiveness of desulfurization is that it is simple and economic.Our review has clearly disclosed that more information is needed for most of the AMD-mitigation techniques available. Silica passivation has shown promise, butmore extensive field-testing is needed to reduce it to commercial viability. Silica is the dominant element in fly ash, and therefore, its use as a low-cost, easily accessible coating should be evaluated. Permanganate passivation also requires further study to understand the role of pH. The secondary formation of Fe-oxyhydroxide minerals from Fe-oxyhydroxides, from the standpoint of their phase transformation,stability and effectiveness, should be assessed over longer experimental periods. All inorganic coatings are designed to inhibit abiotic oxidation of pyrite; however, their effect on biotic pyrite oxidation is not well known and should be further studied.Currently, there is no information available on longer-term field application of organic reagents. Such information is needed to evaluate their lifetime environmental and performance effects. Future studies require spectroscopic analyses of all coating types to achieve a better understanding of their surface chemistry. In addition,a thorough mineralogical and geochemical characterization of waste materialsis essential to understand the acid generating potential, which can indeed help to select better prevention measures.From having performed this review, we have concluded that no single method is technologically mature, although the majority of methods employed are promising for some applications, or at specific sites. Combining techniques can help ac~Ie:eAMD containment in some cases. For example, applying dry cover (e.g., sml) mcombination with liming material or a bactericide, or applying inorganic coatings(e.g., silica) along with organic reagents (e.g., lipids or humic acid) may be moreeffective than utilizing any single technique alone.


Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer.
The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation. Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9 ± 3.8 years, range 28-46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012-2014. Early (PNf, t2-t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB1, and texpB2) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms. Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0-7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB1, and texpB2. The proportion of female embryos was 69-71 and 25-26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74-78 % of them, increasing their proportion by 57 % compared to the average. Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.


Functional Genetic Variants in TGFβ1 and TGFβR1 in miRNA-Binding Sites Predict Outcomes in Patients with HPV-positive Oropharyngeal Squamous Cell Carcinoma.
TGFβ1 and TGFβ receptor 1 (TGFβR1) participate in regulation of the host's immune system and inflammatory responses and may serve as prognostic biomarkers for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). This study included 1,013 patients with incident OPSCC, of whom 489 had tumor HPV16 status determined. All patients were genotyped for two functional polymorphisms: TGFβ1 rs1800470 and TGFβR1 rs334348. Univariate and multivariate Cox regression models were performed to evaluate associations between the polymorphisms and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Patients with TGFβ1 rs1800470 CT or CC genotype had 70%-80% reduced risks of OS, DSS, and DFS compared with patients with TT genotype, and patients with TGFβR1 rs334348 GA or GG genotype had 30%-40% reduced risk of OS, DSS, and DFS compared with patients with AA genotype. Furthermore, among patients with HPV-positive (HPV+) OPSCC, the same patterns were observed but the risk reductions were greater: up to 80%-90% for TGFβ1 rs1800470 CT or CC genotype and 70%-85% for TGFβR1 rs334348 GA or GG genotype. The risk reductions were still greater (up to 17 to 25 times reduced) for patients with both TGFβ1 rs1800470 CT or CC genotype and TGFβR1 rs334348 GA or GG genotype compared with patients with both TGFβ1 rs1800470 TT genotype and TGFβR1 rs334348 AA genotype among patients with HPV+ OPSCC. Our findings indicate that TGFβ1 rs1800470 and TGFβR1 rs334348 may individually or jointly modify risks of death and recurrence in patients with OPSCC, particularly those with HPV+ OPSCC undergoing definitive radiotherapy, and may serve as prognostic biomarkers, which could lead to better personalized treatment and improved prognosis.


Genetic and epigenetic contributors to FSHD.
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscle disorder characterized by distinct chromatin changes including DNA hypomethylation of the D4Z4 macrosatellite repeat array on a disease-permissive 4qA allele and aberrant expression of the D4Z4-embedded DUX4 retrogene in skeletal muscle. Insufficient epigenetic repression of the D4Z4 repeat is the result of at least two different genetic mechanisms leading to two forms of disease, FSHD1 and FSHD2. In the case of FSHD1, a contraction of the D4Z4 repeat array is disease causing whereas FSHD2 is most often caused by mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. Recent studies indicate that a combination of genetic and epigenetic factors that act on the D4Z4 repeat array determine the probability of DUX4 expression in skeletal muscle and disease penetrance and progression.


Silk Fiber as the Support and Reductant for the Facile Synthesis of Ag-Fe₃O₄ Nanocomposites and Its Antibacterial Properties.
We report a facile and environmentally friendly approach to prepare Ag-Fe₃O₄-silk fiber nanocomposites. The Ag-Fe₃O₄-silk fiber acts as: (i) a biocompatible support for the silver nanoparticles; and (ii) a reducing agent for the silver ions. Neither additional reducing agents nor toxic organic solvents were used during the preparation process. The Ag-Fe₃O₄-silk fiber nanocomposites can be actuated by a small household magnet and have high antibacterial activities against both Escherichia coli and Staphylococcus aureus. These nanocomposites could be easily recycled without a decrease in their antibacterial activities due to the synergistic effects between the Ag NPs and Fe₃O₄ NPs with large amounts of active sites.


Defining Transcriptional Signatures of Human Hair Follicle Cell States.
The epidermis and its appendage, the hair follicle, represent an elegant developmental system in which cells are replenished with regularity because of controlled proliferation, lineage specification, and terminal differentiation. Although transcriptome data exists for human epidermal and dermal cells, the hair follicle remains poorly characterized. Through single-cell resolution profiling of the epidermis and anagen hair follicle, we characterized the anatomical, transcriptional, functional, and pathological profiles of distinct epidermal, hair follicle, and hair follicle-associated cell subpopulations including melanocytes, endothelial cells, and immune cells. We additionally traced the differentiation trajectory of interfollicular and matrix cell progenitors and explored the association of specific cell subpopulations to known molecular signatures of common skin conditions. These data simultaneously corroborate prior murine and human studies while offering new insights into epidermal and hair follicle differentiation and pathogenesis.


Inhibition by vasoactive intestinal peptide of antigen-induced histamine release from guinea-pig minced lung.
Vasoactive intestinal peptide (VIP) was found to inhibit ovalbumin-induced histamine release from guinea-pig minced lung. Maximum inhibition occurred with a 10-20 min time of preincubation with VIP. Spontaneous histamine release was not altered by VIP. With 2 x 10(-6) M VIP, the dose-response curve to ovalbumin was shifted about 3-fold to the right, but the maximum histamine release was unaltered. Respiratory tract infection with parainfluenza 3 virus did not influence the inhibitory effect of VIP on histamine release.


Indications for thyroid FNA and pre-FNA requirements: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.
The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussions between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes the indications for performing an FNA of a nodule discovered by physical examination or an imaging study; the indications for using ultrasound versus palpation for guidance when performing a thyroid FNA; the issues surrounding informed consent for thyroid FNA; and the information required on a requisition form that accompanies a thyroid FNA specimen. (http://thyroidfna.cancer.gov/pages/info/agenda/)


A device for the automated monitoring of stereotypic behavior.
1. A novel rotation sensing device has been developed which consists of a linear potentiometer attached to the top of a spherical testing chamber. The potentiometer constantly monitors the precise angular position of the animal inside the chamber. 2. This device allows the automated monitoring of direction and rate of rotation, as well as a variety of other stereotypic behaviors. 3. The effects of morphine, apomorphine and amphetamine on motor activity were assessed by the apparatus.