Latent Hypothyroidism in Adults.
The prevalence of latent/subclinical hypothyroidism is between 3% and 10%, according to epidemiologic studies that have been carried out in the USA, the United Kingdom, and Denmark. As persons with latent hypo - thyroidism are often asymptomatic, the diagnosis is often made incidentally in routine laboratory testing. This review is based on a selective search in PubMed for publications on the diagnosis and treatment of latent hypothyroidism. All pertinent articles and guidelines published from 1 January 2000 to 31 July 2016 were included. The diagnosis of latent hypothyroidism is generally assigned after repeated measurement of a TSH concentration above 4.0 mU/L in a person whose fT4 concentration is in the normal range. The most common cause is autoimmune thyroiditis, which can be detected by a test for autoantibodies. L-thyroxin supplementation is a controversial matter: its purpose is to prevent the development of overt hypothyroidism, but there is a danger of overtreatment, which increases the risk of fracture. To date, no benefit of L-thyroxin supplementation has been demonstrated with respect to morbidity and mortality, health-related quality of life, mental health, cognitive function, or reduction of overweight. There is, however, evidence of a beneficial effect on cardiac function in women, and on the vascular system. At present, treatment is generally considered indicated only if the TSH level exceeds 10.0 mU/L. Limited data are available on the relevant clinical endpoints and undesired side effects of supplementation therapy. Physicians should advise patients about the indications for such treatment on an individual basis after due consideration of the risks and benefits.


In vivo shRNA screens in solid tumors.
Loss-of-function (LOF) experiments targeting multiple genes during tumorigenesis can be implemented using pooled shRNA libraries. RNAi screens in animal models rely on the use of multiple shRNAs to simultaneously disrupt gene function, as well as to serve as barcodes for cell fate outcomes during tumorigenesis. Here we provide a protocol for performing RNAi screens in orthotopic mouse tumor models, referring to glioma and lung adenocarcinoma as specific examples. The protocol aims to provide guidelines for applying RNAi to a diverse spectrum of solid tumors and to highlight crucial considerations when designing and performing these studies. It covers shRNA library assembly and packaging into lentiviral particles, and transduction into tumor-initiating cells (TICs), followed by in vivo transplantation, tumor DNA recovery, sequencing and analysis. Depending on the target genes and tumor model, tumor suppressors and oncogenes can be identified or biological pathways can be dissected in 6-9 weeks.


[Advantages of scalp acupuncture at cranial base zone for refractory ophthalmopathy].
The cranial base zone is located in the lower posterior part of harnpan, the area 0.5 cun up and down from the line from Yamen (GV 15) to Yifeng (TE 17). There are Tianzhu (BL 10) in the bladder meridian, Fengchi (GB 20) and Wangu (GB 12) in the gallbladder meridian, and Yiming (EX-HN 14). The four acupoints own the function of treating eye diseases. The auther find acupuncture at the cranial base zone can obviously improve the effect on refractory eye diseases. The manipulation mainly shows small amplitude lifting and thrusting with multiple filiform needles. The functions of exciting meridian qi, smoothing meridian and collateral, and making qi go into the sick part fast could occur with eye movement and orbital relaxation movement during manipulation. Thus, the effect is achieved. This paper explain the advantages of acupuncture at the cranial base zone for eye diseases in detail, with 1 case for example.


Accuracy of CT guidance of lumbar facet joint block.
Lumbar facet joint block is generally performed under fluoroscopic guidance. The purpose of this study was to assess the technical success rate of facet joint block under CT guidance. The CT scanner was operated tableside with a step-and-shoot mode for intermittent needle visualization, and the amount of radiation used to perform the procedures was estimated. CT-guided facet joint block is safe and rapid. Use of CT ensures reliable needle guidance with extremely high procedural accuracy at an effective radiation dose comparable to that of a procedure performed with 1 minute of fluoroscopic guidance.


Mie and refraction theory comparison for particle sizing with the laser velocimeter.
Symmetries are shown to exist in a Mie theory formulation of interferometric visibility which may be exploited to achieve significant reductions in computer time. Some limits to visibility calculation by refraction theory are noted, and a correlation of symmetry results with Mie and refraction theory agreement is shown to exist.


Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer.
Fetal liver, the major site of hematopoiesis during embryonic development, acquires additional various metabolic functions near birth. Although liver development has been characterized biologically as consisting of several distinct steps, the molecular events accompanying this process are just beginning to be characterized. In this study, we have established a novel culture system of fetal murine hepatocytes and investigated factors required for development of hepatocytes. We found that oncostatin M (OSM), an interleukin-6 family cytokine, in combination with glucocorticoid, induced maturation of hepatocytes as evidenced by morphological changes that closely resemble more differentiated hepatocytes, expression of hepatic differentiation markers and intracellular glycogen accumulation. Consistent with these in vitro observations, livers from mice deficient for gp130, an OSM receptor subunit, display defects in maturation of hepatocytes. Interestingly, OSM is expressed in CD45(+) hematopoietic cells in the developing liver, whereas the OSM receptor is expressed predominantly in hepatocytes. These results suggest a paracrine mechanism of hepatogenesis; blood cells, transiently expanding in the fetal liver, produce OSM to promote development of hepatocytes in vivo.


Thoracoscopy versus thoracotomy: a prospective comparison of trauma and quality of life.
Reliable comparisons of thoracoscopy (TCC) and anterolateral thoracotomy (ATT) with regard to trauma and post-operative quality of life are rare. This study was conducted to quantify the results of TCC, which was expected to show an advantage. Using a matched-pair design (matching criteria: comparable intracavitary procedure, benign/malignant disease and sex), 22 patients were compared who underwent either TCC or ATT (Wilcoxon matched-pairs signed-ranks test, P<0.05). Incision and operation time were shorter for TCC (TCC 5.3 vs ATT 23.7 cm, P=0.003; TCC 64 vs ATT 87 min, P=0.029). Differences in favor of TCC were detected for interleukin 6 (IL6) (TCC 17.2 vs ATT 105.6 pg/ml, P=0.036) in the immediate postoperative period, C-reactive protein (CRP) (TCC 28.2 vs ATT 86.6 mg/l; P=0.010) on the day 1 after the operation, forced vital capacity (FVC) (TCC 2.5 vs ATT 1.5 l, P=0.0173), elevation of the arm (EA) (TCC 143 vs ATT 109; P=0,026), pain on coughing (CP) (TCC 2.5 vs ATT 6.9 patients; P=0.009) and Spitzer Index (SI) (TCC 9.2 vs ATT 7,1 patients; P=0.009), as well as CP (TCC 1.4 vs ATT 4.4 patients; P=0,005) on day 4 after the operation. Forced expiratory volume in the first second, pain, creatin kinase, blood glucose and neopterin showed no differences. In terms of surgical trauma and quality of life ICC is superior to ATT in the immediate postoperative period. With the exception of pain and coughing, there were no differences after postoperative day 4.


Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice.
Mixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1 /2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1 /2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)-pyrene-DNA adduct formation was markedly increased at 6,15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.


Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344.
Numerous studies have indicated that selective agonists of group II metabotropic glutamate (mGlu) receptors, such as LY354740 [(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate] and LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate], may be useful in the treatment of many psychiatric disorders, including psychosis, anxiety, and drug withdrawal. Although animal and human studies demonstrate potential therapeutic utility, poor oral bioavailability is a limiting factor in the clinical development of these compounds. Therefore, a novel prodrug approach is being pursued to increase exposure levels of active compound after oral administration. Here, we demonstrate a 10-fold increase in brain, plasma, and cerebrospinal fluid levels of LY354740 after oral prodrug administration. Furthermore, we compare the oral efficacy of the mGlu2/3 receptor agonist LY354740 and its prodrug LY544344 [(1S,2S,5R,6S)-2-[(2'S)-(2'-amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride] in rodent models of psychosis and anxiety. Phencyclidine (PCP)-induced hyperlocomotion was dose dependently inhibited in rats receiving oral administration of 30 or 100 mg/kg LY544344, whereas LY354740 did not significantly reverse PCP-mediated behaviors at doses up to 100 mg/kg. Orally administered LY544344 (30 mg/kg) and subcutaneously administered LY354740 (10 mg/kg) attenuated stress-induced hyperthermia in DBA/2 mice, with the prodrug producing anxiolytic effects at lower oral doses than the parent compound. Although oral administration of LY354740 did not significantly affect fear-induced suppression of operant responding in rats, subcutaneously administered LY354740 (10 or 20 mg/kg) and orally administered LY544344 (10 or 30 mg/kg) produced significant anxiolytic effects in this model. The present data confirm that mGlu2/3 receptor agonists produce antipsychotic and anxiolytic effects in animal behavioral models and demonstrate that oral bioavailability of LY354740 was substantially increased using a prodrug strategy.


Fluids and hyperosmolar agents in neurocritical care: an update.
To discuss recent updates in fluid management and use of hyperosmolar therapy in neurocritical care. Maintaining euvolemia with crystalloids seems to be the recommended fluid resuscitation for neurocritical care patients. Buffered crystalloids have been shown to reduce hyperchloremia in patients with subarachnoid hemorrhage without causing hyponatremia or hypo-osmolality. In addition, in patients with traumatic brain injury, buffered solutions reduce the incidence of hyperchloremic acidosis but are not associated with intracranial pressure (ICP) alteration. Both mannitol and hypertonic saline are established as effective hyperosmolar agents to control ICP. Both agents have been shown to control ICP, but their effects on neurologic outcomes are unclear. A recent surge in preference for using hypertonic saline as a hyperosmolar agent is based on few studies without strong evidence. Fluid resuscitation with crystalloids seems to be reasonable in this setting although no recommendations can be made regarding type of crystalloids. Based on current evidence, elevated ICP can be effectively reduced by either hypertonic saline or mannitol.


[ARTHROSCOPIC TREATMENT OF ANTERIOR CRUCIATE LIGAMENT TIBIAL EMINENCE AVULSION FRACTURE IN ADOLESCENTS WITH EPIPHYSEAL UNCLOSURE].
To evaluate the clinical results of arthroscopic treatment of anterior cruciate ligament (ACL) tibial eminence avulsion fractures in adolescents with epiphyseal unclosure. Between January 2011 and October 2013, 35 knees with ACL tibial eminence avulsion fractures (35 patients with epiphyseal unclosure) were arthroscopically treated with suture fixation. There were 25 males and 10 females, aged 8-16 years (mean, 14.7 years). The causes included sports injury in 24 cases, traffic accident injury in 9 cases, and daily life injury in 2 cases. According to Meyers-McKeever classification criteria, there were 27 cases of type II and 8 cases of type III. Five cases had meniscus injury. The preoperative the International Knee Documentation Committee (IKDC) score was 48.7 ± 3.2, and Lysholm score was 51.2 ± 4.5. The time from injury to operation was 2-16 days (mean, 5 days). Primary healing of incision was obtained in all patients. The mean follow-up time was 22.4 months (range, 12-32 months). Anatomical reduction was achieved in 28 cases and satisfactory reduction in 7 cases. X-ray films showed all fractures healing at last follow-up. There was no limb shortening deformity, varus knee, or valgus knee. Lachman test results were all negative. The other knees had normal range of motion except 1 knee with limited flexion, whose range of motion returned to 0-120° after treatment. At last follow-up, the IKDC score was significantly improved to 93.2 ± 4.1 (t = -53.442, P = 0.000), and the Lysholm score was significantly increased to 96.2 ± 2.5 (t = -56.242, P = 0.000). The arthroscopic fixation technique has satisfactory results for the reduction and fixation of ACL tibial eminence avulsion fracture in the adolescents with epiphyseal unclosure because of little trauma and quick recovery.


The relationship between composition of gain and circulating hormones in growing beef bulls fed three dietary crude protein levels.
Twenty-one Simmental crossbred bulls (311 +/- 11 kg, 9 mo of age) were used to determine the effect of feeding 10, 12 or 14% CP on concentration of hormones in blood and the relationship of these hormones to composition of gain. Six bulls were slaughtered on d 0 to provide an estimate of initial carcass composition (9-11 rib section). Remaining bulls were assigned to dietary treatments. Blood samples were collected every 30 min from 0800 to 2000 on d 0, 66, 136 and 202 of treatment; bulls were slaughtered on d 203. Across all treatments, growth hormone (GH) declined (P less than .05) from d 0 to d 202. Free insulin-like growth factor I (IGF-I) was lowest (P less than .05) on d 0. In four randomly selected bulls, IGF-I fluctuated during the 12-h sampling periods. Within each treatment group, insulin was greatest on d 202 (P less than .05). Testosterone (T) increased from d 0 to d 66, then declined. Cortisol (C) was lowest on d 66. Thyroid hormones increased (P less than .05) after d 0. Growth hormone and IGF-I were correlated negatively with carcass fat percentage, fat accretion rate and fat thickness. IGF-I concentrations were correlated positively with percentage of carcass protein. Testosterone:cortisol ratio was not related to composition, but high T coupled with low C may be related to carcass leanness (mean carcass fat = 24.4%). These data suggest that GH and IGF-I are the hormones most related to composition of gain in growing beef bulls.


The social dimensions of invasive plants.
Invasive plants pose a major environmental management issue. Research into the social dimensions of this issue has flourished over the past decade, as part of the critical examination of relations between human and nonhuman worlds. The social sciences and humanities have made substantial contributions to conceptualizing invasiveness and nativeness; understanding the perceptions, attitudes and values of diverse stakeholders; and analysing the politics and practices of invasive plant management. Cultural analysis allows areas of conflict and commonality to be identified. Social complexity must be added to ecological complexity to understand the causal relationships underlying invasions; and linear understandings of science-policy relationships are too simplistic. Productive connections have been established between recent social and natural science approaches in the context of rapid environmental change and unpredictable futures. Nonetheless, the prevalence of human exceptionalism in the ecological sciences constitutes a major point of divergence between social and natural science perspectives.


Unconjugated, glycine-conjugated, taurine-conjugated bile acid nonsulfates and sulfates in urine of young infants with cholestasis.
A direct assay system for conjugated bile acids using an enzymatic procedure and high-performance liquid chromatography was used for the analysis of urinary bile acid profiles in young infants with intrahepatic cholestasis (idiopathic neonatal hepatitis syndrome) or extra-hepatic biliary atresia. The major urinary bile acids were cholate and chenodeoxycholate conjugates, but a small amount of deoxycholate and 3 beta-hydroxy-5-cholenate conjugates were detected. Although there was no significant difference in total bile acid excretion between patients with intrahepatic cholestasis and extrahepatic biliary atresia, mean ratios of cholate to chenodeoxycholate and sulfated to total urinary bile acids were different between the two groups examined (5.63 +/- 2.83 vs. 2.50 +/- 1.25, p less than 0.05, 15.8 +/- 9.9 vs. 34.5 +/- 9.9%, p less than 0.005). The proportion of taurine-conjugated chenodeoxycholate in the sulfate fraction to the total bile acid was lower in intrahepatic cholestasis, compared with that in biliary atresia (7.7 +/- 7.5 vs 22.7% +/- 7.8%, p less than 0.005). The greater ratio of cholate to chenodeoxycholate and the reduced excretion of sulfated urinary bile acids in intrahepatic cholestasis was due to decreased taurine-conjugated chenodeoxycholate sulfate excretion.


Transition from treprostinil to selexipag in patients with pulmonary arterial hypertension: Case series.
Safe transition of patients with pulmonary arterial hypertension (PAH) from parenteral treprostinil to oral selexipag therapy in both inpatient and outpatient settings is described. There is a paucity of published data on how to safely transition patients to oral therapy in the event of complications and problems during parenteral administration of prostacyclins, which can include bloodstream infections, injection-site pain (with use of subcutaneous treprostinil), infusion pump malfunction, and dosing errors due to incorrect dose preparation. This case series describes the transition of 4 patients with World Health Organization (WHO) group I PAH (WHO functional classes II-IV) from i.v. (n = 3) and subcutaneous (n = 1) treprostinil infusion therapy to oral selexipag use. The transition process was completed through the use of 2 cross-titration methods (rapid and slow). A rapid approach was used in 2 cases involving inpatients, with parenteral-to-oral transition completed over 8-13 days; a slow transition method was used in 2 cases, in which outpatients completed the transition over 19-25 weeks. Adverse events during the transitions were headache, nausea, vomiting, diarrhea, and jaw pain. Four patients with WHO group I PAH who were not candidates for continued parenteral treprostinil therapy were safely transitioned to oral selexipag in both inpatient and outpatient settings.


"Alcohol During Pregnancy? Nobody Does That Anymore": State Legislators' Use of Evidence in Making Policy on Alcohol Use in Pregnancy.
In recent years, U.S. states have passed many laws addressing alcohol use in pregnancy, despite limited evidence on the impact of such policies. This study explores how state legislators use evidence when making policy on alcohol use in pregnancy. Study data are drawn from semistructured interviews with 29 state lawmakers and their aides in Maryland, North Carolina, and Virginia, conducted in March through July 2017. Interview transcripts were coded and analyzed by inductive and deductive methods. Despite evidence on the harms of alcohol use in pregnancy, most lawmakers did not express concern about this topic. Instead, they expressed concern about opioid use in pregnancy. Personal experiences, anecdotes, and known contacts influenced legislators' views on substance use in pregnancy, whereas evidence, for the most part, did not. The intermediaries who typically bring evidence about problems and solutions to legislators did not appear to be raising the issue of alcohol use in pregnancy on legislators' agenda. Basic evidence on the prevalence and harms of alcohol use in pregnancy did not appear to influence state lawmakers' policy priorities. Concern over opioid use in general may provide a window of opportunity to educate legislators on the relative scope and harms of alcohol and opioid use in pregnancy. It remains unclear why states are passing alcohol-in-pregnancy policies. More research is needed to explore how state lawmakers form their understanding of substance use in pregnancy and related policies.


Neurological manifestations of celiac disease. Importance of searching and understanding the spectrum. Potential novel markers for the diagnosis.
currently Celiac Disease corresponds to an entity mainly managed by expert gastroenterologists on the topic but which must be faced on many occasions by primary care physicians or general gastroenterologists. It is important for a good diagnosis to look closely at all the factors that lead to a correct diagnosis (manifestations, antibodies, biopsy). In the spectrum of manifestations we find the classic ones, where the patient suffers from gastrointestinal symptoms typical of a classic Celiac Disease. At the same time, it is important to know that some of these patients do not have these classic symptoms and sometimes their only expression is neurological.


Clinical Diagnosis and Management of Resistant Hypertension.
Resistant hypertension (RHT) is variably defined as insufficient blood pressure (BP) response to multiple drug treatment. Prevalence of RHT has been thoroughly studied in the recent years, ranging from about 5 to 30 % in various cohorts. Initial management of patients with apparent RHT requires identification of true treatment resistance by out-of-office BP measurements, assessment of adherence and screening for treatable causes of uncontrolled BP. Endorsement of lifestyle modifications and maximisation of the doses of a suitable regimen, preferably with the further addition of an aldosterone antagonist, are the mainstay of treatment. An invasive approach to RHT, mainly represented by renal nerve ablation, should be kept for persistently severe cases managed in a specialised hypertension centre.


[QTL analysis for traits associated with photosynthetic functions in rice (Oryza sativa L.)].
A mapping population of 81 F11 lines (Recombinant Inbred Lines, RILs), derived from a cross between a japonica variety Kinmaze and an indica variety DV85 by single-seed descent method, was used to detect quantitative trait loci (QTL) for traits associated with photosynthetic functions. Total leaf nitrogen content (TLN), chlorophyll a/b ratio (Chl. a:b) and chlorophyll content (Chl) were measured in leaves of rice (Oryza sativa L.) at the 7th day after heading. A total of six putative QTLs were detected with percentage of variance explained (PVE) ranging between 11.2% -29.6%, and LOD of QTLs 2.66-4.81. Of those putative QTLs, three for TLN were detected on chromosomes 1,2 and 11, with PVE of 17.3%, 15.3% and 13.7%, respectively;Two controlling Chl. a:b on chromosomes 3 and 4, PVE of 13.8% and 29.6%, one for Chl on chromosome 1, PVE of 11.2%. Four of those detected QTLs were newly reported in this study. Interestingly, the QTL controlling chlorophyll content,namely qCC-1 reported here,was detected in the region of the RFLP marker C122 on chromosome 1, where harbored NADH-glutamate synthase structure gene according to a previous study. Because the biosynthesis of chlorophyll begins with glutamate, qCC-1 would play a vital role in photosynthetic functions. Whereas,no QTL controlling chlorophyll content were detected at the 30th day after heading, suggesting that the effect of the QTL controlling chlorophyll content decreased during leaf senescence.


Development of and adherence to an ERAS® and prehabilitation protocol for patients undergoing pancreatic surgery: An observational study.
There are still gaps in knowledge concerning the adherence to different multimodal pathways in pancreatic surgery. The aim of this trial was to explore and evaluate an Enhanced Recovery After Surgery (ERAS®) and prehabilitation protocol in patients undergoing open pancreatic surgery. Three groups of patients were included: two prospective series of 75 patients undergoing open pancreatic surgery following an ERAS® protocol with or without prehabilitation, and one group of 55 historical controls. Variables regarding adherence to, and effects of the protocols, were collected from the local database and the patients' hospital records. Patients' adherence to advice given pre-operatively was followed up using a study-specific questionnaire. The patients reported high adherence to remembered advice given. The health care professionals' adherence to the various parts of the concepts varied. ERAS® implementation resulted in more frequent gut motility stimulation (p < 0.001) and shorter duration of epidural anesthesia, site drains, and urinary catheter (p = 0.001). With prehabilitation, more patients were screened concerning nutritional status and prescribed preoperative training (p < 001). There was a significant change in weight before surgery, a shorter time to first flatus and a shorter length of stay after implementation of the concepts (p < 0.05). Complications were rare in all three groups and there were no significant differences between the groups. The implementation of an ERAS® and a prehabilitation protocol increased adherence to the protocols by both patients and healthcare professionals. An implementation of an ERAS® protocol with and without prehabilitation decreases length of stay and may decrease preoperative weight loss and time to bowel movement.


The role of 3,5,3'-triiodothyronine in the physiological action of thyroxine in the premetamorphic tadpole.
In premetamorphic tadpoles precocious metamorphosis can be induced by immersion in water containing either T4 or T3. T3 5-deiodinase (5D) activity is present in most tissues, and T4 5'-deiodinase (5'D) activity is present in gut and skin; both systems can be inhibited by iopanoic acid (IOP). If conversion of T4 to T3 is important for the normal physiological action of T4 in these tadpoles, it follows that IOP should decrease the effects of T4 and increase those of T3 on metamorphic events. To test this, tadpoles were immersed in water containing either T4 or T3 (20 nM) with or without 1.75 microM IOP. Two indices of metamorphosis, increased leg length and hepatic carbamyl phosphate synthetase activity, were studied. In vehicle- or IOP-treated animals, change in leg length and carbamyl phosphate synthetase activity were minimal. Both indices were increased after exposure to T3 for 10 days or to T4 for 21 days. Moreover, the effects of T3 were significantly enhanced while those of T4 were inhibited when IOP was also present. Both 5'D and 5D activities determined in vitro were inhibited (95% and 60%, respectively) in IOP-treated tadpoles, and this was associated with an increase in the plasma concentration of hormone. In separate experiments, vehicle- and IOP-treated tadpoles received [125I]T4 or [125I]T3 ip. Plasma, liver, gut, and skin were examined 12-24 h later for 125I-labeled products. After [125I]T4 treatment [125I]T3 was found in skin and gut, but not in plasma or liver. After [125I]T3 treatment [125I]3,3'-diiodothyronine was identified in all extracts studied. In vivo generation of these products was reduced by 50% in IOP-treated tadpoles. These findings indicate that generation of T3 from T4 can take place in vivo in the premetamorphic tadpole and strongly support the hypothesis that this process plays an important role in the physiological action of T4 in this species.


Combinatorial Chemical Bath Deposition of CdS Contacts for Chalcogenide Photovoltaics.
Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se2 (CIGSe) and Cu2ZnSnSe4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps of CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. The results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.


Correlation lengths of thermal electromagnetic fields in equilibrium and out of equilibrium conditions.
Spatial coherence of thermal fields in far- and near-field zones generated by heated half-space into a vacuum is studied at essentially different thermodynamical conditions. It is shown that correlation lengths of fields in any field zone are different in equilibrium and out of equilibrium systems. In a wide range of distances from a sample surface, the correlation functions should be calculated using a total sum of evanescent and propagating contributions due to their mutual compensation at some conditions because of anticorrelations. It is demonstrated that correlation lengths as calculated with a proposed formula are in agreement with the behavior of correlation functions of thermal fields in the spectral range of surface excitations.


Automatic identification of large collections of protein-coding or rRNA sequences.
The number of available genomic sequences is growing very fast, due to the development of massive sequencing techniques. Sequence identification is needed and contributes to the assessment of gene and species evolutionary relationships. Automated bioinformatics tools are thus necessary to carry out these identification operations in an accurate and fast way. We developed HoSeqI (Homologous Sequence Identification), a software environment allowing this kind of automated sequence identification using homologous gene family databases. HoSeqI is accessible through a Web interface (http://pbil.univ-lyon1.fr/software/HoSeqI/) allowing to identify one or several sequences and to visualize resulting alignments and phylogenetic trees. We also implemented another application, MultiHoSeqI, to quickly add a large set of sequences to a family database in order to identify them, to update the database, or to help automatic genome annotation. Lately, we developed an application, ChiSeqI (Chimeric Sequence Identification), to automate the processes of identification of bacterial 16S ribosomal RNA sequences and of detection of chimeric sequences.


[Evaluation of the Antianginal Efficacy of Ivabradine In Patients With Ischemic Heart Disease Complicated by Heart Failure].
Results of the multicenter open observational program NACHALO (evaluation of therapy in patients with combined coronary artery disease and heart failure as part of daily clinical practice), in which 569 doctors in 58 regions of the Russian Federation participated, were presented. The program included 2751 patients with ischemic heart disease, stable angina complicated by heart failure at the age from 25 to 94 years (mean age 62.6+/-9.3 years). The follow-up period was 3 months, during which two visits were carried out -after 4 weeks and a final visit-12 weeks after the initiation of therapy. Despite treatment, angina attacks (mean 6.7+/-6.1 per week), increased blood pressure (average 145.1+/-20.9/87.2+/-1.8 mm Hg) and heart rate (average 85.8+/-9.5 beats/min) were noted in patients before the inclusion in the program.


Variation in tonsil size in 4- to 17-year-old schoolchildren.
The purpose of this study was to evaluate the variation in tonsil size and prevalence of asymmetric tonsils in 4- to 17-year-old schoolchildren and the relationships between tonsillar hypertrophy and frequent tonsillitis, frequent fever, and sleep-related symptoms observed by parents. Cross-sectional study. Six daycare centres, four primary schools, and four high schools. Questionnaire and physical examination. The size of the tonsils was evaluated and scored on a 4-point scale. The interrelationships between tonsillar hypertrophy and other studied symptoms were examined. In the study, the parents of 1784 children, consisting of 803 (45%) boys and 981 (55%) girls, completed the questionnaires. The prevalence rates of snoring, habitual snoring, observed apnea, and habitual observed apnea were 24.6%, 4.1%, 3.8%, and 0.9%, respectively. The results of tonsil scoring were grade 1, 62.7%; grade 2, 28.4%; grade 3, 3.3%; and grade 4, 0.1%. The prevalence rate of grade 1 tonsils was increasing, whereas the prevalence rates of grade 2 and 3 tonsils were decreasing with increasing age. Tonsil size peaked in 4- to 8-year-old children. The prevalence rates of tonsillar hypertrophy and asymmetric tonsils were 3.4% and 1.7%, respectively. Tonsillar hypertrophy was found to be significantly associated with male gender, a history of frequent tonsillitis, a history of frequent fever, often or always snoring, and often or always observed apnea. A tonsil size curve was developed in 4- to 17-year-old schoolchildren. Children aged 4- to 8 years with oropharyngeal symptoms and particularly male gender should undergo consultation with otorhinolaryngology and pediatric pulmonology physicians for the evalution of adenotonsillar tissue.


TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines.
The nerve growth factor (NGF) receptor tyrosine-kinase TrkA is a well-known determinant of the melanocytic lineage, through modulation of the MAPK and AKT cascades. While TrkA gene is frequently rearranged in cancers, its involvement in malignant melanoma (MM) development is still unclear. We analyzed a dataset of primary cutaneous MM (n = 31) by array comparative genomic hybridization (aCGH), to identify genomic amplifications associated with tumor progression. The analysis was validated by genomic quantitative PCR (qPCR) on an extended set of cases (n = 64) and the results were correlated with the clinical outcome. To investigate TrkA molecular pathways and cellular function, we generated inducible activation of the NGF-TrkA signaling in human MM cell lines. We identified amplification of 1q23.1, where the TrkA locus resides, as a candidate hotspot implicated in the progression of MM. Across 40 amplicons detected, segmental amplification of 1q23.1 showed the strongest association with tumor thickness. By validation of the analysis, TrkA gene amplification emerged as a frequent event in primary melanomas (50 % of patients), and correlated with worse clinical outcome. However, experiments in cell lines revealed that induction of the NGF-TrkA signaling produced a phenotype of dramatic suppression of cell proliferation through inhibition of cell division and pronounced intracellular vacuolization, in a way straightly dependent on NGF activation of TrkA. These events were triggered via MAPK activity but not via AKT, and involved p21(cip1) protein increase, compatibly with a mechanism of oncogene-induced growth arrest. Taken together, our findings point to TrkA as a candidate oncogene in MM and support a model in which the NGF-TrkA-MAPK pathway may mediate a trade-off between neoplastic transformation and adaptive anti-proliferative response.


Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin-radixin-moesin network.
The newly discovered Ca(2+)-activated Cl(-) channel (CaCC), Anoctamin 1 (Ano1 or TMEM16A), has been implicated in vital physiological functions including epithelial fluid secretion, gut motility, and smooth muscle tone. Overexpression of Ano1 in HEK cells or Xenopus oocytes is sufficient to generate Ca(2+)-activated Cl(-) currents, but the details of channel composition and the regulatory factors that control channel biology are incompletely understood. We used a highly sensitive quantitative SILAC proteomics approach to obtain insights into stoichiometric protein networks associated with the Ano1 channel. These studies provide a comprehensive footprint of putative Ano1 regulatory networks. We find that Ano1 associates with the signaling/scaffolding proteins ezrin, radixin, moesin, and RhoA, which link the plasma membrane to the cytoskeleton with very high stoichiometry. Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins. Moreover, interfering RNA for moesin modifies Ano1 current without affecting its surface expression level. Another network associated with Ano1 includes the SNARE and SM proteins VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c, which are integral to translocation of vesicles to the plasma membrane. A number of other regulatory proteins, including GTPases, Ca(2+)-binding proteins, kinases, and lipid-interacting proteins are enriched in the Ano1 complex. These data provide stoichiometrically prioritized information about mechanisms regulating Ano1 function and trafficking to polarized domains of the plasma membrane.


Single-electron force readout of nanoparticle electrometers attached to carbon nanotubes.
We introduce a new technique of probing the local potential inside a nanostructure employing Au nanoparticles as electrometers and using single-electron force microscopy to sense the charge states of the Au electrometers, which are sensitive to local potential variations. The Au nanoelectrometers are weakly coupled to a carbon nanotube through high-impedance molecular junctions. We demonstrate the operation of the Au nanoelectrometer, determine the impedance of the molecular junctions, and measure the local potential profile in a looped nanotube.


Nurses' Knowledge, Perceived Practice, and their Associated Factors regarding Deep Venous Thrombosis (DVT) Prevention in Amhara Region Comprehensive Specialized Hospitals, Northwest Ethiopia, 2021: A Cross-Sectional Study.
Deep venous thrombosis is a preventable and treatable cause of death among hospitalized patients. Nurses' knowledge and proper assessment can play a major role in improving deep venous thrombosis prevention care. To assess the knowledge, practice, and associated factors towards deep venous thrombosis prevention among nurses working at Amhara region hospitals. Institutional-based cross-sectional study was conducted among nurses working at Amhara region comprehensive specialized hospitals, Northwest, Ethiopia, from April 1 to 30, 2021. A simple random sampling technique was used to select 423 samples. A structured pretested self-administered questionnaire was used to collect data. Data were entered in epi-info version 7, analyzed using SPSS version 25, and presented by frequencies, percentages, and tables. Bivariable and multivariable logistic regression was computed, and P value < 0.05 was considered to identify statistically significant factors. Good knowledge and practice of nurses towards DVT prevention were 55.6% and 48.8%, respectively. Working at the medical ward [AOR 3.175, 95% CI (1.42, 7.11)], having a BSc degree [AOR = 3.248(1.245, 8.469)], Master's degree [AOR = 3.48, 95% CI (1.22, 9.89)], obtaining a formal training about deep venous thrombosis [AOR = 1.59; 95% CI (1.03, 2.47)], and working experience of ≥11 years [AOR = 2.11; 95% CI (1.07, 4.16)] were associated with good knowledge of nurses on the prevention of deep venous thrombosis. While having good knowledge about deep venous prevention AOR = 1.75; 95% CI (1.15, 2.65)] and working experience ≥11 years [AOR = 3.44; 95% CI (1.45, 8.13)] were significantly associated with nurses' practice about deep venous thrombosis prevention. Knowledge and practice of the nurses regarding the prevention of deep venous thrombosis were found to be inadequate. Therefore, providing training, creating a conducive environment for sharing of experience, and upgrading the academic status of nurses are measures to scale up the knowledge and practice of nurses regarding deep venous thrombosis prevention.


Neuromodulation of the suprascapular nerve.
The shoulder joint is an enarthrodial or ball-and-socket joint. A complex network of anatomic structures endows the human shoulder with tremendous mobility, greater than any other joint in the body. Many pathologies can been found in those patients with chronic shoulder pain. The painful limitation of shoulder motion affects hand and arm motion as well; therefore, it significantly influences work performance and everyday activities as well as the quality of life. Therefore, the treatment of patients with chronic shoulder pain has major social and health economic implications. In this article we present a patient with a complex history of shoulder pathology including 7 surgeries that left the patient with chronic debilitating shoulder pain. She was suffering from chronic pain and limited mobility of the shoulder joint due to adhesive shoulder capsulitis. She was treated with a multimodality approach with the goals of increasing shoulder range of motion and decreasing her pain. This did not provide significant improvement. The suprascapular nerve supplies motor and sensory innervation to the shoulder, and can be easily accessible in the supraspinatus fossa. A suprascapular nerve block dramatically decreased her pain. This clinical observation along with confirmatory nerve block play an important role during the decision-making process for a trial period of electrical neuromodulation. She was followed for 3 months after the permanent implantation of a suprascapular nerve stimulator. Her pain and shoulder range of motion in all planes improved dramatically. Peripheral nerve stimulation (PNS) of the suprascapular nerve, in addition to multimodality pain management, is one approach to the difficult task of treating adhesive capsulitis with accompanying pain and the inability to move the shoulder. We conducted a literature review on PubMed and found no case describing a similar patient to our knowledge.


Parallel heat flux from low to high parallel temperature along a magnetic field line.
In a long mean-free-path plasma where temperature anisotropy can be sustained, the parallel heat flux has two components with one associated with the parallel thermal energy and the other with the perpendicular thermal energy. In a kinetic simulation with magnetic flux expansion toward an absorbing boundary, the parallel heat flux of the parallel thermal energy is found to flow from a low to high parallel temperature region. This unusual behavior is understood with the help of an analytical calculation of the drift-kinetic model using the same upstream source in the simulation.


Persistence with Anticoagulation for Atrial Fibrillation: Report from the GLORIA-AF Phase III 1-Year Follow-up.
We aimed to assess the extent to which drug persistence is better with non-vitamin K antagonist oral anticoagulants (NOACs) than vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients and to estimate the difference in therapy persistence depending on NOAC dosing regimen (once daily (QD) vs. twice daily (BID)). Consecutive patients were followed for 1 year in phase III of the GLORIA-AF registry. Drug persistence was defined as the use of OAC without any discontinuation in >30 days or switching to alternative therapy. Among 21,109 eligible patients in phase III, 17,266 patients who were prescribed OAC at baseline and those who took ≥1 OAC dose were included. The 1-year proportion of patients receiving NOAC and VKA who persisted on treatment was 80% and 75%, respectively. The 1-year persistence with NOACs BID and NOACs QD was 81% and 80%, respectively. Female gender, hypertension, older age, alcohol use, permanent, asymptomatic, and minimally symptomatic AF were associated with better OAC persistence. Region, medication usage predisposing to bleeding, being a current smoker, treatment reimbursement, and proton pump inhibitors were associated with lower OAC persistence. Drug persistence was higher with NOACs (1-year persistence was 80%) than with VKAs (75%). There was little difference in 1-year persistence between NOAC dosing regimens.


In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons.
To assess the effect of interleukin-6 (IL-6) on the coagulation and the fibrinolytic systems, we administered a single subcutaneous injection of recombinant glycosylated human interleukin-6 (r-hIL-6) 100 micrograms per kg body weight) to four baboons (Papio ursinus). Four saline injected baboons served as controls. In serial plasma or serum samples collected over a period of seven days we measured several key parameters of the coagulation and the fibrinolytic systems, IL-6 and a set of acute phase proteins. Three hours after the injection, the serum IL-6 levels peaked at 50 ng/ml and then gradually declined with a terminal half-life of around 4 hours. The biological efficacy was demonstrated by the significant increases of several acute phase proteins, circulating platelets and the decrease of prealbumin and fibronectin. Between days 1 and 3, marked effects on the coagulation system were observed with a prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time. Plasma concentrations of fibrinopeptide A and D-dimer increased. The antithrombin III antigen and activity levels decreased, but the thrombin-antithrombin III complex concentrations did not change. The fibrinolytic system rapidly showed striking modifications after 6-8 hours, the concentrations of tissue-type plasminogen activator and of plasminogen activator inhibitor type 1 peaked at respectively four and thirty times the basal concentrations. No changes were seen in the control group. We conclude that besides its well-known acute phase inducing and hematopoietic activities, subcutaneous rhIL-6 also modulates several parameters of the coagulation and the fibrinolytic systems.(ABSTRACT TRUNCATED AT 250 WORDS)


Losing a foot versus losing a dollar; a systematic review of cost studies in diabetic foot complications.
Diabetes mellitus is a chronic disease with high prevalence worldwide and a range of serious related complications. Amongst them, diabetic foot is one of the most disabling, posing a substantial health and economic burden on patients and healthcare systems. Areas covered: According to projections, the expected lower limb morbidity is about to increase - in this light the present review aimed at identifying cost-of-illness studies on the management and treatment of conditions related to the diabetic foot, in an aim to provide a body of evidence for an increasing health care burden. Expert commentary: Recent literature review surfaced a plethora of cost studies. Despite heterogeneity of foot complications and geographic variations, the search methodology revealed substantial costs and further healthcare burden for people with diabetes. Amputations due to suboptimally treated foot infections contribute to the already high rates of hospitalizations and readmissions. The cost of amputation ranges between $35,000 and $45,000 in the developed countries, however it largely depends on the amputation type. Moreover, the findings suggest that the cost of amputation in the US is generally higher compared to the cost in European countries. The cost of amputation in developing countries is substantially lower, as it approximates $5,000.


Interleukin-4 down-regulates adult human astrocyte DNA synthesis and proliferation.
The T lymphocyte-derived cytokine, interleukin-4 (IL-4), was found to inhibit dose dependently basal DNA synthesis of cultured non-neoplastic human astrocytes isolated from epilepsy white matter tissue. The mitogenic effect of tumor necrosis factor on astrocytes was also inhibited by IL-4, and the inhibitory effect was abrogated by anti-IL-4 antibody but not by irrelevant IgG. Immunofluorescent analysis indicated significantly reduced numbers of glial fibrillary acidic protein-positive astrocytes incorporating nuclear bromodeoxyuridine in IL-4-treated cultures compared to control. These findings indicate that human adult astrocyte proliferation, in contrast to that reported for endothelial cells or fibroblasts, is sensitive to down-regulation by IL-4.


Endodontic-orthodontic management of fractured anterior teeth.
A case history is presented of a 10-year-old patient, who accidentally injured her maxillary central incisor. The fracture of the crown extended 2 mm below the crest of the alveolar bone. After a pulpotomy was done as a temporary measure, orthodontic appliances were placed by bonding brackets on the maxillary anterior teeth and fitting a sectional arch wire to extrude the fractured tooth. After successful extrusion, the fracture line was brought above the level of alveolar bone where successful restoration of the tooth by the acid-etch method could be accomplished.


Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups.
Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval sample (N = 450) which represented two distinct socio-economic groups. Osteonal parameters were recorded in posterior midshaft femoral sections from adult males (N = 233) and females (N = 217). Using univariate and multivariate statistics, intact, fragmentary, and osteon population densities, Haversian canal area and diameter, and osteon area were compared between the two groups, accounting for sex, age, and estimated femoral robusticity. The size of osteons and their Haversian canals, as well as osteon density, varied significantly between the socio-economic groups, although minor inconsistencies were observed in females. Variation in microstructure was consistent with historical textual evidence that describes differences in mechanical loading and nutrition between the two groups. Results demonstrate that aspects of ancient human lifestyle can be inferred from bone microstructure.


In vivo neuroimaging correlates of the efficacy of paroxetine in the treatment of mood and anxiety disorders.
The advent of neuroimaging technology has brought with it a deeper understanding of brain function and structure in health and psychiatric illness. This article overviews pertinent findings from neuroimaging studies in mood and anxiety disorders. Paroxetine is a particularly well-studied psychopharmacologic agent in this regard. The findings of neuroimaging studies of paroxetine will be placed into perspective for a better understanding of the interaction of this selective serotonin reuptake inhibitor (SSRI) with the serotonergic and noradrenergic systems in the brain that mediate clinical efficacy. When considered in the context of a burgeoning literature on neuroimaging research of the pathophysiology of mood and anxiety disorders, the findings of paroxetine studies suggest a neurobiological explanation for the mechanisms whereby chronic administration of paroxetine affects neural systems involved in the pathophysiology of major depression and several anxiety disorders such as obsessive-compulsive disorder, posttraumatic stress disorder, and social anxiety disorder.


Differential bud activation by a net positive root signal explains branching phenotype in prostrate clonal herbs: a model.
Regulation of branching within perennial prostrate clonal herbs differs from the annual orthotropic species, Arabidopsis and pea, as the dominant signal transported from roots is a branching promoter, not an inhibitor. Trifolium repens, an exemplar of such prostrate species, was used to investigate the interaction between roots and branch development. This study tests whether or not current knowledge when synthesized into a predictive model is sufficient to simulate the branching pattern developing on the shoot distal to a basal root. The major concepts underpinning the model are: (i) bud outgrowth (activation) is stimulated in a dose-dependent manner by branching promoter signals from roots, (ii) the distribution of this net root stimulus (NRS) is uniform throughout the shoot system distal to the basal root but declines geometrically in intensity upon continued enlargement of this shoot system, and (iii) each bud has an outgrowth potential, equal to the activation level of the apical bud in which it forms, that moderates its response to NRS. The validity of these concepts was further tested by running simulations of the branching of a phylogenetically-distanced prostrate perennial monocotyledonous species, Tradescantia fluminensis. For both species the model reasonably accounted for the observed pattern of branching. The outgrowth potential of buds plays an important role in limiting the number of hierarchies of branching that can develop on a plant. In conclusion, for both species, the model accounted for the major factors involved in the correlative regulation of branching and is possibly also pertinent for all prostrate clonal species.


Self-analysis of coherent oscillations in time-resolved optical signals.
The specific origin of oscillations in time-resolved optical signals, in particular, for complex systems with nontrivial interstate couplings and nonseparable electron-nuclear motion, is often difficult to assign. Here, we show that coherent oscillations in two-dimensional photon-echo are capable of self-analysis; their beating maps provide a tool to tell apart ground-state bleach (GSB), stimulated emission (SE), and excited-state absorption (ESA) contributions to the oscillatory signal component. Because GSB carries information on ground-state coherence while SE and ESA reflect the excited-state coherence, the observed oscillations can be unambiguously assigned to ground-state or excited-state coherent motion. The findings prove especially advantageous for systems with dense detectable manifolds of states pertaining to each electronic state. An analogous analysis for frequency-resolved (dispersed) pump-probe spectroscopy is discussed briefly.


Semipermanent microscope slides of microfungi using a sticky tape technique.
A technique is described for making semipermanent microscope slides of fungi using sticky tape. After being touched to a fungal colony, a modified segment of sticky tape is touched to ethyl alcohol and then immersed in a 50% glycerine solution containing cotton blue stain. Finally, it is transferred (sticky side up) to a microscope slide, covered with a cover with a cover glass, and sealed.


Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.
Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance, adverse events and surgical complications. We will measure QoL in both groups. We will analyze molecular indications that may lead to more individually tailored treatments in the future. This will be the first NOM trial utilizing a regression schema for response assessment in a prospective fashion. NCT02008656.


Expression of cytotoxic T lymphocyte-associated antigen 4, CD44, and E-cadherin in the microenvironment of breast carcinomas.
The expression of cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44 in the area of tumor budding was investigated in breast carcinomas in our study. Tumor budding was counted at the invasive margins in 179 breast carcinomas. To understand the microenvironment of tumor budding, we examined the expression status of the immune checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4, E-cadherin, and CD44. Tumors were separated into low (≤5) and high tumor budding groups (>5) based on the median budding number. Lymphovascular, perineural invasion, and the number of metastatic lymph nodes were significantly higher in high-grade budding tumors (p=0.001, p<0.001, and p=0.019, respectively). Tumor-infiltrating lymphocytes were significantly higher in tumors without tumor buddings (p<0.001). When the number of budding increases by one unit, overall survival decreases by 1.07 times (p=0.013). Also, it increases the risk of progression by 1.06 times (p=0.048). In high tumor budding groups, the cytotoxic T lymphocyte-associated antigen 4 staining percentage of lymphocytes was significantly higher (p=0.026). With each increase in the number of buds, an increase in the percentage of cytotoxic T lymphocyte-associated antigen 4 staining was seen in lymphocytes in the microenvironment of TB (p=0.034). Tumor budding could predict poor prognosis in breast carcinomas, and anti-cytotoxic T lymphocyte-associated antigen 4 immunotherapies may be beneficial in patients with high tumor budding tumors.


Effects of finger and mouse pointing on learning from online split-attention examples.
Self-management of cognitive load is a recent development in cognitive load theory. Finger pointing has been shown to be a potential self-management strategy to support learning from spatially separated, but mutually referring text and pictures (i.e., split-attention examples). The present study aimed to extend the prior research on the pointing strategy and investigated the effects of finger pointing on learning from online split-attention examples. Moreover, we examined an alternative pointing strategy using the computer mouse, and a combination of finger pointing and computer-mouse pointing. One-hundred and forty-five university students participated in the present study. All participants studied an online split-attention example about the human nervous system and were randomly allocated to one of four conditions: (1) pointing with the index finger, (2) pointing with the computer mouse, (3) pointing with the index finger and the computer mouse and (4) no pointing. Results confirmed our main hypothesis, indicating that finger pointing led to higher retention performance than no pointing. However, the mouse pointing strategy and the combined finger and mouse pointing strategy did not show supportive effects. Finger pointing can be used as a simple and convenient self-management strategy in online learning environments. Mouse pointing may not be as effective as finger pointing.


Is NO3 formed during the decomposition of nitramine explosives?
Quantum chemistry calculations reveal that it is both thermodynamically and kinetically feasible for NO2 to be oxidized by RDX (1,3,5-trinitrohexahydro-s-triazine) or its initial decomposition products. Thus, NO3 (nitrate radical) may be produced during the thermal decomposition of RDX and other nitramines. However, experimental studies of the gaseous products, by mass spectrometry and microwave spectroscopy, have never detected NO3. This fact is reconciled with the calculations by noting that (1) the electron-impact, positive-ion mass spectrum of NO3 shows little parent ion, (2) NO3 lacks a permanent electric dipole moment and is therefore invisible to microwave spectroscopy, and (3) NO3 is quite reactive. Further experiments are encouraged and could lead to a new method for detecting concealed nitramines.


Cognition in autism: one deficit or many?
The aim of this paper is to provoke discussion concerning the nature of the cognitive impairments that characterize autism. Autism spectrum disorders appear to be heterogeneous at the biological and behavioural levels, but it is currently unclear whether one or more cognitive abnormalities may be universal to people with autism. In addition, it is unknown whether one cognitive deficit is primary and causal, or whether several complimentary accounts are needed to explain the full range of behavioural features. From research to date, it seems that the psychological abnormalities that characterize autism may be dissociable, and it is uncertain whether the degree of social and non-social impairments is related. Possible reasons for the co-occurrence of social and non-social cognitive abnormalities in autism are discussed. One implication is that searching for the biological bases of specific social and non-social deficits may be more profitable than searching for the aetiology of autism per se.


Differential Trends in Hookah Use Among New Jersey Youth.
Use of 2 or more types of tobacco products is common among youth and young adults, highlighting the need for monitoring and intervention activities to encompass products beyond combustible cigarettes. This study documented patterns and trends of ever, current, and frequent hookah use among high school students in New Jersey by other tobacco product use status. We analyzed data from the 2008, 2010, 2012, 2014, 2016 waves of the New Jersey Youth Tobacco Survey. Point estimates and 95% confidence intervals described hookah use stratified by use of other tobacco products. Multivariable logistic regression models assessed trends and correlates of hookah use, controlling for the use of other tobacco products and users' sociodemographic characteristics. Negative binomial regression models examined the association between total number of tobacco products used and hookah use while controlling for sociodemographic variables and survey year. The adjusted odds of current and frequent hookah use among New Jersey high school students were significantly higher in 2014, but not in 2016, compared to 2008. In recent years, hookah use among students who had ever smoked hookah, currently smoked hookah, or frequently smoked hookah was more common among students who had ever or currently smoked cigarettes or e-cigarettes. Hookah users consumed a wider variety of other tobacco products than those who did not use hookah. Hookah use remains a public health concern for adolescents; it is more common among users of other tobacco products, especially cigarette and e-cigarette smokers. Questions remain as to whether users of multiple tobacco products are being adequately reached by existing policies and regulations.


Genes and molecular pathways underpinning ciliopathies.
Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.


Influence of single-walled carbon nanotubes induced crystallinity enhancement and morphology change on polymer photovoltaic devices.
Single-walled carbon nanotubes (SWNTs) were determined to have significant interaction with poly(3-hexylthiophene) (P3HT), which is helpful to form continuous active film with interpenetrating structure and improve the crystallinity of the resultant film for SWNTs/P3HT composite. Photovoltaic devices based on an active film with relatively higher crystallinity display much enhanced performance. The work function of carbon nanotubes modulated by electron transferring from P3HT to SWNTs is proposed to explain the high open-circuit voltage (V(OC)) obtained from the photovoltaic devices based on the SWNTs/P3HT system.


Cyclosporin A in insulin-dependent diabetes mellitus of recent onset: a pilot study in children.
We report on the first pilot study in newly diabetic children treated with cyclosporin A (CsA), for 6 months. Three groups of children were recruited based on the desired CsA plasma level: group I (n = 13) aiming at 100 ng CsA/ml plasma; group II (n = 14) at 200 ng/ml, and group III (n = 13) aiming initially at 200 ng/ml and later on 100 ng/ml. These groups were compared to a control group (n = 12) receiving no CsA but the same insulin regimen. A significant reduction in insulin requirements was observed in the CsA-treated children, more marked in groups II and III (p less than 0.001 vs. control group). The rate of total remissions was 0 in the control group, and 30% in group I; it was 57 and 76% in groups II and III, respectively. CsA also induced an increase in C-peptide secretion after 6 months (p less than 0.01 in groups II and III vs. controls). Side effects of the drug were of minor clinical importance in group I. But in groups II and III, 48% of the children exhibited a reversible increase in blood pressure or plasma creatinine. This study demonstrates a dose-related effect of cyclosporin A (CsA) on the insulin requirements of newly diagnosed diabetic children (more frequent and prolonged remissions with the high CsA dosage). Nevertheless, the noticeable side effects, induced by this high dosage, are of concern for prolonged CsA administration in diabetic children.


Anatomical reconstruction of complete burst vertebral fracture case report-combined reduction methods and armed kyphoplasty with stents filled with bone graft.
Minimally invasive techniques used to augment the fractured vertebral body have acquired popularity thanks to their capacity to stabilize the anterior spine via the percutaneous posterior pathway. We present a clinical case of a 50-year-old male patient with a traumatic complete burst fracture of L1 vertebral body treated by L1 laminectomy, percutaneous pedicle instrumentation D11-D12-L2-L3 and indirect fracture reduction, followed by direct reduction by armed kyphoplasty with stents filled with bone graft. We describe the details of the surgical technique, as well as clinical and imaging outcomes. After 3-year follow-up, the patient is practically asymptomatic and control computed tomography demonstrates vertebral body fracture healing and maintenance of the vertebral heights recorded in the immediate postoperative period, without signs of loosening, migration or failure of intrasomatic stents or pedicle screws, as well as of bone graft resorption, which indicates its osseointegration and healing. We discuss the concepts of indirect and direct reduction and the rationale for anatomical vertebral restoration and for the use of intrasomatic bone graft. We present a detailed description of a promising surgical technique combining indirect and direct reduction and vertebral body interior replacement with stents filled with bone graft, as a treatment that allows for a complete burst fracture to be anatomically restored by a posterior and minimally invasive approach. Also, we demonstrate a fast and full recovery, avoiding the morbidity and risk of serious complications of anterior approaches. Nevertheless, long-term prospective studies are necessary so as to prove the effectiveness and assets of this surgical option versus other common techniques in complete burst fractures.


Prevalence and types of dental anomaly in a Thai non-syndromic oral cleft sample.
To investigate the prevalence and characteristics of dental anomalies (DAs); missing teeth (MT), dens-evaginatus (D-E), dens-invaginatus, dilaceration,fusion, gemination, macrodontia, microdontia (Micro), supernumerary teeth (SNT), and taurodontism, in permanent teeth among subjects with non-syndromic oral cleft. This cross-sectional study was designed to assess DAs from diagnostic records; comprising panoramic radiograph, intraoral photographs, dental casts, and orthodontic clinic charts of 280 Northeastern Thai subjects, mean age 10.3 +/- 3.2 years. Chi-square test was used to compare DA prevalences among cleft phenotypes and genders. There were one or more teeth with DAs in 89.6% of the study population. Highest prevalence was MT (60.4%) followed by Micro (41.4%), dilaceration (6.4%), SNT (6.1%) , and 0.4% in D-E, fusion, gemination, and taurodontism. The most prevalent MT was found in 70.7% of subjects in bilateral cleft lip and palate group. The two predominant DAs were MT and Micro, higher prevalences being found with the more severe cleft conditions. The most affected teeth were cleft-site lateral incisors. There were no differences in distribution of DA in male and female.


SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes.
SOX1 antibodies have been described in patients with Lambert-Eaton myasthenic syndrome (LEMS) in association with voltage-gated calcium channel antibodies as serological markers of small cell lung cancer (SCLC). This study was aimed to screen for additional SOX1 autoimmunity in onconeural antibody-positive sera from patients with paraneoplastic neurological syndromes (PNS) other than LEMS and to identify the clinical-immunological profile and associated tumours of patients with coexisting SOX1 antibodies. We retrospectively analysed sera from 55 patients with different PNS positive for well-characterized antineuronal antibodies for the presence of SOX1 antibodies by recombinant ELISA and immunoblot. Eight (14.5%) patients showed additional SOX1 antibodies in the ELISA and the recombinant immunoblot. Five patients had coexisting Hu antibodies, while the other three showed coexisting CV2/CRMP5, amphiphysin, and coexisting CV2/CRMP5 and Hu antibodies, respectively. PNS included (partially overlapping) subacute sensory neuropathy, subacute sensorimotor neuropathy, cerebellar degeneration, brainstem encephalitis, encephalomyelitis and limbic encephalitis. No tumour was detected in two patients, while the others had lung cancer (four SCLC and two non-SCLC). One patient showed SOX1-specific intrathecal antibody synthesis. We describe SOX1 reactivity for the first time overlapping with CV2/CRMP5 and amphiphysin antibodies. SOX1 reactivity is predominantly associated with Hu antibodies and SCLC, but can occur also in other types of lung cancer. Neurological manifestations present in patients with coexisting SOX1 antibodies and well-characterized antineuronal antibodies do not differ from those previously described in patients positive for antineuronal antibodies but no SOX1-specific anti-glial antibodies.


Randomized controlled trial local injection for treatment of lateral epicondylitis, 5 and 10 mg triamcinolone compared.
To compare the efficacy and adverse effects between 5 and 10 mg triamcinolone local injection for treatment of the lateral epicondylitis. The primary outcome was the improvement of pain after 12 weeks of treatment. The secondary outcome was the adverse effects rate. One hundred and four patients with lateral epicondylitis were randomly allocated into 2 groups. Group A were injected with 5 mg triamcinolone and group B were injected with 10 mg triamcinolone at the maximum tenderness point at the lateral aspect of the elbow. All the patients were followed-up to 12 weeks. Patient satisfaction, pain score (VAS), degree of tenderness, pain on wrist extension against resistance, grip strength and adverse effects were recorded at 12 weeks after the injection. Group A (n = 51) had excellent result 80.39%, good 11.76%, slightly improved 1.96% and not improved 5.88%. Group B (n = 53) had excellent result 73.58%, good 16.98%, slightly improved 3.77% and not improved 5.66%. The adverse effects rate were 9.8% in group A and 13.2% in group B. There were no statistically significant in terms of patient satisfaction, pain score, tenderness at lateral epicondyle, grip strength and adverse effect rate. The use of 5 mg triamcinolone was comparable to 10 mg triamcinolone injected locally to treatment of lateral epicondylitis.


Arterial calcification: Finger-pointing at resident and circulating stem cells.
The term ''Stammzelle'' (stem cells) originally appeared in 1868 in the works of Ernst Haeckel who used it to describe the ancestor unicellular organism from which he presumed all multicellular organisms evolved. Since then stem cells have been studied in a wide spectrum of normal and pathological conditions; it is remarkable to note that ectopic arterial calcification was considered a passive deposit of calcium since its original discovering in 1877; in the last decades, resident and circulating stem cells were imaged to drive arterial calcification through chondro-osteogenic differentiation thus opening the idea that an active mechanism could be at the basis of the process that clinically shows a Janus effect: calcifications either lead to the stabilization or rupture of the atherosclerotic plaques. A review of the literature underlines that 130 years after stem cell discovery, antigenic markers of stem cells are still debated and the identification of the osteoprogenitor phenotype is even more elusive due to tissue degradation occurring at processing and manipulation. It is necessary to find a consensus to perform comparable studies that implies phenotypic recognition of stem cells antigens. A hypothesis is based on the singular morphology and amitotic mechanism of division of osteoclasts: it constitutes the opening to a new approach on osteoprogenitors markers and recognition. Our aim was to highlight all the present evidences of the active calcification process, summarize the different cellular types involved, and discuss a novel approach to discover osteoprogenitor phenotypes in arterial wall.


Wild-Type Monomeric α-Synuclein Can Impair Vesicle Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.
α-Synuclein is a presynaptic protein the function of which has yet to be identified, but its neuronal content increases in patients of synucleinopathies including Parkinson's disease. Chronic overexpression of α-synuclein reportedly expresses various phenotypes of synaptic dysfunction, but the primary target of its toxicity has not been determined. To investigate this, we acutely loaded human recombinant α-synuclein or its pathological mutants in their monomeric forms into the calyces of Held presynaptic terminals in slices from auditorily mature and immature rats of either sex. Membrane capacitance measurements revealed significant and specific inhibitory effects of WT monomeric α-synuclein on vesicle endocytosis throughout development. However, the α-synuclein A53T mutant affected vesicle endocytosis only at immature calyces, whereas the A30P mutant had no effect throughout. The endocytic impairment by WT α-synuclein was rescued by intraterminal coloading of the microtubule (MT) polymerization blocker nocodazole. Furthermore, it was reversibly rescued by presynaptically loaded photostatin-1, a photoswitcheable inhibitor of MT polymerization, in a light-wavelength-dependent manner. In contrast, endocytic inhibition by the A53T mutant at immature calyces was not rescued by nocodazole. Functionally, presynaptically loaded WT α-synuclein had no effect on basal synaptic transmission evoked at a low frequency, but significantly attenuated exocytosis and impaired the fidelity of neurotransmission during prolonged high-frequency stimulation. We conclude that monomeric WT α-synuclein primarily inhibits vesicle endocytosis via MT overassembly, thereby impairing high-frequency neurotransmission.SIGNIFICANCE STATEMENT Abnormal α-synuclein abundance is associated with synucleinopathies including Parkinson's disease, but neither the primary target of α-synuclein toxicity nor its mechanism is identified. Here, we loaded monomeric α-synuclein directly into mammalian glutamatergic nerve terminals and found that it primarily inhibits vesicle endocytosis and subsequently impairs exocytosis and neurotransmission fidelity during prolonged high-frequency stimulation. Such α-synuclein toxicity could be rescued by blocking microtubule polymerization, suggesting that microtubule overassembly underlies the toxicity of acutely elevated α-synuclein in the nerve terminal.


The diagnostic yield of CGH and WES in neurodevelopmental disorders.
Neurodevelopmental disorders are a group of conditions characterized by developmental delays leading to abnormal brain functions. The methods of diagnosis and treatment of these conditions are complicated, and their treatment involves a combination of various forms of therapy. In recent years, the development of high-resolution technologies has played an important role in revealing the microdeletions, microduplications, and single-nucleotide variants of the chromosomes and how they are linked to the development of neurodevelopmental disorders. The wide implementation and application of molecular methodologies have started to shed light on the functional importance of using the appropriate methods in detecting these genetic variations that are categorized as either pathogenic or benign. The study aimed to compare the diagnostic yield of comparative hybridization (CGH) and whole exome sequencing (WES) in neurodevelopmental disorders among children attending the King Abdullah Specialist Children Hospital, Riyadh, Saudi Arabia. A retrospective study was conducted between 2015 and 2018 on 105 patients diagnosed with neurodevelopmental disorders through array-based CGH (Array-CGH) and WES. In a sample of 105 patients, 16% was the hit rate of copy number variations (CNVs). WES was requested for CNV-negative patients (n = 79), of which 30% was the hit rate of pathogenic or likely pathogenic single-nucleotide variants. There was a difference in the diagnostic yield between CGH (16%) and WES (30%). WES was a better approach than Array-CGH to detect various DNA mutations or variants. Our findings could guide clinicians, researchers, and testing laboratories select the most cost-effective and appropriate approach for diagnosing their patients.


Highly stable surface modification of hypercrosslinked monolithic capillary columns and their application in hydrophilic interaction chromatography.
A two-step surface modification of poly(styrene-co-vinylbenzyl chloride-co-divinylbenzene) monolithic stationary phases, including hypercrosslinking and thermally initiated surface grafting of [2-(methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)ammonium hydroxide, has been used to prepare capillary columns for the isocratic separation of small polar compounds in hydrophilic interaction chromatography (HILIC). The prepared monolithic columns provided a dual retention mechanism, combining RP and hydrophilic interaction chromatography, controlled by the composition of the mobile phase. By the optimization of the surface grafting reaction using response surface methodology, we have found that the grafting time is the main synergistic effect controlling the retention of polar compounds in HILIC. The prepared monolithic columns achieved long column lifetimes and did not lose their separation power following >10,000 injections. Finally, hypercrosslinked columns have been used in the 1- and 2D LC of phenolic compounds.


Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.
A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters. Patients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded. Of 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.


The diabetes pandemic and associated infections: suggestions for clinical microbiology.
There are 425 million people with diabetes mellitus in the world. By 2045, this figure will grow to over 600 million. Diabetes mellitus is classified among noncommunicable diseases. Evidence points to a key role of microbes in diabetes mellitus, both as infectious agents associated with the diabetic status and as possible causative factors of diabetes mellitus. This review takes into account the different forms of diabetes mellitus, the genetic determinants that predispose to type 1 and type 2 diabetes mellitus (especially those with possible immunologic impact), the immune dysfunctions that have been documented in diabetes mellitus. Common infections occurring more frequently in diabetic vs. nondiabetic individuals are reviewed. Infectious agents that are suspected of playing an etiologic/triggering role in diabetes mellitus are presented, with emphasis on enteroviruses, the hygiene hypothesis, and the environment. Among biological agents possibly linked to diabetes mellitus, the gut microbiome, hepatitis C virus, and prion-like protein aggregates are discussed. Finally, preventive vaccines recommended in the management of diabetic patients are considered, including the bacillus calmette-Guerin vaccine that is being tested for type 1 diabetes mellitus. Evidence supports the notion that attenuation of immune defenses (both congenital and secondary to metabolic disturbances as well as to microangiopathy and neuropathy) makes diabetic people more prone to certain infections. Attentive microbiologic monitoring of diabetic patients is thus recommendable. As genetic predisposition cannot be changed, research needs to identify the biological agents that may have an etiologic role in diabetes mellitus, and to envisage curative and preventive ways to limit the diabetes pandemic.


[Disability in the elderly owing to cerebrovascular diseases: the leading desadaptive syndromes].
The article presents data on the main desadaptive syndromes have disabilities due to cerebrovascular diseases in the elderly according to the results of analysis of medical expert documents the Bureau of medico-social examination of Saint-Petersburg in the period from 2010 to 2014. The characteristics of the level, structure, dynamics and distribution according to groups of disability due to cerebrovascular diseases in retirement were shown; clinical expert in the features of the population of older people with disabilities due to cerebrovascular diseases were analyzed. We revealed a consistent decrease in the number of persons with disabilities over 5 years, increase the proportion of persons with disabilities of group III and group I disabled. We have determined the structure of the main desadaptive syndromes in the structure of the cerebrovascular diseases, causing dysfunctions of the body and disability.


Patient-Based Real-Time Quality Control: Review and Recommendations.
For many years the concept of patient-based quality control (QC) has been discussed and implemented in hematology laboratories; however, the techniques have not been widely implemented in clinical chemistry. This is mainly because of the complexity of this form of QC, as it needs to be optimized for each population and often for each analyte. However, the clear advantages of this form of QC, together with the ongoing realization of the shortcomings of "conventional" QC, have driven a need to provide guidance to laboratories to assist in deploying patient-based QC. This overview describes the components of a patient-based QC system (calculation algorithm, block size, truncation limits, control limits) and the relationship of these to the analyte being controlled. We also discuss the need for patient-based QC system optimization using patient data from the individual testing laboratory to reliably detect systematic errors while ensuring that there are few false alarms. The term patient-based real-time quality control covers many activities that use data from patient samples to detect analytical errors. These activities include the monitoring of patient population parameters such as the mean or median analyte value or using single within-patient changes such as the delta check. In this report, we will restrict the discussion to population-based parameters. This overview is intended to serve as a guide for the implementation of a patient-based QC system. The report does not cover the clinical evaluation of the population.


[Health and recreational localities in the republic of altai and prospects for the development of spa-and-resort services on their basis].
The objective of the present work was to explore low- and mid-altitude valleys and depressions in the northern and central bioclimatic provinces of Gorny Altai for the identification of the health and recreational localities most promising in terms development of spa-and-resort services. The integral estimation of landscape and climatic conditions in conjunction with the quality of hydromineral resources of therapeutic value provided the data that were used by the authors to propose recommendations for the creation of the system of mountain-climate health resorts and touristic-recreational complexes of regional and federal significance at the territory of the Republic of Altai.


Arbitrary and Parallel Nanofabrication of 3D Metal Structures with Polymer Brush Resists.
3D polymer brushes are reported for the first time as ideal resists for the alignment-free nanofabrication of complex 3D metal structures with sub-100 nm lateral resolution and sub-10 nm vertical resolution. Since 3D polymer brushes can be serially fabricated in parallel, this method is effective to generate arbitrary 3D metal structures over a large area at a high throughput.


[Comments on the Guidelines for the Prudent Use of Antibacterial Veterinary Pharmaceuticals (Guidelines for Antibiotics)].
In 2010 the German Bundestierärztekammer (Federal Chamber of Veterinarians) and the AGTAM (Working Group "Veterinary Pharmaceuticals") published the Guidelines for the prudent use of antibacterial veterinary pharmaceuticals in an updated version. Within the limits of therapeutic freedom, veterinarians are committed to take into account the latest scientific findings in veterinary medicine. These findings may, however, include conflicting interpretations if such an approach is expressed by an accredited university or anywhere else in the field of science. Hence, the state of science in veterinary medicine is not only defined by the Guidelines for Antibiotics, rather, the complete recognized scientific literature has to be considered. The Guidelines for Antibiotics are not legally-binding rules. They define the best approach and not the minimum standard for the use of antibiotics. The clinical examination provides the basis for medical treatment in each specific case. Further laboratory diagnostics represent an additional supportive instrument that is used by the veterinarian at his discretion depending on the necessity. Laboratory tests of bacterial sensitivity (identification of pathogens and antibiogram) may become necessary within the framework of diagnostics. As examples demonstrate, laboratory tests of bacterial sensitivity cannot be performed in every clinical case. It appears to be desirable to further discuss the use of antibacterial veterinary pharmaceuticals in the species-specific attachments in more concrete and specific terms, taking into consideration the standards of evidence-based medicine.


Rat lung transplantation model: modifications of the cuff technique.
Although the cuff technique in rat lung transplantation (LTx) has a long history, it remains technically challenging. We have developed key tricks and modifications in the devices and the cuff technique that optimize the rat LTx model to achieve successful operations during a short learning period. Altogether, 180 consecutive rats underwent orthotopic left LTx performed by a single surgeon using our modified devices and procedures. Allogeneic and syngeneic transplantation were performed using Lewis rats as recipients and Brown Norway and Lewis rats as donors. Allogeneic recipients were treated with cyclosporine during the first week. Recipients were sacrificed at various time points after ≥2 weeks. A special cuff-preparation plate was created using a petri dish and two foam blocks. This modified plate stabilizes the preparation and prevents donor lung compression. A "┴"-shaped incision was carved into the front wall of the pulmonary artery (PA) using micro-scissors. "V"-shaped incisions were made from the inferior-to-superior branches of the pulmonary vein (PV) and bronchus. A "pendulum model" was applied at implantation to make the hilar anastomosis tension-free and technically easier to perform. There were no intraoperative complications. Ten rats (5.6%) experienced partial or full pulmonary atelectasis. Five deaths (2.8%) due to pleural effusion occurred during the follow-up period. The operative times for heart-lung block retrieval, cuff preparation, cold ischemia, warm ischemia, and total procedure time were 8.4±0.8, 11.6±1.5, 25.1±2.2, 8.1±1.2, and 46.7±2.8 min, respectively. The key tricks and improvements we made in the cuff technique for rat LTx provided the advantages of expeditiousness, a low complication rate, and a high success rate.


Do recycled spectacles meet the refractive needs of a developing country?
The aim was to compare the power of spectacles donated to a recycled spectacle program to the custom-made spectacle refractive prescriptions dispensed in a developing country. Two hundred consecutive prescriptions were audited in an optical dispensary in Timor-Leste, a developing nation. These refractions were compared against measurements of 2,075 wearable donated spectacles. We determined how many of the 200 prescriptions could be matched to a donated spectacle measurement, how many donated spectacles could be tried for each prescription and how long it would take to find the matched spectacles. There were 1,854 donated spectacles identified as being suitable for comparison with the 200 refractive prescriptions. Twenty-nine out of 200 prescriptions (14.5 per cent) were matched to at least one pair of donated spectacles. Recycling all spectacles is not cost-effective in a developing country that has the ability to make custom-made spectacles and dispense ready-made spectacles.


Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.
Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.