Sudden vision loss caused by rhino-orbital zygomycosis in diabetic patients: case series.
Rhino-orbital zygomycosis is a life-threatening fungal infection generally occurring in patients with an underlying disorder, such as diabetes mellitus with ketoacidosis or with immunocompromising factors, although it may rarely appear in healthy individuals. The study has been undertaken to discuss the clinical presentation, pathogenesis, diagnostic work up and management of this rapidly progressive disease. Four male patients having uncontrolled diabetes and presenting with signs and symptoms of rhino-orbital zygomycosis were studied to illustrate the serious nature of the disease. All the four patients had rapidly deteriorating vision loss either unilateral or bilateral along with other nasal and orbital signs and symptoms. All the patients were put on liposomal amphotericin B and underwent orbital exenteration and pansinusectomy. One patient died, while the other three were successfully treated. Early diagnosis is critical in the prevention of morbidity and mortality associated with the disease. There is need for a high index of clinical suspicion in immunocompromised patients. Timely medical-surgical treatment proves extremely important for prognosis.


Butyrylcholinesterase, cholinergic neurotransmission and the pathology of Alzheimer's disease.
Butyrylcholinesterase is a serine hydrolase biochemically related to the cholinergic enzyme acetylcholinesterase. It is capable of hydrolyzing esters of choline. Butyrylcholinesterase has unique enzymatic properties and is widely distributed in the nervous system, raising the possibility of its involvement in neural function. In particular, recent evidence indicates that along with acetylcholinesterase, butyrylcholinesterase catalyzes the hydrolysis of acetylcholine, and thus serves as a co-regulator of cholinergic transmission. Accumulating evidence also indicates that butyrylcholinesterase is likely to be involved in neurodegenerative disorders such as Alzheimer's disease. Therefore, inhibition of butyrylcholinesterase will not only lead to enhanced cholinergic transmission but also has the potential to interfere with the disease process in Alzheimer's disease and other dementing disorders.


Suicidal ideation and help-negation: Not just hopelessness or prior help.
Few distressed young people seek professional psychological help and little is known about what sources of help young people seek for different problems. In suicidal youth, the process of help-negation may exacerbate poor help-seeking. Three hundred and two undergraduate university students completed a questionnaire measuring suicidal ideation, hopelessness, prior help-seeking experience, and help-seeking intentions. Participants indicated they would seek help from different sources of help for different types of problems, but friends consistently were rated as the most likely source of help. Help-negation was suggested by higher levels of suicidal ideation being associated with lower help-seeking intentions. However, the negative suicidal ideation/help-seeking-intentions relationship was not explained by hopelessness or prior help-seeking. Help-negation appears to involve more than just negative expectations regarding the future. The discussion proposes social problem-solving orientation as one of a number of potential explanatory variables.


Trans-Sylvian selective amygdalohippocampectomy for medically intractable temporal lobe epilepsy: a single-centre experience.
Selective amygdalohippocampectomy (SelAH) is now widely used in the surgical treatment of patients with medically intractable medial temporal lobe epilepsy (MTLE). We present our single-centre experience of a uniform series of drug-resistant MTLE patients treated exclusively with SelAH. A retrospective study of 50 adult patients (25 males, 25 females, mean age 34 years) suffering from medically intractable MTLE was conducted. All patients has been investigated under the same protocol and operated by SelAH performed by one surgeon. Immediate and long-term follow-up was also available and is presented. Forty-two patients (84%) became seizure free (Engel's I); eight of them (16%) were classified as Engel's II; four (8%) as Engel's III; and one as Engel's IV (2%). In 42 of them the final result has been achieved after a single operation, while in the rest eight after a second or third surgical procedure. The mean follow-up period was 6.2 years. Two permanent complications (4%) with no treatment-related mortality have been detected. SelAH performed in well selected cases, where concordance between electrophysiological and MR findings exists, can be a safe and effective surgical treatment method for medically intractable MTLE.


pH and bicarbonate in the ductuli efferentes testis of the rat.
The pH and bicarbonate concentrations of luminal fluids in the efferent ducts of the rat were estimated from pH measurements of samples in vitro under conditions of controlled temperature and carbon dioxide tension. The pH of scrotal blood was estimated to be more acidic than systemic blood (mean pH=7.44) at either of the putative scrotal carbon dioxide tensions (5% and 7%, pH, respectively,=7.42 and 7.28). For PCO2 tensions of 5% and 7%, respectively, the data indicated that the pH in the efferent ducts was significantly higher (distal initial zone pH=7.55 or 7.41; coni vasculosi pH=7.66 or 7.51; p < 0.01) than in fluid entering (rete testis fluid, pH=7.34 or 7.20) or leaving the ducts (zone 1a of the epididymal duct 7.26 or 7.11). Bicarbonate concentrations were also significantly higher (p < 0.01) in the efferent ducts (35.4 +/- 4.7 mM, distal initial zone; 45.2 +/- 7.6 mM, coni vasculosi) than in fluids entering (22.9 +/- 3.6 mM) or leaving (20.4 +/- 4.9 mM) the ducts. Estimates of the reabsorption of bicarbonate and fluid indicated that 96% of the testicular output of bicarbonate was reabsorbed in the efferent ducts, but there was also some secretion of bicarbonate into the ducts. It is concluded that luminal pH and bicarbonate levels in the efferent ducts of the rat are high relative to those found in the epididymis where low pH and bicarbonate contributes to sperm quiescence during storage. Nevertheless, the high rate of bicarbonate reabsorption in the efferent ducts is a major contributor to the establishment of the low pH and bicarbonate milieu of the epididymis.


An arterially perfused decerebrate preparation of Suncus murinus (house musk shrew) for the study of emesis and swallowing.
Arterially perfused, decerebrate preparations of the insectivore, Suncus murinus were made to determine whether the emetic reflex could be activated in such a preparation using a range of stimuli shown to be emetic in conscious or anaesthetised Suncus. Efferent phrenic and vagus nerve activities and electromyograms (EMGs) from the temporalis, abdominal oesophagus and trapezius muscles were recorded, as well as longitudinal shortening of the oesophagus and dorso-ventral movements of the thorax. The preparations swallowed spontaneously every 0.6 to 6.5 min. The duration of a swallow was 3.1 +/- 0.3 s (recorded as the time taken for the oesophagus to shorten and recover to its resting position) and the oesophagus shortened by 3.5 +/- 0.4 mm during a swallow. The emetic reflex was activated by electrical stimulation (30 Hz, 10-20 V, 0.2 ms pulse width, for 30 s) of abdominal vagal afferents (latency < 30 s) or by arterial perfusion with either 40 nM of the capsaicin analogue resiniferatoxin (latency 1.7 +/- 0.6 min), 6 microM nicotine (latency 1.6 +/- 0.1 min) or 1 microM of the phosphodiesterase IV inhibitor CP-80,633 (latency 8.9 +/- 3.9 min). These emetic stimuli produced somatic and visceral movements in Suncus preparations indicative of activation of the emetic reflex. There were pronounced contractions of the thorax that occurred simultaneously with oesophageal shortening and mouth opening, separated by thorax expansion and a burst of phrenic nerve activity. During emetic-like episodes, oesophageal shortenings were only 0.84 +/- 0.1 s in duration, faster than the duration of shortening observed during swallowing (cf. swallowing, 3.1 +/- 0.3 s; P < 0.0001). The shortening of the oesophagus during emetic-like episodes was 6.2 +/- 0.4 mm, which was greater than the shortening seen during swallowing (cf. swallowing, 3.5 +/- 0.4 mm; P < 0.0001). We conclude that the emetic reflex can be activated in our Suncus preparations and that this non-sentient small adult animal model can now be used to study the neurophysiology and pharmacology of swallowing and emesis.


Increasing Cystatin C and Cathepsin B in Serum of Colorectal Cancer Patients.
The aim of this study was to measure levels of cathepsin B (CatB) and cystatin C (CysC) and determine the CatB/CysC ratio in serum samples from patients with colorectal cancer (CRC), benign diseases of the digestive system, and other malignancies. The serum specimens of 95 patients with CRC, 23 with benign diseases of the digestive system, 60 normal controls and 87 with other cancers were collected to measure the level of CysC and CatB. The CatB/CysC ratio was then calculated. There was a significant difference between the normal group and the CRC group (p < 0.01) in CysC serum levels. There were also differences in CatB levels and in the ratio of CatB/CysC between CRC patients and healthy controls or those with benign diseases of the digestive system (p < 0.01) and between those with carcinoma (highly-differentiated and poorly-differentiated) and those with adenoma (p < 0.01). The CysC, CatB, and CatB/ CysC levels were in the same range in other malignancies and CRC. These results suggest that CysC could exclude normal samples, while the level of CatB and the CatB/ CysC ratio could distinguish CRC from benign diseases of the digestive system and thus has important value in early diagnosis of CRC.


Role of the tetraheme cytochrome CymA in anaerobic electron transport in cells of Shewanella putrefaciens MR-1 with normal levels of menaquinone.
Shewanella putrefaciens MR-1 possesses a complex electron transport system which facilitates its ability to use a diverse array of compounds as terminal electron acceptors for anaerobic respiration. A previous report described a mutant strain (CMTn-1) deficient in CymA, a tetraheme cytochrome c. However, the interpretation of the electron transport role of CymA was complicated by the fact that CMTn-1 was also markedly deficient in menaquinones. This report demonstrates that the depressed menaquinone levels were the result of the rifampin resistance phenotype of the parent of CMTn-1 and not the interruption of the cymA gene. This is the first report of rifampin resistance leading to decreased menaquinone levels, indicating that rifampin-resistant strains should be used with caution when analyzing electron transport processes. A site-directed gene replacement approach was used to isolate a cymA knockout strain (MR1-CYMA) directly from MR-1. While MR1-CYMA retained menaquinone levels comparable to those of MR-1, it lost the ability to reduce iron(III), manganese(IV), and nitrate and to grow by using fumarate as an electron acceptor. All of these functions were restored to wild-type efficacy, and the presence of the cymA transcript and CymA protein was also restored, by complementation of MR1-CYMA with the cymA gene. The requirement for CymA in anaerobic electron transport to iron(III), fumarate, nitrate, and manganese(IV) is therefore not dependent on the levels of menaquinone in these cells. This represents the first successful use of a suicide vector for directed gene replacement in MR-1.


On the pathogenesis of atherosclerosis: enzymatic transformation of human low density lipoprotein to an atherogenic moiety.
Combined treatment with trypsin, cholesterol esterase, and neuraminidase transforms LDL, but not HDL or VLDL, to particles with properties akin to those of lipid extracted from atherosclerotic lesions. Single or double enzyme modifications, or treatment with phospholipase C, or simple vortexing are ineffective. Triple enzyme treatment disrupts the ordered and uniform structure of LDL particles, and gives rise to the formation of inhomogeneous lipid droplets 10-200 nm in diameter with a pronounced net negative charge, but lacking significant amounts of oxidized lipid. Enzymatically modified LDL (E-LDL), but not oxidatively modified LDL (ox-LDL), is endowed with potent complement-activating capacity. As previously found for lipid isolated from atherosclerotic lesions, complement activation occurs to completion via the alternative pathway and is independent of antibody. E-LDL is rapidly taken up by human macrophages to an extent exceeding the uptake of acetylated LDL (ac-LDL) or oxidatively modified LDL. After 16 h, cholesteryl oleate ester formation induced by E-LDL (50 micrograms/ml cholesterol) was in the range of 6-10 nmol/mg protein compared with 3-6 nmol/mg induced by an equivalent amount of acetylated LDL. At this concentration, E-LDL was essentially devoid of direct cytotoxic effects. Competition experiments indicated that uptake of E-LDL was mediated in part by ox-LDL receptor(s). Thus, approximately 90% of 125I-ox-LDL degradation was inhibited by a 2-fold excess of unlabeled E-LDL. Uptake of 125I-LDL was not inhibited by E-LDL. We hypothesize that extracellular enzymatic modification may represent an important step linking subendothelial deposition of LDL to the initiation of atherosclerosis.


Sleep and timekeeping changes, and dysregulation of the biological clock in experimental trypanosomiasis.
The rest-activity and body temperature 24 hours cycles, as well as the pattern of spontaneous sleep, were investigated in rats after infection with Trypanosoma brucei brucei. In the infected rats, which were entrained to a 12 hours/12 hours photoperiod, a considerable hypokinesia was detected during the hours of darkness. In most of the infected animals, the body temperature cycle displayed a lower amplitude and an advance of about 3 hours in respect to control rats; in addition, the body temperature rhythm was not significant in some infected rats. The relative proportion of slow wave synchronized sleep, as well as the rapid-eye movement (REM) latency, were significantly reduced in the infected animals, in which sleep was considerably fragmented. The induction of Fos (the protein encoded by the immediate early gene c-fos), in response to light stimulation during the early subjective night, was severely impaired in the hypothalamic suprachiasmatic nuclei in trypanosome-infected rats. Altogether these data point out a disruption of locomotor activity and body temperature 24 hours cycle and a major disorganization of sleep during experimental trypanosomiasis. In addition, our findings indicate that the molecular and functional correlates of the synchronizing action of the suprachiasmatic nuclei, which play a major role of biological clock of endogenous biological rhythms, could be altered during trypanosome infection.


[Influence of lymphostasis on healing processes of intestinal anastomoses. Experimental research].
The Authors studied the healing of the intestinal anastomoses in rats with mesenteric and celiac lymph-vessels coagulated and cut. The experiment was realized utilizing 104 rats, divided in fours groups: after the induction of the lymphostasis, in the first group an end-to-end ileal anastomosis was made by polyglycolic acid suture, 6/0 in diameter. The control groups consisted of rats with ileal anastomoses, with lymphostasis solely and sham operated. The macroscopic observation and the histological findings were studied 7 and 14 days after the anastomoses' performance. Only in the animals with lymphostasis was observed an anastomosal leakage of 19% at 7th day control. In the same period the histologic sections showed a modified anastomosal healing, related to the significant reduction of the granulomatous tissue formation in presence of the lymphostasis.


Ultrasonography in the diagnosis of obstructive jaundice.
Ultrasonography was employed in the diagnosis of obstructive jaundice. In a group of 38 patients who were studied, Ultrasonography was found to be reliable in confirming the diagnosis. In majority of the cases it was also found to be reliable in revealing the cause of obstruction. Nineteen of these patients were examined by percutaneous transhepatic cholangiography (PTC) and there were 100 per cent correlation with Ultrasonography. Twelve of these patients underwent operation and the findings were in good agreement with those of Ultrasonography.


Relationships between force-feeding and some physiological parameters in geese bred for fatty liver.
The susceptibility of geese of different genotypes and sexes to force-feeding, some plasma biochemical parameters (thyroid hormones, cholesterol, retinoids, total protein and albumin) of force-fed geese, and the relationship between force-feeding, fat storage and the above-mentioned parameters were studied. Sixty (30 male and 30 female) geese of three genotypes (Hungarian, Landes and their crossbred called Babat Hybrid) were divided in two groups at 12 weeks of age. Geese in one group (5 males and 5 females from each genotype) received mixed feeding ad libitum. Birds in the other group were force-fed with maize. After 3 weeks all birds were bled, blood samples were taken, and the above-mentioned plasma parameters were determined. Thyroxine (T4) levels were significantly lower in force-fed (11.6 +/- 3.5 ng/ml) than in control geese (22.7 +/- 4.09 ng/ml). Plasma triiodothyronine (T3) level was also lower in the force-fed than in the control group, but the difference was not significant (1.87 +/- 0.23 ng/ml and 2.11 +/- 0.28 ng/ml, respectively). Plasma total protein (TP, 45.2 +/- 4.5 g/l), albumin (ALB, 16.51 +/- 2.8 g/l), beta-carotene (BC, 3504 +/- 3107 micrograms/l), retinol (ROL, 1160 +/- 505 micrograms/l), retinyl palmitate (RP, 1745 +/- 405 micrograms/l) and total cholesterol (TCh, 4.32 +/- 0.55 mmol/l) levels were elevated in the force-fed group as compared to the control (TP = 36.4 +/- 5.1 g/l, ALB = 15.6 +/- 0.9 g/l, BC = 1657 +/- 1681 micrograms/l, ROL = 687 +/- 375 micrograms/l, RP = 1398 +/- 607 micrograms/l, and TCh = 2.83 +/- 1.98 mmol/l). All differences were significant except those found for albumin and beta-carotene. No significant sex- or genotype-related effects were observed for these parameters.


Supportive Care.
This chapter takes its point of departure in psychosocial aspects of supportive care in adolescent and young adult cancer care. The purpose is to describe some of the challenges that these young people face following a cancer diagnosis and guide healthcare professionals in how to provide care that improves the quality of life. In most hospitals and healthcare systems, adolescents and young adults are cared for and treated in settings for children or adults. Accordingly, healthcare professionals may lack attention to and knowledge about what characterize young peoples' life situation, their special needs and how to meet them. The topics we include in the chapter are the following: the youth friendly environment, social support and social network, parents, information during a psychosocial crisis event, the use of HEADSS, peer support, fertility, body image and self-esteem, after treatment and future challenges and palliative and end of life care.


Dislocation of the sternoclavicular joint. Evaluation using paraxial computed tomographic reconstruction.
Sternoclavicular dislocations are relatively infrequent, constituting less than 1% of somatic dislocations. Despite the fact that the sternoclavicular joint is the only articulation between the upper extremity and the axial skeleton, it possesses the least amount of osseous stability of any joint in the body. Sternoclavicular dislocations are generally divided into anterior and posterior disruptions, the former being the most common. An unusual case of an anterior dislocation of the sternoclavicular joint with a large superior component is described. It was found that coronal paraxial computed tomographic reconstruction of the joint was quite useful in evaluating this injury.


Hydroxylation of tanshinone IIa in human liver microsomes is specifically catalysed by cytochrome P4502A6.
Tanshinone IIa, the primary active component of a traditional Chinese medicine Salvia miltiorrhiza (Danshen), has a wide range of pharmacological activities. In the present study, the metabolism of tanshinone IIa (5 microM) by cytochrome P450s (CYPs) was investigated in human liver microsomes. One mono-hydroxylated metabolite was detected in a reaction catalysed by human liver microsomes, and was identified as tanshinone IIb by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound. The study with a chemical selective inhibitor, cDNA-expressed human cytochrome P450s, correlation assay, and kinetics study demonstrated that CYP2A6 was the specific isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 microM) in human liver microsomes.


Assessment of a method to detect signals for updating systematic reviews.
Systematic reviews are a cornerstone of evidence-based medicine but are useful only if up-to-date. Methods for detecting signals of when a systematic review needs updating have face validity, but no proposed method has had an assessment of predictive validity performed. The AHRQ Comparative Effectiveness Review program had produced 13 comparative effectiveness reviews (CERs), a subcategory of systematic reviews, by 2009, 11 of which were assessed in 2009 using a surveillance system to determine the degree to which individual conclusions were out of date and to assign a priority for updating each report. Four CERs were judged to be a high priority for updating, four CERs were judged to be medium priority for updating, and three CERs were judged to be low priority for updating. AHRQ then commissioned full update reviews for 9 of these 11 CERs. Where possible, we matched the original conclusions with their corresponding conclusions in the update reports, and compared the congruence between these pairs with our original predictions about which conclusions in each CER remained valid. We then classified the concordance of each pair as good, fair, or poor. We also made a summary determination of the priority for updating each CER based on the actual changes in conclusions in the updated report, and compared these determinations with the earlier assessments of priority. The 9 CERs included 149 individual conclusions, 84% with matches in the update reports. Across reports, 83% of matched conclusions had good concordance, and 99% had good or fair concordance. The one instance of poor concordance was partially attributable to the publication of new evidence after the surveillance signal searches had been done. Both CERs originally judged as being low priority for updating had no substantive changes to their conclusions in the actual updated report. The agreement on overall priority for updating between prediction and actual changes to conclusions was Kappa = 0.74. These results provide some support for the validity of a surveillance system for detecting signals indicating when a systematic review needs updating.


Hypophosphatemia and calcium nephrolithiasis.
Our knowledge of phosphate balance under physiological and pathological situations has increased substantially during the last decade thanks to the molecular identification of three dissimilar families of sodium-phosphate cotransport systems, two of them almost exclusively expressed in epithelia whereas the third one has a ubiquitous expression. Intracellular proteins such as NHERF1 (sodium-proton exchanger regulatory factor 1) can interact with phosphate transporters through PDZ domains thus regulating the expression of the transporters at the membrane. Moreover, newly acknowledged paracrine/endocrine peptides, such as fibroblast growth factor 23 (FGF23), also affect the activity of phosphate transporters. Renal phosphate leak, related to invalidation (in the mouse) or to mutations (in humans) of the renal phosphate transporter NPT2a, leads to hypophosphatemia on the one hand, and to nephrolithiasis or bone demineralization on the other hand. Similar features are observed during invalidation of NHERF or in case of overproduction of FGF23. These observations highlight the importance of phosphate homeostasis in common diseases such as renal stones or bone loss.


The Effects of Vitamin D on Immune System and Inflammatory Diseases.
Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.


Subjects older than 60 years with negative findings on sigmoidoscopy should still undergo colonoscopy.
The objective of this study was to evaluate the impact of age on the prevalence of proximal clinically important lesions in subjects without any rectosigmoid neoplasm. The present study involved 497 patients (aged > or = 50 years old) who underwent a colonoscopy because of abdominal symptoms or positive fecal occult blood test. A proximal colon was defined as one proximal to a sigmoid colon. Clinically important lesions were defined as adenocarcinoma, tubular adenoma > or = 1 cm in diameter, or adenoma with villous histology or high-grade dysplasia. Of the 497 patients, 83 had clinically important lesions in the proximal colon. Of those 83, 53 patients had no neoplasm in the distal colon or rectum. In patients with no distal neoplasm, the prevalence of proximal clinically important lesions in subjects over 60 years old significantly exceeded that in patients aged 50-60 (39/105 vs. 14/125; P < 0.0001). In patients with distal neoplasm, the prevalence of proximal clinically important lesions in subjects over 60 was similar to that in 50 to 60-year-old subjects (16/119 vs. 14/148; P = 0.406). Results suggest that subjects older than 60 years old should still undergo a colonoscopy even if they have no neoplasm on sigmoidoscopy.


Investigation of the scope of a new route to ABCD-bilanes and ABCD-porphyrins.
A new route to bilanes and porphyrins bearing four distinct meso substituents has been studied to elucidate the scope and gain entry to previously inaccessible compounds. The route entails (i) synthesis of a 1-bromo-19-acylbilane by acid-catalyzed condensation of a 1-acyldipyrromethane and a 9-bromodipyrromethane-1-carbinol and (ii) intramolecular cyclization of the 1-bromo-19-acylbilane in the presence of a metal salt (MgBr2, 3 mol equiv) and a non-nucleophilic base (DBU, 10 mol equiv) in a noncoordinating solvent (toluene) at 115 degrees C exposed to air to afford the corresponding magnesium(II) porphyrin. In this study, two sets of bilanes were initially prepared to explore substituent effects. In the first set, all bilanes vary only in the nature of the substituent at the 10-position. In the second set, all bilanes vary only in the nature of the substituent attached to the acyl unit (the 20-position). The substituents examined at the 10- and 20-positions include alkyl, aryl (electron-rich, electron-deficient, hindered), heteroaryl, ester, or no substituent (-H). The bilanes were obtained in 35-87% yield, and the target porphyrins in up to 60% yield. Further study of the scope focused on bilanes and porphyrins bearing three heterocyclic substituents (o-, m-, p-pyridyl) or four alkyl groups (ethyl, propyl, butyl, pentyl), in which case microwave irradiation was used for the porphyrin-forming step. Altogether, 17 bilanes and 19 porphyrins were prepared and characterized. In summary, the new route provides access to meso-substituted bilanes and porphyrins for which access is limited via other methods.


[Asthma in children more and more common. A study of medical records shows a doubled increase during a 10-year period].
The number of children with asthma is rising. This is shown by a study of medically diagnosed asthma in a cohort of children born in 1990 in a well defined and limited region. The medical records from all of the health centres in primary health care, privately practising paediatricians and relevant child clinics in the region were examined when the children were 7 years old. The results showed that 10.9% of the children had been diagnosed with asthma. The percentage of children with asthma was highest (14.2%) among boys living in a city environment. Comparison with a similar follow-up study in the same region concerning children born in 1975 showed that the percentage of children with asthma doubled during a period of just over a decade.


Disrupting the adult globin promoter alleviates promoter competition and reactivates fetal globin gene expression.
The benign condition hereditary persistence of fetal hemoglobin (HPFH) is known to ameliorate symptoms of co-inherited β-hemoglobinopathies, such as sickle cell disease and β-thalassemia. The condition is sometimes associated with point mutations in the fetal globin promoters that disrupt the binding of the repressors BCL11A or ZBTB7A/LRF, which have been extensively studied. HPFH is also associated with a range of deletions within the β-globin locus that all reside downstream of the fetal HBG2 gene. These deletional forms of HPFH are poorly understood and are the focus of this study. Numerous different mechanisms have been proposed to explain how downstream deletions can boost the expression of the fetal globin genes, including the deletion of silencer elements, of genes encoding noncoding RNA, and bringing downstream enhancer elements into proximity with the fetal globin gene promoters. Here we systematically analyze the deletions associated with both HPFH and a related condition known as δβ-thalassemia and propose a unifying mechanism. In all cases where fetal globin is upregulated, the proximal adult β-globin (HBB) promoter is deleted. We use clustered regularly interspaced short palindromic repeats-mediated gene editing to delete or disrupt elements within the promoter and find that virtually all mutations that reduce ΗΒΒ promoter activity result in elevated fetal globin expression. These results fit with previous models where the fetal and adult globin genes compete for the distal locus control region and suggest that targeting the ΗΒΒ promoter might be explored to elevate fetal globin and reduce sickle globin expression as a treatment of β-hemoglobinopathies.


BIFI: a Taverna plugin for a simplified and user-friendly workflow platform.
Heterogeneity in the features, input-output behaviour and user interface for available bioinformatics tools and services is still a bottleneck for both expert and non-expert users. Advancement in providing common interfaces over such tools and services are gaining interest among researchers. However, the lack of (meta-) information about input-output data and parameter prevents to provide automated and standardized solutions, which can assist users in setting the appropriate parameters. These limitations must be resolved especially in the workflow-based solution in order to ease the integration of software. We report a Taverna Workbench plugin: the XworX BIFI (Beautiful Interfaces for Inputs) implemented as a solution for the aforementioned issues. BIFI provides a Graphical User Interface (GUI) definition language used to layout the user interface and to define parameter options for Taverna workflows. BIFI is also able to submit GUI Definition Files (GDF) directly or discover appropriate instances from a configured repository. In the absence of a GDF, BIFI generates a default interface. The Taverna Workbench is an open source software providing the ability to combine various services within a workflow. Nevertheless, users can supply input data to the workflow via a simple user interface providing only a text area to enter the input in text form. The workflow may contain meta-information in human readable form such as description text for the port and an example value. However, not all workflow ports are documented so well or have all the required information.BIFI uses custom user interface components for ports which give users feedback on the parameter data type or structure to be used for service execution and enables client-side data validations. Moreover, BIFI offers user interfaces that allow users to interactively construct workflow views and share them with the community, thus significantly increasing usability of heterogeneous, distributed service consumption.


Fine needle aspiration cytology in lesions of oral and maxillofacial region: Diagnostic pitfalls.
Fine needle aspiration cytology (FNAC) of oral and maxillofacial region has not been widely utilized for diagnosis due to diversity of lesion types, heterogeneity of cell populations and difficulties in reaching and aspirating these lesions. Our aim was to demonstrate the effectiveness of this cheap and simple procedure for the diagnosis of tumor and tumor like lesions of oral and maxillofacial region. In addition, we sought to highlight probable causes of errors in the cases showing lack of correlation between cytological and histological diagnoses. The study was conducted on 50 patients of all age groups with various palpable lesions in the oromaxillofacial region. A comparison between cytological and histological diagnosis was done wherever biopsy material was available. The rate of unsatisfactory FNA was 4%. There were six false negative cases but no false positive case. The sensitivity of our study ranged from 77.7 to 75% including and excluding the suspicious cases, respectively. Specificity and positive predictive value was 100%. FNAC is a minimally invasive, highly accurate and cost-effective procedure for the assessment of patients with oromaxillofacial lesions. When applied in a proper manner, FNAC can help avoid a surgical biopsy in many cases.


Inequities in tobacco retailer sales to minors by neighbourhood racial/ethnic composition, poverty and segregation, USA, 2015.
Tobacco retailers are an important source of tobacco products for minors. Previous research shows racial discrimination in sales to minors, but no national study has examined neighbourhood correlates of retailer under-age sales. We accessed publicly available results of 2015 US Food and Drug Administration (FDA) inspections of tobacco retailers (n=108 614). In this cross-sectional study, we used multilevel logistic regression to predict the likelihood of retailer sale to a minor based on tract characteristics. We assessed the proportion of residents identifying as American Indian, Asian, Black, Latino and White; Isolation Index scores for each racial/ethnic group; the proportion of people less than age 65 living in poverty; and the proportion of residents age 10-17 in relation to retailer inspection results. The proportion of American Indian residents, Black residents, Latino residents and residents less than age 65 under the poverty line in a neighbourhood are independently, positively associated with the likelihood that a retailer in that neighbourhood will fail an under-age buy inspection. The proportion of White residents and residents age 10-17 are independently, negatively associated with the likelihood of sale of tobacco products to a minor. Isolation Index scores show a similar pattern. In multivariable models holding neighbourhood characteristics constant, higher proportions of Black (+), Latino (+) and age 10-17 (-) residents remained significant predictors of the likelihood of under-age sale. Regulatory agencies should consider oversampling retailers in areas with higher likelihood of sales to minors for inspection. Interventions with tobacco retailers to reduce inequities in youth access should be implemented.


Ultracentrifugation micromethod for preparation of small experimental animal lipoproteins.
Sequential flotation ultracentrifugation is commonly used in the preparation of plasma lipoproteins. However, protocols often require prolonged centrifugation time (48-72 h) and large plasma volumes (2-20 ml), which makes them unsuitable for studies on small laboratory animals. Although analytical techniques such as FPLC have often small sample requirements, further fraction analysis is often limited to the small fraction volume obtained. A sequential ultracentrifugation micromethod is described to obtain rat lipoprotein fractions from 400 microl of plasma in a cumulative centrifugation time of 7.5 h. Fraction volumes were determined and densities were adjusted to those of rat plasma lipoproteins. Polyacrylamide gel electrophoresis and enzymatic measurements of triglycerides, total cholesterol, and phospholipids were used to assess the purity of the lipoprotein fractions. The results were compared with those obtained from a classical sequential ultracentrifugation protocol. The micromethod presented here can be further adapted to other experimental animal species with little modifications.


Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines.
The effect of interferon beta ser (IFN beta ser) on the growth of three prostatic cancer cell lines DU-145, PC-3 and LNCaP was studied. IFN beta ser inhibited growth of anchorage dependent semiconfluent monolayers and anchorage dependent colony formation of both DU-145 and PC-3 in a dose dependent manner but had no effect on LNCaP. Transforming growth factor beta (TGF beta 1) inhibited proliferation of DU-145 and PC-3 cells in 1% but not 8% fetal calf serum. The combination of TGF beta 1 and IFN beta ser was additive in its effects on growth. Neither epidermal growth factor (EGF) nor transforming growth factor alpha (TGF alpha) reduced the antiproliferative effect of IFN beta ser on these cells. These antiproliferative effects were reproduced in studies on primary epithelial cell cultures derived from prostate specimens with various pathologies. The potential use of IFN beta ser in combination with hormonal therapy to delay the development of hormone refractory tumors is discussed.


Stereoselective Separation of the Fungicide Bitertanol Stereoisomers by High-Performance Liquid Chromatography and Their Degradation in Cucumber.
Bitertanol is a widely used triazole fungicide and consists of four stereoisomers. A new high-performance liquid chromatography (HPLC) method was developed for simultaneous analysis of the four stereoisomers in apple, pear, tomato, cucumber, and soil. The mechanism of separation was explained with molecular docking and effects of thermodynamic parameters on the resolution. The absolute configuration and optical rotation of four stereoisomers were confirmed by X-ray diffraction and HPLC tandem circular dichroism, respectively. A good linearity ( R2 ≥ 0.999) was obtained for four stereoisomers in all matrix-matched calibration curves in the range of 0.02-10 mg/L. The mean recoveries of four stereoisomers in five matrices ranged from 74.6% to 101.0% with an intraday and interday relative standard deviation from 0.6% to 9.9%. Stereoselective degradation of bitertanol in cucumber was observed: (1 R,2 S)-bitertanol and (1 R,2 R)-bitertanol were preferentially degraded with enantiomeric fraction values from 0.5 to 0.43 at 7 d and 0.42 at 5 d, respectively. This research provides a useful tool for the analysis of bitertanol stereoisomers.


An estimate of the global sink for nitrous oxide in soils.
A literature survey of studies reporting nitrous oxide uptake in the soils of natural ecosystems is used to suggest that the median uptake potential is 4 μg m(-2) h(-1). The highest values are nearly all associated with soils of wetland and peatland ecosystems. Globally, the consumption of nitrous oxide in soils is not likely to exceed 0.3 TgN yr(-1), indicating that the projected sink is not more than 2% of current estimated sources of N(2)O in the atmosphere.


Blood pressure trends, plasma insulin levels and risk factors in rural and urban elderly populations of north India.
To compare the prevalence of hypertension and its risk factors with age-specific blood pressures in rural and urban subjects. A cross-sectional survey of two randomly selected villages and 20 randomly selected streets in Moradabad, north India. The subjects were 255 rural people (140 men, 115 women) and 311 urban people (172 men, 139 women) aged 60-84 years. The survey methods were questionnaires, blood pressure and anthropometric measurements and electrocardiography. The mean +/- SD blood pressures, both systolic (137.7 +/- 13 versus 131.2 +/- 12 mmHg) and diastolic (89.8 +/- 41 versus 85.8 +/- 9 mmHg) were significantly higher in urban men than they were in rural men. Similar differences between systolic (135.6 +/- 11 versus 129.2 +/- 10 mmHg) and diastolic (90 +/- 10 versus 87.6 +/- 9 mmHg) blood pressures were found among urban and rural women, respectively. A significant correlation between systolic blood pressures and increasing age was observed both for rural and for urban subjects of both sexes. The overall prevalences of hypertension based on World Health Organization criteria (17.6 versus 5.0%) and Joint National Committee fifth report criteria (34.0 versus 10.1%) were significantly higher among urban than they were among rural subjects. Multivariate logistic regression analysis revealed that age, body mass index, central obesity, glucose intolerance, 2 h plasma insulin and triglyceride level were associated independently with hypertension. The findings indicate that urban subjects had higher blood pressures than did rural subjects and that age, body mass index, central obesity and 2 h plasma insulin levels were significant risk factors for hypertension in an elderly population.


Nitric Oxide Detector Based on WO3-1wt%In2O3-1wt%Nb2O5 with State-of-the-Art Selectivity and ppb-Level Sensitivity.
Fast, sensitive, and precise detection of nitric oxide (NO) is critical to many applications in environmental monitoring and early disease diagnosis via respiratory testing. An effective detection system requires a sensor to detect NO gas at the parts per billion (ppb) level, and this system should possess a high degree of anti-interference selectivity. To achieve these targets, a series of gas sensor thin films based on intrinsic WO3, one-additive-doped WO3 (prepared by doping In2O3 or Nb2O5), and two-additive-doped WO3 (synthesized by doping with In2O3 and Nb2O5) oxides were successfully grown. By analyzing the properties of sensitivity, selectivity, responsiveness, and recovery time of the gas sensors, we found that WO3-1wt%In2O3-1wt%Nb2O5 has overwhelming advantages over intrinsic WO3, WO3-In2O3, and WO3-Nb2O5. A sensing response value of 2.4 was observed for NO concentrations as low as 20 ppb from the WO3-1wt%In2O3-1wt%Nb2O5 sensor. With 100 ppb NO gas, the WO3-1wt%In2O3-1wt%Nb2O5 sensor achieved a high response of 56.1 at 70 °C, which is a state-of-the-art performance for NO detection at low working temperature settings. WO3-1wt%In2O3-1wt%Nb2O5 also yields significantly improved selectivity and stability over intrinsic WO3, WO3-In2O3, and WO3-Nb2O5. Studies on the sensing mechanism show that the grain size, rather than the n-n heterostructure effect, plays a dominant role in the observed results. By decreasing the grain size so that it is close to the thickness of the space-charge layer, the sensing response is enhanced. Although room remains to further improve the sensing properties, the performance of WO3-1wt%In2O3-1wt%Nb2O5 is sufficient for implementation in low-content NO detection devices.


[Cutaneous adverse drug reactions: enhanced imputation score by skin testing].
A careful diagnosis and the identification of the causative drug after a cutaneous adverse reaction can avoid relapses. Skin tests facilitate the identification of the causative molecule by producing a hypersensitivity reaction at the application site. Adverse drug reactions are reported to Pharmacovigilance Centres who determine the imputation score of the suspected drugs. The aim of this study was to assess to what extent skin testing after a suspected allergic drug reaction can be helpful to identify the causative drug and whether an impact on the final imputation score could be evidenced. A 18-month prospective study was performed. All patients with a history of cutaneous adverse drug reaction of suspected immunoallergic origin were included provided skin tests could be performed within 6 to 12 weeks after the adverse drug reaction. The imputation score was determined using the French imputation method prior to and after skin testing. Thirthy-nine patients were included in the study. Positive skin tests were observed in 11 of 20 patients with a C2S2 (I2: plausible) initial imputation score and in 6 of 15 patients with a C2S1 (I1: doubtful) initial imputation score. One patient with a C1S1 (I1: doubtful) initial imputation score had positive skin tests. The results of skin tests helped change the imputation score of the suspected drug in 18 patients out of 39. In 55 p. 100 of cases, the imputation score was increased from C2S2 (I2) to C2S3 (I3: likely) and from C2S1 (I1) to C2S3 (I3) in 40 p. 100 of cases. The increase in imputation scores was helpful to improve warning signals after an immunoallergic reaction. Skin tests led to a more accurate diagnosis in 50 p. 100 of cases. Thus, more adequate advices for further drug treatment were possible, particularly in avoiding the irrelevant prohibition of innocent drugs.


Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.


Altered astronaut lower limb and mass center kinematics in downward jumping following space flight.
Astronauts exposed to the microgravity conditions encountered during space flight exhibit postural and gait instabilities upon return to earth that could impair critical postflight performance. The aim of the present study was to determine the effects of microgravity exposure on astronauts' performance of two-footed jump landings. Nine astronauts from several Space Shuttle missions were tested both preflight and postflight with a series of voluntary, two-footed downward hops from a 30-cm-high step. A video-based, three-dimensional motion-analysis system permitted calculation of body segment positions and joint angular displacements. Phase-plane plots of knee, hip, and ankle angular velocities compared with the corresponding joint angles were used to describe the lower limb kinematics during jump landings. The position of the whole-body center of mass (COM) was also estimated in the sagittal plane using an eight-segment body model. Four of nine subjects exhibited expanded phase-plane portraits postflight, with significant increases in peak joint flexion angles and flexion rates following space flight. In contrast, two subjects showed significant contractions of their phase-plane portraits postflight and three subjects showed insignificant overall changes after space flight. Analysis of the vertical COM motion generally supported the joint angle results. Subjects with expanded joint angle phase-plane portraits postflight exhibited larger downward deviations of the COM and longer times from impact to peak deflection, as well as lower upward recovery velocities. Subjects with postflight joint angle phase-plane contraction demonstrated opposite effects in the COM motion. The joint kinematics results indicated the existence of two contrasting response modes due to microgravity exposure. Most subjects exhibited "compliant" impact absorption postflight, consistent with decreased limb stiffness and damping, and a reduction in the bandwidth of the postural control system. Fewer subjects showed "stiff" behavior after space flight, where contractions in the phase-plane portraits pointed to an increase in control bandwidth. The changes appeared to result from adaptive modifications in the control of lower limb impedance. A simple 2nd-order model of the vertical COM motion indicated that changes in the effective vertical stiffness of the legs can predict key features of the postflight performance. Compliant responses may reflect inflight adaptation due to altered demands on the postural control system in microgravity, while stiff behavior may result from overcompensation postflight for the presumed reduction in limb stiffness inflight.


Direct Observation of Filling Process and Porosity Prediction in High Pressure Die Casting.
Although numerical simulation accuracy makes progress rapidly, it is in an insufficient phase because of complicated phenomena of the filling process and difficulty of experimental verification in high pressure die casting (HPDC), especially in thin-wall complex die-castings. Therefore, in this paper, a flow visualization experiment is conducted, and the porosity at different locations is predicted under three different fast shot velocities. The differences in flow pattern between the actual filling process and the numerical simulation are compared. It shows that the flow visualization experiment can directly observe the actual and real-time filling process and could be an effective experimental verification method for the accuracy of the flow simulation model in HPDC. Moreover, significant differences start to appear in the flow pattern between the actual experiment and the Anycasting solution after the fragment or atomization formation. Finally, the fast shot velocity would determine the position at which the back flow meets the incoming flow. The junction of two streams of fluid would create more porosity than the other location. There is a transition in flow patterns due to drag crisis under high fast shot velocity around two staggered cylinders, which resulted in the porosity relationship also changing from R1 < R3 < R2 (0.88 m/s) to R1 < R2 < R3 (1.59 and 2.34 m/s).


Electrical generation of pure spin currents in a two-dimensional electron gas.
Pure spin currents are generated and detected in micron-wide channels of a GaAs two-dimensional electron gas, using quantum point contacts in an in-plane magnetic field as injectors and detectors. The enhanced sensitivity to spin transport offered by a nonlocal measurement geometry enables accurate spin current measurements in this widely studied physical system. The polarization of the contacts is used to extract the quantum point contact g factor and provides a test for spontaneous polarization at 0.7 structure. The spin relaxation length in the channel is 30-50 microm over the magnetic field range 3-10 T, much longer than has been reported in GaAs two-dimensional electron gases but shorter than that expected from Dyakonov-Perel relaxation.


Glutamate residues located within putative transmembrane helices are essential for TetA(P)-mediated tetracycline efflux.
The tetA(P) gene from Clostridium perfringens encodes a unique membrane protein that is responsible for the active efflux of tetracycline from resistant cells. The novel TetA(P) protein has neither the typical structure nor the conserved motifs that are found in tetracycline efflux proteins from classes A through H or classes K and L. Site-directed mutagenesis of selected residues within TetA(P) was performed to elucidate their role in tetracycline efflux. Glutamate residues 52 and 59, negatively charged residues located within putative transmembrane helix 2, could not be replaced by either glutamine or aspartate and so were essential for tetracycline efflux. Replacement of Glu89, which was located at the end of helix 3, by aspartate but not by glutamine allowed TetA(P) function, indicating the importance of a carboxyl group at this position. After mutation of the Asp67 residue, located within cytoplasmic loop 1, no immunoreactive protein was detected. It is concluded that negatively charged residues that appear to be located within or near the membrane are important for the function of TetA(P).


Transposable elements and the penetrance of quantitative characters in Drosophila melanogaster.
We wanted to determine whether there is a correlation between the quantitative character, the penetrance of the loss of humeral bristles in scute lines, and the distribution of transposable genetic elements in their genomes. We derived 18 isogenic lines with penetrance ranging between 2.8% and 92.0% from six mutant lines. The localization of the transposable elements (TEs) P, mdg1, Dm412, copia, gypsy and B104 was determined in all isogenic derivatives by in situ hybridization. The total number of the TE sites over all lines was 180. A comparison of the distribution of the TEs in the isogenic lines revealed the location of sites typical of lines with similar penetrance, no matter which parental line was involved. The results obtained suggest that such typical sites appear to tag the genome regions where the polygenes affecting the character in question are most likely to be found.


Short-term eplerenone for treatment of chronic central serous chorioretinopathy; a prospective study.
Increased mineralocorticoid activity is one of the plausible causes of chronic central serous chorioretinopathy (CSCR) and mineralocorticoid inhibitors such as eplerenone have been investigated as its potential therapy. This study investigates the short-term safety and efficacy of oral eplerenone in patients with chronic CSCR. Prospective study of 13 eyes of 13 patients with the diagnosis of chronic CSCR. All patients received eplerenone 50 mg/day for 4 weeks. Enhanced depth imaging optical coherence tomography (OCT) was obtained. Best corrected visual acuity (BCVA), and OCT parameters including sub retinal fluid (SRF), choroidal thickness (CT) and central macular thickness (CMT), were measured manually. The mean SRF height decreased slightly at 1-month follow-up as compared to baseline, but the change was not statistically significant (94.18 ± 17.53 vs. 113.15 ± 18.69; p = 0.08). Subfoveal CT and CMT was significantly reduced as compared to baseline (6.6% [p = 0.002] and 7.05% [p = 0.04], respectively). The BCVA did not change significantly (20/28 vs. 20/30 [p = 0.16]). This study suggests that oral eplerenone may be used as a safe and potentially effective treatment in chronic CSCR, however there are minimal short-term effects on subretinal fluid or visual acuity therefore therapeutic trials longer than one month are necessary to test its benefits.Trial registration Clinicaltrials.gov identification number: NCT01822561. Registered 3/25/13, https://clinicaltrials.gov/ct2/show/study/NCT01822561.


Enzymic dissociation of zea shoot cell wall polysaccharides : I. Preliminary characterization of the water-insoluble fraction of zea shoot cell walls.
The water-insoluble fraction, obtained after successive treatment of an insoluble fraction of a buffer-homogenate of Zea mays L. hybrid B73 x Mo 17 shoots with 3 molar LiCl and hot water, was treated with alpha-amylase to remove starch. This fraction has been subjected to sugar composition analysis and the major glycosidic linkages were determined. The results suggest that the water-insoluble fraction is mainly composed of arabinoxylan, (1 --> 3), (1 --> 4-)-beta-d-glucan, xyloglucan, (1 --> 4)-galactan, polygalacturonic acid, and cellulose. The insoluble fraction also contained ferulic acid (about 440 micrograms per 50 milligrams dry weight), which was released from the fraction by treatment with aqueous NaOH.Novo Ban 120 from Bacillus subtilis was found to be an appropriate enzyme source for selective dissociation of Zea shoot wall polysaccharides.


Muscle metabolism in patients with polymyositis simultaneously evaluated by using 31P-magnetic resonance spectroscopy and near-infrared spectroscopy.
Simultaneous measurements of muscle energy metabolism using (31)P-magnetic resonance spectroscopy ((31)P-MRS) and the kinetics of muscular oxygen metabolism using near-infrared spectroscopy (NIRS) were conducted in polymyositis (PM) patients. The subjects were 12 PM patients (age 45 +/- 12 years) and 12 normal controls (age 41 +/- 12 years). The muscle phosphocreatine (PCr) index and intracellular pH (pHi) were determined with (31)P-MRS and the changes in intramuscular oxygenated (oxy-Hb), deoxygenated (deoxy-Hb), and total haemoglobin (total Hb) were evaluated with NIRS . The pHi and PCr index before steroid therapy in PM patients were significantly lower during exercise than in normal controls, and their recovery was statistically significantly delayed compared with the controls. The pattern of changes in NIRS over time before steroid therapy in PM patients differed from that in normal controls. There were smaller changes in deoxy-Hb and oxy-Hb during exercise, and total Hb decreased during exercise. In contrast, the kinetics of muscular metabolism after steroid therapy showed changes similar to those seen in normal controls. Simultaneous (31)P-MRS and NIRS measurements to determine the kinetics of muscular metabolism are expected to be useful as a noninvasive approach for the evaluation of treatment effects in PM patients.


Different Behavior of Enteric Bacteria and Viruses in Clay and Sandy Soils after Biofertilization with Swine Digestate.
Enteric pathogens from biofertilizer can accumulate in the soil, subsequently contaminating water and crops. We evaluated the survival, percolation and leaching of model enteric pathogens in clay and sandy soils after biofertilization with swine digestate: PhiX-174, mengovirus (vMC0), Salmonella enterica Typhimurium and Escherichia coli O157:H7 were used as biomarkers. The survival of vMC0 and PhiX-174 in clay soil was significantly lower than in sandy soil (iT90 values of 10.520 ± 0.600 vs. 21.270 ± 1.100 and 12.040 ± 0.010 vs. 43.470 ± 1.300, respectively) and PhiX-174 showed faster percolation and leaching in sandy soil than clay soil (iT90 values of 0.46 and 2.43, respectively). S. enterica Typhimurium was percolated and inactivated more slowly than E. coli O157:H7 (iT90 values of 9.340 ± 0.200 vs. 6.620 ± 0.500 and 11.900 ± 0.900 vs. 10.750 ± 0.900 in clay and sandy soils, respectively), such that E. coli O157:H7 was transferred more quickly to the deeper layers of both soils evaluated (percolation). Our findings suggest that E. coli O157:H7 may serve as a useful microbial biomarker of depth contamination and leaching in clay and sandy soil and that bacteriophage could be used as an indicator of enteric pathogen persistence. Our study contributes to development of predictive models for enteric pathogen behavior in soils, and for potential water and food contamination associated with biofertilization, useful for risk management and mitigation in swine digestate recycling.


Association between family history and prognosis of patients with colorectal cancer: a systematic review and meta-analysis.
A family history of colorectal cancer (CRC) increases the risk of developing CRC, and numerous studies have assessed the influence of family history on survival among CRC patients. However, the prognostic effect of a family history of CRC remains uncertain. The aim of this meta-analysis was to systematically assess the association between family history and CRC prognosis. A comprehensive literature search was performed in the PubMed, Embase, Medline, Web of Science and Scopus databases up to October 2021, based on the Population, Intervention, Comparator, Outcomes and Study designs framework. Two reviewers independently extracted data on baseline characteristics and outcomes from the included studies. The Newcastle-Ottawa Scale was used for quality assessment of each study. Either a fixed- or a random-effects model was used to calculate the pooled hazard ratio (HR). Eighteen studies comprising 80,093 CRC patients were finally included in this meta-analysis. The Newcastle-Ottawa Scale scores of the included studies ranged from 4 to 8, and 12 studies were of high quality. A significant association between family history and improved overall survival was determined in the CRC patients (HR =0.89, 95% CI: 0.81-0.99) with significant heterogeneity (I2=65.7%, P<0.001). This effect was found in male CRC patients (HR 0.70, 95% CI: 0.56-0.88) but not females (HR =0.77, 95% CI: 0.54-1.09). The association between family history and disease-free survival was not significant (HR =0.94, 95% CI: 0.88-1.01) (I2=21.0%, P=0.263). However, a subgroup analysis supported the prognostic value of disease-free survival in patients with stage III CRC (pooled HR =0.78, 95% CI: 0.67-0.92). In conclusion, a positive family history was associated with improved overall survival in CRC patients. It was also a favorable predictor of disease-free survival in patients with stage III CRC. These findings should be interpreted with caution because of limitations related to study quality and differences in the adjusted factors across studies.


Derivation of a water quality guideline for aluminium in marine waters.
Metal risk assessment of industrialized harbors and coastal marine waters requires the application of robust water quality guidelines to determine the likelihood of biological impacts. Currently there is no such guideline available for aluminium in marine waters. A water quality guideline of 24 µg total Al/L has been developed for aluminium in marine waters based on chronic 10% inhibition or effect concentrations (IC10 or EC10) and no-observed-effect concentrations (NOECs) from 11 species (2 literature values and 9 species tested including temperate and tropical species) representing 6 taxonomic groups. The 3 most sensitive species tested were a diatom Ceratoneis closterium (formerly Nitzschia closterium; IC10 = 18 µg Al/L, 72-h growth rate inhibition) < mussel Mytilus edulis plannulatus (EC10 = 250 µg Al/L, 72-h embryo development) < oyster Saccostrea echinata (EC10 = 410 µg Al/L, 48-h embryo development). Toxicity to these species was the result of the dissolved aluminium forms of aluminate (Al(OH4 (-) ) and aluminium hydroxide (Al(OH)3 (0) ) although both dissolved, and particulate aluminium contributed to toxicity in the diatom Minutocellus polymorphus and green alga Dunaliella tertiolecta. In contrast, aluminium toxicity to the green flagellate alga Tetraselmis sp. was the result of particulate aluminium only. Four species, a brown macroalga (Hormosira banksii), sea urchin embryo (Heliocidaris tuberculata), and 2 juvenile fish species (Lates calcarifer and Acanthochromis polyacanthus), were not adversely affected at the highest test concentration used.


Physical Characteristics of Injection Site Pain After COVID-19 mRNA BNT162b2 Vaccination.
BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients' pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours post-vaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis.


Evidence for an apparent sensory speech disorder in Parkinson's disease.
Twenty eight patients with Parkinson's disease (average age 63 years, average duration of disease 8 years) and 28 normal elderly controls (average age 70 years) were tested for their ability to appreciate the prosodic aspects of their own and others' speech and facial expression. Compared with the controls the Parkinsonian subjects performed worse at these tests, though both groups could easily identify neutral statements. The Parkinsonian subjects were unable to produce statements in an angry or questioning form. These seemed to be features of early Parkinson's disease.


[Effect of wintergreen oil on in vitro transdermal permeation of osthole and geniposide].
The aim of this study was to investigate the transdermal penetration enhancement effect of wintergreen oil and its action mechanisms. The in vitro transdermal tests were carried out to study the transdermal penetration enhancement effect of wintergreen oil by using osthole and geniposide as the lipophilic and hydriphilic model drugs. Fourier-transform infrared spectroscopy was used to investigate the effect of wintergreen oil on the molecular structure of rat stratum corneum, and the scanning electron microscope was employed to observe the change of rat skin surface after treatment by the oil. The wintergreen oil at proper concentrations could effectively promote the transdermal permeation of osthole and geniposide, and exhibited better penetration-enhancing activity for the lipophilic osthole, close to the commonly used classical penetration enhancer azone. The infrared spectroscopy study and scanning electron microscope showed that wintergreen oil mainly acted on the stratum corneum lipids, reduced dense stratum corneum, and reduced the skin barrier function. Thus, the wintergreen oil could effectively facilitate the transdermal absorption of the lipophilic and hydrophilic drugs, resulting from the lowed skin barrier function.


Accurate local blood flow measurements with dynamic PET: fast determination of input function delay and dispersion by multilinear minimization.
Accurate determination of local blood flow in tissue using the Kety-Schmidt one-compartment model for freely diffusible tracers requires knowledge of the true arterial input function in tissue. Because measured input functions are usually delayed and dispersed with respect to true influx, a correction of the experimental input function is necessary. We describe a technique that uses a fast multilinear least-squares minimization procedure to determine simultaneously the dispersion, the blood flow and the partition coefficient as a function of delay. In this approach, a few multilinear fits are sufficient to determine the complete set of parameters necessary to describe the data. Because of the high speed of the procedure, dispersion effects may be taken into account on a pixel-by-pixel basis in calculating parametric images of blood flow and partition coefficient. The described procedure has been used at our institute for about 1 yr in more than 160 investigations and has proven well suited for routine use in a clinical environment.


Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione.
Fibroblasts are key structural cells that can be damaged by cigarette smoke. Cigarette smoke contains many components capable of eliciting oxidative stress, which may induce heme oxygenase (HO)-1, a cytoprotective enzyme. There are no data on HO-1 expression in primary human lung fibroblasts after cigarette smoke extract (CSE) exposure. We hypothesized that human lung fibroblasts exposed to cigarette smoke would increase HO-1 though changes in intracellular glutathione (GSH). Primary human lung fibroblasts were exposed to CSE, and changes in HO-1 expression and GSH levels were assessed. CSE induced a time- and dose-dependent increase in expression of HO-1, but not HO-2 or biliverdin reductase, in two different primary human lung fibroblast strains, a novel finding. This induction of HO-1 paralleled a decrease in intracellular GSH, and a sustained reduction in GSH resulted in a dramatic increase in HO-1. Treatment with the antioxidants N-acetyl-l-cysteine or GSH reduced the expression of HO-1 induced by CSE. We also examined the signal transduction mechanism responsible for HO-1 induction. Nuclear factor erythroid-derived 2, like 2 (Nrf2) was not involved in HO-1 induction by CSE. Activator protein-1 (AP-1) is a redox-sensitive transcription factor shown in other systems to regulate HO-1 expression. CSE exposure resulted in nuclear accumulation of c-Fos and c-Jun, two key AP-1 components. Reduction of c-Fos and c-Jun nuclear translocation by SP-600125 attenuated the CSE-induced expression of HO-1. These data support the concept that changes in the cellular redox status brought on by cigarette smoke induce HO-1 in fibroblasts. This increase in HO-1 may help protect against cigarette smoke-induced inflammation and/or cell death.


Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation.
Dendritic cells (DCs) are crucial in determining the outcome of antigen encounter and integrating signals derived from the antigen, its inflammatory context, and the host environment into a signal that can be read by naive T cells in the lymphoid tissues and by effector T cells in peripheral tissues. Airway DC subsets, however, induce different types of immune responses, with plasmacytoid DCs promoting tolerance and myeloid DCs inducing immunity. We also propose that airway DCs are not only crucial for sensitization to inhaled antigens, leading to allergy, but also play a crucial role in established inflammation and therefore represent a therapeutic target to prevent the development of airway diseases.


Multivariate multilevel models for repeated measures in the study of smoking effects on the association between plaque and gingival bleeding.
Multivariate multilevel modeling was applied to analyze repeated measures data on the influence of heavy smoking on the association between the amount of supragingival plaque and gingival bleeding on probing (BOP) in a steady-state plaque environment. Data acquired in 65 systemically healthy young adults with mild plaque-induced gingivitis were analyzed. 33 heavy smokers consumed at least 20 cigarettes per day while 32 were non-smokers. Periodontal examinations at the outset consisted of periodontal probing depth, clinical attachment level, BOP, plaque index, and presence of calculus at 6 sites of every tooth present. They were repeated 3 times every 8 weeks. A multivariate 4-level variance component model revealed that the odds of BOP was twice as high in smokers. In addition, females had a lower likelihood for BOP but, with increasing bleeding scores during the course of the study, this effect attenuated. Low biserial correlations for BOP at the site level of between 0.11 and 0.2 were found. At the tooth level, correlations were moderate (0.2-0.5), and highest at the subject level (0.8-0.9). Variations at subject and tooth levels were very large at the outset but notably attenuated in the course of the study. Plaque consistently influenced the tendency for BOP with an odds ratio of about 1.7-1.8 for each increase in score in both smokers and non-smokers. The present study did not reveal evidence for attenuation of the plaque/gingival bleeding relationship in heavy smokers.


Microsatellite instability, apoptosis, and loss of p53 function in drug-resistant tumor cells.
We have examined microsatellite instability and loss of p53 function in human tumor cell line models of acquired anticancer drug resistance. We observe acquisition of an RER(+) phenotype in cell lines selected for resistance to cisplatin or doxorubicin. The majority of independent cisplatin-resistant sublines are RER(+), whereas the parental line shows no evidence of microsatellite instability. Microsatellite mutations in random, nonselected subclones of a cislatin-resistant line are observed in the absence of further drug exposure, suggesting that the RER(+) phenotype is a stable phenotype rather than being transiently induced by DNA damage. Furthermore, a cisplatin-resistant derivative shows reduction in a G:T mismatch recognition activity compared to the parental line. Independent lines selected by multiple exposure to cisplatin show resistance factors of up to a 5-fold by clonogenic assay and have reduced cisplatin-induced apoptosis. The resistant lines that are RER(+) show evidence of loss of p53-dependent functions, as measured by a loss of radiation-induced G(1) arrest and reduced CIP1 mRNA. Induced loss of p53 function by transfection of mutant TP53 does not cause a detectable RER(+) phenotype. We speculate that tolerance of DNA damage and expansion of cells with an RER(+) phenotype may select for reduced ability to engage apoptosis and loss of p53 function.


Neuroanatomy from Mesoscopic to Nanoscopic Scales: An Improved Method for the Observation of Semithin Sections by High-Resolution Scanning Electron Microscopy.
Semithin sections are commonly used to examine large areas of tissue with an optical microscope, in order to locate and trim the regions that will later be studied with the electron microscope. Ideally, the observation of semithin sections would be from mesoscopic to nanoscopic scales directly, instead of using light microscopy and then electron microscopy (EM). Here we propose a method that makes it possible to obtain high-resolution scanning EM images of large areas of the brain in the millimeter to nanometer range. Since our method is compatible with light microscopy, it is also feasible to generate hybrid light and electron microscopic maps. Additionally, the same tissue blocks that have been used to obtain semithin sections can later be used, if necessary, for transmission EM, or for focused ion beam milling and scanning electron microscopy (FIB-SEM).


Preliminary studies of photoinactivation of human immunodeficiency virus in blood.
The transmission of human immunodeficiency virus (HIV) by blood or blood components is a major concern in blood banking. A photodynamic flow cell system was designed to inactivate cell-free HIV mixed with blood from a healthy donor. Blood containing 4 x 10(3) infectious units of HIV was treated with 10 and 20 micrograms per mL of commercially available dihematoporphyrin ether (DHE) per mL. Aliquots of this mixture were then held in the dark or irradiated in a flow cell illuminated at a light energy density of 5 J per cm2 provided by a xenon light source equipped with a 630 +/- 5 nm band-pass interference filter; the aliquots were subsequently placed in A.301 cells. All infected cultures were assessed for reverse transcriptase (RT) activity for 17 days. RT activity for either concentration of dye was significantly reduced in irradiated samples as compared to that in samples held in the dark. Blood samples from volunteers also were assessed for the effects of the inactivation process on red cells at concentrations of DHE up to 200 micrograms per mL. No effects were observed on red cell 2,3 DPG or ATP, whole blood potassium concentrations, red cell osmotic fragility, or blood cell antigens.


Use of a simple forearm tourniquet as an adjunct to an intravenous regional block.
Intravenous regional anesthesia (IVRA) is a well-recognized technique for producing anesthesia during surgical procedures of the extremities. It has been suggested that the application of a tourniquet to the forearm may improve the quality of the block. The purpose of this investigation was to determine whether the application of a forearm tourniquet would accelerate onset time and improve the density and quality of an intravenous regional block. Twenty volunteer subjects were enrolled and randomly assigned in this crossover investigation. Control subjects received a standard IVRA technique; experimental subjects received IVRA technique with the application of a simple forearm tourniquet. Pain was elicited by means of an electrical stimulus, and assessments were performed using a 100-mm Visual Analogue Scale (VAS). Paired t tests were used to examine differences between groups on the variables studied. It was noted that the arm with the tourniquet had a shorter time for the onset of anesthesia (P = .0008) and had lower 10-minute VAS tolerance (P = .0469). This investigation suggests that the application of a simple forearm tourniquet as an adjunct to IVRA provides a more rapid onset of anesthesia than when no tourniquet is applied and may improve the density and quality of the block.


Pulmonary function, nutrition, and self-concept in cystic fibrosis summer campers.
Children with cystic fibrosis (CF) often attend special summer camps. We postulated that beyond the simple fun of camp, attendance at camp might improve the clinical status and self-image of the campers. We therefore studied lung function, nutrition, and self-image in 45 children between the ages 6 and 12 years after a two-week CF summer camp. Although there was a 10 percent fall in respiratory rate during camp, spirometry did not change significantly. There were, however, significant gains in weight, skin fold thickness, and midarm circumference after two weeks at camp, and these increases were positively correlated with the number of pancreatic enzymes taken daily by the child. The Primary Self-Concept Inventory test was completed by each camper on the first and last days of camp. Although there was a trend toward increasing self-concept during camp, this did not reach statistical significance. Two weeks' attendance at summer camp appears to be associated with improved nutrition in children with CF. This may be due to increased emphasis on weight gain and appropriate use of pancreatic enzymes or to other factors, like avoidance of tobacco smoke exposure, that are unique to the summer camp setting.


Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine analogues.
A convenient, high-yield synthesis of 7-tert-butoxycarbonyl-7-azabicyclo[2.2.1]hept-2-ene (5), which involved the addition of tributyltin hydride to 7-tert-butoxycarbonyl-2-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-ene (4) followed by elimination of the tributyltin and p-tolylsulfonyl groups using tetrabutylammonium fluoride was developed. The addition of 2-amino-5-iodopyridine to 5 under reductive Heck conditions provided 7-tert-butoxycarbonyl-2-exo-(2'-amino-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (6). Compound 6 was the key intermediate used to prepare epibatidine analogues where the 2'-chloro group on the pyridine ring was replaced with a fluorine (1b), bromine (1c), iodine (1d), hydroxy (1e), amino (1f), dimethylamino (1g), trifluoromethanesulfonate (1h), and hydrogen (1i) group. (+)- and (-)-Epibatidine and compounds 1b-d and 1i all possess similar binding affinities at the alpha(4)beta(2) nAChR receptors labeled by [(3)H]epibatidine. Compound 1f has affinity similar to nicotine, whereas compounds 1e, 1g, and 1h have much lower affinity. The binding affinity appears to be dependent upon the electronic nature of the substituent. However, other factors are also involved. None of the compounds possesses appreciable affinity for the alpha(7) nAChR labeled by [(125)I]iodo-MLA. With the exception of 1f and 1g, all the epibatidine analogues are full agonists (tail flick test) in producing antinociception after intrathecal injection in mice.


An investigation into the roles of photosynthesis and respiration in h efflux from aerated suspensions of asparagus mesophyll cells.
Aerated and stirred suspensions of mechanically isolated Asparagus sprengeri Regel mesophyll cells were used to investigate the roles of respiration and photosynthesis in net H(+) efflux. Rates varied between 0.12 and 1.99 nanomoles H(+) per 10(6) cells per minute or 3 and 40 nanomoles H(+) per milligram chlorophyll per minute. The mean rate of H(+) efflux was 10% greater in the dark. 3-(3,4-Dichlorophenyl)-l,l-dimethylurea, an inhibitor of noncyclic photophosphorylation, did not inhibit H(+) efflux from illuminated cells. Bubbling with N(2) or addition of oligomycin, an inhibitor of mitochondrial ATP production, resulted in rapid and virtually complete inhibition of H(+) efflux in light or dark. In the absence of aeration, H(+) efflux came to a halt but resumed with aeration or illumination. When aeration was switched to CO(2)-free air, rates of H(+) efflux were reduced 43% in the dark and 57% in the light. Oligomycin eliminated dark CO(2) fixation but not photosynthetic CO(2) fixation. It is suggested that H(+) efflux is dependent on respiration and dark CO(2) fixation, but independent of photosynthesis.


Cor triatriatum dexter in two dogs.
Cor triatriatum dexter is a congenital heart defect in which the embryologic right sinus venosus valve persists as a septum within the right atrium. Cor triatriatum dexter was diagnosed in 2 dogs on the basis of clinical signs, two-dimensional echocardiography, and cardiac catheterization. In 1 of the dogs, the condition was successfully treated by surgical resection of the intra-atrial septum. In the second dog, the defect was associated with an incomplete persistent cranial left vena cava and Ebstein's anomaly; surgery was declined.


[Physiologic type reconstruction in upper gastrointestinal caustic strictures].
The authors discuss their experience in the surgical treatment of caustic stenosis in the upper gastrointestinal tract. They present operative solutions using isoperistaltic transverse colonic segment in oesophageal stenosis caused by gastric outlet obstruction, or when these two presented together. Further indications for the above were bronchial or tracheo-oesophageal fistulas and oesophageal perforation. Late adaptation of the colonic grafts were measured by radiokinematography and histochemistry. The overall morbidity was 4.9%. Postoperative salivary fistulas closed spontaneously. Late postoperative complications (13.5%) were treated successfully. The multihaustral motility of the graft prevented the reflux, while the altered mucopolysaccharides of the colonic mucosa prevented the ulcer formation. Orv Hetil. 2019; 160(16): 613-618.


Luteolin enhances TNF-related apoptosis-inducing ligand's anticancer activity in a lung cancer xenograft mouse model.
Sensitization of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by luteolin has been suggested by in vitro studies. However, no in vivo experiment has been reported to validate the potentiation effect of luteolin on TRAIL's anticancer activity. In this report, we first confirmed that luteolin potentiates TRAIL-induced cytotoxicity in A549 cells and HeLa cells in association with increased activation of apoptosis. Then we performed an in vivo experiment with a non-small cell lung cancer xenograft mouse model, which showed for the first time that the in vivo anticancer activity of TRAIL was greatly enhanced by luteolin. Compared with that in untreated control or treatment with TRAIL or luteolin alone, inhibition of tumor growth and apoptotic cell death in xenograft tumors were significantly increased in animals receiving combination treatment with TRAIL and luteolin. Data from this study thus provide strong in vivo evidence supporting that luteolin is a potential sensitizer for TRAIL in anticancer therapy.


Microarray-based detection and typing of the Rhizobium nodulation gene nodC: potential of DNA arrays to diagnose biological functions of interest.
Environmental screening of bacteria for the presence of genes of interest is a challenging problem, due to the high variability of the nucleotide sequence of a given gene between species. Here, we tackle this general issue using a particularly well-suited model system that consists of the nodulation gene nodC, which is shared by phylogenetically distant rhizobia. 41mer and 50mer oligonucleotides featuring the nucleotide diversity of two highly conserved regions of the NodC protein were spotted on glass slides and cross hybridized with the radioactive-labeled target genomic DNA under low-stringency conditions. Statistical analysis of the hybridization patterns allowed the detection of known, as well as new, nodC sequences and classified the rhizobial strains accordingly. The microarray was successfully used to type the nodC gene directly from legume nodules, thus eliminating the need of cultivation of the endosymbiont. This approach could be extended to a panel of diagnostic genes and constitute a powerful tool for studying the distribution of genes of interest in the environment, as well as for bacteria identification.


Diagnosis Test Meta-Analysis for Apolipoprotein E in Alzheimer's Disease.
To evaluate the diagnostic value of apolipoprotein E (APOE) gene in Alzheimer's disease (AD). Databases including PubMed, EMBASE, Google Scholar, Wanfang Med online, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) were searched for literatures in English or Chinese. No limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve (SROC) and Fagan's Nomogram were drawn, and metaregression and subgroup analysis were used to explore the source of heterogeneity. A total of 13 studies, including 2662 cases and 8843 controls, were analyzed. The combined sensitivity (SEN) was 0.62 (95% CI (0.58-0.66)), specificity (SPE) was 0.84 (95% CI (0.81-0.86)), the positive likelihood ratio was 3.8 (95% CI (3.3-4.3)), and the negative likelihood ratio was 0.45 (95% CI (0.41-0.49)). The area under the ROC curve was 0.80, and the diagnostic ratio (DOR) was 8. Neither publication bias was detected in Deeks' funnel plot, nor threshold effect was shown in the SROC. Metaregression analysis showed that the diagnostic methods, experimental design, and sample size contributed to the heterogeneity in SEN, while the diagnostic methods, experimental design, blind evaluation on test results, and sample size contributed to the heterogeneity in SPE. When the pretest probability was set as 50%, the posterior probability in Fagan's Nomogram was 79%, the positive likelihood ratio (LRP) was 5, and the negative likelihood ratio (LRN) was 0.42. AD could neither be confirmed nor excluded by the APOE genotype test. The sensitivity and specificity of the APOE gene test were relatively low in the diagnosis of AD. The diagnostic value of APOE ε4 gene in AD was moderate; it might play an important role in the prevention of AD.


Explicit and implicit self-evaluations in social anxiety disorder.
Cognitive models of social anxiety disorder (SAD) emphasize the role of explicit and implicit self-evaluations (SEs) in the etiology and maintenance of this condition. Whereas individuals with SAD consistently report lower explicit SEs as compared with nonanxious individuals, findings concerning implicit SEs are mixed. To gain a more nuanced understanding of the nature of SEs in SAD, we examined explicit and implicit SEs in two significant interpersonal domains: social rank and affiliation. Consistent with cognitive theorizing, we predicted that, compared to nonclinical controls (NCCs), individuals with SAD would exhibit lower explicit and implicit SEs in both domains. Guided by evolutionary theories we also predicted that the differences in SEs between the groups would be greater in the social rank, as compared to the affiliation, domain. Individuals diagnosed with SAD (n = 38) and NCCs) n = 40) performed two variants of the Self Implicit Association Test: one concerning social rank, and the other concerning affiliation. They also rated themselves on social-rank and affiliation traits. We found that, as compared to NCCs, individuals with SAD exhibited lower social-rank and affiliation SEs. Moreover, differences between the groups in social-rank SEs were greater than in affiliation SEs. Importantly, this pattern was evident in implicit SEs, as much as in explicit SEs. Our findings dovetail with evolutionary accounts highlighting the centrality of the social-rank system in SAD, and refine central tenets of cognitive theories of SAD. A multidomain, multimethod approach to the understanding of the self may broaden our conceptualization of SAD and related disorders. (PsycINFO Database Record


Combined supravital staining and hypoosmotic swelling test.
The parameter of sperm viability in hypoosmotic solution (VHOS) provides information concerning the membrane integrity of the sperm head. The objective of this study was to determine the association between the VHOS parameter and the sperm penetration assay. The VHOS parameter correctly predicted 70.0-71.4% of the failed sperm penetration assay samples in the short duration preincubation groups. A combination of both the VHOS parameter and the hypoosomotic sperm swelling (HOS) test significantly reduced the number of false negative results. In general, a sperm sample with an abnormal VHOS result and an abnormal HOS test result would be associated with a negative sperm penetration assay. Washing by centrifugation appeared to weaken the sperm head membranes while the swim-up method selected for sperm with strong head and tail membranes. After the various processing methods unique changes in the integrity of the sperm head and tail membranes for each sperm sample may help to identify the optimal method of preparation for individual patients undergoing the newer assisted reproductive technologies such as sperm microinjection.


Assessment of the core competencies of veterinarians: implications for policy decisions in India.
he objectives of this study were two-fold - to assess the technical competencies of veterinarians and their application, and to investigate veterinarians' activities and appropriate ways for them to acquire and enhance competencies. The studywas undertaken in three South Indian states: Andhra Pradesh, Karnataka and Telangana. The survey data, collected in 2015-2016 from nine districts in the three states, came from in-depth questionnaires completed by 270 veterinary assistant surgeons (VASs). The key survey questions were related to: specific technical competencies and their application, appropriate ways to acquirethem, additional competencies needed and recommended activities to enhancethem. Each respondent's rating was obtained on a) how important are thesecompetencies and b) what is their current level of knowledge and/or skills toperform them? The findings revealed that the current level of knowledge and/orskills was inadequate in production, para-clinical and clinical areas in the day-todaywork of VASs. The findings suggested that pre-service, in-service and basic induction training, and attending national and international seminars, workshopsand Webinars, are appropriate ways to acquire competencies. Additional skillsperceived as necessary by respondents include: time and stress managementskills, motivational techniques, digital communication technologies, and writing and presentation skills. Specific policy interventions suggested and discussed include: adequate hands-on pre-service instruction in veterinary colleges and assessment of competencies before certification, introducing a veterinary licensing examination, reinforcing competencies through induction training,in-service or continuing veterinary education programmes, and improving theinstitutional mechanisms to assess competencies at regular intervals.


Stereospecific peptide folds. A rationally designed molecular bracelet.
A canonical planar beta-hairpin peptide, stereochemically reengineered into a semicircular bracelet type motif by L-to-D stereochemical inversion in two pairs of its cross-strand neighbor residues, displays protein like ordering including two-state behavior in H2O, which is unusual for a small peptide of this size.


The impact of pre-analytical processing on staining quality for H&E, dual hapten, dual color in situ hybridization and fluorescent in situ hybridization assays.
With the advent of personalized medicine, anatomic pathology-based molecular assays, including in situ hybridization (ISH) and mRNA detection tests, are performed routinely in many laboratories and have increased in their clinical importance and complexity. These assays require appropriately fixed tissue samples that preserve both nucleic acid targets and histomorphology to ensure reliable test results for determining patient treatment options. However, all aspects of tissue processing, including time until tissue fixation, type of fixative, duration of fixation, post-fixation treatments, and sectioning of the sample, impact the staining results. ASCO/CAP has issued pre-analytical guidelines to standardize tissue processing for HER2 testing in breast carcinoma specimens: 10% neutral-buffered formalin (NBF) with a fixation time from at least 6 to 48h [1]. Often, this recommendation is not followed to the detriment of staining results [2]. In this paper, we used a human breast carcinoma cell line (MCF7) generated as xenograft tumors as a model system to analyze the effects of different pre-analytical conditions on ISH staining. We performed H&E, FISH and dual colorimetric HER2 ISH assays using specimens fixed across a range of times in six different commonly used fixatives. Additionally, we investigated the effects of varying tissue section thickness, which also impacted the quality of ISH staining. Finally, we evaluated the effects of three different decalcifying solutions on human breast specimens, typically a treatment that occurs post-fixation for evaluating metastases to bone. The results indicate that time and type of fixation treatment, as well as appropriate tissue thickness and post-fixation treatment, all contribute to the quality of ISH staining results. Our data support the ASCO/CAP recommendations for standardized tissue processing (at least 6h in formalin-based fixatives and 4μm section thickness) and indicate that certain fixatives and post-fixative treatments are detrimental to molecular staining results.


Phosphorylation of extracellular domains of T-lymphocyte surface proteins. Constitutive serine and threonine phosphorylation of the T cell antigen receptor ectodomains.
The extracellular accumulation of ATP after activation of T-lymphocytes, as well as the presence of ecto-protein kinases in these cells, led us to propose that T cell surface receptors could be regulated through the reversible phosphorylation of their extracellular domains (ectodomains). Here, in a model system, we used T cell transfectants which express T cell antigen receptor chains lacking intracellular and transmembrane protein domains and 32Pi metabolic labeling of cells to definitively demonstrate phosphorylation of ectodomains of T cell surface proteins. We show that alphabetaTCR ectodomains were phosphorylated intracellularly and constitutively on serine and threonine residues and were then expressed on the T cell surface in phosphorylated form. TCR ectodomains also could be phosphorylated at the cell surface when extracellular [gamma-32P]ATP or [gamma-32P]GTP were used as phosphate donors with the same cells. Consensus phosphorylation sites for serine and threonine protein kinases were found to be strongly evolutionary conserved in both alpha and beta TCR chains constant regions. These results are consistent with the hypothesis, where T cell surface proteins which are phosphorylated intracellularly on their ectodomains, could subsequently be expressed at the cell surface and then be reversibly modified by ectoprotein phosphatase(s) and by ectokinase(s). Such modifications may change T cells cognate interactions by, e.g. affecting TCR-multimolecular complex formation and antigen binding affinity. It is suggested that alphabetaTCR ectodomain phosphorylation could serve as a potential mechanism for regulation of alphabetaTCR-mediated T-lymphocytes response.