Real-time compound imaging ultrasound of hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a difficult disease to treat. Surgery may be curative, but just like cancer surgery, it must be complete to effect a cure. Preoperative imaging of hidradenitis lesions is therefore of interest. The objective was to study the ultrasound characteristics of hidradenitis and compare these to the clinical findings. Real-time compound imaging ultrasound systems were used (Philips HDI 5000 and iU22) to visualize HS lesions in seven patients and regional controls images from eight healthy volunteers. Hidradenitis-related features were identified: various fluid collections, increased dermal thickness (mean+/-SD, 3.3+/-1.0 mm vs. 1.4+/-0.3 mm for controls) and lower echogenicity of the skin. In comparison with clinical examination, we were able to identify both subclinical lesions and subclinical extension of lesions into clinically normal looking paralesional skin. Hair follicles appeared distended. A number of HS features can be identified by ultrasound. These features include both actual lesions and possible predisposing factors such as skin thickness and hair follicle morphology. Ultrasonography can identify the true extent of lesions in HS, which may be of use in the preoperative planning.


STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.
Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.


An Employment Guarantee for the Urban Worker.
Public attention has focused on the problems of urban migrants returning to rural India due to the Covid-19 crisis. It may be months before the majority of returning migrants, including several different kinds of migrants, go back to urban areas and are absorbed in employment. We know that there is considerable movement of labour between rural and urban areas, some of it long-term and some of it short-term or periodic or circular. This is necessary and is not going to change. There is a case for extending the existing rural employment guarantee to urban India. This works through self-selection and can reach groups not always reached by other, equally important, welfare schemes. Given how little we know about the magnitudes and characteristics of migrant workers, it is desirable to proceed with caution. A pilot project may be started in one or more selected cities, without calling it a guarantee. Based on what we learn from this experience, it can then be extended to the whole of urban India. Components on adult education and training/retraining should be included in the project to improve skills, productivity and worker rights.


Adapting the forms of yesterday to the functions of today and the needs of tomorrow: a genealogical case study of clinical teaching units in Canada.
Emergent discourses of social responsibility and accountability have in part fuelled the expansion of distributed medical education (DME). In addition to its potential for redressing physician maldistribution, DME has conferred multiple unexpected educational benefits. In several countries, its recent rise has occurred around the boundaries of traditional medical education practices. Canada has been no exception, with DME proliferating against a backdrop of its longstanding central node, the clinical teaching unit (CTU). The CTU first appeared just over 50 years ago with its position in Canadian health care largely taken-for-granted. Given the increasing prominence of DME, however, it is timely to reconsider what the place of tertiary centre-based practices such as the CTU might be in shifting medical education systems. From a genealogical perspective, it becomes clear that the CTU did not just "happen". Rather, its creation was made possible by multiple interrelated cultural, social, and political changes in Canadian society that, while subtle, are powerfully influential. Making them visible offers a better opportunity to harmonize the benefits of longstanding entities such as the CTU with novel practices such as DME. In so doing, the medical education field may sidestep the pitfalls of investing significant resources that may only produce superficial changes while unwittingly obstructing deeper transformations and improvements. Although this work is refracted through a Canadian prism, reconceptualizing the overall design of medical education systems to take advantage of both tradition and innovation is a persistent challenge across the international spectrum, resistant to tests of time and constraints of context.


Monooxygenase activity of cytochrome c peroxidase.
Recombinant cytochrome c peroxidase (CcP) and a W51A mutant of CcP, in contrast to other classical peroxidases, react with phenylhydrazine to give sigma-bonded phenyl-iron complexes. The conclusion that the heme iron is accessible to substrates is supported by the observation that CcP and W51A CcP oxidize thioanisole to the racemic sulfoxide with quantitative incorporation of oxygen from H2O2. Definitive evidence for an open active site is provided by stereoselective epoxidation by both enzymes of styrene, cis-beta-methylstyrene, and trans-beta-methylstyrene. trans-beta-methylstyrene yields exclusively the trans-epoxide, but styrene yields the epoxide and phenylacetaldehyde, and cis-beta-methylstyrene yields both the cis- and trans-epoxides and 1-phenyl-2-propanone. The sulfoxide, stereoretentive epoxides, and 1-phenyl-2-propanone are formed by ferryl oxygen transfer mechanisms because their oxygen atom derives from H2O2. In contrast, the oxygen in the trans-epoxide from the cis-olefin derives primarily from molecular oxygen and is probably introduced by a protein cooxidation mechanism. cis-[1,2-2H]-1-Phenyl-1-propene is oxidized to [1,1-2H]-1-phenyl-2-propanone without a detectable isotope effect on the epoxide:ketone product ratio. The phenyl-iron complex is not formed and substrate oxidation is not observed when the prosthetic group is replaced by delta-meso-ethylheme. CcP thus has a sufficiently open active site to form a phenyl-iron complex, to oxidize thioanisole to the sulfoxide, and to epoxidize styrene and beta-methylstyrene. The results indicate that a ferryl (Fe(IV) = O)/protein radical pair can be coupled to achieve two-electron oxidations. The unique ability of CcP to catalyze monooxygenation reactions does not conflict with its peroxidase function because cytochrome c is oxidized at a distinct surface site (DePillis, G. D., Sishta, B. P., Mauk, A. G., and Ortiz de Montellano, P. R. (1991) J. Biol. Chem. 266, 19334-19341).


Reference and normalization methods: essential tools for the intercomparison of NMR spectra.
This review aims at providing an analysis of the various available reference methods in nuclear magnetic resonance, based on recent literature. This paper will provide a tool to help users in choosing the appropriate method depending on the NMR experiment, sample and targeted application. For each method, the crucial parameters that should be particularly considered to reach the accuracy objectives of quantitative NMR are described. After defining the main concepts, the principle, the analytical performance and the main recent applications of each method are described, and a critical discussion is finally provided.


Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease.
Exposure to polychlorinated biphenyls (PCBs) has been associated with liver injury in human cohorts and with nonalcoholic steatohepatitis (NASH) in mice fed a high fat diet (HFD). N (6)-methyladenosine (m6A) modification of mRNA regulates transcript fate, but the contribution of m6A modification on the regulation of transcripts in PCB-induced steatosis and fibrosis is unknown. This study tested the hypothesis that PCB and HFD exposure alters the levels of m6A modification in transcripts that play a role in NASH in vivo. Male C57Bl6/J mice were fed a HFD (12 wks) and administered a single oral dose of Aroclor1260, PCB126, or Aroclor1260 + PCB126. Genome-wide identification of m6A peaks was accomplished by m6A mRNA immunoprecipitation sequencing (m6A-RIP) and the mRNA transcriptome identified by RNA-seq. Exposure of HFD-fed mice to Aroclor1260 decreased the number of m6A peaks and m6A-containing genes relative to PCB vehicle control whereas PCB126 or the combination of Aroclor1260 + PCB126 increased m6A modification frequency. ∼41% of genes had one m6A peak and ∼49% had 2-4 m6A peaks. 117 m6A peaks were common in the four experimental groups. The Aroclor1260 + PCB126 exposure group showed the highest number (52) of m6A-peaks. qRT-PCR confirmed enrichment of m6A-containing fragments of the Apob transcript with PCB exposure. A1cf transcript abundance, m6A peak count, and protein abundance was increased with Aroclor1260 + PCB126 co-exposure. Irrespective of the PCB type, all PCB groups exhibited enriched pathways related to lipid/lipoprotein metabolism and inflammation through the m6A modification. Integrated analysis of m6A-RIP-seq and mRNA-seq identified 242 differentially expressed genes (DEGs) with increased or reduced number of m6A peaks. These data show that PCB exposure in HFD-fed mice alters the m6A landscape offering an additional layer of regulation of gene expression affecting a subset of gene responses in NASH.


Placental prostacyclin production in normal and toxemic pregnancies.
Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Because toxemia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation and reduced uteroplacental blood flow, a deficiency in prostacyclin production during pregnancy could contribute to the development of toxemia. Placentally produced prostacyclin could have both local effects on the uteroplacental vasculature and systemic effects because prostacyclin, unlike the other prostaglandins, is not extensively metabolized by the lungs. Fresh human term placentas were obtained immediately after delivery from 12 normal and 12 toxemic (blood pressure greater than or equal to 140/90 mm Hg, urinary protein greater than 0.3 gm/24 hours) pregnancies. Tissues (300 mg) were incubated in a sterile manner in 5 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto-prostaglandin F1 alpha. Prostacyclin production was significantly decreased in toxemic placental tissue compared with normal placental tissue (2.72 +/- 0.49 versus 7.22 +/- 0.44 pg/mg/hr, mean +/- SE, p less than 0.01). In both normal and toxemic placentas, prostacyclin production was inhibited by indomethacin (5 or 50 mumol/L) and not affected (p greater than 0.10) by arachidonic acid (5 or 100 mumol/L). Lowering the oxygen concentration from 95% to 20% significantly (p less than 0.01) decreased prostacyclin production in normal but not toxemic placentas. Prostacyclin production rates in the amnion and chorion were not affected (p greater than 0.10) by toxemia. The amniotic and chorionic prostacyclin production rates were not different from each other (p greater than 0.10) and were only one seventh of the normal placental production rate. These data indicate that placental prostacyclin production is decreased in toxemia; therefore, this vasoactive prostaglandin may be involved in the causation and the associated hypertension and coagulation abnormalities of this disorder.


Crystallographic data for complexes of the Cro repressor with DNA.
Complexes of the bacteriophage lambda Cro repressor with two DNA duplexes have been crystallized. The DNA sequences are equimolar mixtures of ApTpCpApCpC and its complementary strand and ApCpCpGpCpApApGpG and its complementary strand, which are both parts of the lambda OR3 operator. The space group of both co-crystals is C2221 with cell dimensions a = 81.1 A, b = 89.2 A, and c = 80.0 A. Analysis of dissolved crystals shows that they respectively contain approximately two hexamers per Cro dimer and one nonamer per dimer. The co-crystals diffract to about 3 A resolution and appear suitable for structural studies.


Controllability of Structural Brain Networks and the Waxing and Waning of Negative Affect in Daily Life.
The waxing and waning of negative affect in daily life is normative, reflecting an adaptive capacity to respond flexibly to changing circumstances. However, understanding of the brain structure correlates of affective variability in naturalistic settings has been limited. Using network control theory, we examine facets of brain structure that may enable negative affect variability in daily life. We used diffusion-weighted imaging data from 95 young adults (age [in years]: mean = 20.19, SD = 1.80; 56 women) to construct structural connectivity networks that map white matter fiber connections between 200 cortical and 14 subcortical regions. We applied network control theory to these structural networks to estimate the degree to which each brain region's pattern of structural connectivity facilitates the spread of activity to other brain systems. We examined how the average controllability of functional brain systems relates to negative affect variability, computed by taking the standard deviation of negative affect self-reports collected via smartphone-based experience sampling twice per day over 28 days as participants went about their daily lives. We found that high average controllability of the cingulo-insular system is associated with increased negative affect variability. We also found that greater negative affect variability is related to the presence of more depressive symptoms, yet average controllability of the cingulo-insular system was not associated with depressive symptoms. Our results highlight the role that brain structure plays in affective dynamics as observed in the context of daily life, suggesting that average controllability of the cingulo-insular system promotes normative negative affect variability.


Intraparenchymal migration of an intrathecal catheter three years after implantation.
Intrathecal drug administration using implanted catheter and pump systems has been used in routine clinical practice for more than 20 years to treat chronic refractory pain or spasticity. Complications associated with the use of these systems include drug related adverse events as well as technical problems, most of which are related either to the catheter or the procedure. Although traumatic neural damage is exceedingly rare it is usually associated with significant neurological impairment. We present a case of asymptomatic intraspinal migration of an intrathecal catheter three years after an uneventful implantation. To the best of our knowledge, this complication has never been reported before.


Role of epoxide hydrolase, NAD(P)H:quinone oxidoreductase, cytochrome P450 2E1 or alcohol dehydrogenase genotypes in susceptibility to colorectal cancer.
Colorectal cancer (CRC) is one of the most common forms of cancer in Western countries. CRC has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. Therefore, we determined whether polymorphisms in the genes coding for microsomal epoxide hydrolase (EPHX1), NAD(P)H:quinone oxidoreductase (NQO1), cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase (ADH3) predispose to the development of CRC. DNA samples were obtained from 371 patients with sporadic CRC and 415 healthy controls. Patients and controls were all of Caucasian origin. All genetic polymorphisms were determined by polymerase chain reaction, eventually followed by restriction-fragment-length-polymorphism analyses, except for the EPHX1 codon 113 polymorphism, which was genotyped by an allele-specific discrimination assay. Calculation of crude Odds Ratios (ORs) revealed an increased risk for CRC associated with variant NQO1 (OR 1.5, 95% CI 1.1-2.0) and CYP2E1 intron 6 genotypes (OR 2.2, 95% CI 1.3-3.8). However, after adjustment for age and gender, logistic regression analyses only showed a statistically significant risk for CRC associated with variant NQO1 genotypes (OR 1.6, 95% CI 1.03-2.4). No associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, these data suggest that the presence of variant NQO1 genotypes, with expected reduced enzyme activities might enhance susceptibility to CRC.


Ethics in perioperative practice--principles and applications.
Though often difficult, ethical decision making is necessary when caring for surgical patients. Perioperative nurses have to recognize ethical dilemmas and be prepared to take action based on the ethical code outlined in the American Nurses Association's (ANA's) Code of Ethics for Nurses with Interpretive Statements. In this first of a nine-part series that will help perioperative nurses relate the ANA code to their own area of practice, the author looks at the first statement, which emphasizes respect for people.


Methacholine challenge in pre-school children--which outcome measure?
The aim of our study was to evaluate the utility of interrupter resistance (R(int)), transcutaneous oximetry and auscultation as outcome measures for a recently suggested tripling-dose methacholine (Mch) challenge in pre-school children. We studied 57 children aged 3-6 years. R(int) was measured at baseline and after each Mch dose. Oxygen saturation (SaO(2)) and transcutaneous oxygen pressure (tcpO(2)) were monitored during the challenge. Mch concentrations of 0.22, 0.66, 2.0, 6.0 and 18.0 mg/ml were nebulised during tidal breathing. The challenge was terminated if there was wheeze, SaO(2) below 91% or persistent cough; this final Mch dose was considered as PCW. Nine healthy children, 17 with cough and 25 with wheeze performed the study up to the point of PCW or all five Mch inhalations. If a change of 20% of predicted R(int) or termination by wheeze, desaturation or cough is taken as a completed test, then 39 out of 51 children (78%) had adequate R(int) measurements on each occasions from start to completion. The success rate for tcpO(2) measurements was similar: 38 out of 51 (76%) had complete tcpO(2) data until a 15% fall of tcpO(2) or clinical endpoint was reached. Using the above-mentioned cut-off levels significant change in R(int) or tcpO(2) preceded PCW in most of the cases. Both R(int) and tcpO(2) measurements may allow detection of bronchial hyper-responsiveness at lower Mch doses and also provide a less subjective measure, but will not be feasible in all children.


Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital.
To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.


Near-peer driven dissection selective: A primer to the medical school anatomy course.
In the anatomy laboratory, skill remains a critical component to unlocking the true value of learning from cadaveric dissection. However, there is little if any room for provision of instruction in proper dissection technique. We describe how near-peer instructors designed a supplemental learning activity to enhance the dissection experience for first-year medical students. This study aimed to evaluate the efficacy of this curriculum in improving participants' understanding of dissection technique and its impact on perceived challenges associated with the anatomy course. Curriculum was designed under faculty guidance and included didactic sessions, low-fidelity models, dissection, student presentations, and clinical correlations. Participants' (n = 13) knowledge of basic dissection techniques and concepts were assessed before the selective, and both participants' and nonparticipants' (n = 39) knowledge was assessed at the end of week one and week seven of the anatomy course. Scores were compared using repeated measures ANOVA followed by post hoc t-tests. Thirteen deidentified reflective essays were reviewed by four independent reviewers for themes that aligned with learning objectives. Participants in the selective course scored higher on assessment of dissection techniques and concepts one week after the selective compared to both nonparticipants and their own baseline scores before the selective. Analysis of student reflections resulted in four themes: confidence with dissection skill, sharing resources and transfer of knowledge, learning environment, and psychological impact of perceived challenges of the anatomy course. Near-peer driven supplemental exercises are effective in facilitating dissection skills. This dissection primer increases student confidence and alleviates apprehension associated with anatomy courses.


Determinants and regulating processes in bronchial hyperreactivity.
Bronchial hyperresponsiveness (BHR) can be considered as a feature of asthma, although only a loose relationship is present with symptoms and severity of the disease. Epidemiology of BHR may inform about determining factors in BHR and its role as a risk factor. BHR is found already at a young age, mostly diminishes with age, and increases in many asthmatic patients after midlife. Genetic determinants are suggested by familial segregation and twin studies. Allergy, respiratory infections, and cigarette smoking are found to induce increase in BHR and to modify its degree at the long run. The mechanisms in BHR are being unraveled gradually. A chronic inflammation with an important role for eosinophils, mast cells, and others, is thought to modify bronchial mechanisms, such as smooth muscle, epithelium, and autonomic systems. Growing evidence supports that T lymphocytes are implicated and may determine many of the inflammatory cells, such as eosinophils, neutrophils, and mast cells.


Effect of roxithromycin on mucosal damage, oxidative stress and pro-inflammatory markers in experimental model of colitis.
Roxithromycin, a macrolide antibiotic, exhibits anti-inflammatory property. The present study was designed to evaluate its protective effect in a rat model of colitis. The anti-inflammatory property of roxithromycin was first validated in rat paw edema model at 5 and 20 mg/kg doses where it produced 19 and 51% inhibition of paw swelling induced by carrageenan. The efficacy of roxithromycin was evaluated at these doses in a rat model where colitis was induced by intra-colonic instillation of acetic acid. Rats were divided into six groups viz. normal control, experimental control and drug-treated groups: roxithromycin 5 and 20 mg/kg, diclofenac 10 mg/kg and mesalazine 300 mg/kg. All drugs were given orally 1 h before induction of colitis. The macro and microscopic changes, mean ulcer score, mucus content and markers of oxidative stress and inflammation were evaluated in all the groups after 24 h. Pretreatment with roxithromycin markedly decreased hyperemia, ulceration, edema and restored histological architecture. The protection afforded by roxithromycin was substantiated by dose-dependent increase in mucus content, normalization of markers of oxidative stress (GSH and TBARS) and levels of TNF-α, PGE2 and nitrite along with marked decrease in expression of NFκB (p65), IL-1β and COX-2. The protective effect of roxithromycin was found to be comparable to mesalazine while diclofenac was found ineffective. Our study demonstrates that roxithromycin ameliorates experimental colitis by maintaining redox homeostasis, preserving mucosal integrity and downregulating NFκB-mediated pro-inflammatory signaling and suggests that it has a therapeutic potential in inflammatory conditions of the colon.


Effect of various surfactants (cationic, anionic and non-ionic) on the growth of Aspergillus parasiticus (NRRL 2999) in relation to aflatoxin production.
The effect of surfactants (two cationic, one anionic and three non-ionic) at 0.001, 0.01, 0.1 and 1.0 % concentrations on aflatoxin production, ergosterol content and sugar consumption by Aspergillus parasiticus (NRRL 2999) in YES liquid culture medium is reported. At 0.01% concentration, the cationic surfactants, cetyl dimethyl ammonium bromide (CDAB) and dodecyl trimethyl ammonium bromide (DTAB), and the anionic surfactant, sodium dodecyl sulfate (SDS), completely inhibited spore germination, while DTAB also inhibited the production of ergosterol and toxin (p < 0.05). At a concentration of 0.001%, CDAB was found to enhance toxin production, while SDS was found to inhibit it when compared with other surfactants. Non-ionic surfactants, polyoxyethylene sorbitan monolaurate (Tween-20), polyoxyethylene lauryl ether (Brij-35) and ethoxylated p-tert-octylphenol (Triton X-100) delayed the spore germination up to day 5 at all concentrations and inhibited toxin and ergosterol production at 0.001% concentration. The affect was found to be dose-dependent from 0.001% to 1%, for Triton X-100 only. Positive correlation between ergosterol content and toxin production in the presence of different surfactants at various time periods (3, 5, 7, 9 and 12 days) was found. Tween-20 was most effective in inhibiting toxin production on day 7, when aflatoxin production was found to be maximal in control group. Sugar consumption was directly proportional to the ergosterol content, showing a significant correlation with aflatoxin production.


The spatial attributes of stimulus frequency in the median sagittal plane and their role in sound localization.
Stimulus cues used to locate sounds in the median sagittal plane were investigated. Listeners first were required to report the location of noise bands 1.0 kHz wide whose center frequencies ranged from 4.0 through 14.0 kHz. It was found that the apparent locations of the stimuli depended on their frequency compositions, not their places of origin. As the center frequency was increased from 4.0 to about 12.0 kHz, the apparent location of the sound moved from in front of the subject to the rear. Then, at center frequencies of around 13.0 kHz, the sounds again appeared to come from the front. The authors infer that different frequency regions within the sound's spectrum possess specific spatial referents along the median sagittal plane. When the bandwidth was increased to 4.0 kHz, listeners could locate the stimuli with reasonable proficiency only for the sectors of the median sagittal plane that were represented by the spatial referents inherent in the frequency composition of the stimulus. Finally, a stimulus comprising all audible frequencies above 4.0 kHz could be located proficiently, and it is concluded that this sound, unlike the others, contained all spatial referents for the median sagittal plane, hence the superior performance on the localization task.


Two neuroactive steroids in midpregnancy as measured in maternal and fetal sera and in amniotic fluid.
Allopregnanolone and pregnenolone sulfate, which are neuroactive steroids that differentially modulate the sensitivity of GABA(A) and NMDA receptors, were measured simultaneously in maternal and fetal sera and in amniotic fluid for the first time during the second trimester of gravidity. The study included 33 pregnant women, who underwent cordocentesis due to suspicion of fetal abnormality or alloimmunization. Allopregnanolone concentrations in maternal and fetal sera were similar and close to the previously found levels in healthy controls at 20 weeks of gestation The levels of pregnenolone sulfate in maternal serum were 2-3 times higher and in fetal serum, as much as 10-25 times higher than those found by others in the serum of healthy, non-pregnant women. A positive correlation between maternal and fetal allopregnanolone indicate similar 5alpha-reductase activities or the efficient transport of allopregnanolone between the two subjects. No correlation of pregnenolone sulfate levels between mother and fetus was found. This finding suggests the autonomous production of pregnenolone sulfate in mother and fetus.


Serum substance P levels are associated with severity and mortality in patients with severe traumatic brain injury.
Substance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. SP is released early following acute injury to the CNS, promoting a neurogenic inflammatory response characterized by an increase in the permeability of the blood-brain barrier and the development of vasogenic edema. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Thus, the main goal of the present study was to determine whether serum SP levels are associated with injury severity and mortality in patients with severe TBI. This multicenter, observational, prospective study was carried out in six Spanish intensive care units and included patients with Glasgow Coma Scale (GCS) scores ≤ 8. Patients with an Injury Severity Score ≥ 10 in non-cranial aspects were excluded. Blood samples were collected on day 1 of TBI to measure serum SP levels. The endpoint was 30-day mortality. We found higher serum SP levels (P = 0.002) in non-surviving patients (n = 27) than in surviving patients (n = 73). The area under the curve for serum SP levels with regard to predicting 30-day mortality was 0.70 (95% confidence interval (CI), 0.60 to 0.79; P < 0.001). Survival analysis showed that patients with serum SP levels >299 pg/ml had higher 30-day mortality than patients with lower levels (hazard ratio = 3.7; 95% CI, 1.75 to 7.94; P < 0.001). Multiple binomial logistic regression analysis showed that serum SP levels >299 pg/ml were associated with 30-day mortality when we controlled for APACHE II score and Marshall computed tomography lesion classification (odds ratio (OR) = 5.97; 95% CI, 1.432 to 24.851; P = 0.01) and for GCS score and age (OR = 5.71; 95% CI, 1.461 to 22.280; P = 0.01). We found a negative association between serum SP levels and GCS score (Spearman's ρ = -0.22; P = 0.03). We report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe TBI. These results open the possibility that SP antagonists may be useful in the treatment of patients with severe TBI.


In vivo effects of myocardial creatine depletion on left ventricular function morphology and lipid metabolism: study in a mouse model.
The failing heart is characterized by disturbed myocardial energy metabolism and creatine depletion. The aims of this study were to evaluate in vivo the effects of creatine (Cr) depletion on 1) left ventricular (LV) function, morphology, and lipid metabolism and 2) to test whether functional, morphologic, and metabolic disturbances induced by Cr depletion are reversible. Male Balb/c mice approximately 20 g were used. Two groups were studied: the mice treated with creatine analogue beta-guanidinopropionic acid (BGP) (n = 30) and controls (n = 30). BGP (1 M) were administered by subcutaneously implanted osmotic minipumps for 4 weeks. The mice were examined in vivo using echocardiography. High-performance liquid chromatography was used for measurements of the myocardial creatine, adenosine nucleotides, and lipids. BGP was discontinued in a subgroup of mice and these animals were followed for an additional 4 weeks, after which echocardiography was performed under resting and stress conditions. Body weight was lower in BGP mice (P < .001) compared with the controls after 4 weeks. The total myocardial Cr pool was approximately 40% lower (P < .001), whereas total nucleotide pool (TAN) was 18% lower (P = n.s.) in the BGP group. LV systolic function was disturbed at rest and stress in the BGP mice (both P < .05). LV dimensions and LV mass were increased in the BGP group (P < .05). There was an accumulation of intracellular triglycerides in the BGP-treated mice (P < .05). Four weeks after BGP discontinuation Cr, TAN and TG content were restored to the normal levels while LV function, dimension, and mass were normalized. Myocardial Cr depletion results in LV dysfunction, pathologic remodeling, and lipid accumulation. These alterations are completely reversible on normalization of Cr content. Cr metabolism may be an important target for pharmacologic intervention to increase myocardial efficiency and structural integrity of the failing heart.


Comparative performance analysis for abdominal phantom ROI detectability according to CT reconstruction algorithm: ADMIRE.
We compared and analyzed the detectability performance pertaining to an abdominal phantom including a region of interest (ROI) according to a computed tomography (CT) reconstruction algorithm. Three types of reconstruction algorithms (FBP, SAFIRE, and ADMIRE) were used to evaluate the detectability performance using the abdominal phantom (phantom size: 25 × 18 × 28 cm3 ). The vendor default settings for routine multi-detector computed tomography abdominal scans were used. As the quantitative evaluation method, the contrast-to-noise ratio (CNR), difference in coefficient of variation (COV) with the normalization based on the FBP data, and the noise power spectrum (NPS) were measured. The characteristic of the ADMIRE-3 reconstructed image was higher than those of the FBP and SAFIRE-3 reconstructed images. The CNR values of the SAFIRE and ADMIRE images were much higher than the corresponding values of the FBP images. The difference in COV values for the ADMIRE images was ~1.2 times lower than the corresponding values of the SAFIRE images. The comparative analysis of the abdominal phantom low-contrast resolution differences for each CT exposure parameters showed that ADMIRE demonstrated better results than SAFIRE and FBP in terms of contrast, CNR, COV difference, and 1D NPS. This indicates that ADMIRE can provide a clearer observation even with the same number of contrast objects as compared to SAFIRE and FBP owing to its better contrast resolution in the central part of the contrast hole at low kV.


Unusual sarcomatoid neoplasm of the lung suggesting a myofibrosarcoma.
Myofibrosarcoma is a rare neoplasm that occurs mainly in the head and neck region and extremities of middle-aged patients. It often appears as a low-grade sarcoma and rarely metastasizes. We report the case of a 47-year-old male patient with a malignant mesenchymal pulmonary tumor affecting almost the entire lower left lobe. Clinically suggestive for a lung carcinoma, the tumor showed typical features of a myofibrosarcoma. A major spindle cell component was observed being positive for smooth-muscle actin, calponin, and vimentin, while stainings for desmin, h-caldesmon, alkaline phosphatase (ALK), and extensively studied cytokeratins were negative. Striking was a strong infiltrate with neutrophilic and eosinophilic granulocytes. DNA cytometry revealed aneuploidy with a peak in the near triploid range. Comparative genomic hybridization demonstrated multiple DNA gains and losses correlating with an aggressive clinical course. Shortly after resection of the primary tumor, the patient showed multiple distant metastases in the contralateral lung, the mediastinal lymph nodes, the left adrenal gland, and the pectoral and deltoid muscle, which responded well to chemotherapy. The case report will discuss the evidence for the final diagnosis of a primary pulmonary myofibrosarcoma and the differential diagnosis of sarcomatoid tumors of the lung.


Sentinel lymph node mapping using SPECT-CT fusion imaging in patients with oral cavity squamous cell carcinoma.
Lymphoscintigraphic planar imaging is commonly performed to locate the sentinel lymph nodes (SLN) preoperatively. The images are, however, obscure lacking anatomical information and only rough topographical orientation of the SLNs is possible. Image fusion of Single Photon Emission Computed Tomography (SPECT) and Computed Tomography (CT) has been suggested to be an anatomically more precise method for preoperative SLN mapping. In the present study, preoperative lymphoscintigraphic SLN mapping was performed by using a hybrid gamma-camera with CT system (SPECT-CT) in addition to conventional planar lymphoscintigraphy in 15 consecutive patients with squamous cell carcinoma (SCC) of the oral cavity. The planar images were compared to fused SPECT and CT images. SPECT-CT fusion images showed only one SLN that was not detected in planar images. Two SLNs suspected in planar images could be excluded by SPECT-CT. The location of the SLNs could be determined more accurately by SPECT-CT. SPECT-CT fusion imaging was found feasible for preoperative SLN identification in patients with oral cavity SCC. It enables more accurate localisation of the SLNs, but it rarely reveals SLNs, that are not detected on planar images.


Editorial: Targeting the Core Symptoms of Autism Spectrum Disorder With Mechanism-Based Medications.
Medications can help manage behavioral problems associated with autism spectrum disorder (ASD), but no pharmacological treatment has proved effective for the core symptoms of the disorder. The article by Sprengers et al.1 in this issue of the Journal reports the primary results of the randomized clinical trial Bumetanide in Autism Medication and Biomarker (BAMBI), which tested the efficacy of bumetanide, a loop diuretic acting as a selective antagonist of the chloride importer NKCC1, for the core symptoms of ASD in 92 children 7-15 years of age.1 The study by Sprengers and colleagues was carefully designed and powered to detect a medium treatment effect size. Great attention was paid to protecting the blindness of the experiment in light of the adverse effects of the medication. After the 3-month treatment, bumetanide was not better than placebo at decreasing social communication deficits, as measured with the Social Responsiveness Scale-2 (the primary outcome), although a decrease in repetitive behaviors (a secondary outcome) was found. This study attests to the progress from clinical serendipity to pathogenesis-driven treatment research in ASD and is remarkable in a number of ways.


Bisphenol A as a risk factor for allergic rhinitis in children.
Bisphenol-A (BPA) is an endocrine disrupting compound and may exacerbate or induce allergic diseases. To the best of our knowledge, there is little evidence regarding the effects of BPA exposure on allergic rhinitis (AR) in children. In the present study, we sought to examine whether exposure to BPA in children is associated with AR. This study was designed as a case controlled clinical study. 140 children diagnosed as allergic rhinitis and 140 healthy children as control group were recruited. BPA, interleukin-4, interleukin-13, total IgE and interferon-gamma levels were determined. Skin prick tests were performed in patient group. Total nasal symptom score and ARIA classification were used to predict disease severity. Serum IL-4, IgE and BPA levels of children with allergic rhinitis were found to be significantly higher than the control group. BPA and IL-4 levels were significantly higher in moderate to severe-persistent group. There was a positive correlation between total nasal symptom scores and Bisphenol A levels in children with allergic rhinitis. The present study is the first to observe statistically significant relationship between BPA concentrations and allergic rhinitis in children. Also increased levels of BPA are associated with disease severity.


Genetic elimination of α3(IV) collagen fails to rescue anti-collagen B cells.
Organ deposition of autoantibodies against the noncollagenous-1 domain of the α3 chain of type IV collagen leads to severe kidney and lung injury in anti-glomerular basement membrane disease. The origin and regulation of these highly pathogenic autoantibodies remains unknown. Anti-α3(IV) collagen B lymphocytes are predicted to mature in vivo ignorant of target antigen because α3(IV) collagen expression is highly tissue restricted and pathogenic epitopes are cryptic. However, a recent analysis of an anti-α3(IV)NC1 collagen autoantibody transgenic mouse model revealed that developing B cells are rapidly silenced by deletion and editing in the bone marrow. To dissect the role of collagen as central tolerogen in this model, we determined B cell fate in autoantibody transgenic mice genetically lacking α3(IV) collagen. We found that absence of the tissue target autoantigen has little impact on the fate of anti-α3(IV)NC1 B cells. This implies a more complex regulatory mechanism for preventing anti-glomerular basement membrane disease than has been previously considered, including the possibility that a second antigen present in bone marrow engages and tolerizes anti-α3(IV)NC1 collagen B cells.


Chicken embryonic stem cells: establishment and characterization.
Embryonic stem (ES) cells are unique models for investigating early development and cell differentiation. First identified in mouse and later in other mammals, these cells have also been isolated in avian species. Here, using chicken as a model, we describe a set of protocols allowing the isolation, maintenance, genetic modification, differentiation, and injection of the chicken embryonic stem (cES) cells into embryos for obtaining chimeric animals.


Randomized trial of standard versus magnetic endoscope imaging colonoscopes for unsedated colonoscopy.
Unsedated colonoscopy has potential benefits, including decreased costs and decreased risks. To determine whether patient comfort during unsedated colonoscopy can be improved through the use of a magnetic endoscopic imaging (MEI) colonoscope compared with a standard colonoscope. Prospective, patient-blinded, randomized, controlled trial. San Francisco Veterans Affairs Medical Center. Veterans undergoing outpatient screening or surveillance colonoscopy. Use of a standard or MEI colonoscope during unsedated colonoscopy. The primary outcome variable was patient perception of pain using a 7-point scale. The secondary endpoint was patient willingness to undergo a future unsedated colonoscopy. Of the 160 patients enrolled, 140 completed an unsedated colonoscopy in the study protocol. In a per-protocol analysis, the mean and median pain score was 3.12 (standard deviation 1.22) and 4 (interquartile range 2-4) for the standard colonoscope group and 3.06 (standard deviation 1.13) and 3 (interquartile range 2-4) for the MEI group, where 3 was mild pain (P = not significant). Overall, 80% of subjects were willing to undergo a future unsedated colonoscopy for screening or surveillance. In an intention-to-treat analysis, 80% of subjects (64/80) in the standard colonoscope arm and 79% in the MEI arm (63/80) were willing to undergo a future unsedated colonoscopy (P = not significant). Single-center study of mostly male veterans. This patient-blinded, randomized, controlled trial did not demonstrate any difference in patient perception of pain or willingness to undergo unsedated examinations when using the MEI versus the conventional colonoscope. Unsedated colonoscopy is generally feasible and well tolerated and is associated with high patient satisfaction rates.


Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia.
Spinocerebellar ataxia type 7 is a rare autosomal dominant cerebellar ataxia (ADCA). Herein, we describe the molecular and clinical findings in patients within six generations of a large Chinese family with spinocerebellar ataxia. To identify the genetic cause(s), 4 affected patients and 26 asymptomatic relatives were recruited for the study. Molecular screening of the SCA1 and SCA7 genes was carried out by subcloning and direct PCR-sequencing methods. Both neurological and ophthalmic examinations were performed to investigate the clinical characteristics of the disease. The patients had typical cerebellar ataxia, achromatopsia and macular degeneration, and displayed a rare phenotype manifesting as a combination of cerebellar ataxia and craniocervical dystonia. Mutational analysis of the SCA7 genes demonstrated expanded CAG-repeats in the four patients. In conclusion, we identified expanded CAG-repeats in the SCA7 gene within members of a large Chinese family with spinocerebellar ataxia. The defined phenotypic characteristics of the patients may be helpful for clinical diagnosis and genetic typing of new patients.


Suitability of Bioelectrical Based Methods to Assess Water Compartments in Recreational and Elite Athletes.
It is important for highly active individuals to easily and accurately assess their hydration level. Bioelectrical impedance (BIA) can potentially meet these needs but its validity in active individuals is not well established. We aim to validate total body water (TBW), extracellular water (ECW), and intracellular water (ICW) estimates obtained from 50 kHz BIA, bioelectrical impedance spectroscopy (BIS), and BIA-based models against dilution techniques in 2 populations: active adults and elite athletes. Active males (N = 28, 20-39 years) involved in recreational sports and elite athletes (females: N = 57, 16-35 years; males: N = 127, 16-38 years) participated in this study. TBW and ECW were assessed with deuterium and bromide dilution, respectively. ICW was assessed as their difference. Body water compartments were also assessed by BIA (BIA-101), BIS (model 4200), and BIA-based equations. Small but significant differences were observed between alternative methods and the criterion in all subsamples. In female athletes, r(2) > 0.69, r(2) > 0.57, and r(2) > 0.65 were observed between methods in the TBW, ECW, and ICW estimates. In males, r(2) > 0.75, r(2) > 0.65, and r(2) > 0.68 were found between alternative and reference methods in the TBW, ECW, and ICW estimates, respectively, whereas for male recreational exercisers, r(2) > 0.58, r(2) > 0.73, and r(2) > 0.75 were observed. Pure errors ranged between 0.19 to 3.32 kg for TBW, 0.64 to 1.63 for ECW, and 1.98 to 2.64 in ICW. The highest limits of agreement (LoA) were observed in Van Loan and Mayclin equation and the BIA method, respectively, for TBW and ECW assessment and the lowest LoA were observed in BIS for both TBW and ECW estimates. The higher accuracy of BIS in predicting individual TBW, ECW, and ICW highlights its utility in water assessment of recreational and elite athletes.


Hypothermia and cardiac arrest: the promise of intra-arrest cooling.
Over the past several years, the implementation of therapeutic hypothermia has provided an exciting opportunity toward improving survival from out-of-hospital cardiac arrest. There are compelling data to support the prompt use of therapeutic hypothermia for initial survivors from out-of-hospital cardiac arrest, but animal data have suggested that initiation of therapeutic hypothermia during the intra-arrest period may significantly improve outcomes even further. In the first feasibility study in humans, Bruel and colleagues report on the implementation of this intra-arrest approach among patients suffering out-of-hospital cardiac arrest, an exciting prospect that is discussed in the present commentary.


TEMPORARY REMOVAL: Sand, Sun, Sea and Sex with Strangers, the "five S's". Characterizing "cruising" activity and its environmental impacts on a protected coastal dunefield.
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis.
Psychological stress has recently been described as a risk factor in the development of pancreatic cancer. Here, we reported that increased neurotransmitter adrenaline was associated with the poor survival in pancreatic cancer patients. Moreover, in the cell model study, we found adrenaline promoted pancreatic cell PANC-1 migration in a dose dependent manner. Block of the β2-adrenoreceptor with ICI118,551, significantly reduced cell migration. Further study found that adrenaline induced a cytoplasmic translocation of RNA binding protein HuR, which in turn activated TGFβ, as shown by the SBE luciferase assay and phosphorylation of Smad2/3. Either HuR knockdown or TGFβ inhibition reduced cell migration induced by adrenaline. Taken together, our study here revealed that adrenaline-HuR-TGFβ regulatory axis at least partially contributes to the psychological stress induced metastasis in PANC-1 cells, shedding light on therapeutic targeting psychological stress in improving the prognosis of pancreatic cancer.


Contrastive machine learning reveals the structure of neuroanatomical variation within autism.
Autism spectrum disorder (ASD) is highly heterogeneous. Identifying systematic individual differences in neuroanatomy could inform diagnosis and personalized interventions. The challenge is that these differences are entangled with variation because of other causes: individual differences unrelated to ASD and measurement artifacts. We used contrastive deep learning to disentangle ASD-specific neuroanatomical variation from variation shared with typical control participants. ASD-specific variation correlated with individual differences in symptoms. The structure of this ASD-specific variation also addresses a long-standing debate about the nature of ASD: At least in terms of neuroanatomy, individuals do not cluster into distinct subtypes; instead, they are organized along continuous dimensions that affect distinct sets of regions.


SLC7A8 is a key amino acids supplier for the metabolic programs that sustain homeostasis and activation of type 2 innate lymphoid cells.
Group 2 innate lymphoid cells (ILC2) are innate counterparts of T helper 2 (Th2) cells that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 and IL-13 secretion. ILC2s depend on availability of arginine and branched-chain amino acids for sustaining cellular fitness, proliferation, and cytokine secretion in both steady state and upon activation. However, the contribution of amino acid transporters to ILC2 functions is not known. Here, we found that ILC2s selectively express Slc7a8, encoding a transporter for arginine and large amino acids. Slc7a8 was expressed in ILC2s in a tissue-specific manner in steady state and was further increased upon activation. Genetic ablation of Slc7a8 in lymphocytes reduced the frequency of ILC2s, suppressed IL-5 and IL-13 production upon stimulation, and impaired type 2 immune responses to helminth infection. Consistent with this, Slc7a8-deficient ILC2s also failed to induce cytokine production and recruit eosinophils in a model of allergic lung inflammation. Mechanistically, reduced amino acid availability due to Slc7a8 deficiency led to compromised mitochondrial oxidative phosphorylation, as well as impaired activation of mammalian target of rapamycin and c-Myc signaling pathways. These findings identify Slc7a8 as a key supplier of amino acids for the metabolic programs underpinning fitness and activation of ILC2s.


Analysis of UB and L40 resistance related to deltamethrin in Drosophila kc cells.
Pests have been subjected to heavy selection pressure, and the development of resistance to pyrethroid has been recorded. It is extremely valuable to identify the resistance genes that are relevant for pest control. In our previous studies, we reported that UBL40 is the deltamethrin resistance-associated gene. UBL40 is cleaved by specific endopeptidases to release UB and L40. Whether UB or L40 participates in deltamethrin resistance requires further study. In this study, quantitative real-time PCR was applied to reveal that UB and L40 were both overexpressed in Drosophila kc cells after deltamethrin stimulation. To investigate the roles of UB and L40 further, RNA interferences (RNAi) and cell transfections were utilized. UB and L40 knockdown both significantly reduced the level of resistance of RNAi-treated cells after 48 h, and the overexpressions of UB and L40 in Drosophila kc cells conferred a degree of protection against deltamethrin. These results represent the first evidence that UB and L40 both play roles in the regulation of deltamethrin resistance and that this study could help us to elucidate the resistance mechanisms and identify new target genes associated with resistance.


Operative management of testicular torsion: current practice within the UK and Ireland.
Several methods have been described and are currently used for fixation of testes in the operative treatment of testicular torsion. Although recurrence of torsion is generally viewed as a technical failure, the factors contributing to this failure remain unclear. This survey was conducted to establish current practice amongst paediatric surgeons in the UK and Ireland, in relation to testicular fixation, in an attempt to reflect the level of concern over the potential for recurrence as expressed in choice of procedure. The questionnaire survey indicated that 85% of paediatric surgeons use suture fixation of the testis alone or in combination with additional steps, such as eversion of the tunica vaginalis or creation of a dartos pouch, and 15% use a sutureless technique. The great majority (95%) fix the contralateral testis routinely and 85% routinely excise the appendix testis. Of the respondents, 17% have operated on a torted testis that had been previously fixed. In the absence of data from comparative trials, the method used for fixation remains a matter of personal preference. It was not possible to identify the definitive risk factors for recurrence from this study, but the use of absorbable sutures accompanied recurrence in most instances.


Infusion at constant rate in vivo.
Infusion can be maintained at a constant rate over an extended period of time in vivo by the use of an implanted diffusion chamber. Plasma 59Fe was maintained at a constant level for 10 days when infused from a s.c. implant. Injected isotope was cleared exponentially with a half-clearance time of about 8 h.


Behavioral and neurochemical effects induced by pyrethroid-based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period.
Synthetic pyrethroids, besides their use in agriculture, are prevalently used in our houses as mosquito repellent (MR) in the form of aerosol, mats, coils and liquid vaporizers. Inhalation of fumes of the MR/liquid vaporizers may get entry into the brain by breaching the developing blood-brain barrier, hence deleterious to developing nervous system and can lead to long-term functional deficits. In the present study the consequence of MR exposure has further been investigated at various stages of development, evaluating free radical mediated effect pertinent to neurobehavioral and neurochemical functioning. Rat pups were exposed to pyrethroid-based MR (allethrin 3.6% w/v, 8 h/day through inhalation) during prenatal (GD1-20), postnatal (PND1-30) and perinatal (GD1-PND30) period of development and assessments were made on PND31. We observed significant oxidative stress, where an increase in lipid peroxidation and a decrease in antioxidants, glutathione, superoxide dismutase and catalase in various brain areas (cerebellum, corpus striatum, frontal cortex and hippocampus) were evident at all the exposure schedules. The hippocampus was the most affected region and further exhibited altered cholinergic functioning in the form of significant decrease in cholinergic (muscarinic) receptor binding (prenatal 32%, postnatal 35%, perinatal 38%) and inhibition in acetylcholinesterase activity (prenatal 20%, postnatal 31% and perinatal 33%). The neurochemical changes were found to accompany decrease in learning and memory performance in exposed rats, the function governed by hippocampus. The result suggests that pyrethroid-based MR inhalation during early developmental period may have adverse effect on developing nervous system causing cholinergic dysfunction leading to learning and memory deficit.


Focal myositis in the hand.
Focal myositis is a rare, benign, pseudotumor of skeletal muscle that is usually seen as a steadily enlarging soft tissue tumor in an otherwise healthy patient. Focal involvement of muscle with severe myopathic and inflammatory changes characterize the histology. The natural course of this disorder is spontaneous regression. We report the case of a 7-year-old girl with focal myositis of the index lumbrical muscle. This is the first reported incidence of focal myositis that involves muscle of the hand.


Combined effects of drought and cold acclimation on phospholipid fatty acid composition and cold-shock tolerance in the springtail Protaphorura fimata.
Terrestrial arthropods' ability to survive sub-zero winter temperatures is an important factor influencing their abundance and geographic distribution. It is, therefore, important to understand their physiological mechanisms of low-temperature survival. Acclimation to moderate-low temperature can improve cold tolerance, and pre-acclimation to mild desiccation can also improve survival of a subsequent cold exposure. However, very few studies have assessed the combined actions of cold and drought acclimations. In the present study, we combined cold acclimation with drought acclimation making it possible to assess the interactions between effects of these two stressors using the springtail Protaphorura fimata as a model organism. We investigated the interacting effects of drought and cold acclimation on body fluid osmolality, membrane phospholipid fatty acid (PLFA) composition, and cold-shock tolerance. Acclimation to mild drought (- 2.46 MPa) increased body fluid osmolality from 0.33 to 1.25 Osm at all acclimation temperatures (5, 10, 15, or 20 °C) likely due to accumulation of the compatible osmolytes, trehalose, and alanine. Interestingly, the expected positive effect of drought acclimation on cold-shock tolerance was only evident at high acclimation temperature (20 °C), whereas at intermediate temperatures (10 and 15 °C), there was an interaction between acclimation temperature and drought. At 5 °C, no effect of drought acclimation on cold-shock tolerance was observed despite high osmolality. The positive effect of drought acclimation at 20 °C on subsequent cold-shock survival coincided with a drought-induced effect on PLFA composition only detectable at high temperature. We discuss the possible roles of drought-induced compatible osmolytes and an altered PLFA composition in the cold-shock tolerance of arthropods.


Miniaturized systems for gas chromatography: Developments in sample preparation and instrumentation.
An important field of research is the miniaturization of analytical systems for laboratory applications and on-field analysis. In particular, gas chromatography (GC) has benefited from the recent advances in enabling technologies like photolithography, micromachining, hot embossing, and 3D-printing to improve sampling and sample preparation, microcolumn technologies, and detection. In this article, the developments and applications reported since 2015 were reviewed and summarized. Important applications using benchtop instruments, portable GCs, and micro-GCs (µGCs) were showcased to illustrate the current challenges associated with each miniaturized interfaces and systems. For instance, portable instruments need to be energy-efficient and ideally depend on renewable sources for carrier gas generation. Lastly, multidimensional separations were addressed using miniaturized systems to effectively improve the peak capacity of portable systems.


Risk Factors for Injuries in Professional Football Players.
The aim of this study was to identify risk factors related to the occurrence of injuries in football players. The study included 216 football players from 12 teams in the elite football league. Football-related injury data were collected prospectively during the 2012/2013 competitive season. At baseline the following information was collected for the players: anthropometric measurements (weight, height, BMI, subcutaneous skinfolds), playing experience, injury history, physical fitness performance test (agility run), peak oxygen uptake. The incidence, type and severity of injuries and training and game exposure times were prospectively documented for each player. Most of the players (n = 155, 71.7%) sustained the injures during the study period. The overall injury incidence during the regular season was 6.3 injuries per 1000 athlete-exposures (95% confidence interval, 4.31-9.67). Multivariate logistic regression analysis showed that playing experience (odds ratio [OR] = 0.44; 95% CI = 0.32-0.61, p < 0.01), age (OR = 2.05; 95% CI = 1.49-2.81, p < 0.01) and a previous injury (OR = 4.4; 95% CI = 2.14-9.07, p < 0.01) were significantly correlated to increased risk of injuries. Body mass index was not associated with risk of injury. Strains (34.19%) and sprains (25.81%) were the major injury types. Twenty-seven percent of injured players were absent from football for more than 1 month, with knee injuries (25.42%) being the most severe type. The risk factors that increase injury rates in football players were previous injury, higher age and years of playing. Future research should include adequate rehabilitation program to reduce the risk of injuries.


Structural and exchange properties of "Co(III)-phenanthroline-ATP": a labeling reagent for the active site of ATPases.
This paper reports on 1H and 31P NMR as well as EPR measurements of the labeling reagent of ATPase sites, "Co(III)-(phen)-ATP." This complex is found to be paramagnetic, as deduced both from its EPR spectrum and from the significant broadening, though almost unshifted, proton and phosphorus resonances. This paramagnetism is a result of the incorporation of the superoxide free-radical anion in the coordination sphere of the trivalent cobalt ion. Evidence for the presence of superoxide in the complex is based on competition experiments with cyanide, which is able to displace the superoxide anion. The latter was identified by its inducing effect on the photoreactivity of luminol. The displacement of superoxide by cyanide was accompanied by the abolition of the paramagnetism of the complex. The relative distances between the protons and phosphorus atoms of ATP and the superoxide anion in the complex were calculated using the NMR line-broadening data. Structural models compatible with the experimental results are proposed. Under conditions of excess of adenine nucleotides or phenanthroline, the coordinated ATP molecule becomes exchangeable. This phenomenon is attributed to the labilization of the cobaltic ion ligands induced by the superoxide anion.


Galactoglucomannan-rich hemicellulose extract from Norway spruce (Picea abies) exerts beneficial effects on chronic prostatic inflammation and lower urinary tract symptoms in vivo.
Galactoglucomannan (GGM) is the main hemicellulose class in wood of coniferous trees and could be potentially utilized as a possible health-promoting substance for food and pharmaceutical industry. Our aim was to evaluate effects of orally administered GGM-rich extract from Norway spruce in a rat model of chronic prostatitis associated with lower urinary tract symptoms (LUTS). Prostatic inflammation and LUTS was induced in male rats using testosterone and 17β-estradiol exposure for 18 weeks. Rats were treated with 2% GGM dissolved in drinking water during weeks 13-18. Pelvic pain response, LUT function and histopathological evaluation of the prostate were assessed. The results show that hormonal exposure induced LUTS seen as decreased urine flow rate, increased bladder pressure, voiding times, bladder capacity and residual urine volumes. GGM had positive effects on urodynamical parameters by decreasing the basal bladder pressure, increasing the urine flow rate and volume, reducing the residual volume and increasing micturition intervals. GGM reduced the extent of the hormone exposure-induced prostatic inflammation. Increase of pelvic pain induced by hormone exposure was only slightly affected by GGM treatment. The results suggest that orally administered GGM may have potential usage for improving lower urinary tract function associated with chronic prostatic inflammation.


Evaluation of Brucella abortus S19 vaccine strains by bacteriological tests, molecular analysis of ery loci and virulence in BALB/c mice.
Two Brucella abortus S19 commercial vaccine strains used for vaccination against brucellosis in India and three S19 strains available as international reference were examined by microbiological assays and molecular analysis of the ery loci involved in erythritol metabolism, and tested for residual virulence in BALB/c mice. According to the sensitivity to penicillin and i-erythritol, the five strains tested had the phenotypic characteristics of strain S19. However, on culture medium containing i-erythritol, all strains developed spontaneous i-erythritol resistant colonies at mutation rates ranging from 1.42x10(-2) to 1.33x10(-6). The S19 characteristic 702 bp deletion in the erythrulose 1-phosphate dehydrogenase gene of the ery locus was present only in the three reference strains but not in the two commercial vaccines. Both commercial strains and one of the reference strains showed reduced virulence in BALB/c mice. The presence or absence in S19 strains of the 702 bp deletion in the ery locus had no correlation with either the rates of spontaneous mutation to erythritol resistance or the residual virulence in mice.


Recurrent low-dose chemotherapy to inhibit and oxygenate head and neck tumors.
A lack of strategy to counteract hypoxia (pO₂ < 10-15 mmHg) and technique to repeatedly measure tumor pO₂ has restricted therapeutic optimization. We report the results obtained with an innovative anti-angiogenic strategy of recurrent low-dose (metronomic) chemotherapy to modulate hypoxia and growth of the Head and Neck tumor xenografts.The FaDu tumors were established in the flank of immune deficient mice and EPR oximetry with lithium phthalocyanine crystals was used to follow the temporal changes in tumor pO₂ on treatment with gemcitabine including controls for three weeks. The FaDu tumors were hypoxic with a baseline (pre-treatment) pO₂ of 2-8 mmHg. A transient increase in the tumor pO₂ was evident on day 3 on treatment with a conventional schedule of gemcitabine (150 mg/kg, d1, d8, d15). No significant change in the tumor pO₂ on treatment with metronomic gemcitabine (25 mg/kg on d1, d3, d5 for 3 weeks) was observed. However, tumor pO₂ increased significantly on d15-d18 during treatment with a metronomic schedule of 15 mg/kg gemcitabine (d1, d3, d5 for 3 weeks). A modest decrease in the tumor growth was evident on treatment with conventional gemcitabine. Notably, tumor growth was significantly inhibited by metronomic (25 and 15 mg/kg) gemcitabine treatment. The immunohistochemistry (IHC) analyses of the tumor samples indicate a decrease in HIF-1α and TSP-1 on treatment with metronomic gemcitabine.In conclusion, a significant inhibition of tumor growth on treatment with metronomic gemcitabine was observed; however, the increase in pO₂ was dose dependent. EPR oximetry can be used to follow the temporal changes in tumor pO₂ to identify a therapeutic window on treatment with metronomic chemotherapy for potential combination with radiotherapy.


Nuclear matrix-associated DNA fragments enhance autonomous replication of plasmids in chicken cells.
Most cells of higher eukaryotes may maintain several rounds of replication of circular DNA. Efficiency of replication is usually low, and depends on the length of the circular DNA rather than on the sequence context. We have isolated and characterized several short DNA fragments that form structural sites of attachment to the nuclear matrix (nmDNA) in chicken cells, and tested whether they would enhance autonomous replication of DNA in chicken cells as compared to the vector DNA. Indeed, a several-fold increase in a short-term replication efficiency was detected using a semi-conservative replication and a DpnI-resistance assay. Most of the cloned matrix-associated fragments were recovered in the nuclear matrix fraction when introduced into cultured chicken cells as a circular DNA. The data obtained suggest that the observed enhancement in the replication efficiency of the circular DNA may be due to their recruitment to the nuclear matrix by the nmDNA.


Blood lead concentrations in children with iron deficiency anemia: a systematic review and meta-analysis.
Iron deficiency is the most common nutritional disorder detrimental to the behavior, cognitive performance, immune system, and physical growth of infants and preschool- and school-age children. Iron deficiency anemia (IDA) increases children's susceptibility to some metals, including the highly toxic lead (Pb), but the character of this relationship is still disputed. Thus, this study aimed to review and meta-analyze the association between the IDA and blood lead levels (BLL) among children, based on papers indexed by international scientific databases and published up to September 2021. A search was performed of the literature in several databases including the ISI Web of Science, PubMed, and Scopus. The final papers were assessed concerning their quality based on the Newcastle-Ottawa Scale (NOS) for cross-sectional studies. Moreover, analyses were performed using R statistical software with the "meta" package. Of the 1528 articles found, only 12 studies met the inclusion criteria and were considered in the meta-analysis. Significantly higher BLL in IDA children (SMD = 2.40; CI 95%, 0.93-3.87 µg/L; p = 0.0014) was seen when compared to non-IDA children. Moreover, the pooled OR is equal to 2.75 (CI 95%, 1.10-6.85 µg/L; p = 0.0303) suggesting a higher risk of IDA development among children with BLL > 10 µg/dL. Thus, we recommend systematic monitoring of Fe and Pb levels among children, especially in countries with limited sources of nutritious food. Since only a few studies were available for this meta-analysis, further studies are necessary to examine the association between IDA and BLL in detail.


No sex differences in the economy of load-carriage.
Load transport activities are of vital importance to current foragers for daily subsistence tasks; thus, it has been suggested that these practices have transformed physical and behavioral characteristics through human evolution. Together with the procurement targets and strategies, the transportation of resources acquired while foraging is strongly influenced by the sex of the foragers. In hunter-gatherer societies, women, despite their smaller body size, usually carry heavier burdens than males. In this study, whether those behavioral differences can be explained by a different economy of load-carriage by sex, irrespective of the body mass of the individuals, is investigated. The energy expenditure of a sample of 48 volunteers (21 females, 27 males) during a set of locomotion and burden transport trials was monitored. Two indexes were computed to compare the increment in the cost of locomotion relative to the load carried by sex. The results demonstrate that both males and females, carrying the same relative loads, experience the same increment over the cost of their unloaded locomotion. Therefore, apart from obvious differences in body mass, there is no evidence of a dissimilar economy favoring one sex over the other that would explain the differences in load-carriage activities observed among current foraging populations. These outcomes provide new conclusions about the constraints of the behavioral ecology of burden transport activities, and highlight the necessity to reevaluate, from an evolutionary perspective, the ideas about the sexual division of subsistence labor in hunter-gatherer and agriculturalist populations.


Preconception Maternal Bereavement and Infant and Childhood Mortality: A Danish Population-Based Study.
Preconception maternal bereavement may be associated with an increased risk for infant mortality, although these previously reported findings have not been replicated. We sought to examine if the association could be replicated and explore if risk extended into childhood. Using a Danish population-based sample of offspring born 1979 to 2009 (N = 1,865,454), we analyzed neonatal (0-28 days), postneonatal infant (29-364 days), and early childhood (1-5 years) mortality after maternal bereavement in the preconception (6-0 months before pregnancy) and prenatal (between conception and birth) periods. Maternal bereavement was defined as death of a first-degree relative of the mother. Analyses were conducted using logistic and log-linear Poisson regressions that were adjusted for offspring, mother, and father sociodemographic and health factors. We identified 6541 (0.004%) neonates, 3538 (0.002%) postneonates, and 2132 (0.001%) children between the ages of 1 and 5 years who died. After adjusting for covariates, bereavement during the preconception period was associated with increased odds of neonatal (adjusted odds ratio = 1.87, 95% confidence interval = 1.53-2.30) and postneonatal infant mortality (adjusted odds ratio = 1.52, 95% confidence interval = 1.15-2.02). Associations were timing specific (6 months before pregnancy only) and consistent across sensitivity analyses. Bereavement during the prenatal period was not consistently associated with increased risk of offspring mortality; however, this may reflect relatively low statistical power. Results support and extend previous findings linking bereavement during the preconception period with increased odds of early offspring mortality. The period immediately before pregnancy may be a sensitive period with potential etiological implications and ramifications for offspring mortality.


Counts of stromal precursor cells in heterotopic splenic transplants in CBA mice of different age.
The content of stromal precursor cells in heterotopic splenic transplants from old and young mice changed appreciably after cross transplantation to old and young animals. The content of CFC-F in the young-->old transplants decreased almost 1.5 times in comparison with the young-->young transplants, the counts of CFC-F in old-->old transplants were minimum in comparison with all other groups (2.5+/-0.1), while in the old-->young group transplants this value increased almost 8-fold (to 19.0+/-1.3) and surpassed the control level. Age-associated shifts in the splenic stromal tissue were determined by regulatory influences of the host, rather than by decreased count of stromal precursor cells in the tissue.


AlphaCor keratoprosthesis: postoperative development of six patients.
AlphaCor (Argus Biomedical Pty. Ltd., Perth, Australia) is an artificial, soft, one-piece keratoprosthesis (KPro) indicated for severe corneal conditions not treatable by a donor graft. To evaluate the efficacy and visual restoring of six patients with complete corneal opacification and deep neovascularizations treated with AlphaCor. A retrospective review of six patients with a history of corneal opacification treated with keratoprosthesis surgery. AlphaCor synthetic cornea was implanted into the corneal stroma. During the follow-up time, slit-lamp and ultrasound examinations, best corrected visual acuity (BCVA), and intraocular pressure measurements were performed. Six eyes with corneal scarring and vascularizations in three to four quadrants of six patients to years of age underwent a keratoprosthesis procedure. The follow-up time was 13-36 months; mean 23 months. The operation procedure was not limited by severe complications. The preoperative BCVA was hand movement to light perception. The postoperative BCVA ranged between 20/200 and 80/100. Intraocular pressure was controlled in all cases. Three patients developed a melting of the anterior corneal lamella. The keratoprosthesis had to be explanted (15-34 months after implantation) and was replaced by a donor cornea. Further evaluation is needed to evaluate the role of AlphaCor as a keratoprosthesis.


Dual phenotypic characteristics of P-selectin in a mouse model of hemorrhagic shock and hepatectomy.
Membrane-bound P-selectin induces endothelial adhesion of leucocytes and amplifies organ inflammations during major trauma, while soluble P-selectin (sP-sel) mediates survival rescue properties. This study characterized the differential effects of P-selectin in a "2-hit" model of hemorrhagic shock (HS) and partial hepatectomy (PH). HS was induced by withdrawing blood (0.3 mL) directly from the mouse femoral arteries. 70% or 50% of liver volumes were resected after inducing HS. Time of survival in P-selectin deficient (Selp -/-) mice treated with and without intraperitoneal injections of recombinant P-sel IgG-Fc fusion proteins (rP-sel-Fc, 1.5 mg/kg) were recorded for up to 72h after injury. In addition, liver regeneration at 72h after HS and 50% PH was assessed in wild-type and Selp -/- mice. Compared to wild-types, Selp -/- mice had significantly higher mortality rates post HS and 70% PH, as none of these animals survived up to 48h postoperatively. The survival curve was restored in Selp -/- mice pre-treated with rP-sel-Fc. In the HS followed by 50% PH experimental arm, liver remnant growth ratios were significantly higher in Selp -/- mice (15.7 ± 3.1 vs 11.7 ± 4.9, P = 0.040). The elevated serum concentrations of alanine aminotransferase post-PH were significantly reduced in Selp -/- mice. Hepatocyte proliferation indices (CYP7a1 and PCNA) expression were enhanced and myeloperoxidase activity in the regenerated remnant liver was reduced in the Selp -/- mice. In critical conditions induced by HS and PH, P-selectin mediates two distinct phenotypic characteristics. Soluble-form circulating P-selectin improves survival in the acute stage of HS and extensive loss of liver parenchyma; membrane-bound P-selectin induces regional pro-inflammatory reactions in the remnant liver after the acute stage of two insults, thereby inhibiting hepatic regeneration. The results of this pre-clinical study may provide molecular mechanistic insight and clinical therapeutic applications of P-selectin in the acute and regenerative phases of traumatic hepatic injury.


When a school-age child stutters, let's focus on the primary problem.
In this reply to Yaruss, Coleman, and Quesal (2012), I explain why it is reasonable for speech-language pathologists to focus their attention on helping school-age children who stutter (CWS) achieve natural-sounding fluent speech. I also emphasize the necessity for clinical researchers to conduct high-quality treatment efficacy studies of school-age CWS.


Toxic and other non-IgE-mediated effects of fungal exposures.
There are more than 100000 recognized species of fungi, comprising 25% of the biomass of the earth. Allergic, IgE-induced, manifestations of airborne fungi are common, whereas non-IgE manifestations are rare. Recently, much focus has been placed on the non-IgE-mediated effects of various molds, including hypersensitivity pneumonitis, infectious disease, and mycotoxicoses. Hypersensitivity pneumonitis is a clinical syndrome associated with systemic and interstitial lung disease that occurs in susceptible individuals following fungal inhalation. Most fungi are not pathogenic to man; however, certain fungi are capable of infecting immunocompetent individuals. Although mycotoxins and exposure to mycotoxins ("toxic mold syndrome") are implicated in causing numerous, nonspecific, systemic symptoms, currently, there is no scientific evidence to support the allegation that human health is affected by inhaled mycotoxins. However, if mold is discovered in a home, school, or office setting, the source should be investigated and appropriate remediation undertaken to minimize structural damage and potential allergic sensitization.


Non-invasive haemoglobin measurement as an index test to detect pre-operative anaemia in elective surgery patients - a prospective study.
Non-invasive haemoglobin measurement using absolute values lacks the precision to be the sole basis for the treatment of pre-operative anaemia. However, it can possibly serve as a screening test, indexing 'anaemia' with high sensitivity when values remain under prespecified cut-off values. Based on previous data, non-invasive haemoglobin cut-off values (146 g.l-1 for women and 152 g.l-1 for men) detect true anaemia with 99% sensitivity. An index test with these prespecified cut-off values was verified by prospective measurement of non-invasive and invasive haemoglobin pre-operatively in elective surgical patients. In 809 patients, this showed an estimated sensitivity (95%CI) of 98.9% (94.1-99.9%) in women and 96.4% (91.0-99.0%) in men. This saved invasive blood tests in 9% of female and 28% of male patients. In female patients, a lower non-invasive haemoglobin cut-off value (138 g.l-1 ) would save 28% of invasive blood tests with a sensitivity of 95%. The target 99% sensitivity would be reached by non-invasive haemoglobin cut-off values of 152 g.l-1 in female and 162 g.l-1 in male patients, saving 3% and 9% of invasive blood tests, respectively. Bias and limits of agreement between non-invasive and laboratory haemoglobin levels were 2 and - 25 to 28 g.l-1 , respectively. Patient and measurement characteristics did not influence the agreement between non-invasive and laboratory haemoglobin levels. Although sensitivity was very high, the index test using prespecified cut-off values just failed to reach the target sensitivity to detect true anaemia. Nevertheless, with respect to blood-sparing effects, the use of the index test in men may be clinically useful, while an index test with a lower cut-off (132 g.l-1 ) could be more clinically appropriate in women.


Inactivation of alpha-chymotrypsin by new bifunctional reagents: halomethylated derivatives of dihydrocoumarins.
alpha-Chymotrypsin is rapidly and completely inactivated by a series of halomethylated derivatives of dihydrocoumarins at pH 7 and 25 degrees. The inactivation is pH-dependent and optimal at neutral pH; it is also more or less complete depending on the excess of inhibitor with respect to the enzyme. These compounds are substrates for alpha-chymotrypsin and, during the catalytic process, a latent alkylating function of the reagent is activated at the active site of the enzyme and reacts with some vicinal nucleophilic amino acid residues. The stoichiometry of the reaction of the corresponding radioactive reagents with the enzyme is slightly superior to one, but one histidine residue of alpha-chymotropsin is mainly modified. This histidine is identified as histidine-57 by the diagonal peptide mapping method. In comparison with other reagents, the efficiency of these suicide substrates" and particularly that one of a derivative (compound 2) carrying a substrate-like side chain is found to be very high.


The impact of prehistoric human dispersals on the presence of tobacco-related oral cancer in Northeast India.
Northeast (NE) India is a subject of debate for predicting its involvement in prehistoric anatomically modern human (AMH) dispersal. The unique lifestyle and genetic characteristics of native ethnic groups in this region are believed to be responsible for their susceptibility to tobacco-related oral cancer (TrOC). The present study assessed mitochondrial macro-haplogroup (mHG) diversity and TrOC susceptibility autosomal loci to evaluate the impact of prehistoric AMH dispersal on the present day's high TrOC prevalence in major NE Indian ethnics. We considered 175 unrelated individuals from 35 ethnic groups and previously published 374 sequences for sequencing-based assessment of mtDNA-based marker by subsequent analyses like haplogroup diversity, phylogenetic, genetic structure by AMOVA, and MDS, descriptive statistics of demographic parameters, and migration analysis. Besides, we selected prolonged tobacco-chewing 124 case-control individuals from similar ethnic backgrounds for genotyping 115 autosomal loci in Sequenom iPLEX MassARRAY™ platform and mined 1000genome data (n = 398) for consequent global admixture and ancestry-specific allele frequencies-based analyses. Our mtDNA-based findings suggested that NE populations were distinct from other Indian populations, owing to the first wave of migration from ancient southern China (∼54kya) and two successive spatial expansion events at ∼45kya and ∼43kya. Consequently, it probably acted as another source for prehistoric AMH dispersal in N/NE Asia. Besides, the second wave of back-migration from SE Asia (∼40kya) probably replaced the mitochondrial footprints of survivors from the first migrants and introduced the TrOC susceptibility traits in this region. Afterward, the autosomal marker-based observations on the transition of the disease-associated admixture component 'K6' from SE Asia reconfirmed these results. Moreover, we also observed that the mitochondrial mHG 'R' is significantly associated with the risk of TrOC (OR > 9.5) in NE India. Furthermore, the possible onset of the phenotypic expression of those traits was predicted at ∼4kya, thus, contributing to present-day's TrOC prevalence. This study reflects its uniqueness by revealing an updated AMH dispersal route for the peopling in and out of NE India, which probably introduced the disease-causing traits in the ancestral NE Indian population. Those traits were then imprinted in their genome to get transferred through their respective generations, forming the present-day's TrOC-prevalent NE Indian population.


Variations in the chemical composition and content of salicylic glycosides in the bark of Salix purpurea from natural locations and their significance for breeding.
Willow bark is one of the few plant raw materials which contain natural active substances that have analgesic, fever-reducing, anti-inflammatory and anti-rheumatic effects. Salix purpurea, listed as widespread and common in many countries, belongs to the willow species with the highest content of salicylic compounds. The chemical composition and content of major salicylic glycosides (SGs) in the bark of S. purpurea genotypes from natural locations were investigated in this study to evaluate their applicability for pharmaceutical processing and creative breeding. Secondary metabolites were analyzed in bark extracts from 91 genotypes of S. purpurea selected from natural locations. The bark of all analyzed genotypes contained salicylic glycosides: salicin, salicortin and tremulacin; flavanones: naringenin 5-O-glucoside, naringenin 7-O-glucoside, naringenin, chalcone isosalipurposide and flavan-3-ol: catechin. Picein and populin were detected in 10% of the studied genotypes. The SG content of purple willow bark ranged from 3.04 to 10.96, pointing to high variations between S. purpurea genotypes. This study provides valuable breeding material and offers attractive prospects for the breeding of new and improved willow varieties. Varieties with the most desirable traits, grown under controlled conditions, can supply high-quality herbal materials for the pharmaceutical industry.


Regulatory mechanisms controlling antibiotic production in Streptomyces clavuligerus.
Streptomyces clavuligerus produces a large array of natural compounds with antibiotic, antitumor, beta-lactamase inhibition or inmunomodulating activities. The production of cephamycin C, clavulanic acid and other compounds with a clavam structure has been studied for many years. A network of regulatory mechanisms is present in S. clavuligerus to control the formation of different compounds by pathway-specific regulators or pleiotropic regulators. The possible existence of a gamma-butyrolactone signaling system in this streptomycete is emerging. In addition, S. clavuligerus possesses a stringent control mechanism somehow different from those previously reported in other Streptomyces species.


Imaging of Neutrophils and Neutrophil Extracellular Traps (NETs) with Intravital (In Vivo) Microscopy.
As we have learned during recent years, neutrophils are not just simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions, and instead, they perform sophisticated functions (some of them only recently discovered) both in innate and adaptive immune responses. Neutrophil behavior and functioning should best be studied in situ, at locations where they are executed in a living organism, especially considering that neutrophils are mobile cells, performing their functions in distal body sites and various organs. For this herein we describe an approach to detect neutrophil presence/behavior in various organs (skin, muscle, liver) of alive mice, that is, intravital imaging/microscopy. We describe all surgeries required prior to imaging and share our methods of detection of neutrophils and neutrophil extracellular traps (NETs).


AAEM minimonograph #41: neuromuscular diseases associated with HIV-1 infection.
Neuromuscular diseases occur in as many as 50% of patients infected with human immunodeficiency virus type 1 (HIV-1). All forms of neuromuscular disease have been reported, including axonal neuropathy, demyelinating neuropathy, mononeuropathy multiplex, polyradiculitis, ALS-like syndromes, disorders of neuromuscular transmission, myopathy, and toxic neuropathies due to medication side effects. Neuromuscular disease is often the presenting manifestation of HIV-1 infection. Infection with cytomegalovirus (CMV) is associated with different types of neuropathy including mononeuritis multiplex and polyradiculopathy. There is effective treatment for many of the associated disorders including chronic inflammatory demyelinating neuropathy, CMV-mediated neuropathies, and myopathy. Treatment of CMV-mediated mononeuropathy multiplex may be life saving. The different neuromuscular syndromes associated with different stages of HIV-1 infection may be due, in part, to different levels of immunocompetence.


["We are free to choose the institutions which we visit"].
The role of the Controller General of Places of Deprivation of Liberty (CGLPL) is to ensure the proper management of future prisoners and the guarantee of their fundamental rights. This role concerns the legal framework of measures as well as the conditions of their application and the environment of the person entering a detention centre, a prison or a specially equipped hospital unit (UHSA), for prisoners with psychiatric conditions. Interview with Adeline Hazan, a CGLPL since July 2014.


[Pain control in German pediatric oncology. An inventory].
As part of a nationwide quality improvement programme, our aim is the assessment of the quality of pain control in German paediatric oncology to tailor the intervention to specific needs. Here we report on the results of a questionnaire-based nationwide survey which addressed the head of the department, one supervising physician, one ward physician, one nurse, and one psychologist/social worker in each of the 76 german paediatric oncology departments. 210/380 health care professionals of 60/76 departments responded to the survey. According to 17% of the physicians (41% of the nurses, p = 0.004) there still exists '(very) often' pain despite pain therapy. Procedures are seen as the main causes of pain. According to 58% of the heads of the department and supervising physician (35% of the nurses and ward physicians, p = 0.005), faces scales are regularly used to score pain intensity. In 80% of the departments a written therapy protocol addressing procedure-related, or postoperative pain is lacking. When larger and smaller departments are compared, in former ones the significantly preferred routes for opioid administration are i. v., or oral for slow release preparations (p = 0.01). The i. m. route is exclusively used in smaller departments. In the treatment of neuropathic pain, only 5% of the physicians regard morphine, but 25% of them regard antidepressants and antiepileptics as ineffective. Only 72% of the physicians (39% of the nurses, p = 0.001) are convinced that during opioid-based pain therapy addiction 'seldom/never' developes. Nurses are less satisfied with pain therapy than are physicians, and they feel more frequently that pain therapy '(very) often' starts too late (p <0.005). The questionnaire revealed obvious deficits in both physicians' and nurses' knowledge regarding pain therapy. Deficits were also addressed by the health care professionals themselves.


LPS-induced serum TNF production and lethality in mice: effect of L-carnitine and some acyl-derivatives.
The effect of L-carnitine and some of its acyl derivatives on serum TNF production and lethality in a murine experimental endotoxin shock model was investigated. In some instances, serum IL-6 production was also evaluated. In this experimental model, C57BL/6 mice received 30 mg/kg LPS (E. cell 055:B5) injected intraperitoneally, while L-carnitine and its derivatives were administered according to different schedules. Serum levels of TNF and IL-6 were evaluated 1 h following LPS injection. The treated animals were also monitored daily for differences in body temperature, feeding, and survival for 10 days after LPS injection. Although some derivatives were able to significantly affect TNF production, the marked decrease in serum TNF levels of LPS-treated mice was not paralleled by a substantial increase in survival.


Interventional oncology: pictorial review of post-ablation imaging of liver and renal tumors.
Percutaneous image-guided ablation is now commonly performed in many institutions for the treatment of hepatocellular carcinoma, liver metastases, and renal cell carcinoma in select patients. Accurate interpretation of post-ablation imaging is of supreme importance because treatment algorithms for these diseases rely heavily on imaging to guide management decisions. The purpose of this pictorial essay is to provide abdominal imagers with a review of the indications for percutaneous ablation in the abdomen, a basic overview of ablation modalities in clinical use today, the expected post-ablation imaging findings in the liver and kidney, and potential complications of hepatic and renal ablation procedures.


Does maternal race or ethnicity affect the expression of severe preeclampsia?
There is considerable variation in the expression of severe preeclampsia. Our purpose was to determine if this is associated with maternal race or ethnicity. Individual chart review was performed for women diagnosed with severe preeclampsia at a tertiary care center from 1993 to 2003. Demographic, clinical, and lab findings from diagnosis (Dx) to 6 weeks' postpartum (PP) were documented. Data were compared between Caucasian, African American, and Hispanic women. Data were presented for the total cohort if no significant difference was found. We evaluated 473 pregnancies: 201 (Caucasian), 216 (African American), and 56 (Hispanic). Groups had similar baseline characteristics: chronic hypertension (HTN), diabetes, and initial antenatal blood pressure (mean BP 118/68). Caucasian women were older (27 vs 24 yrs), more likely nulliparous (63 vs 49%), and had more multiple gestations (9 vs 1.5%), P < .002 for each. African Americans had less epigastric pain (7.4 vs 10%) and nausea (2.3 vs 5%), P < .05 for each. Platelets <100,000/microL and asparate aminotransferase >60 mg/dL were more common in Caucasian women at Dx (9 vs 12%, 11 vs 21%) and at delivery (14 vs 24%, 19 vs 34%), P < .05 for each. No difference in severe proteinuria was seen. African Americans had more severe HTN at both Dx (44.9 vs 30%) and peak BP (85 vs 67%), and required more antihypertensive Rx intrapartum (12 vs 6%), PP (38 vs 12%), and at discharge (35 vs. 21%), P < .03 for each. Hispanics presented later (36 vs 34.6 weeks) and had less severe HTN (27 vs 40%), P < .04 for each. BP on DC was not different between groups. Caucasian women had more hemolysis, elevated liver enzymes and low platelets syndrome (29 vs 19%, P = .01). Eclampsia, intrauterine fetal demise, intrauterine growth restriction, abruption, PP preeclampsia, and recurrent preeclampsia were similar between groups. African American women with severe preeclampsia demonstrate more severe hypertension and required more antihypertensive Rx, while Caucasian women have more frequent hemolysis, elevated liver enzymes and low platelets syndrome.