The fine-scale genetic structure of the two-spotted spider mite in a commercial greenhouse.
The fine-scale genetic structure of Tetranychus urticae Koch was studied to estimate local gene flow within a rose tree habitat in a commercial greenhouse using seven microsatellite markers. Two beds of rose trees with different population densities were selected and 18 consecutive quadrats of 1.2 m length were sequentially established in each bed. Heterozygote deficiency was positive within quadrats, which was most likely a result of the Wahlund effect because the mites usually form small breeding colonies. Low population density and frequent inbreeding could also accelerate genetic differentiation among the breeding colonies. A short-range (2.4-3.6 m) positive autocorrelation and clear genetic cline among quadrat populations was detected within a bed. This suggests that gene flow was limited to a short range even if population density was substantially increased. Therefore, large-scale dispersal such as aerial dispersal contributed very little to gene flow in the greenhouse.


Ruptured Distal Superior Cerebellar Artery Aneurysm After Gamma Knife Radiosurgery for Trigeminal Neuralgia: A Case Report and Review of the Literature.
Intracranial aneurysm formation after Gamma Knife radiosurgery (GKRS) is a rare complication that has only recently been reported in the literature. We report the case of a fatal distal superior cerebellar artery (SCA) aneurysm rupture in a woman treated twice with GKRS for trigeminal neuralgia along with a review of the literature regarding radiation-induced aneurysms. A 77-year-old white woman with a history of refractory right-sided trigeminal neuralgia treated with GKRS in 2001, and again in 2006 after a relapse, presented to our emergency department with complaints of a sudden-onset severe headache associated with vomiting, right eye vision loss, left-sided facial droop, and left-sided weakness with no history of hypertension or smoking prior to presentation. Initial head computed tomography scan without contrast demonstrated an intraparenchymal hemorrhage centered in the right middle cerebellar peduncle with subarachnoid hemorrhage in the basal cisterns and extension into the fourth ventricle causing early hydrocephalus. Head computed tomography angiography (CTA) demonstrated a distal right SCA aneurysm adjacent to the hemorrhage. The patient's mental status deteriorated into coma after suspected rerupture during the CTA requiring immediate intubation, external ventricular drain placement, and emergent cerebral angiogram with coil embolization. Ultimately, the patient never recovered despite medical and surgical management; therefore, care was withdrawn in accordance with her known wishes. The pathophysiologic association of aneurysm formation after GKRS remains to be elucidated, but given the potentially fatal consequences of aneurysm rupture, we advocate for further research and propose serial vascular imaging during the postradiosurgery follow-up period for iatrogenic aneurysm formation surveillance.


Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance.
Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of bone-resorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted Il17ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of Il17ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.


Precursor prioritization for p-cymene production through synergistic integration of biology and chemistry.
The strategy of synergistic application of biological and chemical catalysis is an important approach for efficiently converting renewable biomass into chemicals and fuels. In particular, the method of determining the appropriate intermediate between the two catalytic methods is critical. In this work, we demonstrate p-cymene production through the integration of biosynthesis and heterogenous catalysis and show how a preferred biologically derived precursor could be determined. On the biological side, we performed the limonene and 1,8-cineole production through the mevalonate pathway. Titers of 0.605 g/L and a 1.052 g/L were achieved, respectively. This difference is in agreement with the toxicity of these compounds toward the producing microorganisms, which has implications for subsequent development of the microbial platform. On the heterogeneous catalysis side, we performed the reaction with both biological precursors to allow for direct comparison. Using hydrogenation/dehydrogenation metals on supports with acid sites, both limonene and 1,8-cineole were converted to p-cymene with similar yields under equivalent reaction conditions. Thus, we could determine that the most promising strategy would be to target 1,8-cineole, the higher titer and lower toxicity bio-derived precursor with subsequent catalytic conversion to p-cymene. We further optimized the biological production of 1,8-cineole via fed-batch fermentation and reached the titer of 4.37 g/L which is the highest known 1,8-cineole titer from microbial production. This work provides a valuable paradigm for early stage considerations to determine the best route for the high-efficiency production of a target biobased molecule using an integration of biology and chemistry.


[The modified "hanging maneuver" during orthotopic liver transplantation using a technique for conserving the inferior vena cava].
We describe a modification of Belghiti's "liver hanging maneuver" applied to the last phase of hepatectomy during OLT with IVC preservation. The proposed maneuver provides a better exposition of the suprahepatic veins allowing an ortogonal clamping of the suprahepatic confluence and avoiding caval clamping. It allows, moreover, an increase of venous surface available for the anastomosis that results wider and easier to perform. This provides a large outflow anastomotic cloaca and prevents outflow problems of the graft.


Local control of penile erection. Nerves, smooth muscle, and endothelium.
This article reviews the state of knowledge on the neurologic and non-neurologic mechanisms that control the tone of the corpus cavernosum trabecular smooth muscle and the smooth muscles of penile arteries and veins. It includes discussion of the role of the adrenergic, the cholinergic, and the nonadrenergic noncholinergic neuroeffector systems as well as the potential role of the vascular endothelium and prostaglandins in the control of penile erection.


Molecular mechanisms, physiological consequences and pharmacological implications of estrogen receptor action.
The estrogen receptors (ERs), ERalpha and ERbeta, play a central role in mediating the biological effects of estrogen. The transcription rate of estrogen target genes is determined by several parameters including the type of ligand, estrogen receptor subtype and isoform, as well as interactions with receptor-binding cofactor proteins. The ERs regulate gene expression by binding to specific response element sequences in the promoters of estrogen target genes. Alternative pathways have also been described in which the ERs modulate transcription indirectly, via protein : protein interactions. In this regulatory mode, which has been traced to activator protein (AP)-1-, cyclic adenosine monophosphate (cAMP)-, and Sp1-response elements, the ERs appear to be tethered to target gene promoters via heterologous transcription factors. It has been found that ERalpha and ERbeta have opposite effects on transcription mediated via the indirect mode of action. Moreover, recent studies suggest that ERbeta may inhibit the stimulatory effects of ERalpha on cellular proliferation. Estrogen is a key regulatory hormone that affects numerous physiological processes. Estrogen is required for female pubertal development and affects growth, differentiation and function of the female reproductive system. It has recently been suggested that estrogen also has an important role in the male urogenital tract. In addition, estrogens have profound effects in other tissues. For instance, in the skeleton estrogen prevents bone-resorption by inhibition of osteoclast function. Numerous reports have suggested that estrogen has a beneficial effect in the cardiovascular system and in the CNS; however, this has not been confirmed in randomized clinical trials. In fact, a large randomized trial on healthy postmenopausal women receiving oral estrogen plus progestin showed an increased incidence of cardiovascular disease. In addition, this study revealed an increased risk for dementia and impaired cognitive function in the group receiving oral estrogen/progestin. Additional clinical trials are required to determine which hormonal component causes these health risks or whether the effects were due to the combination of estrogen and progestin.


Comorbidity in trichotillomania (hair-pulling disorder): A cluster analytical approach.
A promising approach to reducing the phenotypic heterogeneity of psychiatric disorders involves the identification of homogeneous subtypes. Careful study of comorbidity in obsessive-compulsive disorder (OCD) contributed to the identification of the DSM-5 subtype of OCD with tics. Here we investigated one of the largest available cohorts of clinically diagnosed trichotillomania (TTM) to determine whether subtyping TTM based on comorbidity would help delineate clinically meaningful subgroups. As part of an ongoing international collaboration, lifetime comorbidity data were collated from 304 adults with pathological hair-pulling who fulfilled criteria for DSM-IV-TR or DSM-5 TTM. Cluster analysis (Ward's method) based on comorbidities was undertaken. Three clusters were identified, namely Cluster 1: cases without any comorbidities (n = 63, 20.7%) labeled "simple TTM," Cluster 2: cases with comorbid major depressive disorder only (N = 49, 16.12%) labeled "depressive TTM," and Cluster 3: cases presenting with combinations of the investigated comorbidities (N = 192, 63.16%) labeled "complex TTM." The clusters differed in terms of hair-pulling severity (F = 3.75, p = .02; Kruskal-Wallis [KW] p < .01) and depression symptom severity (F = 5.07, p = <.01; KW p < .01), with cases with any comorbidity presenting with increased severity. Analysis of the temporal nature of these conditions in a subset suggested that TTM onset generally preceded major depressive disorder in (subsets of) Clusters 2 and 3. The findings here are useful in emphasizing that while many TTM patients present without comorbidity, depression is present in a substantial proportion of cases. In clinical practice, it is crucial to assess comorbidity, given the links demonstrated here between comorbidity and symptom severity. Additional research is needed to replicate these findings and to determine whether cluster membership based on comorbidity predicts response to treatment.


Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas.
To evaluate the expression of carbonic anhydrase IX (CA IX) and vascular-endothelial growth factor (VEGF) in esophageal and gastric adenocarcinomas and in turn with the histologic subtype. Tumor hypoxia is an important factor in therapy resistance. A low oxygen concentration in tumors stimulates a.o. the expression of CA IX, a marker of hypoxia, and VEGF, a pro-angiogenic factor. We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). The adenocarcinomas were subtyped according to the Lauren classification (intestinal- and diffuse-type). chi test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model. CA IX and VEGF expression were independent of the localization of the tumor. However, intestinal-type adenocarcinomas showed a significantly higher expression of CA IX as well as VEGF than diffuse-type tumors. VEGF expression was associated with a high microvessel density. Although survival analysis showed that CA IX expression (P = 0.008) as well as the coexpression of CA IX and VEGF (P = 0.008) correlate with a poor outcome, only CA IX expression is an independent prognostic factor for overall survival and metastasis-free survival. The difference in expression of CA IX and VEGF between intestinal- and diffuse-type adenocarcinomas may possibly explain the different clinical behavior of these tumors. CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis.


Hawley retainer and lichenoid reaction: a rare case report.
Oral lichenoid reaction (OLR) is a type IV cell-mediated immune response in the oral cavity. There is an established relationship between various dental materials and OLR, but few cases reports reported the occurrence of a lichenoid reaction in association with the use of a Hawley retainer. A female patient (twenty years of age) has been complaining of a reddish painful area on the tongue, which started one year ago and has been increasing in size over time. The patient completed orthodontic treatment two years ago and has been using a Hawley retainer for orthodontic retention since then. After performing histological analysis and patch test, the lesion was diagnosed as a lichenoid reaction to the Hawley retainer. Topical corticosteroids were prescribed, and the patient was asked to stop using the retainer and followed for six months. It is difficult to diagnose lichenoid lesions and even more challenging to differentiate between OLP and OLR, therefore it is essential to do a full intraoral and extraoral examination. OLL can occur in association with Hawley retainer, which we believe could be because it is made of an acrylic based material. Generally, OLL resolves after removal of the cause.


Roles of substrates in removing antibiotics and antibiotic resistance genes in constructed wetlands: A review.
Antibiotics and corresponding antibiotic resistance genes (ARGs) are emerging pollutants in wastewater that pose a significant threat to the environment and human health. Constructed wetlands (CWs) are a cost-effective technology for eliminating these pollutants through substrates, plants, and microorganisms. Detailed reviews of the roles of CW substrates on antibiotic and ARG removal and recent progress in the field are lacking. This paper reviews the mechanisms influencing antibiotic and ARG (intracellular and extracellular) removal in CWs, and natural, biomass, chemical, modified, industrial, novel, and combined substrates on their removal efficiencies. Generally, substrates remove antibiotics and ARGs mainly through adsorption, biodegradation, chemical oxidation, and filtration. Other mechanisms, such as photolysis, may also contribute to removal. Natural substrates (e.g., gravel, zeolite) are more frequently employed than other types of substrates. The removal performance of antibiotics and intracellular ARGs by zeolite was better than that of gravel through enhanced substrate adsorption, filtration, and biodegradation processes. Moreover, Mn ore showed promising high capability to remove high concentration of antibiotics through various removal pathways. In addition, combined substrates of soil/sand/gravel and other substrates further facilitate antibiotic removal. Future research is suggested to explore the mechanisms of competitive adsorption and redox-controlled biodegradation, investigate the effect of Fe/Mn oxides on the removal of antibiotics and ARGs via chemical oxidation, evaluate the removal of extracellular ARGs by CWs with different substrates, and investigate the effect of substrates on removal of antibiotics and ARGs in full-scale CWs.


Tonic-clonic seizure after unrecognized unintentional dural puncture.
Patients who suffer an unintentional dural puncture have a high risk of developing a post-dural puncture headache. Other neurologic complications have been reported, but seizure is rarely seen. We present a case of a 21-year-old primigravida who experienced an unrecognized unintentional dural puncture that ultimately resulted in a tonic-clonic seizure from intracranial hypotension one week following the dural breach. Her trachea was intubated and she was transferred to the intensive care unit. Two epidural blood patches, performed by neuroradiologists, were needed before the patient experienced complete resolution of her headache. During the re-admission, she also experienced a pulmonary embolus which further lengthened her hospital stay.


Three-dimensional versus two-dimensional imaging during laparoscopic cholecystectomy: a systematic review and meta-analysis of randomised controlled trials.
To evaluate the comparative outcomes of three-dimensional (3D) versus two-dimensional (2D) imaging during laparoscopic cholecystectomy. We conducted a systematic search of electronic information sources and bibliographic reference lists and applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits. Procedure time, Calot's triangle dissection time, gallbladder removal time, gallbladder perforation, intraoperative bleeding, postoperative complications, conversion to open and intraoperative errors were the evaluated outcome parameters. We identified 6 randomised controlled trials (RCT) reporting a total of 577 patients who underwent laparoscopic cholecystectomy using 3D (n = 282) or 2D (n = 295) imaging. The 3D imaging was associated with significantly shorter procedure time (MD - 4.23, 95% CI - 8.14 to - 0.32, p = 0.03), Calot's triangle dissection time (MD - 4.19, 95% CI - 6.52 to - 1.86, p = 0.0004) and significantly lower risk of gallbladder perforation (RR 0.50, 95% CI 0.28-0.88, p = 0.02) compared to the 2D approach. No significant difference was found in gallbladder removal time (MD - 0.79, 95% CI - 2.24 to 0.66, p = 0.28), intraoperative bleeding (RR 1.14, 95% CI 0.68-1.90, p = 0.61), postoperative complications (RD - 0.01, 95% CI - 0.06 to 0.05, p = 0.85), conversion to open (RD 0.00, 95% CI - 0.02 to 0.03, p = 0.70) or intraoperative errors (RR 0.96, 95% CI 0.79-1.17, p = 0.70) between the two groups. Although our findings suggest that the use of 3D imaging during laparoscopic cholecystectomy may be associated with significantly shorter procedure time, Calot's triangle dissection time and gallbladder injury compared to the 2D imaging, the differences seem to be clinically insignificant. Moreover, both approaches carry s similar risk of postoperative morbidities. The impact of the surgeon's level of experience and difficulty of the procedure on the outcomes of each imaging modality remains unknown.


Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID-19.
COVID-19 can present with a variety of clinical features, ranging from asymptomatic or mild respiratory symptoms to fulminant acute respiratory distress syndrome (ARDS) depending on the host's immune responses and the extent of the associated pathologies. This implies that several measures need to be taken to limit severely impairing symptoms caused by viral-induced pathology in vital organs. Opioids are most exploited for their analgesic effects but their usage in the palliation of dyspnoea, immunomodulation and lysosomotropism may represent potential usages of opioids in COVID-19. Here, we describe the mechanisms involved in each of these potential usages, highlighting the benefits of using opioids in the treatment of ARDS from SARS-CoV-2 infection.


Detection of Borrelia burgdorferi sensu lato in endomyocardial biopsy specimens in individuals with recent-onset dilated cardiomyopathy.
Recent studies in patients with dilated cardiomyopathy (DCM) have detected the genome of Borrelia burgdorferi sensu lato (BBSL) in endomyocardial biopsy (EMB) specimens using a qualitative polymerase chain reaction (PCR), suggesting a causal link between Lyme disease and DCM in areas in which Lyme disease is endemic. We aimed to study this relationship using a comprehensive molecular analysis detecting BBSL in EMB samples. We performed a comprehensive histopathological, immunohistochemical, ultrastructural, and molecular analysis targeting cardiotropic viruses and BBSL in EMB specimens of 41 individuals with recent-onset DCM and 15 controls with end-stage coronary artery disease. Specifically, quantitative PCR and electron microscopy of EMB specimens were employed. In addition, autoantibodies and manifestation of autoimmune diseases were evaluated in both groups. Individuals with recent-onset DCM presented more frequently with myocardial BBSL persistence as compared with the control group (24% vs. 0%, P = 0.035). In contrast, the prevalence of parvovirus B19 and cytomegalovirus was similar in both groups. Sequence analysis of borrelial DNA revealed the following genospecies: Borrelia burgdorferi sensu stricto in three patients (30%), Borrelia afzelii in two patients (20%), and Borrelia garinii in four patients (40%), the results being inconclusive in one case. BBSL-positive DCM patients had a higher prevalence of organ-specific autoimmune diseases in comparison with the remaining DCM patients (50% vs. 16%, P = 0.030). Myocardial persistence of BBSL may be involved in the pathophysiology of DCM in individuals living in areas in which Lyme disease is endemic.


Static versus dynamic predictions of protective stepping following waist-pull perturbations in young and older adults.
The purposes of this study were: (1) to determine the frequency of protective stepping for balance recovery in subjects of different ages and fall-status, and (2) to compare predicted stepping based on a dynamic model (Pai and Patton, 1997. Journal of Biomechanics 30, 347 354) involving displacement and velocity combinations of the center of mass (COM) versus a static model based on displacement alone against experimentally induced stepping. Responses to three different magnitudes of forward waist pulls were recorded for 13 young, 18 older-non-fallers and 18 older-fallers. The COM phase plane trajectories derived from motion analysis were compared with the model-predicted threshold values for stepping. We found that the older fallers had the highest percentage of stepping trials (52%), followed by older-non-fallers (17.3%), and young (2.7%) at the lowest perturbation level. Younger subjects stepped less often than the elderly at the middle level. Everyone consistently stepped at the highest level of perturbation. Overall, the dynamic model showed better predictive capacity (65%) than the static model (5%) for estimating the initiation of stepping. Furthermore, the threshold for step initiation derived from the dynamic model could consistently predict when a step must occur. However, it was limited, especially among older fallers at the low perturbation level, in that it considered some steps 'unnecessary' that were presumably triggered by fear of falling or other factors.


Assimilation of thorium isotopes into terrestrial vegetation.
Vegetation and root zone soil from 17 locations within and near the boundaries of a former thorium processing plant were collected and analyzed for 232Th, 228Th and 230Th in order to evaluate the degree of movement of these radionuclides from soil to root tissue, as well as the extent of their translocation into above-ground plant compartments. Concentration ratio (CR) values ranged as follows: 232Th: 0.0003-0.3218 (shoots), 0.0065-0.9057 (roots); 228Th: 0.0038-0.3300 (shoots), 0.0183-0.7335 (roots); 230Th: 0.0007-0.4560 (shoots), 0.0076-1.252 (roots). Root/shoot ratios were 1.03-85.6 (232Th), 1.54-45.8 (228Th) and 1.36-54.5 (230Th). In nearly all instances, the CR values for 228Th exceeded those for 232Th, with the average 228Th/232Th CR ratios being 3.36 and 1.68 for shoots and roots, respectively. No discernable difference was observed between 230Th and 232Th concentration patterns. The increased 228Th/232Th CR ratio observed is presumably due to the intake of 228Ra into the plant structure, leading to subsequent production of 228Th, through decay, within the plant. It is estimated that approximately 80% of the resident 228Th in above-ground vegetation originates through this mechanism.


Concurrent Change in Quadriceps Strength and Physical Function Over Five Years in the Multicenter Osteoarthritis Study.
Quadriceps weakness, associated with functional limitations, is a target of treatment of knee osteoarthritis (OA). Limited data exist on the relationship between modest strength increases and improvements in function. The aim of this study was to evaluate concurrent change in strength and physical function over 5 years. Among subjects from the Multicenter Osteoarthritis (MOST) study, we excluded those with knee replacement after baseline. A 3-category variable defined whether, at 5 years, knee extensor strength increased, decreased, or remained within 15% of baseline, a clinically important cut-off. The outcomes were the 5-times sit-to-stand test, 20-meter walk test, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function score, and 3 individual physical functions from WOMAC: arising from a chair, going up stairs, and getting on/off toilet. Linear and logistic models, stratified by sex, evaluated associations between change in strength and change in physical function over 5 years. To compare weaker versus stronger women, we stratified analyses at 56 Nm baseline strength. Among 1,534 participants (60.6% women), 22% of men and 30% of women increased strength by at least 15% at 5 years. Compared with women whose strength did not change, women whose strength increased had improved chair stand performance (odds ratio 2.27 [95% confidence interval 1.56, 3.30]) but no improvement in other functions. In men, an increase in strength was not associated with significant improvement in physical function. Similar results were observed for a 20% or 30% increase. Modest improvement in quadriceps strength was associated with improved chair stand performance in women but not in men. Most functions did not improve with an increase in strength, and targeted interventions may be required to improve functional status.


Integrative medicine utilization among infertility patients.
Previous research suggests that some women are using integrative and complementary holistic approaches to optimize their own health and treat infertility. We aimed to determine patterns of integrative medicine use among those seeking fertility optimization by 1) Characterizing patterns of integrative medicine use to increase fertility; 2) Identifying demographic predictors associated with such integrative medicine use; and 3) Exploring cultural and religious influences on use of integrative medicine. Cross-sectional self-reported survey data were collected from 1460 patients presenting to an academic fertility center in Chicago, Illinois. Variables were described with univariate frequencies and proportions, unadjusted bivariate comparisons were made between patient-level factors and reported integrative modality use, and multivariable logistic regression evaluated the strength of covariate-adjusted predictors of reported integrative medicine utilization. 80.4% of respondents reported using at least one integrative medicine modality to treat infertility (Acupuncture: 38.5%, Yoga: 27.6%, Massage: 25.8%, Meditation: 16.7%, and Herbal supplements: 18.5%). Diet therapy was the most frequently utilized modality (74.0%) followed by body therapy (45.2%), traditional alternative medicine (42.0%), mind therapy (32.1%), and senses therapy (23.0%). Any integrative medicine modality use was 4.03 times more likely among Hindu respondents compared to participants that identified as not religious (95% CI 1.2-13.7, p < 0.026). Significant differences in specific modality use were observed by race, religious affiliation, age, income, and insurance coverage. Most infertility patients in our study reported using at least one integrative medicine modality to help them conceive. Utilization was associated with age of participant, religious affiliation, annual income, and insurance coverage. Further research is needed to assess the impact of integrative medicine utilization on patient quality of life and outcomes.


A second gene for type I signal peptidase in Bradyrhizobium japonicum, sipF, is located near genes involved in RNA processing and cell division.
The TnphoA-induced Bradyrhizobium japonicum mutant 184 shows slow growth and aberrant colonization of soybean nodules. Using a DNA fragment adjacent to the transposon insertion site as a probe, a 3.4-kb BglII fragment of B. japonicum 110spc4 DNA was identified and cloned. Sequence analysis indicated that two truncated ORFs and three complete ORFs were encoded on this fragment. A database search revealed homologies to several other prokaryotic proteins: PdxJ (an enzyme involved in vitamin B6 biosynthesis), AcpS (acyl carrier protein synthase), Lep or Sip (prokaryotic type I signal peptidase), RNase III (an endoribonuclease which processes double-stranded rRNA precursors and mRNA) and Era (a GTP-binding protein required for cell division). The mutation in strain 184 was found to lie within the signal peptidase gene, which was designated sipF. Therefore, sipF is located in a region that encodes gene products involved in posttranscriptional and posttranslational processing processes. By complementation of the lep(ts) E. coli mutant strain IT41 it was demonstrated that sipF indeed encodes a functional signal peptidase, and genetic complementation of B. japonicum mutant 184 by a 2.8-kb SalI fragment indicated that sipF is expressed from a promoter located directly upstream of sipF. Using a non-polar kanamycin resistance cassette, a specific sipF mutant was constructed which exhibited defects in symbiosis similar to those of the original mutant 184.


Expression of BCL10 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan.
This study used an immunohistochemical technique to examine the expression of BCL10 in 93 specimens of oral squamous cell carcinoma (OSCC) and 21 specimens of normal oral mucosa (NOM). We found a significant correlation between the higher mean BCL10 labeling index (LI) and OSCCs at the tongue, with larger tumor size, with positive lymph node metastasis, with more advanced clinical stages, or with recurrence (all p-values=0.000). Positive lymph node metastasis (p=0.044) and BCL10 LI>50% (p=0.037) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. The Kaplan-Meier curve showed that OSCC patients with a BCL10 LI>50% had a significantly poorer cumulative survival than those with a BCL10 LI<50% (log-rank test, p<0.00001). We conclude that the BCL10 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.


Extradural haematoma. Report of 132 cases.
In a consecutive unselected series of 132 cases of acute extradural haematoma among 9,600 patients who sustained a head injury and were admitted without delay to a regional neurosurgical department during the years 1964 to 1975 the overall mortality was 23 per cent. Associated intradural lesions, the relative infrequency of the lucid interval, sustained loss of consciousness from the time of admission, lack of the classical pupillary changes, and the rapid rise in intracranial pressure in some patients are factors of importance for the prognosis. It should be possible to improve the results and lower the mortality if due consideration is taken of these factors.


Cloning and expression of murine interleukin-1 cDNA in Escherichia coli.
Interleukin-1 (IL-1), a peptide hormone produced by activated macrophages, possesses the ability to modulate the proliferation, maturation and functional activation of a broad spectrum of cell types and may play a major role in the initiation and amplification of immune and inflammatory responses through its action on these diverse cell populations. IL-1 exhibits microheterogeneity in terms of its relative molecular mass (Mr, 13,000-19,000) and charge properties, and although murine IL-1 has been purified and some of its basic structure-function relationships have been elucidated, it has proved difficult to prepare sufficient amounts of IL-1 for direct and detailed sequence and structural studies. Here we report the cloning, sequence analysis and expression of murine IL-1 cDNA in Escherichia coli. The IL-1 cDNA codes for a polypeptide precursor of 270 amino acids. Biologically active IL-1 was produced in E. coli by expressing the carboxy-terminal 156 amino acids of the IL-1 precursor.


Effect of rosiglitazone on peroxisome proliferator-activated receptor gamma gene expression in human adipose tissue is limited by antiretroviral drug-induced mitochondrial dysfunction.
Treatment of human immunodeficiency virus (HIV)-1 with thymidine-analogue nucleoside reverse-transcriptase inhibitors (tNRTIs) causes lipoatrophy, mitochondrial toxicity, and lower adipose tissue expression of peroxisome proliferator-activated receptor gamma (PPARgamma [PPARG gene]). Rosiglitazone (RSG), a PPARgamma agonist, improves congenital lipoatrophy but not HIV lipoatrophy. Serial fat biopsies were taken from HIV-infected, lipoatrophic men randomized to receive RSG or placebo for 48 weeks. Adipose tissue mitochondrial and nuclear gene expression and mitochondrial DNA content were quantified by real-time polymerase chain reaction. Nonparametric analyses were applied. Subjects receiving tNRTI-containing antiretroviral therapy had lower baseline mitochondrial RNA expression and DNA content. In subjects receiving tNRTIs, exposure to RSG did not affect PPARG expression at either week 2 or 48. At week 2, RSG increased PPARG expression only in subjects not treated with tNRTIs, whereas at week 48, increased PPARG expression was observed in subjects not treated with tNRTIs, regardless of RSG use. Similar findings were observed for the PPARG-responsive gene fatty acid-binding protein 4. Changes in PPARG expression were associated with increases in limb fat mass. These data suggest that in HIV-infected, lipoatrophic men, adipose PPARG expression and function are dependent on intact mitochondrial function. These data support a direct link between mitochondrial toxicity and adipose tissue PPARG expression and help explain the poor clinical response to RSG observed in clinical trials.


Classification and Pathology of Lung Cancer.
Advancement in the understanding of lung tumor biology enables continued refinement of lung cancer classification, reflected in the recently introduced 2015 World Health Organization classification of lung cancer. In small biopsy or cytology specimens, special emphasis is placed on separating adenocarcinomas from the other lung cancers to effectively select tumors for targeted molecular testing. In resection specimens, adenocarcinomas are further classified based on architectural pattern to delineate tissue types of prognostic significance. Neuroendocrine tumors are divided into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma based on a combination of features, especially tumor cell proliferation rate.


Students' time on learning tasks in special education.
The purpose of this study was to measure, through naturalistic observation procedures, the use of time among handicapped students in four special education alternatives--regular class, resource room, special class, and special school. The sample included 230 elementary age students enrolled in 58 classes in 16 schools. ANOVA comparisons revealed that the least restrictive alternatives, particularly the resource room, made more in-class learning time available. Discussion includes recommendations for increasing learning time.


Quality Characteristics and Functional and Antioxidant Capacities of Algae-Fortified Fish Burgers Prepared from Common Barbel (Barbus barbus).
Algae have been used as natural ingredients to produce new canned fish burgers prepared from minced flesh of common barbel. In this research, the impact of the addition of Cystoseira compressa and Jania adhaerens at concentrations of 0.5, 1, and 1.5% w/v on the texture and sensory characteristics of fish burgers were investigated. Compared to controls, fish burgers containing 1% algae had better texture and sensory properties (P < 0.05). Also, these burger formulations had higher water and oil holding capacities as well as swelling ability, due to the important polysaccharides and dietary fibers contents of algae. In addition, algae-supplemented burgers were characterized as having low L⁎, a⁎, and b⁎ values, which made the color appear to be paler. Thanks to their high richness in pigments (chlorophylls and carotenoids) and polysaccharides, algae considerably enhance the antioxidant activities of the new ready-to-eat fish burgers. So, Cystoseira compressa and Jania adhaerens could be used as nutritious additives to produce new fish-based products.


IL-21 induces pyroptosis of Treg cells via Akt-mTOR-NLRP3-caspase 1 axis in eosinophilic chronic rhinosinusitis.
Regulatory T (Treg) cells, which prevent inflammation-induced eosinophil infiltration, are deficient in nasal polyps (NPs) in patients with eosinophilic chronic rhinosinusitis (ECRS). It is concomitant with loss of Foxp3 after certain inflammatory stimuli. We sought to determine the inflammatory cytokines involved in inducing the loss of Treg cells in NPs. The abundance of cytokines in ECRS patients or mice were tested using ELISA, immunochemistry, immunofluorescence, quantitative reverse transcription PCR (qPCR), and/or flow cytometry. Expression of eosinophil cationic protein (ECP), CD4+ T cells, IL-4, and IL-17A and eosinophils in nasal mucosa of mouse model was investigated by immunochemistry, immunofluorescence, and hematoxylin and eosin staining. The percentage and death of induced Treg (iTreg) cells, source of IL-21 in NPs from ECRS and non-ECRS patients, and abundance of different systemic phenotypes of CD4+ T cells in a mouse model were studied by flow cytometry. Western blot analysis, scanning, and transmission electronic microscopy were used to detect pyroptosis of iTreg cells. IL-21 was highly expressed in nasal mucosa of ECRS patients and mice, causing pyroptosis and preventing development of iTreg cells in vitro. The elevated IL-21 in NPs from ECRS patients was mainly produced by CD3+ T cells, including T follicular helper, T peripheral helper, TH2, and TH17 cells and CD3+CD4- T cells. T peripheral helper cells and CD3+CD4- T cells were the predominant source of IL-21 in NPs from non-ECRS patients. Blocking IL-21/IL-21R signaling significantly reduced the number of eosinophils and CD4+ T cells along with ECP, IL-4, and IL-17A expression in the nasal mucosa of ECRS mice. It also increased Treg cell percentage and systemically decreased TH2 and TH17 ratios. Akt-mTOR inhibition prevented IL-21-induced pyroptosis in human and mouse iTreg cells. Elevated IL-21 drives pyroptosis and prevents Treg cell development in ECRS patients. IL-21 induced pyroptosis via activating Akt-mTOR-NLRP3-caspase 1 signaling.


Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.
Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.


Polyhydroxyalkanoates (PHA) production from synthetic waste using Pseudomonas pseudoflava: PHA synthase enzyme activity analysis from P. pseudoflava and P. palleronii.
Synthetic wastewater (SW) at various carbon concentrations (5-60g/l) were evaluated for polyhydroxyalkanoates (PHA) production using the bacteria Pseudomonas pseudoflava. Bacteria showed highest PHA production with 20g/l (57±5%), and highest carbon removal at 5g/l (74±6%) concentrations respectively. Structure, molecular weight, and thermal properties of the produced PHA were evaluated using various analytical techniques. Bacteria produced homo-polymer [poly-3-hydroxybutyrate (P3HB)] when only acetate was used as carbon source; and it produced co-polymer [poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV)] by addition of co-substrate propionate. PHA synthase, the enzyme which produce PHA was extracted from two bacterial strains i.e., P. pseudoflava and P. palleronii and its molecular weight was analysed using SDS-PAGE. Protein concentration, and PHA synthase enzyme activity of P. pseudoflava and P. palleronii was carried out using spectrophotometer. Results denoted that P. pseudoflava can be used for degradation of organic carbon persistent in wastewaters and their subsequent conversion into PHA.


Learning curve of transvaginal ultrasound for the diagnosis of endometriomas assessed by the cumulative summation test (LC-CUSUM).
A specific statistical tool (the cumulative summation test for learning curve or LC-CUSUM) was used to monitor the learning curve of four trainees for the diagnosis of endometriomas by transvaginal ultrasound. A large intertrainee variability in the learning curves was found, justifying a tailored training to learn this diagnosis.


Pharmacological treatment of depression in children and adolescents.
Major depression is a common disorder during childhood and adolescence. Over the past decade, many new antidepressants have been marketed in the US. In adults, these newer agents have been shown to be as effective as the prototypic tricyclic antidepressants (TCAs). Further, when compared with the TCAs these medications are better tolerated and are safer in overdose. Although TCAs are effective in the treatment of depressed adults, controlled clinical trials have not demonstrated their efficacy in either children or adolescents. In addition, concerns about the safety of TCAs and the monoamine oxidase inhibitors has left disappointingly few pharmacological treatment options available for depressed children and adolescents. For this reason, clinicians have begun to prescribe the newer agents for this population, despite the fact that relatively little is known about their disposition, safety or effectiveness in the young. Investigators have begun to examine whether the use of newer antidepressant medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone, and venlafaxine is truly indicated for children and adolescents with major depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have been performed in depressed youths. The results of these studies have provided data for rational administration strategies for these agents. They have also provided evidence that these agents may be well tolerated in children and adolescents. Further evidence that these agents are often well tolerated when prescribed to depressed youths has been obtained from both open-label and double-blind studies. Published studies have generally shown that open-label treatment with these newer agents often leads to symptom amelioration in paediatric patients with major depression. Since high rates of placebo response are often seen in depressed children and adolescents, results from these studies cannot be interpreted to suggest that these medications have true antidepressant efficacy in this population. At present, the results of only two such studies have been published. The results of one of these trials are difficult to interpret because of methodological considerations. The other study reported that treatment with fluoxetine was superior to placebo. This paper critically reviews what has been published about the pharmacological treatment of depressed paediatric patients and provides some guidance to the use of antidepressants in this patient population, paying particular attention to what is known about the newer antidepressants as well as considering directions for future research.


Population-specific patterns of linkage disequilibrium in the human 5q31 region.
Linkage disequilibrium across the human genome is generally lower in West Africans than Europeans. However in the 5q31 region, which is rich in immune genes, we find significantly more examples of apparent nonrecombination between distant marker pairs in West Africans. Much of this effect is due to SNPs that are absent in Europeans, possibly reflecting recent positive selection in the West African population.


Effects of soy protein and isoflavone on hepatic fatty acid synthesis and oxidation and mRNA expression of uncoupling proteins and peroxisome proliferator-activated receptor gamma in adipose tissues of rats.
Soy protein rich in isoflavones profoundly affects lipid metabolism in experimental animals. To distinguish the roles of the protein and isoflavone components of a soy protein preparation in regulating lipid metabolism, we compared the effects of diets containing methanol-washed soy protein low in isoflavone supplemented with a 0-, 0.5- and 4-g/kg isoflavone preparation on hepatic fatty acid metabolism and adipose tissue gene expression in rats. Diets containing soy protein irrespective of the isoflavone levels decreased the activities and mRNA expression of enzymes involved in hepatic fatty acid synthesis to similar levels. Methanol-washed soy protein compared to casein increased the mRNA expression of peroxisome proliferator-activated receptor (PPAR) alpha, and supplementing the soy protein diet with isoflavone further increased this parameter dose-dependently. However, methanol-washed soy protein compared to casein was totally ineffective in altering the activities and mRNA levels of enzymes involved in fatty acid oxidation. Supplementation of soy protein diets with isoflavone slightly increased these parameters. The mRNA level of uncoupling protein (UCP) 1 in brown adipose tissue was significantly increased and mRNA levels of UCP2 and 3, and PPARgamma2 tended to be higher in rats fed methanol-washed soy protein not supplemented with isoflavone than in the animals fed casein. Adding isoflavone to the soy protein diets dose-dependently increased these parameters. These results suggested that the protein rather than isoflavone component is primarily responsible for the physiological activity of soy protein rich in isoflavones in reducing hepatic lipogenesis. However, isoflavones may have a role in regulating heptic fatty acid oxidation and adipose tissue gene expression.


Metabolic fate and cardiovascular effects of arsenic in rats and rabbits chronically exposed to trivalent and pentavalent arsenic.
Male rats and female rabbits exposed for eighteen and ten months, respectively, to 50 micrograms/ml of trivalent arsenic (As III) in drinking water showed reduction of stroke volume (SV) and cardiac output (CO) and increase of vascular resistance (VR), while no cardiovascular change was observed in male rats receiving 50 micrograms/ml of pentavalent arsenic (As V) for eighteen months. The exposed animals showed specific alterations in some neurohumoral and effector mechanisms regulating cardiovascular function (CF). Elevated levels of urinary As were found in all treated groups. However, there were significant differences in the urinary levels of dimethylarsenic acid (DMA), monomethylarsenic acid (MMA) and inorganic As, which depended on both animal species and the valency state of As. Thus, As(III) was methylated to a greater extent than As(V) in rats, with less elimination of inorganic As, while rabbits had a lower capacity to methylate As and to retain As in tissues than rats. Either cardiovascular effects or metabolism of As seemed to depend on its valency state and animal species.


Alpha-synuclein and Parkinson's disease: a proteomic view.
In this review, we report how proteomic methodologies have been used to investigate cellular and animal models of Parkinson's disease (PD), with a special focus on alpha-synuclein. PD is a complex, multifactorial neurodegenerative disease affecting approximately 2% of the population over 65 years of age, pathologically characterized by alpha-synuclein intraneuronal inclusions. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis; for example, alpha-synuclein aggregation and altered dopamine homeostasis. Proteomic studies on cellular and animal models have not only confirmed existing theories on PD pathogenesis (mitochondrial impairment, oxidative stress, failure of the ubiquitine-proteasome system), but also allowed the discovery of new important common features of presymptomatic (or premotor) stages of PD, such as dysregulation of cytoskeletal proteins that could be involved at the origin of the disorder.


Time trends in first-diagnosis rates of colorectal adenomas: a 24-year population-based study.
Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population. To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma-bearing individuals detected over a 24-year period. A total of 11,027 patients were first-diagnosed with colorectal adenomas among Côte-d'Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma-bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area. Standardized diagnosis rates were 89.6/100,000 men and 50.3/100,000 women. During the period 1976-1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994-1999. The estimated proportion of adenoma-bearing individuals diagnosed during the 24-year period was 20.0% in men and 16.0% in women. Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma-bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence.


The number of limiting resources in the environment controls the temporal diversity patterns in the algal benthos.
The role of the number of limiting resources (NLR) on species richness has been the subject of much theoretical and experimental work. However, how the NLR controls temporal beta diversity and the processes of community assembly is not well understood. To address this knowledge gap, we initiated a series of laboratory microcosm experiments, exposing periphyton communities to a gradient of NLR from 0 to 3, generated by supplementation with nitrogen, phosphorus, iron, and all their combinations. We hypothesized that similarly to alpha diversity, shown to decrease with the NLR in benthic algae, temporal beta diversity would also decline due to filtering. Additionally, we predicted that the NLR would also affect turnover and community nestedness, which would show opposing responses. Indeed, as the NLR increased, temporal beta diversity decreased; turnover, indicative of competition, decreased; and nestedness, suggestive of complementarity, increased. Finally, the NLR determined the role of deterministic versus stochastic processes in community assembly, showing respectively an increasing and a decreasing trend. These results imply that the NLR has a much greater, yet still unappreciated influence on producer communities, constraining not only alpha diversity but also temporal dynamics and community assembly.


[Infected hematoma of Douglas pouch: a specific complication of the surgical excision of deep endometriosis involving the vagina].
Surgical management of deep pelvic endometriosis may be responsible for various complications, such as infected pelvic haematic collection of the Douglas pouch. The aim of this study is to describe this unfavourable outcome and to estimate its frequency in the series of women managed by our team. Retrospective study enrolling 163 women undergoing surgical removal of deep posterior endometriosis involving the vagina, from January 2008 to September 2011. We indentified women presenting with postoperative fever associated with computed tomographic findings suggesting an abscess of the Douglas pouch. Women characteristics, complication's management and outcomes were analysed in each case. Ten patients presented an inflammatory syndrome associated to hypothetical Douglas pouch abscess, revealed 6 days postoperatively on average. All women reported increasing pelvic pain, fever higher than 38.5°C, increased level of leucocytes and C reactive protein, and liquid collection of the Douglas pouch. Surgical management was carried out in nine women, revealing a pelvic collection of cloudy haematic liquid. Various bacteria were identified in six cases out of nine, suggesting liquid contamination through vagina opening. Postoperative outcome were immediately favourable. Inflammatory syndrome associated with infected haematic collection of the Douglas pouch is a postoperative complication of the surgical removal of deep endometriosis involving the posterior vagina. Surgical removal of the haematic collection allows rapid and definitive favourable outcomes.


A case of metastatic renal cell carcinoma successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy.
Combination therapy using immuno-oncology drugs with tyrosine kinase inhibitors is increasingly important in the therapeutic strategy for metastatic renal cell carcinomas. Here, we report a case of metastatic renal cell carcinoma that was successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy. A 49-year-old man was referred to our hospital with a diagnosis of advanced right kidney cancer with multiple lung metastases (cT3aN0M1). The size of the primary tumor was so huge that it exceeded 20 cm in diameter, pushing the liver and intestines to the left. After administration of lenvatinib and pembrolizumab combination as first-line treatment, all the metastatic lung lesions disappeared, and the primary lesion shrank significantly. Robot-assisted radical nephrectomy was successfully performed, resulting in complete surgical remission. Deferred cytoreductive nephrectomy following a lenvatinib plus pembrolizumab combination is a useful therapeutic strategy for achieving complete remission of metastatic renal cell carcinomas.


Afferent influences on the development of the brain stem auditory nuclei of the chicken: otocyst ablation.
The effects of embryonic deafferentation on the morphological development of the avian cochlear nuclei, n. angularis (NA) and n. magnocellularis (NM), were investigated. The right otocyst was surgically removed from chick embryos at 55 to 60 hours of incubation and the subsequent development of total volume, neuron number, and neuron cross-sectional area were studied with quantitative methods in animals sacrificed at 2-day intervals between embryonic days 9 and 19 and at 28 days posthatching. The development of NA and NM is severely affected by otocyst ablation. Between embryonic days 9 and 19, a large group of NA neurons in the medioventral portion of the nucleus on the operated side moves to an ectopic ventromedial position, while the remainder of this nucleus stays in its normal dorsolateral position. Beginning about day 13 of incubation, the normal increase in the volume of NA and the size of its neurons becomes progressively retarded and 40% of its neurons are lost. The growth of NM is also retarded after day 11 of incubation and the growth of mean neuron size is retarded after day 15. There is a 30% loss of neurons in NM which begins after embryonic day 11. The results indicate the primary cochlear fibers make a critical contribution to the growth and maintenance of their target neurons. The absence of this facilitative influence following otocyst ablation becomes apparent just at the time synapses would normally be formed between the the primary auditory afferents and the brain stem auditory neurons. The abnormal movement of neurons in nucleus angularis to an ectopic position after otocyst ablation suggests that primary auditory afferents may serve to stabilize the position of their target cells within the developing brain.


AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells.
The intestinal epithelium plays a central role in immune homeostasis in the intestine. AhR, a ligand-activated transcription factor, plays an important role in diverse physiological processes. The intestines are exposed to various exogenous and endogenous AhR ligands. Thus, AhR may regulate the intestinal homeostasis, directly acting on the development of intestinal epithelial cells (IEC). In this study, we demonstrated that 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited the in vitro development of mouse intestinal organoids. The number of Paneth cells in the small intestine and the depth of crypts of the small and large intestines were reduced in mice administrated with FICZ. Immunohistochemical and flow cytometric assays revealed that AhR was highly expressed in Lgr5(+) stem cells. FICZ inhibited Wnt signaling lowering the level of β-catenin protein. Gene expression analyses demonstrated that FICZ increased expression of Lgr5, Math1, BMP4, and Indian Hedgehog while inhibiting that of Lgr4.


Methotrexate metabolism by bone marrow cells from patients with leukemia.
Bone marrow cells from children with leukemia in remission and lymphoblasts and myeloblasts from children with early and late-stage leukemia all accumulated methotrexate during short-term culture and converted it to poly-gamma-glutamyl derivatives. This metabolism was time and dose-dependent. Leukemia cells from two patients with chronic myelocytic leukemia also synthesized methotrexate polyglutamates. Patients varied one from another in the quantity of total non-exchangeable methotrexate and methotrexate polyglutamates present in cells, but highest levels of each of these were seen in late acute lymphoblastic leukemia and in acute myeloblastic leukemia. Co-incubation of leukemic cells with both methotrexate and a ten-fold excess of folinic acid decreased accumulation and polyglutamylation of methotrexate to the same extent as achieved by reducing methotrexate concentration ten-fold. Co-incubation with methotrexate and a ten-fold excess of vincristine did not increase total cell methotrexate and methotrexate polyglutamates in leukemic cells in culture. Such an increase had been anticipated from earlier studies with other cells. Indeed, levels of methotrexate and its derivatives were modestly reduced.


Acquisition of bioluminescent trait by non-luminous organisms from luminous organisms through various origins.
Bioluminescence is a natural light emitting phenomenon that occurs due to a chemical reaction between luciferin and luciferase. It is primarily an innate and inherited trait in most terrestrial luminous organisms. However, most luminous organisms produce light in the ocean by acquiring luminous symbionts, luciferin (substrate), and/or luciferase (enzyme) through various transmission pathways. For instance, coelenterazine, a well-known luciferin, is obtained by cnidarians, crustaceans, and deep-sea fish through multi-level dietary linkages from coelenterazine producers such as ctenophores, decapods, and copepods. In contrast, some non-luminous Vibrio bacteria became bioluminescent by obtaining lux genes from luminous Vibrio species by horizontal gene transfer. Various examples detailed in this review show how non-luminescent organisms became luminescent by acquiring symbionts, dietary luciferins and luciferases, and genes. This review highlights three modes (symbiosis, ingestion, and horizontal gene transfer) that allow organisms lacking genes for autonomous bioluminescent systems to obtain the ability to produce light. In addition to bioluminescence, this manuscript discusses the acquisition of other traits such as pigments, fluorescence, toxins, and others, to infer the potential processes of acquisition.


LncRNA Blnc1 mediates the permeability and inflammatory response of cerebral hemorrhage by regulating the PPAR-γ/SIRT6/FoxO3 pathway.
Intracerebral hemorrhage (ICH) induces serious neuroinflammation and damage of blood-brain barrier. We aim to investigate the role of brown fat enriched lncRNA 1 (Blnc1) in the development of ICH in mice. An ICH model was established with autologous blood injection in C57BL/6 mice, and Blnc1 siRNA was injected intracranially. Blnc1 levels were detected and brain injury was evaluated at day 3. Primary brain microvascular endothelial cells (BMVECs) were isolated from new born mice and gain- and loss-of-function experiments were performed to investigate the role of Blnc1. Then, ICH cell model was established by treating BMVECs with oxygen and glucose deprivation (OGD) plus hemin, and Blnc1 siRNA was transfected into the cells. BMVEC functions, including viability, invasion, apoptosis, permeability and secretion of inflammatory cytokines were analyzed. Blnc1 was upregulated in perihematomal edema, hematoma and microvessel in the brain of ICH mice. Blnc1 negatively regulated viability and migration, and facilitated apoptosis, permeability and inflammatory cytokine secretion in BMVECs. Silencing Blnc1 restrained OGD plus hemin-caused reduction of BMVEC viability and migration and the induction of apoptosis, permeability and inflammation response, and suppressed PPAR-γ/SIRT6-mediated FoxO3 activation, which could be reversed by T0070907 (PPAR-γ inhibitor). Downregulation of Blnc1 ameliorated ICH-induced nerve injury, brain edema, blood brain barrier destruction, inflammation response and hematoma. Moreover, Blnc1 levels were positively correlated with PPAR-γ levels, and Blnc1 interference suppressed PPAR-γ/SIRT6-mediated activation of FoxO3 signaling in ICH mice. Silencing Blnc1 alleviated nerve injury and inflammatory response caused by ICH through activating PPAR-γ/SIRT6/FoxO3 pathway.


[Compatibility of family and profession. Survey of radiologists and medical technical personnel in clinics with different organizations].
The compatibility of family and profession is especially difficult for employees in medical professions because of shift work and overtime. It seems that in the future women are going to represent the majority of medical professionals in Germany. Hence, with the forthcoming lack of physicians in Germany social aspects will also play a greater role in the choice of the place of employment. Therefore a statistical survey was made among employees on how they judge the compatibility of family and job and what they would like to improve. From autumn 2009 until spring 2010 a total of 115 questionnaires were distributed to 8 different academic radiology departments. The anonymous questionnaire with partially open, partially graded questions and partially multiple answer questions was designed with the help of an expert for statistics and analytics and included questions about the employment and family situation, plans for the future, requested flexible working hours and childcare models, as well as ideas for improvement. Of the questionnaires 87 were analyzed with a specially designed access database using, for example descriptive statistics and histogram analyses. Of the interviewees 68% were female and 31% were male (1% not significant n.s.), 46% had children and 49% were childless (5% n.s.), 63% were medical doctors, 33% radiographers (3% other) and 82% worked full-time. Of the male respondents with children 42% indicated that their spouse was at home, 18% of female respondents with children indicated that their spouse was at home and only mothers worked part-time. Of the male respondents 73% would like to take parental leave, 44% of all respondents (70% of the male respondents and 34% of the female respondents) agreed that radiology is more compatible with family than other medical disciplines and 87% would like to have a childcare possibility in close proximity to the working place. In most of the families the classic role model prevails, although women are well-educated and men also set a high value on the compatibility of family and profession and would like to take parental leave and work flexible working hours. This is a chance especially for radiology.


Combined use of complement and anti-immunoglobulin in an enhanced neutralization assay for antibodies to varicella-zoster virus.
An enhanced neutralization assay was developed to permit the sensitive, specific, and reproducible measurement of antibodies to varicella-zoster virus (VZV). Optimal neutralization was achieved using a combination of guinea pig complement (C') and rabbit anti-human IgG. This provided 625-, 160- and 13- to 64-fold increases in dilution endpoints of human post-zoster serum, varicella-zoster immune globulin and representative sera from recipients of live attenuated varicella vaccine, respectively, above those measured in the absence of C' and anti-IgG. The specificity of the assay was shown by the absorption of serum neutralization capacity with VZV-specific antigen and the lack of concordance between antibody titers to VZV with those to either herpes simplex virus type-2 or cytomegalovirus. The antibody status of recipients of live attenuated varicella vaccine was established from the amount of neutralizing activity produced at a single optimal serum dilution.


World Assumptions as a measure of meaning in rural road crash victims.
To explore the effect of experiencing a road crash on aspects of psychological meaning. A 12-month repeated measures prospective design was used. Data were collected from admissions to a hospital in central Victoria. Seventy-two injured road crash victims took part in the study. Three measures of psychological trauma and the World Assumptions Scale. World Assumptions Scale scores did not change significantly over the year, despite improvements in other trauma scores. This study does shed some light on the psychological effects of road trauma, but further research is needed to create more sophisticated measures.


Bariatric Surgery and Solid-Organ Transplantation.
Morbid obesity and being overweight are a growing problem worldwide. They also affect patients with end-stage solid-organ disease and patients after transplant. Bariatric surgery is the most effective available weight loss procedure. Bariatric surgery can be helpful for the treatment of some conditions, such as nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, which may lead to transplant, and weight loss can improve or even reverse them. In other cases, morbid obesity is a limitation to accessing a transplant program, so bariatric surgery can serve as a conduit to transplant. After transplant, obesity and obesity-related comorbidities can be a significant health problem that may be treated, as in patients without a transplant, with bariatric surgery. There are some specific conditions and issues to be considered in patients with end-stage solid-organ disease who are candidates for bariatric surgery, such as increased morbidity and mortality. After transplant, immunosuppressant regimens and technical limitations may be also significant.


Genetic diversity and multiplicity of infection of Plasmodium falciparum isolates from Kolkata, West Bengal, India.
The study of genetic diversity of Plasmodium falciparum is necessary to understand the distribution and dynamics of parasite populations. The genetic diversity of P. falciparum merozoite surface protein-1 and 2 has been extensively studied from different parts of world. However, limited data are available from India. This study was aimed to determine the genetic diversity and multiplicity of infection (MOI) of P. falciparum population in Kolkata, West Bengal, India. A total of 80day-zero blood samples from Kolkata were collected during a therapeutic efficacy study in 2008-2009. DNA was extracted; allelic frequency and diversity were investigated by PCR-genotyping method for msp1 and msp2 gene and fragment sizing was done by Bio-Rad Gel-Doc system using Image Lab (version 4.1) software. P. falciparum msp1 and msp2 markers were highly polymorphic with low allele frequencies. In Kolkata, 27 msp1 different genotypes (including 11of K1, 6 of MAD20 and 10 of Ro33 allelic families) and 30 different msp2 genotypes (of which 17 and 13 belonged to the FC27 and 3D7 allelic families, respectively) were recorded. The majority of these genotypes occurred at a frequency below 10%. The mean MOI for msp1 and msp2 gene were 2.05 and 3.72, respectively. The P. falciparum population of Kolkata was genetically diverse. As the frequencies of most of the msp1 and msp2 alleles were low, the probability of new infection with genotype identical to that in pretreatment infection was very rare. This information will serve as baseline data for evaluation of malaria control interventions as well as for monitoring the parasite population structure.


Covalent attachment of insulin to the outer surface of liposomes.
We describe a method for covalent binding of insulin to the outer surface of multilamellar liposomes loaded with spin label. Encapsulation of the label Tempocholine-nitroxide within the aqueous phases of liposomes is controlled by Electron Spin Resonance. The binding of insulin is performed using the Carlsson's heterobifunctional reagent: N-succinimidyl 3-(2-pyridyldithio) propionate. The coupling method results in efficient attachment of 2. 64.10(-4) mole of insulin per mole of phospholipid; the integrity of these vesicles is not modified as confirmed by spin resonance analysis. Moreover, the liposome-coupled insulin retains its antigenic specificity as shown by radioimmunoassays.


Bisphenol S exposure modulate macrophage phenotype as defined by cytokines profiling, global metabolomics and lipidomics analysis.
As an important structural analogue of bisphenol A (BPA), bisphenol S (BPS) has been used as alternatives to BPA in industrialized production. However, the immunotoxicity of BPS remains poorly understood. As a critical model in inflammatory responses, macrophages are used to explore the immunotoxic potential and mechanisms of BPS at environmentally relevant concentrations in our study. Here, we are combining molecular toxicology and mass spectrometry (MS)-based global metabolomics and lipidomics study together to estimate the variation of cytokines profiling and metabolism characteristic following BPS exposure. Our results demonstrated that BPS exposure induced pro-inflammatory phenotype by activating the immuno-related cytokines which include TNF-α, IL-1β and IL-6, modulating metabolic pathways which include glycolytic, glutathione (GSH), sphingomyelin (SM)-ceramide (Cer), glycerophospholipids (GPs) and glycerolipids (GLs). These toxicological mechanisms are providing us with a deeper understanding of the critical role of metabolites and lipids reprogramming in immunotoxicity of BPS.


Polysaccharide extraction from Abelmoschus esculentus: optimization by response surface methodology.
Crude polysaccharide extraction from the Iranian Abelmoschus esculentus was performed using water decoction. Response surface methodology (RSM), based on a five level, four variable central composite rotatable design (CCRD), was employed to obtain the best possible combination of extraction time (X1: 0.5-6.5 h), extraction temperature (X2: 80-100 °C), number of extraction (X3: 1-5), and water to the raw material ratio (X4: 4-28) for maximum polysaccharide extraction. The experimental data obtained were fitted to a second-order polynomial equation using multiple regression analysis and also analyzed by appropriate statistical methods (ANOVA). The optimum extraction conditions were as follows: extraction time of 4.94 h, extraction temperature of 94.97 °C, number of extraction of 4, and the ratio of water to raw material of 21.74. Under these conditions, the experimental yield was 16.895±0.29%, which is well in close agreement with the value predicted by the model 16.916%.


Anogenital Distance in Healthy Infants: Method-, Age- and Sex-related Reference Ranges.
The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes in AGD in children is scarce. To create age-, sex-, and method-related reference ranges of AGD in healthy boys and girls aged 0-24 months, to assess the age-related changes in AGD and to evaluate the 2 predominantly used methods of AGD measurement. The International AGD consortium comprising 4 centers compiled data from 1 cross-sectional and 3 longitudinal cohort studies (clinicaltrials.gov [NCT02497209]). All data were collected from population-based studies, recruiting from 4 maternity or obstetric centers (United States, Cambridge [United Kingdom], Odense, and Copenhagen [Denmark]). This study included a total of 3705 healthy, mainly Caucasian children aged 0-24 months on whom 7295 measurements were recorded. AGDAS (ano-scrotal), AGDAF (ano-fourchette), AGDAP (ano-penile), AGDAC (ano-clitoral), AGD body size indices (weight, body mass index [BMI], body surface area, and length), and intra- and interobserver biases. We created age-specific reference ranges by centers. We found that AGD increased from birth to 6 months of age and thereafter reached a plateau. Changes in AGD/BMI during the first year of life were minor (0-6% and 0-11% in boys and girls, respectively). Reference ranges for AGD can be used in future epidemiological research and may be utilized clinically to evaluate prenatal androgen action in differences-in-sex-development patients. The increase in AGD during the first year of life was age-related, while AGD/BMI was fairly stable. The TIDES and Cambridge methods were equally reproducible.


Unusual mucopolysaccharide disorder with corneal and scleral involvement.
A 68-year-old man and a 66-year-old woman had diffuse corneal stromal deposits that stained with alcian blue and colloidal iron but did not react with periodic acid-Schiff stain and lipid stains. Similar deposits were found within postmortem sclera in one case, but not in other ocular or extraocular tissues. The abnormal material was sensitive to testicular hyaluronidase and chondroitinase. The material reacted with monoclonal antibody 9-A-2 after digestion by chondroitinase AC in one case and ABC in both cases, which is consistent with the identification of the glycosaminoglycans chondroitin 4-sulfate and dermatan sulfate. Electron microscopic examination of the cornea in both cases disclosed granular material in vacuoles dispersed extracellularly and, rarely, in keratocytes. Results of blood and skin fibroblast enzyme assays for clinically relevant mucopolysaccharidoses and mucolipidoses were normal in both patients, and there were no somatic abnormalities suggesting a storage disease.


Readmission Rates of Patients with Schizophrenia Treated with Depot Antipsychotics versus Oral Antipsychotics in a Community Hospital.
This is a pilot study comparing the 30 and 60 day relapse rates for schizophrenic patients treated with long-acting injectable antipsychotics versus traditional oral antipsychotics in a community hospital setting. This is a retrospective cohort study and medical records were reviewed to gather data involving readmission rates. We analyzed the data using relative risk (RR) for the 30 days and 60 days after patient discharge from the behavioral health unit of a community hospital.


Comparison of laparoscopic and mini incision open donor nephrectomy: single blind, randomised controlled clinical trial.
To determine the best approach for live donor nephrectomy to minimise discomfort to the donor and to provide good graft function. Single blind, randomised controlled trial. Two university medical centres, the Netherlands. 100 living kidney donors. Participants were randomly assigned to either laparoscopic donor nephrectomy or to mini incision muscle splitting open donor nephrectomy. The primary outcome was physical fatigue using the multidimensional fatigue inventory 20 (MFI-20). Secondary outcomes were physical function using the SF-36, hospital stay after surgery, pain, operating times, recipient graft function, and graft survival. Conversions did not occur. Compared with mini incision open donor nephrectomy, laparoscopic donor nephrectomy resulted in longer skin to skin time (median 221 v 164 minutes, P < 0.001), longer warm ischaemia time (6 v 3 minutes, P < 0.001), less blood loss (100 v 240 ml, P < 0.001), and a similar number of complications (intraoperatively 12% v 6%, P = 0.49, postoperatively both 6%). After laparoscopic nephrectomy, donors required less morphine (16 v 25 mg, P = 0.005) and shorter hospital stay (3 v 4 days, P = 0.003). During one year's follow-up mean physical fatigue was less (difference - 1.3, 95% confidence interval - 2.4 to - 0.1) and physical function was better (difference 6.2, 2.0 to 10.3) after laparoscopic nephrectomy. Function of the graft and graft survival rate of the recipient at one year censored for death did not differ (100% after laparoscopic nephrectomy and 98% after open nephrectomy). Laparoscopic donor nephrectomy results in a better quality of life compared with mini incision open donor nephrectomy but equal safety and graft function.


Neural Reanimation Advances and New Technologies.
Facial paralysis can have a profound effect on the patient from both an aesthetic and functional point of view. Just as there are numerous etiologies of facial paresis, there are as many therapeutic options and variations of these options. The purpose of this article was to review the most current surgical options for neural reanimation of a damaged facial nerve, including recent advances in nerve repair, conduit technology, and nerve transfers, as well as emerging technology in translational research with biomedical engineering and tissue engineering.


Vitamin D receptor and binding protein genes variants in patients with migraine.
Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25-hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single-nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case-control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. We genotyped 290 patients diagnosed with migraine and 300 age-matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies.


[Rifampicin-protamine sulfate solution in dialysis patients].
Bacteria from the exit site of dialysis catheter can grow into microcolonies in biofilm. It has been hypothesized that rifampin-protamine combination may have an effect on the biofilm. In hemodialysis centre a combination of rifampin mixed with protamine is commonly used in some centre in order to prevent catheter related infections in hemodialysis patients. Therefore, a pharmaceutical assessment of the rifampin-protamine mixture is clearly mandatory. The aim of this study is to evaluate the stability and the sterility of the rifampin-protamine solution. Five milliliters of protamine (10 mg) was mixed with 10 mL of Rifampin (600 mg). The solution was kept at -20 degrees C temperature for two weeks and subsequently at 4 degrees C for two additional weeks. Stability and sterility were evaluated the first day and two weeks, three weeks and four weeks after the preparation. Concentration of rifampin in the solution was assessed by HPLC. Protamine concentration was evaluated by the effect of the solution on the heparin activity of a heparinized plasma. The solution was cultured on broth media and mannitol agar plate. Areas under curve of rifampin were similar between the four different evaluations. The effect of the solution on the heparin activity was comparable at the four different evaluations. Our results demonstrate the stability and the compatibility of the solution. However, there was biological interference between broth media and the solution. It was, therefore, impossible to make any conclusion after broth culture. Culture on mannitol agar plate did not show any microbiological growth. Based on this finding, we recommend preparing the rifampin-protamine combination in individual conditioning at the time of the utilization.


Pharmacological profile of the rat intestinal crypt peptide YY receptor vs. the recombinant rat Y5 receptor.
Peptide YY and neuropeptide Y have potent antisecretory effects in rat small intestine. Scatchard analysis of [125I]peptide YY binding revealed a 10-fold higher concentration of receptors in rat jejunal crypt cells than in villus cells and no detectable receptors in colonic epithelium. Reverse transcription polymerase chain reaction analysis of neuropeptide Y Y5 receptor mRNA indicated that they are mainly expressed in rat jejunal crypts with very few or no expression in villus cells and colon epithelium, respectively. In order to determine whether neuropeptide Y Y5 receptors could represent the intestinal crypt receptor for peptide YY and neuropeptide Y, the ability of peptide YY, neuropeptide Y, pancreatic polypeptide and analogues to inhibit [125I]peptide YY binding to membrane prepared from rat crypt cells and COS-7 cells (African green monkey kidney cells) transfected with the rat neuropeptide Y Y5 receptor cDNA was tested. It appeared that several analogues displayed different inhibition constants (Ki) in the two binding assays, more especially N-alpha-acetyl-peptide YY-(22-36) which was 1200 x more potent in the crypt cell binding assay than in the recombinant neuropeptide Y Y5 receptor binding assay. These data support that the intestinal crypt peptide YY receptor is not a Y5 receptor. reserved.


Pathogenesis of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a major cause of blindness in children in developed countries. ROP, a two-phase disease, is initiated with delayed retinal vascular growth after premature birth (phase I). Insufficient vascularization of the developing retina creates hypoxia, which precipitates the release of factors stimulating new and abnormal blood vessel growth (phase II). ROP develops because of abnormalities in both oxygen-regulated and non-oxygen-regulated factors, which affect both phases of the disease. Vascular endothelial growth factor (VEGF) is an important oxygen-regulated factor that, if suppressed, inhibits normal vessel growth, but in excess, precipitates retinal neovascularization. A critical non-oxygen-regulated growth factor is insulin-like growth factor (IGF-1). Similar to VEGF, low levels of IGF-1 prevent normal vessel growth (phase I), and higher levels allow neovascularization (phase II). We found that premature infants who develop ROP have low levels of serum IGF-1 compared with age-matched infants without disease. IGF-1 is critical to normal vascular development. Low IGF-1 predicts ROP, and restoration of IGF-1 to normal levels might prevent ROP.


Pericardial parenteral nutrition infusion following acute angulation of a neonatal polyurethane central venous catheter tip.
Life threatening cardiac tamponade developed in a premature infant due to perforation of the heart by a 2F central venous catheter used to administer parenteral nutrition. Abnormal orientation of the catheter tip preceded the appearance of the pericardial effusion. Unusual angulation of the tip of central venous lines in premature infants may be an important warning sign of impending cardiac perforation and its potentially major sequelae and should therefore prompt immediate repositioning of the catheter.


Association between molar hypomineralization, genes involved in enamel development, and medication in early childhood: A preliminary study.
Molar hypomineralization (MH) is defined as a multifactorial condition, and thus, its presence may be defined by interactions between environmental and genetic factors. To evaluate the association between MH, genes involved in enamel development, and the use of medication during pregnancy in early childhood. One hundred and eighteen children, 54 with and 64 without MH, were studied. The data collected included demographics, socioeconomic data, and the medical history of mothers and children. Genomic DNA was collected from saliva. Genetic polymorphisms in ameloblastin (AMBN; rs4694075), enamelin (ENAM; rs3796704, rs7664896), and kallikrein (KLK4; rs2235091) were evaluated. These genes were analyzed by real-time polymerase chain reaction using TaqMan chemistry. The software PLINK was used to compare allele and genotype distributions of the groups and to assess the interaction between environmental variables and genotypes (p < .05). The variant allele KLK4 rs2235091 was associated with MH in some children (odds ratio [OR]: 3.75; 95% confidence interval [CI] = 1.65-7.81; p = .001). Taking medications in the first 4 years of life was also associated with MH (OR: 2.94; 95% CI = 1.02-6.04; p = .041) and specifically in association with polymorphisms in ENAM, AMBN, and KLK4 (p < .05). The use of medications during pregnancy was not associated with MH (OR: 1.37; 95% CI = 0.593-3.18; p = .458). The results of this study suggest that taking medication in the postnatal period appears to contribute to the etiology of MH in some evaluated children. There may be a possible genetic influence of polymorphisms in the KLK4 gene with this condition.


Developmental exposure to low-dose PBDE-99: tissue distribution and thyroid hormone levels.
Thyroid hormone concentrations, hepatic enzyme activities and tissue concentrations of 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99) were evaluated in Wistar rats (dams and offspring) after treatment by gavage on gestation day (GD) 6 with a single low dose of either 60 or 300 microg PBDE-99/kg body weight (bw), respectively. Tissue concentration analysis confirmed that PBDE-99 is persistent in rodents as significant amounts of the parent compound were detected in adipose tissue 37 days after exposure. The dose of 300 microg PBDE-99/kg bw reduced thyroxin (T4) concentration in dams at the beginning of lactation (post-gestational day [PGD] 1), and caused a slight reduction in T4 on PGD 22, although not statistically significant. In offspring, reduced T4 was observed only at PND 22, probably due to cumulative effects of PBDE-99 during lactation. PBDEs have been shown to reduce T4 concentrations in several studies, but this is the first study demonstrating endocrine disruption at low doses. The adipose tissue concentration of PBDE-99 measured in this study was close to those reported for PBDE-99 in non-occupationally exposed humans. In addition, we have previously reported permanent changes in the reproductive systems and locomotor activity of male and female offspring using these same dosages.


[Determination of triacontanol and octacosanol in fenglasu and fenglasu capsules by capillary gas chromatography].
The method was established for the determination of triacontanol and octacosanol in fenglasu and fenglasu capsules. The solvent was chloroform. The internal standard was hexatriacontanol. Using SIMPLCITY-1 capillary column, flame ionization detector was specified, injector temperature was 300 degrees C, and the column temperature rise by programming. [Initial temperature was 240 degrees C, maintaining 1 min and then rising the temperature (5 degrees C.min-1) to 300 degrees C for 15 min]. The flow rate of Nitrogen was 27 ml.min-1. The calibration curves were linear in the range of 0.4-1.6 mg/ml for triacontanol(r = 0.999), 0.2-0.6 mg/ml for octacosanol(r = 0.9996) respectively. The average recovery (n = 9) was 99.2% for triacontanol (RSD = 1.15%), 99.91% for octacosanol (RSD = 1.40%). The method is rapid, accurate and reliable for the quality control of fenglasu and fenglasu capsules.


Non-Hodgkin's lymphoma and skin malignancies--shared etiology?
The Stockholm-Gotland Cancer Register was used to evaluate the clinical observation that patients with non-Hodgkin's lymphoma (NHL) had an increased risk of malignant melanoma or squamous-cell carcinoma of the skin (SCCS) and vice versa. During 1958-1992, NHL was diagnosed in a total of 6,176 patients. Of these patients, 504 developed a second primary cancer of any type except NHL, compared to 301.9 expected, giving a standardized incidence ratio (SIR) of 1.7 [95% confidence interval (CI) 1.5-1.8]. The risk of SCCS and malignant melanoma in patients with NHL was 4.8 (95% CI 3.6-6.2; n = 54) and 1.7 (95% CI 0.8-3.1; n = 10), respectively. The hazard risk for a second malignancy was relatively constant over time, whereas the skin malignancies revealed the highest risks 3-10 years after initial diagnosis. Similarly, the risk of a secondary NHL was studied in patients with malignant melanoma and SCCS during the same period and found to be 1.3 (95% CI 0.8-2.1; n = 17) and 1.8 (95% CI 1.2-2.5; n = 34), respectively. The highest risk for NHL following malignant melanoma was seen 3-10 years after first diagnosis, while the highest risk following SCCS was observed 0-2 years after initial diagnosis. One of several possible explanations or the development of NHL and a skin malignancy in the same patient is an immunological defect caused by sun exposure.


Incidence of child marriage among refugees and internally displaced persons in the Middle East and South Asia: evidence from six cross-sectional surveys.
To examine incidence of child marriage among displaced and host populations in humanitarian settings. Cross-sectional surveys. Data were collected in Djibouti, Yemen, Lebanon and Iraq in the Middle East and in Bangladesh and Nepal in South Asia. Adolescent girls aged 10-19 in the six settings and age cohort comparators. Cumulative incidence of marriage by age 18. In Bangladesh and Iraq, the hazard of child marriage did not differ between internally displaced populations (IDPs) and hosts (p value=0.25 and 0.081, respectively). In Yemen, IDPs had a higher hazard of child marriage compared with hosts (p value<0.001). In Djibouti, refugees had a lower hazard of child marriage compared with hosts (p value<0.001). In pooled data, the average hazard of child marriage was significantly higher among displaced compared with host populations (adjusted HR (aHR) 1.3; 95% CI 1.04 to 1.61).In age cohort comparisons, there was no significant difference between child marriage hazard across age cohorts in Bangladesh (p value=0.446), while in Lebanon and Nepal, younger cohorts were less likely to transition to child marriage compared with older comparators (p value<0.001). Only in Yemen were younger cohorts more likely to transition to child marriage, indicating an increase in child marriage rates after conflict (p value=0.034). Pooled data showed a downward trend, where younger age cohorts had, on average, a lower hazard of child marriage compared with older cohorts (aHR 0.36; 95% CI 0.29 to 0.4). We did not find conclusive evidence that humanitarian crises are associated with universal increases in child marriage rates. Our findings indicate that decision-making about investments in child marriage prevention and response must be attuned to the local context and grounded in data on past and current trends in child marriage among communities impacted by crisis.


Soil translocation by pocket gophers in a Mima moundfield.
We measured soil translocation due to the tunneling of valley pocket gophers (Thomomys bottae) in a Mima moundfield at Miramar Mounds National Landmark, San Diego, California, from December, 1984 through December, 1985. We placed 1-l soil plugs containing 20 11-g iron pellets into pocket gopher tunnels at locations between mound tops and points about one mound radius beyond mound edges. After about 4-10 d, sites to which the marker-containing soil had been translocated were located with a metal detector and the horizontal and vertical displacements measured. Between 1 October and 15 May (the cooler, wetter portion of the year), pocket gophers removed an average of 63% of the experimental plugs and moved an average of 38% of the markers that we recovered. From 15 May through 1 October (the hotter, drier portion of the year), only 32% of plugs were cleared and 12% of the recovered markers were moved. On average, markers that were moved were displaced 41 cm moundward and 4.9 cm upward in elevation. The intensity of moundward translocation increased with distance from the mound center. At a distance of 0.5-1.0 mound radius beyond the edge of the mound, the moundward translocation tendency averaged 71 cm. The intensity of moundward translocation was also inversely related to maximum mound height. These observations provide strong support for the fossorial rodent hypothesis of Mima mound origin, and constitute a first step in development of a mathematical model of mound formation.


Valorization of renewable resources to functional oligosaccharides: Recent trends and future prospective.
Lignocellulosic wastes have the ability to be transformed into oligosaccharides and other value-added products. The synthesis of oligosaccharides from renewable sources bestow to growing bioeconomies. Oligosaccharides are synthesized chemically or biologically from agricultural residues. These oligosaccharides are functional food supplements that have a positive impact on humans and livestock. Non-digestible oligosaccharides, refered as prebiotics are beneficial for the colonic microbiota inhabiting the f the digestive system. These microbiota plays a crucial role in stimulating the host immune system and other physiological responses. The commonly known prebiotics, galactooligosaccharides (GOS), xylooligosaccharides (XOS), fructooligosaccharides (FOS), mannanooligosaccharides (MOS), and isomaltooligosaccharides (IOS) are synthesized either through enzymatic or whole cell-mediated approaches using natural or agricultural waste substrates. This review focusses on recent advancements in biological processes, for the synthesis of oligosaccharides using renewable resources (lignocellulosic substrates) for sustainable circular bioeconomy. The work also addresses the limitations associated with the processes and commercialization of the products.


Biopolymer Micro/Nanogel Particles as Smart Drug Delivery and Theranostic Systems.
In recent years, micro/nanogels have become an important topic of interdisciplinary research, especially in the fields of polymer chemistry and material science, with a focus on their use in drug delivery applications [...].