Gastric Syphilis Mimicking Lymphoma: A Case Report.
Gastric syphilis is a rare manifestation of syphilis that occurs in about 1% of cases and is often overlooked due to its non-specific signs and symptoms. We report a case of a 28-year-old Chinese woman who presented with epigastric pain, nausea, vomiting, hematemesis, alopecia, and weight loss. She tested positive for Helicobacter pylori (H. pylori), with rapid plasma reagin (RPR) and Treponema pallidum particle assay (TPPA) tests showing titers of 1:128 and 1:320, respectively. CT imaging revealed thickening of the gastric wall, exudation around the antrum, and multiple lymphadenopathies. Gastroscopy showed multiple irregular ulcers, which resembled lymphoma. However, biopsy results did not support the presence of lymphoma, but immunohistochemistry showed an abundance of syphilis spirochetes in the mucosal lamina propria and glands. This led to a diagnosis of gastric syphilis. The patient received standard treatment for syphilis as well as anti-H. pylori therapy, and her symptoms and endoscopic findings gradually improved and eventually resolved. We hope that this case report can provide valuable insights into the diagnosis and management of gastric syphilis, which can mimic other diseases like lymphoma.


Severe Polyethylene Wear Requiring Revision Total Hip Arthroplasty in Three Dogs.
To describe the occurrence of severe polyethylene wear of the acetabular component in 3 dogs that ultimately led to implant failure, and to report the outcome of revision of total hip arthroplasty (THA) in these cases. Case report Dogs (n=3). Three dogs with hip dysplasia underwent routine THA before 2 years of age. All dogs became acutely lame 4-5 years after THA. Radiographs revealed acetabular cup wear in all cases, shell fragmentation in 2 cases, and additional stem failure in 1 case. All dogs underwent successful revision surgery, during which severe polyethylene wear and metallosis was observed. Revision surgery provided an excellent clinical outcome in all dogs from 10 months to 4 years post revision. Polyethylene wear and implant failure may be a significant long-term complication of THA not previously recognized, which may be especially true when placed at an early age in a large breed, active dog, or in a dog with significant morbidity associated with other limbs. A successful revision was achieved in all 3 dogs. Additional investigation is warranted to document the risk factors associated with severe polyethylene wear in canine THA.


Prevalence and patterns of gender-based violence and revictimization among women attending antenatal clinics in Soweto, South Africa.
Gender-based violence is a key health risk for women globally and in South Africa. The authors analyzed data from 1,395 interviews with women attending antenatal clinics in Soweto, South Africa, between November 2001 and April 2002 to estimate the prevalence of physical/sexual partner violence (55.5%), adult sexual assault by nonpartners (7.9%), child sexual assault (8.0%), and forced first intercourse (7.3%). Age at first experience of each type of violence was modeled by the Kaplan-Meier method, and Cox hazard models with time-varying covariates were used to explore whether child sexual assault and forced first intercourse were associated with risk of violent revictimization in adulthood. Child sexual assault was associated with increased risk of physical and/or sexual partner violence (risk ratio = 2.43, 95% confidence interval: 1.93, 3.06) and with adult sexual assault by a nonpartner (risk ratio = 2.33, 95% confidence interval: 1.40, 3.89). Forced first intercourse was associated with increased risk of physical and/or sexual partner violence (risk ratio = 2.64, 95% confidence interval: 2.07, 3.38) and nonsignificantly with adult sexual assault by a nonpartner (risk ratio = 2.14, 95% confidence interval: 0.92, 4.98). This study confirms the need for increased attention by the public health community to primary and secondary prevention of gender-based violence, with a specific need to reduce risk among South African adolescents.


Higher cost of single incision laparoscopic cholecystectomy due to longer operating time. A study of opportunity cost based on meta-analysis.
We aimed to calculate the opportunity cost of the operating time to demonstrate that single incision laparoscopic cholecystectomy (SILC) is more expensive than classic laparoscopic cholecystectomy (CLC). We identified studies comparing use of both techniques during the period 2008-2016, and to calculate the opportunity cost, we performed another search in the same period of time with an economic evaluation of classic laparoscopy. We performed a meta-analysis of the items selected in the first review considering the cost of surgery and surgical time, and we analyzed their differences. We subsequently calculated the opportunity cost of these time differences based on the design of a cost/time variable using the data from the second literature review. Twenty-seven articles were selected from the first review: 26 for operating time (3.138 patients) and 3 for the cost of surgery (831 patients), and 3 articles from the second review. Both echniques have similar operating costs. Single incision laparoscopy surgery takes longer (16.90min) to perform (p <0.00001) and this difference represents an opportunity cost of 755.97 € (cost/time unit factor of 44.73 €/min). SILC costs the same as CLC, but the surgery takes longer to perform, and this difference involves an opportunity cost that increases the total cost of SILC. The value of the opportunity cost of the operating time can vary the total cost of a surgical technique and it should be included in the economic evaluation to support the decision to adopt a new surgical technique.


Molecular determinants of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding to transient receptor potential V1 (TRPV1) channels.
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate. Utilizing a combined approach of mutagenesis and molecular modeling, we identified a PI(4,5)P2 binding site located between the TRP box and the S4-S5 linker. At this site, PI(4,5)P2 interacts with the amino acid residues Arg-575 and Arg-579 in the S4-S5 linker and with Lys-694 in the TRP box. We confirmed that PI(4,5)P2 behaves as a channel agonist and found that Arg-575, Arg-579, and Lys-694 mutations to alanine reduce PI(4,5)P2 binding affinity. Additionally, in silico mutations R575A, R579A, and K694A showed that the reduction in binding affinity results from the delocalization of PI(4,5)P2 in the binding pocket. Molecular dynamics simulations indicate that PI(4,5)P2 binding induces conformational rearrangements of the structure formed by S6 and the TRP domain, which cause an opening of the lower TRPV1 channel gate.


Wischnewsky Spots in Fatal Hypothermia: Case Report.
69-year-old male was found dead at the roadside in October month, death was declared suspicious by local prosecutor and autopsy was mandated. At autopsy, a large number of dark brown colored, ovalshaped lesions ranging from 1-15 mm under the mucosa defined as Wischnewsky spots, when stomach was dissected were observed. For the formation mechanism of Wischnewsky spots, there has no definite conclusions; more studies are needed on a case series.


Estradiol-binding proteins from mycelial and yeast-form cultures of Paracoccidioides brasiliensis.
Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, causes disease much more frequently in men than it does in women, suggesting that the hormonal milieu of the host might influence P. brasiliensis pathogenicity. We recently demonstrated that cytosol from yeast cultures of P. brasiliensis contains a high-affinity, low-capacity, tritiated 17 beta-estradiol [( 3H]estradiol)-binding protein. Estradiol and, to a lesser degree, diethylstilbestrol (DES), inhibited the transformation of P. brasiliensis cultures from the mycelial to the yeast form, an event critical to the establishment of infection. Our current studies demonstrated a somewhat higher affinity (apparent dissociation constant [Kd], approximately equal to 6 to 12 nM) of the estrogen-binding protein for [3H]estradiol than was previously described for yeast cytosol. The presence of both high- and low-affinity estrogen-binding sites in yeast-form P. brasiliensis cytosol was detected after warming the cytosol to 37 degrees C. The high-affinity protein was labile to further heating (56 degrees C), although the low-affinity protein was stable. Additional experiments demonstrated the presence of an estrogen-binding protein in cytosol prepared from mycelial-form P. brasiliensis. This estrogen-binding protein had a slightly lower affinity for [3H]estradiol (Kd approximately equal to 13 nM), and its cytosol contained somewhat fewer binding sites (approximately equal to 78 fmol/mg of protein) than did yeast-form P. brasiliensis cytosol. Of particular interest was the finding that DES, a weak competitor for [3H]estradiol binding in yeast cytosol, displaced [3H]estradiol from the mycelial-form binding moiety. DES had a 50- to 100-fold-lower affinity for the [3H]estradiol-binding protein than did estradiol, consistent with its lower bioactivity in the mycelial-to-yeast-form transformation studies. The current results lend further support to our hypothesis that endogenous estrogens in the host, acting through the cytosol binding protein in the fungus, inhibit mycelial-to-yeast-form transformation, thus explaining the resistance of women to paracoccidioidomycosis.


Blood cardiac troponin in toxic myocardial injury: archetype of a translational safety biomarker.
A translational safety biomarker for toxic myocardial injury is needed in drug discovery and development. This need reflects the increasing recognition of occurrence of cardiotoxicities, prior lack of preclinical blood biomarkers for toxic cardiac injury, introduction of troponin as a biomarker, and regulatory and industry drivers. Cardiac troponin is considered the gold-standard biomarker in humans for cardiac injury due to ischemic injury and drug toxicity. It has been demonstrated to correlate highly with histopathological extent of injury, degree of impairment of cardiac function, and prognosis. Numerous studies have now clearly demonstrated that both cardiac troponin T and cardiac troponin I are sensitive and specific biomarkers of cardiac injury in laboratory animals. Their use is highly recommended for incorporation into preclinical drug-safety studies, especially whenever there is any history of cardiac effect in prior studies with a compound of the same or similar chemical or pharmacological class. The main caveats with respect to cross-species use of specific cardiac troponin assays are the need for species-specific validation, definition of cut-offs based on relevant assessments of imprecision and reference ranges or concurrent controls, and knowledge of the species-dependent kinetics of release into, and clearance from, the blood. Future development of high-sensitivity assays should determine whether minimal increases below a threshold concentration of troponin might reflect reversible myocardial effects.


Whole-body dose evaluation with an adaptive treatment planning system for boron neutron capture therapy.
Dose evaluation for out-of-field organs during radiotherapy has gained interest in recent years. A team led by University of Tsukuba is currently implementing a project for advancing boron neutron capture therapy (BNCT), along with a radiation treatment planning system (RTPS). In this study, the authors used the RTPS (the 'Tsukuba-Plan') to evaluate the dose to out-of-field organs during BNCT. Computed tomography images of a whole-body phantom were imported into the RTPS, and a voxel model was constructed for the Monte Carlo calculations, which used the Particle and Heavy Ion Transport Code System. The results indicate that the thoracoabdominal organ dose during BNCT for a brain tumour and maxillary sinus tumour was 50-360 and 120-1160 mGy-Eq, respectively. These calculations required ∼29.6 h of computational time. This system can evaluate the out-of-field organ dose for BNCT irradiation during treatment planning with patient-specific irradiation conditions.


Identification and characterization of Deoxyribonuclease II in planarian Dugesia japonica.
Deoxyribonuclease II (DNase II) has been found to regulate inflammation, autoimmunity and apoptosis in vertebrates and invertebrates. The strong capacity of degrading DNA makes DNase II play an important role in the immune process. Planarian has become one of the model references due to its strong immune system, the environment they live makes planarians face the threat of microorganisms and injury, the strong immune system can protect planarians from the threat of bacterial and infection. In this study, we found that there was DNase in the lysis buffer of planarians, then we acquired the sequence of DjDN2s (Dugesia japonica DNase2s) and confirmed the DjDN2s were conserved DNase IIs. The predicted structure showed the active sites and binding patterns of DjDN2s. Whole-mount in situ hybridization results showed DjDN2s mainly expressed in immune organs. Quantitative real-time PCR revealed that the expression of DjDN2s upregulated in varying degrees when got hurt and challenged with bacteria, and the knockdown of DjDN2s led to the slower repair of wound. The recombinant phages which take DjDN2 also had the ability to degrade DNA and clear young biofilm of Gram-negative bacteria. Collectively, DNase II of planarian might play a role in the antimicrobial response and wound-induced response.


Birth Weight in Different Etiologies of Disorders of Sex Development.
It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the International Disorders of Sex Development (I-DSD) Registry (www.i-dsd). BW standard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR) mutation-positive cases in disorders of androgen action groups] were similar to normal children with the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. BW dimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinization are more frequently associated with fetal growth restriction, SGA, and concomitant conditions.


Association Between Body Composition and Bone Mineral Density in Men on Hemodialysis.
Studies have revealed complex interactions between bone and fat, however there are few studies about this crosstalk in patients with chronic kidney disease. This study investigated possible relationship between bone mineral density (BMD) and body composition in patients who underwent hemodialysis. Twenty patients were enrolled in a cross-sectional study (47.0 [42.3-56.8] years, body mass index 26.0 ± 4.2 kg/m, dialysis vintage of 48.5 [26.7-95.7] months). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. Leptin and parathormone levels were analyzed using Multiplex kits (R&D System Inc). Low bone mass in the femoral neck was reported in 54.8% of patients. Total BMD and total T-score were positively correlated with lean mass (r = 0.46, P = 0.04; r = 0.47, P = 0.04, respectively), but not with leptin or body fat mass. In conclusion, lean body mass is probably important to maintain bone health in male patients who underwent hemodialysis.


Single and multiple CH (calponin homology) domain containing multidomain proteins in Arabidopsis and Saccharomyces: an inventory.
Genes for individual domains such as CH, lim, ankyrin, PH and RhoGAP, IQ motif, Ig_FLMN, spectrin, and EF hand probably existed in early evolution before there were plants, fungi or animals so that when we examine multidomain proteins in Arabidopsis, Saccharomyces, Dictyostelium or Homo Sapiens we encounter various combinations of such domains. While all of these four species express Fimbrin and EB1, the lists of CH containing multidomain proteins, however, differ in number and in type for each of them. There was no further great increase in the number of new single domain proteins. Still many new multidomain genes evolved--but far more so in metazoans--than in plants or fungi. In both plants and fungi only singlet CH domains but no doublets (other than those forming the Fimbrin quadruplet) were incorporated. That is in these two branches one finds no alpha actinin, dystrophin or filamin even though the individual building blocks (i.e. domains such as spectrin or IG-FLMN) were available in Arabidopsis. Possibly transposons create new chimeric multidomain genes by mixing and matching genes or gene fragments.


Clinical correlates of sudden auditory-vestibular loss in a cochlear implant patient.
The precise electrophysiologic mechanism for sudden sensorineural auditory-vestibular loss has yet to be defined. No human models exist for this idiopathic phenomenon. A 67-year-old cochlear implant (CI) patient experienced what could be termed a "typical" acute sudden auditory-vestibular loss. Vestibular and CI electrical psychophysical changes were monitored over a 22-month period. Once the acute vestibular problems diminished, CI electrical parameters returned to near pre-episode levels. Some improvement occurred in rotational chair phase lag and asymmetry. While improving, platform posturography continued to show difficulty performing sensory organization tests V and VI. These clinical findings may imply that ganglion cell and neuronal population are responsible for the auditory findings in sudden auditory-vestibular loss. Secondly, a CI patient may serve as an ideal human model for further study of this phenomenon, should it occur.


Symptom Perception, Evaluation, Response to Symptom, and Delayed Care Seeking in Patients With Acute Heart Failure: An Observational Study.
Exacerbation of heart failure (HF) requires early intervention to prevent hospital admission and to reduce mortality. Early care seeking requires that patients perceive symptoms, accurately evaluate perceived symptoms, and respond appropriately. How perception, evaluation, and response to symptoms are associated with delay in seeking care for worsening symptoms has rarely been studied. The aims of this study were to investigate the associations of perception of symptoms, evaluation of symptoms, and response to symptoms with delayed care seeking in patients with HF and to identify factors associated with delayed care seeking. Patients admitted for acute exacerbation of HF were enrolled in this cross-sectional observational study. We used structured interviews, questionnaires, and medical record review to collect data. Factors related to delayed care seeking were identified using nonlinear regression. Analysis was performed in 109 patients with HF. The median delay time was 124 hours. Delayed care seeking was associated with younger age and perception of fatigue, whereas evaluation of and response to symptoms were not associated with delay. Few characteristics of the symptom experience are associated with delayed care seeking among patients with HF who experience an exacerbation of symptoms. Further research is needed to determine why early care seeking is difficult among patients with HF.


Phenolic compounds of barley grain and their implication in food product discoloration.
Barley grains contain significant amounts of phenolic compounds that may play a major role in the discoloration of food products. Phenolic acid and proanthocyanidin (PA) composition of 11 barley genotypes were determined, using high-performance liquid chromatography and liquid chromatography-mass spectrometry, and their significance on food discoloration was evaluated. Abraded grains contained 146-410 microg/g of phenolic acids (caffeic, p-coumaric, and ferulic) in hulled barley and 182-282 microg/g in hulless barley. Hulled PA-containing and PA-free genotypes had comparable phenolic acid contents. Catechin and six major barley PAs, including dimeric prodelphinidin B3 and procyandin B3, and four trimers were quantified. PAs were quantified as catechin equivalents (CE). The catechin content was higher in hulless (48-71 microg/g) than in hulled (32-37 microg/g) genotypes. The total PA content of abraded barley grains ranged from 169 to 395microg CE/g in PA-containing hulled and hulless genotypes. Major PAs were prodelphinidin B3 (39-109 microg CE/g) and procyanidin B3 (40-99 microg CE/g). The contents of trimeric PAs including procyanidin C2 ranged from 53 to 151 g CE/g. Discoloration of barley flour dough correlated with the catechin content of abraded grains (r = -0.932, P < 0.001), but not with the content of individual phenolic acids and PAs. Discoloration of barley flour dough was, however, intensified when total PA extracts and catechin or dimeric PA fractions were added into PA-free barley flour. The brightness of dough also decreased when the total PA extract or trimeric PA fraction was added into heat-treated PA-free barley flour. Despite its low concentration, catechin appears to exert the largest influence on the discoloration of barley flour dough among phenolic compounds.


Insights on the design of free-spanning pipelines.
The design of free-spanning pipelines is performed with the aim of ensuring their integrity against permanent loads generated by seabed roughness, functional loads induced by internal pressure and temperature, and dynamic loads induced by marine currents and direct wave action. In particular, a load and resistance factored design is applied that focuses on extreme environmental loads, and a fatigue limit state approach is applied as a consequence of free-span dynamics due to vortex shedding-induced vibration and direct wave action. The pipeline free-span scenario can be permanent, when generated by seabed roughness, or characterized by short- to long-term evolution, when generated by seabed mobility and scouring in shallow waters. Free-span analysis is generally a task involving a number of disciplines and should be carried out using a multidisciplinary approach. The paper illustrates various themes related to free-span analysis: (i) free-span scenarios, (ii) characterization of the environment from deep to shallow water related to proper seabed properties, (iii) hydrodynamic load regimes, (iv) pipeline free-span design assessment aiming to reduce overstress and fatigue damage, (v) erodible seabed mobility and local scour, and (vi) some experiences of inspection surveys chosen as representative of a free-spanning pipeline in sandy soils.


Cytotoxic Effects of 24-Methylenecyloartanyl Ferulate on A549 Nonsmall Cell Lung Cancer Cells through MYBBP1A Up-Regulation and AKT and Aurora B Kinase Inhibition.
Lung cancer is the second most prevalent cancer. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer. The low efficacy in current chemotherapies impels us to find new alternatives to prevent or treat NSCLC. Rice bran oil is cytotoxic to A549 cells, a NSCLC cell line. Here, we identified 24-methylenecyloartanyl ferulate (24-mCAF) as the main component responsible for the cytotoxicity in A549 cells. An iTRAQ-based quantitative proteomics analysis revealed that 24-mCAF inhibits cell proliferation and activates cell death and apoptosis. 24-mCAF induces up-regulation of Myb binding protein 1A (MYBBP1A), a tumor suppressor that halts cancer progression. 24-mCAF inhibits the activity of AKT and Aurora B kinase, two Ser/Thr kinases involved in MYBBP1A regulation and that represent important targets in NSCLC. This study provides the first insight of the effect of 24-mCAF, the main component of rice bran oil, on A459 cells at the cellular and molecular levels.


Anaerobic biodegradation of aromatic compounds.
Many aromatic compounds and their monomers are existing in nature. Besides they are introduced into the environment by human activity. The conversion of these aromatic compounds is mainly an aerobic process because of the involvement of molecular oxygen in ring fission and as an electron acceptor. Recent literatures indicated that ring fission of monomers and obligomers mainly occurs in anaerobic environments through anaerobic respiration with nitrate, sulphate, carbon dioxide or carbonate as electron acceptors. These anaerobic processes will help to work out the better situation for bioremediation of contaminated environments. While there are plenty of efforts to reduce the release of these chemicals to the environment, already contaminated sites need to be remediated not only to restore the sites but to prevent the leachates spreading to nearby environment. Basically microorganisms are better candidates for breakdown of these compounds because of their wider catalytic mechanisms and the ability to act even in the absence of oxygen. These microbes can be grouped based on their energy mechanisms. Normally, the aerobic counterparts employ the enzymes like mono-and-dioxygenases. The end product is basically catechol, which further may be metabolised to CO2 by means of quinones reductases cycles. In the absense of reductases compounds, the reduced catechols tend to become oxidised to form many quinone compounds. The quinone products are more recalcitrant and lead to other aesthetic problems like colour in water, unpleasant odour, etc. On the contrary, in the reducing environment this process is prevented and in a cascade of pathways, the cleaved products are converted to acetyl co-A to be integrated into other central metabolite paths. The central metabolite of anaerobic degradation is invariably co-A thio-esters of benzoic acid or hydroxy benzoic acid. The benzene ring undergoes various substitution and addition reactions to form chloro-, nitro-, methyl- compounds. For complete degradation the side chains must be removed first and then the benzene ring is activated by carboxylation or hydroxylation or co-A thioester formation. In the next step the activated ring is converted to a form that can be collected in the central pool of metabolism. The third step is the channeling reaction in which the products of the catalysis are directed into central metabolite pool. The enzymes involved in these mechanisms are mostly benzyl co-A ligase, benzyl alcohol dehydrogenase. Other enzymes involved in this path are yet to be purified though many of the reactions products that have been theoretically postulated have been identified. This is mainly due to the instability of intermediate compounds as well as the association of the enzyme substrate is femoral and experimental conditions need to be sophisticated further for isolation of these enzymes. The first structural genes of benzoate and hydroxy benzoate ligases were isolated from Rhodopseudomonas palustris. This gene cluster of 30 kb size found in Rhodopseudomonas palustris coded for the Bad A protein. Similarly, some of the bph A,B,C and D cluster of genes coding for the degradation of pentachlorobenzenes were located in Pseudomonas pseudoalgaligenesKF 707.


Diaryl ether and diaryl thioether syntheses on solid supports via copper (I)-mediated coupling.
An efficient method to synthesize diaryl ethers and thioethers on solid supports is described. Starting from immobilized phenols or arylhalides, coupling with an access of aryliodides/arylbromides or phenolic/thiophenolic substrates in solution was successful in the presence of CuCl and Cs(2)CO(3) as base. Coupling conditions known from solution-phase syntheses of diaryl ethers have been effectively modified and adapted to solid-phase synthesis. Optimized conditions enabled the coupling of sterically hindered and/or electronically deactivated aryl moieties. After coupling, a newly developed diversity-generating linker based on cinnamic acid allowed the diaryl ethers to be cleaved from the resin either via saponification/transesterification or via ozonolysis. Latter offers the possibility of generating several additional compounds by simple variation of the cleavage conditions. The target substances were generally isolated in good to excellent yields and high purities.


Complement C3 participation in monocyte adhesion to different surfaces.
As part of an ongoing investigation into the role of the monocyte/macrophage in biocompatibility, a major goal is to identify the adhesion mechanisms that initiate and promote the observed in vivo morphologic progression of monocyte-to-macrophage-to-foreign body giant cell on biomaterials. We have exploited differently modified polystyrenes, specific component-depleted sera, and monoclonal antibodies (mAbs) to leukocyte integrins to ask what adhesion mechanisms mediate human blood monocyte adhesion to different surfaces in vitro. Preliminary findings are that monocyte interactions with fluorinated, siliconized, nitrogenated, and oxygenated surfaces are reduced by 50-100% when complement component C3-depleted serum is used for adsorption; reductions vary with material surface properties. Adhesion is restored on all surfaces when C3-depleted serum is replenished with purified C3. Monocyte adhesion to serum-adsorbed surfaces is inhibited by mAbs to the leukocyte integrin beta subunit, CD18 (mAbs 60.3 and MHM23), and partially inhibited by a mAb to the alpha subunit, CD11b (mAb 60.1), suggesting adhesive interactions between adsorbed C3bi (the hemolytically inactive form of the C3b fragment) and the leukocyte integrin CD11b/CD18. However, adsorbed fibrinogen reduces the effectiveness of these mAbs, indicating that alternative adhesion mechanisms may operate depending on the propensities of critical adhesion-mediating components to be adsorbed onto different surfaces.


Initial Coronavirus Disease-2019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research.
School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.


Noninvasive determination of fetal RhD status using fetal DNA in maternal serum and PCR.
Because prenatal testing of fetal RhD status by amniocentesis carries small yet finite risks to the fetus and mother, this study sought to determine whether fetal DNA in maternal serum could be used to detect fetal RhD status by polymerase chain reaction (PCR). A retrospective analysis was made of frozen serum specimens from 20 sensitized RhD-negative pregnant women (ranging from 15.0 to 36.0 weeks' gestation) who were confirmed by serology at birth to have been carrying RhD-positive fetuses. Eleven serum specimens from RhD-negative individuals served as controls. DNA was isolated from serum and used in two PCR-based methods to detect a 99 base pair (bp) DNA fragment specific for the RhD gene and a 113 bp fragment specific for the RhCE gene as control. Overall, in 14 (70%) of 20 RhD-positive fetuses the 99 base pair RhD-specific PCR product was detected. There was no false positive detection among the 11 control serum specimens. The results illustrate the ability to detect fetal RhD sequences in maternal serum of sensitized women. Moreover, the findings demonstrate that fetal single-gene disorders can be detected prenatally by using DNA isolated only from maternal serum.


Extranuclear Sirtuins and Metabolic Stress.
Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications, and adenosine diphosphate-ribosylation. Large-scale studies have revealed hundreds of target proteins regulated by different sirtuin modifications. Sensing of the metabolic state and regulation of the sirtuin function and expression are critical components of the machinery, optimizing cellular functions in the switch from fed to fasting condition. Overfeeding, obesity, and metabolic diseases cause metabolic stress that dysregulates the sirtuins, which may play a role in the pathogenesis and complications of metabolic diseases such as type 2 diabetes, fatty liver disease, and cardiac diseases. In the current review, we will discuss the significance of the extranuclear sirtuins as metabolic regulators and in protection against the reactive oxygen species, and also how these sirtuins are regulated by metabolic status and their putative role in metabolic diseases. To efficiently utilize sirtuins as drug targets for treatment of the metabolic diseases, better understanding of the sirtuin functions, targets, regulation, and cross talk is needed. Furthermore, more studies in humans are needed to confirm the many observations mainly made in animal and cell models so far. Antioxid. Redox Signal. 28, 662-676.


[MiR- 4719 inhibits migration and invasion of human breast cancer cells via targeting ARHGAP36].
To detect the expression of miR-4719 in breast cancer tissues and cells and explore its role in regulating invasion and migration of breast cancer cells. qRT-PCR was used to detect the expression of miR-4719 and ARHGAP36 in 30 pairs of human breast cancer tissues and adjacent tissues, two breast cancer cell lines (BT549 and MDA-MB- 231) and normal breast cells (MCF-10A). Bioinformatic methods were utilized to analyze the relationship between miR-4719 expression and overall survival of breast cancer patients and predict the potential target gene miR- 4719. miR-4719 mimics, ARHGAP36 shRNA and ARHGAP36 plasmids were transfected into breast cancer cells to test the effects of miR-4719 overexpression, ARHGAP36 knockdown and ARHGAP36 overexpression on cell migration and invasion using wound healing assay and Transwell assay. A dual-luciferase reporter assay was used to verify the direct binding between miR-4719 and 3'-UTR of ARHGAP36. Compared with those in adjacent tissues or normal breast cells, the expressions of miR-4719 were significantly decreased and the expression of ARHGAP36 was increased in breast cancer tissues (P < 0.001) and breast cancer cell lines (P < 0.01). A low expression of miR-4719 was correlated with a poorer overall survival of breast cancer patients (P < 0.05). Overexpression of miR-4719 and ARHGAP36 knockdown both significantly attenuated the invasion and migration abilities of breast cancer cells (P < 0.05). The expression of miR-4719 was inversely correlated to that of ARHGAP36 in breast cancer tissues (P < 0.01). Dual-luciferase reporter assay confirmed that ARHGAP36 was the target gene of miR-4719 (P < 0.01), and exogenous miR-4719 could significantly lower the expression of ARHGAP36 (P < 0.05). ARHGAP36 overexpression significantly reversed the inhibitory effects of miR-4719 mimics on migration and invasion of breast cancer cells (P < 0.05). The expression of miR-4719 is aberrantly decreased in breast cancer tissues to promote migration and invasion of breast cancer cells by up-regulating ARHGAP36 expression.


First-Generation Subporphyrinatoboron(III) Sensitizers Surpass the 10 % Power Conversion Efficiency Threshold.
Subporphyrinatoboron(III) (SubB) sensitizers were synthesized for use in dye-sensitized solar cells (DSSCs). The prototype, which comprises a sterically demanding 3,5-di-tert-butylphenyl scaffold, a meso-ethynylphenyl spacer, and a cyanoacrylic acid anchoring group, achieved an open-circuit voltage VOC of 836 mV, short-circuit current density JSC of 15.3 mA cm(-2) , fill factor of 0.786, and a photon-to-current conversion efficiency of 10.1 %. Such astonishing figures suggest that a bright future lies ahead for SubB in the realm of DSSCs.


Closed versus open suctioning techniques.
Airway suctioning is classically performed with the disconnection of the patient from the ventilator and the introduction of the suction catheter into the endotracheal tube. Alternatively, it can be accomplished with a closed suctioning system included in the ventilatory circuit, allowing to introduce the suction catheter into the airways without disconnecting the patient from the ventilator. The closed-suction system has some advantages compared to the conventional, open-suction technique. It can be helpful in limiting environmental, personnel and patient contamination and in preventing the loss of lung volume and the alveolar derecruitment associated with standard suctioning in the severely hypoxemic patients. However, the impact of the closed system on ventilator-associated pneumonia as well as its cost-effectiveness and the influence of such devices with ventilatory support remain to be assessed.


Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient mice.
Multiple lines of evidence indicate that thrombopoietin (TPO) substantially impacts the number of hematopoietic stem cells and progenitors of all myeloid lineages. Nevertheless, tpo knock-out mice (T(-)) display thrombocytopenia only; blood erythroid and neutrophil levels are normal despite 60% to 85% reductions in stem and progenitor cells. The compensatory mechanism(s) for these deficiencies remains uncertain; lineage-specific cytokines such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) have been postulated but never proven to be responsible. To directly test whether G-CSF can compensate for the myeloid progenitor cell reduction in the T(-) model of hematopoietic deficiency, T(-) and G-CSF-receptor knock-out (GR(-)) mice were crossed, and F1 animals bred to obtain doubly nullizygous mice (T(-)GR(-)). This experiment also allowed us to test the hypothesis that G-CSF contributes to the residual platelet production in T(-) mice. We found that T(-)GR(-) F2 mice displayed similar blood platelet levels as that seen in T(-) mice, indicating that G-CSF does not account for the residual megakaryopoiesis in T(-) mice. However, we also noted excessive perinatal mortality of T(-)GR(-) animals, caused by infection due to a profound and significant decrease in marrow and peripheral blood neutrophils, far greater than that seen in either T(-) or GR(-) mice. These data indicate that in the additional absence of GR, T(-) mice cannot compensate for their 62% reduction in myeloid progenitors and become profoundly neutropenic, supporting the hypothesis that G-CSF can compensate for the myeloid effects of TPO deficiency by expanding the pool of cells between the granulocyte-macrophage colony-forming unit and mature neutrophil stages of granulopoiesis.


Effects of dexamethasone on excretion of urinary kallikrein and urinary protein in Dahl salt-sensitive and salt-resistant rats.
The effect of glucocorticoid treatment on urinary kallikrein excretion was assessed in Dahl salt-hypertension susceptible (S) and salt-hypertension resistant (R) rats. A single dose of dexamethasone (100 micrograms) caused a marked water diuresis and a slight decrease in urinary kallikrein excretion in both S and R rats. A single dose of dexamethasone also caused the S rat to excrete massive amounts of protein into the urine, almost 3-fold higher than S rats treated with oil; the effect on R rat urinary protein was similar, but less severe. Daily administration of dexamethasone (100 micrograms/day) for 7 days caused marked suppression of urinary kallikrein excretion in both S and R rats. Increased urinary protein following chronic treatment was still evident in the dexamethasone-treated S rats but not in the dexamethasone-treated R rats. Chronic glucocorticoid treatment probably inhibits urinary kallikrein activity by suppressing pituitary and adrenal function which would remove the stimulatory effect of aldosterone on urinary kallikrein excretion. There was no evidence for a stimulatory role of glucocorticoids on urinary kallikrein.


A simple, cost-effective method for practicing phacoemulsification in the cadaveric eye.
The authors describe an inexpensive, reliable method for practicing intraocular surgery using a rigid contact lens as a temporary keratoprosthesis. This method allows clear visualization of the anterior chamber and lenticular structures for practicing modern cataract surgery, including capsulorhexis, hydrodissection, phacoemulsification, cortical aspiration, and intraocular lens insertion.


A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human.
Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. In this study, NMR-based metabolomic analysis in conjunction with multivariate statistics was applied to examine the urinary metabolic changes in two rodent models of type 2 diabetes mellitus as well as unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes. 1H-NMR spectra of urine were used in conjunction with uni- and multivariate statistics to identify disease-related metabolic changes in these two animal models and human sufferers. This study demonstrates metabolic similarities between the three species examined, including metabolic responses associated with general systemic stress, changes in the TCA cycle, and perturbations in nucleotide metabolism and in methylamine metabolism. All three species demonstrated profound changes in nucleotide metabolism, including that of N-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide unique biomarkers for following type 2 diabetes mellitus progression.


POTENTIAL SHARED DISEASE RISK AMONG DOGS AND COYOTES (CANIS LATRANS) EXEMPLIFIED BY THE ECOLOGY OF RICKETTSIOSIS IN A ROCKY MOUNTAIN SPOTTED FEVER-EPIDEMIC REGION IN NORTHERN MEXICO.
Rocky Mountain spotted fever (RMSF), caused by the bacterium Rickettsia rickettsii, is a re-emerging tick-borne zoonosis in North America, with hundreds of human fatalities in multiple outbreaks in northern Mexico and the southwestern US in the past few decades. Free-roaming dogs are key because they are reservoirs for the pathogen and the main hosts of the brown dog tick (Rhipicephalus sanguineus), which vectors RMSF in this region. Because coyotes (Canis latrans) can be infected with R. rickettsii and infested with Rh. sanguineus, we hypothesized that space sharing among dogs and coyotes could enhance disease risks. In summer 2021, we captured and sampled 11 coyotes at two sites in Baja California, Mexico, near population centers with human cases of RMSF, and fitted seven individuals with GPS logging collars. We also tested tissue samples, sera, and ectoparasites for DNA of R. rickettsii with PCR and used serology to detect antibodies to R. rickettsii. Finally, we deployed an array of cameras to document dog-coyote interactions. Mean home range size was 40.37 km2. Both GPS and camera data showed considerable home range overlap both between individual coyotes and between coyotes and dogs. Coyotes were active in areas where dogs occur including the domestic interface surrounding human settlements. Although none of our samples were positive for R. rickettsii on PCR, 72.7% (8/11) of the samples were seropositive with titers ≥64. Our data confirm shared space use and risk of shared parasites and disease between coyotes and dogs.


Effect of pretransplant dialysis vintage on clinical outcomes in deceased donor kidney transplant.
The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69-7.63; P < 0.001; aHR 2.37; 95% CI 1.06-5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94-25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.


Children with severe early childhood caries: streptococci genetic strains within carious and white spot lesions.
Mutans streptococci (MS) are one of the major microbiological determinants of dental caries. The objectives of this study are to identify distinct MS and non-MS streptococci strains that are located at carious sites and non-carious enamel surfaces in children with severe early childhood caries (S-ECC), and assess if cariogenic MS and non-cariogenic streptococci might independently exist as primary bacterial strains on distinct sites within the dentition of individual children. Dental plaque from children (N=20; aged 3-6) with S-ECC was collected from carious lesions (CLs), white spot lesions (WSLs) and non-carious enamel surfaces. Streptococcal isolates (N=10-20) from each site were subjected to polymerase chain reaction (PCR) to identify MS, and arbitrarily primed-PCR for assignment of genetic strains. Primary strains were identified as ≥50% of the total isolates surveyed at any site. In several cases, strains were characterized for acidurity using ATP-driven bioluminescence and subjected to PCR-determination of potential MS virulence products. Identification of non-MS was determined by 16S rRNA gene sequencing. Sixty-four independent MS or non-MS streptococcal strains were identified. All children contained 1-6 strains. In many patients (N=11), single primary MS strains were identified throughout the dentition. In other patients (N=4), primary MS strains were identified within CLs that were distinct from primary strains found on enamel. Streptococcus gordonii strains were identified as primary strains on enamel or WSLs in four children, and in general were less aciduric than MS strains. Many children with S-ECC contained only a single primary MS strain that was present in both carious and non-carious sites. In some cases, MS and non-cariogenic S. gordonii strains were found to independently exist as dominant strains at different locations within the dentition of individual children, and the aciduric potential of these strains may influence susceptibility in the development of CLs.


A novel electrolyte-responsive membrane with tunable permeation selectivity for protein purification.
A novel electrolyte-responsive membrane, RC-g-PSBMA, was successfully prepared from regenerated cellulose (RC) membrane through surface-initiated atom transfer radical polymerization (ATRP) of a zwitterionic monomer, sulfobetaine methacrylate (SBMA). Different degrees of polymerization for the grafted SBMA polymers (i.e., PSBMA) on the RC membrane were easily obtained by adjusting the ATRP reaction conditions. The electrolyte-responsive behavior of RC-g-PSBMA was first evaluated through the permeation experiments with sodium chloride (NaCl) solutions of different concentrations. It was found that the permeability of RC-g-PSBMA showed a clear dependence on NaCl concentration in the solutions. To further examine the potential of RC-g-PSBMA for protein purification, bovine serum album (BSA) was chosen as a model protein and polystyrene nanoparticles (NPs) of different sizes were used as representative impurities in the solutions. The rejection rates of BSA and NPs by RC-g-PSBMA were examined with the solutions containing BSA and NPs at different NaCl concentrations. The results showed that the rejection rates of BSA were at a very low level regardless of the concentration of NaCl in the solutions, indicating that the membrane allowed BSA to permeate. However, the rejection rates of NPs of different sizes by RC-g-PSBMA changed remarkably with the concentration of NaCl in the solutions. The study has demonstrated the possibility to separate BSA from NPs of different sizes by using the same membrane but simply altering the concentration of NaCl in the solutions. Membranes with such properties will have a great potential for protein purification as well as for many other separation applications.


Responding to Adverse Childhood Experiences: It Takes a Village.
In working to improve the health of North Carolinians, a broader emphasis has been placed on determinants of health, or non-medical drivers of health. Critical examples of health determinants are adverse childhood experiences, or ACEs, that affect early brain development and lifelong health and function. Multiple organizations and communities have come together to acknowledge the importance of prevention, address toxic stress and trauma in childhood, promote resiliency and trauma-informed care, and invest in the future of North Carolina through its children. This issue of the NCMJ highlights the prevalence and magnitude of ACEs in North Carolina and the effects on our children and the impact into adulthood, and how people and communities can come together to improve public health over the life course by addressing ACEs.


Wide-field imaging combined with confocal microscopy using a miniature f/5 camera integrated within a high NA objective lens.
Wide-field (WF) imaging paired with reflectance confocal microscopy can noninvasively detect skin cancer with high accuracy. However, two separate devices are required to perform each imaging procedure. We describe a new concept that integrates the two into one device: a miniature WF color camera within the objective lens used for confocal microscopy, providing simultaneous sub-surface cellular imaging and WF surface morphologic imaging. The camera, inserted between a hyperhemisphere front lens and a back lens group of the objective, commands a field of view of 4.0 mm, with a resolution better than 30 μm, while confocal optical sectioning is preserved at sharper than 2.5 μm.


Clustering of Subgingival Microbiota Reveals Microbial Disease Ecotypes Associated with Clinical Stages of Periodontitis in a Cross-Sectional Study.
Periodontitis is characterized by chronic inflammation associated with alteration of the oral microbiota. In contrast to previous microbiome studies focusing a priori on comparison between extreme phenotypes, our study analyzed a random sample of 85 people. The aim of this study was to link microbial differences to disease's prevalence and severity. Using next generation sequencing of 16S rRNA amplicons and cluster analysis, we observed that the population can be divided into two major ecotypes: One mainly contained periodontal healthy/mild periodontitis individuals whereas the second ecotype showed a heterogeneous microbial distribution and clustered into three distinct sub-ecotypes. Those sub-ecotypes differed with respect to the frequency of diseased patients and displayed a gradual change in distinct subgingival microbiota that goes along with clinical disease symptoms. In ecotype 2, the subgroup with no clinical signs of disease was linked to an increase of F. nucleatum vincentii but also several other species, while only in "end-stage" dysbiosis classical red complex bacteria gained overweight. Therefore, the microbial disease ecotypes observed in our population can lead to an establishment of an early microbial risk profile for clinically healthy patients.


Stressful parental bonding exaggerate the functional and emotional disturbances of primary dysmenorrhea.
Some evidence suggests that women with primary dysmenorrhea (or painful period) often have traumatic experience with parental attachments, but the exact relationship between styles of the parental bonding and the detailed aspects of the disorder is unclear. From university-student women, we invited 50 primary dysmenorrhea patients and 111 healthy volunteers to undergo tests of the functional and emotional measure of dysmenorrhea (FEMD), the Family Relationship Questionnaire (FRQ), and the visual analog scale for the pain intensity experienced. Besides the high scores of the FEMD functional and emotional scales, the dysmenorrhea patients also scored significantly higher than the healthy controls on the FRQ scales of paternal dominance and maternal abuse. In patients, the FEMD Emotional scale was negatively predicted by the Paternal Freedom Release scale and the FEMD functional scale was positively predicted by the Maternal Dominance scale. Inappropriate parental bonding or chronic traumatic attachment styles have respective relationships with the functional and emotional disturbances experienced by the primary dysmenorrhea patients.


[Tumour necrosis factor antagonists: infliximab, adalimumab and etanercept].
Tumour necrosis factor (TNF) a has been identified through basic research as a molecule that has a central role in the regulation of many autoimmune chronic inflammatory diseases. Experimental and clinical research with TNF antagonists has validated this observation. At this time, TNF blockade is indicated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriasis. Recent clinical study with this type of molecularly targeted intervention has determined that chronic inflammatory diseases can share some pathophysiological mechanisms, while others are more specific for certain diseases. Therefore, TNF appears to play a central role in multiple forms of inflammation, but the underlying pathogenic mechanism remains intact during TNF blockade. For this reason, there is much interest in studies of combination therapy in which TNF antagonists are added to other treatments, such as methotrexate. Anti-TNF therapy is expensive; therefore, treatment strategies are needed that are affordable and provide optimal care for groups of patients that do not adequately respond to conventional therapy.


Heart rate reserve is a long-term risk predictor in women undergoing myocardial perfusion imaging.
Although women with cardiovascular disease experience relatively worse outcomes as compared to men, substantial knowledge gaps remain regarding the unique female determinants of cardiovascular risk. Heart rate (HR) responses to vasodilator stress mirror autonomic activity and may carry important long-term prognostic information in women. Hemodynamic changes during adenosine stress were recorded in a total of 508 consecutive patients (104 women) undergoing clinically indicated 13N-ammonia Positron-Emission-Tomography (PET) at our institution. Following propensity matching, 202 patients (101 women, mean age 61.3 ± 12.6 years) were analyzed. During a median follow-up of 5.6 years, 97 patients had at least one cardiac event, including 17 cardiac deaths. Heart rate reserve (% HRR) during adenosine infusion was significantly higher in women as compared to men (23.8 ± 19.5 vs 17.3 ± 15.3, p = 0.009). A strong association between 10-year cardiovascular endpoints and a blunted HRR was observed in women, while this association was less pronounced in men. Accordingly, in women, but not in men, reduced HRR was selected as a strong predictor for adverse cardiovascular events in a Cox regression model fully adjusted for imaging findings and traditional risk factors (HR 2.41, 95% CI 1.23-4.75, p = 0.011). Receiver operating characteristics (ROC) curves revealed that a blunted HRR <21% was a powerful predictor for MACE in women with a sensitivity of 77% and a specificity of 68%. Blunted HRR to adenosine stress adds incremental prognostic value for long-term cardiovascular outcomes in women beyond that provided by traditional risk factors and imaging findings.


Computational prediction and interpretation of both general and specific types of promoters in Escherichia coli by exploiting a stacked ensemble-learning framework.
Promoters are short consensus sequences of DNA, which are responsible for transcription activation or the repression of all genes. There are many types of promoters in bacteria with important roles in initiating gene transcription. Therefore, solving promoter-identification problems has important implications for improving the understanding of their functions. To this end, computational methods targeting promoter classification have been established; however, their performance remains unsatisfactory. In this study, we present a novel stacked-ensemble approach (termed SELECTOR) for identifying both promoters and their respective classification. SELECTOR combined the composition of k-spaced nucleic acid pairs, parallel correlation pseudo-dinucleotide composition, position-specific trinucleotide propensity based on single-strand, and DNA strand features and using five popular tree-based ensemble learning algorithms to build a stacked model. Both 5-fold cross-validation tests using benchmark datasets and independent tests using the newly collected independent test dataset showed that SELECTOR outperformed state-of-the-art methods in both general and specific types of promoter prediction in Escherichia coli. Furthermore, this novel framework provides essential interpretations that aid understanding of model success by leveraging the powerful Shapley Additive exPlanation algorithm, thereby highlighting the most important features relevant for predicting both general and specific types of promoters and overcoming the limitations of existing 'Black-box' approaches that are unable to reveal causal relationships from large amounts of initially encoded features.


Perianal condylomas, anal squamous intraepithelial neoplasms and screening: a review of the literature.
Anal squamous intraepithelial lesions (ASILs) are the precursors to anal cancer. Human papillomavirus infection has a direct link to ASIL formation and is responsible for up to 80% of anal cancers. But while much importance has been focused on targeting cancer precursors in the cervix, relatively little concern has been afforded to the anal canal. With the advent of cervical Pap smear screening in various regions, the incidence of cervical cancer has declined. However, marked similarities in the biological and pathological profiles of cervical cancer and anal cancer mean that anal cancer should be preventable in the same way - by curbing the progression of ASIL to cancer. This article explores the literature on ASILs and the growing problem of anal cancer in the community, along with the literature surrounding the current progress towards implementing a screening programme for ASIL in the future.


'Omics' and endocrine-disrupting chemicals - new paths forward.
The emerging field of omics - large-scale data-rich biological measurements of the genome - provides new opportunities to advance and strengthen research into endocrine-disrupting chemicals (EDCs). Although some EDCs have been associated with adverse health effects in humans, our understanding of their impact remains incomplete. Progress in the field has been primarily limited by our inability to adequately estimate and characterize exposure and identify sensitive and measurable outcomes during windows of vulnerability. Evolving omics technologies in genomics, epigenomics and mitochondriomics have the potential to generate data that enhance exposure assessment to include the exposome - the totality of the lifetime exposure burden - and provide biology-based estimates of individual risks. Applying omics technologies to expand our knowledge of individual risk and susceptibility will augment biological data in the prediction of variability and response to disease, thereby further advancing EDC research. Together, refined exposure characterization and enhanced disease-risk prediction will help to bridge crucial gaps in EDC research and create opportunities to move the field towards a new vision - precision public health.


Anther culture as an effective tool in winter wheat (Triticum aestivum L.) breeding.
The aim of this study was to determine the effect of genotype and induction medium in anther culture of wheat (Triticum aestivum L.). Ten F1 winter wheat genotypes were tested in anther culture (AC) to compare the two most frequently applied induction media (W14mf and P4mf). Androgenesis was induced during the treatment of each tested genotypes and green plants were produced from them using both media. Based on statistical analysis, the genotypes significantly influenced (at the 0.001 probability level) the efficiency of AC (embryo-like structures (ELS), albinos, green plantlets and transplanted plantlets) and the media also had a significant effect on the number of ELS and albino plantlets. Both media can be used for AC in wheat doubled haploid (DH) plant production. The production of ELS and green plantlets was higher in P4mf medium (48.84 ELS/100 anthers, 4.82 green plantlets/100 anthers) than in W14mf medium (28.14 ELS/100 anthers, 4.59 green plantlets/100 anthers). However, the green plant regeneration efficiency of the microspore-derived structures was 16.9% when using W14mf medium, while this value was 9.6% in the case of ELS induced with P4mf medium. The application of W14mf medium thus proved to be time- and labour-saving medium in the large-scale production of DH wheat plants. In our experiments, 267 DH plants were produced for our winter wheat breeding program. The spontaneous rediploidization rate was 32.72%.


"It has to be more than exercise": exploring multiple perspectives to community-based exercise program design for persons with breast cancer.
Connecting persons with cancer to exercise resources and/or supports requires a diverse team of professionals. As such, there is merit to engaging multiple individuals or "partners" along the cancer pathway to explore the relevant features of community-based exercise program (CBEP) design. The purpose of this study was to explore multi-partner perspectives to CBEP design for persons diagnosed with breast cancer (PWBC) to inform the implementation of a CBEP in a local setting. PWBC, health care professionals and qualified exercise professionals participated in one of four 60-min focus group discussions. Rich dialogue about preferred program environments, program delivery teams, and core program practices was encouraged using a semi-structured discussion guide. Focus groups were audio recorded, transcribed verbatim, and analyzed using inductive thematic analysis. Five main themes were identified based on focus group discussions, each pointing to an important feature of CBEP design for PWBC. Themes included the desire for CBEPs to incorporate elements designed to improve cancer literacy, provide opportunities to participate with peers, foster self-efficacy, prioritize program accessibility, and meaningfully integrate CBEPs within a network of supportive cancer care. The collective effect of fostering such elements in CBEPs may serve to increase the uptake and maintenance of exercise among PWBC; ultimately enhancing their overall well-being and quality of life.


Mechanical Fourier transform for programmable metamaterials.
Proactively programming materials toward target nonlinear mechanical behaviors is crucial to realize customizable functions for advanced devices and systems, which arouses persistent explorations for rapid and efficient inverse design strategies. Herein, we propose a "mechanical Fourier transform" strategy to program mechanical behaviors of materials by mimicking the concept of Fourier transform. In this strategy, an arbitrary target force-displacement curve is decomposed into multiple cosine curves and a constant curve, each of which is realized by a rationally designed multistable module in an array-structured metamaterial. Various target curves with distinct shapes can be rapidly programmed and reprogrammed through only amplitude modulation on the modules. Two exemplary metamaterials are demonstrated to validate the strategy with a macroscale prototype based on magnet lattice and a microscale prototype based on an etched silicon wafer. This strategy applies to a variety of scales, constituents, and structures, and paves a way for the property programming of materials.


Certification, Accreditation, and Credentialing for 503A Compounding Pharmacies.
The terms certification, accreditation, and credentialing are often used interchangeably when they apply to compounding-pharmacy qualifications, but they are not synonymous. The reasons for obtaining each, the requirements for each, and the benefits of each differ. Achieving such distinctions can negatively or positively affect the status of a pharmacy among peers and prescribers as well as a pharmacy's relationships with third-party payors. Changes in the third-party payor industry evolve constantly and, we suggest, will continue to do so. Compounding pharmacists must be aware of those changes to help ensure success in a highly competitive marketplace. To our knowledge at the time of this writing, there is no certification program for compounding pharmacists, although pharmacy technicians can achieve certification and may be required to do so by the state in which they practice (a topic beyond the scope of this article). For that reason, we primarily address accreditation and credentialing for 503A compounding pharmacies. In this article, the evolution of the third-party payment system for compounds is reviewed; the definitions of certification, accreditation, and credentialing are examined; and the benefits and recognition of obtaining accredited or credentialed status are discussed. Suggestions for selecting an appropriate agency that offers accreditation or credentialing, preparing for and undergoing an onsite survey, responding to findings, and maintaining a pharmacy practice that enables a successful survey outcome are presented. The personal experience of author CK during accreditation and credentialing is discussed, as is the role of a consultant (author BJ) in helping compounders prepare for the survey process. A list of agencies that offer accreditation and credentialing for compounding pharmacies is included for easy reference.


Molecular network of cartilage homeostasis and osteoarthritis.
This review article presents the current understanding of the molecular basis of articular cartilaginous homeostasis, and outlines potential areas to focus on within the developing field of therapeutics for cartilage disorders. Articular cartilage, an integral component of joints in extremities and the vertebral column, is essential for locomotion. Disturbance of joint development or cartilage homeostasis causes congenital osteocartilaginous dysplasia or osteoarthritic diseases, respectively. Symptomatic treatments and surgical replacement of joints are effective but can also be problematic in terms of quality of life over time. Recently, new insights into the molecular biological basis of chondrocyte differentiation and cartilage homeostasis have been reported. While joint formation is regulated by several growth factors such as Wnts (wingless-related MMTV integration site) and Gdfs (growth and differentiation factors), the pathology of osteoarthritis is now interpreted as the disruption of balance between anabolic and catabolic signals. Current findings in molecular biology on joint development are reviewed concisely to aid in the understanding of the molecular network that governs articular cartilage development and homeostasis.


In vitro acaricidal activity of Atropa belladonna and its components, scopolamine and atropine, against Rhipicephalus (Boophilus) microplus.
In vitro efficacy of methanolic extract of Atropa belladonna and its components scopolamine and atropine was assessed against Rhipicephalus (Boophilus) microplus. Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) were used whereas scopolamine and atropine were each tested at 0.1%. In adult immersion test, the extract was lethal to ticks at 20% concentration. The LC50 and LC95 values were determined as 6.875% and 17.306%, respectively. The extract caused a significant reduction (P < 0.05) in egg mass production at 10% concentration. In larval packet test, the extract was lethal to larvae in the concentrations of 10% and 20% after 24 h, with LC50 and LC95 values of 1.321% and 4.935%, respectively. Scopolamine and atropine showed 93.3% and 60.0% mortality of adult ticks, respectively, but they caused complete (100%) blocking of hatching as well as 100% larval mortality. Scopolamine and atropine were observed to be more potent than the crude extract at an equivalent concentration in both the bioassays.


Influence of age on results of resection of hepatocellular carcinoma.
One hundred and fifty-eight elective hepatectomies carried out between 1976 and 1989 for hepatocellular carcinoma were classified into three groups according to age: group I (n = 20) under 30 years of age; group II (n = 102) 30 to 60; and group III (n = 36) over 60. The number of operations carried out on patients in group III has increased since 1983, and the types of hepatic resection in the three different age groups were slightly but not significantly different. The incidence of small tumours (diameter less than 5 cm) and associated cirrhosis were relatively low in the younger patients. Postoperative complications developed in 4 patients (20%) in group I, 18 (18%) in group II and 8 (22%) in group III, the main ones being hepatic failure and intraabdominal sepsis. Operative mortality was 4%; one patient (5%) died in group I, 4 (4%) in group II, and 2 (6%) in group III, and the principal causes were hepatic failure and massive haemorrhage. Hepatic resection for hepatocellular carcinoma in most patients over 60 years old was associated with slightly higher operative morbidity and mortality, but the risks were such that we recommend that operation should not be denied to selected patients in this age group.


Distributions, sources and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in subsurface water of urban old industrial relocation areas: A case study in Shenyang, China.
During a 12-month study period, the levels, distributions, sources and ecological risk of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated in subsurface water of Shenyang (the largest urban industrial relocation base in China). The results showed that ΣPAH concentration ranged from 0.21 to 1.07 µg/L, in descending order as follows, summer, autumn, spring and winter. Comparing with the situations before relocation, there was a significant decrease in Fluorene, Phenanthrene and Anthracene levels. The content of Banzo[a]pyrene was in high level. Relatively high 16 EPA-PAHs concentrations were observed at downstream sites suggesting that after the industrial relocation, residual 16 EPA-PAHs in soil and sediments could be desorbed and resuspended in water. From a global perspective, contamination of subsurface water PAHs can be categorized as moderate level. Source analysis suggested that without industrial waste input, pyrogenic soureces were the major contributors for PAHs pollution in winter. Petrogenic and pyrogenic inputs were equally important sources for PAHs pollution in other seasons. Due to incomplete combustion of wood and coal, ecological risk of Banzo[a]pyrene was high in the winter, indicating that to alleviate 16 EPA-PAH contamination, segmented remediation and energy structure adjustment would be equally important in urban industrial relocation areas.


Unsuspected coeliac disease in chronic 'cryptogenic' liver disease.
Earlier reports have suggested that a relationship exists between chronic liver disease and coeliac disease (CD). Gliadin antibodies (GA) have been used to screen for CD. Using a micro-enzyme-linked immunosorbent procedure, we analysed sera from 327 consecutive patients with chronic liver disease for GA (IgA and IgG) and evaluated their clinical significance. GA were detected in 19 patients (6%), a prevalence six times greater than that found in healthy blood donors. In 9 of the 19 patients the liver disease had been classified as cryptogenic. The occurrence of GA was independent of the degree of hepatocellular impairment. A diagnosis of CD was confirmed in 5 of the 10 patients who underwent small-bowel biopsy. Our findings suggest the prevalence of CD in patients with chronic liver disease to be at least 1.5%--that is, 15 times higher than in the general population. They also suggest that the possible presence of CD should be considered in cases of chronic 'cryptogenic' liver disease.


Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.
When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells.


Nuclear dynamics of parthenogenesis of human oocytes: effect of oocyte aging in vitro.
We investigated in detail the nuclear kinetics of oocyte activation of aged human oocytes following combined activation treatment with calcium ionophore and puromycin. Two types of oocytes were used: (a) 1-day-old oocytes after 20-24 h retrieval, and (b) 2-day-old oocytes after 44-50 h retrieval. A total of 185 unfertilized aged oocytes, 91 1-day-old and 94 2-day-old oocytes, were fixed at 1, 2, 4, 6 and 8 h after activation treatment and then metaphase II (MII), anaphase or telophase II (A/T II) or pronuclear stage were recorded. We demonstrated that a combined calcium ionophore and puromycin treatment induced a high activation rate in both 1-day-old (95.6%) and 2-day-old oocytes (95.2%). Our results also demonstrated that the nuclear progression was faster in 2-day-old oocytes than in 1-day-old oocytes, although nuclear progression in parthenogenetically activated human oocytes requires the longer time periods compared with ICSI fertilization. It is concluded that combined treatment of the calcium ionophore and puromycin allows a high rate of parthenogenetic activation and the nuclear kinetics of parthenogenetically activated human oocytes appears to be more rapid in in vitro aging oocytes.


Timing of oceans on Mars from shoreline deformation.
Widespread evidence points to the existence of an ancient Martian ocean. Most compelling are the putative ancient shorelines in the northern plains. However, these shorelines fail to follow an equipotential surface, and this has been used to challenge the notion that they formed via an early ocean and hence to question the existence of such an ocean. The shorelines' deviation from a constant elevation can be explained by true polar wander occurring after the formation of Tharsis, a volcanic province that dominates the gravity and topography of Mars. However, surface loading from the oceans can drive polar wander only if Tharsis formed far from the equator, and most evidence indicates that Tharsis formed near the equator, meaning that there is no current explanation for the shorelines' deviation from an equipotential that is consistent with our geophysical understanding of Mars. Here we show that variations in shoreline topography can be explained by deformation caused by the emplacement of Tharsis. We find that the shorelines must have formed before and during the emplacement of Tharsis, instead of afterwards, as previously assumed. Our results imply that oceans on Mars formed early, concurrent with the valley networks, and point to a close relationship between the evolution of oceans on Mars and the initiation and decline of Tharsis volcanism, with broad implications for the geology, hydrological cycle and climate of early Mars.


Intracellular mediators in regulation of leptin secretion from adipocytes.
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mammalian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca(2+) concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca(2+) in the regulation of leptin secretion from adipocytes is discussed.


DISPERSAL AND EVOLUTION OF THE PACIFIC BASIN GEKKONID LIZARDS GEHYRA OCEANICA AND GEHYRA MUTILATA.
The Pacific island geckos Gehyra mutilata and Gehyra oceanica were studied on several Pacific Basin archipelagos to determine the degree that their distributions have been modified by humans (as commensals), through the analysis of protein variation using starch gel electrophoresis. Gehyra mutilata is an anthropophilic species that is widespread in the Pacific Basin and Southeast Asia. No protein variation was found in the Pacific Basin and southern Asia, although there were fixed allelic differences between populations of southern Asia and those further north. These results suggest possible recent human-aided transport across the Pacific from a population that experienced a genetic bottleneck in southern Asia. Gehyra oceanica, based on protein variation, consists of two natural groups in the Pacific, a northern (Micronesian) form and a southern (Melanesian and Polynesian) form. The northern form has very similar gene frequencies across its range in Micronesia. The southern form has its greatest allelic diversity in the south-central Pacific. F-statistics for G. oceanica in the south fall within the range of values in the literature for mainland Australian species of Gehyra that are not human commensals and for other island lizards that have been considered as natural dispersers. These values are consistent with the hypothesis that G. oceanica was naturally dispersed across the Pacific, prior to the arrival of humans and that the equatorial currents are a barrier to natural, north-south gene flow/dispersal in Pacific Basin lizards. However, human-aided dispersal within the northern and southern regions cannot be ruled out. By comparing the ecology of these two species, G. oceanica has the adaptations necessary for natural oversea dispersal, whereas G. mutilata has an ecology consistent with human-mediated dispersal, in support of the conclusions from the genetic data.


The Association of Polish Surgeons (APS) clinical guidelines for the use of laparoscopy in the management of abdominal emergencies. Part II.
Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. The recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The second part of the guidelines covers sections 6 to12 and the following challenges for surgical practice: acute appendicitis, acute mesenteric ischemia, abdominal injuries, bowel obstruction, diverticulitis, laparoscopy in pregnancy and postoperative complications requiring a reoperation.


Supporting Client and Family Engagement in Care Through the Planning and Implementation of an Online Consumer Health Portal.
Web-based portals and electronic health records are making it easier for clients and families to access health information. This improved transparency and access to information has the potential to promote activation and improve outcomes, but to realize these benefits, the information needs to be valuable, meaningful, and understandable. Engagement of the end users in the planning and implementation will ensure that the product meets the needs of the consumers. The purpose of this case study is to describe the client and family engagement strategies that were employed to support the process of planning and implementing an online consumer health portal at a pediatric rehabilitation hospital to support the successful launch of this new information-sharing technology platform.


Meningomyelocele. Assessment and management.
Failure of the neural tube to close in a fetus is one of the most devastating and yet common congenital malformations. Various organ systems including the skeletal, muscular, urologic, digestive, respiratory, skin and central nervous systems are involved. This involvement results in complicated and interrelated problems requiring services from the medical specialties of pediatrics, orthopedics, urology and neurosurgery; the allied health professions of physical therapy, occupational therapy, speech pathology, nutrition, social work and nursing; and the psychoeducational professions of education and psychology. This article attempts to summarize the information about the current needs and management techniques of children with meningomyelocele for the general pediatrician who is frequently called upon to play an important role in coordination and communication with the families and other professionals caring for these children.


Huge enhancement of upconversion luminescence by broadband dye sensitization of core/shell nanocrystals.
Upconversion nanocrystals (UCNCs) hold promise for bioimaging, solar cells, photocatalysis and volumetric displays. However, their upconversion luminescence intensities are usually low due to the weak and narrowband near-infrared absorption of lanthanide ions. Herein, we introduce and validate a strategy to hugely enhance upconversion luminescence intensity by using an organic near-infrared dye as an antenna to sensitize core/shell UCNCs. The dye can increase absorptivity and broaden the absorption spectrum of the UCNCs. Such dye sensitization, in combination with a core/shell structure, can tremendously enhance the upconversion luminescence (UCL) intensity of the UCNCs. The UCL intensity of dye-sensitized UCNCs excited at 820 nm is 800-folds higher than that of pure UCNCs excited at 980 nm. Further enhancement can be obtained by optimization of the dye emission and UCNC absorption spectral overlap. Moreover, the proposed approach can be extended to cover any part of the solar spectrum by using a set of dyes. This work provides new insights into the efficient enhancement of upconversion luminescence of the UCNCs and facilitates their applications.


Thyroidectomy over a quarter of a century in the Belgian Ardennes: a retrospective study of 1207 patients.
The general surgeon has been practising thyroid surgery for over 70 years and has done it well. The exposure to short-lived isotopes of iodine is a risk factor in the development of thyroid cancer. Therefore, the objective of this study was two-fold. Firstly, to reemphasize the importance of the general surgeon in thyroid surgery. Secondly, to examine the possible links between the incidence of thyroid cancer in Belgium and the radiation exposure caused by the Chernobyl cloud. To carry out this study we retrospectively analysed the files of 1207 patients who had undergone thyroid surgery between 1978 and 2004 in a hospital in the south of Belgium; all operations were performed by the same surgeon. The study showed that surgery of the thyroid is carried out safely and effectively by the general surgeon. The study included 18 haemorrhagic complications (1.5%) of which 9 needed reintubation and further emergency surgery; 8 recurrent laryngeal nerve damage (0.66%); 73 cases of transitory symptomatic hypocalcaemia requiring the administration of oral calcium (6%) and 15 cases of postoperative infection of the surgical wound (1.24%). This level of complication proves that accurate, well-regulated procedures always carried out by the same surgeon make it possible to reduce the number of complications relating to thyroidectomy. The study also shows us that the question of the link with the Chernobyl accident remains open. Several facts may be emphasized. The annual average rate for cancer went from 1 before the nuclear plant accident of Chernobyl to 3.6 after April 1986. There was also an "increase" of thyroid surgical operations in 1999 (13 years after the accident). In this particular year there were 79, while the usual annual average is 46 surgery cases per year. Of these 79 surgical cases, there were 16 cancers (20.25%), while the percentage of cancer cases for the entire study was 6% of patients. Before 1986, of the 286 cases operated on, 8 were cancer, which represented 2.8%. After 1986, 921 patients underwent thyroid surgery and 64 cancers were found (7%). The cases of the three youngest whose thyroid cancer appeared after 1986 should also be noted. They were aged 13, 14 and 19 in April 1986 and had developed cancer 13 to 15 years after the Chernobyl accident. It can be said that a meticulous surgical technique followed by an experienced surgeon who continually repeats the same procedures can reduce the number of postoperative complications in thyroid surgery and that the link between cancer of the thyroid in the Belgian population after 1986 and radiation exposure caused by the radioactive cloud released by the explosion of the Chernobyl nuclear plant is still open for debate. Nothing is certain and the numbers of thyroid cancers should continue to be documented in the coming years especially for patients aged less than 10 year old in April 1986.


Problem solving and collaborative involvement among adolescents with spinal cord injury and their caregivers.
To determine the relationship between constructive adolescent problem solving (positive problem-solving orientation and rational problem-solving style) and caregiver problem solving and collaborative involvement with primary caregiver among adolescents with spinal cord injuries (SCIs). Positive constructive adolescent problem solving was hypothesized to be predicted by more effective caregiver problem solving and higher collaborative involvement. Participants in this cross-sectional study were 79 adolescent and primary caregiver dyads recruited from a pediatric rehabilitation care system in North America. All participants completed a standardized problem-solving instrument and adolescent participants completed an adapted measure of collaborative parent involvement. More effective caregiver problem solving and adolescent perceptions of more collaboration with caregivers around SCI care were significantly associated with higher positive problem-solving orientation and higher rational problem-solving style among adolescents. Results underscore the importance of caregiver problem-solving skills and their collaboration with adolescents with SCI when addressing care needs. Clinically, findings highlight opportunities for parent involvement and skill-building as an important factor of rehabilitation for adolescents with SCI.


The role of inhalation rewarming in the early management of hypothermia.
To evaluate the effectiveness of inhalation rewarming in early resuscitative efforts for hypothermic victims. Search of MEDLINE and manual retrieval using the terms hypothermia, resuscitation, inhalation and treatment. All articles and papers published within the last 5 years were searched. Earlier literature was also included if considered vital to documenting the scientific basis and rationale for using airway rewarming. Letters to the editor, review articles, case reports and original research were included in this review. Material was considered for inclusion if it contributed generally to the understanding of the role of inhalation rewarming in the stabilization or treatment of accidental hypothermia. The literature reported many instances in which inhalation rewarming appeared to contribute to a successful outcome during hypothermic resuscitative efforts. The maximum contribution that inhalation rewarming provides to overall core rewarming does not appear to endorse it as a sole method of core rewarming. The safety and efficacy of inhalation rewarming suggest that it is a viable adjunct of treatment during hypothermic resuscitation. Its routine use may be more appropriate for a field rescue situation where more advanced rewarming modalities may not be available or practicable. Also, its primary value may be to minimize further core temperature loss during early management of accidental hypothermia.


The research school of Marie Curie in the Paris faculty, 1907-14.
As the most famous woman scientist of the twentieth century, there has been no shortage of books and articles on the life and career of Marie Curie (1867-1934). Her role as director of a laboratory-based research school in the new scientific field of radioactivity, a field which embraced both chemistry and physics, however, has never been examined. In recent years, there has been a growing interest in the question of research schools, and Morrell, Ravetz, Geison, and Klosterman, amongst others, have written on this subject. Using, in part, the methodology of Morrell, this paper investigates the role of Marie Curie as a school director in the Paris Faculty in the years 1907-14, examining the work and characteristics of her school and assessing her effectiveness as a director.


Peptides generated from milk proteins in the bovine mammary gland during involution.
Proteolytic activity in mammary gland secretions is associated with hydrolysis of secretory proteins during involution. Peptides generated from hydrolysis of milk proteins were characterized in secretions from the bovine mammary gland during involution to understand the fate of the milk proteins better. Mass spectral analysis of mammary secretions showed numerous peptides ranging between 0.7 and 14 kDa during mammary involution, but these peptides were not observed in normal milk. Mass spectral profiles representing discrete peptide fragments were similar on d 7, 14, and 21 of involution, suggesting that milk proteins were only partially hydrolyzed during involution. N-Terminal amino acid sequences of four peptides indicated that they were produced by hydrolysis of beta-casein during involution and probably resulted from plasmin hydrolysis. A 20-kDa peptide was identified as a fragment of a 39-kDa protein that was previously identified in bovine mammary secretions during involution. Mass spectral analysis of lactoferrin isolated from mammary secretions during involution showed major hydrolytic products. Immunoblot analysis confirmed that lactoferrin that was isolated from mammary secretions during involution contained a number of hydrolytic products. Intramammary hydrolysis of milk proteins by plasmin probably leads to the generation of the discrete peptides observed in the mammary secretions and contributes to the fate of these proteins during involution of the bovine mammary gland.


The Transcriptional Repressor Gfi1 Plays a Critical Role in the Development of NKT1- and NKT2-Type iNKT Cells.
Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of Gfi1-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific Gfi1-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1pos iNKT cells was significantly reduced. Furthermore, CD4pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific Gfi1-deficient mice. The α-GalCer-dependent production of IFN-γand Th2 cytokines, but not IL-17A, was severely reduced in T cell-specific Gfi1-deficient mice. In addition, a reduction of the α-GalCer-induced anti-tumor activity was observed in Gfi1-deficient mice. These findings demonstrate the important role of Gfi1 in regulating the development and function of NKT1- and NKT2-type iNKT cell subsets.


Detection and characterization of mutations in genes related to isoniazid resistance in Mycobacterium tuberculosis clinical isolates from Iran.
The global rise in drug-resistant Mycobacterium tuberculosis (M.tb), and especially the significant prevalence of isoniazid (INH)-resistance constitute a significant challenge to global health. Therefore, the present study aimed to investigate mutations in prevalent gene loci-involved in INH-resistance phenotype-among M.tb clinical isolates from southwestern Iran. Drug susceptibility testing (DST) was performed using the conventional proportional method on confirmed 6620 M.tb clinical isolates, and in total, 15 INH-resistant and 18 INH-susceptible isolates were included in the study. Fragments of six genetic loci most related to INH-resistance (katG, inhA promoter, furA, kasA, ndh, oxyR-ahpC intergenic region) were PCR-amplified and sequenced. Mutations were explored by pairwise alignment with the M.tb H37Rv genome. The analysis of gene loci revealed 13 distinct mutations in INH-resistant isolates. 60% (n = 9) of the INH-resistant isolates had mutations in katG, with codon 315 predominately (53.3%, n = 8). Mutation at InhA - 15 was found in 20% (n = 3) of resistant isolates. 26.7% (n = 4) of the INH-resistant isolates had kasA mutations, of which G269S substitution was the most common (20%, n = 3). The percentage of mutations in furA, oxyR-ahpC and ndh was 6.7% (n = 1), 46.7% (n = 7), and 20% (n = 3), respectively. Of the mutations detected in ndh and oxyR-ahpC, 5 were also observed in INH-susceptible isolates. This study revealed seven novel mutations, four of which were exclusively in resistant isolates. This study supports the usefulness of katG and inhA mutations as a predictive molecular marker for INH resistance. Co-detection of katG S315 and inhA-15 mutations identified 73.3% (11 out of 15 isolates) of INH-resistant isolates.