Identification of 526 conserved metazoan genetic innovations exposes a new role for cofactor E-like in neuronal microtubule homeostasis.
The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and immune systems. In an effort to understand the molecular underpinnings of such metazoan innovations, we carried out a comparative genomics analysis for genes found exclusively in, and widely conserved across, metazoans. Using this approach, we identified a set of 526 core metazoan-specific genes (the 'metazoanome'), approximately 10% of which are largely uncharacterized, 16% of which are associated with known human disease, and 66% of which are conserved in Trichoplax adhaerens, a basal metazoan lacking neurons and other specialized cell types. Global analyses of previously-characterized core metazoan genes suggest a prevalent property, namely that they act as partially redundant modifiers of ancient eukaryotic pathways. Our data also highlights the importance of exaptation of pre-existing genetic tools during metazoan evolution. Expression studies in C. elegans revealed that many metazoan-specific genes, including tubulin folding cofactor E-like (TBCEL/coel-1), are expressed in neurons. We used C. elegans COEL-1 as a representative to experimentally validate the metazoan-specific character of our dataset. We show that coel-1 disruption results in developmental hypersensitivity to the microtubule drug paclitaxel/taxol, and that overexpression of coel-1 has broad effects during embryonic development and perturbs specialized microtubules in the touch receptor neurons (TRNs). In addition, coel-1 influences the migration, neurite outgrowth and mechanosensory function of the TRNs, and functionally interacts with components of the tubulin acetylation/deacetylation pathway. Together, our findings unveil a conserved molecular toolbox fundamental to metazoan biology that contains a number of neuronally expressed and disease-related genes, and reveal a key role for TBCEL/coel-1 in regulating microtubule function during metazoan development and neuronal differentiation.


Implication of amino acid metabolism and cell surface integrity for the thermotolerance mechanism in the thermally adapted acetic acid bacterium Acetobacter pasteurianus TH-3.
Acetobacter pasteurianus, an industrial vinegar-producing strain, is suffered by fermentation stress such as fermentation heat and/or high concentrations of acetic acid. By an experimental evolution approach, we have obtained a stress-tolerant strain, exhibiting significantly increased growth and acetic acid fermentation ability at higher temperatures. In this study, we report that only the three gene mutations of ones accumulated during the adaptation process, ansP, dctD, and glnD, were sufficient to reproduce the increased thermotolerance of A. pasteurianus. These mutations resulted in cell envelope modification, including increased phospholipid and lipopolysaccharide synthesis, increased respiratory activity, and cell size reduction. The phenotypic changes may cooperatively work to make the adapted cell thermotolerant by enhancing cell surface integrity, nutrient or oxygen availability, and energy generation.


A 16S rRNA-based PCR assay for detection and identification of granulocytic Ehrlichia species in dogs, horses, and cattle.
A PCR-based assay was developed for detecting DNA of granulocytic ehrlichiae in blood samples from dogs, horses, and cattle, Primers were designed from 16S rRNA sequence information to specifically amplify DNA from a newly identified Swedish Ehrlichia species. The 16S rRNA nucleotide sequence of this Swedish species differs in only two and three positions from the sequences of Ehrlichia phagocytophila and Ehrlichia equi, respectively, which were also amplified by this PCR system. For evaluation, PCR results were compared with microscopic examination of stained blood smears for the detection of granulocytes containing ehrlichiae (morulae). Thirty-four of 36 microscopically positive samples were also positive by PCR, and 6 microscopically negative samples were negative by PCR as well. Six samples, in which morulae-like structures had been seen, were negative by PCR, also at a lower annealing temperature and when a reamplification of the first PCR products was performed. The identities of the PCR products from some canine and equine isolates were verified by direct DNA sequencing and were found to be identical with the Ehrlichia sequence found in these animal species that had been obtained earlier. The sequences of a segment of approximately 600 nucleotides from two bovine isolates were identical to that of E. phagocytophila, whereas the sequence of another bovine isolate differed in two positions from that of E. phagocytophila and in three positions from the sequences of the canine and equine isolates. Serum samples were analyzed by indirect fluorescent-antibody testing. Seventy-three percent of the animals which were positive by microscopy and PCR also had positive antibody titers. However, it was not possible to rely on a single serological result for diagnosis of present infection. It was, therefore, concluded that PCR was the most reliable method, useful in the clinical laboratory for specific and early diagnosis of granulocytic ehrlichiosis in animals.


Upstream stimulatory factors, USF1 and USF2 are differentially expressed during Xenopus embryonic development.
Upstream stimulatory factors (USF) 1 and 2 are members of the basic helix-loop-helix leucine zipper transcription factor family. They are considered to play critical roles in cell-cycle regulation and chromatin remodeling. Their gene expression patterns are considered ubiquitous but have not been fully investigated in terms of embryogenesis. We examined the expression of the genes encoding USF1 and USF2 in Xenopus laevis during embryonic development. Expression of both genes was first detected as maternal transcripts and was observed continuously throughout development. However, in situ hybridization analysis revealed that the two genes were expressed differentially. In the late blastula, both genes were expressed in the blastocoel roof and marginal zone. At the gastrula stage, USF2 was strongly expressed in the sensorial layer of the ectoderm and in the mesoderm, whereas USF1 expression was hardly detectable. From the neurula stage onward, expression of both genes was markedly enhanced in the neural tissues, neural crest, eye and otic vesicle. However, spatial expression of the genes within the neural tube differed in that the strongest USF1 signals were observed in the lateral region of the basal plate and the strongest USF2 ones in the dorsal region of the neural tube. Expression of the two genes occurred in different mesoderm derivatives at the tailbud stage (USF1, somite; USF2, pronephros and lateral plate mesoderm of the tail region). USF1 was expressed in the notochord of the early neurula, but was lost at the stage.


Candida biome of severe early childhood caries (S-ECC) and its cariogenic virulence traits.
The protected niche of deep-caries lesions is a distinctive ecosystem. We assessed the Candida biome and its cariogenic traits from dentin samples of 50 children with severe-early childhood caries (S-ECC). Asymptomatic, primary molars belonging to International Caries Detection and Assessment-ICDAS caries-code 5 and 6 were analyzed, and C. albicans (10-isolates), C. tropicalis (10), C. krusei (10), and C. glabrata (5) isolated from the lesions were then evaluated for their biofilm formation, acidogenicity, and the production of secreted hydrolases: hemolysins, phospholipase, proteinase and DNase. Candida were isolated from 14/43 ICDAS-5 lesions (32.5%) and 44/57 ICDAS-6 lesions (77.2%). Compared to, ICDAS-5, a significantly higher frequency of multi-species infestation was observed in ICDAS-6 lesions (p=0.001). All four candidal species (above) showed prolific biofilm growth, and an equal potency for tooth demineralization. A significant interspecies difference in the mean phospholipase, as well as proteinase activity was noted (p < 0.05), with C. albicans being the predominant hydrolase producer. Further, a positive correlation between phospholipase and proteinase activity of Candida-isolates was noted (r = 0.818, p < 0.001). Our data suggest that candidal mycobiota with their potent cariogenic traits may significantly contribute to the development and progression of S-ECC.


Low rates of both lipid-lowering therapy use and achievement of low-density lipoprotein cholesterol targets in individuals at high-risk for cardiovascular disease across Europe.
To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients' 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE ≥5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE ≥10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels (≥2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as ≥1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72% and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin ≥40 mg/day or rosuvastatin ≥20 mg/day). Among very-high-risk patients, this figure was 8.4%. There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in Europe.


[Long-distance learning on surgical material sterilization processes].
This study had the following goals: describing the development of a distance learning (DL) course on Surgical Material Sterilization Processes, to be given over the Internet; having the course evaluated by specialists in sterilization processes and in DL; describing students' and evaluators' profiles, and to evaluate the students' participation and their opinions about the course. The chosen course environment was TelEduc, and the teaching method was Case-Based Learning. The target population consisted of nurses from the greater Campinas area and other cities of the state of São Paulo. Fifty-eight nurses were invited, 14 were enrolled and 11 finished the course. The course was evaluated by specialists before and after its application. In order to evaluate the students' opinion of the course, a Likert questionnaire was used. The Case-Based Learning methodology helped student participation and the course was evaluated positively.


IS200/IS605 family single-strand transposition: mechanism of IS608 strand transfer.
Transposase, TnpA, of the IS200/IS605 family member IS608, catalyses single-strand DNA transposition and is dimeric with hybrid catalytic sites composed of an HUH motif from one monomer and a catalytic Y127 present in an α-helix (αD) from the other (trans configuration). αD is attached to the main body by a flexible loop. Although the reactions leading to excision of a transposition intermediate are well characterized, little is known about the dynamic behaviour of the transpososome that drives this process. We provide evidence strongly supporting a strand transfer model involving rotation of both αD helices from the trans to the cis configuration (HUH and Y residues from the same monomer). Studies with TnpA heterodimers suggest that TnpA cleaves DNA in the trans configuration, and that the catalytic tyrosines linked to the 5'-phosphates exchange positions to allow rejoining of the cleaved strands (strand transfer) in the cis configuration. They further imply that, after excision of the transposon junction, TnpA should be reset to a trans configuration before the cleavage required for integration. Analysis also suggests that this mechanism is conserved among members of the IS200/IS605 family.


[Permanent vascular catheters: Effectiveness and duration of the Ash-Split Cath].
In absence of a permanent and useful native arterio-venous fistula, the use of a tunnelled catheter allows dialysis therapy to be carried out. The Ash Split Cath is a recently introduced chronic hemodialysis catheter. An ASC was inserted in nine patients (7.1% of our prevalent dialysis population), for repeated venous thrombosis in seven patients and a poor venous tree in two. The average blood flow rate was 250 +/- 50 mL/minute and the mean venous pressure measured was 140mm Hg +/- 35. Recirculation determined by low flow technique was less than 5% and 4 months after the catheter placement, calculated Kt/V, was 1.2 +/- 0.02. During the follow up we did not document any infection of the exit site or related to the catheter.


Oral sildenafil for treatment of severe pulmonary hypertension in an infant.
We report the use of oral sildenafil in a 5-month-old preterm infant with severe bronchopulmonary dysplasia and pulmonary arterial hypertension refractory to inhaled nitric oxide treatment, maximal ventilatory support and conventional vasodilator therapy. Sildenafil was prepared as a liquid suspension by the method of trituration and administered via an orogastric tube to the patient. Forty-eight hours after sildenafil treatment, echocardiography revealed that the tricuspid incompetence was substantially diminished and the contractility of both ventricles improved, indicating a marked reduction in pulmonary arterial pressure. Oral sildenafil treatment was continued for 6 months until complete resolution of pulmonary arterial hypertension, and oxygen supplement was weaned off. There was no adverse effect during the treatment period. Oral sildenafil may be useful in reducing pulmonary vascular resistance and can be considered for treatment of severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.


Erythropoietin critically regulates the terminal maturation of murine and human primitive erythroblasts.
Primitive erythroid cells, the first red blood cells produced in the mammalian embryo, are necessary for embryonic survival. Erythropoietin and its receptor EpoR, are absolutely required for survival of late-stage definitive erythroid progenitors in the fetal liver and adult bone marrow. Epo- and Epor-null mice die at E13.5 with a lack of definitive erythrocytes. However, the persistence of circulating primitive erythroblasts raises questions about the role of erythropoietin/EpoR in primitive erythropoiesis. Using Epor-null mice and a novel primitive erythroid 2-step culture we found that erythropoietin is not necessary for specification of primitive erythroid progenitors. However, Epor-null embryos develop a progressive, profound anemia by E12.5 as primitive erythroblasts mature as a synchronous cohort. This anemia results from reduced primitive erythroblast proliferation associated with increased p27 expression, from advanced cellular maturation, and from markedly elevated rates of apoptosis associated with an imbalance in pro- and anti-apoptotic gene expression. Both mouse and human primitive erythroblasts cultured without erythropoietin also undergo accelerated maturation and apoptosis at later stages of maturation. We conclude that erythropoietin plays an evolutionarily conserved role in promoting the proliferation, survival, and appropriate timing of terminal maturation of primitive erythroid precursors.


An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders.
Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age. Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration. REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly. Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children.


Managing mobility outcomes in vulnerable seniors ( MMOVeS): a randomized controlled pilot study.
To estimate feasibility and potential for efficacy of an individualized, exercise-focused, self-management program (i.e. Managing Mobility Outcomes In Vulnerable Seniors ( MMOVeS)), in comparison to exercise information in improving mobility after six months among seniors recently discharged from hospital. Randomized pilot study. Two McGill University-teaching hospitals. Community dwelling seniors, aged 70 years and older, recently discharged from either participating hospitals. The physiotherapy-facilitated intervention consisted of (1) evaluation of mobility capacity, (2) setting short- and long-term goals, (3) delineation of an exercise treatment plan, (4) an educational booklet to enhance mobility self-management skills, and (5) six monthly telephone calls. Control group received a booklet with information on exercises targeting mobility limitations in seniors. Mobility, pain, and health status were assessed at baseline and at six months using multiple indicators drawn from Disabilities of the Arm, Shoulder, and Hand (DASH) Score, Lower Extremity Functional Scale (LEFS) and Short-Form (SF)-36. In all, 26 people were randomized to the intervention (mean age: 81 ± 8; 39% women), and 23 were randomized to the control (mean age: 79 ± 7; 33% women). The odds ratio for the mobility outcomes combined was 3.08 and the 95% confidence interval excluded 1 (1.65-5.77). The odds ratio for pain and health perception favored the MMOVeS group, but the 95% confidence interval included the null value. This feasibility study highlights the potential for efficacy of an individualized, exercise-focused, self-management program in comparison to exercise information in improving mobility outcome for seniors. Furthermore, a home-program combining self-management skills and exercise taught with minimal supervision prove to be feasible. Finally, data from this study can be used to estimate sample size for a confirmatory trial.


[Epidemiology of cancer of the breast in Mexico. Consequences of demography transition].
Analyze the relation between reductions in fertility and the inverse en breast cancer mortality in the different states of Mexico for the period 1979-1994. Fertility rates and beast cancer mortality rates were utilized to analyze the proposed relationship in the states of the country. Principal component analysis and classification analysis were then used in the confirmatory analysis of this relationship. There is an important decrease in fertility trends overall with regional differences: the northern states of Mexico have lowest then the southern states. These regional differences are inversely related to the observed differences in breast cancer mortality within the states: the northern states have levels of breast cancer mortality much higher than the southern states. The increase in mortality due to breast cancer and its relation to the decrease in fertility illustrates the importance that must be given to the preventive aspect of health services since in the near future Mexican women will exhibit reproductive behaviors similar to women in developed countries.


Design and performance investigation of a highly accurate apodized fiber Bragg grating-based strain sensor in single and quasi-distributed systems.
In this work, fiber Bragg grating (FBG) strain sensors in single and quasi-distributed systems are investigated, seeking high-accuracy measurement. Since FBG-based strain sensors of small lengths are preferred in medical applications, and that causes the full width at half-maximum (FWHM) to be larger, a new apodization profile is introduced for the first time, to the best of our knowledge, with a remarkable FWHM at small sensor lengths compared to the Gaussian and Nuttall profiles, in addition to a higher mainlobe slope at these lengths. A careful selection of apodization profiles with detailed investigation is performed-using sidelobe analysis and the FWHM, which are primary judgment factors especially in a quasi-distributed configuration. A comparison between the elite selection of apodization profiles (extracted from related literature) and the proposed new profile is carried out covering the reflectivity peak, FWHM, and sidelobe analysis. The optimization process concludes that the proposed new profile with a chosen small length (L) of 10 mm and Δnac of 1.4×10-4 is the optimum choice for single stage and quasi-distributed strain-sensor networks, even better than the Gaussian profile at small sensor lengths. The proposed profile achieves the smallest FWHM of 15 GHz (suitable for UDWDM), and the highest mainlobe slope of 130 dB/nm. For the quasi-distributed scenario, a noteworthy high isolation of 6.953 dB is achieved while applying a high strain value of 1500 μstrain (με) for a five-stage strain-sensing network. Further investigation was undertaken, proving that consistency in choosing the apodization profile in the quasi-distributed network is mandatory. A test was made of the inclusion of a uniform apodized sensor among other apodized sensors with the proposed profile in an FBG strain-sensor network.


Effusive molecular beam study of C2H6 dissociation on Pt(111).
The dissociative sticking coefficient for C2H6 on Pt(111) has been measured as a function of both gas temperature (Tg) and surface temperature (Ts) using effusive molecular beam and angle-integrated ambient gas dosing methods. A microcanonical unimolecular rate theory (MURT) model of the reactive system is used to extract transition state properties from the data as well as to compare our data directly with supersonic molecular beam and thermal equilibrium sticking measurements. We report for the first time the threshold energy for dissociation, E0 = 26.5 +/- 3 kJ mol(-1). This value is only weakly dependent on the other two parameters of the model. A strong surface temperature dependence in the initial sticking coefficient is observed; however, the relatively weak dependence on gas temperature indicates some combination of the following (i) not all molecular excitations are contributing equally to the enhancement of sticking, (ii) that strong entropic effects in the dissociative transition state are leading to unusually high vibrational frequencies in the transition state, and (iii) energy transfer from gas-phase rovibrational modes to the surface is surprisingly efficient. In other words, it appears that vibrational mode-specific behavior and/or molecular rotations may play stronger roles in the dissociative adsorption of C2H6 than they do for CH4. The MURT with an optimized parameter set provides for a predictive understanding of the kinetics of this C-H bond activation reaction, that is, it allows us to predict the dissociative sticking coefficient of C2H6 on Pt(111) for any combination of Ts and Tg even if the two are not equal to one another.


Photoluminescence and scintillation characteristics of Bi-loaded PVK-based plastic scintillators for the high counting-rate measurement of high-energy X-rays.
We synthesized Bi-loaded poly(9-vinylcarbazole) (PVK)-based plastic scintillators for high-energy X-ray detection. PVK, triphenylbismuth (BiPh3), and 1,4-bis(2-methylstyryl)benzene (bis-MSB) served as the host polymer, heavy metal compound, and organic phosphor, respectively. The emission peaks at approximately 440 nm in the photoluminescence emission and X-ray-excited radioluminescence spectra of the synthesized scintillators are attributed to bis-MSB. The scintillation decay time constants of the 1st exponential components are 1.6 ns. The presence of BiPh3 in the synthesized scintillators successfully enhanced their efficiency in the detection of 67.41 keV X-rays. The detection efficiency per 1 mm thickness achieved by a PVK-based plastic scintillator loaded with 10 wt% Bi was 2.5-times higher than that achieved by a commercial polyvinyltoluene (PVT)-based plastic scintillator loaded with 5 wt% Pb, EJ-256. The light yield of the PVK-based plastic scintillator loaded with 10 wt% Bi was 5600 photons per MeV, which was higher than that of EJ-256. We successfully enhanced the high-energy X-ray detection efficiency of PVK-based plastic scintillators, through the addition of BiPh3, while maintaining a short decay time of nanoseconds.


[Does hospital structure influence the outcome of operative treatment of femoral neck fractures?].
Data on 32 007 patients suffering from a medial fracture of the femoral neck have been collected between 1993 and 1999 in a database for external quality assurance organized by the chamber of physicians in Westfalia-Lippe. A statistical analysis (ANOVA, chi-square-test) has been performed to find out whether factors like specialization, annual volume or level of the hospital (primary, secondary or tertiary hospital) influence the outcome. Patients with higher preoperative risk-factors are treated more often in primary hospitals. These clinics perform conservative treatment significantly more often than tertiary hospitals (6.5 % vs. 3.8 %). Osteosyntheses are performed more often in departments specialized in traumatology (13 %) or tertiary hospitals (16.8 %). Preoperative length of stay was 0.5-0.7 days shorter in these hospitals. There is no significant difference in postoperative complications all together (23.2-25.6 %), but a significantly lower rate in postoperative complications after osteosynthesis performed by departments specialized in traumatology (11.3 % vs. 18.8 %). A volume load of more than 50 cases per year correlates with a significant decline in postoperative complications (22.5 % vs. 28.2 %). Risk adjusted mortality does not show significant differences among the different levels of hospitals. There are distinct differences regarding the way of treatment and procedural quality, but not concerning the short-term outcome between hospitals of different levels.


In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation.
In endothelial cells, investigate if the soluble guanylate cyclase (sGC) activation or stimulation is able to potentiate the relaxation in vessels. Aortic and coronary rings with and without endothelium were placed in a myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were performed. Nitric oxide (NO) were measured by fluorescence or by selective electrode in human umbilical endothelial cells (HUVECs) in response to some treatments, including ataciguat, 8-Br-cGMP and A23187. The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished. Our results suggest that in aortic and coronary rings the endothelium potentiates the relaxation induced by activation or stimulation of sGC through a mechanism dependent of NOS activation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Risk factors associated with post-acute sequelae of SARS-CoV-2: an N3C and NIH RECOVER study.
More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). The objective is to identify risk factors associated with PASC/long-COVID diagnosis. This was a retrospective case-control study including 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system and COVID index date within ± 45 days of the corresponding case's earliest COVID index date. Measurements of risk factors included demographics, comorbidities, treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. Among 8,325 individuals with PASC, the majority were > 50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30 + days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. This national study identified important risk factors for PASC diagnosis such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.


[Study of the growth zone of the thymus during the spontaneous development of mammary tumors in rats].
The methods of quantitative histochemistry were employed to study a subcapsular zone of the thymus under development of spontaneous mammary tumors in rats. In case of pretumor changes (fibrous-cystic mastopathy) some alterations in the metabolism of thymocytes were noted, which were manifested in the absence of DNA gain, a reduced level of cytoplasmatic and nuclear RNA, and a lack of correlation between NADP-diaphorase and DNA dispersion. Changes in the metabolism of T-lymphocytes at the initial stage of their maturation are likely to contribute to the occurrence of immunodepression followed by tumor appearance.


Insect-attracting and antimicrobial properties of antifreeze for monitoring insect pests and natural enemies in stored corn.
Insect infestations in stored grain cause extensive damage worldwide. Storage insect pests, including the Indianmeal moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae); Sitophilus spp. (Coleoptera: Curculionidae); and their natural enemies [e.g., Cephalonomia tarsalis (Ashmead) (Hymenoptera: Bethylidae), and Anisopteromalus calandrae (Howard) (Hymenoptera: Pteromalidae)] inhabit a temporary, but stable ecosystem with constant environmental conditions. The objective of the present experiment was to assess the efficacy of using ethylene glycol antifreeze in combination with nutrient solutions to monitor storage insect pest and natural enemy populations in three bins of corn, Zea mays L. The treatments were deionized water, a diluted (1:5 antifreeze:water) antifreeze solution, 10% honey, 10% honey in the diluted antifreeze solution, 10% beer in the diluted antifreeze solution, 10% sucrose in the diluted antifreeze solution, and a commercial pheromone trap suspended in a 3.8-liter container filled with 300-ml of diluted antifreeze solution. The seven treatments captured storage insect pests and their natural enemies in the bins at 33-36 degrees C and 51-55% RH. The pheromone trap in the container with the diluted antifreeze captured significantly more P. interpunctella than the other treatments, but a lower percentage (7.6%) of these captures were females compared with the rest of the treatments (> 40% females). All trapping solutions also captured Sitophilus spp. and other beetle species, but the captures of the coleopteran pests were not significantly different among the seven treatments (P > 0.05). Two parasitoid wasps also were captured in the study. The number of A. calandrae was different among the seven treatments (P < 0.05), whereas the number of C. tarsalis was not different among the treatments (P > 0.05). Most A. calandrae adults were captured by the 10% honey in the diluted antifreeze, whereas the fewest were captured in the deionized water. Microbial growth was observed in the 10% honey solution, but no microbial growth occurred in the rest of the treatments, including 10% honey in the diluted antifreeze solution. The results of insect captures and microbial growth demonstrated that antifreeze could be used as a part of storage insect monitoring and/or control programs.


Increased susceptibility of asymmetrically prominent cortical veins correlates with misery perfusion in patients with occlusion of the middle cerebral artery.
To evaluate tissue perfusion and venous susceptibility in ischaemic stroke patients as a means to predict clinical status and early prognosis. A retrospective study of 51 ischaemic stroke patients were enrolled in this study. Susceptibility, perfusion and National Institute of Health stroke scale (NIHSS) were compared between patients with and without asymmetrically prominent cortical veins (APCVs). The correlation between susceptibility, perfusion and NIHSS was performed. Compared to patients without APCVs, the age of patients with APCVs was statistically older (p = 0.017). Patients with APCVs at discharge showed clinical deterioration in their NIHSS. Mean transit time (MTT), time to peak (TTP) and cerebral blood flow (CBF) in the stroke hemisphere were statistically delayed/decreased in patients with and without APCVs (all p < 0.05). In patients with APCVs, the changes in susceptibility positively correlated with increases in MTT and TTP (p < 0.05). Susceptibility and TTP positively correlated and CBF negatively correlated with NIHSS both at admission and discharge (p < 0.05). Patients with APCVs have a tendency of deterioration. The presence of APCVs indicates the tissue has increased oxygen extraction fraction. Increased susceptibility from APCVs positively correlated with the delayed MTT and TTP, which reflects the clinical status at admission and predicts an early prognosis. • Patients with and without APCVs have similar misery perfusion. • Patients with APCVs have a tendency of deterioration compared to those without. • The presence of APCVs indicated the tissue has increased oxygen extraction fraction. • Increased susceptibility from APCVs positively correlated with the MTT and TTP. • Increased susceptibility from APCVs reflected the clinical status at admission.


[Cerebrogenic disorders of cardiac rhythm and conductivity in epilepsy patients].
51 epileptic patients aged 16-32 years without any signs of cardiovascular pathology were examined. The primary generalized epilepsy was diagnosed in 24 cases while a partial one--in 27 patients. Were examined a state of the heart (echo- and electrocardiography, Holter's monitoring of ECG), of the brain (computed echoencephalography, visual evoked potentials) and of the autonomic nervous system (variability of cardiac rhythm, autonomic tonus). A control group included 15 healthy individuals. Significantly higher prevalence of the disorders of the cardiac rhythm and conduction was found in patients with epilepsy as compared with a control group (p < 0.001). More frequently there were sino-atrial blocks of the II degree of the I type (p < 0.01), heterotopic rhythms (p < 0.05), supraventricular extrasystole (p < 0.1), supraventricular paroxysmal tachycardia (p < 0.05), supraventricular migration of the pacemaker (p < 0.01). It was found that close relationship between cardiac arrhythmias and epilepsy was mobided by a complex of pathophysiologic mechanisms. Among them a leading role belongs to dysfunction of suprasegmental autonomic centers with a predominant activation of sympathetic or parasympathetic departments of the autonomic nervous system. Significant arrhythmogenic factors appeared to be: presence of organic damages in the brain, frequency of epileptic fits, dysfunction of suprasegmental autonomic centers with activation of cerebral ergotropic systems.


Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique.
Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries. A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised. Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 μm and 900 μm in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 μm microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 μm Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted. In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles.


Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer's disease.
Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD.


Gender asymmetry in healthcare-facility attendance of people living with HIV/AIDS in Burkina Faso.
Anthropological research in Burkina Faso indicates that more HIV-positive women than HIV-positive men are attending care facilities for people living with HIV/AIDS (PLWH) and accessing antiretroviral medicine. This article, situated in the field of study of interactions between gender and AIDS, offers a description of this asymmetry and an anthropological analysis of the socio-cultural determinants, through analysis of data from ethnographic research among PLWH and health actors. Examining social representations of femininity and masculinity in Burkinabe society and the organisation of the healthcare system in connection with gender shed light on the decision-making processes of both sexes around therapeutic choices and the itinerary of care. On the one hand, the social values attached to femininity, maternity and the status of wife create conditions for women that favour their attendance at care facilities for PLWH and encourage a widespread practice where wives take the place of their husbands in healthcare queues. Moreover, health policies and the effects of women's empowerment within the healthcare system strengthen women's access to health services. On the other hand, representations of masculinity are fully implicated in the cultural construction of men's reluctance to attend care facilities for PLWH. The values associated with this masculinity cause men to run great health, economic and social risks, not only for themselves, but also for their wives and children. By better understanding the interaction between gender, the experience of HIV and the institutional organisation of healthcare, we can identify ways to reduce men's reluctance to attend care facilities for PLWH and improve both prevention and treatment-oriented programmes.


Work-related musculoskeletal disorders among clinical laboratory workers.
The aim of this study was to estimate the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) among clinical laboratory workers. This questionnaire-based cross-sectional study included the clinical laboratory departments of six governmental tertiary and secondary hospitals in Riyadh, Saudi Arabia. The selected instrument was a self-administered adapted standardized questionnaire. The sample comprised 306 laboratory workers, and the selected sampling technique was a non-random convenient method. The overall prevalence of WMSDs in any body region was 82% in the last 12 months; it was mainly linked to lower back pain (61%). In the logistic regression, age <30 years, working in specific laboratories and working in hematology/flow-cytometry laboratory divisions were all found to be significant risk factors (P < 0.05). Clinical laboratory workers are at a high risk for WMSDs; it is essential that we take preventative action to address this.


Why control activity? Evolutionary selection pressures affecting the development of physical activity genetic and biological regulation.
The literature strongly suggests that daily physical activity is genetically and biologically regulated. Potential identities of the responsible mechanisms are unclear, but little has been written concerning the possible evolutionary selection pressures leading to the development of genetic/biological controls of physical activity. Given the weak relationship between exercise endurance and activity levels and the differential genomic locations associated with the regulation of endurance and activity, it is probable that regulation of endurance and activity evolved separately. This hypothesis paper considers energy expenditures and duration of activity in hunter/gatherers, pretechnology farmers, and modern Western societies and considers the potential of each to selectively influence the development of activity regulation. Food availability is also considered given the known linkage of caloric restriction on physical activity as well as early data relating food oversupply to physical inactivity. Elucidating the selection pressures responsible for the genetic/biological control of activity will allow further consideration of these pressures on activity in today's society, especially the linkages between food and activity. Further, current food abundance is removing the cues for activity that were present for the first 40,000 years of human evolution, and thus future research should investigate the effects of this abundance upon the mechanisms regulating activity.


Surgical treatment of infective endocarditis with special reference to prosthetic valve endocarditis.
Patients with native valve endocarditis treated surgically between 1968 and 1978 (n = 15) and all patients presenting with prosthetic valve endocarditis during this period (n = 21) were followed up for at least four years. Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died. The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement. The 21 patients with prosthetic valve endocarditis suffered 25 attacks. Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment. The incidence of early prosthetic valve endocarditis--that occurring within two months of operation--was 0.67%, but that of late prosthetic valve endocarditis could not be determined. Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery. When such indications exist surgery should not be delayed.


Giving everyone the health of the educated: an examination of whether social change would save more lives than medical advances.
Social determinants of health, such as inadequate education, contribute greatly to mortality rates. We examined whether correcting the social conditions that account for excess deaths among individuals with inadequate education might save more lives than medical advances (e.g., new drugs and devices). Using US vital statistics data for 1996 through 2002, we applied indirect standardization techniques to estimate the maximum number of averted deaths attributable to medical advances and the number of deaths that would have been averted if mortality rates among adults with lesser education had been the same as those among college-educated adults. Medical advances averted a maximum of 178193 deaths during the study period. Correcting disparities in education-associated mortality rates would have saved 1369335 lives during the same period, a ratio of 8:1. Higher mortality rates among individuals with inadequate education reflect a complex causal pathway and the influence of confounding variables. Formidable efforts at social change would be necessary to eliminate disparities, but the changes would save more lives than would society's current heavy investment in medical advances. Spending large sums of money on such advances at the expense of social change may be jeopardizing public health.


Diagnostic challenges of posterior fossa hemangioblastomas: Refining current radiological classification scheme.
Hemangioblastomas (HBMs) are known to exhibit very typical radiological features and thus classified by well-established radiological classification scheme. We reviewed our series of posterior fossa HBMs in order not only to evaluate the relevance of current classification scheme, but also to possibly refine it. Also, we added descriptions on several cases with unusual radiological magnetic resonance imaging (MRI) findings in which differential diagnosis was challenging. We retrospectively reviewed preoperative MRI of 118 patients with pathologically diagnosed posterior fossa HBMs at our institution between 2002 and 2015. Total 128 tumors were included to this study and classified into four categories based on the presence and nature of cystic components: extratumoral cystic (Type Ce, classical cystic with a mural nodule), intratumoral cystic (Type Ci), mixed cystic (Type Cm), and solid (Type S). The association with von Hippel-Lindau (VHL) disease was also investigated. In 118 patients (65 male and 53 female), 79 (66.9%) had solitary HBMs and 39 (33.1%) were diagnosed with VHL disease. Type Ce with typical radiological findings was the most prevalent type of HBM (63.3%), followed by Type S (21.1%). HBMs with intratumoral cysts were uncommon (Type Ci, 11.7%) and mixed extratumoral and intratumoral cysts (Type Cm) accounted for only 3.9%. No intergroup differences were observed in the proportions of each subtype between the solitary and VHL disease-associated HBMs. The blood loss was much lower in Type Ce than in other subtypes. In Type Cm, radical resection was often challenging as the differentiation between intratumoral and extratumoral cysts was difficult resulting in incomplete resection. Refined radiological classification scheme is more practical because it does not only help surgeons determine whether the cystic wall should be removed or not, but also covers cases with atypical radiological presentations. For solid and extraparenchymal HBMs, differential diagnosis is more difficult as well as very critical as surgical removal is often very challenging.


The waterbodies of the halo-volcanic Dallol complex: earth analogs to guide us, where to look for life in the universe.
Microbes are the Earth life forms that have the highest degree of adaptability to survive, live, or even proliferate in very hostile environments. It is even stated that microbes can cope with any extreme physico-chemical condition and are, therefore, omnipresent all over the Earth: on all the continents, inside its crust and in all its waterbodies. However, our study suggests that there exists areas and even water rich environments on Earth where no life is possible. To support the fact that water rich environments can be lifeless, we performed an extensive survey of 10 different hyper extreme waterbodies of the halo-volcanic Dallol complex (Danakil depression, Ethiopia, Horn of Africa). In our study, we combined physico-chemical analyses, mineralogical investigations, XRD and SEM-EDX analyses, ATP measurements, 16S rDNA microbial community determinations, and microbial culturing techniques. According to our findings, we suggest that the individual physico-chemical parameters, water activity, and kosmo-chaotropicity, are the two most important factors that determine whether an environment is lifeless or capable of hosting specific extreme lifeforms. Besides, waterbodies that contained saturated levels of sodium chloride but at the same time possessed extreme low pH values, appeared to be poly-extreme environments in which no life could be detected. However, we clearly discovered a low diversity microbial community in waterbodies that were fully saturated with sodium chloride and only mildly acidic. Our results can be beneficial to more precisely classify whole or certain areas of planetary bodies, including water rich environments, as either potentially habitable or factual uninhabitable environments.


The Efficacy of Electro-Acupuncture Added to Standard Therapy in the Management of Bell Palsy.
To investigate the comparative efficacy of electro-acupuncture when added to standard therapy in patients with Bell palsy in terms of clinical and neurophysiologic outcomes. A total of 88 patients with Bell palsy who received standard treatment (ST group; n = 40, mean ± standard deviation age: 39.2 ± 6.6 years, 60.0% were males) or standard treatment plus electro-acupuncture (ST-EA group; n = 48, mean ± standard deviation age: 39.5 ± 6.9 years, 58.3% were males) were included. Data on patient demographics, symptoms, comorbidities, and 3-month outcomes on treatment response assessed via House-Brackmann grading system and facial nerve recovery profile and electromyography were recorded. Application of ST-EA versus ST was associated with a significantly higher rate of normal nerve function on 12th week electromyography (66.7% versus 25.0%, P = 0.020), higher frequency of patients with House-Brackmann grade ≤2 in the 3rd week (79.2% versus 45.0%, P = 0.029), 6th week (87.5% versus 45.0%, P = 0.004), and 12th week (95.8% versus 50.0%, P = 0.001), and those with facial nerve recovery profile scores ≥8 in the 6th week (83.3% versus 45.0%, P = 0.011) and 12th week (87.5% versus 50.0%, P = 0.009) of treatment. In conclusion, our findings in patients with Bell palsy revealed superiority of electro-acupuncture added to standard therapy over standard therapy alone in terms of improvement of nerve dysfunction, decrease in paralysis severity, and better functional recovery. This seems to indicate the likelihood of electro-acupuncture to be a safe and promising adjunct in the achievement of more satisfactory clinical outcomes in the management of Bell palsy when used in combination with standard medical and physiotherapy.


[Development of the taste buds in rat embryogenesis].
Electron microscopic studies have been made on the developing taste buds in fungiform and vallate papillae of prenatal rats. Three stages of differentiation of these buds are described. The first stage is characterized by presence of the nervous fibers in the connective tissue of the papillae and dense granules of various size, as well as dense-cored vesicles (500-700 A in diameter) in the basal parts of some epithelial cells at the top of the papillae (16-17th days of gestation). The second stage is characterized by nerve processes entering the epithelium and by formation of afferent synaptic contacts between the differentiating epithelial cells and the nervous fibers (19th day of gestation). At the third stage, the cluster of differentiating epithelial cells attains a form which is similar to mature taste buds (21-22nd days of gestation). Thus, to the birthday of rats, differentiation of the basal parts of the taste buds takes place, whereas the apical parts of the taste buds remain undeveloped and do not communicate with the oral cavity. Peculiarities of fine structure of differentiating epithelial cells at the three stages are discussed.


Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia.
For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with "B" symptoms or bulky [> 10 cm] disease) DLBCL. A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.


Tumor cell heterogeneity.
The paper deals with the analysis of literary data on the tumor cell heterogeneity. Phenotypic, genetic and epigenetic mechanisms of heterogeneity are considered. The heterogeneity of metastasis is considered too. The importance for the biology of populations of tumor cells and the sensitivity of tumors to therapeutic treatment are discussed.


A study of the relationship among fear-avoidance beliefs, pain and disability index in patients with low back pain.
This study was conducted in order to determine the relationship among fear-avoidance beliefs, pain and disability index in patients with low back pain as well as to identify factors having an influence on fear-avoidance beliefs, pain and disability index. The subjects used in this study were 55 patients with low back pain. All subjects completed a fear-avoidance beliefs questionnaire (FABQ) which was divided into two subscales, FABQ for physical activity (FABQ-P) and FABQ for work (FABQ-W), Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Roland Morris Disability Questionnaire (RMDQ). In correlation analysis, FABQ-P appeared to show significant correlation with FABQ-W, FABQ-total, VAS and RMDQ, and all variables showed significant correlation with each other. Findings of this study suggest that screening for fear-avoidance beliefs may be useful for identification of patients at risk of psychosocial problems as well as pain intensity and physical impairment.


The investigation of foxe1 variations in papillary thyroid carcinoma.
Recent reports indicated that incidence of thyroid carcinoma is increasing throughout the worldwide. The aim of our study was to determine a possible relationship between Forkhead box E1 (FOXE1) gene variants and histopathological features of papillary thyroid carcinoma. FOXE1 gene variations; rs894673, rs1867277 and rs3758249 were analyzed in 57 Papillary thyroid carcinoma patients and 51 age matched healthy control subjects. Restriction fragment length polymorphism (RFLP) technique was used to specifically detect the variations. There was a significant difference in the distribution of rs894673 genotypes in Papillary thyroid carcinoma cases (P=0.01). AA genotype presence of rs1867277 was more significantly associated with several histopathological parameters such as focal and diffuse capsular invasion, lymphatic invasion, P3 with P4 tumor grade and surgical margins. AA genotype presence in rs1867277 variation was significantly associated with the classical variant which is subtype of papillary thyroid carcinoma. Furthermore, the presence of the allel A was found to be related with lymph node invasion risk by 2.46 fold, capsular invasion risk by 2.97 fold, and pT3 with pT4 pathological stage risk by 4.13 fold and the presence of allele A in rs1867277 was significantly associated with classic variants. The presence of allele A in rs1867277 was more significantly associated with several histopathological parameters in classic variant in papillary thyroid carcinoma cases such as, the presence of the A allele was found relationship with lymph node invasion risk by 2.0 fold, capsular invasion risk by 2.39 fold , and pT3 with pT4 pathological stage risk by 3.57 fold. In addition, AATT, AAAA and GATT haplotypes (rs1867277 and rs894673) were evaluated for association with papillary thyroid carcinoma cases. Our results indicate that the significant difference according to two-allele haplotype distribution between papillary thyroid carcinoma cases and control groups. Our findings suggest that FOXE1 variations generate a higher risk for poor histopathological features of papillary thyroid carcinoma.


Culturing the unculturables: strategies, challenges, and opportunities for gut microbiome study.
Metagenome sequencing techniques revolutionized the field of gut microbiome study. However, it is equipped with experimental and computational biases, which affect the downstream analysis results. Also, live microbial strains are needed for a better understanding of host-microbial crosstalks and for designing next-generation treatment therapies based on probiotic strains and postbiotic molecules. Conventional culturing methodologies are insufficient to get the dark gut matter on the plate; therefore, there is an urgent need to propose novel culturing methods that can fill the limitations of metagenomics. The current work aims to provide a consolidated evaluation of the available methods for host-microbe interaction with an emphasis on in vitro culturing of gut microbes using organoids, gut on a chip, and gut bioreactor. Further, the knowledge of microbial crosstalk in the gut helps us to identify core microbiota, and key metabolites that will aid in designing culturing media and co-culturing systems for gut microbiome study. After the deeper mining of the current culturing methods, we recommend that 3D-printed intestinal cells in a multistage continuous flow reactor equipped with an extended organoid system might be a good practical choice for gut microbiota-based studies.


[Perioperative management of lung transplantations in patients with pulmonary arterial hypertension compared with that in patients with lymphangiomyomatosis].
The number of lung transplantation has tended to increase as a treatment for patients with pulmonary arterial hypertension (PAH) and lymphangiomyomatosis (LAM) in Japan. However, we have little evidence about the comparison of perioperative management in patients with PAH and that in patients with LAM. In this retrospective study, ten patients with PAH and seventeen patients with LAM who underwent the lung transplantations between 2006 and 2011 were enrolled. PAH patients received double lung transplantation with intraoperative cardiopulmonary bypass (CPB) support. Before anesthesia induction, percutaneous cardiopulmonary support (PCPS) was begun. Most of LAM patients received single lung transplantation without using CPB support and PCPS support before anesthesia induction. But sometimes during an operation PCPS support was necessary. Postoperative PCPS support showed no significant differences between PAH and LAM. The four year survival rate was 80% (PAH) and 87.8% (LAM). Pao2/FIo2 in patients with PAH and in those with LAM, %FEV10 in those with LAM after surgery improved when compared to those before surgery. The large difference in perioperative management between patients with PAH and those with LAM is an important knowledge for anesthesist.


Bridging and depletion mechanisms in colloid-colloid effective interactions: A reentrant phase diagram.
A general class of nonadditive sticky-hard-sphere binary mixtures, where small and large spheres represent the solvent and the solute, respectively, is introduced. The solute-solute and solvent-solvent interactions are of hard-sphere type, while the solute-solvent interactions are of sticky-hard-sphere type with tunable degrees of size nonadditivity and stickiness. Two particular and complementary limits are studied using analytical and semi-analytical tools. The first case is characterized by zero nonadditivity, lending itself to a Percus-Yevick approximate solution from which the impact of stickiness on the spinodal curves and on the effective solute-solute potential is analyzed. In the opposite nonadditive case, the solvent-solvent diameter is zero and the model can then be reckoned as an extension of the well-known Asakura-Oosawa model with additional sticky solute-solvent interaction. This latter model has the property that its exact effective one-component problem involves only solute-solute pair potentials for size ratios such that a solvent particle fits inside the interstitial region of three touching solutes. In particular, we explicitly identify the three competing physical mechanisms (depletion, pulling, and bridging) giving rise to the effective interaction. Some remarks on the phase diagram of these two complementary models are also addressed through the use of the Noro-Frenkel criterion and a first-order perturbation analysis. Our findings suggest reentrance of the fluid-fluid instability as solvent density (in the first model) or adhesion (in the second model) is varied. Some perspectives in terms of the interpretation of recent experimental studies of microgels adsorbed onto large polystyrene particles are discussed.


Peritoneal mesothelioma.
Peritoneal mesothelioma is a rare neoplasm often related to previous asbestos exposure. In 14 cases the diagnosis before surgery was virtually impossible, as patients presented with vague abdominal complaints and nonspecific physical examination findings. Laboratory testing (including computed tomography) was of no added diagnostic help. Widespread peritoneal neoplastic growth was the common finding at laparotomy. The tumor was grossly indistinguishable from other types of abdominal carcinomatosis. Electron microscopy proved to be the diagnostic tool of choice. Routine histologic techniques often gave nondiagnostic results. Intraperitoneal asbestos fibers were not observed. Treatment with radiation, chemotherapy, or both produced a 50% partial response rate, but survival was not affected. Malignant ascites was effectively palliated without complication in two of three patients with peritoneovenous shunting. An unusual case occurred in which histologic material from a second-look laparotomy documented complete response to a new regimen of intraperitoneal chemotherapy.


Green tea polyphenols and metabolites in prostatectomy tissue: implications for cancer prevention.
Epidemiologic, preclinical, and clinical trials suggest that green tea consumption may prevent prostate cancer through the action of green tea polyphenols including (-)-epigallocatechin-3-gallate (EGCG). To study the metabolism and bioactivity of green tea polyphenols in human prostate tissue, men with clinically localized prostate cancer consumed six cups of green tea (n = 8) daily or water (n = 9) for 3 to 6 weeks before undergoing radical prostatectomy. Using high-performance liquid chromatography, 4''-O-methyl EGCG (4''-MeEGCG) and EGCG were identified in comparable amounts, and (-)-epicatechin-3-gallate was identified in lower amounts in prostatectomy tissue from men consuming green tea (38.9 +/- 19.5, 42.1 +/- 32.4, and 17.8 +/- 10.1 pmol/g tissue, respectively). The majority of EGCG and other green tea polyphenols were not conjugated. Green tea polyphenols were not detected in prostate tissue or urine from men consuming water preoperatively. In the urine of men consuming green tea, 50% to 60% of both (-)-epigallocatechin and (-)-epicatechin were present in methylated form with 4'-O-MeEGC being the major methylated form of (-)-epigallocatechin. When incubated with EGCG, LNCaP prostate cancer cells were able to methylate EGCG to 4''-MeEGCG. The capacity of 4''-MeEGCG to inhibit proliferation and NF-kappaB activation and induce apoptosis in LNCaP cells was decreased significantly compared with EGCG. In summary, methylated and nonmethylated forms of EGCG are detectable in prostate tissue following a short-term green tea intervention, and the methylation status of EGCG may potentially modulate its preventive effect on prostate cancer, possibly based on genetic polymorphisms of catechol O-methyltransferase.


Forest responses to increasing aridity and warmth in the southwestern United States.
In recent decades, intense droughts, insect outbreaks, and wildfires have led to decreasing tree growth and increasing mortality in many temperate forests. We compared annual tree-ring width data from 1,097 populations in the coterminous United States to climate data and evaluated site-specific tree responses to climate variations throughout the 20th century. For each population, we developed a climate-driven growth equation by using climate records to predict annual ring widths. Forests within the southwestern United States appear particularly sensitive to drought and warmth. We input 21st century climate projections to the equations to predict growth responses. Our results suggest that if temperature and aridity rise as they are projected to, southwestern trees will experience substantially reduced growth during this century. As tree growth declines, mortality rates may increase at many sites. Increases in wildfires and bark-beetle outbreaks in the most recent decade are likely related to extreme drought and high temperatures during this period. Using satellite imagery and aerial survey data, we conservatively calculate that ≈ 2.7% of southwestern forest and woodland area experienced substantial mortality due to wildfires from 1984 to 2006, and ≈ 7.6% experienced mortality associated with bark beetles from 1997 to 2008. We estimate that up to ≈ 18% of southwestern forest area (excluding woodlands) experienced mortality due to bark beetles or wildfire during this period. Expected climatic changes will alter future forest productivity, disturbance regimes, and species ranges throughout the Southwest. Emerging knowledge of these impending transitions informs efforts to adaptively manage southwestern forests.


[Spondylodiscitis in Côte d'Ivoire: findings of computed tomography scan in 18 cases].
The aim of this study was to document computed tomography (CT) scan findings and nosological characteristics in patients managed for spondylodiscitis in Abidjan, Côte d'Ivoire. This retrospective study was carried out over a two-year period (January 2006 to December 2007). A total of 18 cases of spondylodiscitis assessed in the radiology department of Yopougon Teaching Hospital in Abidjan were included. Mean patient age was 39.4 years. Seven patients (38.9%) had positive HIV serology. Mycobacterium tuberculosis was the main causative agent of spondylodiscitis accounting for 94.4% of cases. Only one case (5.6%) of pyogenic spondylodiscitis (staphylococcus aureus) was observed. The upper back was the preferential location (55.6%) of spondylodiscitis. Both discs and vertebral bodies were involved in all cases. Associated manifestations included balance impairment (dorsal kyphosis) (11.2%), soft tissue abscess (44.4%), vertebral compression (11.2%), epiduritis (16.7%), and medullar compression (16.7%). This study shows that CT scan not only plays a decisive role in early positive diagnosis of spondylodiscitis but also contributes to therapy by guiding biopsy to obtain samples necessary to identify the causal germ and assess disco-vertebral involvement. Findings also show that most cases of spondylodiscitis in Abidjan are related to tuberculosis and located in the upper back.


Genomic instability and cancer.
Tumorigenesis can be viewed as an imbalance between the mechanisms of cell-cycle control and mutation rates within the genes. Genomic instability is broadly classified into microsatellite instability (MIN) associated with mutator phenotype, and chromosome instability (CIN) recognized by gross chromosomal abnormalities. Three intracellular mechanisms are involved in DNA damage repair that leads to mutator phenotype. They include the nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR). The CIN pathway is typically associated with the accumulation of mutations in tumor suppressor genes and oncogenes. Defects in DNA MMR and CIN pathways are responsible for a variety of hereditary cancer predisposition syndromes including hereditary non-polyposis colorectal carcinoma (HNPCC), Bloom syndrome, ataxia-telangiectasia, and Fanconi anaemia. While there are many genetic contributors to CIN and MIN, there are also epigenetic factors that have emerged to be equally damaging to cell-cycle control. Hypermethylation of tumor suppressor and DNA MMR gene promoter regions, is an epigenetic mechanism of gene silencing that contributes to tumorigenesis. Telomere shortening has been shown to increase genetic instability and tumor formation in mice, underscoring the importance of telomere length and telomerase activity in maintaining genomic integrity. Mouse models have provided important insights for discovering critical pathways in the progression to cancer, as well as to elucidate cross talk among different pathways. This review examines various molecular mechanisms of genomic instability and their relevance to cancer.


The significance of Mg in prebiotic geochemistry.
Magnesium plays a special role in biochemistry because of its ability to coordinate six oxygen atoms efficiently in its first coordination shell. Such oxygen atoms may be part of one or two charged oxyanions, which means that Mg²⁺ can, for instance, tie together two different phosphate groups that are located at distance from each other in a macromolecule, and in this way be responsible for the folding of molecules like RNA. This property of Mg²⁺ also helps the stabilization of diphosphate and triphosphate groups of nucleotides, as well as promoting the condensation of orthophosphate to oligophosphates, like pyrophosphate and trimetaphosphate. Borates, on the other hand, are known to promote the formation of nucleobases and carbohydrates, ribose in particular, which is yet another constituent of nucleotides. The oldest borate minerals that we find on Earth today are magnesium borates. Dissolved borate stabilizes pentose sugars by forming complexes with cis-hydroxyl groups. In the furanose form of ribose, the preferential binding occurs to the 2 and 3 carbon, leaving the 5 carbon free for phosphorylation. The central role of Mg²⁺ in the function of ribozymes and its 'archaic' position in ribosomes, and the fact that magnesium generally has coordination properties different from other cations, suggests that the inorganic chemistry of magnesium had a key position in the first chemical processes leading to the origin and early evolution of life.


Smoking and outcome of traumatic brain injury.
There is evidence that the cholinergic system is involved in cognitive sequels of traumatic brain injury (TBI). Nicotinic acetylcholine receptors (nAChRs) are known to have a major role in cognitive functions. Smokers have up-regulation of these receptors. This study investigated whether smoking is associated with the outcome from TBI. A specific questionnaire was sent, after checking inclusion and exclusion criteria, to 1022 subjects with TBI who had visited the neurological outpatient clinic of a university hospital during a 14-year period. Of these, 689 (67.4%) responded, forming the final study population. Associations between demographic variables, injury severity and outcome and smoking history were analysed using multivariate methods. Smokers were more often men (p < 0.001), younger at the time of the injury (p = 0.008) and had less education (p < 0.0001). In univariate analysis, non-smokers did not differ for outcome of TBI by GOS-E (p = 0.08). Furthermore, in multivariate analysis, no association was found between smoking history and TBI outcome. This study does not suggest that smoking affects the outcome of TBI.


Amyloid-beta peptide enhances tumor necrosis factor-alpha-induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes.
Although accumulating evidence demonstrates that white matter degeneration contributes to pathology in Alzheimer's disease (AD), the underlying mechanisms are unknown. In order to study the roles of the amyloid-beta peptide in inducing oxidative stress damage in white matter of AD, we investigated the effects of amyloid-beta peptide 25-35 (Abeta) on proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)-induced inducible nitric oxide synthase (iNOS) in cultured oligodendrocytes (OLGs). Although Abeta 25-35 by itself had little effect on iNOS mRNA, protein, and nitrite production, it enhanced TNF-alpha-induced iNOS expression and nitrite generation in OLGs. Abeta, TNF-alpha, or the combination of both, increased neutral sphingomyelinase (nSMase) activity, but not acidic sphingomyelinase (aSMase) activity, leading to ceramide accumulation. Cell permeable C2-ceramide enhanced TNF-alpha-induced iNOS expression and nitrite generation. Moreover, the specific nSMase inhibitor, 3-O-methyl-sphingomyelin (3-OMS), inhibited iNOS expression and nitrite production induced by TNF-alpha or by the combination of TNF-alpha and Abeta. Overexpression of a truncated mutant of nSMase with a dominant negative function inhibited iNOS mRNA production. 3-OMS also inhibited nuclear factor kappaB (NF-kappaB) binding activity induced by TNF-alpha or by the combination of TNF-alpha and Abeta. These results suggest that neutral sphingomyelinase/ceramide pathway is required but may not be sufficient for iNOS expression induced by TNF-alpha and the combination of TNF-alpha and Abeta.


Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer.
Members of the early growth response (EGR) family of transcription factors play diverse functions in response to many cellular stimuli, including growth, stress, and inflammation. Egr3 has gone relatively unstudied, but here through use of the SPECS (Strategic Partners for the Evaluation of Predictive Signatures of Prostate Cancer) Affymetrix whole genome gene expression database we report that Egr3 mRNA is significantly over-expressed in prostate cancer compared to normal prostate tissue (5-fold). The Human Protein Atlas (http://www.proteinatlas.org), a database of tissue microarrays labeled with antibodies against over 11,000 human proteins, was utilized to quantify Egr3 protein expression in normal prostate and prostate cancer patients. In agreement with the SPECS data, we found that Egr3 protein is significantly increased in prostate cancer. The SPECS database has the benefit of extensive clinical follow up for the prostate cancer patients. Analysis of Egr3 mRNA expression in relation to the relapse status reveals that Egr3 mRNA expression is increased in tumor cells of non-relapsed samples (n = 63) compared to normal prostate cells, but is significantly lower in relapsed samples (n = 38) compared to non-relapse. The observations were confirmed using an independent data set. A list of genes correlating with this unique expression pattern was determined. These Egr3-correlated genes were enriched with Egr binding sites in their promoters. The gene list contains inflammatory genes such as IL-6, IL-8, IL1β and COX-2, which have extensive connections to prostate cancer.


Adaptive behavior ratings correlate with symptomatology and IQ among individuals with high-functioning autism spectrum disorders.
Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD group, adaptive communication skills were positively related to IQ while global adaptive functioning was negatively associated with autism symptomatology. Autistic behavior ratings related negatively to ABAS scores in the TD but not the ASD group. This investigation demonstrates: the utility of an adaptive functioning checklist for capturing impairments, even in high-functioning individuals with ASD; and that a relationship between social abilities and autism exists independently of intelligence.


Household Food Insecurity and Demographic Factors, Low Birth Weight and Stunting in Early Childhood: Findings from a Longitudinal Study in South Africa.
Low birthweight (LBW) as well as early childhood stunting are risk factors for increased childhood morbidity in low-and middle-income countries (LMIC). The Covid 19 pandemic has exacerbated food insecurity and unemployment globally, prompting concerns for maternal and child health. We used data from the great recession of 2008 to examine the relationship between household food security and other risk factors with LBW and stunting using a longitudinal sample of South African women and their offspring. Food security indicators, alcohol use, blood pressure and other characteristics were examined in relation to LBW (≤ 2500 g), stunting (height for age ≤ 2SD) and severe stunting (height for age ≤ 3SD). Regression modelling with clustering at maternal ID level were employed to adjust for maternal characteristics and women who gave birth more than once during the reference period. Birthweight data were available for 1173 children and height for age 1216 children. The prevalence of LBW was 14.7% while stunting and severe stunting was 17.8% and 14.5%. Child hunger in the household, maternal hypertension and alcohol use were associated with low birthweight. Food expenditure below the Stats SA poverty line and low dietary diversity was associated with stunting and severe stunting respectively. Maternal height and low birthweight were associated with both stunting and severe stunting. Interventions that can improve household food security and nutritional status during the periconceptional and antenatal period may reduce the prevalence of low birthweight and subsequent stunting in low- and middle-income countries.


Problem Gambling Among Australian Male Prisoners: Lifetime Prevalence, Help-Seeking, and Association With Incarceration and Aboriginality.
Prisoners represent a group containing the highest problem gambling (PG) rate found in any population. PG is of particular concern among Indigenous Australians. Little data exist concerning PG rates among Indigenous Australian prisoners. The present study aimed to address this gap in the literature by examining the lifetime prevalence of PG among male prisoners, whilst identifying prisoners of Aboriginal background. The EIGHT Gambling Screen (Early Intervention Gambling Health Test) was administered to 296 prisoners across three male prisons in South Australia. Previous help-seeking behaviour and forms of gambling were also examined. Sixty percent of prisoners indicated a lifetime prevalence of PG with 18% reporting they were incarcerated due to offending relating to their gambling problem. Indigenous Australian prisoners indicated a significantly higher prevalence of PG (75%) than non-Indigenous prisoners (57%) and reported less than half the rate of help-seeking. Given the high levels of PG and overall low rates of help-seeking among prisoners, prisons may provide an important opportunity to engage this high-risk population with effective treatment programs, in particular culturally appropriate targeted interventions for Australian Indigenous prisoners.


Cost-Benefit Analysis of a Mass Vaccination Strategy to Control Brucellosis in Sheep and Goats in Northern Iraq.
Brucellosis is a major economic and production-limiting disease for livestock owners and the community in Iraq. A cost-benefit analysis was conducted to evaluate the impact of an expanded annual mass vaccination programme of sheep and goats that involves all female and male sheep and goats over the age of 3 months with Rev. 1 vaccine. The proposed expanded vaccination programme was compared to the current annual vaccination program, which involved only vaccinating female sheep and goats between the ages of 3 and 6 months of age with Rev. 1. The cost-benefit analysis model was developed utilizing data collected in Dohuk Governorate, northern Iraq. The seroprevalence in small ruminants (using Rose Bengal test and ELISA in series) was predicted to decrease from 9.22% to 0.73% after 20 years of implementing the proposed annual mass vaccination program. The net present value of the mass vaccination program was estimated to be US$ 10,564,828 (95% Confidence Interval (CI): -16,203,454 to 37,049,245), the benefit-cost ratio was estimated to be 4.25 (95% CI: -2.71 to 11.22), and the internal rate of return was 91.38% (95% CI:11.71 to 190.62%). The proposed vaccination strategy was predicted to decrease the overall financial loss caused by brucellosis from 1.75 to 0.55 US$ per adult female animal. The results of this economic analysis highlight the benefit of implementing an annual mass vaccination program of small ruminants with Rev. 1 vaccine to reduce the prevalence of brucellosis in northern Iraq.


The intraclass correlation coefficient applied for evaluation of data correction, labeling methods, and rectal biopsy sampling in DNA microarray experiments.
We show that the intraclass correlation coefficient (ICC) can be used as a relatively simple statistical measure to assess methodological and biological variation in DNA microarray analysis. The ICC is a measure that determines the reproducibility of a variable, which can easily be calculated from an ANOVA table. It is based on the assessment of both systematic deviation and random variation, and it facilitates comparison of multiple samples at once. We used the ICC first to optimize our microarray data normalization method and found that the use of median values instead of mean values improves data correction. Then the reproducibility of different labeling methods was evaluated, and labeling by indirect fluorescent dye incorporation appeared to be more reproducible than direct labeling. Finally, we determined optimal biopsy sampling by analyzing overall variation in gene expression. The variation in gene expression of rectal biopsies within persons decreased when two biopsies were taken instead of one, but it did not considerably improve when more than two biopsies were taken from one person, indicating that it is sufficient to use two biopsies per person for DNA microarray analysis under our experimental conditions. To optimize the accuracy of the microarray data, biopsies from at least six different persons should be used per group.


Stature in children with chronic kidney disease: analysis of NAPRTCS database.
Despite recent advances in the management of children with chronic kidney disease (CKD), growth remains suboptimal. The purpose of this study was to evaluate factors associated with short stature in children with CKD. We evaluated the chronic renal failure registry of the North American Pediatric Renal Transplant Cooperative Studies (NAPRTCS) to determine the relations among primary diagnosis, age, race, residual renal function, acidosis, anemia, serum phosphorous, calcium, parathyroid hormone (PTH), albumin, and height at entry into the registry in children with CKD. A total of 5,615 patients were entered into the registry between January 1994 and January 2004. We found that older patients, those with glomerular filtration rate (GFR) >50 ml min(-1) 1.73 m(-2), black patients and patients with focal segmental glomerulosclerosis (FSGS) were at lower risk of being short at entry. Anemia (hematocrit below 33%) was an independent risk factor for short stature. Acidosis, serum phosphorous, calcium, albumin and PTH at registration were poor predictors of short stature. Age, race, primary diagnosis, and residual renal function were associated with short stature in children with CKD.


Spatial localization of cardiac optical mapping with multiphoton excitation.
Depth and radius of regions interrogated by cardiac optical mapping with a laser beam depend on photon travel inside the heart. It would be useful to limit the range of depth and radius interrogated. We modeled the effects of a condensing lens to concentrate laser light at a target depth inside the heart, and near infrared excitation to increase penetration and produce two-photon absorption. A Monte Carlo simulation that incorporated a 0.55-NA lens, and absorption and scattering of 1064- or 488-nm laser light in 3-D cardiac tissue indicated the distribution of excitation fluence inside the tissue. A subsequent simulation incorporating absorption and scattering of transmembrane voltage-sensitive fluorescence (wavelength 669 nm) indicated locations from which fluorescence photons exiting the tissue surface originated. The results indicate that mapping at depths up to 300 microm in hearts can provide significant improvement in localization over existing cardiac optical mapping. The estimated interrogation region is sufficiently small to examine cardiac events at a cellular or subcellular scale and may allow mapping at various depths in the heart.


DNA adducts in aldehyde dehydrogenase-positive lung stem cells of A/J mice treated with the tobacco specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
Lung cancer is the leading cause of cancer death in the world. Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells. Aldehyde dehydrogenase (ALDH) is a marker of stem cells. To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Using LC-NSI-HRMS/MS-PRM, O(6)-methyl-G, 7-POB-G, and O(2)-POB-dT were positively identified in ALDH-positive cell DNA. This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis.


New insights about the monomer and homodimer structures of the human AOX1.
Human aldehyde oxidase (hAOX1) is a molybdenum dependent enzyme that plays an important role in the metabolism of various compounds either endogenous or xenobiotics. Due to its promiscuity, hAOX1 plays a major role in the pharmacokinetics of many drugs and therefore has gathered a lot of attention from the scientific community and, particularly, from the pharmaceutical industry. In this work, homology modelling, molecular docking and molecular dynamics simulations were used to study the structure of the monomer and dimer of human AOX. The results with the monomer of hAOX1 allowed to shed some light on the role played by thioridazine and two malonate ions that are co-crystalized in the recent X-ray structure of hAOX1. The results show that these molecules endorse several conformational rearrangements in the binding pocket of the enzyme and these changes have an impact in the active site topology as well as in the stability of the substrate (phthalazine). The results show that the presence of both molecules open two gates located at the entrance of the binding pocket, from which results the flooding of the active site. They also endorse several modifications in the shape of the binding pocket (namely the position of Lys893) that, together with the presence of the solvent molecules, favour the release of the substrate to the solvent. Further insights were also obtained with the assembled homodimer of hAOX1. The allosteric inhibitor (THI) binds closely to the region where the dimerization of both monomers occur. These findings suggest that THI can interfere with protein dimerization.


An assessment of the role of white-tailed deer in the epizootiology of anaplasmosis in the southeastern United States.
The role of white-tailed deer (Odocoileus virginianus) in the epizootiology of anaplasmosis in the southeastern United States was examined through retrospective and prospective serosurveys and by experimental infection studies. No serum antibody reactive to Anaplasma marginale was detected with an indirect fluorescent antibody (IFA) assay from any of 1,376 free-ranging deer sampled from 1968 through 1990 from 13 states and Puerto Rico. Thirty-one additional deer from three bovine anaplasmosis enzootic premises also were negative by IFA and Giemsa-stained blood films. Three captive deer given A. marginale intravenously developed antibodies 38 to 41 days post-inoculation (DPI) and remained seropositive for the duration of the study (161 to 287 DPI). At 42 DPI, rickettsemias of approximately 0.0001% infected erythrocytes were observed in all three deer using a DNA probe; low rickettsemias (maximum 0.01%) persisted through 56, 63, and 87 DPI, respectively. One deer had a recrudescent infection from 126 to 146 DPI (maximum rickettsemia 0.001%). We believe that white-tailed deer in the southeastern United States, even though susceptible to A. marginale infection, are not exposed naturally, even at enzootic sites. Furthermore, white-tailed deer did not develop rickettsemias sufficient to support mechanical transmission by biting flies, which is believed to be the primary means of anaplasmosis transmission in this region.


Academia-industry symbiosis in organic chemistry.
Collaboration between academia and industry is a growing phenomenon within the chemistry community. These sectors have long held strong ties since academia traditionally trains the future scientists of the corporate world, but the recent drastic decrease of public funding is motivating the academic world to seek more private grants. This concept of industrial "sponsoring" is not new, and in the past, some companies granted substantial amounts of money per annum to various academic institutions in exchange for prime access to all their scientific discoveries and inventions. However, academic and industrial interests were not always aligned, and therefore the investment has become increasingly difficult to justify from industry's point of view. With fluctuating macroeconomic factors, this type of unrestricted grant has become more rare and has been largely replaced by smaller and more focused partnerships. In our view, forging a partnership with industry can be a golden opportunity for both parties and can represent a true symbiosis. This type of project-specific collaboration is engendered by industry's desire to access very specific academic expertise that is required for the development of new technologies at the forefront of science. Since financial pressures do not allow companies to spend the time to acquire this expertise and even less to explore fundamental research, partnering with an academic laboratory whose research is related to the problem gives them a viable alternative. From an academic standpoint, it represents the perfect occasion to apply "pure science" research concepts to solve problems that benefit humanity. Moreover, it offers a unique opportunity for students to face challenges from the "real world" at an early stage of their career. Although not every problem in industry can be solved by research developments in academia, we argue that there is significant scientific overlap between these two seemingly disparate groups, thereby presenting an opportunity for a symbiosis. This type of partnership is challenging but can be a win-win situation if both parties agree on some general guidelines, including clearly defined goals and deliverables, biweekly meetings to track research progress, and quarterly or annual meetings to recognize overarching, common objectives. This Account summarizes our personal experience concerning collaborations with various industrial groups and the way it impacted the research programs for both sides in a symbiotic fashion.


Spousal Relative Income and Male Psychological Distress.
Using Panel Study of Income Dynamics 2001-2015 dataset (6,035 households, 19,688 observations), this study takes a new approach to investigating the relationship between wife's relative income and husband's psychological distress, and finds it to be significantly U-shaped. Controlling for total household income, predicted male psychological distress reaches a minimum at a point where wives make 40% of total household income and proceeds to increase, to reach highest level when men are entirely economically dependent on their wives. These results reflect the stress associated with being the sole breadwinner, and more significantly, with gender norm deviance due to husbands being outearned by their wives. Interestingly, the relationship between wife's relative income and husband's psychological distress is not found among couples where wives outearned husbands at the beginning of their marriage pointing to importance of marital selection. Finally, patterns reported by wives are not as pronouncedly U-shaped as those reported by husbands.