On the origin of cerebrovascular microemboli associated with prosthetic heart valves.
Application of transcranial Doppler ultrasonography to asymptomatic prosthetic heart valve patients can result in the detection of transient high intensity signals, similar to those induced by the passage of emboli. However, the origin of these signals is unknown. An in vitro study has been undertaken to investigate the capacity of prosthetic heart valves to generate high intensity Doppler signals in the absence of blood. A pulse duplicator, filled with a seeded saline solution, was used to function prosthetic heart valves under mock-physiological conditions. A Björk-Shiley Monostrut valve was mounted in the aortic port while a tri-leaflet control valve was fixed in the mitral port. At stations upstream and downstream from the Björk-Shiley valve, flow was monitored using pulsed wave Doppler ultrasound (Nicolet TC-2000, 2 MHz probe). The effect of damping the harsh closure of the mechanical valve was investigated by applying a thin layer of soft adhesive tape between the valve occluder and outer ring. For all valve configurations, transient high intensity Doppler signals, characteristic of microemboli and similar to those observed in clinical studies of prosthetic heart valve patients, were detected downstream from the aortic port. The number of microemboli signals did not change significantly between sites at 20 cm and 40 cm downstream from the aortic valve. Damping the Björk-Shiley valve closure greatly reduced (by 80%) the number of microemboli signals detected. It is concluded that Doppler microemboli signals can be generated by prosthetic heart valves while functioning in the absence of the formed elements of blood, and that the number of microemboli signals produced depends upon the rate of energy dissipation at valve closure.


Bispectral Index Measurements Are Not Degraded During Aeromedical Evacuations.
For a decade, depth of anesthesia monitoring has become a reality in the operating room. It provides valuable help for managing anesthesia, especially for unstable patients. This might be particularly relevant during aeromedical evacuation. In this study, we aimed to assess the validity of the bispectral index (BIS) during long-range patient transportation aboard fixed-wing aircraft. BIS was recorded in 30 patients, 25 under anesthesia and 5 awake, during aeromedical evacuations performed by the French Air Force. BIS index was available and analyzable (signal quality index above 50%) more than 90% of time. Despite potential pitfalls related to mechanical or electrical interference, BIS monitor can be reliably used to monitor depth of anesthesia during individual strategic aeromedical evacuations.


Finding the evidence in CAM: a student's perspective.
This commentary offers a future health care provider's perspective on the role of complementary and alternative medicine (CAM) in Western (namely, in US) medical education and practice. As a student of both public health and medicine in the United States, Jeffrey Ghassemi is interested in CAM's contribution to improving medical practice and teaching. The commentary highlights the ambiguous definitions of CAM to Westerners despite the rising popularity of and expenditures for alternative modalities of care. It then argues for collaboration between alternative and established medical communities to ascertain the scientific merits of CAM. It concludes by calling for a new medical paradigm that embraces the philosophies of both communities to advance education and patient care.


Epigenetic Alterations Associated With Early Prenatal Dexamethasone Treatment.
Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). It has potential short- and long-term risks and has been shown to affect cognitive functions. Here, we investigate whether epigenetic modification of DNA during early developmental stages may be a key mediating mechanism by which prenatal DEX treatment could result in poor outcomes in the offspring. We analyzed genome-wide CD4+ T cell DNA methylation, assessed using the Infinium HumanMethylation450 BeadChip array in 29 individuals (mean age = 16.4 ± 5.9 years) at risk for CAH and treated with DEX during the first trimester and 37 population controls (mean age = 17.0 years, SD = 6.1 years). We identified 9672 differentially methylated probes (DMPs) associated with DEX treatment and 7393 DMPs associated with a DEX × sex interaction. DMPs were enriched in intergenic regions located near epigenetic markers for active enhancers. Functional enrichment of DMPs was mostly associated with immune functioning and inflammation but also with nonimmune-related functions. DEX-associated DMPs enriched near single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease, and DEX × sex-associated DMPs enriched near SNPs associated with asthma. DMPs in genes involved in the regulation and maintenance of methylation and steroidogenesis were identified as well. Methylation in the BDNF, FKBP5, and NR3C1 genes were associated with the performance on several Wechsler Adult Intelligence Scale-Fourth Edition subscales. In conclusion, this study indicates that DNA methylation is altered after prenatal DEX treatment. This finding may have implications for the future health of the exposed individual.


[Use of botulinum toxin in the treatment of laryngeal dystonia (spasmodic dysphonia): preliminary study of twelve patients].
Laryngeal dystonia (spasmodic dysphonia) is a movement disorder characterized by involuntary contractions of laryngeal muscles involved with vocalization. The introduction of botulinum toxin in the treatment of laryngeal dystonia had a major clinical impact due to the striking improvement of symptoms. We report the preliminary results of therapeutical use of botulinum toxin in the treatment of twelve patients with laryngeal dystonia. After an extensive clinical evaluation, the patients underwent a videostroboscopic exam for diagnostic confirmation. Botulinum toxin was injected in the cricothyreoid membrane, directed towards the thyreoaritenoid muscle, with the aid of eletromyography needles. Most of patients who underwent botulinum toxin injection had a significant improvement of their symptoms (83%), with effects lasting for four months in average and without important side effects.


Influence of mild to moderate obesity on left ventricular stress filling pattern in hypertension.
In resting condition, obese subjects are described as having impaired diastolic filling. To examine the effect of mild to moderate obesity on left ventricular diastolic performance during stress in hypertension, we determined the filling responses to dynamic submaximal exercise in 19 obese hypertensive patients (body mass index, 26 to 30 kg/m2) with a normal left ventricular structure, 19 age- and sex-matched, non-obese hypertensive patients, and 19 age- and sex-matched, non-obese normotensive controls (mean age, 55+/-3 yr). Doppler echocardiographic studies were performed at baseline and 1 min after exercise on a supine ergometer bicycle. At rest, systolic function and filling indices, peak velocities of early (E) and late (A) filling, and their ratio (E/A), were similar in the two hypertensive groups, while normotensive controls had higher peak velocities of E and E/A. At a maximum workload of 75 W, blood pressure and heart rate increased similarly in the two hypertensive groups. Peak velocities of E and A increased significantly after exercise. The percentage change in the peak velocity of E was greater in obese hypertensive patients than in non-obese hypertensive patients and normotensive controls (23+/-4 vs. 12+/-3 and 14+/-3%, p < 0.05). Percentage changes in A and E/A were similar in the three groups. Our study suggests that mild to moderate obesity does not further worsen left ventricular diastolic filling at rest and mitigates diastolic filling abnormalities after exercise in hypertensive patients.


Classification of Psychoses Based on Immunological Features: A Machine Learning Study in a Large Cohort of First-Episode and Chronic Patients.
For several years, the role of immune system in the pathophysiology of psychosis has been well-recognized, showing differences from the onset to chronic phases. Our study aims to implement a biomarker-based classification model suitable for the clinical management of psychotic patients. A machine learning algorithm was used to classify a cohort of 362 subjects, including 160 first-episode psychosis patients (FEP), 70 patients affected by chronic psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder) with psychosis (CRO) and 132 health controls (HC), based on mRNA transcript levels of 56 immune genes. Models distinguished between FEP, CRO, and HC and between the subgroup of drug-free FEP and HC with a mean accuracy of 80.8% and 90.4%, respectively. Interestingly, by using the feature importance method, we identified some immune gene transcripts that contribute most to the classification accuracy, possibly giving new insights on the immunopathogenesis of psychosis. Therefore, our results suggest that our classification model has a high translational potential, which may pave the way for a personalized management of psychosis.


Prebiotic chemistry and the origin of the RNA world.
The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World. The central problem for origin-of-life studies, therefore, is to understand how a protein-free RNA World became established on the primitive Earth. We first review the literature on the prebiotic synthesis of the nucleotides, the nonenzymatic synthesis and copying of polynucleotides, and the selection of ribozyme catalysts of a kind that might have facilitated polynucleotide replication. This leads to a brief outline of the Molecular Biologists' Dream, an optimistic scenario for the origin of the RNA World. In the second part of the review we point out the many unresolved problems presented by the Molecular Biologists' Dream. This in turn leads to a discussion of genetic systems simpler than RNA that might have "invented" RNA. Finally, we review studies of prebiotic membrane formation.


Cytoskeletal discontinuities in the cell body cortex initiate basal body assembly and oral development in the ciliate Stentor.
My previous work has shown that disconnecting the oral apparatus of Stentor into two parts induces mass assembly of basal bodies on the ventral cell surface and thus initiates oral development. This operation severs the extensive microtubule tracts joining the oral membranelles at their bases. To determine whether basal body assembly and oral development are also induced by permanently disconnecting the longitudinal microtubule fibre tracts (mt fibre tracts) of the cell body cortex, I interposed a ring of inverted (heteropolar) cortex between the anterior and posterior halves of interphase stentors. When successful, this operation made it impossible for these fibre tracts to rejoin at the heteropolar boundaries and always induced basal body assembly and oral development in the graft complex. By contrast, tripartite homopolar graft complexes rarely initiated oral development; when they did, it was apparently in response to the presence of disproportionately small oral structures, which is the normal stimulus for oral development in Stentor. The mt fibre tracts of tripartite homopolar grafts also eventually became continuous. These results support the hypothesis that permanent, extensive discontinuities anywhere within the cortical cytoskeleton can trigger basal body assembly and oral development. Since the onset of these processes is known to initiate cell division in Stentor, the results also suggest that development of discontinuities within the cortical cytoskeleton during interphase growth may be the endogenous stimulus initiating cell division in Stentor.


What is the effect of physical activity on the knee joint? A systematic review.
Although several studies have examined the relationship between physical activity and knee osteoarthritis, the effect of physical activity on knee joint health is unclear. The aim of this systematic review was to examine the relationships between physical activity and individual joint structures at the knee. Computer-aided searches were conducted up until November 2008, and the reference lists of key articles were examined. The methodological quality of selected studies was assessed based on established criteria, and a best-evidence synthesis was used to summarize the results. We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects. This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health.


Human Bocavirus: Can It Trigger Hemophagocytic Lymphohistiocytosis?
With improvements in molecular diagnostic methods, report of Human bocavirus (HBoV) as an etiologic agent in many studies on viral respiratory and gastrointestinal infections has been increasing. Two pediatric patients who presented with secondary hemophagocytic lymphohistiocytosis were examined for etiologic causes, including viruses. Whole bacterial and fungal cultures and viral serological studies were negative. Viral polymerase chain reaction of nasopharyngeal secretions showed HBoV. One was successfully treated with intravenous immunoglobulins, whereas the other died with multiorgan failure. Here we report 2 pediatric patients with secondary hemophagocytic lymphohistiocytosis and detection of HBoV as the sole agent, predicting an association.


Screening for and identification of starch-, amylopectin-, and pullulan-degrading activities in bifidobacterial strains.
Forty-two bifidobacterial strains were screened for alpha-amylase and/or pullulanase activity by investigating their capacities to utilize starch, amylopectin, or pullulan. Of the 42 bifidobacterial strains tested, 19 were capable of degrading potato starch. Of these 19 strains, 11 were able to degrade starch and amylopectin, as well as pullulan. These 11 strains, which were shown to produce extracellular starch-degrading activities, included 5 strains of Bifidobacterium breve, 1 B. dentium strain, 1 B. infantis strain, 3 strains of B. pseudolongum, and 1 strain of B. thermophilum. Quantitative and qualitative enzyme activities were determined by measuring the concentrations of released reducing sugars and by high-performance thin-layer chromatography, respectively. These analyses confirmed both the inducible nature and the extracellular nature of the starch- and pullulan-degrading enzyme activities and showed that the five B. breve strains produced an activity that is consistent with type II pullulanase (amylopullulanase) activity, while the remaining six strains produced an activity with properties that resemble those of type III pullulan hydrolase.


Treatment of dyskeratosis congenita with granulocyte-macrophage colony-stimulating factor and erythropoietin.
Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy, mucosal leucoplakia, and bone marrow failure. Pancytopenia is difficult to manage in patients with this disorder. We describe a 13-month-old-boy who presented with reticulate skin lesions, paleness, and hepatosplenomegaly. Anemia and leukopenia developed by the age of 43 months. The patient was treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) (5 microg/kg/d, subcutaneously) for 19 months and erythropoietin (150 U/kg 3 days in a week, subcutaneously) for 8 months, with excellent neutrophil and hemoglobin response. Recurrent infections were not developed after starting GM-CSF, and packed red blood cell transfusion was not given to the patient after starting erythropoietin. GM-CSF combined with erythropoietin may be used in the treatment of bone marrow failure in patients with DC without an HLA-identical donor.


Simultaneous determination of catecholamines and their metabolites related to Alzheimer's disease in human urine.
A simple and specific high-performance liquid chromatography method coupled with fluorescence detection (HPLC-FL) has been developed for the simultaneous determination of L-3,4-dihydroxyphenylalanine, norepinephrine, dopamine, epinephrine and 3,4-dihydroxyphenylacetic acid in human urine. The samples were derivatized by 1,2-diphenylethylenediamine with isoprenaline as internal standard. The factors affecting the fluorescence yield were investigated, including the reaction and separation conditions. The catecholamine derivatives were separated on a Kromasil C(18) column with methanol and sodium acetate buffer as mobile phase. The limits of detection for all catecholamines ranged from 0.2 to 1.1 ng/mL. The linear ranges were from 2.5 to 200 ng/mL except 3,4-dihydroxyphenylacetic acid from 5 to 200 ng/mL. The intra- and interday RSDs for all catecholamines were 1.0-8.0 and 2.1-14%, respectively. The method was successfully applied to determine the catecholamines in human urine from 14 Alzheimer's disease patients and 14 healthy volunteers. It was concluded that the mean levels of catecholamines in urine of Alzheimer's disease patients were all lower than those in healthy volunteers. The cluster analysis and independent samples T-test were used to distinguish the Alzheimer's disease patients and healthy volunteers.


Analyses of multi-irradiation film for system alignments in stereotactic radiotherapy (SRT) and radiosurgery (SRS).
In stereotactic radiosurgery, a seven-irradiation film was used to define any discrepancy between the beam and target centres. A mathematical model based on the linac alignment and target set-up was developed to diagnose the discrepancies of the seven-irradiation film between the beam and simulation target centres. From the measured data of the multi-irradiation film, this mathematical model leads to five parameters in seven equations. Twin computer codes were employed to solve the five parameters from the seven equations. By feeding the discrepancy data into the two computer codes, the sources of the target-to-beam discrepancy were revealed. From these decoded sources, the target coordinates were adjusted and then the seven-irradiation film procedure was repeated. This discrepancy thus obtained was found to be drastically reduced. Some decoded parameters were consistently verified by direct measurements. This demonstrates that the present mathematical model and computer code do reveal the causes of the target-to-beam misalignment and gantry sag. In a further effort to test the feasibility of the mathematical model and the computer codes, the target's lateral coordinate was deliberately offset by 1.5 mm and then another seven-irradiation film was taken. By inserting these discrepancies into the computer codes, it was found that the deviation was consistent with the intentional offset. In addition, the mathematical model and computer codes are applicable to any multi-irradiation technique.


Optimization of resonantly cladding-pumped erbium-doped fiber amplifiers for space-borne applications.
Lasers for use in space-borne applications require ultrahigh efficiency due to limited heat dissipation and power generation capacity. In particular, interplanetary optical communication systems require high-efficiency, moderate-power (>4 W) optical transmitters in the 1600 nm wavelength range. Resonantly pumped dual-clad erbium-doped fiber lasers are best suited for this purpose. Parametric numerical optimizations are performed using a two-level propagation model modified to include spatial effects specific to large-mode-area fibers. Propagation loss mechanisms are found to be limiting factors due to the relatively low cross-sections and low quenching-free doping densities of erbium. Although experimental reports have demonstrated efficiencies up to 33%, simulation results indicate that over 53% power-conversion efficiency can be achieved using commercial fibers, and over 75% can be achieved using custom fibers employing propagation-loss mitigation strategies.


Quantifying the effect of crop spatial arrangement on weed suppression using functional-structural plant modelling.
Suppression of weed growth in a crop canopy can be enhanced by improving crop competitiveness. One way to achieve this is by modifying the crop planting pattern. In this study, we addressed the question to what extent a uniform planting pattern increases the ability of a crop to compete with weed plants for light compared to a random and a row planting pattern, and how this ability relates to crop and weed plant density as well as the relative time of emergence of the weed. To this end, we adopted the functional-structural plant modelling approach which allowed us to explicitly include the 3D spatial configuration of the crop-weed canopy and to simulate intra- and interspecific competition between individual plants for light. Based on results of simulated leaf area development, canopy photosynthesis and biomass growth of the crop, we conclude that differences between planting pattern were small, particularly if compared to the effects of relative time of emergence of the weed, weed density and crop density. Nevertheless, analysis of simulated weed biomass demonstrated that a uniform planting of the crop improved the weed-suppression ability of the crop canopy. Differences in weed suppressiveness between planting patterns were largest with weed emergence before crop emergence, when the suppressive effect of the crop was only marginal. With simultaneous emergence a uniform planting pattern was 8 and 15 % more competitive than a row and a random planting pattern, respectively. When weed emergence occurred after crop emergence, differences between crop planting patterns further decreased as crop canopy closure was reached early on regardless of planting pattern. We furthermore conclude that our modelling approach provides promising avenues to further explore crop-weed interactions and aid in the design of crop management strategies that aim at improving crop competitiveness with weeds.


Prox1 Inhibits Proliferation and Is Required for Differentiation of the Oligodendrocyte Cell Lineage in the Mouse.
Central nervous system injury induces a regenerative response in ensheathing glial cells comprising cell proliferation, spontaneous axonal remyelination, and limited functional recovery, but the molecular mechanisms are not fully understood. In Drosophila, this involves the genes prospero and Notch controlling the balance between glial proliferation and differentiation, and manipulating their levels in glia can switch the response to injury from prevention to promotion of repair. In the mouse, Notch1 maintains NG2 oligodendrocyte progenitor cells (OPCs) in a progenitor state, but what factor may enable oligodendrocyte (OL) differentiation and functional remyelination is not understood. Here, we asked whether the mammalian homologue of prospero, Prox1, is involved. Our data show that Prox1 is distributed in NG2+ OPCs and in OLs in primary cultured cells, and in the mouse spinal cord in vivo. siRNA prox1 knockdown in primary OPCs increased cell proliferation, increased NG2+ OPC cell number and decreased CC1+ OL number. Prox1 conditional knockout in the OL cell lineage in mice increased NG2+ OPC cell number, and decreased CC1+ OL number. Lysolecithin-induced demyelination injury caused a reduction in CC1+ OLs in homozygous Prox1-/- conditional knockout mice compared to controls. Remarkably, Prox1-/- conditional knockout mice had smaller lesions than controls. Altogether, these data show that Prox1 is required to inhibit OPC proliferation and for OL differentiation, and could be a relevant component of the regenerative glial response. Therapeutic uses of glia and stem cells to promote regeneration and repair after central nervous system injury would benefit from manipulating Prox1.


Prevalence and in-hospital mortality during arrhythmia-related admissions in adults with tetralogy of Fallot.
Although outcomes of arrhythmia diagnosis have been described in ambulatory tetralogy of Fallot (TOF) patients, these have not been studied in hospitalized patients. The purpose of this study was to determine the prevalence and in-hospital mortality due to arrhythmias in TOF patients based on a review of the National Inpatient Sample database. Admissions in adult TOF patients (2000-2014) were categorized as arrhythmia-related admission (ARA) or non-arrhythmia-related admission (NRA) based on arrhythmia diagnostic codes. Of 18,353 admissions, 5071 (27.6%) were ARA. The most common arrhythmias were atrial fibrillation (15.5%), atrial flutter (8.4%) and ventricular tachycardia (8.2%), and the prevalence of overall ARA as well as specific arrhythmia types increased over time. In-hospital mortality for ARA was 5.4%, and decreased over time. Arrhythmia diagnosis was an independent predictor of in-hospital mortality (odds ratio [OR] 1.63, 1.34-2.01, p = 0.001). Similarly, atrial fibrillation (OR 1.49, 1.18-1.89, p = 0.001) and ventricular tachycardia (OR: 2.01, 1.55-2.98, p = 0.001) were independent predictors of in-hospital mortality. Compared to small bed-size hospital, ARA in large hospital bed-size hospital was associated with a lower in-hospital mortality (OR 0.71, 0.53-0.96, p = 0.03). Atrial fibrillation was the most common arrhythmia in hospitalized TOF patients, and arrhythmia diagnosis (specifically atrial fibrillation and ventricular tachycardia) was an independent predictor of in-hospital mortality, while admission to a large bed-size hospital was associated with a lower risk of in-hospital mortality. Further studies are required to determine if a more proactive approach to arrhythmia management in the ambulatory TOF population will reduce hospitalizations and mortality.


A brief history of CD8 T cells.
CD8 T cells comprise a powerful branch of the adaptive immune system, yet were not formally recognized until long after the discovery of antibody. CD8 T cells contribute to the eradication of intracellular infections and to the control of many chronic infections. There is tempered optimism that CD8 T cell memory elicited via vaccination may hold the key to manufacturing protective immunity against pathogens that cause chronic infections in humans. The specificity and destructive capabilities of CD8 T cells may also be harnessed for the eradication of tumors. However, CD8 T cells also contribute to a variety of clinical difficulties such as immune mediated pathology, rejection of organ transplants, and autoimmunity. Clearly, learning how to safely generate protective long-lived CD8 T cell memory and how to control or eliminate specific unwanted responses could deliver substantial clinical rewards, and there is a great need for continued research on the biology and therapeutic potential of these cells. Herein, we recount the historical developments leading to the discovery of CD8 T cells, highlight a few of the important discoveries that have followed, and discuss some of the critical issues on the horizon.


Supervised learning with complex spikes and spike-timing-dependent plasticity.
One distinctive feature of Purkinje cells is that they have two types of discharge: in addition to simple spikes they fire complex spikes in response to input from the climbing fibers. These complex spikes have an initial rapid burst of spikes and spikelets followed by a sustained depolarization; in some models of cerebellar function this climbing fiber input supervises learning in Purkinje cells. On the other hand, synaptic plasticity is often thought to rely on the timing of pre-synaptic and post-synaptic spikes. It is suggested here that the period of depolarization following a complex spike, combined with a simple spike-timing-dependent plasticity rule, gives a mechanism for the climbing fiber to supervise learning in the Purkinje cell. This proposal is illustrated using a simple simulation in which it is seen that the climbing fiber succeeds in supervising the learning.


Suppression of tumorigenicity in hybrids of normal and oncogene-transformed CHEF cells.
Somatic cell hybridization experiments were carried out to determine whether normal cells have the ability to suppress the transforming effects of a defined oncogene. A nontransformed Chinese hamster embryo fibroblast cell line (CHEF/18-dm2) was used as the normal parent, and a CHEF/18 transfectant carrying the human mutant c-Ha-ras (EJ) oncogene was used as the tumorigenic parent. Selected hybrids (L318 cell lines) were assayed for the presence of EJ DNA, for the p21 product of the c-Ha-ras gene, and for various indices of cell transformation. These hybrids exhibited a fibroblastic morphology similar to the normal parent, although they contained the EJ gene and expressed its p21 protein product at levels comparable with the transformed parent. They had a reduced capacity for anchorage-independent growth (plating efficiency in methylcellulose of less than 0.3-13%, as compared with greater than 90% for the transformed parent) and decreased tumor-forming ability in athymic mice. These findings show that normal CHEF/18 cells contain suppressor genes capable of inhibiting expression of the transformed phenotype, and tumor-forming ability, in the presence of an activated EJ oncogene.


B cell MALT lymphoma diagnosed by labial minor salivary gland biopsy in patients screened for Sjögren's syndrome.
Three patients presented to the Sjögren's syndrome (SS) Clinic at the National Institute of Dental and Craniofacial Research for screening. The records of patients with SS with a diagnosis of lymphoma were examined to determine whether the diagnosis was made in any of the cases as a result of labial salivary gland (LSG) biopsies. All patients had typical features of primary SS according to the American-European Consensus Group criteria. B cell mucosa associated lymphoid tissue (MALT) lymphoma was diagnosed based upon the LSG biopsy. This report underlines the advantages of performing LSG biopsies as a routine part of screening for SS, and shows that it may in some instances lead to early diagnosis of MALT lymphomas in patients who show no signs of pre-existing lymphoma.


Solar radiation during rewarming from torpor in elephant shrews: supplementation or substitution of endogenous heat production?
Many small mammals bask in the sun during rewarming from heterothermy, but the implications of this behaviour for their energy balance remain little understood. Specifically, it remains unclear whether solar radiation supplements endogenous metabolic thermogenesis (i.e., rewarming occurs through the additive effects of internally-produced and external heat), or whether solar radiation reduces the energy required to rewarm by substituting (i.e, replacing) metabolic heat production. To address this question, we examined patterns of torpor and rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in outdoor cages with access to either natural levels of solar radiation or levels that were experimentally reduced by means of shade cloth. We also tested whether acclimation to solar radiation availability was manifested via phenotypic flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST) capacity and/or summit metabolism (Msum). Rewarming rates varied significantly among treatments, with elephant shrews experiencing natural solar radiation levels rewarming faster than conspecifics experiencing solar radiation levels equivalent to approximately 20% or 40% of natural levels. BMR differed significantly between individuals experiencing natural levels of solar radiation and conspecifics experiencing approximately 20% of natural levels, but no between-treatment difference was evident for NST capacity or Msum. The positive relationship between solar radiation availability and rewarming rate, together with the absence of acclimation in maximum non-shivering and total heat production capacities, suggests that under the conditions of this study solar radiation supplemented rather than substituted metabolic thermogenesis as a source of heat during rewarming from heterothermy.


Transcriptomic and Proteomic Characterization of the Immune Response to Elective Spinal Reconstructive Surgery: Impact of Aging and Comparisons with the Traumatic Injury Response.
Major surgery triggers trauma-like stress responses linked to age, surgery duration, and blood loss, resembling polytrauma. This similarity suggests elective surgery as a surrogate model for studying polytrauma immune responses. We investigated stress responses across age groups and compared them to those of polytrauma patients. Patients undergoing major spinal reconstruction surgery were divided into older (age > 65, n=5) and young (age=18-39, n=6) groups. A comparison group consisted of matched trauma patients (n=8). Blood samples were collected before, during, and after surgery. Bone marrow and peripheral blood mononuclear cells (BMMC and PBMC) were analyzed using CITEseq/scRNAseq. Plasma was subjected to dual-platform proteomic analysis (Somalogic and O-link). Response to polytrauma was highest within 4 hrs. By comparison, the response to surgery was highest at 24 hrs. Both insults triggered significant changes in CD14+ monocytes, with increased inflammation and lower MHC-II expression. Older patient's CD14+ monocytes displayed higher inflammation and less MHC-II suppression; a trend also seen in BMMCs. While NK cells were markedly activated after polytrauma; NK cells were suppressed after surgery, especially in older patients. In plasma, innate immunity proteins dominated at 24 hours, shifting to adaptive immunity proteins by 6 weeks with heightened inflammation in older patients. SASP proteins were higher in older patients at baseline and further elevated during and after surgery. While both major surgery and polytrauma initiate immune and stress responses, substantial differences exist in timing and cellular profiles, suggesting major elective surgery is not a suitable surrogate for the polytrauma response. Nonetheless, distinct responses in young vs. older patients highlight the utility of elective spinal in studying patient-specific factors affecting outcomes following major elective surgery.


The randomized clinical trial in orthopaedics: obligation or option?
The classic randomized clinical trial is difficult to apply to the evaluation of surgical procedures. After reviewing the structure and rationale of cohort studies and randomized clinical trials, four types of bias in randomized clinical trials that present difficulties in clinical studies are identified. Other problems that may limit the willingness of orthopaedic surgeons to conduct randomized clinical trials relate to the surgical procedure itself, the outcome of the trial of interest, surgical philosophy, and the ethical implications for a surgeon of a randomized clinical trial. A recently proposed variation of the classic randomized clinical-trial model, the randomized-surgeon design, appears to solve some of these problems.


Impact of oil prices, the U.S interest rates on Turkey's real estate market. New evidence from combined co-integration and bootstrap ARDL tests.
The research aims to provide new empirical evidence by testing the impact of the external shocks namely: oil prices and the U.S interest rate on Turkey's real estate market by using three techniques of co-integration tests namely: the newly developed bootstrap autoregressive distributed lag (ARDL) testing approach as proposed by (McNown et al. 2018), the new approach involving the Bayer-Hanck (2013) combined co-integration test, Hatemi-J (2008) co-integration testing approach. The ARDL model is utilized to explore the relationship between the variables. The findings show that the oil prices have a positive impact on Turkey's real estate market, the results confirm that there is a significant impact of oil prices on Turkey's real estate market through the domestic interest rate. Furthermore, the results demonstrated that there is a significant spillover influence of the U.S. interest rates on Turkey's real estate market through oil prices and domestic interest rates. This study suggests that the following factors led to increasing the sensitivity and volatility of the Turkish real estate market to oil prices and the U.S. interest rate fluctuations: the presence of economic interdependence between the USA and Turkey, and the majority of the external debts and the reserve currency in Turkey are composed in the USD, and Turkey's oil imports hit record high in last years. Finally, this article suggests that policymakers in Turkey should pay close attention to the effects of external shocks namely the oil prices and U.S. interest rates on Turkish markets to maintain economic and financial stability.


Interaction of diet and photoperiod on growth and reproduction in male golden hamsters.
Two basic diets (commercial rodent pellets or seeds) with or without supplements of carbohydrate were tested for growth and development, and effects on organ weights and serum calcium in male golden hamsters. The additional influence of photoperiod was measured. The data suggest that a seed diet alone is not adequate for growth. Addition of seeds and/or carbohydrate to the pellet diet increases growth rates substantially compared to the pellet diet alone. There are significant interaction effects on reproduction between diet and photoperiod indicating that diet can modify responses to short photic input. While reproduction remains essentially normal in seed-fed animals in long photoperiods, the rate of reproductive involution in short photoperiods is greatly enhanced. Added carbohydrate appears to offer some protection against the adverse effect of short photoperiods on reproduction. Even though calcium supplements to the diet increase serum calcium levels toward normal, growth rates are not improved. Addition of Tenebrio (grain beetle) larvae to the seed diet induces growth rates comparable to those of control animals, yet serum calcium levels remain significantly lower.


Phospho-regulation of kinesin-5 during anaphase spindle elongation.
The kinesin-5 Saccharomyces cerevisiae homologue Cin8 is shown here to be differentially phosphorylated during late anaphase at Cdk1-specific sites located in its motor domain. Wild-type Cin8 binds to the early-anaphase spindles and detaches from the spindles at late anaphase, whereas the phosphorylation-deficient Cin8-3A mutant protein remains attached to a larger region of the spindle and spindle poles for prolonged periods. This localization of Cin8-3A causes faster spindle elongation and longer anaphase spindles, which have aberrant morphology. By contrast, the phospho-mimic Cin8-3D mutant exhibits reduced binding to the spindles. In the absence of the kinesin-5 homologue Kip1, cells expressing Cin8-3D exhibit spindle assembly defects and are not viable at 37°C as a result of spindle collapse. We propose that dephosphorylation of Cin8 promotes its binding to the spindle microtubules before the onset of anaphase. In mid to late anaphase, phosphorylation of Cin8 causes its detachment from the spindles, which reduces the spindle elongation rate and aids in maintaining spindle morphology.


Flexible fibreoptic sigmoidoscopy--an alternative to colonoscopy?
The results of 166 colonoscopic examinations are reported with particular reference to site and nature of the lesion identified. One hundred and fifty-five polyps and 13 colorectal cancers were found, 62 polyps and five cancers being beyond 50 cm from the anal verge. It is suggested that the number of lesions beyond the reach of a flexible fibreoptic sigmoidoscope would be unacceptably high and that there can be no justification for the purchase of such an instrument as an alternative to a full length colonoscope. Whilst the fibreoptic instrument does have advantages as a sigmoidoscope its cost will preclude its widespread use in New Zealand at the present time.


[Oxidation and assimilation pathways of methylated amines in Arthrobacter globiformis].
The oxidation by Arthrobacter globiformis B-175 of tertiary, secondary, and primary amines is catalyzed by specific induced enzymes. Trimethylamine is oxidized to dimethylamine via trimethylamine N-oxide by monooxygenase and demethylase. Dimethylamine is converted to methylamine by another monooxygenase. Methylamine is oxidized to ammonia and formaldehyde by aminoxidase. Formaldehyde is assimilated via ribulose monophosphate cycle, which is confirmed by the presence of hexose-phosphate synthase and by the early and predominant formation of radioactive sugar phosphates during short-term incubation of the cells with labelled methylated amines. Hexose-phosphate synthase was also found in two other strains of A. globiforms (B-126, B-53) which assimilated methylated amines. This methylotroph contains the enzymes of the Krebs cycle which seems to be involved in the synthesis of organic acids. The participation of ammonium nitrogen in anabolic processes is accomplished by reductive amination of alpha-ketoglutarate, glyoxylate, and pyruvate.


Relationship of pulmonary dysfunction to respiratory infection. A study of New York City office workers.
Pulmonary function tests were administered to 1,573 male and female office workers 30 years of age or older during their annual periodic health examinations. The frequency of respiratory infections was established from the workers' medical records. Fourteen percent had pulmonary function abnormalities; the men and women were equally abnormal. A comparison of the frequency of respiratory infections in subjects with normal and abnormal pulmonary function, matched according to age, sex and smoking history, showed no significant differences. Two subsequent years of retesting produced similar data for pulmonary function as well as for the occurrence of respiratory infections.


A genetic interaction between RAP1 and telomerase reveals an unanticipated role for RAP1 in telomere maintenance.
RAP1 is one of the components of shelterin, the capping complex at chromosome ends or telomeres, although its role in telomere length maintenance and protection has remained elusive. RAP1 also binds subtelomeric repeats and along chromosome arms, where it regulates gene expression and has been shown to function in metabolism control. Telomerase is the enzyme that elongates telomeres, and its deficiency causes a premature aging in humans and mice. We describe an unanticipated genetic interaction between RAP1 and telomerase. While RAP1 deficiency alone does not impact on mouse survival, mice lacking both RAP1 and telomerase show a progressively decreased survival with increasing mouse generations compared to telomerase single mutants. Telomere shortening is more pronounced in Rap1-/- Terc-/- doubly deficient mice than in the single-mutant Terc-/- counterparts, leading to an earlier onset of telomere-induced DNA damage and degenerative pathologies. Telomerase deficiency abolishes obesity and liver steatohepatitis provoked by RAP1 deficiency. Using genomewide ChIP sequencing, we find that progressive telomere shortening owing to telomerase deficiency leads to re-localization of RAP1 from telomeres and subtelomeric regions to extratelomeric sites in a genomewide manner. These findings suggest that although in the presence of sufficient telomere reserve RAP1 is not a key factor for telomere maintenance and protection, it plays a crucial role in the context of telomerase deficiency, thus in agreement with its evolutionary conservation as a telomere component from yeast to humans.


Activation and metacognition of inaccessible stored information: potential bases for incubation effects in problem solving.
Two experiments were conducted with a hybrid procedure that involved a battery of indirect criterion tests designed to study the activation and metacognition of inaccessible stored information. In each experiment, subjects first attempted to recall some rare target words in response to a series of definitions meant to cue retrieval from long-term semantic memory. For the words that could not be recalled initially, the subjects rated their feelings of knowing. They then performed a lexical-decision task in which the target words and other control words were presented. Reaction times were measured as a function of the feeling-of-knowing ratings and the length of the interval between the initial exposure to the definitions and the subsequent lexical decisions. Faster decisions occurred for the target words than for the controls, especially when strong feelings of knowing had been expressed about the targets. Similar facilitation was obtained in a subsequent old-new recognition task. It appears that unsuccessful attempts to retrieve inaccessible stored information prime the later recognition of the information through a process of spreading activation. Such activation may sensitize people to future occurrences of stimulus inputs needed for insightful solutions of semantically rich problems.


The protein kinase p90 rsk as an essential mediator of cytostatic factor activity.
Persistent activation of p42 mitogen-activated protein kinase (p42 MAPK) during mitosis induces a "cytostatic factor" arrest, the arrest responsible for preventing the parthenogenetic activation of unfertilized eggs. The protein kinase p90 Rsk is a substrate of p42 MAPK; thus, the role of p90 Rsk in p42 MAPK-induced mitotic arrest was examined. Xenopus laevis egg extracts immunodepleted of Rsk lost their capacity to undergo mitotic arrest in response to activation of the Mos-MEK-1-p42 MAPK cascade of protein kinases. Replenishing Rsk-depleted extracts with catalytically competent Rsk protein restored the ability of the extracts to undergo mitotic arrest. Rsk appears to be essential for cytostatic factor arrest.


Depression recognition and capacity for self-report among ethnically diverse nursing homes residents: Evidence of disparities in screening.
To examine agreement between Minimum Data Set clinician ratings and researcher assessments of depression among ethnically diverse nursing home residents using the 9-item Patient Health Questionnaire. Although depression is common among nursing homes residents, its recognition remains a challenge. Observational baseline data from a longitudinal intervention study. Sample of 155 residents from 12 long-term care units in one US facility; 50 were interviewed in Spanish. Convergence between clinician and researcher ratings was examined for (i) self-report capacity, (ii) suicidal ideation, (iii) at least moderate depression, (iv) Patient Health Questionnaire severity scores. Experiences by clinical raters using the depression assessment were analysed. The intraclass correlation coefficient was used to examine concordance and Cohen's kappa to examine agreement between clinicians and researchers. Moderate agreement (κ = 0.52) was observed in determination of capacity and poor to fair agreement in reporting suicidal ideation (κ = 0.10-0.37) across time intervals. Poor agreement was observed in classification of at least moderate depression (κ = -0.02 to 0.24), lower than the maximum kappa obtainable (0.58-0.85). Eight assessors indicated problems assessing Spanish-speaking residents. Among Spanish speakers, researchers identified 16% with Patient Health Questionnaire scores of 10 or greater, and 14% with thoughts of self-harm whilst clinicians identified 6% and 0%, respectively. This study advances the field of depression recognition in long-term care by identification of possible challenges in assessing Spanish speakers. Use of the Patient Health Questionnaire requires further investigation, particularly among non-English speakers. Depression screening for ethnically diverse nursing home residents is required, as underreporting of depression and suicidal ideation among Spanish speakers may result in lack of depression recognition and referral for evaluation and treatment. Training in depression recognition is imperative to improve the recognition, evaluation and treatment of depression in older people living in nursing homes.


Psychiatric comorbidities in adult survivors of major trauma: findings from the Midland Trauma Registry.
INTRODUCTION Information for primary care providers about the outcomes of adult survivors of major medical trauma in the first year of recovery is not widely available. In particular, risks of impairment across multiple domains of functioning are poorly understood. AIM To determine the extent to which adults' experience impaired health-related quality of life (QoL), symptoms of post-traumatic stress disorder, depression, chronic pain and harmful alcohol use during the year following major trauma, and to identify factors associated with outcomes. METHODS Adults (aged ≥16 years) admitted to Waikato Hospital following major trauma sustained in Waikato District between 1 June 2010 and 1 July 2011 were sent a questionnaire in their first year of recovery. They were asked about their QoL, mental health, experiences of pain, post-traumatic stress disorder symptoms and use of alcohol. RESULTS Sixty-five questionnaires were completed (40% response rate). In the year following major trauma, trauma survivors met criteria for post-traumatic stress disorder (45%), harmful alcohol use (26%), moderate to severe chronic pain (23%) and depression (18%). Reports of poor health-related QoL were common, ranging from self-care difficulties (31%) to pain and discomfort (72%). Younger age, previous psychiatric illness, substance use, intensive care unit admission and length of hospitalisation were associated with symptoms. Thirty-seven adults (57%) reported symptoms in at least two domains. DISCUSSION A significant proportion of adults experience adverse psychosocial outcomes in the first year following major trauma. Screening and management of potentially comorbid psychosocial needs could improve care and outcomes for survivors.


Retinoic acid cross-talk with calcitriol activity in Atlantic salmon (Salmo salar).
Vitamins A (VA) and D (VD) are metabolised by vertebrates to bioactive retinoic acid (RA) and calcitriol (CTR). RA and CTR involvement in bone metabolism requires fine-tuned regulation of their synthesis and breakdown. In mammals antagonism of VA and VD is observed, but the mechanism of interaction is unknown. We investigated VA-VD interactions in Atlantic salmon (Salmo salar L.) following i.p. injection of RA and/or CTR. VA metabolites, CTR, calcium (Ca), magnesium (Mg) and phosphorus (P) were determined in plasma. Expression of bone matrix Gla protein (mgp), collagen 1 alpha2 chain (col1a2) and alkaline phosphatase (alp) mRNA was quantified to reflect osteogenesis. Branchial epithelial Ca channel (ecac listed as trpv6 in ZFIN Database) mRNA levels and intestinal Ca and P influx were determined to study Ca/P handling targets of RA and CTR. RA-injection (with or without CTR) decreased plasma CTR-levels three- to sixfold. CTR injection did not affect RA metabolites, but lowered CTR in plasma 3 and 5 days after injection. Lowered plasma CTR correlated with decreased mgp and col1a2 expression in all groups and with decreased alp in CTR-injected fish. RA-treated salmon had enhanced alp expression, irrespective of reduced plasma CTR. Expression of ecac and unidirectional intestinal influx of Ca were stimulated following RA-CTR treatment. Plasma Ca, Mg and P were not affected by any treatment. The results suggest cross-talk of RA with the VD endocrine system in Atlantic salmon. Enhanced Ca flux and osteogenesis (alp transcription) in RA-treated fish and inhibition of mgp expression revealed unprecedented disturbance of Ca physiology in hypervitaminosis A.


Unexpected high binding energy of CO2 on CH3NH3PbI3 lead-halide organic-inorganic perovskites via bicarbonate formation.
The adsorption kinetics of CO2 was experimentally characterized in ultra-high vacuum (UHV). Unexpectedly, high desorption temperatures (640 K, 170 kJ mol-1) were seen. Density functional theory (DFT) calculations suggest the stabilization mechanism: bicarbonate formation in the defected perovskite film due to CO2 and H2O coadsorption.


Rhizobia use a pathogenic-like effector to hijack leguminous nodulation signalling.
Legume plants form a root-nodule symbiosis with rhizobia. This symbiosis establishment generally relies on rhizobium-produced Nod factors (NFs) and their perception by leguminous receptors (NFRs) that trigger nodulation. However, certain rhizobia hijack leguminous nodulation signalling via their type III secretion system, which functions in pathogenic bacteria to deliver effector proteins into host cells. Here, we report that rhizobia use pathogenic-like effectors to hijack legume nodulation signalling. The rhizobial effector Bel2-5 resembles the XopD effector of the plant pathogen Xanthomonas campestris and could induce nitrogen-fixing nodules on soybean nfr mutant. The soybean root transcriptome revealed that Bel2-5 induces expression of cytokinin-related genes, which are important for nodule organogenesis and represses ethylene- and defense-related genes that are deleterious to nodulation. Remarkably, Bel2-5 introduction into a strain unable to nodulate soybean mutant affected in NF perception conferred nodulation ability. Our findings show that rhizobia employ and have customized pathogenic effectors to promote leguminous nodulation signalling.


Biological properties of structurally related alpha-helical cationic antimicrobial peptides.
A series of alpha-helical cationic antimicrobial peptide variants with small amino acid changes was designed. Alterations in the charge, hydrophobicity, or length of the variant peptides did not improve the antimicrobial activity, and there was no statistically significant correlation between any of these factors and the MIC for Pseudomonas aeruginosa, Escherichia coli, or Salmonella typhimurium. Individual peptides demonstrated synergy with conventional antibiotics against antibiotic-resistant strains of P. aeruginosa. The peptides varied considerably in the ability to bind E. coli O111:B4 lipopolysaccharide (LPS), and this correlated significantly with their antimicrobial activity and ability to block LPS-stimulated tumor necrosis factor and interleukin-6 production. In general, the peptides studied here demonstrated a broad range of activities, including antimicrobial, antiendotoxin, and enhancer activities.


Risks of Plastic Debris: Unravelling Fact, Opinion, Perception, and Belief.
Researcher and media alarms have caused plastic debris to be perceived as a major threat to humans and animals. However, although the waste of plastic in the environment is clearly undesirable for aesthetic and economic reasons, the actual environmental risks of different plastics and their associated chemicals remain largely unknown. Here we show how a systematic assessment of adverse outcome pathways based on ecologically relevant metrics for exposure and effect can bring risk assessment within reach. Results of such an assessment will help to respond to the current public worry in a balanced way and allow policy makers to take measures for scientifically sound reasons.


Factors associated with chronic plantar heel pain: a systematic review.
Chronic plantar heel pain (CPHP) is one of the most common soft tissue disorders of the foot, yet its aetiology is poorly understood. The purpose of this systematic review was to examine the association between CPHP and the various aetiological factors reported in the literature. Seven electronic databases and the reference lists of key articles were searched in August 2005. The resulting list of articles was assessed by two independent reviewers according to pre-determined selection criteria and a final list of articles for review was created. The methodological quality of the included articles was assessed and the evidence presented in each of the articles was descriptively analysed. From the 16 included articles, body mass index in a non-athletic population and the presence of calcaneal spur were the two factors found to have an association with CPHP. Increased weight in a non athletic population, increased age, decreased ankle dorsiflexion, decreased first metatarsophalangeal joint extension and prolonged standing all demonstrated some evidence of an association with CPHP. Evidence for static foot posture and dynamic foot motion was inconclusive and height, weight and BMI in an athletic population were not associated with CPHP. The findings of this review should be used to guide the focus of prospective cohort studies, the results of which would ultimately provide a list of risk factors for CPHP. Such a list is essential in the development of new and improved preventative and treatment strategies for CPHP.


Hierarchical Classification Strategy for Mitigating the Impact of The Presence of Pain in fNIRS-based BCIs.
Brain computer interfaces (BCIs) can find applications in assistive systems for patients who experience conditions that impede their motor abilities. A BCI uses signals acquired from the brain to control external devices. As physical pain influences cortical signals, the presence of pain can negatively impact the performance of the BCI. In this work, we propose a strategy to mitigate this negative impact. Cortical signals are acquired from test subjects while they performed two mental arithmetic tasks, in the presence and the absence of painful stimuli. The task of the BCI is to reliably classify the two mental arithmetic tasks from the cortical recordings, irrespective of the presence or the absence of pain. We propose to do this classification, hierarchically, in two levels. In the first level, the data is classified into those captured in the presence and the absence of pain. Depending on the results of the classification from the first level, in the second level, the BCI performs the classification of tasks using a classifier trained either in the presence or the absence of pain. A 1-dimensional convolutional neural network (1D-CNN) is used for classification at both levels. It is observed that using this hierarchical strategy, the BCI is able to classify the tasks with an accuracy greater than 90%, irrespective of the presence or the absence of pain. Given that the presence of physical pain has shown previously to reduce the classification accuracy of a BCI to almost chance levels, this mitigation strategy will be a significant step towards enhancing the performance of BCIs when they are used in assistive systems for patients.


Applicability of the "Frame of Reference" approach for environmental monitoring of offshore renewable energy projects.
This paper assesses the applicability of the Frame of Reference (FoR) approach for the environmental monitoring of large-scale offshore Marine Renewable Energy (MRE) projects. The focus is on projects harvesting energy from winds, waves and currents. Environmental concerns induced by MRE projects are reported based on a classification scheme identifying stressors, receptors, effects and impacts. Although the potential effects of stressors on most receptors are identified, there are large knowledge gaps regarding the corresponding (positive and negative) impacts. In that context, the development of offshore MRE requires the implementation of fit-for-purpose monitoring activities aimed at environmental protection and knowledge development. Taking European legislation as an example, it is suggested to adopt standardized monitoring protocols for the enhanced usage and utility of environmental indicators. Towards this objective, the use of the FoR approach is advocated since it provides guidance for the definition and use of coherent set of environmental state indicators. After a description of this framework, various examples of applications are provided considering a virtual MRE project located in European waters. Finally, some conclusions and recommendations are provided for the successful implementation of the FoR approach and for future studies.


Psychosocial Adjustment to Illness among HIV-Positive People from Buenos Aires, Argentina.
To analyze the process of psychosocial adjustment to illness in a sample of people living with the Human Immunodeficiency Virus from Buenos Aires, Argentina. Cross-sectional analytical study. The sample consisted of 144 HIV-positive people chosen by simple random sampling. The PAIS-SR questionnaire was used to measure the Psychosocial Adjustment process, which is made up of 46 items organized into 7 domains, whose final score ranges between 0 and 100, interpreted so that the higher the score, the worse the psychosocial adjustment process. The respondents reported were mostly male (82.63%), single (61.80%), with university studies (50.00%), without children (74.30%), and with a steady job (88.19%); the mean age of the participants was 43.8 years. The median global score was 51.4 (IQR: 12). The domains with the worst perception of psychosocial adjustment were: Health care orientation (Me: 56, IQR: 20), extended family relationship (Me: 55, IQR: 20), and Sexual relationship (Me: 54, IQR: 14), while those who had a better perception of adjustment were: Domestic environment (Me: 48, IQR: 8), Psychological distress (Me: 48, IQR: 17), Social environment (Me: 50, IQR: 18) and Vocational environment (Me: 50, IQR: 12). It was found that patients with a poor psychosocial adjustment process had low adherence to treatment, higher frequency of smoking, and sedentary lifestyle (p < 0.001), while male sex, older age, and employment were related to a better psychosocial adjustment process (p < 0.001). The process of psychosocial adjustment to illness in the study group is medium; adjustment was positively related to self-care habits such as better adherence to pharmacological treatment, physical activity, and not smoking.


The neuropathology of bipolar disorder: systematic review and meta-analysis.
Various neuropathological findings have been reported in bipolar disorder (BD). However, it is unclear which findings are well established. To address this gap, we carried out a systematic review of the literature. We searched over 5000 publications, identifying 103 data papers, of which 81 were eligible for inclusion. Our main findings can be summarised as follows. First, most studies have relied on a limited number of brain collections, and have used relatively small sample sizes (averaging 12 BD cases and 15 controls). Second, surprisingly few studies have attempted to replicate closely a previous one, precluding substantial meta-analyses, such that the latter were all limited to two studies each, and comprising 16-36 BD cases and 16-74 controls. As such, no neuropathological findings can be considered to have been established beyond reasonable doubt. Nevertheless, there are several replicated positive findings in BD, including decreased cortical thickness and glial density in subgenual anterior cingulate cortex, reduced neuronal density in some amygdalar nuclei, and decreased calbindin-positive neuron density in prefrontal cortex. Many other positive findings have also been reported, but with limited or contradictory evidence. As an important negative result, it can be concluded that gliosis is not a feature of BD; neither is there neuropathological evidence for an inflammatory process.


"Coming out" in the age of social constructionism.
Abstract This article examines sexual identity formation among 346 lesbian-identified and 60 bisexual-identified women. On average, bisexuals come out at later ages and exhibit less "stable" identity histories. However, variations in identity history among lesbians and bisexuals overshadow the differences between them and demonstrate that coming out is not a linear, goal-oriented, developmental process. Sexual identity formation must be reconceptualized as a process of describing one's social location within a changing social context. Changes in sexual identity are, therefore, expected of mature individuals as they maintain an accurate description of their position vis-à-vis other individuals, groups, and institutions.


Could cellular proliferation be a predictive index for the relapse of nasal polyposis and down-regulated by nasal steroid treatment?
The aim of this article is to identify the cellular mitotic activity using Ki-67 monoclonal antibody for predicting relapses of nasal polyposis after surgery. A prospective study was conducted at Kartal Training and Research Hospital Otolaryngology Department between January 2006 and September 2008. Nasal polyps were obtained from all patients and pathological materials were analyzed for the Ki-67 staining using immunohistochemistry. Patients were followed after surgery for 12 months for relapse. There was no statistically significant difference between recurrent and nonrecurrent polyps. Polyp recurrence has a multifactorial origin. Ki-67 index alone does not provide sufficient information about polyp recurrence before the operation.


Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.
The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation.


Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation.
Although many algorithms exist for estimating haplotypes from genotype data, none of them take full account of both the decay of linkage disequilibrium (LD) with distance and the order and spacing of genotyped markers. Here, we describe an algorithm that does take these factors into account, using a flexible model for the decay of LD with distance that can handle both "blocklike" and "nonblocklike" patterns of LD. We compare the accuracy of this approach with a range of other available algorithms in three ways: for reconstruction of randomly paired, molecularly determined male X chromosome haplotypes; for reconstruction of haplotypes obtained from trios in an autosomal region; and for estimation of missing genotypes in 50 autosomal genes that have been completely resequenced in 24 African Americans and 23 individuals of European descent. For the autosomal data sets, our new approach clearly outperforms the best available methods, whereas its accuracy in inferring the X chromosome haplotypes is only slightly superior. For estimation of missing genotypes, our method performed slightly better when the two subsamples were combined than when they were analyzed separately, which illustrates its robustness to population stratification. Our method is implemented in the software package PHASE (v2.1.1), available from the Stephens Lab Web site.


Tailoring of integrin ligands: probing the charge capability of the metal ion-dependent adhesion site.
Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid function, a consistent feature of all integrin ligands. With the exception of the recently discovered hydroxamic acids, all bioisosteric attempts to replace the carboxylic acid of integrin ligands failed. We report that phosphinates as well as monomethyl phosphonates represent excellent isosters, when introduced into integrin antagonists for the platelet integrin αIIbβ3. The novel inhibitors exhibit in vitro and ex vivo activities in the low nanomolar range. Steric and charge requirements of the MIDAS region were unraveled, thus paving the way for an in silico prediction of ligand activity and in turn the rational design of the next generation of integrin antagonists.


Psychopathic Personality as a Moderator of the Relationship Between Atypical Sexuality and Sexual Coercion Proclivity in the General Population.
Being sexually coerced can have long-lasting psychological impacts on victims; with perpetration strongly predicted by elevated psychopathic traits. Owing to recent legislative developments in the United Kingdom that criminalize coercive control under the Domestic Abuse Act (2021), this study offers a timely investigation into the mechanisms of sexual coercion in domestic abuse across sexual abuse and coercive control. We used moderation analysis (n = 405) to investigate whether sexual coercion proclivity was predicted by facets of atypical sexuality (non-clinical elevated levels of sex drive, sexual sadism, and sexual masochism), and whether this relationship was moderated by psychopathic personality traits specifically the factor one components, which encompasses interpersonal and affective characteristics. Psychopathic personality traits significantly moderated the positive association between sex drive and sexual coercion proclivity, and between sexual sadism and sexual coercion proclivity in males (but not females), but psychopathic personality traits had no such moderating effect in the sexual masochism model. Results are discussed in terms of identifying risk factors of sexual coercion within a general population sample and international application. Open data and a preprint of this paper are available at [https://osf.io/xkcah/?view_only=134ff9c93ad24ba286515b348ce79c0c].


Immune function and vaccine responses in healthy advanced elderly patients.
Decline in immune function has been reported to predictably accompany advancing age. However, to our knowledge, few studies have specifically characterized the rapidly expanding advanced elderly population or controlled adequately for concurrent diseases. To assess whether successfully reaching an advanced age in good health is associated with preserved immune function. We prospectively compared in vivo with in vitro variables of immune function in 29 healthy, independently living elderly subjects (mean age, 80 years; age range, 75-103 years) and in 21 healthy young control subjects (mean age, 29 years; age range, 25-35 years) in a Veterans Affairs Medical Center. In vivo, among elderly and young subjects, numbers of total white blood cells, monocytes, lymphocytes, and lymphocyte subsets (CD4(+) and CD8(+) T lymphocytes and CD20(+) B cells) were similar, as were levels of total serum IgG and IgM. Only levels of serum IgA were higher in the elderly subjects (3.0 vs 1.7 g/L; P=.001). Functionally, both groups showed vigorous responses to protein (tetanus and diphtheria toxoids) and polysaccharide (23-valent pneumococcal) vaccines. Although levels varied, the fold increases in vaccine antigen-specific IgG were not significantly different in young and elderly subjects, and the avidities of IgG to pneumococcal polysaccharides 14 and 19F were similar before and after vaccination. In vitro, proliferative responses of blood mononuclear cells to T-lymphocyte and B-cell mitogens (pokeweed mitogen, Staphylococcus aureus Cowan strain I, and S aureus Cowan strain I plus interleukin 2), and lipopolysaccharide-induced production of tumor necrosis factor alpha, were comparable in elderly vs young subjects. Successful aging, defined by reaching an advanced age with one's overall health intact, may be associated with preserved immune function and adequate responses to vaccines.


Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients.
The thymus is believed to play a central role in the pathogenesis of Myasthenia gravis (MG). According to a previous hypothesis, MG is initiated within the thymus by immunogenic presentation of locally produced nicotinic acetylcholine receptor (AChR) to potentially autoimmune T cells. Data of 10 consecutive MG patients demonstrate two critical features of MG thymuses that support the concept of intrathymic activation of autoreactive, AChR-specific lymphocytes. Morphologically, the thymuses showed lympho-follicular hyperplasia in nine cases and benign thymoma in one case. The paramount feature revealed by immunohistological double marker analyses was the intimate association of myoid cells (antigen producing) with interdigitating reticulum cells (potentially antigen presenting cells), both of which were surrounded by T3+ lymphocytes in thymus medulla. All 10 thymuses contained T lymphocytes reactive with AChR. This was in contrast to the peripheral immune compartment (blood) where in only 3 of 10 patients, significant T cell responses to AChR were observed. AChR-specific T cell lines could be established from 8 of 10 thymuses, all members of the helper/inducer subset as indicated by the expression of markers T3 and T4.


Monitoring of bedridden patients: development of a fall detection tool.
Falls of patients are an important issue in hospitals nowadays; it causes severe injuries, increases hospitalization time and treatment costs. The detection of a fall, in time, provides faster rescue to the patient, preventing more serious injuries, as well as saving nursing time. The MovinSense® is an electronic device designed for monitoring patients to prevent pressure sores, and the main goal of this work was to develop a new tool for this device, with the purpose of detecting if the patient has fallen from the hospital bed, without changing any of the device's original features. Experiments for gathering data samples of inertial signals of falling from the bed were obtained using the device. For fall detection a sensitivity of 72% and specificity of 100% were reached. Another algorithm was developed to detect if the patient got out of his/her bed.


Impacts of Cortical Regions on EEG-based Classification of Lexical Tones and Vowels in Spoken Speech.
Speech impairment is one of the most serious problems for patients with communication disorders, e.g., stroke survivors. The brain-computer interface (BCI) systems have shown the potential to alternatively control or rehabilitate the neurological damages in speech production. The effects of different cortical regions in speech-based BCI systems are essential to be studied, which are favorable for improving the performance of speech-based BCI systems. This work aimed to explore the impacts of different speech-related cortical regions in the electroencephalogram (EEG) based classification of seventy spoken Mandarin monosyllables carrying four vowels and four lexical tones. Seven audible speech production-related cortical regions were studied, involving Broca's and Wernicke's areas, auditory cortex, motor cortex, prefrontal cortex, sensory cortex, left brain, right brain, and whole brain. Following the previous studies in which EEG signals were collected from ten subjects during Mandarin speech production, the features of EEG signals were extracted by the Riemannian manifold method, and a linear discriminant analysis (LDA) was regarded as a classifier to classify different vowels and lexical tones. The results showed that when using electrodes from whole brain, the classifier reached the best performances, which were 48.5% for lexical tones and 70.0% for vowels, respectively. The vowel classification results under Broca's and Wernicke's areas, auditory cortex, or prefrontal cortex were higher than those under the motor cortex or sensory cortex. No such differences were observed in the lexical tone classification task.


Focal childhood-onset, action induced primary hip dystonia treated with pallidal deep brain stimulation.
Focal proximal lower limb dystonias are rare. Unlike the adult form, focal lower limb dystonias in children usually become generalized. The condition is often unrecognized and the patient often receives orthopedic or psychiatric treatment for years before the diagnosis eventually made. Previously reported cases of isolated lower limb dystonias have been managed nonsurgically. We present a case of a childhood-onset action-induced primary hip dystonia that has remained focal even in adulthood and which responded successfully to pallidal deep brain stimulation. Additionally, our results suggest that neurons representing the leg lie within the most ventral aspect of the globus pallidus interna.


Revising two-point discrimination assessment in normal aging and in patients with polyneuropathies.
To revise the static and dynamic normative values for the two-point discrimination test and to examine its applicability and validity in patients with a polyneuropathy. Two-point discrimination threshold values were assessed in 427 healthy controls and 99 patients mildly affected by a polyneuropathy. The controls were divided into seven age groups ranging from 20-29, 30-39,..., up to 80 years and older; each group consisted of at least 30 men and 30 women. Two-point discrimination examination took place under standardised conditions on the index finger. Correlation studies were performed between the scores obtained and the values derived from the Weinstein Enhanced Sensory Test (WEST) and the arm grade of the Overall Disability SumScore (ODSS) in the patients' group (validity studies). Finally, the sensitivity to detect patients mildly affected by a polyneuropathy was evaluated for static and dynamic assessments. There was a significant age-dependent increase in the two-point discrimination values. No significant gender difference was found. The dynamic threshold values were lower than the static scores. The two-point discrimination values obtained correlated significantly with the arm grade of the ODSS (static values: r = 0.33, p = 0.04; dynamic values: r = 0.37, p = 0.02) and the scores of the WEST in patients (static values: r = 0.58, p = 0.0001; dynamic values: r = 0.55, p = 0.0002). The sensitivity for the static and dynamic threshold values was 28% and 33%, respectively. This study provides age-related normative two-point discrimination threshold values using a two-point discriminator (an aesthesiometer). This easily applicable instrument could be used as part of a more extensive neurological sensory evaluation.


Attitudes justifying domestic violence predict endorsement of corporal punishment and physical and psychological aggression towards children: a study in 25 low- and middle-income countries.
The Convention on the Rights of the Child has prompted countries to protect children from abuse and exploitation. Exposure to domestic violence and corporal punishment are risk factors in children's development. This study investigated how women's attitudes about domestic violence are related to attitudes about corporal punishment and harsh behaviors toward children, and whether country-wide norms regarding domestic violence and corporal punishment are related to psychological aggression and physical violence toward children. Data were drawn from the Multiple Indicator Cluster Survey, a nationally representative and internationally comparable household survey developed by the United Nations Children's Fund. Measures of domestic violence and discipline were completed by 85 999 female caregivers of children between the ages of 2 and 14 years from families in 25 low- and middle-income countries. Mothers who believed that husbands were justified in hitting their wives were more likely to believe that corporal punishment is necessary to rear children. Mothers who believed that husbands were justified in hitting their wives and that corporal punishment is necessary to rear children were more likely to report that their child had experienced psychological aggression and physical violence. Countrywide norms regarding the acceptability of husbands hitting wives and advisability of corporal punishment moderated the links between mothers' attitudes and their behaviors toward children. Pediatricians can address parents' psychological aggression and physical violence toward children by discussing parents' attitudes and behaviors within a framework that incorporates social norms regarding the acceptability of domestic violence and corporal punishment.


Thoracoscopic primary repair with mediastinal drainage is a viable option for patients with Boerhaave's syndrome.
Spontaneous esophageal rupture (Boerhaave's syndrome) is an emergency that can cause life-threatening conditions. Various procedures have been used to treat Boerhaave's syndrome. However, a standard surgical procedure has not been established. Herein, we report our experience with primary suture of the ruptured esophagus via a thoracoscopy or laparotomy. Between November 2002 and May 2015, 11 patients with Boerhaave's syndrome presented to our department and were managed using one of two surgical procedures based on the surgeon's discretion. Six patients underwent a thoracoscopic primary suture and drainage (group A); 5 patients underwent a primary suture via laparotomy followed by thoracoscopic drainage (group B). Patient medical records were retrospectively reviewed. The mean interval between initial perforation and surgery was 13.7 h (group A) and 17.2 h (group B) (P=0.7307). The mean operative time was 190 min (group A) and 249 min (group B) (P=0.106). Patient baseline characteristics and surgical outcomes were similar for both surgical procedures. One patient in each group experienced postoperative leakage that did not require surgical intervention. The results suggest that thoracoscopic esophageal repair, as well as suturing via laparotomy, is a good surgical alternative for patients with Boerhaave's syndrome.


Liability of physicians supervising nonphysician clinicians.
Physicians confront a variety of liability issues when supervising nonphysician clinicians (NPC) including: (1) direct liability resulting from a failure to meet the state-defined standards of supervision/collaboration with NPCs; (2) vicarious liability, arising from agency law, where physicians are held accountable for NPC clinical care that does not meet the national standard of care; and (3) responsibility for medical errors when the NPC and physician are co-employees of the corporate enterprise. Physician-NPC co-employee relationships are highlighted because they are new and becoming predominant in existing healthcare models. Because of their novelty, there is a paucity of judicial decisions determining liability for NPC errors in this setting. Knowledge of the existence of these risks will allow physicians to make informed decisions on what relationships they will enter with NPCs and how these relationships will be structured and monitored.


Reporting of financial conflicts of interest in meta-analyses of drug trials published in high-impact medical journals: comparison of results from 2017 to 2018 and 2009.
A previous study found that 2 of 29 (6.9%) meta-analyses published in high-impact journals in 2009 reported included drug trials' funding sources, and none reported trial authors' financial conflicts of interest (FCOIs) or industry employment. It is not known if reporting has improved since 2009. Our objectives were to (1) investigate the extent to which pharmaceutical industry funding and author-industry FCOIs and employment from included drug trials are reported in meta-analyses published in high-impact journals and (2) compare current reporting with results from 2009. We searched PubMed (January 2017-October 2018) for systematic reviews with meta-analyses including ≥ 2 randomized controlled trials (RCTs) of patented drugs. We included 3 meta-analyses published January 2017-October 2018 from each of 4 high-impact general medicine journals, high-impact journals from 5 specialty areas, and the Cochrane Database of Systematic Reviews, as in the previous study. Among 29 meta-analyses reviewed, 13 of 29 (44.8%) reported the funding source of included trials compared to 2 of 29 (6.9%) in 2009, a difference of 37.9% (95% confidence interval, 15.7 to 56.3%); this included 7 of 11 (63.6%) from general medicine journals, 3 of 15 (20.0%) from specialty medicine journals, and 3 of 3 (100%) Cochrane reviews. Only 2 of 29 meta-analyses (6.9%) reported trial author FCOIs, and none reported trial author-industry employment. A protocol was uploaded to the Open Science Framework prior to initiating the study. https://osf.io/8xt5p/ LIMITATIONS: We examined only a relatively small number of meta-analyses from selected high-impact journals and compared results to a similarly small sample from an earlier time period. Reporting of drug trial sponsorship and author FCOIs in meta-analyses published in high-impact journals has increased since 2009 but is still suboptimal. Standards on reporting of trial funding described in the forthcoming revised PRISMA statement should be adapted and enforced by journals to improve reporting.


Genes polymorphism as risk factor of recurrent urolithiasis: a systematic review and meta-analysis.
Urolithiasis is one of the most prevalent diseases worldwide. Its prevalence is rising, both in developing and developed countries. It is known that genetic factors play big roles in the development of urolithiasis. One of the suspected factors is gene polymorphism. This study aims to find an accurate estimate of the association between genetic polymorphism and the risk of recurrent urolithiasis. A systematic review and meta-analysis were performed on 12 studies from 3 databases that investigated gene polymorphism as an risk factor of urolithiasis. The review was done using Review Manager® version 5.3. Insignificant heterogenicity was found in this study. Populations from Asia and the Middle East are more likely to experience recurrent urolithiasis. Additionally, variation in the VDR and urokinase genes, particularly in the Asian population, increases the risk of developing recurrent urolithiasis. Gene polymorphisms have significant roles in the development of urolithiasis, especially in the Middle Eastern region.


Pulmonary tuberculosis: contributions of radiology in diagnosis and treatment.
This review records the important place that radiologic examinations have had in the diagnosis and treatment of pulmonary tuberculosis in the past nine decades. Very soon after the discovery of x-rays it became apparent that chest roentgenograms would be a help in identifying pulmonary lesions. As the quality of the examinations improved, the benefits became significantly better. Earlier lesions were diagnosed. Follow-up studies after medical or surgical treatment were increasingly helpful. Newly developed techniques allowed demonstration of extrapulmonary complications. Radiologic monitoring of collapse therapy played a critical role in the successes achieved. Even after the medical conquest of active tuberculous lesions by drug therapy, identification of new lesions and follow-up of treated patients remains a significant role for radiology. Control of this once fatal and widely feared disease depends on continued early recognition and appropriate treatment.


Porphyrins fused with unactivated polycyclic aromatic hydrocarbons.
A systematic study of the preparation of porphyrins with extended conjugation by meso,β-fusion with polycyclic aromatic hydrocarbons (PAHs) is reported. The meso-positions of 5,15-unsubstituted porphyrins were readily functionalized with PAHs. Ring fusion using standard Scholl reaction conditions (FeCl(3), dichloromethane) occurs for perylene-substituted porphyrins to give a porphyrin β,meso annulated with perylene rings (0.7:1 ratio of syn and anti isomers). The naphthalene, pyrene, and coronene derivatives do not react under Scholl conditions but are fused using thermal cyclodehydrogenation at high temperatures, giving mixtures of syn and anti isomers of the meso,β-fused porphyrins. For pyrenyl-substituted porphyrins, a thermal method gives synthetically acceptable yields (>30%). Absorption spectra of the fused porphyrins undergo a progressive bathochromic shift in a series of naphthyl (λ(max) = 730 nm), coronenyl (λ(max) = 780 nm), pyrenyl (λ(max) = 815 nm), and perylenyl (λ(max) = 900 nm) annulated porphyrins. Despite being conjugated with unsubstituted fused PAHs, the β,meso-fused porphyrins are more soluble and processable than the parent nonfused precursors. Pyrenyl-fused porphyrins exhibit strong fluorescence in the near-infrared (NIR) spectral region, with a progressive improvement in luminescent efficiency (up to 13% with λ(max) = 829 nm) with increasing degree of fusion. Fused pyrenyl-porphyrins have been used as broadband absorption donor materials in photovoltaic cells, leading to devices that show comparatively high photovoltaic efficiencies.


Nucleic acid-based approaches to investigate microbial-related cheese quality defects.
The microbial profile of cheese is a primary determinant of cheese quality. Microorganisms can contribute to aroma and taste defects, form biogenic amines, cause gas and secondary fermentation defects, and can contribute to cheese pinking and mineral deposition issues. These defects may be as a result of seasonality and the variability in the composition of the milk supplied, variations in cheese processing parameters, as well as the nature and number of the non-starter microorganisms which come from the milk or other environmental sources. Such defects can be responsible for production and product recall costs and thus represent a significant economic burden for the dairy industry worldwide. Traditional non-molecular approaches are often considered biased and have inherently slow turnaround times. Molecular techniques can provide early and rapid detection of defects that result from the presence of specific spoilage microbes and, ultimately, assist in enhancing cheese quality and reducing costs. Here we review the DNA-based methods that are available to detect/quantify spoilage bacteria, and relevant metabolic pathways in cheeses and, in the process, highlight how these strategies can be employed to improve cheese quality and reduce the associated economic burden on cheese processors.


Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins.
The electrophilic eicosanoids prostaglandins A(1) or A(2) impaired p53-dependent transcription of endogenous genes and exogenous p53-luciferase reporter plasmids in RKO and HCT 116 colon cancer cells. Cellular accumulation of genetically wild-type, but transcriptionally silent p53 varied as a function of exposure time and concentration of prostaglandins A(1) and A(2). Prostaglandins A(1) and A(2) induced a conformational change in wild-type p53 that corresponded with its inactivation and its aberrant redistribution from the cytosol to the nucleus. Derangement of its transcriptional activity manifested as inhibition of p53-mediated apoptosis by etoposide, a representative antineoplastic agent. We conclude that electrophilic eicosanoids impair the role of wild-type p53 as a guardian of genomic integrity by a process distinct from somatic mutation or viral oncoprotein binding. This process may pertain to malignant and premalignant conditions, such as colon carcinoma and adenoma, which often harbor a genetically wild-type, but inactive form of p53 tumor suppressor.


Taurodontism in children with hypodontia and supernumerary teeth: a case control study.
The aim of the present investigation was to compare the prevalence of taurodontism in the permanent mandibular first molars of nonsyndromic children with hypodontia and supernumerary teeth with age- and gender-matched controls. The crown-body root ratios of the permanent first molars were determined from orthopantomograms of 83 children with hypodontia (> or =1 missing teeth) and 37 children with supernumerary teeth (> or =1 extra teeth) compared with normal case controls. In children with hypodontia, only girls showed a significantly higher tendency for taurodontism compared to case controls (P=.003), while boys with hypodontia showed a similar prevalence of taurodontism as controls (P=.83). Children with multiple missing teeth were significantly more susceptible to taurodontism than children with a single missing tooth (P=.004). By contrast, the prevalence of taurodontism in children with supernumerary teeth was not significantly different from that of controls. Compared to normal case controls, children with nonsyndromic hypodontia are more likely to show taurodontism of the permanent first molar teeth whereas children with nonsyndromic supernumerary teeth are not.


Mediators of the association between low socioeconomic status and chronic kidney disease in the United States.
Using data collected from 9,823 participants in the 2007-2008 and 2009-2010 cycles of the National Health and Nutrition Examination Survey, we formally investigated potentially modifiable factors linking low socioeconomic status (SES) to chronic kidney disease (CKD) for their presence and magnitude of mediation. SES was defined using the poverty income ratio. The main outcome was CKD, defined as estimated glomerular filtration rate <60 mL/minute/1.73 m(2) (using the Chronic Kidney Disease Epidemiology Collaboration equation) and/or urinary albumin:creatinine ratio ≥30 mg/g. In mediation analyses, we tested the contributions of health-related behaviors (smoking, alcohol intake, diet, physical activity, and sedentary time), comorbid conditions (diabetes, hypertension, obesity, abdominal obesity, and hypercholesterolemia), and access to health care (health insurance and routine health-care visits) to this association. Except for sedentary time and diet, all examined health-related behaviors, comorbid conditions, and factors related to health-care access mediated the low SES-CKD association and contributed 20%, 32%, and 11%, respectively, to this association. In race/ethnicity-specific analyses, identified mediators tended to explain more of the association between low SES and CKD in non-Hispanic blacks than in other racial/ethnic groups. In conclusion, potentially modifiable factors like health-related behaviors, comorbid conditions, and health-care access contribute substantially to the association between low SES and CKD in the United States, especially among non-Hispanic blacks.


Improving mental health following multiple disasters in Australia: a randomized controlled trial of the Skills for Life Adjustment and Resilience (SOLAR) programme.
Background: The mental health impacts of climate change-related disasters are significant. However, access to mental health services is often limited by the availability of trained clinicians. Although building local community capability for the mental health response is often prioritised in policy settings, the lack of evidence-based programs is problematic. The aim of this study was to test the efficacy of the Skills for Life Adjustment and Resilience programme (SOLAR) delivered by trained local community members following compound disasters (drought, wildfires, pandemic-related lockdowns) in Australia.Method: Thirty-six community members were trained to deliver the SOLAR programme, a skills-based, trauma informed, psychosocial programme. Sixty-six people with anxiety, depression and/or posttraumatic stress symptoms, and impairment were randomised into the SOLAR programme or a Self-Help condition. They were assessed pre, post and two months following the interventions. The SOLAR programme was delivered across five 1-hourly sessions (either face to face or virtually). Those in the Self-Help condition received weekly emails with self-help information including links to online educational videos.Results: Multigroup analyses indicated that participants in the SOLAR condition experienced significantly lower levels of anxiety and depression, and PTSD symptom severity between pre - and post-intervention (T1 to T2), relative to the Self-Help condition, while controlling for scores at intake. These differences were not statistically different at follow-up. The SOLAR programme was associated with large effect size improvements in posttraumatic stress symptoms over time.Conclusion: The SOLAR programme was effective in improving anxiety, depression and posttraumatic stress symptoms over time. However, by follow-up the size of the effect was similar to an active self-help condition. Given the ongoing stressors in the community associated with compounding disasters it may be that booster sessions would have been useful to sustain programme impact.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12621000283875..