Ethnobotanical study of medicinal plants utilized in the management of candidiasis in Northern Uganda.
The emergence of resistant Candida species to antifungal drugs has led to resurgence in herbal usage globally. However, little is known about anti-candida plants. This study explored ethnomedicinal plants as treatment option for candidiasis in Pader, Northern Uganda. A cross-sectional survey of potential anti-candida plants was conducted using questionnaires, focus group discussions and field observations in March 2022. Sixty-three respondents were selected by snowball technique. The frequencies of respondents/responses were analyzed, associations of respondents' socio-demographics with indigenous knowledge of herbal usage established by Chi-square (χ2) test using SPSS 27. Informant Consensus Factor was computed to establish level of agreement on herbal usage, and thematic analysis done for focus group discussions. Candidiasis is still common and troublesome in Pader. All herbalist had equal chances of receiving and treating candidiasis patients irrespective of herbalist's gender, age, education level, occupation, marital status and religion (p > 0.05). About 39.7% of herbalists received candidiasis patients weekly (p < 0.01). All herbalists had knowledge on candidiasis. Death (56.8%) and discomfort (36.8%) were the major health risks of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC), respectively. A total of 32 potential anti-candida plant species in 18 families were identified. Families of Fabaceae (9 species) and Asteraceae (5 species) had most plant species. Trees (50.0%) and herbs (43.8%) were the dominant life forms. The commonest plants by frequency of mention were: Momordica foetida (26), Sansevieria dawei (20), Khaya anthotheca (15), Piliostigma thonningii (10), Clerodendrum umbellatum (7), Hallea rubrostipulata (5) and unidentified plant, 'Agaba/daa layata' in Acholi dialect (5). Plant parts mainly used were roots (56.3%) and stem barks (15.6%) harvested majorly by cutting (46.9%) and uprooting (12.5%). Most respondents (females, 95%) preferred herbal to western medication (p < 0.01) due to its perceived effectiveness. There was high consensus among herbalists on herbal remedies for OPC and VVC (FIC = 0.9). Pader communities have diverse indigenous knowledge on candidiasis and prefer herbal medicines to orthodox treatment for candidiasis. However, the herbalists use unsustainable harvesting techniques like uprooting whole plants and cutting main roots. Hence, the need to document such indigenous knowledge before being lost for community usage and scientific validation.


Tunable hydrogel thin films from reactive synthetic polymers as potential two-dimensional cell scaffolds.
This article describes the formation of cross-linked 10-200-nm-thick polymer hydrogel films by alternating the spin-coating of two mutually reactive polymers from organic solutions, followed by hydrolysis of the resulting multilayer film in aqueous buffer. Poly(methyl vinyl ether-alt-maleic anhydride) (PMM) was deposited from acetonitrile solution, and poly(N-3-aminopropylmethacrylamide-co-N-2-hydroxypropylmethacrylamide) (PAPMx, where x corresponds to the 3-aminopropylmethacrylamide content ranging from 10 to 100%) was deposited from methanol. Multilayer films were formed in up to 20 deposition cycles. The films cross-linked during formation by reaction between the amine groups of PAPMx and the anhydride groups of PMM. The resulting multilayer films were covalently postfunctionalized by exposure to fluoresceinamine, decylamine, d-glucamine, or fluorescently labeled PAPMx solutions prior to the hydrolysis of residual anhydride in aqueous PBS buffer. This allowed tuning the hydrophobicity of the film to give static water contact angles ranging from about 5 to 90°. Increasing the APM content in PAPMx from 10 to 100% led to apparent Young's moduli from 300 to 700 kPa while retaining sufficient anhydride groups to allow postfunctionalization of the films. This allowed the resulting (PMM/PAPMx) multilayer films to be turned into adhesion-promoting or antifouling surfaces for C2C12 mouse myoblasts and MCF 10A premalignant human mammary epithelial cells.


Clinico-pathologic and dynamic prognostic factors in sporadic and familial medullary thyroid carcinoma: an Israeli multi-center study.
Multiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC patients followed for long period are scarce. This study evaluated the association between baseline clinico-pathologic variables and response to initial treatment and short- and long-term disease outcomes in sporadic and familial MTC. Patients treated for MTC at four tertiary medical centers were retrospectively analyzed. Clinical and pathological data were collected. The outcomes measured included disease persistence 1 year after diagnosis, disease persistence at last follow-up, disease-related mortality (DRM) and all-cause mortality. The study enrolled 193 patients (mean age: 48.9 ± 18.7, 44.7% males), of whom 18.1% were familial cases. The mean follow-up period was 10.1 ± 9.4 years (8.5 ± 8.1 in sporadic and 16.9 ± 11.6 in familial MTC). Disease persistence 1-year after diagnosis and at last follow-up was detected in 56.1 and 60.4% patients, respectively. All-cause and DRM were 28.5 and 12.6%, respectively. Extra-thyroidal extension (ETE) and distant metastases (DM) were associated with disease persistence at last follow-up. ETE and DM were also significantly associated with DRM. Complete remission 1 year after diagnosis had high correlation with no evidence of disease at last follow-up (Cramer's V measure of association 0.884, P < 0.001) and with 100% disease-specific survival (Cramer's V measure of association 0.38, P < 0.001). Apart from clinico-pathologic parameters, close correlation was found between 1-year status and long-term prognosis. These results underscore the importance of combining classical and dynamic factors for both sporadic and familial MTC prognostication and treatment decision making.


Beyond RNAi: antiviral defense strategies in Drosophila and mosquito.
Virus transmission and spread by arthropods is a major economic and public health concern. The ongoing dissemination of arthropod-borne viruses by blood-feeding insects is an important incentive to study antiviral immunity in these animals. RNA interference is a major mechanism for antiviral defense in insects, including the fruit fly Drosophila melanogaster and several vector mosquitoes. However, recent data suggest that the evolutionary conserved Toll, Imd and Jak-Stat signaling pathways also contribute to antiviral immunity. Moreover, symbionts, such as the intracellular bacterium Wolbachia and the gut microflora, influence the course of virus infection in insects. These results add an additional level of complexity to antiviral immunity, but also provide novel opportunities to control the spread of arboviruses. In this review, we provide an overview of the current knowledge and recent developments in antiviral immunity in Dipteran insects, with a focus on non-RNAi mediated inducible responses.


Five Decades of Cuprizone, an Updated Model to Replicate Demyelinating Diseases.
Demyelinating diseases of the central nervous system (CNS) comprise a group of neurological disorders characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter tracts. Some of myelin disorders include: Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others. To date, the etiology of these disorders is not well known and no effective treatments are currently available against them. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology and clinical signs of these diseases. Herein, we describe the model of toxic demyelination induced by cuprizone (CPZ), a copper chelator that reduces the cytochrome and monoamine oxidase activity into the brain, produces mitochondrial stress and triggers the local immune response. These biochemical and cellular responses ultimately result in selective loss of oligodendrocytes and microglia accumulation, which conveys to extensive areas of demyelination and gliosis in corpus callosum, superior cerebellar peduncles and cerebral cortex. Remarkably, some aspects of the histological pattern induced by CPZ are similar to those found in multiple sclerosis. CPZ exposure provokes behavioral changes, impairs motor skills and affects mood as that observed in several demyelinating diseases. Upon CPZ removal, the pathological and histological changes gradually revert. Therefore, some authors have postulated that the CPZ model allows to partially mimic the disease relapses observed in some demyelinating diseases. for five decades, the model of CPZ-induced demyelination is a good experimental approach to study demyelinating diseases that has maintained its validity, and is a suitable pharmacological model for reproducing some key features of demyelinating diseases, including multiple sclerosis.


Expression of viral p21ras during acquisition of a transformed phenotype by rat adrenal cortex cells infected with Kirsten murine sarcoma virus.
Rat adrenal cortex cells infected with Kirsten murine sarcoma virus acquire a transformed phenotype in a progressive fashion. The expression of the viral p21ras does not appear to correlate with the degree of transformation of the adrenocortical cells but rather is produced at similar levels as the culture becomes transformed. This indicates that the expression of an oncogenic form of p21ras is not of itself sufficient to completely transform rat adrenal cortex cells.


Clinical outcomes of different revascularization approaches for patients with multi-vessel coronary artery disease: A network meta-analysis.
As surgical techniques continue to evolve, the optimal approach for revascularizing multi-vessel coronary artery disease (CAD) remains a matter of ongoing debate. Accordingly, our objective was to compare and contrast various surgical techniques utilized in the management of multi-vessel CAD. A systematic literature review was performed using PubMed, Embase, and Cochrane central register of controlled trials from inception to May 2022. Random-effects network meta-analysis was performed for the primary outcome; target vessel revascularization (TVR), and secondary outcomes; mortality, major adverse cardiac and cerebrovascular events, postoperative myocardial infarction, new-onset atrial fibrillation, stroke, new-onset dialysis, in patients undergoing percutaneous coronary intervention (PCI) with a stent, off-pump coronary bypass graft, on-pump coronary artery bypass graft (ONCABG), hybrid coronary revascularization, minimally-invasive coronary artery bypass, or robot-assisted coronary artery bypass (RCAB) surgeries. A total of 8841 patients were included from 23 studies. The analysis showed that ONCABG had the highest freedom from TVR, with a mean (SD) absolute risk of 0.027 (0.029); although ONCABG was found to be superior to all other methods, it was only significantly better than first-generation stent PCI. While RCAB did not demonstrate significant superiority over other treatments, it showed a greater probability of preventing postoperative complications. Notably, no significant heterogeneity was calculated for any of the reported outcomes. ONCABG shows a better rank probability compared to all other techniques for preventing TVR, while RCAB offers greater freedom from most postoperative complications. However, given the absence of randomized controlled trials, these results should be interpreted with caution.


[Non-alcoholic steato-hepatitis].
The term Non-Alcoholic Steatohepatitis (NASH) was introduced to describe a group of patients in whom liver biopsy shows the typical morphology of Alcoholic Steatohepatitis, without the presence of any significant alcohol consumption. The presence of steatosis and inflammatory infiltrate in liver biopsy is essential for the diagnosis of NASH. Other chronic liver diseases--such as Hepatitis B and C as well as Autoimmunohepatitis--which can cause similar morphologies have to be excluded. The pathophysiology of NASH is essentially still unclear. On the one hand toxic effects of oxidated fatty acids are suspected, on the other hand it is postulated that the fatty liver is very vulnerable and that actual hepatitis is triggered by an additional stressor. The disease has a benign clinical course and the typical patient is asymptomatic with elevated liver enzymes. Despite the paucity of symptoms the risk of cirrhosis is approximately 8-17%. No established treatment exists. Preliminary reports suggest a positive effect of gradual weight loss and ursodeoxycholic-acid but further studies are needed to confirm this observation.


Roles of Health Care Providers and Patients in Initiation of Unnecessary Papanicolaou Testing After Total Hysterectomy.
To assess Papanicolaou (Pap) testing use among US adult women with a history of a total hysterectomy for a benign condition and the roles of health care providers and patients in the initiation of screening Pap tests. We used 2000 to 2013 data from the National Health Interview Survey on women aged 20 years or older who had undergone a hysterectomy (n = 11 616) to estimate unnecessary Pap test use. The percentage of self-reported Pap testing in the preceding 3 years among women who had undergone a hysterectomy decreased from 72.2% in 2000 to 53.3% in 2013. In 2013, 42.4% of women who had undergone a hysterectomy reported receiving recommendations for screening from a health care provider in the past year (32% of which were unnecessary), and 32.1% reported undergoing Pap tests in the preceding year (22.1% of which were unnecessary). Although the majority of Pap tests were performed at a clinician's recommendation, approximately one fourth were initiated by patients without clinician recommendations. Health care providers should advise women who have had a total hysterectomy for a benign condition on appropriate use of screening services.


Physician Experience and Risk of Rituximab Discontinuation in Older Adults With Non-Hodgkin's Lymphoma.
Provider experience, or clinical volume, is associated with improved outcomes in many complex healthcare settings. Despite increased complexity of anticancer therapies, studies evaluating physician-level experience and cancer treatment outcomes are lacking. A population-based study was conducted of older adults (aged ≥66 years) diagnosed with B-cell non-Hodgkin's lymphoma in 2004 through 2011 using SEER-Medicare data. Analysis focused on outcomes in patients receiving rituximab, the first approved monoclonal anticancer immunotherapy. We hypothesized that lower physician experience using rituximab and managing its infusion-related reactions would be associated with early treatment discontinuation. A 12-month look-back from each initiation of rituximab was used to categorize physician volume (0, 1-2, or ≥3 initiations per year). Modified Poisson regression was used to account for provider-level correlation and estimated relative risk (RR) of early rituximab discontinuation (<3 cycles within 180 days of rituximab initiation). Cox proportional hazards were used to measure the impact of rituximab discontinuation on survival. Among 15,110 patients who initiated rituximab with 2,684 physicians, 7.6% experienced early rituximab discontinuation. Approximately one-fourth of patients (26.1%) initiated rituximab with a physician who had no rituximab initiations during the preceding 12 months. Compared with patients treated by physicians who had ≥3 rituximab initiations in the prior year, those treated by physicians without initiations were 57% more likely to experience early discontinuation (adjusted RR [aRR], 1.57; 95% CI, 1.35-1.82; P<.001 for 0 vs ≥3, and aRR, 1.19; 95% CI, 1.03-1.37; P=.02 for 1-2 vs ≥3). Additionally, rituximab discontinuation was associated with higher risk of death (adjusted hazard ratio, 1.39; 95% CI, 1.28-1.52; P<.001). Lower oncologist experience with rituximab was associated with increased risk of early rituximab discontinuation in Medicare beneficiaries with non-Hodgkin's lymphoma. Physician-level volume may be an important factor in providing high-quality cancer care in the modern era.


Reduced Reward Processing in Schizophrenia: A Comprehensive EEG Event-Related Oscillation Study.
It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia (SZ). Reduced reward anticipation has been suggested as a core symptom of SZ. The present study aims to evaluate the event-related oscillations (EROs) delta, theta, alpha, beta, and gamma in patients with SZ during the Monetary Incentive Delay (MID) task, which elicits the neural activity of reward processing. Twenty-one patients with SZ and twenty-two demographically matched healthy controls were included in the study. EROs were compared between groups and correlation analyses were conducted to determine a possible relationship between clinical scores and ERO values. Compared with healthy controls, the SZ group had reduced (1) delta and theta amplitudes in the reward condition (2) total beta and non-incentive cue-related beta amplitudes, and (3) incentive cue-related frontal gamma amplitudes. These reductions can be interpreted as impaired dopaminergic neurotransmission and disrupted cognitive functioning in the reward processing of SZ. In contrast, SZ patients showed higher incentive cue-related theta and occipital gamma amplitudes compared to controls. These increments may reflect negative symptoms in SZ. Moreover, theta amplitudes showed a negative correlation with Calgary Depression Scale for Schizophrenia scores and a positive correlation with attentional impulsivity. This is the first study showing the impairments of SZ patients in EROs from delta to gamma frequency bands compared with healthy controls during reward anticipation. Being the first comprehensive study, our results can be interpreted as providing evidence for disrupted brain dynamics in the reward processing of SZ studied by EROs. It may become possible to help patients' wellness by improving our understanding of reward processing in schizophrenia and developing innovative rehabilitation treatments based on these findings.


Assessment of ventricular contractile function during orthotopic liver transplantation.
Hemodynamic alterations are a well-known phenomenon that influence the outcome of orthotopic liver transplantation (OLT). Whether or not myocardial dysfunction, which has various causes, contributes to this instability is still debated. Previous transesophageal echocardiography (TEE) studies have presented controversial data, not leading to final clarification. This is mainly because the impact of other contributing factors (inotropic support, alternating preload conditions and temperature) remained unaccounted for. We therefore measured the left ventricular shortening fraction (LVSF), a parameter reflecting myocardial contractility, in 10 consecutive patients undergoing OLT without veno-venous bypass. We measured during preparation (PP), during the anhepatic (AP) phase and the immediate reperfusion phase (RP). During the AP we observed a significant decrease of LVSF which never fell to subnormal levels in the majority of our patients, whereas during the RP, LVSF returned to PP values. These findings support the assumption that myocardial function is influenced by OLT, but that it plays only a minor role in the occurrence of hemodynamic instability, which could mainly be attributed to volume fluctuations.


Effects of probiotics on the lipid profile: systematic review.
Alterations in the intestinal microbiota can modulate mechanisms involving risk factors for cardiovascular diseases, including dyslipidemias The objective was to review the effects of probiotic supplementation on the prevention and treatment of changes to the lipid profile. The searches were run on the PubMed database, using the descriptors "probiotics and lipid profile" and "probiotics and dyslipidemia," with publication dates restricted to 2013 to 2018. Supplementation with probiotics significantly reduced total cholesterol, LDL-c, and triglycerides and increased HDL-c. Some benefits were observed on anthropometric variables, glycemic control, oxidative stress, inflammation, and immune system. The present study suggests that probiotic supplementation should be indicated as adjunctive treatment for dyslipidemias. Further studies should be developed to clarify long-term effects, as well as the influence of probiotics in combination with drug therapy.


Long-term care for people with dementia: environmental design guidelines.
A large and growing number of people with dementia are being cared for in long-term care. The empirical literature on the design of environments for people with dementia contains findings that can be helpful in the design of these environments. A schema developed by Marshall in 2001 provides a means of reviewing the literature against a set of recommendations. The aims of this paper are to assess the strength of the evidence for these recommendations and to identify those recommendations that could be used as the basis for guidelines to assist in the design of long term care facilities for people with dementia. The literature was searched for articles published after 1980, evaluating an intervention utilizing the physical environment, focused on the care of people with dementia and incorporating a control group, pre-test-post-test, cross sectional or survey design. A total of 156 articles were identified as relevant and subjected to an evaluation of their methodological strength. Of these, 57 articles were identified as being sufficiently strong to be reviewed. Designers may confidently use unobtrusive safety measures; vary ambience, size and shape of spaces; provide single rooms; maximize visual access; and control levels of stimulation. There is less agreement on the usefulness of signage, homelikeness, provision for engagement in ordinary activities, small size and the provision of outside space. There is sufficient evidence available to come to a consensus on guiding principles for the design of long term environments for people with dementia.


Designing Epidemiology Studies to Determine the Incidence and Prevalence of Encapsulating Peritoneal Sclerosis (EPS).
The reported incidence and prevalence of encapsulating peritoneal sclerosis (EPS) varies markedly between North America, Europe, Japan, and Australia. Although this could reflect differences in clinical practice patterns and access to transplantation as there is no current test for early detection, and some patients may present many years after discontinuation of peritoneal dialysis (PD), there are concerns about under-reporting, particularly for those with milder forms. Currently, only PD vintage has been identified as a significant risk factor for developing EPS, although some patients can develop EPS within months of starting PD. As such, there is a need for epidemiological studies to determine the incidence and prevalence of EPS to allow for patient education and counselling in terms of dialysis modality choice and length of treatment. In addition, carefully designed epidemiological studies could potentially allow for the identification of risk factors and bio-markers that could then be used to identify patients at increased risk of developing EPS in the future. Typically, studies to date have been underpowered with inadequate longitudinal follow-up. We review the different types of epidemiological studies and provide information as to the number of patients to be recruited and the duration of follow-up required to determine the incidence and prevalence of EPS.


A case of primary systemic necrotizing vasculitis presenting primarily with neurologic involvement.
Systemic necrotizing vasculitis (SNV) is a type of vasculitis that presents with necrosis, predominantly involving large, medium-sized and small arteries. Peripheral neuropathy is a major clinical feature of the primary and secondary systemic vasculitides, and is often observed during the early phases of the disease, causing axonal neuropathy. The prevalence of central nervous system (CNS) involvement ranges from 4% to 45%. Encephalopathy, focal neurological deficits, and seizures are the most common manifestations and usually occur late during the course of SNV. In this report, we describe a 61-year-old woman with SNV who had both CNS and peripheral nervous system vasculitic involvement. We also discuss the pathophysiology of nervous system involvement in patients with SNV.


Potential Uses of Nonthermal Atmospheric Pressure Technology for Dermatologic Conditions in Children.
Nonthermal atmospheric plasma (NTAP)(also known as cold atmospheric plasma [CAP]) is a rapidly emerging technology showing promising treatment results for a wide variety of dermatologic conditions. Research on NTAP for the treatment of pediatric dermatologic conditions is limited. We conducted a systematic review to elucidate reported applications of NTAP for skin conditions in children. Overall, NTAP offers a promising safety profile and painless treatment option that has the potential to deliver similar efficacy to many standard therapies in pediatric dermatology.


Losing the match game: few residency slots leave more graduates unmatched.
An increasing number of medical graduates in the country, particularly in Texas, are finding it hard to match to a residency program in their preferred specialty. While medical educators say there are various reasons for that, almost all point to a growing imbalance in the ratio of medical graduates to residency slots. That imbalance is particularly apparent in Texas, where the state offered fewer first-year residency positions in 2010 than it had medical graduates.


Wheat cytoplasmic arginine tRNA isoacceptor with a U*CG anticodon is an efficient UGA suppressor in vitro.
Many RNA viruses express part of their genomic information by read-through over internal termination codons. We have recently characterized tobacco cytoplasmic (cyt) and chloroplast (chl) tRNACmCATrp and tRNAGCACys as natural suppressor tRNAs that are able to read the leaky UGA codon in RNA-1 of tobacco rattle virus, albeit with different efficiencies. Here we have identified a third natural UGA suppressor in plants. We have purified and sequenced four cyt tRNAArg isoacceptors with ICG, CCG, U*CG and CCU anticodons from wheat germ. With the exception of tRNAICGArg, these are the first sequences of plant tRNAsArg. In order to study the potential suppressor activity of wheat tRNAsArg we have used in vitro synthesized mRNA transcripts in which different viral read-through regions had been placed. In vitro translation was carried out in a homologous wheat germ extract. We found that tRNAU*CGArg is an efficient UGA suppressor in vitro, whereas the other three tRNAArg isoacceptors exhibit no or very low suppressor activity. Interaction of tRNAU*CGArg with the UGA codon requires a G:U base pair at the third anticodon position. This is the first time that an arginine-accepting tRNA has been characterized as a natural UGA suppressor. A remarkable feature of cyt tRNAU*CGArg is its ability to misread the UGA at the end of the coat protein cistron in RNA-1 of pea enation mosaic virus, which is not accomplished by cyt tRNACmCATrp or cyt tRNAGCACys, due to an unfavourable codon context.


Crowdsourcing the Ideal Nipple-Areolar Complex Position for Chest Masculinization Surgery.
Chest masculinization surgery is increasing in prevalence. However, the ideal location of the nipple-areolar complex (NAC) is unknown. Our purpose was to determine the most aesthetically favorable male NAC position for use in chest masculinization through crowdsourcing. Using Adobe Photoshop CC 2017, 8 locations for the NAC were created based on previous literature descriptions. Amazon Mechanical Turk was utilized as a crowdsourcing interface-respondents were asked to rank the top 3 most favorable and least favorable images. Analysis of variance with subsequent Tukey HSD was used for a statistical comparison of favorability scores for different NAC localizations. Values were considered significant with P < 0.05. Eight hundred nineteen respondents participated in the survey. NAC positions of Images C (mean score = 1.9222) and A (mean score = 1.7365) received higher favorability scores than those of Images D, E, F, G, and H (all P < 0.05). There were no significant differences between Images C and A (C versus A: P = 0.6412). NAC localizations from Images G (mean score = -2.0353) and H (mean score = -1.6908) received lower favorability scores than Images A, B, C, D, E, and F (all P < 0.05). There were no significant differences between Images G and H (P = 0.2279). Most respondents preferred Images C and A, and few favored Images G and H, suggesting that lateral NAC placement is favored over more medial localizations. Additionally, both Images C and A utilize relatively inferior NAC placements. Therefore, we recommend a location inferior and lateral to the NAC. Ultimately, NAC localization during chest masculinization will be the result of shared decision-making between the patient and the surgeon to fulfill each patient's aesthetic goals.


Pathogenicity and virulence of Acinetobacter baumannii: Factors contributing to the fitness in healthcare settings and the infected host.
Acinetobacter baumannii is a common cause of healthcare-associated infections and hospital outbreaks, particularly in intensive care units. Much of the success of A. baumannii relies on its genomic plasticity, which allows rapid adaptation to adversity and stress. The capacity to acquire novel antibiotic resistance determinants and the tolerance to stresses encountered in the hospital environment promote A. baumannii spread among patients and long-term contamination of the healthcare setting. This review explores virulence factors and physiological traits contributing to A. baumannii infection and adaptation to the hospital environment. Several cell-associated and secreted virulence factors involved in A. baumannii biofilm formation, cell adhesion, invasion, and persistence in the host, as well as resistance to xeric stress imposed by the healthcare settings, are illustrated to give reasons for the success of A. baumannii as a hospital pathogen.


Is urgent coronary artery bypass grafting a safe option in octogenarians? A developing country perspective.
Life expectancy has increased during recent decades leading to a growing number of older population. The objective of this study was to evaluate the outcomes of coronary artery bypass grafting (CABG) in octogenarians and to compare the outcomes of the emergent CABG with elective surgery. Prospectively collected data from 31 consecutive octogenarian patients who underwent CABG between 1 January 2006 and 31 December 2008 were analyzed. Main outcomes of interest included mortality, length of ICU stay, length of hospital stay, priority of surgery, postoperative complications and functional status on follow-up. Fifteen patients were operated on an urgent basis. Patients operated on an urgent basis were in NYHA class III or IV preoperatively (P=0.0016). There were no significant differences in operative and postoperative variables. There were three in-hospital deaths and 23 patients (82%) were alive on follow-up and 19 were in functional class I or II. Quality of life assessment was performed using Seattle Angina Questionnaire and patients reported remarkable improvement in quality of life. Overall, 90% patients were not or slightly disabled in their daily activity. Satisfaction with their current quality of life was reported by 95% of patients. CABG may be performed in octogenarians with remarkable outcomes and improvement in quality of life.


[Partial androgen deficiency in aging male (Padam syndrome): terminology and current approaches to choice of replacement hormonal therapy].
The authors propose a novel approach to treatment of PADAM syndrome based on stimulation of synthesis of endogenic testosterone. A total of 150 patients with PADAM were examined in the Endocrinological Research Center. The examination included physical and andrological examinations with digital rectal investigation of the prostate, filling-in questionnaires, hormonal and biochemical tests. In view of positive test with chorionic gonadotropin (CG), therapy of choice was stimulating therapy with CG. The dose was adjusted individually - from 1000 to 3000 units once in 4 days (1000 units dose was given to 20% patients, 2000 - to 70% and 3000 - to 10% patients). Efficacy did not reduce in long-term treatment. The authors make the following conclusion: choice of PADAM therapy should be individual and based on the age of the patient, body mass index, the necessity to retain spermatogenesis, packed cell volume, associated diseases. Secondary nature of PADAM and positive test for CG allows usage of CG as a perspective therapy in prevention and treatment of age-related lowering of testosterone.


Ectopic thyroid tissue on thallium/technetium parathyroid scan.
The thallium 201/technetium 99m pertechnetate radionuclide study is becoming widely accepted as a means of localizing abnormal or aberrantly located parathyroid tissue. We describe a case in which ectopic retrosternal thyroid tissue appeared as a parathyroid adenoma on thallium-201/technetium-99m pertechnetate scan. Physicians who use this radionuclide study should be aware of the possibility of false-positive images within the mediastinum.


The role of coherence in a systems view of cancer development.
Theories of cancer origin are going through a paradigm shift, opening cancer research to new hypotheses. Accumulating evidence from the tissue microenvironment research, from bioenergetics, epigenetics, systems biology and thermodynamics tends to converge in characterising cancer as essentially a genetically non-deterministic disease. Instead, it is characterised by progressive disorganisation at a variety of organisational levels, from the genome and metabolic networks, to tissue integrity. As biological self-organisation is fuelled by the continuous supply of energy and infdrmation, these represent systemic roots of cancer origin, when compromised. The coherence of molecular dynamics has been recognised as an organising principle behind the long-range coordination of biological processes which can explain the remarkable efficiency of biological systems. Recent methodological advances have enabled the rapid accumulation of experimental evidence pointing to coherence as indeed playing an active role in mediating the flow of energy and information in diverse molecular systems, which is sufficient reason to apply it to a systems view on cancer development. We review theoretical models of how impaired coherence dynamics could lead to cancer as well as propose a new hypothesis based on the quantum electrodynamic theory of coherence. We discuss how the concept of coherence could connect different aspects of cancer and possibly represent their underlying theoretical framework, thus combining biological and physical approaches to understanding this complex pathology.


"We are unique": organizational stressors, peer support and attitudes toward mental health treatment among airport firefighters.
Airport firefighters are responsible for providing emergency responses to aviation incidents on a runway or in the vicinity of an airport, including airplane crashes, mass casualty events, emergency landings and many other concerns on airport grounds. While data exist on the occupational stressors of firefighters and public safety personnel in general, there is a gap in knowledge regarding the experiences of airport firefighters, particularly in relation to their organizational stressors, peer supports and attitudes toward mental health treatment. We conducted two focus groups with 10 career firefighters working at an airport in Atlantic Canada in 2019. Focus groups were recorded; the recordings were transcribed and later coded using thematic analysis, which took an inductive, iterative, narrative approach. Airport firefighters face unique challenges, and operational stressors are overshadowed by organizational stressors. Additionally, peer support is an integral aspect of coping with both organizational stressors and critical incidents. Firefighters were found to have positive attitudes toward mental health treatment in general, but several barriers still remain, such as stigma, fear of being placed on leave and fear of confidentiality breach. Specialized treatment options for public safety personnel and airport firefighters who engage in serious incidents outside of their regular duties are needed.


Design and synthesis of a vanadate-based ratiometric fluorescent probe for sequential recognition of Cu2+ ions and biothiols.
A novel YVO4:Eu3+@CDs core-shell nanomaterial with two main emission peaks at 405 and 617 nm was synthesized through a simple mixing method, in which the carbon quantum dots (CDs) self-assembled with the YVO4:Eu3+ nanoparticle, due to the high affinity of oxygen-containing groups such as -COOH or -OH of CDs to the metal ions on the surface of YVO4:Eu3+. The red fluorescence of YVO4:Eu3+@CDs located at 617 nm can be quenched by Cu2+ ions efficiently, while the blue emission remains invariable; based on this, we construct a ratio fluorescent probe YVO4:Eu3+@CDs for Cu2+ ion detection, in which the blue emission of CDs is selected as the reference signal, and the red emission of YVO4:Eu3+ acts as an output signal. Furthermore, the addition of biothiol recovers the quenched red fluorescence quickly, which can be completed in 18 minutes. Thus, YVO4:Eu3+@CDs can also be used as a 'turn on' ratio fluorescent probe for biothiol rapid detection. Taking l-cysteine (l-Cys) as the model, the fluorescence intensity of the 617 nm peak increases with increasing Cys, and the ratio of F617/F405 is linear to the concentration of Cys in the range of 0.1 μM to 10 μM with a detection limit of 41 nM. Compared with these single wavelength emission biothiol fluorescent probes, an obvious change in the fluorescence color from blue to pink can be conveniently observed by the naked eye under a UV lamp. Meanwhile, this ratiometric probe has also been demonstrated to be used for the visual identification of biothiols in real blood serum samples.


The automatic regulation of the basal dose on the insulin pump for the treatment of patients that have Diabetes type 1.
Diabetes mellitus type 1 is a chronic metabolic disorder, and its main characteristic is Hyperglycemia. It usually occurs in the early years because of the absolute or relative absence of the active insulin that is caused by the autoimmune disease of the beta cells of the pancreas. Despite the numerous researches and efforts of the scientists, the therapy for Diabetes type 1 is based on the substitution of insulin. Even though the principles of the therapy have not changed so much, still some important changes have occurred in the production and usage of insulin. Lately, the insulin pumps are more frequent in the therapy for Diabetes type 1. The functioning of the pump is based on the continuing delivery of insulin in a small dose ("the basal dose"), that keeps the level of glycemia in the blood constant. The increase of glycemia during the meal is reduced with the additional dose of insulin ("the bolus dose"). The use of the insulin pumps and the continuing glucose sensors has provided an easier and more efficient monitoring of the diabetes, a better metabolic control and a better life quality for the patient and his/her family. This work presents the way of automatic regulation of the basal dose of insulin through the synthesis of the functions of the insulin pump and the continuing glucose sensor. The aim is to give a contribution to the development of the controlling algorithm on the insulin pump for the automatic regulation of the glucose concentration in the blood. This could be a step further which is closer to the delivery of the dose of insulin that is really needed for the basic needs of the organism, and a significant contribution is given to the development of the artificial pancreas.


Ectodomain shedding of EGFR ligands and TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis in mice.
The cell death receptor Fas plays a role in the establishment of fulminant hepatitis, a major cause of drug-induced liver failure. Fas activation elicits extrinsic apoptotic and hepatoprotective signals; however, the mechanisms by which these signals are integrated during disease are unknown. Tissue inhibitor of metalloproteinases 3 (TIMP3) controls the critical sheddase a disintegrin and metalloproteinase 17 (ADAM17) and may dictate stress signaling. Using mice and cells lacking TIMP3, ADAM17, and ADAM17-regulated cell surface molecules, we have found that ADAM17-mediated ectodomain shedding of TNF receptors and EGF family ligands controls activation of multiple signaling cascades in Fas-induced hepatitis. We demonstrated that TNF signaling promoted hepatotoxicity, while excessive TNF receptor 1 (TNFR1) shedding in Timp3-/- mice was protective. Compound Timp3-/-Tnf-/- and Timp3-/-Tnfr1-/- knockout conferred complete resistance to Fas-induced toxicity. Loss of Timp3 enhanced metalloproteinase-dependent EGFR signaling due to increased release of the EGFR ligands TGF-alpha, amphiregulin, and HB-EGF, while depletion of shed amphiregulin resensitized Timp3-/- hepatocytes to apoptosis. Finally, adenoviral delivery of Adam17 prevented acetaminophen-induced liver failure in a clinically relevant model of Fas-dependent fulminant hepatitis. These findings demonstrate that TIMP3 and ADAM17 cooperatively dictate cytokine signaling during death receptor activation and indicate that regulated metalloproteinase activity integrates survival and death signals during acute hepatotoxic stress.


Possible mechanisms underlying the slow lactose fermentation phenotype in Shigella spp.
A Southern hybridization analysis revealed that the region homologous to Escherichia coli lacZ was present on the chromosomal DNAs of beta-galactosidase-positive Shigella strains, such as Shigella dysenteriae serovar 1 and Shigella sonnei strains, whereas this region was absent from chromosomal DNAs of beta-galactosidase-negative strains of Shigella flexneri and Shigella boydii. We found that the lacY-A region was deficient in S. dysenteriae serovar 1 and believe that this is the reason for the slow fermentation of lactose by this strain. S. sonnei strains possessed the region which hybridized with E. coli lacY-A despite their slow hydrolysis of lactose. The whole lactose-fermenting region was cloned from S. sonnei and compared with the cloned lac operon of E. coli K-12. Both clones directed the synthesis of beta-galactosidase in an E. coli K-12 strain lacking indigenous beta-galactosidase activity (strain JM109-1), and we observed no difference in the expression of beta-galactosidase activity in S. sonnei and E. coli. However, E. coli JM109-1 harboring the lactose-fermenting genes of S. sonnei exhibited the slow lactose fermentation phenotype like the parental strain. S. sonnei strains had no detectable lactose permease activities. E. coli JM109-1 harboring the lactose-fermenting genes of S. sonnei had a detectable permease activity, possibly because of the multicopy nature of the cloned genes, but this permease activity was much lower than that of strain JM109-1 harboring the lac operon of E. coli K-12. From these results we concluded that slow lactose fermentation by S. sonnei is due to weak lactose permease activity.


Fine structural effects of hypophysectomy on the aging rat pineal gland.
A study was undertaken to examine the effects of pituitary removal on age-related changes in the female rat pineal. Three 9-month-old controls, three 23-month-old controls and three rats hypophysectomized at 19 months and sacrificed at 23 months of age were utilized. Electron microscopic evaluation indicated that following hypophysectomy there was a significant loss of lipid droplets, no change in the frequency of light and dark pinealocytes or cytoplasmic dense bodies (probably lipofuscin), a trend towards increased granular deposits between cells, no change in the number of pinealocytes with nuclear invaginations and decreased numbers of cells with nuclear inclusions. The results indicate that while some tissues (kidney) may show reduced aging indices following hypophysectomy other tissues such as the pineal may be detrimentally affected.


Transcriptional regulation of voltage-gated Ca2+ channels.
The transcriptional regulation of voltage-gated Ca2+ (CaV ) channels is an emerging research area that promises to improve our understanding of how many relevant physiological events are shaped in the central nervous system, the skeletal muscle and other tissues. Interestingly, a picture of how transcription of CaV channel subunit genes is controlled is evolving with the identification of the promoter regions required for tissue-specific expression and the identification of transcription factors that control their expression. These promoters share several characteristics that include multiple transcriptional start sites, lack of a TATA box and the presence of elements conferring tissue-selective expression. Likewise, changes in CaV channel expression occur throughout development, following ischaemia, seizures or chronic drug administration. This review focuses on insights achieved regarding the control of CaV channel gene expression. To further understand the complexities of expression and to increase the possibilities of detecting CaV channel alterations causing human disease, a deeper knowledge on the structure of the 5' upstream regions of the genes encoding these remarkable proteins will be necessary.


Linking trauma to mental health in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN).
Rates of youth depression and suicide are rising worldwide and represent public health crises. The present study examined the relationship between trauma history and symptoms of depression, suicidal ideation, and anxiety among suicidal and depressed youth. A diverse group of 1000 8-20-year-olds enrolled in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN) reported their trauma history (Traumatic Events Screening Inventory for Children) and symptoms of depression (Patient Health Questionnaire for adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder scale; GAD-7), and suicidality (Concise Health Risk Tracking scale; CHRT-SR). Nearly half of the sample reported exposure to multiple categories of traumatic experiences. Number of trauma exposure categories significantly predicted PHQ-A and GAD-7 scores. Exposure to interpersonal trauma and to sexual trauma were significantly associated with PHQ-A, GAD-7, and CHRT-SR scores. The number of trauma exposure categories was associated with increased levels of anxiety and depression; however, only exposure to interpersonal or sexual trauma was associated with more suicidality. Clinicians should assess trauma exposure in patients seeking psychiatric care, especially for interpersonal and sexual trauma, which may be predictive of increased risk for suicidality in depressed youth. Future work should disentangle the effects of specific trauma types from multiple trauma exposure.


Passive immunization with human neutralizing monoclonal antibodies: correlates of protective immunity against HIV.
Passive immunization with synergistic combinations of human monoclonal antibodies (mAbs) directed against conserved epitopes of the human immunodeficiency virus (HIV) envelope completely protected 13 out of 16 rhesus monkeys challenged intravenously or orally with chimeric simian-human immunodeficiency virus (SHIV) strains; partial protection was seen in another two. A high degree of protection was seen among orally challenged neonates. Thus, we propose that passive immunization with synergistic combinations of neutralizing human mAbs may be effective in preventing maternal HIV transmission when given as post-exposure prophylaxis at birth and as prophylaxis against milk-borne transmission. Because we only used mAbs with well-defined epitope specificities, our studies also yield key information for designing AIDS vaccines: the correlates of immune protection. Vaccine strategies that can evoke antibody responses to epitopes recognized by the mAbs used in our primate studies could be important components of successful AIDS vaccines.


Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression.
Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in vitro, but the extent to which they can transdifferentiate to mature, functional neurons is uncertain. We examined the effects of different growth factors and combinations thereof on the expression of neuronal marker proteins in cultures of BMC enriched in marrow stromal cells. Patterns of neuronal marker expression varied depending on the growth factor or factors to which BMC cultures were exposed. Cultures treated for up to 5 weeks with epidermal growth factor, fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed neuron-like cellular processes and expressed neuronal markers, including the neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau, synaptophysin, alpha(1A) and alpha(1B) calcium channel subunits, NR2A glutamate receptor subunits, and gamma-aminobutyric acid. However, the intracellular distribution of these markers was distinct from their usual distribution in mature neurons. We conclude that a variety of growth factors can drive BMC toward a neuronal phenotype or phenotypes, but that morphological neuronal features and the ectopic expression of neuronal proteins and neurotransmitters may not equate with the ability to execute normal neuronal functions.


Interarm Systolic and Diastolic Blood Pressure Difference Is Diversely Associated With Cerebral Atherosclerosis in Noncardioembolic Stroke Patients.
Interarm systolic and diastolic blood pressure differences (IASBD, IADBD) are not infrequent in various populations. Cerebral atherosclerosis, including extracranial cerebral atherosclerosis (ECAS) and intracranial cerebral atherosclerosis (ICAS), is an important risk factor for stroke. In this study, we aimed to investigate the relationship of IASBD, IADBD with presence and burden of ICAS and ECAS. This was a retrospective hospital-based cross-sectional study. In total, 1,063 consecutive noncardioembolic ischemic stroke patients, who were checked for bi-brachial blood pressures from ankle-brachial index and brain magnetic resonance angiographic images of cerebral arteries, were included. The IASBD and IADBD were defined as absolute value of the blood pressure difference in both arms. In all included patients, patients with IASBD ≥10 and IADBD ≥10 were noted in 9.4% (100/1,063) and 5.3% (56/1,063). The patients with IASBD ≥10 mm Hg were more frequently burdened with ICAS (P = 0.001) and ECAS (P = 0.027) and patients with IADBD ≥10 mm Hg were more frequently burdened with ICAS (P = 0.042) but not ECAS (P = 0.187). Multivariate analysis after adjusting gender, age, and a P value <0.1 in univariate analysis showed IASBD ≥10 mm Hg was associated with the presence of both ECAS and ICAS [odds ratio (OR): 2.96, 95% confidence interval (CI): 1.65-5.31]. The IADBD ≥10 mm Hg was related with presence of ICAS only (OR: 1.87, 95% CI: 1.05-3.37) but not with ECAS only (OR: 1.50, 95% CI: 0.73-3.06). Our study showed IASBD and IADBD were diversely associated with cerebral atherosclerosis. In noncardioembolic stroke patients with IASBD ≥10 or IADBD ≥10, the possibility of accompanying cerebral atherosclerosis should be considered.


Network thermodynamic modeling of hormone regulation of active Na+ transport in cultured renal epithelium (A6).
A network thermodynamic model was developed to describe steady-state ion flows (Na+,K+, and Cl-) and related electrical events in a cultured renal epithelium (A6) derived from toad kidney. Three hypotheses for explaining the steady-state increases in short-circuit current (SCC) produced by aldosterone and/or insulin were examined using the model. Changing only the number of basolateral Na+-K+ pumps produced virtually no change in SCC and was ruled out. Changing only the number of apical Na+ channels could produce sufficient increases in SCC but presented problems in the pattern of changes produced in cell ion concentrations and therefore appeared unlikely. Changing both apical and basolateral parameters in a balanced, coordinated manner produced the maximal changes in SCC with the minimal changes in cell ion concentrations and appeared to be the "best" hypothesis. In addition, it was found necessary for tight junction permeability to increase as active Na+ transport increased under open-circuit conditions. Simulations, using these results, compared favorably with experimental data on the stimulatory effects of aldosterone and insulin, both separately and together, on active Na+ transport.


Effects of ozone oxidative preconditioning on TNF-alpha release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock.
Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-alpha levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-alpha levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-alpha production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems.


Survival of patients with cancer in a medical critical care unit.
The records of 40 patients with cancer and 684 patients without cancer admitted to a medical critical care unit were reviewed for the purpose of comparing survival. Patients with cancer had a higher mortality (55%, 22/40) than the patients without cancer (17%, 118/864). Patients with cancer and respiratory failure had a higher mortality (75%, 18/24) than patients without cancer but with respiratory failure (25%, 66/273) and a higher mortality than patients with cancer but without respiratory failure (25%, 4/16). In patients with cancer, the manifestation of respiratory failure as the adult respiratory distress syndrome (ARDS) was associated with a high mortality (86%, 12/14), which was not statistically higher than in patients with cancer with non-ARDS respiratory failure (60%, 6/10) or in patients without cancer with ARDS (65%, 28/43). Patients with cancer but without respiratory failure had a mortality of 25% (4/16). All eight patients with cancer admitted to the hospital because of life-threatening metabolic disturbances survived. In deciding whether to apply critical care techniques to a patient with cancer, the physician should consider the specific nature of the life-threatening illness.


Induction of Sublethal Oxidative Stress on Human Sperm before Cryopreservation: A Time-Dependent Response in Post-Thawed Sperm Parameters.
A recent innovative approach, based on induction of sublethal oxidative stress to enhance sperm cryosurvival, has been applied before sperm cryopreservation. The purpose of this study was to investigate the effects of different induction times of sublethal oxidative stress before cryopreservation on human post-thawed sperm quality. In this experimental study, we selected semen samples (n=20) from normozoospermic men according to 2010 World Health Organization (WHO) guidelines. After processing the samples by the density gradient method, we divided each sample into 5 experimental groups: fresh, control freezing, and 3 groups exposed to 0.01 μM sodium nitroprusside (SNP) [nitric oxide (NO) donor] for 30 (T30), 60 (T60), or 90 minutes (T90) at 37˚C and 5% CO2 before cryopreservation. Motion characteristics [computer-assisted sperm analyser], viability, apoptosis [annexin V/propidium iodide (PI) assay], DNA fragmentation [sperm chromatin structure assay (SCSA)], and caspase 3 activity (FLICA Caspase Detection Kit) were assessed after thawing. The results were analysed by using one-way ANOVA and Tukey's test. The means were significantly different at P<0.05. Cryopreservation significantly decreased sperm viability and motility parameters, and increased the percentage of apoptosis, caspase 3 activity, and DNA fragmentation (P<0.01) compared to the fresh group. The T60 group had a higher significant percentage of total motility (TM) and progressive motility compared with other cryopreserved groups (P<0.05). We observed a significantly lower percentage of apoptotic rate and caspase 3 activity in the T60 group compared to the other cryopreserved groups (P<0.05). DNA integrity was not significantly affected by this time of sublethal stress induction (P>0.05). Our results have demonstrated that the application of sublethal oxidative stress by using 0.01 μM NO for 60 minutes before the freezing process can be a beneficial approach to improve post-thawed human sperm quality.


Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus.
The risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy. We examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis. During a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20-2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29-2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19-1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01-1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up. Among patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.


[Condition of the microcirculatory bed of the bulbar conjunctiva in physiological and pathological pregnancies].
By means of biomicroscopic method the bulbar conjunctiva in 150 women (18-35 years of age) have been examined. Of them: 30 healthy women make the control group; the second group includes 60 healthy women at their first and second half of pregnancy; the third group includes 60 women with pregnancy developing against the background of noncomplicated insulin-dependent diabetus mellitus during their first and second half of pregnancy. In the healthy women there are not any significant changes in most of the parameters of the microcirculatory bed during the first half of their pregnancy, and in the second half of their pregnancy a great density of the blood vascular bed is determined. Diameters of all vessels in the hemomicrocirculatory bed are significantly increased, as compared to those in the control group. In the women suffering from diabetus mellitus, during the first half of pregnancy certain changes in the picture of the vascular network is observed, as well as an increased convolution. uneveness in distribution of blood vessels; in the second half of their pregnancy a pronounced deformity of the vacular network is observed, decreasing diameter of afferent vessels and an essential dilatation of postcapillaries and venules are registered. Certain signs of aggregation of blood formed elements is noted.


Human intervertebral disc stiffness correlates better with the Otsu threshold computed from axial T2 map of its posterior annulus fibrosus than with clinical classifications.
Degeneration of the intervertebral disc, sometimes associated with low back pain and abnormal spinal motions, represents a major health issue with high costs. A non-invasive degeneration assessment via qualitative or quantitative MRI (magnetic resonance imaging) is possible, yet, no relation between mechanical properties and T2 maps of the intervertebral disc (IVD) has been considered, albeit T2 relaxation time values quantify the degree of degeneration. Therefore, MRI scans and mechanical tests were performed on 14 human lumbar intervertebral segments freed from posterior elements and all soft tissues excluding the IVD. Degeneration was evaluated in each specimen using morphological criteria, qualitative T2 weighted images and quantitative axial T2 map data and stiffness was calculated from the load-deflection curves of in vitro compression, torsion, lateral bending and flexion/extension tests. In addition to mean T2, the OTSU threshold of T2 (TOTSU), a robust and automatic histogram-based method that computes the optimal threshold maximizing the distinction of two classes of values, was calculated for anterior, posterior, left and right regions of each annulus fibrosus (AF). While mean T2 and degeneration schemes were not related to the IVDs' mechanical properties, TOTSU computed in the posterior AF correlated significantly with those classifications as well as with all stiffness values. TOTSU should therefore be included in future degeneration grading schemes.


Variability of transient elastography-based spleen stiffness performed at 100 Hz.
Spleen stiffness measurement (SSM) performed by transient elastography at 100 Hz is a novel technology for the evaluation of portal hypertension in advanced chronic liver disease, but technical aspects are lacking. We aimed to evaluate the intraexamination variability of SSM and to determine the best transient elastography protocol for obtaining robust measurements to be used in clinical practice. We analyzed 253 SSM exams with up to 20 scans for each examination, performed between April 2021 and June 2022. All SSM results were evaluated according to different protocols by dividing data into groups of n measurements (from 2 to 19). Considering as reference the median SSM values across all the 20 measurements, we calculated the distribution of the absolute deviations of each protocol from the reference median. This analysis was repeated 1,000 times by resampling the data. Distributions were also stratified by etiology (chronic liver disease versus clinically significant portal hypertension) and different SSM ranges: < 25 kPa, 25-75, and > 75 kPa. Overall, we observed that the spleen stiffness exam had less variability if it exceeded 12 measurements, i.e., absolute deviations ≤ 5 kPa at 95% confidence. For exams with higher SSM values (> 75 kPa), as seen in clinically significant portal hypertension, at least 15 measurements are highly recommendable. Fifteen scans per examination should be considered for each SSM exam performed at 100 Hz to achieve a low intraexamination variability within a reasonable time in clinical practice. Performing at least 15 scans per examination is recommended for 100 Hz SSM in order to achieve a low intraexamination variability, in particular for values > 75 kPa compatible with clinically significant portal hypertension. • Spleen stiffness measurement by transient elastography is used for stratification in patients with portal hypertension. • At 100 Hz, this method may have intraexamination variability. • A minimum of 15 scans per examination achieves a low intraexamination variability.


Endovascular treatment of a superior mesenteric artery aneurysm secondary to Behcet's disease with Onyx (ethylene vinyl alcohol copolymer).
Behcet's disease is a complex multisystemic chronic inflammatory disease that is characterized by oral and genital aphtous ulcers and vasculitis. Aneurysms of major arteries are the most important cause of mortality in Behcet's disease. Four patients with superior mesenteric artery (SMA) aneurysms related to Behcet's disease have been reported in the literature. We report here the first successful endovascular treatment of a giant, wide-necked SMA aneurysm secondary to Behcet's disease. We performed a balloon-assisted embolization technique using ethylene vinyl alcohol copolymer (Onyx, ev3, Irvine, CA, USA). There were no signs of recurrence during 2-year follow-up.


Generalization in Aphasia Treatment: A Tutorial for Speech-Language Pathologists.
Generalization has been defined and instantiated in a variety of ways over the last half-century, and this lack of consistency has created challenges for speech-language pathologists to plan for, implement, and measure generalization in aphasia treatment protocols. This tutorial provides an overview of generalization with a focus on how it relates to aphasia intervention, including a synthesis of existing principles of generalization and examples of how these can be embedded in approaches to aphasia treatment in clinical and research settings. Three articles collectively listing 20 principles of generalization formed the foundation for this tutorial. The seminal work of Stokes and Baer (1977) focused attention on generalization in behavioral change following treatment. Two aphasia-specific resources identified principles of generalization in relation to aphasia treatment (Coppens & Patterson, 2018; Thompson, 1989). A selective literature review was conducted to identify evidence-based examples of each of these 20 principles from the extant literature. Five principles of generalization were synthesized from the original list of 20. Each principle was supported by studies drawn from the aphasia treatment literature to exemplify its application. Generalization is an essential aspect of meaningful aphasia intervention. Successful generalization requires the same dedication to strategic planning and outcome measurement as the direct training aspect of intervention. Although not all people with aphasia are likely to benefit equally from each of the principles reviewed herein, our synthesis provides information to consider for maximizing generalization of aphasia treatment outcomes. https://doi.org/10.23641/asha.24714399.


Further development of a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of foot-and-mouth disease virus and validation in the field with use of an internal positive control.
Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hooved animals. Global outbreaks have highlighted the significant economic, trade, psychosocial and animal welfare impacts that can arise from the detection of disease in previously 'FMD-free' countries. Rapid and early diagnosis provides significant advantages in disease control and minimization of deleterious consequences. We describe the process of further development and validation of a reverse-transcription loop-mediated isothermal amplification foot-and-mouth disease virus (RT-LAMP-FMDV) test, using a published LAMP primer set, for use in the field. An internal positive control (IPC) was designed and introduced for use with the assay to mitigate any intrinsic interference from the unextracted field samples and avoid false negatives. Further modifications were included to improve the speed and operability of the test, for use by non-laboratory trained staff operating under field conditions, with shelf-stable reaction kits which require a minimum of liquid handling skills. Comparison of the assay performance with an established laboratory-based real-time reverse transcriptase PCR (rRT-PCR) test targeting the 3D region of FMD virus (Tetracore Inc) was investigated. LAMP has the potential to complement current laboratory diagnostics, such as rRT-PCR, as a preliminary tool in the investigation of FMD. We describe a strategic approach to validation of the test for use in the field using extracted RNA samples of various serotypes from Thailand and then finally unextracted field samples collected from FMD-suspected animals (primarily oral lesion swabs) from Bhutan and Australia. The statistical approach to validation was performed by Frequentist and Bayesian latent class methods, which both confirmed this new RT-LAMP-FMDV test as fit-for-purpose as a herd diagnostic tool with diagnostic specificity >99% and sensitivity 79% (95% Bayesian credible interval: 65, 90%) on unextracted field samples (oral swabs).


Oil weathering after the Deepwater Horizon disaster led to the formation of oxygenated residues.
Following the Deepwater Horizon disaster, the effect of weathering on surface slicks, oil-soaked sands, and oil-covered rocks and boulders was studied for 18 months. With time, oxygen content increased in the hydrocarbon residues. Furthermore, a weathering-dependent increase of an operationally defined oxygenated fraction relative to the saturated and aromatic fractions was observed. This oxygenated fraction made up >50% of the mass of weathered samples, had an average carbon oxidation state of -1.0, and an average molecular formula of (C(5)H(7)O)(n). These oxygenated hydrocarbon residues were devoid of natural radiocarbon, confirming a fossil source and excluding contributions from recent photosynthate. The incorporation of oxygen into the oil's hydrocarbons, which we refer to as oxyhydrocarbons, was confirmed from the detection of hydroxyl and carbonyl functional groups and the identification of long chain (C(10)-C(32)) carboxylic acids as well as alcohols. On the basis of the diagnostic ratios of alkanes and polycyclic aromatic hydrocarbons, and the context within which these samples were collected, we hypothesize that biodegradation and photooxidation share responsibility for the accumulation of oxygen in the oil residues. These results reveal that molecular-level transformations of petroleum hydrocarbons lead to increasing amounts of, apparently recalcitrant, oxyhydrocarbons that dominate the solvent-extractable material from oiled samples.


Non-smokers seeking help for smokers: a preliminary study.
To examine the phenomenon of non-smokers spontaneously taking action to seek help for smokers; to provide profiles of non-smoking helpers by language and ethnic groups. A large, statewide tobacco quitline (California Smokers' Helpline) in operation since 1992 in California, providing free cessation services in English, Spanish, Mandarin, Cantonese, Korean, and Vietnamese. Callers between August 1992 and September 2005 who identified themselves as either white, black, Hispanic, American Indian, or Asian (n = 349,110). A subset of these were "proxies": callers seeking help for someone else. For more detailed analysis, n = 2143 non-smoking proxies calling from October 2004 through September 2005. Proportions of proxies among all callers in each of seven language/ethnic groups; demographics of proxies; and proxies' relationships to smokers on whose behalf they called. Over 22 000 non-smoking proxies called. Proportions differed dramatically across language/ethnic groups, from mean (+/-95% confidence interval) 2.7 (0.3)% among English-speaking American Indians through 9.3 (0.3)% among English-speaking Hispanics to 35.3 (0.7)% among Asian-speaking Asians. Beyond the differences in proportion, however, remarkable similarities emerged across all groups. Proxies were primarily women (79.2 (1.7)%), living in the same household as the smokers (65.0 (2.1)%), and having either explicit or implicit understandings with the smokers that calling on their behalf was acceptable (90.0 (1.3)%). The willingness of non-smokers to seek help for smokers holds promise for tobacco cessation and may help address ethnic and language disparities. Non-smoking women in smokers' households may be the first group to target.


["Farmer Field School", a participatory educational approach for improving the fight against malaria vectors in irrigated rice-growing areas in Benin].
Malaria is a major health problem in Benin where it is the main cause of morbidity and mortality, particularly among children under 5 and pregnant women. Although the vast majority of malaria cases occurs in rural and agricultural areas and are often associated with development projects, very few interventions target the agro-ecosystem. In Benin, irrigated rice growing is expanding to meet the increasing demand of the population. However, continuous flooding and tillage systems induce the development and proliferation of malaria and other diseases vectors. Intermittent flooding of rice plots and minimal tillage can reduce significantly the proliferation of mosquitoes including Anopheles in rice fields. However, the dissemination and implementation of these agricultural practices require community-wide action for greater effectiveness. As part of strengthening the capacity of farming communities in the fight against malaria vectors, the "Farmer Field School" appears to be an innovative approach. This learning by doing method promotes interactions between groups of producers to disseminate proven technologies. This study aims to disseminate among rice producers the agricultural practices of intermittent flooding and minimal tillage, likely to reduce the proliferation of malaria vectors in the rice fields. This study was carried out in the rice-growing perimeter of Malanville, Benin (11° 52' 5" North, 3° 22' 59" East) which covers an area of 516 hectares. Farmer Field Schools were set up after a basic survey at producer level. This survey was carried out through in-depth interview, focus group discussions and direct field observation with producers. Focus groups discussions and interviews made it possible to understand the perception of rice farmers on the link between rice production and the transmission of malaria. In order to disseminate new agricultural practices such as intermittent flooding and minimal tillage among producers, twelve plots have been set up. Farmer Field Schools were monitored weekly with rice producers accompanied by a facilitator and a medical entomologist (learning facilitator or moderator) helping the farmers with the collection and identification of mosquito larvae. According to the different stages of rice development (transplanting, tillering, maturation), the mosquito larvae were collected in the test and control plots from 10 a.m. to 2 p.m. by the dipping method. Then the water in the test compartments (intermittent flooding) was emptied. A cycle of 7 days of flooding and 2 days of drying was carried out for intermittent flooding. Mosquito larvae were identified morphologically using the identification key and Anopheles genus larvae were isolated in plastic cups. The impacts of intermittent flooding and minimum tillage in reducing breeding sites and larval densities were established by determining and comparing the larval densities of mosquitoes and of Anopheles between the test and control plots. Direct observations in the field allowed to identify three tillage systems, which include the use of tiller (28%), plow (66%) and hoe (6%) on the rice field. Continuous flooding was the only irrigation system used by farmers. The water used for irrigation comes either from boreholes installed individually or from the Niger River. The volume of water used varies with the seasons, the size of the farms and the variety of rice grown. Farmers observe that the nuisance of mosquitoes increases during the rice production period with an outbreak of malaria cases, especially among children, which leads to crowds in health centers. The preventive measures against malaria among farmers are the use of impregnated mosquito nets distributed free of charge by the national program against malaria, and of insecticide bombs or spirals. Considering the development stages of the rice, the larval densities varied according to the treatments. Overall, minimal tillage applied to intermittent flooding significantly reduced the density of mosquito larvae of all species. The reduction rates were 10.5, 5.4 and 2.5 during transplanting, tillering and maturation, respectively. Considering only the Anopheles larvae, minimal tillage applied to intermittent flooding reduced their density by 16, 5.5 and 4 respectively during transplanting, tillering and maturation. The rice-growing area of Malanville has many favorable conditions for rice production, including the presence of water supply sources such as the Niger River located near the rice field and numerous boreholes. The availability of water pockets for mosquito breeding during irrigation appeared to contribute to the extension of malaria transmission. The present study showed that the intermittent flooding coupled with minimal tillage could reduce the proliferation of malaria vectors. The results suggested that with technical support to farmers through the "Farmer Field School", the malaria incidence could be reduced in the farming community.


Aquarium nitrification revisited: Thaumarchaeota are the dominant ammonia oxidizers in freshwater aquarium biofilters.
Ammonia-oxidizing archaea (AOA) outnumber ammonia-oxidizing bacteria (AOB) in many terrestrial and aquatic environments. Although nitrification is the primary function of aquarium biofilters, very few studies have investigated the microorganisms responsible for this process in aquaria. This study used quantitative real-time PCR (qPCR) to quantify the ammonia monooxygenase (amoA) and 16S rRNA genes of Bacteria and Thaumarchaeota in freshwater aquarium biofilters, in addition to assessing the diversity of AOA amoA genes by denaturing gradient gel electrophoresis (DGGE) and clone libraries. AOA were numerically dominant in 23 of 27 freshwater biofilters, and in 12 of these biofilters AOA contributed all detectable amoA genes. Eight saltwater aquaria and two commercial aquarium nitrifier supplements were included for comparison. Both thaumarchaeal and bacterial amoA genes were detected in all saltwater samples, with AOA genes outnumbering AOB genes in five of eight biofilters. Bacterial amoA genes were abundant in both supplements, but thaumarchaeal amoA and 16S rRNA genes could not be detected. For freshwater aquaria, the proportion of amoA genes from AOA relative to AOB was inversely correlated with ammonium concentration. DGGE of AOA amoA genes revealed variable diversity across samples, with nonmetric multidimensional scaling (NMDS) indicating separation of freshwater and saltwater fingerprints. Composite clone libraries of AOA amoA genes revealed distinct freshwater and saltwater clusters, as well as mixed clusters containing both freshwater and saltwater amoA gene sequences. These results reveal insight into commonplace residential biofilters and suggest that aquarium biofilters may represent valuable biofilm microcosms for future studies of AOA ecology.


Dietary patterns and prevention of type 2 diabetes: from research to clinical practice; a systematic review.
The prevalence of type 2 diabetes, a disease difficult to treat and expensive to manage, is increasing rapidly worldwide. It is also known that lifestyle, and particularly dietary habits, play an important role in the development of diabetes. Adherence to a healthy dietary pattern, like the Mediterranean diet, exerts a beneficial role regarding the development of diabetes. Additionally certain individual food groups and components of the diet, such as monounsaturated fatty acids, fruits, vegetables, whole grain cereals, dietary fiber, fish and moderate consumption of alcohol, also may protect against the development of diabetes, possibly through the amelioration of insulin sensitivity and their anti-inflammatory actions. Unfortunately, dietary habits in the developed world are changing towards an unhealthier direction. Consequently, emphasis should be given on encouraging at population and individual level for adopting a healthier lifestyle, including dietary habits, in order to prevent the development of type 2 diabetes.


Early Clinical Outcomes of Short versus Long Proximal Femoral Nail Anti-rotation (PFNA) in the Treatment of Intertrochanteric Fractures.
Both short and long PFNA are employed to treat intertrochanteric fractures. Controversy exists in the choice between the two nails as each implant has specific characteristics and theoretical advantages. This retrospective study seeks to examine the operative complication rates and clinical outcomes of short versus long (Proximal Femoral Nail Antirotation) PFNA in the treatment of intertrochanteric fractures. Between July 2011 and February 2015, 155 patients underwent PFNA insertion. The decision on whether to use a short or long PFNA nail, locked or unlocked, was determined by the attending operating surgeon. Visual Analogue Pain Score (VAS) Harris Hip Scores (HHS), Short-form 36 Health Questionnaire (SF-36) and Parker Mobility Scores (PMS) were collected at six weeks, six months and one year post-operatively. A total of 137 (88.4%) patients were successfully followed-up. Forty-two (30.7%) patients received a short PFNA. The patients were similar in baseline characteristics of age, gender, and comorbidities. Operative time was significantly longer in the short PFNA group (62 ±17 mins) versus the long PFNA group (56±17). While the patients in both groups achieved improvement in all outcome measures, there was no significant difference between the groups in terms of HHS (61.0 ±16.0 vs 63.0 ±16.8, p=0.443), PMS (2.3±1.5 vs 2.7±2.1, p=0.545) and VAS (1.7±2.9 vs 1.8 ±2.2 p=0.454). There were 3 (7.1%) and 7 (7.4%) complications in the short versus long PFNA group, respectively. Both short and long PFNA had similar clinical outcomes and complication rates in the treatment of intertrochanteric fractures in an Asian population.


Mathematical modelling of animate and intentional motion.
Our aim is to enable a machine to observe and interpret the behaviour of others. Mathematical models are employed to describe certain biological motions. The main challenge is to design models that are both tractable and meaningful. In the first part we will describe how computer vision techniques, in particular visual tracking, can be applied to recognize a small vocabulary of human actions in a constrained scenario. Mainly the problems of viewpoint and scale invariance need to be overcome to formalize a general framework. Hence the second part of the article is devoted to the question whether a particular human action should be captured in a single complex model or whether it is more promising to make extensive use of semantic knowledge and a collection of low-level models that encode certain motion primitives. Scene context plays a crucial role if we intend to give a higher-level interpretation rather than a low-level physical description of the observed motion. A semantic knowledge base is used to establish the scene context. This approach consists of three main components: visual analysis, the mapping from vision to language and the search of the semantic database. A small number of robust visual detectors is used to generate a higher-level description of the scene. The approach together with a number of results is presented in the third part of this article.


Machine learning-based preoperative predictive analytics for lumbar spinal stenosis.
OBJECTIVEPatient-reported outcome measures (PROMs) following decompression surgery for lumbar spinal stenosis (LSS) demonstrate considerable heterogeneity. Individualized prediction tools can provide valuable insights for shared decision-making. The authors aim to evaluate the feasibility of predicting short- and long-term PROMs, reoperations, and perioperative parameters by machine learning (ML) methods.METHODSData were derived from a prospective registry. All patients had undergone single- or multilevel mini-open facet-sparing decompression for LSS. The prediction models were trained using various ML-based algorithms to predict the endpoints of interest. Models were selected by area under the receiver operating characteristic curve (AUC). The endpoints were dichotomized by minimum clinically important difference (MCID) and included 6-week and 12-month numeric rating scales for back pain (NRS-BP) and leg pain (NRS-LP) severity and the Oswestry Disability Index (ODI), as well as prolonged surgery (> 45 minutes), extended length of hospital stay (> 28 hours), and reoperations.RESULTSA total of 635 patients were included. The average age was 62 ± 10 years, and 333 patients (52%) were male. At 6 weeks, MCID was seen in 63%, 76%, and 61% of patients for ODI, NRS-LP, and NRS-BP, respectively. At internal validation, the models predicted MCID in these variables with accuracies of 69%, 76%, and 85%, and with AUCs of 0.75, 0.79, and 0.92. At 12 months, 66%, 63%, and 51% of patients reported MCID; the observed accuracies were 62%, 74%, and 66%, with AUCs of 0.68, 0.72, and 0.79. Reoperations occurred in 60 patients (9.5%), of which 27 (4.3%) occurred at the index level. Overall and index-level reoperations were predicted with 69% and 63% accuracy, respectively, and with AUCs of 0.66 and 0.61. In 15%, a length of surgery greater than 45 minutes was observed and predicted with 78% accuracy and AUC of 0.54. Only 15% of patients were admitted to the hospital for longer than 28 hours. The developed ML-based model enabled prediction of extended hospital stay with an accuracy of 77% and AUC of 0.58.CONCLUSIONSPreoperative prediction of a range of clinically relevant endpoints in decompression surgery for LSS using ML is feasible, and may enable enhanced informed patient consent and personalized shared decision-making. Access to individualized preoperative predictive analytics for outcome and treatment risks may represent a further step in the evolution of surgical care for patients with LSS.


Exploring the Catalytic Properties of Unsupported and TiO2-Supported Cu5 Clusters: CO2 Decomposition to CO and CO2 Photoactivation.
In this work, we explore the decomposition of CO2 on unsupported and TiO2-supported Cu5 clusters via computational modeling, using both finite cluster and periodic slab structures of the rutile TiO2(110) surface. While the energy needed for C=O bond breaking is already significantly reduced upon adsorption onto the unsupported metal catalyst (it drops from 7.8 to 1.3 eV), gas desorption before bond activation is still the inevitable outcome due to the remaining barrier height even at 0 K. However, when the Cu5 cluster itself is supported on TiO2, reactant and product adsorption is strongly enhanced, the barrier for bond breaking is further reduced, and a spontaneous decomposition of the molecule is predicted. This finding is linked to our previous work on charge-transfer processes in the Cu5-TiO2 system triggered by solar photons, since a combination of both phenomena at suitable temperatures would allow for a photoinduced activation of CO2 by sunlight.


Antidepressant use and depressive symptomatology among older people from the Australian Longitudinal Study of Ageing.
Depression is one of the leading contributors to the burden of non-fatal diseases in Australia. Although there is an overall increasing trend in antidepressant use, the relationship between use of antidepressants and depressive symptomatology is not clear, particularly in the older population. Data for this study were obtained from the Australian Longitudinal Study of Ageing (ALSA), a cohort of 2087 people aged over 65 years at baseline. Four waves of home interviews were conducted between 1992 and 2004 to collect information on sociodemographic and health status. Depressive symptoms were measured by the Center for Epidemiologic Studies - Depression Scale. Use of antidepressants was based on self-report, with the interviewer able to check packaging details if available. Longitudinal analysis was performed using logistic generalized estimating equations to detect if there was any trend in the use of antidepressants, adjusting for potential confounding factors. The prevalence of depressive symptoms was 15.2% in 1992 and 15.8% in 2004 (p > 0.05). The prevalence of antidepressant users increased from 6.5% to 10.9% (p < 0.01) over this period. Among people with depressive symptoms, less than 20% were taking antidepressants at any wave. Among people without depressive symptoms, the prevalence of antidepressant use was 5.2% in 1992 and 12.0% in 2004 (p < 0.01). Being female (OR = 1.67, 95%CI: 1.25-2.24), having poor self-perceived health status (OR = 1.17, 95%CI: 1.04-1.32), having physical impairment (OR = 1.48, 95%CI: 1.14-1.91) and having depressive symptoms (OR = 1.62, 95%CI: 1.24-2.13) significantly increased the use of antidepressants, while living in community (OR = 0.51, 95%CI: 0.37-0.71) reduced the risk of antidepressant use. Use of antidepressants increased, while depressive symptoms remained stable, in the ALSA over a 12-year period. Use of antidepressants was low for people with depressive symptoms.


Frataxin-Mediated PINK1-Parkin-Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin.
Naturally occurring quercetin has been found to induce mitophagy and prevent nonalcoholic fatty liver disease (NAFLD). However, it still remains elusive whether frataxin upregulation by quercetin contributes to the beneficial effect through mitophagy or not. Adult male C57BL/J mice were fed a high-fat diet (HFD, 60% of energy from fat) with quercetin (100 mg kg-1 body weight) or not for 10 weeks. Quercetin alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, quercetin blocked mitophagy suppression by HFD based on the increased LC3II, PTEN-induced putative kinase 1 (PINK1) and Beclin1 expressions, as well as decreased p62 levels. Quercetin also improved the Parkin translocation to mitochondria confirmed by immunofluorescence. Specifically, frataxin was lowered in the liver of HFD-fed mice or HepG2 cell incubated with oleate/palmitate but restored by quercetin, and quercetin's regulation of frataxin may depend on p53. Furthermore, lentivirus-mediated stable knockdown of frataxin in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Frataxin was further decreased by free fatty acids in knockdown cells concomitantly with depressed PINK1-Parkin-associated mitophagy, which was partially normalized by quercetin. Quercetin alleviated hepatic steatosis by enhancing frataxin-mediated PINK1/Parkin-dependent mitophagy, highlighting a promising preventive strategy and mechanism for NAFLD by quercetin.


Normative data for the Fototest from neurological patients with no cognitive impairment.
To contribute normative data for the Fototest from neurological patients with no cognitive impairment, including disaggregated data on each domain of the test (naming, free recall, total recall, and naming fluency). We performed a cross-sectional study in which neurological patients with no cognitive impairment were tested with the Fototest; we recorded total and domain scores. We performed a descriptive study of the total and domain scores, with data disaggregated by sex, age (over/under 65 years), and level of education (primary education completed/not completed; further study completed). We included a sample of 1055 patients, who were mainly women (57.1%), aged over 65 (60.6%), and had a low level of education (38.6% had not completed primary education). Sex, age, and level of education influence total Fototest score (34.6 ± 5.3; P10: 28; P5: 27) and free recall (8.5 ± 2.2; 6; 4), total recall (10.0 ± 1.5; 8; 7), and naming fluency scores (18.7 ± 4.9; 13; 12). For total score, the multivariate analysis revealed values of 1.5 ± 0.3 (ß ± SD) for sex (female), -2.4 ± 0.3 for age (>65), and -1.6 ± 0.4 and 3.3 ± 0.4 for incomplete primary education and completed post-primary education, respectively (completed primary study was used as a reference). We provide normative data for total and domain Fototest results for each of the groups defined according to sex, age, and level of education. We also provide a percentile distribution of scores. We hope that these normative data will translate into increases in efficiency in Fototest administration in the clinical setting.


Nuclear encoding of a plastid sigma factor in rice and its tissue- and light-dependent expression.
A full-length cDNA encoding a putative sigma factor for a plastid RNA polymerase was isolated from the higher plant Oryza sativa . The nucleotide sequence of the corresponding nuclear gene, named Os-sigA ( O.sativa sigma A), predicts a polypeptide of 519 amino acids that contains a putative plastid-targeting sequence in its N-terminal region. The predicted mature protein shows extensive sequence homology to bacterial sigma factors, encompassing the conserved regions 1.2, 2.1, 2.2, 2.3, 2.4, 3, 4.1 and 4.2 implicated in binding to -10 promoter elements, promoter melting and interaction with the core RNA polymerase enzyme. RNA blot analysis revealed that the abundance of Os-sigA transcripts was markedly greater in green shoots than in roots or in dark-grown etiolated shoots of rice seedlings. Furthermore, exposure of dark-grown etiolated seedlings to light resulted in a rapid increase in the amount of Os-sigA mRNA in the shoot. These observations suggest that regulation of expression of the nuclear gene for this putative plastid RNA polymerase sigmafactor by light contributes to light-dependent transcriptional regulation of plastid genes.


The effects of dietary myoinositol on lung tumor development in tobacco smoke-exposed mice.
The purpose of these experiments was to investigate whether a diet containing myoinositol could prevent the development of tobacco smoke-induced lung tumors in strain A/J mice. In a positive control experiment, 1% and 3% of myoinositol in AIN-93 diet reduced the development of lung tumors induced by NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] by 69% and 75%. In animals exposed for 5 mo, 6 h/day, 5 days/wk, to a mixture of tobacco sidestream and mainstream smoke, and then fed myoinositol-containing diets once smoke exposure had ceased, no chemopreventive effect was observed. When animals were fed myoinositol during both tobacco smoke exposure and the recovery period, a slight but statistically not significant reduction in tumor multiplicities was found. It was concluded that myoinositol has less chemopreventive activity against the full complex mixture of tobacco smoke than it has against selected constituents such as NNK or benzo[a]pyrene.