Dietary and lifestyle factors of DNA methylation.
Lifestyle factors, such as diet, smoking, physical activity, and body weight management, are known to constitute the majority of cancer causes. Epigenetics has been widely proposed as a main mechanism that mediates the reversible effects of dietary and lifestyle factors on carcinogenesis. This chapter reviews human studies on potential dietary and lifestyle determinants of DNA methylation. Apart from a few prospective investigations and interventions of limited size and duration, evidence mostly comes from cross-sectional observational studies and supports some associations. Studies to date suggest that certain dietary components may alter genomic and gene-specific DNA methylation levels in systemic and target tissues, affecting genomic stability and transcription of tumor suppressors and oncogenes. Most data and supportive evidence exist for folate, a key nutritional factor in one-carbon metabolism that supplies the methyl units for DNA methylation. Other candidate bioactive food components include alcohol and other key nutritional factors of one-carbon metabolism, polyphenols and flavonoids in green tea, phytoestrogen, and lycopene. Some data also support a link of DNA methylation with physical activity and energy balance. Effects of dietary and lifestyle exposures on DNA methylation may be additionally modified by common genetic variants, environmental carcinogens, and infectious agents, an aspect that remains largely unexplored. In addition, growing literature supports that the environmental conditions during critical developmental stages may influence later risk of metabolic disorders in part through persistent programming of DNA methylation. Further research of these modifiable determinants of DNA methylation will improve our understanding of cancer etiology and may present certain DNA methylation markers as attractive surrogate endpoints for prevention research. Considering the plasticity of epigenetic marks and correlated nature of lifestyle factors, more longitudinal studies of healthy individuals of varying age, sex, and ethnic groups are warranted, ideally with comprehensive data collection on various lifestyle factors.


How technological innovation and electricity consumption affect environmental quality? A road map towards achieving environmental sustainability.
Still the world witnessed an upturn in environmental degradation in spite of commitment to climate change across the nations. However, this study attempts to examine linkages among environmental degradation, technological innovation, and electricity consumption in India from 1981 to 2018 using time series data. To examine the long-run equilibrium relationship among the studied variables, we used robust econometric methods such as the autoregressive distributed lag (ARDL), fully modified ordinary least square (FMOLS), and dynamic ordinary least square (DOLS) methods. Furthermore, Granger causality also investigates through the vector error correction model (VECM) model, to assess inter-connotation among the underlying variables. From our empirical findings, urbanization, financial development, and technological innovation have a negative impact on carbon emissions, indicating long-term improvements in environmental quality. While economic development and electricity consumption are deteriorating environmental quality in India. The study's findings suggest that policymakers should prioritize renewable energy, which decreases environmental damage without impeding economic growth.


Brain structure and executive functions in children with cerebral palsy: a systematic review.
This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures.


Analysis of fixed and variable operating room (or) time point efficiency in partial nephrectomies: open versus robotic-assisted.
To analyze operating room (OR) efficiency by evaluating fixed and variable OR times for open (OPN) and robotic-assisted partial nephrectomies (RAPN). We analyzed consecutive OPN and RAPN performed by one surgeon over a 24-month period. All patients were placed in the lateral decubitus position and secured with a beanbag regardless of approach. Fixed (non-procedural) OR times were prospectively collected and defined as: in-room to anesthesia-release time (IRAT), anesthesia release to cut time (ARCT), and close to wheels-out time (CTWO). Variable OR time was procedural cut to close time (CTCT). Comparisons of fixed and variable OR time points between OPN and RAPN were performed using the Wilcoxon rank-sum test. 146 RAPN and 31 OPN were evaluated from 2019-2020. Median IRAT was similar for RAPN versus OPN [20 min (IQR: 16-25) vs. 20 min (IQR: 16-26), P = 0.57]. Median ARCT was longer for RAPN than it was for OPN [40 min (IQR: 36-46) vs. 34 min (IQR: 30-39), P < 0.001]. Median CTWO was similar for OPN (12 min, IQR: 9-14) and RAPN (11 min, IQR: 7-15) (P = 0.89). Median CTCT was longer for RAPN (202 min, IQR: 170-236) compared to OPN (164 min, IQR: 154-184) (P < 0.001). In a single surgeon, partial nephrectomy series with the same patient positioning, utilization of robotic technology was associated with longer surgeon operating time as well as less efficient fixed OR times, specifically ARCT.


Preliminary proteomic analysis of human serum from patients with laryngeal carcinoma.
To better evaluate the serum protein alterations in patients with laryngeal carcinoma during surgical treatment process, a comparative proteomic analysis of human serum from patients with laryngeal carcinoma between pre- and post-operation group was performed using two-dimensional gel electrophoresis, in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry and database searching. Statistical analysis indicated that 16 gel spots corresponding to 12 proteins altered their expression significantly between the two groups of patients with laryngeal carcinoma. Of these 12 proteins, 6 proteins were up-regulated in the pre-operation group. The subsequent Western blot confirmed the results of proteome analysis. Measurement of MDA and SOD levels in serum combining with bioinformatics analysis indicated the potential roles of the oxidant stress and immune response as target in monitoring and treating laryngeal carcinoma. The study provides new insight into the laryngeal carcinoma development and treatment, and the identified proteins are warranted to be further studied.


Electrospun nanostructured polystyrene as a new coating material for solid-phase microextraction: Application to separation of multipesticides from honey samples.
For the first time, electrospun polystyrene nanostructure was used as coating material on a stainless steel wire for solid-phase microextraction. Surface morphology of the coating was studied by scanning electron microscopy which showed the formation of nanofibers on the wire. The coating was stable after conditioning at 250°C for 2h. The efficiency of the polystyrene coating was approved by extracting a mixture of seven pesticides (polar and apolar) from head space of honey samples followed by gas chromatography-mass spectrometry. The important parameters affecting extraction efficiency such as, extraction time and temperature, desorption conditions, agitation rate and ionic strength were investigated. Under optimized experimental conditions, detection limits for the investigated pesticides ranged from 0.1-2μgL(-1). The intra- and inter-day precisions of the developed method were 3.5-17.6% and 10.0-25.0%, respectively. Finally, all the investigated pesticides were spiked to honey samples and extracted by the proposed method. The accuracies of determination of all the species were found to be in the range of 81-125%.


Using lipoate enantiomers and thioredoxin to study the mechanism of the 2-oxoacid-dependent dihydrolipoate production by the 2-oxoacid dehydrogenase complexes.
The thioredoxin-catalyzed insulin reduction by dihydrolipoate was applied to study the 2-oxoacid: lipoate oxidoreductase activity of 2-oxoacid dehydrogenase complexes. The enzymatic and non-enzymatic mechanisms of the transfer of reducing equivalents from the complexes to free lipoic acid (alpha-lipoic acid, 6,8-thiooctic acid) were distinguished using the high stereoselectivity of the complex enzymes to the R-enantiomer of lipoate. Unlike these enzymes, thioredoxin from E. coli exhibited no stereoselectivity upon reduction with chemically obtained dihydrolipoate. However, coupled to the dihydrolipoate production by the dehydrogenase complexes, the process was essentially sensitive both to the enantiomer used and the dihydrolipoyl dehydrogenase activity of the complexes. These results indicated the involvement of the third complex component, dihydrolipoyl dehydrogenase, in the 2-oxoacid-dependent dihydrolipoate formation. The implication of the investigated reaction for a connection between thioredoxin and the 2-oxoacid dehydrogenase complexes in the mitochondrial metabolism are discussed.


What is the failure rate of constrained liners in complex revision total hip arthroplasty?
Recurrent hip dislocation after multiple revision total hip arthroplasty is a severe complication. Therefore, constrained acetabular liners (CL) have been used during salvage procedures. We report our experience of constrained liners in a re-revision setting with focus on re-dislocation. We also evaluated acetabular and femoral bone loss as potential risk factor. Between January 2013 and December 2016, 65 patients were treated in a single institution for revision and re-revision hip arthroplasty using CL. The indication for using a CL was a high risk of re-redislocation after multiple recurrent hip dislocation including failed Dual Mobility Cups (DMC). Compromising soft tissue defects as well as severe bone defect were therefore regarded as high risks. Thirty-eight patients (77.6%) underwent a minimum of three surgical procedures before the index revision procedure. Sixteen patients (24.6%) were excluded as they were lost to follow-up, expired before minimum follow-up or refused study participation, leaving 49 patients in the analysis (75.4%). The mean follow-up was 62 months (44-74; SD = 7.7). We assessed the following potential risk factors for revision or dislocation: type of surgical setting (septic/aseptic), BMI, cup inclination angle, size of liner used and acetabular and femoral bone loss according to Paprosky classification. The primary endpoints were dislocation or repeat revision for any reason. Of the 49 patients, we found an overall re-revision rate of 40.8% (20/49) and a dislocation rate of 30.6% (15/49). There were no significant differences among the surgical re-revision rate or dislocation rate as a factor of patient characteristics. In terms of bone loss, there was a trend towards higher revision rates for increasing acetabular and femoral bone loss, but without statistical significance. We found the use of a constrained liner in a re-revision setting still bears a high risk of re-revision and re-dislocation. Therefore we restrained from using constrained liners in favour of Dual mobility cups. In this study there was no significant higher dislocation rate in the subgroup of periprosthetic infection. Furthermore the rigid design of a constrained liner bears the known risk of structural failure of acetabular reconstruction implants. Severe acetabular or femoral bone defects seem to have an impact on the revision rate, but not on the dislocation rate with regards to the restored offset and center of the hip. Results have to be taken into context such that the study population inherently has a predisposition for poorer outcomes. Indications should be strongly filtered for patients at high risk for recurrent hip joint dislocation including failed DMCs with only limited bone loss and moderate soft tissue defects. Our modification to the existing classification with a high inter and intraobserver reliability will make future studies more comparable regarding revisions and bone stock loss. Still further research using objective and reproducible parameters is needed to better analyze data especially in the background of complex revision hip arthroplasty.


Methylprednisolone reduces adhesion molecules in blood and cerebrospinal fluid in patients with MS.
To analyze the expression of adhesion molecules on mononuclear cells from blood and CSF of patients with exacerbations of MS before and after megadose IV methylprednisolone (MP). Adhesion molecules regulate transmigration of lymphocytes and monocytes/macrophages to the CNS and have an important role in the pathogenesis of MS. The expression of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1, lymphocyte function-associated antigen 1 (LFA-1), and intercellular adhesion molecule 1 (ICAM-1) was analyzed immunocytologically on lymphocytes and monocytes from blood and CSF of 23 patients and 11 healthy control subjects. The results were correlated with the Expanded Disability Status Scale and in half of the patients with the number of T2-weighted MS plaques and brain atrophy analyzed by MRI. After treatment, the mean proportions of VLA-4, LFA-1, and ICAM-1 on blood lymphocytes (p < 0.0003, p < 0.00001, p < 0.01) and monocytes (p < 0.0001, p < 0.0002, p < 0.007) of 23 patients decreased. The expression of these adhesion proteins was also diminished on CSF leukocytes. However, even after treatment, the levels of VLA-4 and LFA-1 on lymphocytes from blood of MS patients remained higher than in the control subjects. The level of VLA-4 and LFA-1 on blood lymphocytes (r=0.67, p=0.023) and VLA-4 on monocytes (r=0.61, p=0.047) correlated with the number of T2-weighted lesions. Megadose MP may suppress brain inflammation by reducing the expression of adhesion molecules on mononuclear cells from blood and CSF of MS patients. The inhibition of cellular trafficking in MS by MP offers an important means of altering the autoimmune response in MS.


Prevalence of endometriosis in women undergoing laparoscopic surgery for various gynaecological indications at a Jordanian referral centre: gaining insight into the epidemiology of an important women's health problem.
Endometriosis is a considerable health challenge for women of reproductive age. Information about its prevalence in the Jordanian population is sparse. The objective of this research was to evaluate the presence of endometriosis in gynaecological patients undergoing laparoscopic surgery for various indications and to correlate the finding of endometriosis with variables, including patient demographics, obstetric history, type, and indication of laparoscopic procedure. A retrospective cohort study involving 460 women who underwent different laparoscopic procedures for a variety of indications was conducted in the Department of Obstetrics and Gynaecology in Jordan University Hospital, a tertiary referral hospital in Jordan, between January 2015 and September 2020. The prevalence of endometriosis in this patient group was higher than that of the general population (13.7% vs. 2.5%), and the mean age at diagnosis (31.9 years) was younger than the general population's age of peak incidence (35-45 years). It was significantly higher in women with lower numbers of pregnancies (p = 0.01) and a lower number of Caesarean sections (p = 0.05) and in those where the indication for surgery was related to decreased fertility or pelvic pain (p = 0.02). Women with high parity or where the surgery's indication suggested normal fertility, such as family planning, were less likely to have endometriosis. To our knowledge, this is the first Jordanian study to assess the prevalence of endometriosis in women undergoing gynaecological laparoscopy. This study suggests that the epidemiology of endometriosis in this region follows similar trends to what has been previously documented in international literature, while emphasizing the need for further research into this important women's health issue in this part of the world.


A randomized controlled pilot study of an HIV risk-reduction intervention for sub-Saharan African university students.
This pilot study used a randomized controlled trial to test the efficacy of an HIV risk-reduction intervention for university students in Eastern Cape Province, South Africa. Randomly selected second-year students were randomized to one of two interventions based on social cognitive theory and qualitative research: HIV risk-reduction, targeting sexual-risk behaviors; health-promotion control, targeting health behaviors unrelated to sexual risks. Participants completed behavioral assessments via audio computer-assisted self-interviewing pre-intervention, 6, and 12 months post intervention, with 97.2% retained at 12-month follow-up. Averaged over the 2 follow-ups, HIV risk-reduction intervention participants reported less unprotected vaginal intercourse and more frequent condom use than control participants, with greater efficacy in non-South Africans than South Africans. Positive changes were also observed on theoretical mediators of condom use that the intervention targeted. Interventions based on social cognitive theory integrated with qualitative information from the population may reduce sexual risk behaviors among university students in sub-Saharan Africa.


Structural features affecting the enzymatic digestibility of pine wood pretreated with ionic liquids.
Pretreating lignocellulosic biomass with certain ionic liquids results in structural and chemical changes that make the biomass more digestible by enzymes. In this study, pine wood was pretreated with 1-ethyl-3-methylimidazolium chloride/acetate ([C2 mim]Cl and [C2 mim][OAc]) at different temperatures to investigate the relative importance of substrate features, such as accessible surface area, cellulose crystallinity, and lignin content, on enzymatic digestibility. The ionic liquid pretreatments resulted in glucan conversions ranging from 23% to 84% on saccharification of the substrates, with [C2 mim][OAc] being more effective than [C2 mim]Cl. The pretreatments resulted in no delignification of the wood, some loss of cellulose crystallinity under certain conditions, and varying levels of increased surface area. Enzymatic digestibility closely correlated with accessible surface area and porosity measurements obtained using Simons' staining and thermoporosimetry techniques. Increased accessible surface area was identified as the principal structural feature responsible for the improved enzymatic digestibility.


Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation.
In neurodegenerative diseases including Alzheimer's and amyotrophic lateral sclerosis, proteins that bind RNA are found in aggregated forms in autopsied brains. Evidence suggests that RNA aids nucleation of these pathological aggregates; however, the mechanism has not been investigated at the level of atomic structure. Here, we present the 3.4-Å resolution structure of fibrils of full-length recombinant tau protein in the presence of RNA, determined by electron cryomicroscopy (cryo-EM). The structure reveals the familiar in-register cross-β amyloid scaffold but with a small fibril core spanning residues Glu391 to Ala426, a region disordered in the fuzzy coat in all previously studied tau polymorphs. RNA is bound on the fibril surface to the positively charged residues Arg406 and His407 and runs parallel to the fibril axis. The fibrils dissolve when RNase is added, showing that RNA is necessary for fibril integrity. While this structure cannot exist simultaneously with the tau fibril structures extracted from patients' brains, it could conceivably account for the nucleating effects of RNA cofactors followed by remodeling as fibrils mature.


Quality of ambulatory care for women and men in the Veterans Affairs Health Care System.
Gender differences in inpatient quality of care are well known. However, whether men and women receive equivalent ambulatory care is less well understood. To study gender differences in quality of care for patients receiving primary care in the Veterans Affairs (VA) Health Care System. Cross-sectional samples of VA enrollees during fiscal years 1999 to 2000. Samples of 6,442 to 86,405 men and women treated at VA facilities for whom at least 1 of 9 quality measures was available. Appropriate general preventive services (pneumococcal vaccination, influenza vaccination, colorectal cancer screening), and specific services for diabetes (annual hemoglobin A1c [HbA1c] testing, good glycemic control, annual diabetic eye exam), hypertension (good blood pressure control), or prior myocardial infarction (use of beta-blockers or aspirin). In adjusted analyses, there were no substantial gender differences in rates of appropriate care. For women compared with men, the adjusted relative risk for appropriate care ranged from 0.96 for blood pressure control (95% confidence interval: 0.93 to 0.99; P=.02) to 1.05 for HbA1c< or =8.0% (95% confidence interval: 1.03 to 1.07; P<.01). Analyses stratified by age demonstrated equivalent care between men and women in 9 of the 14 subgroups evaluated. In this large national health care system that predominantly serves men, the quality of ambulatory care is equivalent for women and men on numerous measures.


Evaluation of the Lawrence Livermore National Laboratory (LLNL) torso phantom by bone densitometry and x-ray.
The recent Workshop on Standard Phantoms recommended that the LLNL torso phantom be adopted as a calibration standard for the quantitation of in vivo radioactivity. This phantom was designed for the calibration of systems for the detection of x-rays of less than 20 keV. The anthropomorphic characteristics and tissue substitute composition of the phantom were assessed with techniques using photons of higher energy. Dual photon absorptometry at 42 and 100 keV showed that the phantom was representative of in vivo tissue composition. Chest radiography showed that the phantom was representative of a human even though the stomach, GI tract and the scapulae were not present and air gaps were observed at organ boundaries.


Human Immunodeficiency Virus (HIV) Disclosure and Sexual Behaviors among Kenyan Women.
Disclosure of HIV status is crucial to the adoption of preventive behaviors for HIV transmission. This study was conducted to investigate HIV status disclosure and its impact on sexual practices among HIV-positive women in Nairobi, Kenya. A cross-sectional study was conducted among HIV-positive women seeking care at two hospitals in Nairobi. A questionnaire and known self-efficacy scales were administered to eligible women to collect information on sociodemographic factors, HIV disclosure and beliefs, healthcare provider advice on disclosure, sexual practices, and self-efficacy. Of 497 women who were included in this analysis, 95.8% had disclosed their HIV status to someone. Women who disclosed were more likely to be in a relationship (p 0.0017) and to be the heads of their households (p 0.0042). Women who reported that their healthcare provider advised them to disclose and told them of ways to disclose were significantly more likely to have disclosed (p=0.0237 and p=0.0294, respectively). The belief that HIV status disclosure is important for HIV prevention and control and that the benefits of disclosure outweigh the risks was also significantly associated with disclosure (p<0.0001 for both). The prevalence of disclosure among HIV-positive individuals' in hospital settings in Nairobi is high. These findings indicate that encouraging and suggesting ways to disclose by healthcare providers and individuals' beliefs about the benefits of disclosure can increase the rate of HIV disclosure. Prospective studies to assess these observations would provide reliable guidance on how to increase disclosure by all women.


Self-care practice and associated factors among hypertensive follow-up patients at East Gojam zone public hospitals, North West Ethiopia, 2021.
Uncontrolled hypertension leads to cardiovascular complications and organ damage. Self-care practice is crucial for the prevention and management of hypertension by improving quality of life, preventing complications and decreasing health care expenditure. The study aimed to assess self-care practice and its associated factors among hypertensive follow up patients at East Gojjam Zone public hospitals; in Northwest Ethiopia. Quantitative cross-sectional study design and qualitative phenomenological approach were applied. The quantitative result was supported by in-depth interview. Out of 480 patients included in the study, 49% have good self-care practices. Out of the total participants 44.6% have poor in antihypertensive medication adherence, 92.5% have low in diet management, 82.8% were poorly practiced physical activity and 62.5% poor practice to weight management. Participants who cannot read and write (AOR = 3.1, 95% CI: 1.6-5.9), and have no comorbidity (AOR = 0.4, 95% CI: 0.2-0.6), uncontrolled blood pressure status (AOR = 2.1, 95% CI: 1.2-3.6), poor social support status (AOR = 2.5, 95% CI: 1.5-4.3) and unfavorable attitude (AOR = 3.1, 95% CI: 1.9-5.2) are the factors for poor self-care practice. During interview; family meal preparation habits, inadequate information about self-care practice during follow-up time, inconvenient working environment, pressure during social events to share food, negligence, and poor self-efficacy were highly described as challenges for practicing and sustaining self- care. The level of hypertension self-care practices was found to be low. Therefore, hypertension self-care practices should be strengthened throughout their follow-up time, and creating awareness in the community is highly encouraged.


Discussion of Average versus Extreme Case Severity in Pandemic Risk Communications.
To investigate determinants of the public's perceptions of disease threat, in 2015 we conducted a randomized survey experiment in the Netherlands. Adults who read a mock news article describing average +or extreme outcomes from a hypothetical influenza pandemic were more influenced by average than by extreme case information. Presenting both types of information simultaneously appeared counterproductive.


Antimicrobial resistance genes associated with Salmonella enterica serovar newport isolates from food animals.
Salmonella enterica serotype Newport is an important cause of salmonellosis, with strains increasingly being resistant to multiple antimicrobial agents. The increase is associated with the acquisition of multiple resistance genes. This study characterizes the genetic basis of resistance of serotype Newport isolates collected from veterinary sources by PCR and DNA sequencing analysis.


Evidence for Surface Recognition by a Cholesterol-Recognition Peptide.
Two cholesterol recognition/interaction amino-acid consensus peptides, N-acetyl-LWYIKC-amide, and N-acetyl-CLWYIK-amide, have been coupled to exchangeable mimics of Chol (cholesterol) and Phos (1,2-dipalmitoyl-sn-glycerol-3-phospho-(1'rac-glycerol)) via disulfide bond formation. Equilibration between Chol and Phos via thiolate-disulfide interchange reactions has revealed that both peptides favor Chol as a nearest-neighbor in liquid-disordered (ld) bilayers to the same extent. In contrast, no Chol- or Phos-recognition could be detected by these peptides in analogous liquid-ordered (lo) bilayers. Fluorescence measurements of the tryptophan moiety have shown that both peptides favor the membrane-water interface. Taken together, these results provide strong evidence that the recognition behavior of the LWYIK motif is, fundamentally, a surface phenomenon but that partial penetration into the bilayer is also necessary.


The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms.
This review addresses current knowledge of the molecular trafficking signals involved in the migration of circulating leukocytes across the highly specialized blood-central nervous system (CNS) barriers during immunosurveillance and inflammation. In this regard, adhesion molecules and activating and chemotactic factors are also discussed and the regional variability in the brain and spinal cord parenchyma are also considered. Furthermore, direct passage into cerebrospinal fluid (CSF) is discussed, in the context of CNS immunosurveillance. The potential differences that characterize leukocyte entry into these varied anatomical sites are highlighted, with special emphasis on studies of the pathogenesis of multiple sclerosis and its animal models. An update on findings from clinical trials of natalizumab is also provided.


The association between serum albumin and depressive symptoms: a cross-sectional study of NHANES data during 2005-2018.
The association between serum albumin and depressive symptoms has been unclear in previous epidemiological studies. We explored whether serum albumin is associated with depressive symptoms based on the National Health and Nutrition Examination Survey (NHANES) data. This cross-sectional study included 13,681 participants aged ≥ 20 years from the NHANES performed during 2005-2018, which produced nationally representative database. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Serum albumin concentration was measured using the bromocresol purple dye method, and participants were divided into quartiles of serum albumin concentrations. Weighted data were calculated according to analytical guidelines. Logistics regression and linear regression models were used to assess and quantify the association between serum albumin and depressive symptoms. Univariate and stratified analyses were also performed. There were 1551 (10.23%) adults (aged ≥ 20 years) with depressive symptoms among the 13,681. A negative association was found between serum albumin concentration and depressive symptoms. Compared with the lowest albumin quartile, the multivariate-adjusted effect size (95% confidence interval) for depressive symptoms of the fully adjusted model in the highest albumin quartile was 0.77 (0.60 to 0.99) and - 0.38 (- 0.66 to - 0.09) using logistics regression and linear regression models respectively. Current smoking status modified the association between serum albumin concentration and PHQ-9 scores (p for interaction = 0.033). This cross-sectional study revealed that albumin concentration is significantly more likely to be a protective factor for depressive symptoms, with the association being more pronounced in non-smokers.


A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft.
In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.


Assessment of two-dose vaccination schedules: availability for vaccination and catch-up strategies.
An age-specific transmission model is used to discuss aspects of two-dose vaccination schedules. Motivated by measles, the model allows for a period of maternally acquired immunity and assumes that infection leads to permanent immunity. The model expresses the coverage at the second dose in terms of the availability of individuals for vaccination, where availability depends on whether the individual received the first vaccination and the time between the first and second doses. It is emphasized by illustration that medium-term performance is a more appropriate assessment of vaccination schedules than eventual outcome, particularly since elimination of measles does not seem possible at this time. Failure to take account of individuals' availability for vaccination when designing vaccination schedules can lead to a poor control strategy and to unjustified optimism. When disease transmission is in equilibrium, an instantaneous change to a vaccination schedule with high coverage often results in a period of low incidence followed by a series of substantial epidemics occurring over a long period of time. A gradual increase to the same level of vaccination can dampen these epidemic waves significantly and gives similar numbers of cases in the medium and long terms. It is found that a strategy based on doses offered at ages 1 and 11 years is far from optimal, but the inclusion of a catch-up vaccination at school entry, offered only to previously unvaccinated individuals, can improve this two-dose strategy dramatically.


Adenosine A1 receptor antagonists in the kidney: effects in fluid-retaining disorders.
Adenosine A(1) receptor antagonists have been used effectively as potassium-sparing and renal-function-protective diuretics in new studies. In addition, the role of adenosine--acting through adenosine A(1) receptors--in renal autoregulation has been clarified. Finally, the application of adenosine receptor antagonists has been implicated in protection from acute renal failure associated with radiocontrast media treatment.


Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line.
JMJD3, a Jumonji C family histone demethylase, is induced by transcription factor, nuclear factor-kappa B (NF-κB), in response to various stimuli. JMJD3 is crucial for erasing histone-3 lysine-27 trimethylation (H3K27me3), a modification associated with transcriptional repression and is responsible for the activation of a diverse set of genes. Here, we identify the genes in human leukaemia monocyte (THP-1) human monocytic cells that are significantly affected by the stable knockdown (kd) of JMJD3. Global gene expression levels were detected in stable JMJD3 knockdown THP-1 cells and in tumor necrosis factor-alpha (TNF-α)-stimulated JMJD3-kd THP-1 cells by using a 12-plex NimbleGen human whole genome array. In addition, datasets were analysed by using Ingenuity Pathway Analysis. Stable knockdown of JMJD3 in THP-1 cells affected particularly in expression levels and in downstream effects on inflammatory signalling pathways. JMJD3 attenuation down-regulates various key genes in NF-κB, chemokine and CD40 signalling, and mostly affects inflammatory disease response molecules. In addition, chromatin immunoprecipitation revealed that JMJD3-kd could inhibit several NF-κB-regulated inflammatory genes by recruiting repressive histone-3 lysine-27 trimethylation to their promoters. Moreover, this study significantly highlights the connexion of NF-κB with JMJD3, which suggests an epigenetic regulation in different signalling pathways. Finally, this study establishes novel JMJD3 targets through Ingenuity Pathway Analysis.


TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespan.
We recently reported that CCT chaperonin subunits are upregulated in a cardiac-specific manner under time-restricted feeding (TRF) [Gill S et al. (2015) Science 347, 1265-1269], suggesting that TRiC/CCT has a heart-specific function. To understand the CCT chaperonin function in cardiomyocytes, we performed its cardiac-specific knock-down in the Drosophila melanogaster model. This resulted in disorganization of cardiac actin- and myosin-containing myofibrils and severe physiological dysfunction, including restricted heart diameters, elevated cardiac dysrhythmia and compromised cardiac performance. We also noted that cardiac-specific knock-down of CCT chaperonin significantly shortens lifespans. Additionally, disruption of circadian rhythm yields further deterioration of cardiac function of hypomorphic CCT mutants. Our analysis reveals that both the orchestration of protein folding and circadian rhythms mediated by CCT chaperonin are critical for maintaining heart contractility.


F-wave normative studies in different nerves of healthy subjects.
F-wave main characteristics were investigated following stimulation of 8 different nerves (facial, axillary, radial, median, ulnar, femoral, deep peroneal, posterior tibial) in a population of normal healthy subjects. Additional studies compared different stimulation and recording techniques (stimulus intensity, stimulus duration, number of consecutive stimuli, facilitating maneuvers, type of recording electrodes). F-wave persistency varied markedly among the different nerves. Mean latencies were correlated to subjects' height, whereas conduction velocity was related to age. The optimal stimulation and recording parameters to obtain reliable information on F-wave studies were: stimulation duration of 0.2 msec with a strength adjusted 30% supramaximal to the direct M-response; administration of a train composed of 10 consecutive stimuli at rest and recording by concentric needle electrodes.


Coronary heart disease risk and bone mineral density among U.S. women and men.
Low bone mineral density (BMD) has been shown to predict cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in both women and men. The purpose of the current study was to determine whether a CHD risk assessment tool might be useful for identifying persons likely to have low BMD in a multiethnic population of women and men. Cross-sectional data for 3881 women and men aged 50-74 years without overt CHD or stroke from the Third National Health and Nutrition Examination Survey (NHANES III) were used to explore the relationship between BMD and 10-year CHD risk, as estimated using the Framingham CHD risk prediction algorithm, in gender-stratified multiple logistic regression models. When compared with women who had a <10% CHD risk, women with a 10%-19% CHD risk were 45% more likely and those with a > or =20% CHD risk were 73% more likely to have low BMD. Similar increases in low BMD risk were not detected in men. In the United States, 10-year Framingham CHD risk assessment may be useful for identifying older women who should be evaluated for osteoporosis and referred for BMD measurement. The impact of such a screening strategy on fracture prevention needs further elucidation.


The role of plant growth-promoting rhizobacteria (PGPR) in improving iron acquisition by altering physiological and molecular responses in quince seedlings.
Due to insoluble iron (Fe) sources in soil, limited Fe availability leads to the disruption of the photosynthetic apparatus; this affects the growth and productivity of plants such as quince (Cydonia oblonga) that are very sensitive to low Fe content. Plant growth-promoting rhizobacteria (PGPR) play an important role in the regulation of Fe uptake under its limited availability. Therefore, in this research, two PGPR (Pseudomonas fluorescens and Microccucuce yunnanensis), at two Fe levels [50 μM (Fe-sufficiency) or 5 μM (Fe-deficiency)], were used to investigate the impact of the given bacteria on improving the acquisition of Fe in quince seedlings. Upon Fe-deficiency, the highest shoot and root biomass (7.14 and 6.04 g plant-1 respectively), the greatest chlorophyll concentration (0.89 mg g-1FW), and the largest Fe concentrations in roots and shoots (30% and 48.7%, respectively) were shown in the quince treated with M. yunnanensis. Both PGPR increased the root citric acid and the phenolic compound concentration. Two days after Fe-deficiency and PGPR treatments, a 1.5- fold increase, was observed in the expression of HA7. The highest PAL1 gene expression and the greatest PAL activity (95.76 μmol cinnamic acid g-1FW) were obtained from the M. yunnanensis treatment. The expression of the FRO2 gene was also affected by Fe-deficiency and PGPR treatments, resulting in an increase in the FCR activity and a surge in the Fe concentrations of leaves and roots. It could, therefore, be concluded that the PGPR modulated Fe acquisition in the quince seedlings upon Fe-deficiency by influencing the physico-chemical and molecular responses.


Differences in antibiotic prescribing in three university hospitals in the Baltic region revealed by a simple protocol for quality assessment of therapeutic indications.
To identify inexpensive and simple quality parameters for the surveillance of antibiotic use in hospital settings. A modified point-prevalence study was conducted in three university hospitals in Huddinge, Sweden, Riga, Latvia, and Vilnius, Lithuania. Each ward was visited once during May in the year 2002. All patients receiving antibiotics were identified and their medical records were reviewed by the authors according to the same protocol. Only data from corresponding departments were evaluated and compared. The prevalence of antibiotic use was 35%, 25% and 24% in Huddinge, Riga and Vilnius, respectively. Almost 2/3 of antibiotics were prescribed for treatment and 1/3 for either surgical or medical prophylaxis. Parenteral administration was significantly more common in Riga and Vilnius than in Huddinge. The most commonly prescribed antibiotics were cephalosporins and fluoroquinolones. Prescription of antibiotics for different diagnoses showed large variation between and within hospitals. The first or second generation cephalosporins were prescribed in most cases of surgical prophylaxis. The duration of surgical prophylaxis exceeded one day in 57%, 63% and 87% of cases in Huddinge, Riga and Vilnius, respectively. All antibiotics in Huddinge, and all except five in Riga were supplied by the hospital pharmacy. Antibiotics bought by patients and donated made up 41% of prescribed antibiotics in Vilnius. This point-prevalence survey using a simple and inexpensive method for benchmarking demonstrated quantitative and qualitative differences in the use of antibiotics between three university hospitals in the Baltic region, differences that now calls for explanations to their rationality. We suggest that the choice of an antibiotic, rates of intravenously administered treatment and duration of surgical prophylaxis are examples of suitable indicators of rational antibiotic use within a hospital but that comparison of such rates between hospitals is less meaningful.


Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury.
Müller cells maintain homeostatic functions in the retina. Their dysfunction leads to irreversible retinal diseases. Oxidative injury is a leading cause of retinal cytotoxicity. Our previous studies reported several betulinic acid (BA) derivatives can protect Müller cells from oxidative injury but achieving pharmacologically effective concentrations in the Müller cells could be a limitation. To optimise cellular delivery, we encapsulated the BA analogues H3, H5 and H7 into the clinically approved Compritol 888 and HD5 ATO solid lipid nanoparticles (SLNs) using the micro-emulsion method. The cytoprotective effects of these SLN-formulations were determined in human MIO-M1 cells. We found cytoprotection by H3 and H5 SLN-formulations was significantly enhanced, which was evident at concentrations much lower than those required with the free agents. Both SLN-formulations prolonged the duration of action of these agents. The most effective agent H5 delivered in 888 ATO SLNs attenuated glutamate-induced ROS formation and the associated necrosis in MIO-M1 cells. Overall, SLNs have emerged as promising delivery carriers for BA derivatives enhancing their protective effects against oxidative injury in human Müller cells. Our study is the first to show SLNs can be a viable route to delivery agents with improved efficacy and stability into human Müller cells favoring the treatment/prevention of retinal diseases.


Analysis of D-penicillamine in plasma by fluorescence derivatisation with N-[p-(2-benzoxazolyl)-phenyl] maleimide and high-performance liquid chromatography.
A high-performance liquid chromatographic assay for penicillamine in plasma is described. The method is based on the derivatisation of penicillamine in acidified protein-free plasma supernatants with the sulphydryl-specific reagent N-[p-(2-benzoxazolyl)-phenyl] maleimide (BOPM) to give a stable fluorescent product. After separation of the penicillamine-BOPM derivative by reversed-phase high-performance liquid chromatography, fluorescence detection enables the quantitation of plasma penicillamine concentrations in the range 0.25-500 mumol/l. The method is selective and reproducible, and since chromatography time is less than 7 min the method is readily applicable to the analysis of the large number of samples associated with pharmacokinetic studies.


Bimodal porous silica microspheres decorated with polydopamine nano-particles for the adsorption of methylene blue in fixed-bed columns.
Bimodal meso/macro-porous silica microspheres (MSM) were synthesized by a modified sol-emulsion-gel method and then the surface was coated with polydopamine (PDA) nano-particles of 39nm in size. Focusing on the encouraging properties of the synthesized adsorbent, such as high specific surface area (612.3m(2)g(-1), because of mesopores), fast mass transfer (0.9-2.67×10(-3)mLmin(-1)mg, because of macropores), and abundant "adhesive" functional groups of PDA, it was used for the removal of methylene blue (MB) from aqueous solution in a fixed-bed column. The effect of different parameters such as pH, initial concentration, and flow rate was studied. The results revealed that an appropriate sorption condition is an alkaline solution of MB (e.g., pH 10) at low flow rate (less than 5mLmin(-1)). Furthermore, the compatibility of the experimental data with mathematical models such as Thomas and Adams-Bohart was investigated. Both of the models showed a good agreement with the experimental data (R(2)=0.9954-0.9994), and could be applied for the prediction of the column properties and breakthrough curves. Regeneration of the column was performed by using HCl solution with a concentration of 0.1M as an eluent.


The relationship between flow cytometer crossmatch results and subsequent rejection episodes in cadaver renal allograft recipients.
Flow cytometry (FC) T and B cell crossmatches were done retrospectively for 38 cadaver renal transplant recipients (29 first and 9 retransplants--minimum follow-up 12 months) using both current pretransplant serum and peak-reactive sera. An increase in median fluorescence intensity (channel shift) and/or an increase in the number of donor T and/or B cells binding antibody in test sera occurred in 23 cases. These 23 patients experienced a greater number of reversible rejection episodes as compared with patients with negative FC crossmatches (65% vs. 33%), P = 0.031. Graft outcome, however, was not different in the two groups. Thus, a positive FC crossmatch allows for the detection of subliminal levels of donor presensitization and is associated with a greater number of rejection episodes. A positive FC crossmatch is not predictive of ultimate graft loss.


Assessment of prospective foodchain doses from radioactive discharges from BNFL Sellafield.
This paper presents the method used by the UK Food Standards Agency (FSA) to assess the potential impact of proposed radioactive discharges from the Sellafield nuclear site on food and determine their acceptability. It explains aspects of a cautious method that has been adopted to reflect the UK government policy and uncertainties related to people's habits with regard to food production and consumption. Two types of ingestion doses are considered in this method: 'possible' and 'probable' doses. The method is specifically applied to Sellafield discharge limits and calculated possible and probable ingestion doses are presented and discussed. Estimated critical group ingestion doses are below the dose limit and constraint set for members of the public. The method may be subject to future amendments to take account of changes in government policy and the outcome of a recent Consultative Exercise on Dose Assessments carried out by FSA. Uncertainties inherent in dose assessments are discussed and quantified wherever possible.


Signaling-competent receptor chimeras allow mapping of major insulin receptor binding domain determinants.
Chimeric receptors were generated in which structurally defined subdomains of the insulin receptor (IR) and insulin growth factor-I receptor (IGF-1R) alpha-subunits were exchanged between their respective receptor backbone structures. Upon expression in human fibroblasts, nine IR/IGF-1R chimeras were transported to the cell surface, where they formed binding sites with differential properties. One IGF-1R/IR chimera (C3') exhibited to some extent high insulin specificity, demonstrating the presence of major insulin binding determinants within the amino acid 325-524 region of the IR alpha-subunit. Complementation of this region with subdomain 1 (amino acids 1-137) reconstituted full insulin binding potential within an IGF-1R framework. In addition, both the IGF-1R/IR C3' chimera and another chimera (C13') displayed high affinity binding properties for IGF-1, which suggests distinct locations for major insulin and IGF-1 binding determinants in their respective receptors, in agreement with our previous findings (Schumacher, R., Mosthaf, L., Schlessinger, J., Brandenburg, D., and Ullrich, A. (1991) J. Biol. Chem. 266, 19288-19295). The binding characteristics of all receptor chimeras correlated directly with the ability of the ligands to regulate their tyrosine kinase activity in intact cells. These results demonstrate direct coupling of ligand binding affinity and capacity for tyrosine kinase activation.


Echinococcal hepatic disease: magnetic resonance appearance.
The magnetic resonance (MR) appearance of an echinococcal hepatic cyst is described. A previous report has suggested that a low-intensity rim surrounding the cyst may be useful in differentiating hydatid cysts from other hepatic lesions. No such rim was identified in our case; however, MR was found to be superior to other modalities in delineating the internal contents of the hydatid cyst.


Role of Estrogen Receptor β, G-Protein Coupled Estrogen Receptor and Estrogen-Related Receptors in Endometrial and Ovarian Cancer.
Ovarian and endometrial cancers are affected by estrogens and their receptors. It has been long known that in different types of cancers, estrogens activate tumor cell proliferation via estrogen receptor α (ERα). In contrast, the role of ERs discovered later, including ERβ and G-protein-coupled ER (GPER1), in cancer is less well understood, but the current state of knowledge indicates them to have a considerable impact on both cancer development and progression. Moreover, estrogen related receptors (ERRs) have been reported to affect pathobiology of many tumor types. This article provides a summary and update of the current findings on the role of ERβ, GPER1, and ERRs in ovarian and endometrial cancer. For this purpose, original research articles on the role of ERβ, GPER1, and ERRs in ovarian and endometrial cancers listed in the PubMed database have been reviewed.


Surface hardening of Ti-Al-V superalloy spinal implant by using the boronization method.
We compared the raw Ti-Al-V super alloy transpedicular implant screws with boronized and surface-hardened transpedicular implant screws. To improve patients' postoperative prognosis with the production of harder and less fragile screws. Surface hardening was achieved by applying green-body encapsulation of the specimen with elemental boron paste which is sintered at elevated temperatures to ensure the boron-metal diffusion. Boron transported into the Ti-Al-V super alloy matrix gradually while suppressing aluminum and a homogeneously boronized surface with a thickness of ∼15 microns was obtained. The uniform external shell was enriched with TiB2, which is one of the hardest ceramics. The Ti-Al-V core material, where boron penetration diminishes, shows cohesive transition and ensures intact core-surface structure. Scanning electron microscope images confirmed a complete homogeneous, uniform and non-laminating surface formation. Energy-dispersive X-ray monitored the elemental structural mapping and proved the replacement of the aluminum sites on the surface with boron ending up the TiB2. The procedure was 8.6 fold improved the hardness and the mechanical resistance of the tools. Surface-hardened, boronized pedicular screws can positively affect the prognosis. In vivo studies are needed to prove the safety of use.


Maximal thymectomy in children with myasthenia gravis.
We performed this study to evaluate the benefit of thymectomy in children with myasthenia gravis (MG). Over a period of 15 years from 1986 to 2001, we collected data on 30 children with MG and retrospectively reviewed the outcome of maximal thymectomy. There were 23 females and seven males with a mean age of 13.2 years (range 4-16). The mean duration of the disease was 19.3 months (range 2-144). According to Osserman classification, there were 14 children in class II; 12 in class III; and four children in class IV. One child in class IV required postoperative ventilation and one was re-explored to drain a pericardial effusion secondary to central line leak. We found ectopic thymic tissue in 10 cases (33.3%). During a mean follow-up period of 53.5 months (range 9-180), complete remission was noted in 13 children (43.4%) and improvement in 14 (46.6%). The remaining three children (10%) did not improve following surgery. Univariate analysis (P < 0.05) showed that ectopic thymic tissue is a significant prognostic factor for outcome. Maximal thymectomy appears to provide a high rate of remission and improvement in children with MG. However, the presence of ectopic thymic tissue has poor prognostic value.


Use of Self-Study Resources Among Medical Students-Towards Avoiding Death by PowerPoint.
Reliance on PowerPoint (PPT) slides for self-studying may encourage lower-order cognition due to learning by rote dominating the educational process. On anecdotal evidence, PPT slides have become ubiquitous among Saudi medical students as the chief format of self-study material. We present the scale of the problem in Saudi medical colleges and then discuss the relevant potential implications and remedies. Using a piloted, face-validated, web-based, and self-administered questionnaire, we asked 379 medical students from 22 Saudi medical colleges to answer a few questions related to the use of PPT slides (and other resources) to self-study in preparation for the pediatric course final exam. By far, PPT slides represented the dominant format of self-study resources for most students (n = 359; 94.7%). One-third of students (n = 115; 30.3%) reported they had never or only rarely to occasionally used their basic pediatric textbooks for self-study. Most students (n = 260; 68.6%) reported that > 80% of the final written exam questions stemmed from the PPT slides provided by lecturers. As this study's result underscores the notion that PPT slides have become the customary primary self-study material used by Saudi medical students, we tried to discuss the associated threats to learning and teaching and suggest practical solutions.


Localized microbubble cavitation-based antivascular therapy for improving HCC treatment response to radiotherapy.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and the fastest growing malignancy in the United States. With a 5-year survival rate below 12%, effective therapies for HCC are needed. Current treatments for HCC include microwave and radiofrequency ablation, high intensity focused ultrasound, liver transplant, surgical resection, and localized embolizations. However, each of these approaches has some limitation, making it imperative to develop improved methods for sensitizing tumors prior to therapy. We hypothesized that the use of ultrasound-triggered microbubble destruction (UTMD), which sensitizes tumors to radiotherapy by inducing vascular endothelial cell apoptosis, will selectively sensitize malignant tissue to radiotherapy and improve outcomes. To test this, 18 nude rats were inoculated in the right liver lobe with Hu7.5 HCC cells and after tumor formation, received 5 Gy radiotherapy, UTMD, or UTMD prior to radiotherapy. Compared to radiotherapy alone, there was a 170% reduction in tumor growth 7 days post treatment and a 3.2X improvement in median survival time when radiotherapy was combined with UTMD. These results indicate that UTMD is an effective adjunct when combined with radiotherapy to treat HCC.


The Metal Ion Release of Manganese Ferrite Nanoparticles: Kinetics, Effects on Magnetic Resonance Relaxivities, and Toxicity.
Mn2+ release is particularly important for biological application of manganese-based nanomaterials. However, the Mn2+ release profiles of the manganese ferrite nanoparticles are under clarification. Here, we synthesized 3, 10, and 18 nm manganese ferrite nanoparticles (MFNPs) as model systems to study the Mn2+ release behavior, size, and pH-dependent kinetics. The Mn2+ release kinetic study showed that the first-order kinetic model was suitable for 3 and 10 nm MFNPs, while the Higuchi model was suitable for 18 nm MFNPs in a neutral PBS buffer (pH 7.4). In an acidic PBS buffer (pH 4.8), the Mn2+ release from all sizes of MFNPs follows first-order kinetics, which is possible due to the reaction between MFNPs and H+. The influence of Mn2+ release was evaluated by comparing the variations of magnetic resonance (MR) relaxation and magnetic properties before and after Mn2+ release of MFNPs. The results showed that the saturation magnetization (Ms), longitudinal relaxivity (r1), and transverse relaxivity (r2) values declined due to Mn2+ release, while the ratio of r2/r1 increased slightly, showing that all sizes of MFNPs exhibited the same MR mode as the synthesized MFNPs. More importantly, the release kinetics were employed to estimate the toxicity of the released Mn2+in vivo. The potential toxicity is acceptable for MFNP administration since the calculated amount of Mn2+ is in the range of safe doses.


Interventions of river network structures on urban aquatic microplastic footprint from a connectivity perspective.
Microplastic footprint in urban river networks can be disturbed by multiple urbanization features, and regional river structures are generally overlooked. In this research, we analyzed the distribution of microplastics and potential impact pattern of river structures on it in a typical urban river network in Nanjing, China. Surface waters of the river network were jointly detected by multiple methods, and the Renkonen similarity index was used to study spatial variabilities of microplastics characteristics. Microplastics were ubiquitous and abundant, showing five (>50 μm) and six (20∼50 μm) hotspots, and heterogeneities in the shape and type of microplastics larger than 100 μm were prominent, presumably influenced by river network scale and connectivity. River structure parameters associated with network connectivity were obtained by combining graph theory and an entropy-based set-pair analysis model. Aiming at the action pathway of river structures, by using correlation and partial least squares regression analysis, we found that river node (confluences and sluices) ratio, river frequency, river network density, and water system circularity were significantly positively correlated with microplastic abundance, and confluences with poor connectivity had a greater indirect intervention intensity on the microplastic distribution. The land use characteristics dominated the fitting of microplastic abundance, which was about 1.2 times better than river structures, and the comprehensive land use intensity and river network connectivity were the critical factors, respectively. Potential ecological risks of microplastics were evaluated, resulting in relatively severe levels. This study proposed targeted measures to control urban microplastic pollution by combining the perspective of river network characteristics. To summarize, our exploration of microplastic footprint based on urban river network structures from the perspective of river network connectivity provides new insights into microplastic management.


Recolonization of group B Streptococcus (GBS) in women with prior GBS genital colonization in pregnancy.
The purpose of the study is to evaluate the incidence of women with prior GBS genital colonization who have recolonization in subsequent pregnancies. This is a retrospective, cohort study of patients with a prior GBS genital colonization in pregnancy and a subsequent pregnancy with a recorded GBS culture result, from January 2000 through June 2007. Documentation of GBS status was through GBS culture performed between 35 to 37 weeks gestation. Exclusion criteria included pregnancies with unknown GBS status, patients with GBS bacteriuria, women with a previous neonate with GBS disease and GBS finding prior to 35 weeks. Data was analyzed using SPSS 15.0. The sample proportion of subjects with GBS genital colonization and its confidence interval were computed to estimate the incidence rate. Logistic regression was performed to assess potential determinants of GBS colonization. Regression coefficients, odds ratios and associated confidence intervals, and p-values were reported, with significant results reported. There were 371 pregnancies that met the test criteria. There were 151 subsequent pregnancies with GBS genital colonization and 220 without GBS recolonization. The incidence of GBS recolonization on patients with prior GBS genital colonization was 40.7% (95% confidence interval 35.7-45.69%). The incidence rate for the sample was significantly larger than 30% (p < .001), which is the estimated incidence rate for all pregnant women who are GBS carriers regardless of prior history. These results suggest that patients with a history of GBS are at a significantly higher risk of GBS recolonization in subsequent pregnancies.


Phenotypic and genotypic comparison of ESBL production by vaginal Escherichia coli isolates from pregnant and non-pregnant women.
Vaginal Escherichia coli is a reservoir along the fecal-vaginal-urinary/neonatal course of transmission in extraintestinal E. coli infections. They also causes genital tract infections especially vaginitis, so that detection of their antibiotic resistance is an important approach to control these infections. One important mechanism of resistance is ESBL production by Enterobacteriaceae especially Klebsiella spp. and Escherichia coli, which is now a worldwide problem that limits therapeutic options. Sixty one vaginal E. coli isolates from pregnant and non-pregnant women, were detected phenotypically and genotypically for ESBL production. Most of pregnant and non-pregnant women's isolates, were resistant to cefotaxime (100% vs. 81.5%, respectively) and more than half of them to ceftazidime (56.5% vs. 71.0%, respectively). One hundred percent each, 52.1% vs. 68.4%, and 73.9% vs. 60.5%%, were ESBL producers by screening, confirmatory, and PCR tests, respectively. Pregnant women's isolates had: CTX-M- (69.5%), SHV- and OXA-type (each 4.3%) ESBLs. Only one isolate (4.3%) had two types of ESBLs. All 16 CTX-M-positive (100%) isolates had CTX-M-1. Non-pregnant women's isolates were predominated by SHV and CTX-M -type (44.7% vs. 39.4%, respectively), followed by OXA- (15.7%), and TEM-type (2.6%). Of these isolates, 42.1% had two types of ESBL genes. All 15 CTX-M-positive (100%) isolates had CTX-M-1. Pregnant and non-pregnant women's isolates differed significantly (P≤ 0.05) regarding the expression of SHV- (4.3% vs. 44.7%, respectively) and CTX-M-type (69.5% vs. 39.4%, respectively) ESBLs. In both, CTX-M-1 was the predominant CTX-M group (each 100%). All of the isolates were susceptible to imipenem and meropenem, while the highest rate of resistance was against β-lactams. Multidrug resistance was noted in 56.2% of ESBL-producing isolates. Ggenital tracts of pregnant and non-pregnant women represent different environments for propagation of ESBL-producing E. coli. In Iraq, nationwide study is required to make a precise estimation of this widespread of ESBL-producing bacteria.


MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid.
MicroRNAs (miRNAs) are small, noncoding RNAs that function in complex networks to regulate protein expression. In the brain, they are involved in development and synaptic plasticity. In this study, we aimed to identify miRNAs with a differential expression in either hippocampus or cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and age-matched nondemented control subjects using quantitative polymerase chain reaction. In hippocampus, we also differentiated between AD patients with an intermediate stage, according to Braak III/IV stage, and a late stage, characterized according to Braak VI stage. Eight selected miRNAs were analyzed in hippocampus, and the expression of miR-16, miR-34c, miR-107, miR-128a, and miR-146a were differentially regulated. In CSF, out of 8 selected miRNAs only miR-16 and miR-146a could be reliably detected. In addition, we identified an effect of blood contamination on the CSF levels of miR-16, miR-24, and miR-146a. For group comparisons, we therefore selected CSF samples absent of, or containing only low numbers of blood cells. Levels of miR-146a were significantly decreased in CSF of AD patients. In conclusion, the abnormal expression of several miRNAs in hippocampus of intermediate- and late-stage AD patients suggests their involvement in AD pathogenesis, and low levels of miR-146a in CSF were associated with AD.


Haplotypes in cathechol-O-methyltransferase gene confer increased risk for psychosis in Alzheimer disease.
The gene encoding catechol-O-methyltransferase (COMT) has been suggested as a candidate for Alzheimer-related psychosis (AD-P) susceptibility, and an association between AD-P and a functional valine to methionine polymorphism has been reported. The aim of this study was to assess the genetic contribution of other COMT variants to the risk of AD-P. Two hundred and forty-six AD patients underwent clinical and neuropsychological examination as well as an evaluation of behavioural and psychiatric disturbances. They were subsequently divided into two subgroups according to the presence (AD-P) or the absence (AD-nP) of psychotic symptoms. Four single-nucleotide polymorphisms (SNPs) within COMT gene were evaluated, i.e. rs737865, rs737864, intron 1 C2754delC, and the well-known valine/methionine variant (rs4680). Analyses were performed on the single locus and pairwise disequilibrium of loci, and multi-locus haplotype. The individual SNP analysis confirmed an association for the valine/methionine variant with AD-P. Haplotype analyses revealed that the alleles at four loci (rs737865, rs737864, intron 1 C2754delC, rs4680) interacted to create the risk of psychosis in AD, as A-C-C-G haplotype (OR=2.08, 95% CI=1.02-4.27, P=0.044) and G-C-delC-G haplotype (OR=2.54, 95% CI=1.32-4.90, P=0.006) in respect to the most common and not-at-risk A-C-C-A haplotype which was significantly overrepresented in AD-P. The present findings provide evidence of COMT genetic variations' role in the susceptibility to AD-related psychosis. The observation of a haplotype effect of different polymorphisms within the COMT gene puts emphasis on the usefulness of haplotype analysis in better defining individualized genetic risk profiles in AD.


In Vitro Comparison of Porcelain Fused to Metal Crown Retention after Endodontic Access and Subsequent Restoration: Composite, Amalgam, Amalgam with Composite Veneer, and Fiber Post with Composite.
The aim of this study was to evaluate the effect of different access opening restorative materials on crown retention. Thirty-eight extracted molars were mounted in resin and prepared for porcelain fused to metal (PFM) crowns. The crowns were fabricated and cemented with zinc phosphate, and the force to displace it was measured with a tensile-testing machine before and after endodontic access preparations. The endodontic access area, crown preparation axial wall, and preparation surface area were measured for comparison. The crowns were then recemented, and access openings were restored with either amalgam or composite before displacement force was remeasured. The restorative material was removed from each access opening; access area was measured and restored again (amalgam with composite or fiber post with composite) for displacement force to be remeasured. Paired t test was used to compare the means of displacement between groups. One-way analysis of variance was used to compare the mean outcome measure within the groups. Statistical analyses showed retention after unfilled access was significantly lower than intact crowns. Amalgam, composite, amalgam + composite, and fiber post + composite increased retention beyond the original value. There was no statistical difference among the different restorative protocols. Qualitative results indicate that the restorative material remains in the crown after displacement regardless of the material used to restore the access. The results from this study suggest that an endodontic access cavity decreases retention of a PFM crown. However, subsequent restoration with amalgam, composite, amalgam + composite, or post + composite may increase the original retention of the crown.


Isolated olfactory cleft involvement in SARS-CoV-2 infection: prevalence and clinical correlates.
Smell alterations are a symptom of COVID-19 and have been associated with olfactory cleft mucosal thickening (OCMT). Although their pathogenesis is unclear, evidences link them to viral neuroinvasive potential. This study aims at estimating the prevalence of OCMT in CT scans of COVID-19 patients and investigating its clinical correlates. In a single-institution retrospective cross-sectional study, we included all patients hospitalized for COVID-19 undergoing head CT scan for any reason. Exclusion criteria were history of recent head trauma or chronic rhinosinusitis; opacification > 2 mm in any sinonasal space other than the olfactory cleft; CT performed during/after invasive ventilation or feeding via nasogastric tube. We recorded the prevalence of OCMT and related it to age, sex, need for invasive ventilation during hospital stay, outcome, length of hospital stay, diffusion of lung SARS-CoV-19 lesions and outcome. 63 eligible patients were identified (39 male, 24 female; median age 77.82 ± 17.77 years). OCMT was identified in 16 patients (25.4%; 95% CI 15.3-37.9%). Patients with OCMT had longer hospital stays (median 16 ± 4 vs. 9 ± 14.5 days, p = .009, Mann-Whitney U test) and required invasive ventilation more frequently than patients without mucosal thickening (OR 4.89, 95% CI 0.96-24.89, p = .063, Fisher's test). No other difference was observed. OCMT affects nearly one in four patients hospitalized for COVID-19. It is associated with a worse disease course irrespective of age, sex and diffusion of lung lesions, although with no direct effect on survival.


Revision of the Australian genus Logasa Chandler (Staphylinidae, Pselaphinae, Faronitae) with description of three new species.
The Australian genus Logasa Chandler, 2001 (type species: L. novaeanglia Chandler) is comprised of six species, three of which are described as new: Logasa newtoni sp. nov., Logasa thayerae sp. nov., and Logasa comforti sp. nov. Examination of the types of L. tricolor (Oke) and L. ventralis (Oke) revealed that they do not share some of the diagnostic characters used here to characterize the type, and other species of the genus, but they are retained in Logasa until the group is revised. A key to species, illustrations of their habitus, and diagnostic characters are provided.


Transuranic and fission product contamination in lake sediments from an alpine wetland, Boréon (France).
Transuranics and fission products have been measured in lake sediment samples, collected in an alpine wetland, to determine their vertical distribution and calculate inventories. The radionuclides considered are 90Sr, 137Cs, 238Pu, 239/240Pu and 241Am. From the results, a better knowledge of radionuclide accumulation mode and behaviour was obtained. In addition, the origins of the individual pollutants could be deduced from activity ratios. Analyses were made on different sediment cores. The sampling sites were chosen to enable future determination of the mass balances of the radiopollutants. As the selected study area is in a recreational area used by urban populations, a rough estimate was made of the mean external dose from 137Cs for comparison with the French regulation.


Computed tomography and ultrasound demonstration of squamous cell carcinoma of the kidney.
The computed tomography and ultrasound appearance of a case of squamous cell carcinoma of the kidney is reported and the relevant clinical and urographic findings in this rare entity are reviewed.


Surgical technique: when to arthroscopically repair the torn posterior cruciate ligament.
Posterior cruciate ligament injuries can occur as isolated ligament ruptures or in association with the multiligament-injured knee. Delayed reconstruction, at 2-3 weeks post-injury, is predominantly recommended for posterior cruciate ligament tears in the multiligament-injured knee. While acute bone and soft tissue avulsion patterns of injury can be amenable to repair, the described techniques have been associated with some difficulties attaching the avulsed ligament. As part of a reconstruction/repair of a multiligament-injured knee, we performed arthroscopic primary repair of the posterior cruciate ligament by passing Bunnell-type stitches into the substance of the ligament using a reloadable suture passer. We then passed the sutures through drill holes into the femoral footprint of the ligament and tied them over a bony bridge. We retrospectively reviewed three patients with posterior cruciate ligament tears associated with a multiligament-injured knee. All patients had posterior cruciate ligament soft tissue avulsions or "peel off" injuries diagnosed by MRI. The described repair technique was used to repair the posterior cruciate ligament avulsion. Minimum followup was 64 months (mean, 68 months; range, 64-75 months). ROM, stability testing, and functional outcome scores (Lysholm and modified Cincinnati) were recorded. Mean ROM was 0° to 127°. Posterior drawer testing was negative in all three patients. The mean Lysholm score was 92 and the mean modified Cincinnati score was 94. Followup MRI confirmed ligament healing in all patients. We believe arthroscopic posterior cruciate ligament repair for soft tissue peel off injuries is a technique that, when applied to carefully selected patients, may be helpful to the surgeon treating patients with a multiligament-injured knee. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Spatial and temporal variation of nitrogen exported by runoff from sandy agricultural soils.
The eutrophication problem has drawn attention to nutrient leaching from agricultural soils, and an understanding of spatial and temporal variability is needed to develop decision-making tools. Thus, eleven sites were selected to monitor, over a two-year period, spatial and temporal variation of runoff discharge and various forms of N in surface runoff in sandy agricultural soils. Factors influencing the variation of runoff discharge and various forms of N in surface runoff were analyzed. Variation of annual rainfall was small among 11 sites, especially between 2001 and 2002. However, variation of annual discharge was significant among the sites. The results suggest that rainfall patterns and land use had significant effect on discharge. The concentrations of total N, total kjeldahl N (TKN), organic matter-associated N (OM-N), NO3(-)-N, and NH4(+)-N in the runoff ranged widely from 0.25 to 54.1, 0.15 to 20.3, 0.00 to 14.6, 0.00 to 45.3, and 0.00 to 19.7 mg/L, respectively. Spatial and temporal variations in the N concentration and runoff discharge were noted among the different sites. Annual loads of N in the runoff varied widely among monitoring sites and depend mainly on runoff discharge. High loads of total N, OM-N, NO3(-)-N, and NH4(+)-N in the runoff either in citrus groves or on vegetable farms occurred from June to October for each year, which coincided with the rainy season in the region. This study found that N in surface runoff was related to rainfall intensity, soil N level, and fertilizer use.


Selective effects of cyclosporin A on colony-forming lymphoid and myeloid cells in man.
THE properties of the fungus metabolite, cyclosporin A, have suggested its potential as a clinically valuable immunosup-pressive agent(1,2). Experiments in animals have demonstrated that its suppressive action against cell-mediated and humoral immunity is not accompanied by any appreciable myelotoxicity(3,4). In this respect, cyclosporin A contrasts with other immunosuppressants in current use, such as antilymphocyte globulin and azathioprine. There are, however, few data to substantiate a selective toxicity of cyclosporin A against human lymphocytes. Here, we have compared its effects against human lymphoid and myeloid cells, using colony formation by the different cell types as the end point. We found that the compound exhibited far greater toxicity towards a sub-population of T cells than towards either B lymphocytes or haematopoietic precursor cells.


Dexamethasone-sensitive and -insensitive responses during in vitro differentiation of Friend erythroleukemia cells.
We have investigated the mechanism(s) by which dexamethasone inhibit DMSO-induced Friend erythroleukemia cell differentiation in vitro. In particular, we examined the effects of dexamethasone on (a) the early events of differentiation such as cell volume alterations and 'memory response' and (b) the onset of biochemical events associated with terminal erythroid cell differentiation. By analysing kinetics of commitment of Friend cells to terminal erythroid differentiation on a clonal basis, we have observed that dexamethasone inhibited the completion of the latent period (time elapsed prior to commitment) and impaired "memory" (ability to inducer-treated cells to continue differentiation after a discontinuous exposure to inducer). Treatment of Friend cells with dexamethasone did not prevent the occurrence of DMSO-induced alterations in cell volume. However, dexamethasone treatment prevented a series of biochemical events associated with terminal Friend cell differentiation. These include the decrease in the rate of both cytoplasmic and nuclear RNA synthesis as well as the induction of cytidine deaminase activity and hemoglobin synthesis. These data indicate that the dexamethasone-sensitive process(es) operate during the early stages of Friend cell differentiation and that they are responsible for the inhibition of terminal erythroid maturation. These dexamethasone-sensitive processes, however, appear to be different from those regulating cell volume alterations during the early steps of DMSO-induced Friend cell differentiation.


Limited doses of immunotherapy use in advanced non-small cell lung cancer elderly patients with ECOG of 2 and high PDL-1 expression.
Immunotherapy is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with high PDL-1 expression. Here, we report three such patients with durable response despite limited doses immunotherapy.


Learning inequality during Covid-19: Evidence from secondary schools in Colombia.
During 2020, the Covid-19 pandemic unleashed a socioeconomic crisis in most countries, as well as strict restrictions on mobility and social distancing were implemented. The pandemic brought a severe socioeconomic shock -decreasing economic activity- and forced policy responses that affected the education sector -notably school closures-. There is scarce evidence on the implications of the pandemic and its socioeconomic consequences on learning inequality, particularly in the Latin-American context. The aim of this paper is to measure the change in learning inequality during the years of the pandemic (2020-2021) in Colombia. To measure learning inequality, we use the results of a standardize exam taken by all upper secondary education graduates in the country. To capture inequality, we use secondary-level students' characteristics, their households, and schools' characteristics. Our econometric results suggest an increase in learning inequality between 48% and 372% depending on the dimension studied, except for gender where learning inequality decreased. Moreover, through dynamic specifications, we determine that for all the analyzed dimensions the 2020-2021 period represents a change in the trend of learning inequality as in the periods prior to the pandemic inequality gaps decreased or, at least, remained constant. We conclude with concrete and immediate policy recommendations to target the learning processes of vulnerable students and bridge learning gaps.


Diagnostic testing for Legionnaires' disease in the Netherlands between 2007 and 2009: a possible cause for the decline in reported Legionnaires' disease patients.
Legionnaires' disease (LD) is an acute pneumonia caused by the inhalation or aspiration of aerosols contaminated with the Legionella bacteria. In the Netherlands, around 300 LD cases per year were reported between 2000 and 2008, but in 2009, the number dropped to 251, which was the lowest number in the previous 5 years of surveillance. We investigated if this decrease could be explained by the number of performed Legionella diagnostic tests in this year. We analyzed the number of tests performed between 2007 and 2009 in three large microbiological laboratories in different geographical regions in the Netherlands. Our data showed that there was no decrease in the number of patients for whom a diagnostic test for Legionella was performed in this period. These results are not in line with our hypothesis that the decrease in reported Legionella pneumonia patients in 2009 would be due to a decrease in patients for whom a diagnostic test was performed. We conclude that it is more likely that other factors such as the influence of weather patterns might explain the sudden drop in reported Legionella pneumonia patients in 2009 compared to the previous years, and it would be interesting to investigate this for the period described.


Identification of copy number alternation profiles in metastatic oral squamous carcinoma patients by using microarray-based comparative genomic hybridization: A study on Turkish patients.
Oral squamous cell carcinoma (OSCC) is a severe form of cancer affecting different anatomic sites of the oral cavity. OSCC ranks as the sixth most common cancer type with an increasing prevalence globally. However, the mechanisms of OSCC process at later stages are not well understood. In this study, we aimed to determine genetic alternations in metastatic OSCC patients to identify genomic changes occurred at metastatic phase of the disease. The Illumina CytoSNP-12 Array was used to determine copy number variations in OSCC cancer genome. Hybridization procedures were performed according to the manufacturer procedures (Illumina). Arrays were scanned on iScan System (Illumina). Data were analyzed using Illumina Genotyping module of Genome Studio software (version 1.2, Illumina). Multiple CNV algorithms and copy number alternations were accessed by Genome Studio. CNVs in whole genome were investigated by using a chromosomal heat map. We reported that gains in 8q21.11-ter, 9p21.3, 13q14.11-ter, 13q13.3-ter and losses in 5q14.3-ter, 5q35 and 17p13.3-12 were associated with the development of OSCC. In addition, we also detected that deletion in 2q33.2-ter and 2q35-37.3 regions were also associated with OSCC metastasis process. Our results were also showed that gains in 11q13.3-q13.4 and 2q13.2 chromosomal regions could promote the metastatic OSCC process. We believe that results of the study will help to find new biomarkers for diagnosis at later stage of OSCC.


Low-level Laser Therapy in the Management of Oral Mucositis Induced by Radiotherapy: A Randomized Double-blind Clinical Trial.
The present study evaluated the effect of LLLT at red and infrared wavelengths associated with therapeutic measures from the Mucositis Study Group of the Multinational Association of Supportive Care of Cancer and International Society of Oral Oncology (MASCC/ISOO) for preventing and treating RT-induced oral mucositis (OM). For the study, 80 subjects diagnosed with head and neck cancer (HNC) undergoing treatment were randomized into three groups to apply different photobiomodulation protocols for 42 days, as follows: Group I-LLLT of 660 nm; Group II-LLLT of 810 nm; and Group III-association of wavelengths of 660 and 810 nm. The treatments were performed by properly trained professionals and with equipment calibrated for the intervention. Different OM scores were noted for the groups studied, and the third group had lower scores than Groups I and II (p = 0.012). No difference was noted in the pain score analyzing the groups (p = 0.49). The LLLT was effective for OM lesions in individuals treated with radiotherapy associated or not with chemotherapy. When combined, the red and infrared lasers reduce OM scores. OM is one of the main adverse effects of antineoplastic therapy in head and neck cancer patients. The evidence supporting the validity of LLLT for OM can improve patients' quality of life.


Comparative studies for the biotechnological production of L-Lysine by immobilized cells of wild-type Corynebacterium glutamicum ATCC 13032 and mutant MH 20-22 B.
Establishing a cost and time efficient approach for bioprocess optimization is desired but is challenging. In the present work, we have addressed the effectiveness of using immobilized cells for aerobic processes, behaviour of immobilized cells, optimization and upstream bioprocess analysis for the production of lysine by immobilized cells of Corynebacterium glutamicum ATCC 13032 and MH 20-22 B in stirred tank bioreactor. Optimized operational conditions for maximal yield and productivity were determined with six parameters i.e., pH, temperature, fermentation time, airflow rate, glucose concentration and aeration rate. With the obtained results, it was evident that the optimum values for the upstream parameters viz., fermentation time, pH, temperature, glucose concentration, air flow rate and agitation rate are 96 h, 7.5, 30 °C, 90 g/l, 1.0 vvm and 200 rpm for both immobilized cells of C. glutamicum ATCC 13032 and MH 20-22 B. Immobilized cells of C. glutamicum MH 20-22 B, which is a leucine auxotroph has yielded more L-lysine compare to the immobilized cells of wild type strain C. glutamicum ATCC 13032.


Machine learning and pre-medical education.
Machine learning and artificial intelligence (AI)-driven technologies are contributing significantly to various facets of medicine and care management. It is likely that the next generation of healthcare professionals will be confronted with a series of innovations that are powered by AI, and they may not have sufficient time during their professional tenure to learn about the underlying machine learning frameworks that are driving these systems. Educating the aspiring clinicians and care providers with the right foundational courses in machine learning as part of postsecondary education will likely transform them as high-tech physicians and care providers of the future.


Optimization and kinetic modeling of media composition for hyaluronic acid production from carob extract with Streptococcus zooepidemicus.
Hyaluronic acid (HA), a mucopolysaccharide belonging to the glycosaminoglycan family, consists of repeating disaccharide units and has been used directly or indirectly in numerous human health practices. This study focused on evaluating carob pods for microbial HA production and kinetic modeling of HA fermentation. Therefore, the optimal medium composition was determined using Plackett-Burman Design (PBD) for HA production from carob extract with Streptococcus zooepidemicus. Maximum HA production of shake flask fermentation was 2.6 g/L (1.25 × 106) in the optimum medium, comprising 10°Bx of carob pods extract, 0.5 g/L of MgSO4.7H2O, 10.0 g/L of casein, 2.5 g/L of KH2PO4, 2.0 g/L of NaCl, 1.5 g/L of K2HPO4, 0.002 g/L of FeSO4 and 10.0 g/L of beef extract. In the continuation of the study, the fermentation performed with the optimal medium composition was modeled using three different models including the logistic model for biomass production, the Luedeking-Piret model for HA production, and the modified Luedeking-Piret model for substrate consumption. Based on the results, the experimental HA production data agreed with the Luedeking-Piret model with an R2 of 0.989. Since the α value was 63-fold higher than the value of β, the HA production is growth-associated. Consequently, carob extract can be evaluated as a promising carbon source for producing HA.


Successful surgical intervention for active infective endocarditis on a hemodialysis patient with cerebral infarction and disseminated intravascular coagulopathy.
A 48-year-old woman on hemodialysis developed congestive heart failure, neurologic deficits and disseminated intravascular coagulopathy (DIC) caused by methicillin resistant staphylococcus aureus infective endocarditis. Echocardiography showed large vegetation attached to the anterior leaflet of the mitral valve, severe mitral and aortic regurgitation, and poor left ventricular function. Computed tomography findings revealed recurrent embolic events including cerebral and splenic infarction, but no evidence of intracranial bleeding. Abnormal laboratory findings included DIC in addition to the administration of the daily dose of ticlopidine hydrochloride. Aortic and mitral valves were urgently replaced with bioprosthetic valves after the transfusion of fresh frozen plasma and platelet. During the follow-up period of one year, she was free from any cardiac events and infectious signs. Even though this report is limited to a case and its follow-up, it is sensible to conclude that only aggressive and timely surgical intervention can be the only lifesaving action for patients with highly infective endocarditis.


Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines.
Immunosuppressed individuals are at a high risk of latent tuberculosis infection (LTBI) and clinical practice guidelines for the screening and management of LTBI in at-risk patients have been developed. We assessed the scope, quality and consistency of clinical practice guidelines on screening for LTBI and the prevention of tuberculosis infection (TB) in high-risk patient populations. We conducted a systematic review of clinical practice guidelines. Methodological quality of these guidelines was assessed using the Appraisal of Guidelines for Research and Education (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations. Electronic databases (MEDLINE, EMBASE, PsycINFO) and guideline registries were searched from inception to December 2017. Thirty-eight guidelines were included. Nineteen focused on patients receiving medical immunosuppression, seven on transplantation, three on patients with HIV and nine were generalised across all at risk populations. Most guidelines (n=32, 84%) used a systematic approach to identify and appraise the evidence. The methodological quality of the guidelines varied with the overall mean AGREE II scores ranging from 35% to 80%. Guidelines performed poorly in terms of editorial independence (average score 35%, range 0%-92%); however, most were robust in defining their scope and purpose (average score 80%, range 56%-100%). Guidelines recommended either or both the tuberculin skin test and the interferon gamma release assay for screening. Treatment of LTBI with isoniazid was consistently recommended. Clinical practice guidelines on LTBI vary in quality and scope. The recommendations for screening varied across guidelines, while recommendations for treatment were largely consistent. Improving the consistency and quality of guidelines may help to optimise the screening and management of LTBI for improved patient outcomes.


Goldilocks mastectomy for obese Japanese females with breast ptosis.
The Goldilocks mastectomy is a method that uses redundant mastectomy flap tissue alone to create a breast mound in female American patients with macromastia. Goldilocks mastectomy was performed for obese Japanese females with breast ptosis, and its indications were considered for Japanese female patients. This report presents the results of five patients who underwent Goldilocks mastectomy, including one with bilateral breast cancer. The average age of the patients was 72 years (range: 67-76 years). The body mass index (BMI) was more than 25 in all the cases. Four patients had invasive ductal carcinoma, and one patient had noninvasive ductal carcinoma of bilateral breasts. The cosmetic results were found to be good in two cases [a patient with bilateral breast cancer and a severely obese patient (BMI = 39)]. The cosmetic results in the other three cases were poor. Although the reconstructed breast size was small, this procedure resulted in better cosmetic results than what would be achieved with the usual method of mastectomy for Japanese patients with bilateral breast cancer and severely obese Japanese patients.


A Reconstructed Human Melanoma-in-Skin Model to Study Immune Modulatory and Angiogenic Mechanisms Facilitating Initial Melanoma Growth and Invasion.
Invasion, immune modulation, and angiogenesis are crucial in melanoma progression. Studies based on animals or two-dimensional cultures poorly recapitulate the tumor-microenvironmental cross-talk found in humans. This highlights a need for more physiological human models to better study melanoma features. Here, six melanoma cell lines (A375, COLO829, G361, MeWo, RPMI-7951, and SK-MEL-28) were used to generate an in vitro three-dimensional human melanoma-in-skin (Mel-RhS) model and were compared in terms of dermal invasion and immune modulatory and pro-angiogenic capabilities. A375 displayed the most invasive phenotype by clearly expanding into the dermal compartment, whereas COLO829, G361, MeWo, and SK-MEL-28 recapitulated to different extent the initial stages of melanoma invasion. No nest formation was observed for RPMI-7951. Notably, the integration of A375 and SK-MEL-28 cells into the model resulted in an increased secretion of immune modulatory factors (e.g., M-CSF, IL-10, and TGFβ) and pro-angiogenic factors (e.g., Flt-1 and VEGF). Mel-RhS-derived supernatants induced endothelial cell sprouting in vitro. In addition, observed A375-RhS tissue contraction was correlated to increased TGFβ release and α-SMA expression, all indicative of differentiation of fibroblasts into cancer-associated fibroblast-like cells and reminiscent of epithelial-to-mesenchymal transition, consistent with A375's most prominent invasive behavior. In conclusion, we successfully generated several Mel-RhS models mimicking different stages of melanoma progression, which can be further tailored for future studies to investigate individual aspects of the disease and serve as three-dimensional models to assess efficacy of therapeutic strategies.


Formation of systemic structural trace in rat kidneys after cold adaptation.
We studied the adaptive response of rats to cold exposure. It was found that the development of the adaptive response and formation of systemic structural trace in the kidneys occurred within 1 month after the start of adaptation. Activation of proliferative processes in the kidneys was accompanied by an increase in intracellular calcium concentration.


Correction: Inhibition of H3K9 Methyltransferase G9a Repressed Cell Proliferation and Induced Autophagy in Neuroblastoma Cells.
[This corrects the article DOI: 10.1371/journal.pone.0106962.].


Dislocation of a polyethylene insert in an infected knee joint after a Triathlon total knee arthroplasty.
This report presents the case of a 57-year-old male patient who underwent a total knee arthroplasty (TKA) using an uncemented Triathlon system and subsequently went on to develop a prosthetic joint infection (PJI) with eventual polyethylene insert dislocation. This report presents the clinical, radiological and surgical findings of the insert dislocation on the background of PJI and explores this rare complication of TKA by providing a summary of the literature on this topic.