Battery incidents and batterers in a maximum security hospital.
Of 638 reported assaultive and disruptive incidents in 1979 in a maximum security hospital, 221 (34.6%) were batteries. Whether an incident was a battery or not was a function of time and location. Preludes to battery were noted by staff in only 23.1% of cases and were high-frequency behaviors with low predictive value. Impact and injury to patients and officers occurred through both batteries themselves and efforts to subdue the batterer. With length of hospitalization controlled, the distributions of preadmission criminal charges were not significantly different between batterers and controls. Policies that alter patterns in the timing and location of interaction among patients and in the response of officers or other personnel to batteries in progress offer promise for reducing incident and injury rates.


Expansion for the Brachylophosaurus canadensis Collagen I Sequence and Additional Evidence of the Preservation of Cretaceous Protein.
Sequence data from biomolecules such as DNA and proteins, which provide critical information for evolutionary studies, have been assumed to be forever outside the reach of dinosaur paleontology. Proteins, which are predicted to have greater longevity than DNA, have been recovered from two nonavian dinosaurs, but these results remain controversial. For proteomic data derived from extinct Mesozoic organisms to reach their greatest potential for investigating questions of phylogeny and paleobiology, it must be shown that peptide sequences can be reliably and reproducibly obtained from fossils and that fragmentary sequences for ancient proteins can be increasingly expanded. To test the hypothesis that peptides can be repeatedly detected and validated from fossil tissues many millions of years old, we applied updated extraction methodology, high-resolution mass spectrometry, and bioinformatics analyses on a Brachylophosaurus canadensis specimen (MOR 2598) from which collagen I peptides were recovered in 2009. We recovered eight peptide sequences of collagen I: two identical to peptides recovered in 2009 and six new peptides. Phylogenetic analyses place the recovered sequences within basal archosauria. When only the new sequences are considered, B. canadensis is grouped more closely to crocodylians, but when all sequences (current and those reported in 2009) are analyzed, B. canadensis is placed more closely to basal birds. The data robustly support the hypothesis of an endogenous origin for these peptides, confirm the idea that peptides can survive in specimens tens of millions of years old, and bolster the validity of the 2009 study. Furthermore, the new data expand the coverage of B. canadensis collagen I (a 33.6% increase in collagen I alpha 1 and 116.7% in alpha 2). Finally, this study demonstrates the importance of reexamining previously studied specimens with updated methods and instrumentation, as we obtained roughly the same amount of sequence data as the previous study with substantially less sample material. Data are available via ProteomeXchange with identifier PXD005087.


Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response.
The epithelial cells in an adult woman's breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells.


12-Year Use of a Digital Reference Library (VitalBook) at a U.S. Dental School: Students' and Alumni Perceptions.
Digital textbooks are being used to reduce production and storage costs of printed copies, enhance usage, and include search capabilities, but the use of digital texts is not universally accepted. In 2001, the New York University College of Dentistry introduced a digital reference library, the VitalBook. Beginning in 2005, the college annually surveyed senior students and, from 2012, also surveyed alumni on their opinions and extent of use of the VitalBook. The aim of this study was to evaluate 12 years of students' perspectives and three years of alumni perspectives on the value of the VitalBook to their dental educational experience. Students were asked how frequently they used the VitalBook, if it was a good investment, if they would use it after graduation, and if they would recommend it to others. Alumni were asked the last three questions. This study reports the results from 4,105 students over 12 years (average response rate 95.3%) and 184 alumni over three years (average response rate 17.4%). The results indicated that students used the VitalBook on average 24% of their study time, but they were split regarding the other questions. The majority opinion in 2005 was negative on all questions. These opinions shifted to become more favorable to a peak in 2010, but declined since then to a more negative overall view of the VitalBook. A split opinion among students continued through 2016, with fewer recommending it although more considered it a good investment with plans to use it after graduation. Alumni mirrored their responses as students. These results suggest that, as more flexible and dynamic digitized reference systems emerge, the use of student-paid traditional digitized textbooks may become an even less favored choice.


Pre-reproductive stress and fluoxetine treatment in rats affect offspring A-to-I RNA editing, gene expression and social behavior.
Adenosine to inosine RNA editing is an epigenetic process that entails site-specific modifications in double-stranded RNA molecules, catalyzed by adenosine deaminases acting on RNA (ADARs). Using the multiplex microfluidic PCR and deep sequencing technique, we recently showed that exposing adolescent female rats to chronic unpredictable stress before reproduction affects editing in the prefrontal cortex and amygdala of their newborn offspring, particularly at the serotonin receptor 5-HT2c (encoded by Htr2c). Here, we used the same technique to determine whether post-stress, pre-reproductive maternal treatment with fluoxetine (5 mg/kg, 7 days) reverses the effects of stress on editing. We also examined the mRNA expression of ADAR enzymes in these regions, and asked whether social behavior in adult offspring would be altered by maternal exposure to stress and/or fluoxetine. Maternal treatment with fluoxetine altered Htr2c editing in offspring amygdala at birth, enhanced the expression of Htr2c mRNA and RNA editing enzymes in the prefrontal cortex, and reversed the effects of pre-reproductive stress on Htr2c editing in this region. Furthermore, maternal fluoxetine treatment enhanced differences in editing of glutamate receptors between offspring of control and stress-exposed rats, and led to enhanced social preference in adult offspring. Our findings indicate that pre-gestational fluoxetine treatment affects patterns of RNA editing and editing enzyme expression in neonatal offspring brain in a region-specific manner, in interaction with pre-reproductive stress. Overall, these findings imply that fluoxetine treatment affects serotonergic signaling in offspring brain even when treatment is discontinued before gestation, and its effects may depend upon prior exposure to stress.


Evaluation of substance P as a biomarker for pain in equine colic.
Equine colic is an important condition associated with acute abdominal pain and one of the leading causes of death in horses. As such, objectively evaluating pain is of interest for attending veterinarians. Pain scales for assessment are present, but no single pain-specific biomarker has been reported. The aim of this study was to determine if substance P (SP) could be a reliable biomarker to reflect pain and serve as a parameter to predict outcome in equine colic. The hypothesis was that horses displaying severe colic signs present with higher values of SP in contrast to those with mild colic signs. Thirty warmblood horses, aged between 3 and 20 years were recruited; evenly distributed (10 horses each) in three colic groups (mild, moderate, severe). To classify the colic signs, the horses were graded by the Equine Acute Abdominal Pain Scale (EAAPS). Clinical examination and EAAPS were performed at arrival in the hospital. Blood samples were collected four times in hourly intervals commencing from arrival. For comparison, already established parameters for prognosticating equine colic (heart rate, serum cortisol, and blood lactate concentration) were also measured. The assumption of increasing SP concentrations along with pain could not be confirmed. SP did not show any association with heart rate, cortisol, lactate, or EAAPS. Whereas the established parameters increased according to the EAAPS, SP remained stable in individual horses regardless of clinical signs, treatment, and disease progression. Consequently, SP was not a reliable parameter to reflect painful conditions or to predict outcome in equine colic.


Metabolism of the tobacco specific nitrosamines, N'-nitrosonornicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone.
The metabolism, in the F-344 rat, of the tobacco-specific carcinogens, N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studied. NNN was hydroxylated at each position of the pyrrolidine ring; 2'-hydroxylation gave 4-hydroxy-1-(3-pyridyl)-1-butanone in vitro and the corresponding acid in vivo, 3'-hydroxylation gave 3'-hydroxyNNN, 4'-hydroxylation gave 4'-hydroxy-NNN and 5'-hydroxylation gave 4-hydroxy-4-(3-pyridyl)butanal (in vitro) and 4-hydroxy-4-(3-pyridyl) butanoic acid (in vivo). The principle ring hydroxylation in the untreated F-344 rat was 5'-hydroxylation. Pyridine N-oxidation was also observed, giving NNN-1-N-oxide as a major metabolite. The principle urinary metabolites of NNN were formed by 5'-hydroxylation and pyridine-N-oxidation. For NNK, a major process was reduction of the carbonyl to give 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanol. alpha-Hydroxylation of both the N-methyl and N-methylene groups was also observed, as was formation of NNK-N-oxide in vitro and in vivo.


The Breadth of Viruses in Human Semen.
Zika virus RNA is frequently detected in the semen of men after Zika virus infection. To learn more about persistence of viruses in genital fluids, we searched PubMed for relevant articles. We found evidence that 27 viruses, across a broad range of virus families, can be found in human semen.


Effects of saliva or serum coating on adherence of Streptococcus oralis strains to titanium.
The use of dental implants to treat tooth loss has increased rapidly over recent years. 'Smooth' implants showing high long-term success rates have successively been replaced by implants with rougher surfaces, designed to stimulate rapid osseointegration and promote tissue healing. If exposed in the oral cavity, rougher surfaces may promote bacterial adhesion leading to formation of microbial biofilms which can induce peri-implant inflammation. Streptococcus oralis is an early colonizer of oral surfaces and has been recovered from titanium surfaces in vivo. The purpose of this study was to examine the adherence of clinical strains of S. oralis to titanium with smooth or moderately rough surface topography and to determine the effect of a saliva- or serum-derived coating on this process. Adherence was studied using a flow-cell system with confocal laser scanning microscopy, while putative adhesins were analysed using proteomics of bacterial cell wall proteins. This showed that adherence to moderately rough surfaces was greater than to smooth surfaces. Serum did not promote binding of any of the studied S. oralis strains to titanium, whereas a saliva coating increased adherence in two of three strains tested. The higher level of adherence to the moderately rough surfaces was maintained even in the presence of a saliva coating. The S. oralis strains that bound to saliva expressed an LPXTG-linked protein which was not present in the non-adherent strain. Thus strains of S. oralis differ in their capacity to bind to saliva-coated titanium and we propose that this is due to differential expression of a novel adhesin.


Transient Production of Recombinant Pharmaceutical Proteins in Plants: Evolution and Perspectives.
During the last two decades, the production of pharmaceutical proteins in plants evolved from proof of concept to established technology adopted by several biotechnological companies. This progress is particularly based on intensive research starting stable genetic transformation and moving to transient expression. Due to its advantages in yield and speed of protein production transient expression platforms became the leading plant-based manufacturing technology. Current transient expression methods rely on Agrobacteriummediated delivery of expression vectors into plant cells. In recent years, great advances have been made in the improvement of expression vectors, host cell engineering as well as in the development of commercial manufacturing processes. Several GMP-certified large-scale production facilities exist around the world to utilize agroinfiltration method. A number of pharmaceutical proteins produced by transient expression are currently in clinical development. The great potential of transient expression platform in respect to rapid response to emerging pandemics was demonstrated by the production of experimental ZMapp antibodies against Ebola virus as well as influenza vaccines. This review is focused on current design, status and future perspectives of plant transient expression system for the production of biopharmaceutical proteins.


A model of Na-K-2Cl cotransport based on ordered ion binding and glide symmetry.
In the duck red blood cell, Na-K-2Cl cotransport exhibits two modes of ion movement: net cotransport and obligate cation exchange. In high-K cells, the predominant exchange is K/K (or K/Rb). In high-Na cells, it becomes Na/Na (or Na/Li). Both represent partial reactions in which a fully loaded carrier releases part of its cargo, rebinds fresh ions, and returns back across the membrane fully loaded. Net cotransport occurs when the carrier unloads completely and returns empty. This mode has a fixed stoichiometry of 1Na:1K:2Cl under all conditions tested. The ion requirements of the two exchanges differ: K/K exchange requires only K and Cl outside but all three ions inside. Na/Na exchange requires all three ions outside but only Na inside. We propose a simple model in which the carrier can only move when either fully loaded or completely empty and in which the ions bind in a strictly ordered sequence. For example, externally, a Na binds first and then a Cl, followed by a K and a second Cl. Internally, the first on is the first off (glide symmetry), so the Na is released first and then the first Cl, followed by the K and finally by the second Cl. Only then can the empty form return to the outside to start a new cycle.


Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population.
Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.


Visual-Spatial and Verbal Remote Association: An fMRI Study.
Although idea connections at verbal and conceptual levels have been explored by remote associates tests, the visual-spatial level is much less researched. This study investigated the visual-spatial ability via Chinese Radical Remote Associates Test (CRRAT), wherein respondents consider the positions of the stimulus and target Chinese radicals. Chinese Compound Remote Associates Test (CCRAT) questions also feature stimuli of a single Chinese character; therefore, it was adopted for comparison to distinguish the roles played by verbal and visual-spatial associations in a remote associative process. Thirty-six adults responded to CRRAT and CCRAT; their brain activities were analyzed. Upon excluding the influence of age, verbal comprehension, and working memory, it was found that the caudate, posterior cingulate cortex, postcentral gyrus, and medial frontal gyrus were activated when the respondents answered CCRAT, but only the caudate showed significant activation when they answered CRRAT. The Chinese radical remote association minus the Chinese compound remote association showed that the middle frontal gyrus, inferior parietal lobule, and precuneus demonstrated significant activation. Therefore, this study demonstrated differences in brain mechanisms between visual-spatial and verbal remote associations.


Changes in global electrical heterogeneity associated with dofetilide, quinidine, ranolazine, and verapamil.
Electrocardiographic (ECG) markers of antiarrhythmic drug (AAD) activity could be used to optimize efficacy and minimize toxicity. Vectorcardiographic global electrical heterogeneity (GEH) is associated with ventricular arrhythmias and sudden death, but it is unclear how GEH measurements change in response to AADs. The purpose of this study was to characterize acute effects of AADs on GEH measurements. We analyzed double-blind placebo-controlled trial data from healthy volunteers given 1 dose of placebo, dofetilide, quinidine, ranolazine, or verapamil on subsequent visits. Serial ECGs and plasma drug concentrations were collected. Vectorcardiographic GEH parameters (spatial ventricular gradient [SVG], spatial QRST angle, sum absolute QRST integral, and SVG-QRS peak angle) were measured. Placebo-corrected change from baseline was regressed on drug concentration stratified by sex using linear mixed effects models. Among 22 persons (11 (50%) male median age 27 ± 5 years), 5232 ECGs were analyzed. Dofetilide and quinidine were associated with significant changes in more GEH parameters (5) compared with verapamil (2) and ranolazine (1). The most notable change occurred in SVG azimuth, with largest changes (degrees per unit normalized drug concentration) in dofetilide (6.1; 95% confidence interval [CI] 4.2-8.0) and quinidine (9.4; 95% CI 6.7-12.0), and smaller effects in verapamil (4.4; 95% CI 2.9-5.9) and ranolazine (5.4; 95% CI 3.5-7.3). AAD-induced GEH changes significantly differed in men and women. AADs change GEH measurements. These changes, which differ by sex, are likely driven by alterations in ion channel function and dispersion of depolarization or repolarization. GEH measurement may allow early assessment of favorable or adverse AAD effects.


Ammonia determines transcriptional profile of microorganisms in anaerobic digestion.
Anaerobic digestion is important for the management of livestock manure with high ammonia level. Although ammonia effects on anaerobic digestion have been comprehensively studied, the molecular mechanism underlying ammonia inhibition still remains elusive. In this study, based on metatranscriptomic analysis, the transcriptional profile of microbial community in anaerobic digestion under low (1500mgL-1) and high NH4+ (5000mgL-1) concentrations, respectively, were revealed. The results showed that high NH4+ concentrations significantly inhibited methane production but facilitated the accumulations of volatile fatty acids. The expression of methanogenic pathway was significantly inhibited by high NH4+ concentration but most of the other pathways were not significantly affected. Furthermore, the expressions of methanogenic genes which encode acetyl-CoA decarbonylase and methyl-coenzyme M reductase were significantly inhibited by high NH4+ concentration. The inhibition of the co-expressions of the genes which encode acetyl-CoA decarbonylase was observed. Some genes involved in the pathways of aminoacyl-tRNA biosynthesis and ribosome were highly expressed under high NH4+ concentration. Consequently, the ammonia inhibition on anaerobic digestion mainly focused on methanogenic process by suppressing the expressions of genes which encode acetyl-CoA decarbonylase and methyl-coenzyme M reductase. This study improved the accuracy and depth of understanding ammonia inhibition on anaerobic digestion.


Short-stay rural and remote placements in dental education, an effective model for rural exposure: a review of eight-year experience in Western Australia.
The increase in demand for dental care over the next 10 years is expected to outstrip the supply of dental visits in Australia, resulting in an ongoing shortage of dental practitioners. As trends in medicine have shown, the greatest effect will be felt in rural and remote regions, where an undersupply of dentists already exists. It is clearly evident that it is important to provide strategies that will increase the recruitment and retention of practitioners in rural and remote areas. Previous research suggested an increased likelihood for health graduates to choose rural practice if they have a rural background, or were exposed to rural practice during their education. Short-stay (three to four weeks) placements for final-year dental students has been part of dental education in Western Australia for near on a decade. This paper reflects on the experiences gained from managing this placement program. Short-stay placements are a quality learning initiative but need a high level of planning and a clear vision to be effective. The key factors in ensuring sustainable, student centred learning is driven through a small core group of staff who have strong direct links with rural and remote communities, students and support providers. The integration of service, education and research goals have played a critical role in sustaining placements. The philosophy underpinning the rural placements needs to be clearly articulated and applied effectively in each step of their implementation and a highly focused customer-service driven implementation is required to make short-stay rural and remote placements effective.


Ecology and Life Cycle Patterns of Echinococcus Species.
The genus Echinococcus is composed of eight generally recognized species and one genotypic cluster (Echinococcus canadensis cluster) that may in future be resolved into one to three species. For each species, we review existing information on transmission routes and life cycles in different geographical contexts and - where available - include basic biological information of parasites and hosts (e.g., susceptibility of host species). While some Echinococcus spp. are transmitted in life cycles that involve predominantly domestic animals (e.g., dog - livestock cycles), others are wildlife parasites that do or do not interact with domestic transmission. In many cases, life cycle patterns of the same parasite species differ according to geography. Simple life cycles contrast with transmission patterns that are highly complex, involving multihost systems that may include both domestic and wild mammals. Wildlife transmission may be primary or secondary, i.e., resulting from spillovers from domestic animals. For most of the species and regions, existing information does not yet permit a conclusive description of transmission systems. Such data, however, would be highly relevant, e.g., for anticipation of geographical changes of the presence and frequency of these parasites in a warming world, or for initiating evidence-based control strategies.


Clinician-Created Video Education for Patients With AF: A Randomized Clinical Trial.
Patient education is a critical aspect of atrial fibrillation (AF) management. However, there is limited time to provide effective patient education during routine care, and resources available online are of variable quality. To determine whether clinician-led creation of video-based AF education is feasible and improves knowledge of AF. This single-center randomized clinical trial was conducted between 2020 and 2022. Outcomes were assessed prior to their clinic visit and 2 and 90 days after the visit by blinded assessors. Participants included adults with AF and congestive heart failure, hypertension, age at least 75 years (doubled), diabetes, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and sex category scores of 1 or greater presenting for routine care at publicly funded outpatient cardiology clinics within a tertiary teaching hospital. Individuals too unwell to participate or with limited English were excluded. Data were assessed as intention to treat and analyzed from December 2022 to October 2023. Intervention participants viewed a series of 4 videos designed and narrated by clinicians that aimed to improve understanding of AF pathophysiology, clinical presentation, diagnosis, and management. After viewing the videos, participants received weekly email links to review the videos. The control group received usual care. The prospectively selected primary outcome was AF knowledge at 90 days, measured by the validated Jessa Atrial Fibrillation Knowledge Questionnaire (JAFKQ). Among 657 individuals screened, 208 adults with AF were randomized (mean [SD] age, 65.0 [12.2] years; 133 [65.2%] male) and included in analysis. Participants were randomized 1-to-1, with 104 participants in the control group and 104 participants in the video intervention group. At 90 days after the baseline clinic visit, intervention participants were more likely to correctly answer JAFKQ questions than control participants (odds ratio [OR], 1.23 [95% CI, 1.01-1.49]). The difference was greater in participants who remotely accessed videos on 3 or more occasions during the study (OR, 1.46 [95% CI, 1.14-1.88]). In this randomized clinical trial of patients with AF, remotely delivered, clinician-created video education improved medium-term AF knowledge beyond usual care of standard in-clinic education. The improvement demonstrated in this study provides support for the implementation of clinician-created educational resources across the care continuum. Further work is needed to assess for impact on clinical outcomes. anzctr.org.au Identifier: ANZCTRN12620000729921.


Genovo: de novo assembly for metagenomes.
Next-generation sequencing technologies produce a large number of noisy reads from the DNA in a sample. Metagenomics and population sequencing aim to recover the genomic sequences of the species in the sample, which could be of high diversity. Methods geared towards single sequence reconstruction are not sensitive enough when applied in this setting. We introduce a generative probabilistic model of read generation from environmental samples and present Genovo, a novel de novo sequence assembler that discovers likely sequence reconstructions under the model. A nonparametric prior accounts for the unknown number of genomes in the sample. Inference is performed by applying a series of hill-climbing steps iteratively until convergence. We compare the performance of Genovo to three other short read assembly programs in a series of synthetic experiments and across nine metagenomic datasets created using the 454 platform, the largest of which has 311k reads. Genovo's reconstructions cover more bases and recover more genes than the other methods, even for low-abundance sequences, and yield a higher assembly score. Supplementary Material is available at www.liebertoinline.com/cmb .


CROI 2023: Epidemiology, Diagnosis, and Management of MPox.
The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) emphasized emerging infectious diseases such as COVID-19 and mpox. Despite emerging from countries in which it was endemic only 9 months before the conference, mpox was well covered, with more than 60 presentations addressing various topics. There was a focus on the rapid development and implementation of tests to reduce the time to diagnosis, as well as multiplex panels to increase the accuracy of differential diagnosis. Presenters also highlighted the ability to diagnose mpox from multiple compartments, such as with rectal and pharyngeal swabs, and provided crucial information on the duration of positivity that may impact isolation requirements. Clinical experiences were described, including risk factors for severe disease and syndemic management. High rates of concomitant sexually transmitted infection (STI) were reported. Finally, prevention was a key topic, with presenters pointing to the contributions of individual behavioral changes and vaccine efficacy to reducing new cases.


Ultrasonography of normal and abnormal appendix in children.
Appendicitis is the most common acute surgical emergency of childhood. Since the original report by Puylaert in 1986, the use of ultrasonography in the diagnosis of appendicitis has been the subject of considerable study. Among the reported diagnostic criteria, the maximal outer diameter (MOD) of the appendix is accepted as the one of the most reliable criteria used to differentiate between a normal appendix and acute appendicitis. However, MOD measurement is subject to inaccuracies because luminal distention by non-compressible, non-inflammatory material such as fecal material, or increased maximal mural thickness due to reactive mucosal lymphoid hyperplasia, or a medical cause due to a generalized gastrointestinal disease, such as Crohn's disease, can cause the measurement to exceed the upper limits of normality. The aim of this article is to introduce the spectrum of ultrasonographic findings in the normal and abnormal appendix and eventually to reduce unnecessary surgery in children.


Non-invasive brain stimulation for smoking cessation: a systematic review and meta-analysis.
Non-invasive brain stimulation (NIBS) methods have showed promising results for the treatment of tobacco use disorder, but little is known about the efficacy of NIBS on sustained tobacco abstinence. We aimed to assess its effectiveness for long-term smoking cessation. Systematic review and meta-analysis of randomized controlled trials (RCT). PubMed, Cochrane library, Embase, PsycINFO and clinical trials registries were systematically searched for relevant studies up to May 2021. Relevant studies included adult smokers seeking smoking cessation, included in an RCT using NIBS [specifically repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)], and with follow-up of more than 4 weeks. There were no restrictions on location. Abstinence rates in the active NIBS groups were compared with abstinence rates in sham NIBS or in usual treatment groups, from 4 weeks to 12 months following the quit attempt. Smoking abstinence was measured on an intention-to-treat basis and we used risk ratios (RRs) as measures of effect size. Seven studies were included (n = 699 patients). In all included studies, the control groups were receiving sham NIBS and only data from 3 to 6 months were analysable. By pooling the seven included studies, the RR of sustained abstinence of any form of NIBS relative to sham NIBS was 2.39 [95% confidence interval (CI) = 1.26-4.55; I2 = 40%]. Subgroup analyses found that the RR was even higher when excitatory rTMS was used on the left dorsolateral prefrontal cortex (RR = 4.34; 95% CI = 1.69-11.18; I2 = 0%) or when using deep rTMS targeting the lateral prefrontal cortex and insula bilaterally (RR = 4.64; 95% CI = 1.61-13.39; I2 = 0%). A high risk of bias was found in four included studies. We also determined, using grades of recommendation, assessment, development and evaluation, that overall there was a low level of confidence in the results. Non-invasive brain stimulation (NIBS) may improve smoking abstinence rates from 3 to 6 months after quitting smoking, compared with sham NIBS or usual treatment.


[Effect of adrenocorticotropin on progesterone, 20alpha-OH- progesterone and adenosine 3',5'-monophosphate in isolated luteal cells from rat ovaries].
The present investigation was designed to study the effect of synthetic ACTH on the synthesis of progesterone, 20 alpha-OH-progesterone and adenosine-3', 5'-monophosphate (cAMP) in isolated luteal cells. Experiments were conducted on rats from three groups. Group I: PMS primed immature rats. Group II: PMS plus hCG primed immature rats. Group III: pregnant rats. Luteal cells were isolated by the Kumai Method (7) using a sucrose density gradient after digestion with trypsin and collagenase. Luteal cells were divided into three fractions; S-1, S-2 and S-3. Following an 18 hr-incubation of S-1 cells of day 7 after PMS injection, a significant increase in progesterone release by ACTH lasted from 6 to 18 hr, whereas 20 alpha-OH-progesterone decreased significantly by ACTH from 8 to 18 hr. There were no differences in progesterone and 20 alpha-OH-progesterone releases from S-2 cells of day 7 between media with and without ACTH. Progesterone release without ACTH reached the peak on day 7 in Group I and on day 6 in Group II. ACTH stimulated progesterone and inhibited 20 alpha-OH-progesterone releases in Groups I and II. The maximum effect of ACTH in both Groups was noted on days 6 and 7. There were no differences in the Effective Dose (ED50) and the Inhibitory Dose (ID50) of ACTH between Group I and Group II. In Group III, releases of progesterone and 20 alpha-OH-progesterone from S-1 cells to media with or without ACTH decreased remarkably after 11 days of gestation. On days, 3, 5 and 8 of gestation, a significant increase in progesterone release from S-1 cells was noted by the ACTH addition. 20 alpha-OH-progesterone release from S-1 cells to media with or without ACTH decreased as the pregnancy advanced. Total cAMP of intra- and extra-cellular S-1 cells (Group II) on day 5 after PMS injection was assayed. ACTH induced an increase in intracellular cAMP. The present results indicate the following: (1) In Group I and Group II, progesterone release increased with the age of the luteal cells and ACTH dose. In Group III, ACTH stimulated progesterone release in a dose-dependent manner in early gestation. (2) 20 alpha-OH-progesterone release decreased by ACTH dose in Group I and Group II, and decreased in Group III as the gestation advanced. (3) Intracellular cAMP increased by ACTH in Group II.


Completely intracorporeal anastomosis in robotic left colonic and rectal surgery: technique and 30-day outcomes.
As robotic surgery continues to disseminate into the field of colon and rectal surgery, there is a growing interest in the utilization of intracorporeal anastomosis to potentially improve surgical outcomes. The purpoe of this study was to compare feasibility, safety, and short-term outcomes of robotic sigmoid and low anterior resections performed with completely intracorporeal anastomosis (CICA) technique to the traditional extracorporeal assisted anastomosis (ECAA) technique. Consecutive series of patients who underwent elective robotic sigmoid or low anterior resections for benign or malignant disease utilizes either CICA or ECAA between August 2017 and November 2019. Surgical complications were assessed until 30 postoperative days and compared between the two groups. A total of 160 patients were identified; 73 (45.6%) in the CICA group and 87 (54.4%) in the ECAA group. Most of the procedures were performed for malignancy (76%). Estimated blood loss was lower in the CICA group (80.7 mL vs. 110.2 mL; p = 0.048), while operative times were longer (5.9 ± SD hours vs. 4.9 ± SD hours; p = < 0.001). Overall conversion rate was 1.9%, with no conversions in the CICA group. Overall complications occurred in 54 patients (33.8%) with 13 (8.3%) representing major complications. There were no significant differences in 30 day outcomes between the two groups. This study demonstrates the feasibility and safety of robotic sigmoid and low anterior resections with CICA. Outcomes for robotic sigmoid and low anterior resections are encouraging regardless of anastomotic technique (CICA vs ECAA).


Prediction of cognitive and motor outcome of preterm infants based on automatic quantitative descriptors from neonatal MR brain images.
This study investigates the predictive ability of automatic quantitative brain MRI descriptors for the identification of infants with low cognitive and/or motor outcome at 2-3 years chronological age. MR brain images of 173 patients were acquired at 30 weeks postmenstrual age (PMA) (n = 86) and 40 weeks PMA (n = 153) between 2008 and 2013. Eight tissue volumes and measures of cortical morphology were automatically computed. A support vector machine classifier was employed to identify infants who exhibit low cognitive and/or motor outcome (<85) at 2-3 years chronological age as assessed by the Bayley scales. Based on the images acquired at 30 weeks PMA, the automatic identification resulted in an area under the receiver operation characteristic curve (AUC) of 0.78 for low cognitive outcome, and an AUC of 0.80 for low motor outcome. Identification based on the change of the descriptors between 30 and 40 weeks PMA (n = 66) resulted in an AUC of 0.80 for low cognitive outcome and an AUC of 0.85 for low motor outcome. This study provides evidence of the feasibility of identification of preterm infants at risk of cognitive and motor impairments based on descriptors automatically computed from images acquired at 30 and 40 weeks PMA.


Revisiting the concept of the 'problem young driver' within the context of the 'young driver problem': who are they?
For decades there have been two young driver concepts: the 'young driver problem' where the driver cohort represents a key problem for road safety; and the 'problem young driver' where a sub-sample of drivers represents the greatest road safety problem. Given difficulties associated with identifying and then modifying the behaviour of the latter group, broad countermeasures such as graduated driver licensing (GDL) have generally been relied upon to address the young driver problem. GDL evaluations reveal general road safety benefits for young drivers, yet they continue to be overrepresented in fatality and injury statistics. Therefore it is timely for researchers to revisit the 'problem young driver' concept to assess its potential countermeasure implications. This is particularly relevant within the context of broader countermeasures that have been designed to address the 'young driver problem' Personal characteristics, behaviours and attitudes of 378 Queensland novice drivers aged 17-25 years were explored during their pre-, Learner and Provisional 1 (intermediate) licence as part of a larger longitudinal project. Self-reported risky driving was measured by the Behaviour of Young Novice Drivers Scale (BYNDS), and five subscale scores were used to cluster the drivers into three groups (high risk n=49, medium risk n=163, low risk n=166). High risk 'problem young drivers' were characterised by greater self-reported pre-Licence driving, unsupervised Learner driving, and speeding, driving errors, risky driving exposure, crash involvement, and offence detection during the Provisional period. Medium risk drivers were also characterised by more risky road use than the low risk group. Interestingly problem young drivers appear to have some insight into their high-risk driving, since they report significantly greater intentions to bend road rules in future driving. The results suggest that tailored intervention efforts may need to target problem young drivers within the context of broad countermeasures such as GDL which address the young driver problem in general. Experiences such as crash-involvement could be used to identify these drivers as a preintervention screening measure.


Negative correlation between male allocation and rate of self-fertilization in a hermaphroditic animal.
Sex-allocation theory predicts that the evolution of increased rates of self-fertilization should be accompanied by decreased allocation to male reproduction (sperm production and broadcast). This prediction has found support in plants but has not previously been tested in animals, which, in contrast to biotically pollinated plants, are free of complications associated with incorporating the costs of attractive structures such as petals. Here we report rates of self-fertilization as well as proportional allocation to male reproductive tissues within populations of the simultaneous hermaphrodite Utterbackia imbecillis, a freshwater mussel. Individuals from populations with higher selfing rates devoted a lower proportion of reproductive tissue to sperm production (correlation = -0.99), in support of theory.


Tracking the fate of pasta (T. Durum semolina) immunogenic proteins by in vitro simulated digestion.
The aim of the present study was to identify and characterize the celiacogenic/immunogenic proteins and peptides released during digestion of pasta (Triticum durum semolina). Cooked pasta was digested using a harmonized in vitro static model of oral-gastro-duodenal digestion. The course of pasta protein digestion was monitored by SDS-PAGE, and gluten proteins were specifically analyzed by Western blot using sera of celiac patients. Among the allergens, nonspecific lipid-transfer protein was highly resistant to gastro-duodenal hydrolysis, while other digestion-stable allergens such as α-amylase/trypsin inhibitors were not detected being totally released in the pasta cooking water. To simulate the final stage of intestinal degradation, the gastro-duodenal digesta were incubated with porcine jejunal brush-border membrane hydrolases. Sixty-one peptides surviving the brush-border membrane peptidases were identified by liquid chromatography-mass spectrometry, including several gluten-derived sequences encrypting different motifs responsible for the induction of celiac disease. These results provide new insights into the persistence of wheat-derived peptides during digestion of cooked pasta samples.


Evaluation of top-down mass spectrometry and ion-mobility spectroscopy as a means of mapping protein-binding motifs within heparin chains.
Identifying structural elements within heparin (as well as other glycosaminoglycan) chains that enable their interaction with a specific client protein remains a challenging task due to the high degree of both intra- and inter-chain heterogeneity exhibited by this polysaccharide. The new experimental approach explored in this work is based on the assumption that the heparin chain segments bound to the protein surface will be less prone to collision-induced dissociation (CID) in the gas phase compared to the chain regions that are not involved in binding. Facile removal of the unbound chain segments from the protein/heparin complex should allow the length and the number of sulfate groups within the protein-binding segment of the heparin chain to be determined by measuring the mass of the truncated heparin chain that remains bound to the protein. Conformational integrity of the heparin-binding interface on the protein surface in the course of CID is ensured by monitoring the evolution of collisional cross-section (CCS) of the protein/heparin complexes as a function of collisional energy. A dramatic increase in CCS signals the occurrence of large-scale conformational changes within the protein and identifies the energy threshold, beyond which relevant information on the protein-binding segments of heparin chains is unlikely to be obtained. Testing this approach using a 1 : 1 complex formed by a recombinant form of an acidic fibroblast growth factor (FGF-1) and a synthetic pentasaccharide GlcNS,6S-GlcA-GlcNS,3S,6S-IdoA2S-GlcNS,6S-Me as a model system indicated that a tri-saccharide fragment is the minimal-length FGF-binding segment. Extension of this approach to a decameric heparin chain (dp10) allowed meaningful binding data to be obtained for a 1 : 1 protein/dp10 complex, while the ions representing the higher stoichiometry complex (2 : 1) underwent dissociation via asymmetric charge partitioning without generating truncated heparin chains that remain bound to the protein.


Improving Disaster Readiness and the Response of Nurses in Saudi Arabia.
Nurses in Saudi Arabia face several challenges in all phases of disaster nursing, such as the infancy of the specialty and a lack of education, preparedness, research, and expertise in both the clinical field and in academics. Overcoming these challenges will help both nurses and the development of the specialty itself in aspects such as policies and procedures, education, and research. Thus, the aim of this study was to explore strategies for improving disaster nursing in Saudi Arabia. A cross-sectional study with a principal component analysis (PCA) was conducted to identify the factors affecting disaster nursing in Saudi Arabia. The sample of the study was Saudi Arabian nurses, as they are first-line responders in disasters and pandemics. From 800 distributed questionnaires, 569 completed questionnaires were returned, for a response rate of 71%. The findings of the PCA revealed two components that can be extracted from the data. The first is preparedness, which involves 13 items related to the actions that must be taken before a disaster occurs, with a loading range of 0.82 to 0.70. The second factor is the action taken after a disaster occurs, and there are seven items with a loading range of 0.83 to 0.73. For improved disaster nursing, it is essential to develop evaluation tools, create specific nursing legislation for disaster situations, provide personal protective equipment to nurses to minimize the risk of infection, and encourage nurses by appreciating their efforts to minimize their stress level during a disaster. It is also important to make sufficient supplies and equipment available to nurses during a disaster and provide them with psychological support while acknowledging the importance of contact with their families and friends.


Effect of soya protein on digestive enzymes, gut hormone and anti-soya antibody plasma levels in the preruminant calf.
The effect of a milk substitute diet containing concentrated soya protein on secretory functions of the abomasum and pancreas and on plasma concentrations of gut hormones and soya antibodies was studied. Sixteen calves aged 12-19 weeks were given a milk substitute in which a major part of the protein source was either soya concentrate (soya diet) or skim milk (control diet). The soya diet was prepared by hot aqueous ethanol extraction of soya bean meal to remove oligosaccharides and inactivate antigenic constituents. Circulatory IgG antibodies against soya proteins were found in all of the calves when they were 16 weeks of age. Their titres increased slightly between 16 and 19 weeks, irrespective of the diet. It seems unlikely that the presence of these antibodies was related specifically to the feeding of the soya concentrate. At slaughter the weight of the gastric mucosa and pancreas and quantities of pancreatic protein together with specific activities of trypsin and chymotrypsin were significantly lower (17, 20, 16, 30 and 36%, respectively) with the soya diet. The quantities of enzymes in the gastric mucosa or the specific activity of pancreatic amylase were not affected, whereas that of lipase increased by 26%. Total enzyme activities as well as units per kg live weight gave significant differences only for trypsin and chymotrypsin which were reduced by 43 and 38%, respectively. With the soya diet, fasting concentrations of gastric inhibitory peptide (GIP) and secretin in plasma samples were significantly lower (49 and 34%, respectively). Values of GIP were also lower (54%) 1 h after feeding. In contrast, postprandial values of cholecystokinin (CCK) were 1.4 times greater. No significant differences were found between the two diets for gastrin, vasoactive intestinal peptide (VIP), bovine pancreatic polypeptide (BPP), somatostatine and motilin. In general these observations could be explained, in part, by the more rapid passage of protein and fat from the abomasum to the duodenum following feeds containing soya concentrate. However, these differences in concentrations of gut hormones did not seem to be related to variations in the weights of gastric mucosa and pancreas or activities of pancreatic enzymes.


Cohort changes in active life expectancy in the U.S. elderly population: experience from the 1982-2004 National Long-Term Care Survey.
To understand declines in chronic disability prevalence in the U.S. elderly population, we examined cohort changes in active life expectancy, a health measure relating population disability and longevity dynamics. We computed active life expectancy and life expectancy using the six National Long-Term Care Surveys done from 1982 to 2004 and linked to continuous-time Medicare service data for the same time period by using a stochastic process model based on disability scores calculated using grade of membership analyses. We simultaneously estimated continuous-time disability dynamic and mortality functions to calculate life tables for specific disability states and for temporally changing mixtures of disability states. Disability dynamics, measured as changes in grade of membership scores, showed significant variation across two birth cohorts followed for 24 years. Disability dynamics and disability-specific hazard functions were significantly improved in the younger cohort (persons aged 65-74 in 1982). Our results, supporting the hypothesis of morbidity compression, indicate that younger cohorts of elderly persons are living longer in better health. The methods describe individual disability transitions and mortality and other factors associated with disability changes, making it possible to better evaluate interventions to promote future declines in disability.


Marital status as an independent prognostic factor in patients with glioblastoma: a population-based study.
This study was aimed to investigate the effects of marital status on overall survival (OS) and cancer-specific survival (CSS) in patients with glioblastoma (GBM) and to develop nomograms for predicting prognosis in GBM patients. All patients were selected from the Surveillance, Epidemiology, and End Results (SEER) cancer registry program. We used propensity score matching to balance the baseline characteristics of married and unmarried patients. The effects of marital status on OS and CSS were then assessed using Kaplan-Meier curves and Cox proportional hazard regression, and the magnitude of each factor was visualized in the form of forest maps. The impact of marriage on the survival of GBM patients was further explored by stratifying several demographic factors. Finally, the nomograms were constructed and verified based on Cox proportional risk regression model. 17,517 patients with GBM (11,818 married patients, 67.5%) were enrolled in the study cohort. After PSM, there were 5699 patients in both the married and unmarried groups. Multivariate Cox regression analysis showed that both married and single patients had better OS (Married: HR 0.824, 95% CI: 0.788-0.862, P <0.001; Single: HR 0.764, 95% CI: 0.722-0.808, P <0.001) and CSS (Married: HR 0.833, 95% CI: 0.796-0.872, P <0.001; Single: HR 0.761, 95% CI: 0.718-0.806, P <0.001) than divorced, separated, and widowed (DSW) patients. Marital status was an independent prognostic factor in patients with GBM. The nomograms constructed in this study could help medical professionals to provide personalized prognostic assessment and treatment decisions for patients with GBM.


Persistent Hypoxia After Blunt Thoracic Trauma due to Flail Tricuspid Valve Leaflet and Patent Foramen Ovale.
Structural cardiac injury after blunt trauma is uncommon but usually life-threatening. While tricuspid injury is very rare and potentially lethal, the right heart can accommodate larger volumes and higher pressures in acute tricuspid insufficiency and facilitate initial stabilization prior to definitive valvular repair. ECMO may be used to ameliorate resulting right heart failure. The traumatic force required to cause cardiac structural injury is also associated with pulmonary complications related to pneumothorax, hemothorax, effusion, acute pain secondary to rib fractures, and pulmonary contusions causing hypoxia. We present an unusual case of hypoxia in a trauma patient caused by acute tricuspid regurgitation with pre-existing patent foramen ovale.


Anti-Trypanosoma cruzi Potential of Vestitol Isolated from Lyophilized Red Propolis.
Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 μg/mL and 31.25 μg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.


Complex genetic and epigenetic regulation deviates gene expression from a unifying global transcriptional program.
Environmental or genetic perturbations lead to gene expression changes. While most analyses of these changes emphasize the presence of qualitative differences on just a few genes, we now know that changes are widespread. This large-scale variation has been linked to the exclusive influence of a global transcriptional program determined by the new physiological state of the cell. However, given the sophistication of eukaryotic regulation, we expect to have a complex architecture of specific control affecting this program. Here, we examine this architecture. Using data of Saccharomyces cerevisiae expression in different nutrient conditions, we first propose a five-sector genome partition, which integrates earlier models of resource allocation, as a framework to examine the deviations from the global control. In this scheme, we recognize invariant genes, whose regulation is dominated by physiology, specific genes, which substantially depart from it, and two additional classes that contain the frequently assumed growth-dependent genes. Whereas the invariant class shows a considerable absence of specific regulation, the rest is enriched by regulation at the level of transcription factors (TFs) and epigenetic modulators. We nevertheless find markedly different strategies in how these classes deviate. On the one hand, there are TFs that act in a unique way between partition constituents, and on the other, the action of chromatin modifiers is significantly diverse. The balance between regulatory strategies ultimately modulates the action of the general transcription machinery and therefore limits the possibility of establishing a unifying program of expression change at a genomic scale.


Photophysical studies on antimalarial drugs.
Most drugs used in the treatment of malaria produce phototoxic side effects in both the skin and the eye. Cutaneous and ocular effects that may be caused by light include changes in skin pigmentation, corneal opacity, cataract formation and other visual disturbances including irreversible retinal damage (retinopathy) leading to blindness. The mechanism for these reactions in humans is unknown. We irradiated a number of antimalarial drugs (amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine and quinacrine) with light (lambda > 300 nm) and conducted electron paramagnetic resonance (EPR) and laser flash photolysis studies to determine the possible active intermediates produced. Each antimalarial drug produced at least one EPR adduct with the spin-trap 5,5-dimethyl-1-pyrroline N-oxide in benzene: superoxide/hydroperoxyl adducts (chloroquine, mefloquine, quinacrine, amodiaquine and quinine), carbon-centered radical adducts (all but primaquine), or a nitrogen-centered radical adduct only (primaquine). In ethanol all drugs except primaquine produced some superoxide/hydroperoxyl adduct, with quinine, quinacrine, and hydroxychloroquine also producing the ethoxyl adduct. As detected with flash photolysis and steady-state techniques, mefloquine, quinine, amodiquine and a photoproduct of quinacrine produced singlet oxygen ([symbol: see text]delta = 0.38; [symbol: see text]delta = 0.36; [symbol: see text]delta = 0.011; [symbol: see text]delta = 0.013 in D2O, pD7), but only primaquine quenched singlet oxygen efficiently (2.6 x 10(8) M-1 s-1 in D2O, pD7). Because malaria is a disease most prevalent in regions of high light intensity, protective measures (clothing, sunblock, sunglasses or eye wraps) should be recommended when administering antimalarial drugs.


Immunosuppression-associated posterior reversible encephalopathy syndrome in an acute leukemia case.
Posterior reversible encephalopathy syndrome (PRES) was described in 1996. Herein, we aimed to report an immunosuppression- related PRES case. A 34-year-old woman was diagnosed as t-cell acute lymphoblastic leukemia and allogeneic hematopoietic stem cell transplantation (HSCT) was performed. Cyclosporine was given for GVHD prophylaxis in addition to the other routine medications of HSCT. She was hospitalized for acute renal failure and due to the possible contribution of acute renal failure cyclosporine was stopped. Tacrolimus was started for GVHD prophylaxis at a dose of 1 mg/day. However, fifteen days after the initiation of tacrolimus, blurred vision occurred in our patient. Petechial bleeding sites were detected in bilateral cerebral and cerebellar hemisphere by MR imaging. Tacrolimus dosage was reduced to 0.5 mg/day. She had hypertension which was difficult to control and followed-up in the intensive care unit. She had seizures. Control cranial MR resulted as diffusion limitation in bilateral cerebellar hemisphere, bilateral occipital and frontal-parietal regions with vasogenic edema findings; contrast involvement in left frontal-parietal and right cerebellar regions. She had vision loss and lethargy. Control cranial MR favored PRES syndrome secondary to immunosuppression. Hypertensive state was taken under control with antihypertensive treatment and all immunosuppressive agents were stopped. Two weeks later her clinical condition was slightly improved. MR test which was conducted 2 weeks after the diagnosis revealed the regression of PRES lesions. The characteristic signs on neuroimaging are the symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parietal- occipital regions. In conclusion, PRES rarely develops secondary to the immunosuppressive agents and the clinicians should suspect and promptly diagnose PRES which might cause otherwise serious irreversible clinical complications.


Identification and characterization of a porcine parvovirus nonstructural polypeptide.
Sera from porcine parvovirus (PPV)-infected swine fetuses immunoprecipitated and 84- to 86-kilodalton polypeptide in addition to the A and B virion structural proteins. This polypeptide, designated NS-1, was present in PPV-infected cell lysates but not in purified virions. Partial proteolysis mapping revealed that NS-1 was not related to the A and B viral structural proteins. All three proteins in infected cells were phosphorylated at serine residues, and NS-1 also contained phosphothreonine. From pulse-labeling experiments with either 32Pi or [35S]methionine, NS-1 was found to first appear 5 to 7 h postinfection, whereas the viral structural polypeptides were first synthesized 9 to 11 h postinfection. Pulse-chase experiments revealed that NS-1 initially appeared as an 84-kilodalton protein and was subsequently structurally modified to forms of slower electrophoretic mobilities. The time of appearance of NS-1 after virus infection coincided with the initiation of viral DNA synthesis, suggesting that this polypeptide (and the modified forms thereof) may be involved in PPV replication.


Self-assessment of independence in older people: First results from an open-access website for senior citizens and caregivers in France.
E-health initiatives on the Internet can be used to provide support to people with chronic diseases and to their caregivers. In 2014/2015, we created a free website called jesuisautonome.fr where older people, or their carers on their behalf, can assess their independence in daily living by filling out a simple questionnaire. To evaluate the interest of the public in websites of this kind, by analysing home care plans obtained via the self-assessment questionnaire. We also describe patterns of use and visitor behaviour. Over a period of 6 months, we analysed data from the website in terms of the basic characteristics of the user; the number of questionnaires completed; the main types of needs in terms of home support; and data from Google Analytics about the number of visitors, user behaviour and behaviour flow. During the 6-month study period, 439 visitors to the site either viewed, part-completed or fully completed the questionnaire. A total of 190 users completed the questionnaire. Seventy-one per cent of the completed questionnaires were from family caregivers, and 29% were from senior citizens. The mean age of those receiving care was 78 ± 10.46 years. Their main needs were for domiciliary care (29.3%). Data from Google Analytics showed about 420 visits per month. Approximately 7.5% completed a questionnaire, approximately 5.3% downloaded a home care plan and there was a bounce rate of about 62%. First results from this website tend to endorse its use as a means of making practical solutions available to caregivers and older people.


A dynamic leaching method for the assessment of trace metals released from hydraulic binders.
With respect to sustainable development, the leachability of trace metal from solid materials in contact with water has focused much attention over the years. Portland cements produced in industrial kilns generally contain from 10 to 300 mg/kg of trace metals. The behaviour of these endogenous metals has been, in this regard, the target of different leaching studies. Many of these researches concluded that heavy metals release are lower than analytical detection limits. Although satisfying from an environmental point of view, it induces a lack in the knowledge about the trace metals behavior during the leaching of cement based material. Accordingly, we designed the CTG-LEACHCRETE device, a dynamic leaching system (modified Soxhlet type) that overcomes this difficulty and allows long term monitoring. The experimental procedure is presented and preliminary results are discussed.


Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKCε, Stat3, and Epithelial-to-Mesenchymal Transition Markers.
Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.


"Telling me not to worry…" Hyperscanning and Neural Dynamics of Emotion Processing During Guided Imagery and Music.
To analyze how emotions and imagery are shared, processed and recognized in Guided Imagery and Music, we measured the brain activity of an experienced therapist ("Guide") and client ("Traveler") with dual-EEG in a real therapy session about potential death of family members. Synchronously with the EEG, the session was video-taped and then micro-analyzed. Four raters identified therapeutically important moments of interest (MOI) and no-interest (MONI) which were transcribed and annotated. Several indices of emotion- and imagery-related processing were analyzed: frontal and parietal alpha asymmetry, frontal midline theta, and occipital alpha activity. Session ratings showed overlaps across all raters, confirming the importance of these MOIs, which showed different cortical activity in visual areas compared to resting-state. MOI 1 was a pivotal moment including an important imagery with a message of hope from a close family member, while in the second MOI the Traveler sent a message to an unborn baby. Generally, results seemed to indicate that the emotions of Traveler and Guide during important moments were not positive, pleasurably or relaxed when compared to resting-state, confirming both were dealing with negative emotions and anxiety that had to be contained in the interpersonal process. However, the temporal dynamics of emotion-related markers suggested shifts in emotional valence and intensity during these important, personally meaningful moments; for example, during receiving the message of hope, an increase of frontal alpha asymmetry was observed, reflecting increased positive emotional processing. EEG source localization during the message suggested a peak activation in left middle temporal gyrus. Interestingly, peaks in emotional markers in the Guide partly paralleled the Traveler's peaks; for example, during the Guide's strong feeling of mutuality in MOI 2, the time series of frontal alpha asymmetries showed a significant cross-correlation, indicating similar emotional processing in Traveler and Guide. Investigating the moment-to-moment interaction in music therapy showed how asymmetry peaks align with the situated cognition of Traveler and Guide along the emotional contour of the music, representing the highs and lows during the therapy process. Combining dual-EEG with detailed audiovisual and qualitative data seems to be a promising approach for further research into music therapy.


The development of perineuronal nets around parvalbumin gabaergic neurons in the medial prefrontal cortex and basolateral amygdala of rats.
Perineuronal nets (PNNs) are extracellular matrix structures that preferentially surround mature GABAergic neurons that express the calcium-binding protein parvalbumin (PV). It has been suggested that aberrant PNN formation in humans may contribute to psychological disorders, many of which emerge during childhood and adolescence. The present experiment investigated the normative developmental trajectory of PNN formation in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in juvenile (P24), adolescent (P35-36), and adult (∼P70) rats. Dual-immunofluorescence staining revealed that there was a marked increase in the number of PNNs in both the prelimbic and infralimbic regions of the mPFC across the transition from the juvenile to adolescent period. Although there were no differences in the number of PV neurons across age groups, adolescent and adult rats had more PNNs surrounding PV neurons than juveniles. In contrast to the mPFC, juvenile and adolescent rats had similar total numbers of PNNs in the BLA, and total numbers of PNNs were even higher in adults in this region. In the BLA, adults had more PNNs around non-PV cells whereas the number of PV cells with PNNs did not differ across ages. However, expression patterns differed within subregions of the BLA such that adults had the most PNNs around both PV and non-PV cells in the lateral nucleus, with no age differences observed in the basal nucleus. These findings demonstrate that the juvenile to adolescent developmental period is an important time for the formation of prefrontal PNNs and the maturation of PV inhibitory neurons. (PsycINFO Database Record


White spot lesions: Does etching really matter?
The clinical significance of acid etching prior to orthodontic bonding is controversial. In the present study, we evaluated the effect of 15 seconds of acid etching on enamel demineralization. Twenty-seven human molars were sectioned and assigned to two groups. Under standardized conditions, the enamel surfaces were imaged using FluoreCam to obtain baseline data. Group 1 was etched using 37% phosphoric acid for 15 seconds, rinsed with water, and then imaged again; group 2 was only rinsed with water. Water rinse was collected for calcium chemical analysis using inductively-coupled plasma auger electron spectrometry. Both groups were subjected to 9 days of pH cycling, after which final FluoreCam images were obtained. Group 1 showed a significant increase in lesion area (P=.012), decrease in light intensity (P=.009), and decrease in impact (P=.007) after acid etching. The amount of calcium that leached out over the 15 seconds was 14 ppm ±2.4 (0.35 mmol/L±0.06). Following pH cycling, there was no statistically-significant between-group difference in overall enamel demineralization. Initial demineralization caused by 15 seconds of acid etching does not increase enamel susceptibility to further demineralization. This suggests that acid etching does not increase the risk of developing white spot lesions during orthodontics.


Evolution of ant-cultivar specialization and cultivar switching in Apterostigma fungus-growing ants.
Almost all of the more than 200 species of fungus-growing ants (Formicidae: Attini) cultivate litter-decomposing fungi in the family Lepiotaceae (Basidiomycota: Agaricales). The single exception to this rule is a subgroup of ant species within the lower attine genus Apterostigma, which cultivate pterulaceous fungi distantly related to the Lepiotaceae. Comparison of cultivar and ant phylogenies suggests that a switch from lepiotaceous to pterulaceous fungiculture occurred only once in the history of the fungus-growing ants. This unique switch occurred after the origin of the genus Apterostigma, such that the basal Apterostigma lineages retained the ancestral attine condition of lepiotaceous fungiculture, and none of the Apterostigma lineages in the monophyletic group of pterulaceous fungiculturists are known to have reverted back to lepiotaceous fungiculture. The origin of pterulaceous fungiculture in attine ants may have involved a unique transition from the ancestral cultivation of litter-decomposing lepiotaceous fungi to the cultivation of wood-decomposing pterulaceous fungi. Phylogenetic analyses further indicate that distantly related Apterostigma ant species sometimes cultivate the same cultivar lineage, indicating evolutionarily frequent, and possibly ongoing, exchanges of fungal cultivars between Apterostigma ant species. The pterulaceous cultivars form two sister clades, and different Apterostigma ant lineages are invariably associated with, and thus specialized on, only one of the two cultivar clades. However, within clades Apterostigma ant species are able to switch between fungi. This pattern of broad specialization by attine ants on defined cultivar clades, coupled with flexible switching between fungi within cultivar clades, is also found in other attine lineages and appears to be a general phenomenon of fungicultural evolution in all fungus-growing ants.


Bone Mineral Parameters in Peritoneal Dialysis Patients after Lowering Calcium Concentration in Dialysis Fluids: A Case Series in Patients Using Icodextrin.
In patients treated with peritoneal dialysis (PD), lowering the calcium level in PD fluids results in lower serum calcium levels and higher parathyroid hormone (PTH) levels. It is hypothesized that this effect is attenuated when patients are using icodextrin 7.5% for the once-daily long dwell (containing high calcium concentration). In this case series, we included 8 stable PD patients (mean age 68 ± 13 years, 7 male), all using icodextrin 7.5% (containing 1.75 mmol/L calcium) for the once-daily long dwell. The calcium content of the PD fluids for the remaining dwells was lowered from 1.75 mmol/L to 1.25 mmol/L. Bone mineral parameters and phosphate prescription at baseline, 6 weeks after this change, and after 6 months were compared. After lowering calcium concentration of the PD fluids - except for the icodextrin 7.5% - from 1.75 mmol/L to 1.25 mmol/L, calcium levels changed from 2.32 ± 0.11 to 2.29 ± 0.12 (p = NS); intact PTH (iPTH) from 39.6 ± 28.3 to 64.9 ± 34.5 pmol/L (p = 0.045); and alkaline phosphatase from 104.13 ± 48.75 to 101.38 ± 32.39 (p = NS). After 6 months, all bone mineral parameters were similar to baseline levels; however, slightly higher calcium-based phosphate binders were prescribed. Lowering calcium content from 1.75 mmol/L to 1.25 mmol/L in PD fluids in patients on icodextrin resulted in stable calcium values, a temporal increase in iPTH and a modest increase in calcium-based phosphate binder prescription. Using icodextrin for the long once-daily dwell appears to attenuate the effects on bone mineral parameters when lowering the calcium concentration of the short dwells.


Physiological responses to short-term thermal stress in mayfly (Neocloeon triangulifer) larvae in relation to upper thermal limits.
Understanding species' thermal limits and their physiological determinants is critical in light of climate change and other human activities that warm freshwater ecosystems. Here, we ask whether oxygen limitation determines the chronic upper thermal limits in larvae of the mayfly Neocloeon triangulifer, an emerging model for ecological and physiological studies. Our experiments are based on a robust understanding of the upper acute (∼40°C) and chronic thermal limits of this species (>28°C, ≤30°C) derived from full life cycle rearing experiments across temperatures. We tested two related predictions derived from the hypothesis that oxygen limitation sets the chronic upper thermal limits: (1) aerobic scope declines in mayfly larvae as they approach and exceed temperatures that are chronically lethal to larvae; and (2) genes indicative of hypoxia challenge are also responsive in larvae exposed to ecologically relevant thermal limits. Neither prediction held true. We estimated aerobic scope by subtracting measurements of standard oxygen consumption rates from measurements of maximum oxygen consumption rates, the latter of which was obtained by treating with the metabolic uncoupling agent carbonyl cyanide-4-(trifluoromethoxy) pheylhydrazone (FCCP). Aerobic scope was similar in larvae held below and above chronic thermal limits. Genes indicative of oxygen limitation (LDH, EGL-9) were only upregulated under hypoxia or during exposure to temperatures beyond the chronic (and more ecologically relevant) thermal limits of this species (LDH). Our results suggest that the chronic thermal limits of this species are likely not driven by oxygen limitation, but rather are determined by other factors, e.g. bioenergetics costs. We caution against the use of short-term thermal ramping approaches to estimate critical thermal limits (CTmax) in aquatic insects because those temperatures are typically higher than those that occur in nature.


The evolution, distribution and diversity of endogenous circoviral elements in vertebrate genomes.
Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe are a useful source of information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe.


[Relationship between certain risk factors, age and ischemic heart disease according to simultaneous epidemiological study].
The measure of the difference according to certain risk factors and their combination in population subgroups differing in age and health (with or without ischemic heart disease) is appraised. The lowest measures of difference were revealed between elderly subgroups (55--59 years) with or without ischemic heart disease, as well as between young and middle-age subgroups with ischemic heart disease. Risk factors associated with lipid metabolism and also those such as the blood sugar level on a fasting stomach and the blood fibrinogen level carried more information when subgroups with ischemic heart disease and those without it were compared, while factors associated with arterial pressure proved more informative in comparison between subgroups of elderly and young individuals. When all the subgroup pairs were considered, significance proved to be highest for the levels of pulse, systolic pressure and blood serum triglycerides and lowest for the levels of blood fibrinogen and blood sugar on a fasting stomach.


Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterised by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances and a distinctive mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS. We sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next-generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion algorithm with an optimised score cut-off. We identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a 'pure JS' phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS subtypes. This work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes and enable gene-specific treatments in the future.


Enhanced Immune Response by Vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 Macrophages.
Vacuoles are membrane vesicles in eukaryotic cells, the digestive system of cells that break down substances absorbed outside the cell and digest the useless components of the cell itself. Researches on anti-cancer and intractable diseases using vacuoles are being actively conducted. The practical application of this study to animals requires the determination of the biocompatibility of vacuole. In the present study, we evaluated the effects of vacuoles isolated from S. cerevisiae in RAW264.7 cells. This showed a significant increase in the production of nitric oxide produced by macrophage activity. Using Reactive Oxygen Species (ROS) Assay, we identified that ROS is increased in a manner dependent on vacuole concentration. Western blot analysis showed that vacuole concentration-dependently increased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). Therefore, iNOS expression was stimulated to induce Nitric oxide (NO) production. In addition, pro-inflammatory cytokines levels promoted, such as interleukin 6 and tumor necrosis factor -α. In summary, vacuoles activate the immune response of macrophages by promoting the production of immune-mediated transporters NO, ROS, and pro-inflammatory cytokines.


[Home visits by a pharmacist after discharge from hospital].
Elderly patients using many medicines are at particular risk of making medication errors after discharge from hospital. This pilot study aims at investigating the feasibility and acceptance of improved written discharge information and home visits (by a pharmacist) to elderly patients who have newly been discharged from a medical department in a hospital. Patients (70 years and older) who needed at least 5 medicines and were about to be discharged from a medical department in a hospital, were offered home visits by a pharmacist 1, 5 and 26 weeks after discharge. A copy of the medication list was sent to their general practitioner (GP) the day the patient went home. During the home visit, the pharmacist provided information and training and recorded discrepancies between the hospital's medication list and the patients' actual medication use. 57 were invited to participate and 51 accepted the offer. During the 6-month project period, 5 patients died, one moved to a nursing home and one patient dropped out. Patients' and physicians' views on these measures were recorded. 53 discrepancies were disclosed for 29 of 51 patients during the first home visit. 26 discrepancies were disclosed during both the second and third visit; for 15/49 patients during the second and for 14/44 during the third visit. All involved GPs agreed that the medication list should be sent to the patient's GP the day the patient was discharged. Both hospital doctors and GPs regarded home visits by pharmacists to be useful for selected patients. In conclusion, home visits by a pharmacist is feasible, well accepted by doctors and patients and may represent a useful method for reducing medication errors in newly discharged elderly patients. The improved routines for informing the GPs about patients' medication use at discharge were appreciated. A controlled intervention study is needed to substantiate the effects of the measures undertaken in this pilot study.


Weight regain does not eliminate the long term benefits of weight management programmes.
The studyHartmann-Boyce J, Theodoulou A, Oke JL, et al. Long term effect of weight regain following behavioral weight management programs on cardiometabolic disease incidence and risk: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2023;16:263-76.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weight-regain-does-not-eliminate-the-long-term-benefits-of-weight-management-programmes/#:~:text=Study%20author&text=Many%20people%20believe%20that%20if,been%20the%20case%20without%20it.


Phylogenetic plant community structure along elevation is lineage specific.
The trend of closely related taxa to retain similar environmental preferences mediated by inherited traits suggests that several patterns observed at the community scale originate from longer evolutionary processes. While the effects of phylogenetic relatedness have been previously studied within a single genus or family, lineage-specific effects on the ecological processes governing community assembly have rarely been studied for entire communities or flora. Here, we measured how community phylogenetic structure varies across a wide elevation gradient for plant lineages represented by 35 families, using a co-occurrence index and net relatedness index (NRI). We propose a framework that analyses each lineage separately and reveals the trend of ecological assembly at tree nodes. We found prevailing phylogenetic clustering for more ancient nodes and overdispersion in more recent tree nodes. Closely related species may thus rapidly evolve new environmental tolerances to radiate into distinct communities, while older lineages likely retain inherent environmental tolerances to occupy communities in similar environments, either through efficient dispersal mechanisms or the exclusion of older lineages with more divergent environmental tolerances. Our study illustrates the importance of disentangling the patterns of community assembly among lineages to better interpret the ecological role of traits. It also sheds light on studies reporting absence of phylogenetic signal, and opens new perspectives on the analysis of niche and trait conservatism across lineages.


[On publishing and publications].
The publication of a scientific article represents the culmination of work by a group of researchers who at some point decided to pool their efforts to shed light on a scientific problem. Before an article appears in a biomedical journal, an original manuscript will have passed through a series of filters known as the "editorial process". That process provides a guarantee to future readers that information in the article contains a full and critical view of the subject. It is the authors' job to make their best effort when drafting and revising a report and checking the final version before submitting it for review. The manuscript should have the 3 main attributes of scientific writing: clarity, accuracy, and economy. In this article we discuss the sections of an article and guidelines for good clinical research practice. We also review how to present a manuscript that meets style requirements for publication.


Aspects of oral health and dementia among Swiss nursing home residents.
Little empirical evidence of high levels of oral diseases of people in need of care and the impact of dementia is available. The resident assessment instrument minimum data set (RAI-MDS) is an evaluation tool for caregivers. The aim of this study was to show oral health of nursing home residents through RAI-MDS 2.0 data as a function of the cognitive impairment. A retrospective analysis of RAI-MDS (general, cognitive, oral health variables) of 357 long-term care facilities in Switzerland (data of 105,835 residents) was carried out. The final sample size was 7922 residents after applying the inclusion/exclusion criteria in four evaluation groups (no dementia, moderate, severe and incident dementia). As dementia developed and severity increased over time, subjects often had fewer or no teeth and did not wear removable dentures. Chewing problems increased over time regardless of the dementia severity. Oral complaints increased over time in subjects with severe dementia, which in turn led to low body mass index (BMI) values (<23 kg/m2) and was associated with an higher risk of mortality. This dataset provides an overview on dental aspects in patients with dementia in nursing homes. The accuracy of the assessment of a given dental situation by nursing staff is to be questioned. The results indicated an underdetection of oral illnesses by nurses.


Multilocus loss of DNA methylation in individuals with mutations in the histone H3 lysine 4 demethylase KDM5C.
A number of neurodevelopmental syndromes are caused by mutations in genes encoding proteins that normally function in epigenetic regulation. Identification of epigenetic alterations occurring in these disorders could shed light on molecular pathways relevant to neurodevelopment. Using a genome-wide approach, we identified genes with significant loss of DNA methylation in blood of males with intellectual disability and mutations in the X-linked KDM5C gene, encoding a histone H3 lysine 4 demethylase, in comparison to age/sex matched controls. Loss of DNA methylation in such individuals is consistent with known interactions between DNA methylation and H3 lysine 4 methylation. Further, loss of DNA methylation at the promoters of the three top candidate genes FBXL5, SCMH1, CACYBP was not observed in more than 900 population controls. We also found that DNA methylation at these three genes in blood correlated with dosage of KDM5C and its Y-linked homologue KDM5D. In addition, parallel sex-specific DNA methylation profiles in brain samples from control males and females were observed at FBXL5 and CACYBP. We have, for the first time, identified epigenetic alterations in patient samples carrying a mutation in a gene involved in the regulation of histone modifications. These data support the concept that DNA methylation and H3 lysine 4 methylation are functionally interdependent. The data provide new insights into the molecular pathogenesis of intellectual disability. Further, our data suggest that some DNA methylation marks identified in blood can serve as biomarkers of epigenetic status in the brain.


Sad as a Matter of Choice? Emotion-Regulation Goals in Depression.
Research on deficits in emotion regulation has devoted considerable attention to emotion-regulation strategies. We propose that deficits in emotion regulation may also be related to emotion-regulation goals. We tested this possibility by assessing the direction in which depressed people chose to regulate their emotions (i.e., toward happiness, toward sadness). In three studies, clinically depressed participants were more likely than nondepressed participants to use emotion-regulation strategies in a direction that was likely to maintain or increase their level of sadness. This pattern was found when using the regulation strategies of situation selection (Studies 1 and 2) and cognitive reappraisal (Study 3). The findings demonstrate that maladaptive emotion regulation may be linked not only to the means people use to regulate their emotions, but also to the ends toward which those means are directed.


Prediction of the chemosensitivity of lung cancer by 99mTc-hexakis-2-methoxyisobutyl isonitrile SPECT.
99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) has been reported to accumulate in various tumors and to be a transport substrate for P-glycoprotein (Pgp). The aim of this study was to evaluate the usefulness of 99mTc-MIBI SPECT for in vivo assessment of lung cancer chemosensitivity. Also examined was the relationship between 99mTc-MIBI uptake and Pgp expression. Ten lung cancer patients who had undergone surgery were examined. Before surgery, 99mTc-MIBI SPECT was performed 15 and 120 min after injection, and the early uptake (L/Ne), delayed uptake (L/Nd) and washout rate (L/Nwr) of 99mTc-MIBI were calculated by the count ratio of lesion to contralateral normal lung tissue. The results were then compared with chemosensitivity determined by the succinate dehydrogenase inhibition test using six antitumor drugs (doxorubicin, mitomycin C [MMC], vindesine, etoposide [VP-16], cyclophosphamide and cisplatin). Pgp expression was determined by immunohistochemical staining. Sensitivity to MMC correlated significantly with L/Ne (P < 0.01) and L/Nwr (P < 0.05). Sensitivity to VP-16 correlated weakly and insignificantly with L/Nwr. L/Nd showed no correlation with sensitivity to any drug. Neither L/Ne, L/Nd nor L/Nwr was significantly different between the Pgp-positive group (n = 2) and the Pgp-negative group (n = 8). The results suggest that 99mTc-MIBI SPECT, a noninvasive in vivo examination, can predict the chemosensitivity of lung cancer to MMC and VP-16 independently of Pgp expression.


Evaluation of the Gore TAG thoracic branch endoprosthesis in the treatment of proximal descending thoracic aortic aneurysms.
Thoracic endovascular aortic repair has radically transformed the treatment of descending thoracic aortic aneurysms. However, when aneurysms involve the aortic arch in the region of the left subclavian artery, branch vessel preservation must be considered. Branched aortic endografts have provided a new option to maintain branch patency. Six investigative sites enrolled 31 patients in a nonrandomized, prospective investigational device exemption feasibility trial of a single branched aortic endograft for the management of aneurysms that include the distal aortic arch. The Gore TAG thoracic branch endoprosthesis (W. L. Gore & Associates, Inc, Flagstaff, Ariz), an investigational device, allows for graft placement proximal to the left subclavian artery and incorporates a single side branch for left subclavian perfusion. All 31 patients (100%) had undergone successful implantation of the investigational device in landing zone 2. Men slightly outnumbered women (51.6%). Their average age was 74.1 ± 10.4 years. The aneurysm morphology was fusiform in 12 and saccular in 19 patients, with a mean maximum aortic diameter of 54.8 ± 10.9 mm. The mean follow-up period for the cohort was 25.2 ± 11.1 months. We have reported the patient outcomes at 1 month and 1 year. At 1 month, the side branch patency was 100% and the freedom from core laboratory-reported device-related endoleak (types I and III) was 96.7%, without 30-day death or permanent paraplegia. One patient experienced a procedure-related stroke. Through 1 year, five patients had died; none of the deaths were related to the device or procedure (clinical endpoint committee adjudicated). One thoracic reintervention was required. No conversions were required, and no aneurysm growth (core laboratory) was reported. One case of the loss of side branch patency was diagnosed in the left subclavian artery in an asymptomatic individual from computed tomography at 6 months, with no reported subsequent adverse events due to loss of patency. Endoleaks were reported by the core laboratory in five patients at 12 months (two, type II; and three, indeterminate). The present investigational device exemption feasibility study has reported the preliminary results of the use of a single side branch endograft to treat patients with proximal descending thoracic aortic aneurysms.