Disruption of the dopamine beta-hydroxylase gene in mice suggests roles for norepinephrine in motor function, learning, and memory.
Mice unable to synthesize norepinephrine (NE) were created by targeted disruption of the dopamine beta-hydroxylase (DBH) gene. DBH-deficient (DBH -/-) mice display normal home cage activity; however, they swim more slowly than their littermates, and some drown. The mutant mice also perform less well on a rapidly rotating rod, and approximately 20% do not learn to walk when the rod begins to turn. Restoration of NE with dihydroxyphenylserine eliminated these motor deficits. DBH -/- mice exhibit normal learning and retention of a passive avoidance paradigm; however, they do not master an active-avoidance paradigm as readily as controls and exhibit more rapid extinction of the active-avoidance task. DBH -/- mice learn to find the hidden platform in the Morris water maze in spite of their slower swim speed and show normal preference for the correct quadrant in the transfer test immediately after training. However, this preference declines relative to controls during the next 2 days.


COVID-19 vaccine uptake and hesitancy survey in Northern Ireland and Republic of Ireland: Applying the theory of planned behaviour.
The Coronavirus Disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China in late 2019 and since then has caused unprecedented economic and social disruption as well as presenting a major challenge to public health. Despite mass progress in COVID-19 vaccination uptake, vaccine hesitancy or anti-vax information has been reported that can delay public acceptance of a vaccine. An online cross-sectional survey (n = 439) assessed COVID-19 vaccine uptake and hesitancy in adults in Northern Ireland and the Republic of Ireland. Participants completed an adapted version of the Theory of Planned Behaviour Vaccine Questionnaire, the Vaccine Attitudes Scale (VAX), Vaccine Confidence Scale, and questions on previous experience of COVID-19. Results showed that 66.7% of the sample intended to get a vaccination as soon as possible, 27.15% reported they will get a vaccine when others get theirs and when it is clear there are no side effects. 6.15% had no intention of getting a vaccine. Overall, there is a high mean intention (M = 6.12) and confidence to get a COVID-19 vaccine. There was low vaccine hesitancy (M = 2.49) as measured by the VAX scale. A further analysis of the sub factors of the VAX showed there is uncertainty and mistrust of side effects for children. The finding demonstrate that the Theory of Planned Behaviour can be useful in making recommendations for public health considerations when encouraging vaccine uptake and reducing vaccine hesitancy.


Genomic features of the human dopamine transporter gene and its potential epigenetic States: implications for phenotypic diversity.
Human dopamine transporter gene (DAT1 or SLC6A3) has been associated with various brain-related diseases and behavioral traits and, as such, has been investigated intensely in experimental- and clinical-settings. However, the abundance of research data has not clarified the biological mechanism of DAT regulation; similarly, studies of DAT genotype-phenotype associations yielded inconsistent results. Hence, our understanding of the control of the DAT protein product is incomplete; having this knowledge is critical, since DAT plays the major role in the brain's dopaminergic circuitry. Accordingly, we reevaluated the genomic attributes of the SLC6A3 gene that might confer sensitivity to regulation, hypothesizing that its unique genomic characteristics might facilitate highly dynamic, region-specific DAT expression, so enabling multiple regulatory modes. Our comprehensive bioinformatic analyzes revealed very distinctive genomic characteristics of the SLC6A3, including high inter-individual variability of its sequence (897 SNPs, about 90 repeats and several CNVs spell out all abbreviations in abstract) and pronounced sensitivity to regulation by epigenetic mechanisms, as evident from the GC-bias composition (0.55) of the SLC6A3, and numerous intragenic CpG islands (27 CGIs). We propose that this unique combination of the genomic features and the regulatory attributes enables the differential expression of the DAT1 gene and fulfills seemingly contradictory demands to its regulation; that is, robustness of region-specific expression and functional dynamics.


Making senses development of vertebrate cranial placodes.
Cranial placodes (which include the adenohypophyseal, olfactory, lens, otic, lateral line, profundal/trigeminal, and epibranchial placodes) give rise to many sense organs and ganglia of the vertebrate head. Recent evidence suggests that all cranial placodes may be developmentally related structures, which originate from a common panplacodal primordium at neural plate stages and use similar regulatory mechanisms to control developmental processes shared between different placodes such as neurogenesis and morphogenetic movements. After providing a brief overview of placodal diversity, the present review summarizes current evidence for the existence of a panplacodal primordium and discusses the central role of transcription factors Six1 and Eya1 in the regulation of processes shared between different placodes. Upstream signaling events and transcription factors involved in early embryonic induction and specification of the panplacodal primordium are discussed next. I then review how individual placodes arise from the panplacodal primordium and present a model of multistep placode induction. Finally, I briefly summarize recent advances concerning how placodal neurons and sensory cells are specified, and how morphogenesis of placodes (including delamination and migration of placode-derived cells and invagination) is controlled.


Observations on the accuracy of point counting including a description of a new graticule.
The accuracy of point counting as a histometric technique depends very much on the number of points counted, and the number necessary varies greatly with both the level of accuracy required and the proportion the relevant tissue occupies in the section. It is shown that the number of "hits" is a more useful measure than the total number of points counted, and a simple rule derived for determining the number of hits necessary to achieve any necessary degree of accuracy. A method of progressive estimation of accuracy when attempting to measure the proportion of a tissue that is unevenly distributed is also described. The point-counting graticules commonly used, with 25 points, are inadequate with tissue proportions below 10%. A new graticule design, with 100 points optimally distributed, and usable as a 25-point array if required, is illustrated.


Community-based exercise for health promotion and secondary cancer prevention in Canada: protocol for a hybrid effectiveness-implementation study.
Cancer care has expanded from a disease-focused, survival-oriented model to an approach that now considers how survivors can live well in the aftermath of intensive therapy, where they may deal with significant changes to their bodies, mental health or emotional well-being. Research evidence supports the benefit of exercise during and following cancer treatments for cancer-related symptoms, physical functioning and fitness, and health-related quality of life. To move this efficacy evidence into practice, we designed and launched a 5-year study to evaluate the relative benefit from implementing a clinic-to-community-based cancer and exercise model of care. A hybrid effectiveness and implementation trial design is being used to evaluate the effectiveness of delivery of community-based exercise and to collect data on implementation of the programme. The study opened in January 2017, with estimated completion by January 2022. The programme will be delivered in seven cities across the province of Alberta, Canada, with sites including three academic institutions, six YMCA locations, Wellspring Edmonton and Calgary, and six municipal fitness centres. Participants are adult cancer survivors (n=2500) from all tumour groups and stages and at any time point along their cancer treatment trajectory, up to 3 years post treatment completion. Survivors take part in a minimum of 60 min of mild-to-moderate intensity full body exercise twice weekly for a 12-week period. The primary effectiveness outcome is the proportion of participants meeting or exceeding 150 min of moderate intensity exercise per week at 1-year follow-up. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework will be utilised to capture individual-level and organizational-level impact of the exercise programme at 12 and 24 weeks and 1-year follow-up. The cohort of survivors participating in the study will allow for long-term (>5-year) evaluation of rates of cancer recurrence and secondary cancers beyond the funding period. The study was approved by the Health Research Ethics Board of Alberta. The study is funded by Alberta Innovates and the Alberta Cancer Foundation. The study will help to answer critical questions on the effectiveness of cancer-specific community-based exercise programming in both the short-term and the long-term. Collectively, the findings will help to inform the acceptability, adoption, feasibility, reach and sustainability of community-based exercise. NCT02984163; Pre-results.


Secreted enteric antimicrobial activity localises to the mucus surface layer.
The intestinal mucosa is constantly exposed to a dense and highly dynamic microbial flora and challenged by a variety of enteropathogenic bacteria. Antibacterial protection is provided in part by Paneth cell-derived antibacterial peptides such as the alpha-defensins. The mechanism of peptide-mediated antibacterial control and its functional importance for gut homeostasis has recently been appreciated in patients with Crohn's ileitis. In the present study, the spatial distribution of antimicrobial peptides was analysed within the small intestinal anatomical compartments such as the intestinal crypts, the overlaying mucus and the luminal content. Preparations from the different intestinal locations as well as whole mouse small intestine were extracted and separated by reversed-phase high-performance liquid chromatography. Antibacterial activity was determined in extracts, and the presence of antimicrobial peptides/proteins was confirmed by N-terminal sequencing, mass spectrometry analysis and immunodetection. The secreted antibacterial activity was largely confined to the layer of mucus, whereas only minute amounts of activity were noted in the luminal content. The extractable activity originating from either crypt/mucus/lumen compartments respectively (given as a percentage) was for Listeria monocytogenes, 48 (4)/44 (4)/8 (8); Enterococcus faecalis, 44 (10)/49 (3)/7 (7); Bacterium megaterium, 56 (4)/42 (3)/2 (1); Streptococcus pyogenes, 48 (4)/46 (3)/6 (6); Escherichia coli, 46 (4)/47 (3)/7 (7); and Salmonella enterica sv. Typhimurium, 38 (3)/43 (7)/19 (10). A spectrum of antimicrobial peptides was identified in isolated mucus, which exhibited strong and contact-dependent antibacterial activity against both commensal and pathogenic bacteria. These findings show that secreted antimicrobial peptides are retained by the surface-overlaying mucus and thereby provide a combined physical and antibacterial barrier to prevent bacterial attachment and invasion. This distribution facilitates high local peptide concentration on vulnerable mucosal surfaces, while still allowing the presence of an enteric microbiota.


Coronary artery disease in young women.
Although unusual, coronary artery disease does occur in young women. It may be present to a severe degree between ages 20 and 30, but a typical history of angina pectoris by no means assures the presence of significant coronary artery disease. Proof that oral contraceptives predispose to coronary artery disease is lacking. It seems wise not to recommend them to young women with other known risk factors. Significant risk factors in a group of 1000 women under age 50 studied by cinecoronary arteriography for the evaluation of chest pain included cigarette smoking, hypertension, hypercholesteremia, and glucose intolerance. Combinations of factors increased the risk. Electrocardiographic abnormalities in themselves did not seem to increase the risk of coronary artery disease, but did seem to enhance it in combination with other factors. Electrocardiographic evidence of transmural myocardial infarction without significant coronary artery disease was more common in young women than in young men. Cinecoronary arteriography may possibly be performed after resolution of more severe lesions related to lysis of emboli or thrombi. Special conditions may temporarily increase myocardial oxygen requirements. Angia-like chest pain has been described in patients without significant coronary artery disease. Many have normal electrocardiograms and no known risk factors. Spasm has been mentioned among many possible causes, but is very difficult to tell whether or not underlying atherosclerotic lesions may be present. Whatever the cause, the prognosis for patients with angina-like chest pain and normal coronary arteriography seems excellent; early death is a rarity and improvement is common.


[The Interplanta system model knee joint prosthesis. Preliminary results].
The SKI-knee joint is used since three years. Our experiences comprise 220 cases up to now. The follow-up time is still short, but the implant, which is partially designed very close to normal anatomy and on the other hand regards fundamental biomechanical aspects is showing a comparably low incidence of complications. The complications specifically due to the endoprosthetic system sums up to 10%. It is obvious that patellar complications are leading. This fact should be seen in close connexion to the anatomical design of the femoral component. With increasing experience these problems are diminished. Causes and potential elimination of patellar complications are discussed. Surgical procedure, especially advantages in comparison with other knee joints are described. The SKI-System in combination with its aligning instruments allow the surgeon anatomical reconstruction, very exact alignment of the implant and precise correction of preexisting deformities. In general the results are encouraging in comparison with formerly used knee joints after the same follow-up period.


Divergence among genes encoding the elongation factor Tu of Yersinia Species.
Elongation factor Tu (EF-Tu), encoded by tuf genes, carries aminoacyl-tRNA to the ribosome during protein synthesis. Duplicated tuf genes (tufA and tufB), which are commonly found in enterobacterial species, usually coevolve via gene conversion and are very similar to one another. However, sequence analysis of tuf genes in our laboratory has revealed highly divergent copies in 72 strains spanning the genus Yersinia (representing 12 Yersinia species). The levels of intragenomic divergence between tufA and tufB sequences ranged from 8.3 to 16.2% for the genus Yersinia, which is significantly greater than the 0.0 to 3.6% divergence observed for other enterobacterial genera. We further explored tuf gene evolution in Yersinia and other Enterobacteriaceae by performing directed sequencing and phylogenetic analyses. Phylogenetic trees constructed using concatenated tufA and tufB sequences revealed a monophyletic genus Yersinia in the family Enterobacteriaceae. Moreover, Yersinia strains form clades within the genus that mostly correlate with their phenotypic and genetic classifications. These genetic analyses revealed an unusual divergence between Yersinia tufA and tufB sequences, a feature unique among sequenced Enterobacteriaceae and indicative of a genus-wide loss of gene conversion. Furthermore, they provided valuable phylogenetic information for possible reclassification and identification of Yersinia species.


Single-cell genomics reveals new rozellid lineages and supports their sister relationship to Microsporidia.
The phylum Rozellomycota has been proposed for a group of early-branching holomycotan lineages representing obligate parasites and hyperparasites of zoosporic fungi, oomycotes or phytoplankton. Given their predominantly intracellular lifestyle, rozellids are typically known from environmental ribosomal DNA data, except for the well-studied Rozella species. To date, the phylogenetic relationship between rozellids and microsporidians (Microsporidia) is not fully understood and most reliable hypotheses are based on phylogenomic analyses that incorporate the only publicly available rozellid genome of Rozella allomycis. Here, we provide genomic data of three new rozellid lineages obtained by single-cell sequencing from environmental samples and show with a phylogenomic approach that rozellids form a monophyletic group that is sister to microsporidians, corroborating the previously proposed phylum Rozellomycota. Whereas no mitochondrial genes coding for the respiratory Complex I could be found, we discovered a gene coding for a nucleotide phosphate transporter in one of the three draft genomes. The scattered absence of Complex I genes and scattered presence of nucleotide transporter genes across diverse microsporidian and rozellid lineages suggest that these adaptations to a parasitic lifestyle, which reduce the parasite's capability to synthesize ATP but enables it to steal ATP from its host, evolved independently in microsporidians and rozellids.


Preparing for Future Adversities: Lessons From the COVID-19 Pandemic in Australia for Promoting Relational Resilience in Families.
Background: The COVID-19 pandemic has placed considerable pressure on families, testing the quality of relationships and the strength of social support within and beyond the family network. However, little is known about the pre-pandemic factors that predict family relational resilience and social functioning during times of natural disaster or global crisis. Here we use data from one of Australia's longest running studies of social and emotional development to examine the nature and timing of possible relational and social support intervention aimed at preparing families for future adversities. Methods: Data were from the Australian Temperament Project Generation 3 (ATPG3) Study, a population representative three generation cohort study of families established in 1983. A subset of Generation 2 parents completed a COVID-19 specific survey in May-September 2020 (502 parents of 871 children; 60% mothers; 37-38 years). These participants had completed the Quality of Relationships Inventory to assess social support during young adulthood, at 23-24 years (2006) and 27-28 years (2010), before next generation conception. Participants had also completed the Maternity Social Support Scale 1 year postpartum for each child born across the ATPG3 assessment period (2012-2019). In 2020, during the height of the Australian lockdowns, participants rated the quality of their relationships with their partners, children and broader family and friends, in addition to social support within and extended beyond their family. Results: Pre-pandemic partner support was associated with partner relationship quality during the pandemic (β = 0.22). Pre-pandemic support from friends was associated with relationship quality with other family and friends during the pandemic (β = 0.12 - 0.18). Pre-pandemic support (from partner, family and friends) was consistently associated with social support within families during the pandemic (β = 0.11 - 0.21). Pre-pandemic support from friends was also associated with family support extended to others within their local community during the pandemic (β = 0.12 - 0.13). Conclusions: Strengthening supportive relationships during major life transitions, prior to the start of family life and in early parenthood, may have long-term and intergenerational benefits years into the future for both families and communities. This may promote resilience during future crises and other more normative stressful life events.


T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin.
Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders. We investigated the variable region (V beta) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls. We determined the frequency of the V beta in normal and inflamed skin and compared it to the percentage of the respective V beta in the malignant clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the V beta families in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL, 1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2 (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta 17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF), 1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded well to the repertoire of V beta in eczematous skin but not to the repertoire in PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The V beta usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.


Surgical lung biopsies in 418 patients with suspected interstitial lung disease in China.
The present study was aimed to evaluate the role and safety of surgical lung biopsies (SLB) in patients with interstitial lung disease (ILD) in China. A retrospective analysis of 418 patients with ILD undergoing SLB from Chinese literature and the data of our hospital during the past ten years was performed. A total of 418 cases underwent SLB, including open lung biopsy (OLB) in 229 cases and video-assisted thoracoscopic lung biopsy (VATLB) in 189 cases. SLB yielded a specific diagnosis for 88.0% cases, and unclassifiable idiopathic interstitial pneumonia diagnosis was seen in 9.1% cases. The total postoperative complication rate was 12.0% and mortality rate was 1.9%. The diagnostic yield, post-operative complication rate, and mortality rate between VATLB and OLB had no significant difference. SLB is a very useful and relatively safe procedure for diagnosis of ILD.


Usefulness of a job-exposure matrix 'MADE' as a decision tool for compensation of work-related musculoskeletal disorders.
We aimed to assess the predictivity of the biomechanical job-exposure matrix 'MADE' using compensation data from the National Health Insurance for work-related disorders. Data were obtained from 2013 to 2015, area under curves (AUC), sensitivity, specificity and predictive values were calculated using compensation results as reference. We collected 163 128 cases data. AUC ranged from 0.64 for shoulders disorder to 0.82 for knee disorders. If two thresholds were considered, 28.7% of the sample fit under or over those. The matrix showed a fair predictivity. Such matrix cannot replace expertise but might be a tool used for improving compensation process.


Enhanced alpha2A-autoreceptor reserve for clonidine induced by reserpine and cholinomimetic agents in the rat vas deferens.
1. The adaptive changes in the functional parameters of the presynaptic alpha2A-adrenoceptors in rat vas deferens were examined after treatments with the monoamine depleter reserpine or with the direct/indirect cholinomimetic agents pilocarpine and neostigmine. 2. For this purpose, we studied the inhibition induced by the alpha2-adrenoceptor agonist clonidine on the twitch contraction of the vas deferens elicited by electrical field stimulation, in animals that had been treated with acute (single dose), short-term (for 4 days) and chronic (for 11 days) regimens of reserpine (0.25 mg kg(-1), s.c., every 48 h), pilocarpine (10 mg kg(-1), i.p., every 12 h) or neostigmine (0.1 mg kg(-1), i.p., every 12 h). The irreversible receptor alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 300 nM) was used to block partially the alpha2A-adrenoceptor-mediated effect of clonidine. 3. In control (untreated) animals, clonidine inhibited concentration-dependently the twitch response of the vas deferens (pEC50 = 8.66) with a maximal effect near 100%. The apparent affinity constant for clonidine was estimated with the nested hyperbolic methodology (pK(A) = 7.10). The analysis of the occupancy-effect relation for clonidine revealed a large receptor reserve at alpha2A-adrenoceptors. 4. Acute, short-term and chronic treatments with reserpine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3, 4 and 9 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 4, 10 and 10 fold, respectively. Receptor affinity values were not changed after treatments. 5. Short-term and chronic, but not acute, treatments with pilocarpine and neostigmine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3 and 2 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 2 and 3 fold, respectively. Receptor affinity values were not changed after these treatments. 6. These results indicate that an enhancement of the receptor reserve for clonidine might account for the supersensitivity of alpha2A-adrenoceptors induced by reserpine, pilocarpine or neostigmine treatments in the rat vas deferens.


Marrow regeneration after mechanical depletion.
The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.


[Mechanisms of ureteral contraction-relaxation in nephritic colic].
From the clinical perspective, pharmacological research on ureteral dynamics--the contraction-relaxation mechanisms of the ureter--, has been prompted by renal colic. Studies of the events triggered by the calculus have been conducted to identify the pharmacological aspects that permit pain relief, passage of the calculus and protection of the kidney from injury caused by acute obstruction. Many and varied studies on ureteral pharmacology, both in vivo and in vitro, have been carried out since the beginning of the 20th century. Numerous studies on the anatomical, neurophysiological and hormonal aspects, and different neuroactive substances have attempted to identify the behavior of the ureter under normal and pathological conditions. Since 1967, the Urology Department of the 'Jiménez Díaz' Foundation has investigated the mechanisms of ureteropelvic dynamics utilizing techniques developed at this institution, such as pyelomanometry, pressure/flow to constant pressure studies and antegrade pyelography. The different behavior of the ureter and the stimuli it receives according to the zone analyzed, are known. The classical neurohumoral mechanisms (adrenergic and cholinergic), ureteral pacemaker, effects of urinary pH and infection, action of glucagons, prostaglandins, as well as the new mechanisms of action mediated by substances and non-adrenergic non-cholinergic (NANC) receptors (tachykinins, nitric oxide (NO), vasoactive intestinal peptide (VIP), neuropeptide Y, etc.) have led to new concepts of ureteral contraction-relaxation. The current therapeutic strategy in renal colic utilizes non-steroidal antiinflammatory drugs (NSAID) and extracorporeal shock wave lithotripsy (ESWL) in situ for analgesia and resolution. Recent insight into ureteral dynamics attempt to promote the development of new drugs for enhanced and more effective management of renal colic.


Carbon and Nitrogen Speciation in N-poor C-O-H-N Fluids at 6.3 GPa and 1100-1400 °C.
Deep carbon and nitrogen cycles played a critical role in the evolution of the Earth. Here we report on successful studying of speciation in C-O-H-N systems with low nitrogen contents at 6.3 GPa and 1100 to 1400 °C. At fO2 near Fe-FeO (IW) equilibrium, the synthesised fluids contain more than thirty species. Among them, CH4, C2H6, C3H8 and C4H10 are main carbon species. All carbon species, except for C1-C4 alkanes and alcohols, occur in negligible amounts in the fluids generated in systems with low H2O, but С15-С18 alkanes are slightly higher and oxygenated hydrocarbons are more diverse at higher temperatures and H2O concentrations. At a higher oxygen fugacity of +2.5 Δlog fO2 (IW), the fluids almost lack methane and contain about 1 rel.% C2-C4 alkanes, as well as fractions of percent of C15-18 alkanes and notable contents of alcohols and carboxylic acids. Methanimine (CH3N) is inferred to be the main nitrogen species in N-poor reduced fluids. Therefore, the behaviour of CH3N may control the nitrogen cycle in N-poor peridotitic mantle. Oxidation of fluids strongly reduces the concentration of CH4 and bulk carbon. However, higher alkanes, alcohols, and carboxylic acids can resist oxidation and should remain stable in mantle hydrous magmas.


Value of evaluating procalcitonin kinetics in diagnosis of infections in patients undergoing laparoscopic radical cystectomy.
Postsurgery infection is a common complication after laparoscopic radical cystectomy (LRC) followed by urinary diversion. White blood cell (WBC) values and C-reactive protein (CRP) are routinely used as markers for infection, but lack of specificity and their elevation is often delayed in clinically significant events. In this study, we aimed to investigate the value of procalcitonin (PCT) kinetics in assisting early diagnosis of infection in patients undergoing LRC.The patients' medical records between May 2013 and May 2016 were reviewed retrospectively. WBC, CRP, and PCT plasma levels as well as clinical symptoms were registered in 306 patients preoperatively (day 0), and 5 consecutive days postoperatively. Based on microbiological and clinical data, patients were grouped into noninfection- (NI-) and infection- (I-) groups. The day of new onset infection was observed were defined as day t0 and the day after that as day t1. For the NI-group, the day on which PCT was at the peak was defined as day t1 and the previous day as day t0.Of the 306 patients, 46 (15.03%) have proven infection. PCT levels were analogous at day t0:NI-group [median (interquartile range)]: 0.69(1.99) vs I-group [median (interquartile range)]: 1.0[0.75], P = .1. PCT levels were significantly increased at day t1 in the I-group[median (interquartile range)]:2.9(1.3) vs NI-group[median (interquartile range)]: 1.3(1.5), P < .01. The area under the curve for the prediction of infection was 0.72 [95% confidence interval (CI) = 0.63-0.81] for the absolute value of PCT; and for delta PCT:0.88 (95% CI = 0.81-0.94), P < .01. The optimal cut-off value was 0.79 ng/mL with the highest Youden index of 0.80 for delta-PCT to indicate infection. Neither absolute values nor changes in CRP, or WBC could predict infection better. The "delta" was considered as the changes in the absolute values (subtracting day t0 from day t1) of PCT, CRP, and WBC.This study suggest that early elevation of PCT within the first 24 hours of new onset infection, interpreted with clinical results, appears to be a promising indicator for the diagnosis of infections following LRC.


Fear of COVID-19 and future anxiety among Polish university students during a pandemic.
The pandemic poses a threat to human health and life, and anxiety is the most common psychological problem occurring during the COVID-19 pandemic. The aim of the study was to establish the differences in the fear of COVID-19 infection and the future anxiety experienced by students during the pandemic by gender, field of study, place of study and paid employment, and their relationships to psychological well-being. The study involved 1294 university students aged 18-30. The Future Anxiety Scale and short version of the Psychological General Well-Being Index were used. In addition, students stated whether they were concerned about the possibility of contracting the coronavirus and falling ill with COVID-19. One-third of respondents stated that they felt fear of contracting the coronavirus. Women experienced a significantly stronger fear of COVID-19 and future anxiety than men. The observed interaction effects show that female students of medical faculties experienced a higher fear of COVID-19 than women studying fields of study related to physical activity and working students experienced a slightly higher future anxiety. A positive, but weak correlation between fear of COVID-19 and future anxiety was found. Psychological well-being correlated poorly with fear of COVID-19 and moderately with future anxiety. Because future anxiety was stronger in women, medical students, some master's students and working people, preventive measures should be taken to prevent excessive anxiety and to promote mental health in these groups.


[A case of reversible cerebral vasoconstriction syndrome (RCVS) triggered by human placenta extract].
We present a case of a female patient with reversible cerebral vasoconstriction syndrome (RCVS) arising after receiving subcutaneous injection of human placenta extract. A 44-year-old woman started taking human placenta extract with the aim of improving her menopausal symptoms, fatigue, and beauty. However, 18 days after taking human placenta extract, she had three episodes of thunderclap headache. Repeated cranial CT did not show subarachnoid hemorrhage; CSF examination showed neither xanthochromia nor inflammation. Brain diffusion weighted and FLAIR images were normal. However, magnetic resonance angiography showed multifocal segmental stenosis of the right middle cerebral artery and bilateral anterior cerebral arteries. Follow-up angiography, which performed 12 days after the oncet of thunderclap headache, revealed almost normalized flow in all cerebral arteries; we made a diagnosis of RCVS. She has had no symptoms and signs since the third attack of headache. The only identified etiologic factor was subcutaneous injection of human placenta extract started 18 days prior to onset. This is the first report of RCVS triggered by human placenta extract.


Multipurpose made colorimetric materials for amines, pH change and metal ion detection.
Sensors are routinely developed for specific applications, but multipurpose sensors are challenging, due to stability and poor functional design. We report organic materials that operate in solution and gas phase. They show a strong response behaviour to at least three types of environmental changes: pH, amine and metal ion binding/detection. We have confirmed and validated our findings using various analytical and computational methods. We found that the changes in polarity of the solvent and pH not only red shift the tail of the absorption spectra, but also extend the peak optical absorption of these structures by up to 100 nm, with consequential effects on the optical gap and colour changes of the materials. Acid-base response has been studied by spectrophotometric titrations with trifluoroacetic acid (TFA) and triethyl amine (TEA). The experiments show excellent reversibility with greater sensitivity to base than acid for all compounds. Analysis into metal sensing using Zn(ii) and Cu(ii) ions as analytes show that the materials can successfully bind the cations forming stable complexes. Moreover, a strong suppression of signal with copper gives an operative modality to detect the copper ion as low as 2.5 × 10-6 M. The formation of the metal complexes was also confirmed by growing crystals using a slow diffusion method; subsequent single crystal X-ray analysis reveals the ratio of ligand to metal to be 2 to 1. To test sensitivity towards various amine vapours, paper-based sensors have been fabricated. The sensors show a detection capability at 1 ppm of amine concentration. We have employed CIE L*a*b* colour space as the evaluation method, this provides numeric comparison of the samples from different series and allows comparison of small colour differences, which are generally undetectable by the human-eye. It shows that the CIE L*a*b* method can assess both sensitivity to a particular class of analytes and a specificity response to individual amines in this subclass offering an inexpensive and versatile methodology.


0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease.
To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation (rTMS) on Parkinson's disease (PD), 85 patients with PD were enrolled into three groups: 1). motor cortical, 2). occipital, and 3). sham stimulation. A round coil was centered over the vertex in motor cortical stimulation, and over the inion in occipital stimulation. In one session, 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold (AMT) were given. In sham stimulation, electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation. Each session was carried out once a week for the first 8 weeks. The Unified Parkinson Disease Rating Scale (UPDRS), Hamilton Rating Scale for Depression (HRSD) and subjective score (visual analogue scale) were assessed. There were no significant differences in clinical features among the three groups. Total and motor score of UPDRS were improved to the same extent by rTMS over Cz, inion, and sham stimulation. HRSD was improved by rTMS over Cz and sham stimulation in the same manner. Subjective score was not significantly improved by any methods of stimulation. 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD. Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation.


Human meniscus allograft augmentation by allogeneic mesenchymal stromal/stem cell injections.
Meniscus allograft transplantations (MATs) represent established surgical procedures with proven outcomes. Yet, storage as frozen specimens and limited cellular repopulation may impair graft viability. This proof-of-concept study tests the feasibility of injecting allogeneic mesenchymal stromal/stem cells (MSCs) in meniscus allograft tissue. We investigated the injectable cell quantity, survival rate, migration, and proliferation ability of MSCs up to 28 days of incubation. In this controlled laboratory study, seven fresh-frozen human allografts were injected with human allogeneic MSCs. Cells were labeled and histological characteristics were microscopically imaged up to 28 days. Mock-injected menisci were included as negative controls in each experiment. Toluidine blue staining demonstrated that a 100-µl volume can be injected while retracting and rotating the inserted needle. Immediately after injection, labeled MSCs were distributed throughout the injection channel and eventually migrated into the surrounding tissues. Histological assessment revealed that MSCs cluster in disc-like shapes, parallel to the intrinsic lamination of the meniscus and around the vascular network. Quantification showed that more than 60% of cells were present in horizontally injected grafts and more than 30% were observed in vertically injected samples. On Day 14, cells adopted a spindle-shaped morphology and exhibited proliferative and migratory behaviors. On Day 28, live/dead ratio assessment revealed an approximately 80% cell survival. The study demonstrated the feasibility of injecting doses of MSCs (>0.1 million) in meniscus allograft tissue with active cell proliferation, migration, and robust cell survival.


Eccentric-concentric Ratio: A Key Factor for Defining Strength Training in Soccer.
The aims of this study were to analyse the effect of chronic strength training over concentric power (CON), eccentric power (ECC), ECC/CON ratio, and 20 m linear sprint performance in elite young soccer players. Twenty young elite Spanish soccer players were assigned to an experimental group (CPG) which performed a front-step exercise using a conical pulley, 2-3 sets of 6 repetitions each leg, during 9 weeks (CPG, n=10) in addition to its usual strength training, or to a control group (CG, n=10). The improvements in the ECC mean power (36%, ES=1.61), and ECC / CON ratio (17%, ES=1.77) were substantially greater in the CPG than in the CG while the CON mean power (16%, ES=0.83) was substantially greater in the CG than in the CPG. The sprinting time for 10 m (2.8%, ES=0.78) and the 10 m flying time between 10-20 m (1.72%, ES=0.41) were substantially enhanced in CPG and CG respectively. To be efficient when defining a functional strength training and performance increments using an inertial device, the mean power output need to be measured during the CON and ECC phases and an analysis of the ECC / CON ratio should be included.


Effect of static magnetic field-assisted freezing at different temperatures on muscle quality of pacific white shrimp (Litopenaeus vannamei).
The effect of static magnetic field-assisted freezing (MF) at different temperatures (-35, -30, -25, and -20 °C) on the muscle quality of pacific white shrimp (Litopenaeus vannamei) was evaluated to investigate the possibility of energy saving by MF. The results showed that the -35 °C MF treatment increased the water-holding capacity of shrimp muscle, and maintained the wholeness of the microstructure compared to -35 °C immersion freezing (control group, IF). With the increase in freezing temperature in the MF treatments, the size of ice crystals gradually increased, and the sensory properties of shrimp decreased. The water-holding capacity, sensory properties, and water distribution of shrimp muscle subjected to MF at -25 °C were still no significantly different from those of the IF at -35 °C (P > 0.05). In summary, the utilization of MF enhanced the quality of frozen pacific white shrimp, which has the potential to provide energy saving benefits.


Maxillary sinus floor augmentation in patients with maxillary sinus pseudocyst: case report.
The maxillary sinus floor elevation procedure has gained popularity with predictable results, and is a safe, acceptable technique for bone augmentation, providing a base for dental implant treatment. Faint radiopaque lesions at the base of the maxillary sinus are frequent diagnoses on radiographs and must be identified during dental implant planning. Pseudocysts classically appear hemispheric, homogeneously opaque, and well delineated in panoramic and periapical radiographs. The great majority of these lesions are asymptomatic and do not require surgical treatment. In this case report, we present 4 patients who had a maxillary sinus floor elevation procedure using either crestal or lateral approaches in the presence of antral pseudocysts. No complications were encountered during follow-up periods in these patients and all implants are functioning successfully.


Association of obesity and age-related macular degeneration in Indian population.
The aim of this study was to establish the prevalence and association of age-related macular degeneration (AMD) and obesity which was not studied extensively in Indian population over 60 years of age. This was a cross-sectional, population-based study. A total of 4791 patients with gradable fundus photography were included. All patients underwent detailed ophthalmic examination and AMD was graded with retinal photographs. Grading of AMD was done according to the International ARM Epidemiological Study Group and staged based on grading in worse eye. The association of AMD severity and obesity (based on body mass index, waist-hip ratio, waist circumference, isolated abdominal obesity, isolated generalized obesity, and combined obesity) was assessed. The main outcome variable was an association between the presence and severity of AMD with different grades of obesity. No direct significant association was noted between the presence and severity of AMD and any obesity indices. Subgroup analyses based on lifestyle patterns and common systemic pathologies in AMD population were done. Late AMD was significantly associated with tobacco consumption in population with combined obesity (P = 0.033 and odds ratio = 2.998). No direct association was noted between the presence or severity of AMD and obesity in South Indian population. However, indirect associations between the severity of AMD and combined obesity were found.


Ramapithecines from China: evidence from tooth dimensions.
Data obtained from ramapithecine specimens found in Asia, Africa and Europe have suggested the existence of two major subgroups, Ramapithecus and Sivapithecus, with Ramapithecus having pre-human status. Recently, however, it has been proposed that the fossils all belong to a single group, Sivapithecus, which is more closely related to the apes, in particular the orang-utan. Here we analyse data from a series of similar fossils which have been found in late Miocene coalfields in Lufeng, Yunnan Province, China. These include a number of almost complete jaws and five partial skulls which are more complete than any others so far known. A statistical analysis of the overall dimensions of the large number of teeth included in these finds shows that the differences between the groups previously assigned to Ramapithecus and Sivapithecus are greater than those found between the sexes in the most sexually dimorphic of the living great apes. Within the groups the distribution is bimodal and we suggest each group contains sex subgroups.


An introduction to deep learning on biological sequence data: examples and solutions.
Deep neural network architectures such as convolutional and long short-term memory networks have become increasingly popular as machine learning tools during the recent years. The availability of greater computational resources, more data, new algorithms for training deep models and easy to use libraries for implementation and training of neural networks are the drivers of this development. The use of deep learning has been especially successful in image recognition; and the development of tools, applications and code examples are in most cases centered within this field rather than within biology. Here, we aim to further the development of deep learning methods within biology by providing application examples and ready to apply and adapt code templates. Given such examples, we illustrate how architectures consisting of convolutional and long short-term memory neural networks can relatively easily be designed and trained to state-of-the-art performance on three biological sequence problems: prediction of subcellular localization, protein secondary structure and the binding of peptides to MHC Class II molecules. All implementations and datasets are available online to the scientific community at https://github.com/vanessajurtz/lasagne4bio. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Renal disease in patients with celiac disease.
Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.


Adding Fuel to the Collective Fire: Stereotype Threat, Solidarity, and Support for Change.
We hypothesize a yet-unstudied effect of experiencing systemic stereotype threat on women's collective action efforts: igniting women's support for other women and motivation to improve organizational gender balance. Hypotheses are supported in two surveys (Study 1: N = 1,365 business school alumnae; Study 2: N = 386 women Master of Business Administration [MBA]), and four experiments (Studies 3-6; total N = 1,897 working women). Studies 1 and 2 demonstrate that experiencing stereotype threat is negatively associated with women's domain-relevant engagement (supporting extant work on the negative effects of stereotype threat), but positively associated with women's support and advocacy of gender balance. Studies 3 to 6 provide causal evidence that stereotype threat activation leads to greater attitudes and intentions to support gender balance, ruling out negative affect as an alternative explanation and identifying ingroup solidarity as a mechanism. We discuss implications for working women, women leaders, and organizations striving to empower their entire workforce through developing equitable and inclusive practices.


Biogeochemical cycling and microbial diversity in the thrombolitic microbialites of Highborne Cay, Bahamas.
Thrombolites are unlaminated carbonate build-ups that are formed via the metabolic activities of complex microbial mat communities. The thrombolitic mats of Highborne Cay, Bahamas develop in close proximity (1-2 m) to accreting laminated stromatolites, providing an ideal opportunity for biogeochemical and molecular comparisons of these two distinctive microbialite ecosystems. In this study, we provide the first comprehensive characterization of the biogeochemical activities and microbial diversity of the Highborne Cay thrombolitic mats. Morphological and molecular analyses reveal two dominant mat types associated with the thrombolite deposits, both of which are dominated by bacteria from the taxa Cyanobacteria and Alphaproteobacteria. Diel cycling of dissolved oxygen (DO) and dissolved inorganic carbon (DIC) were measured in all thrombolitic mat types. DO production varied between thrombolitic types and one morphotype, referred to in this study as 'button mats', produced the highest levels among all mat types, including the adjacent stromatolites. Characterization of thrombolite bacterial communities revealed a high bacterial diversity, roughly equivalent to that of the nearby stromatolites, and a low eukaryotic diversity. Extensive phylogenetic overlap between thrombolitic and stromatolitic microbial communities was observed, although thrombolite-specific cyanobacterial populations were detected. In particular, the button mats were dominated by a calcified, filamentous cyanobacterium identified via morphology and 16S rRNA gene sequencing as Dichothrix sp. The distinctive microbial communities and chemical cycling patterns within the thrombolitic mats provide novel insight into the biogeochemical processes related to the lithifying mats in this system, and provide data relevant to understanding microbially induced carbonate biomineralization.


Does social integration really protect against loneliness? Gender determinants in a rural population in Senegal
This study aims to test a measure of loneliness and to document its determinants among rural men and women in Senegal. Data from the Niakhar Social Networks and Health Project were used. The analysis sample was composed of 1261 residents aged 16 years and older. Analyses were stratified by gender. Associations between loneliness and its determinants (socio-demographic characteristics and level of social integration) were examined with multivariate logistic regressions. Loneliness affects almost one in three people. Its prevalence is more significant for women. Multivariate analyses indicate that for both men and women, older age intensifies loneliness and recent migration experience protects against loneliness. Other factors act differently according to gender. Widowhood or divorce for men, and residential isolation for women, worsen the experience of loneliness. Social integration protects men against loneliness, but this relationship is not found for women. Finally, the effect of the level of social integration on loneliness varies with age. This study, which documents a phenomenon which is often neglected by misconceptions about social solidarities in these societies, suggests that loneliness is not linked to the same issues for men and women. For men, being socially integrated and being in a union are protective, whereas for women, poor social integration does not appear to be a clear source of loneliness, unlike residential isolation.


The inhibitor of phagocytosis, O-phospho-L-serine, suppresses Müller glia proliferation and cone cell regeneration in the light-damaged zebrafish retina.
The damaged zebrafish retina replaces lost neurons through a regenerative response that initiates with the asymmetric cell division of Müller glia to produce neuronal progenitor cells that proliferate and migrate to the damaged retinal layer, where they differentiate into the lost neuronal cell types. Because Müller glia are known to phagocytose apoptotic retinal cells during development, we tested if Müller glia engulfed apoptotic rod cell bodies in light-damaged retinas. After 24h of constant intense light, damaged retinas revealed both a strong nuclear TUNEL signal in photoreceptors and a weak cytoplasmic TUNEL signal in Müller glia, although Müller glial apoptosis is not observed in the light-damaged retina. Light damage of a rod-specific transgenic reporter line, Tg(XlRho:EGFP)(fl1), resulted in some Müller glia containing both TUNEL signal and EGFP, which indicated that this subset of Müller glia engulfed apoptotic photoreceptor cell bodies. To determine if phagocytosis induced the Müller glial proliferative response in the light-damaged retina, we utilized O-phospho-l-serine (L-SOP), a molecule that mimics the phosphatidylserine head group and partially blocks microglial phagocytosis of apoptotic cells. Intravitreal injection of L-SOP immediately prior to beginning constant intense light treatment: i) did not significantly reduce light-induced photoreceptor cell death, ii) significantly reduced the number of PCNA-positive Müller glia, and iii) significantly reduced the number of cone photoreceptors in the regenerated retina relative to control retinas. Because L-SOP is also a specific group III metabotropic glutamate receptor (mGluR) agonist, we also tested if the more potent specific group III agonist, L-2-amino-4-phosphonobutyrate (L-AP4), the specific group III antagonist (RS)-α-Methylserine-O-phosphate (MSOP) or the specific group I antagonist, L-2-amino-3-phophonopropanoic acid (L-AP3) affected Müller glial proliferation. We found no changes with any of these factors compared to control retinas, revealing that metabotropic glutamate receptors were not necessary in the Müller glia proliferative response. Furthermore, ascl1a and stat3 expression were unaffected in either the L-SOP or MSOP-injected retinas relative to controls, suggesting L-SOP disrupts Müller glia proliferation subsequent to or in parallel with ascl1a and stat3 activation. This implies that at least one signaling mechanism, in addition to the process disrupted by L-SOP, is required to activate Müller glia proliferation in the light-damaged retina.


Posttraumatic growth and demoralization after cancer: The effects of patients' meaning-making.
It is common for patients to experience positive and negative psychological changes (e.g., posttraumatic growth or demoralization) after being diagnosed with cancer. Although demoralization and posttraumatic growth are both related to meaning-making, little attention has been paid to the associations among these concepts. The current study investigated the relationship between demoralization, posttraumatic growth, and meaning-making (focusing on sense-making and benefit-finding during the experience of illness) in cancer patients. Some 200 cancer patients (with lung cancer, lymphoma, or leukemia) at the MacKay Memorial Hospital in New Taipei completed the Demoralization Scale-Mandarin Version (DS-MV), the Chinese Posttraumatic Growth Inventory (CPTGI), and a self-designed questionnaire for assessing sense-making and benefit-finding. Demoralization was negatively correlated with posttraumatic growth, sense-making, benefit-finding, and time-since-diagnosis. Multiple regression analysis showed that meaning-making had different effects on demoralization and posttraumatic growth. The interactions of sense-making with either benefit-finding or time-since-diagnosis significantly predicted demoralization. Individuals with relatively higher sense-making and benefit-finding or shorter time-since-diagnosis experienced less demoralization. The suffering of cancer may turn on the psychological process of demoralization, posttraumatic growth, and meaning-making in patients. Cancer patients who evidenced higher posttraumatic growth experienced less demoralization. Trying to identify positive changes in the experience of cancer may be a powerful way to increase posttraumatic growth. As time goes by, patients experienced less demoralization. Facilitating sense-making can have similar effects. Cancer patients with less benefit-finding experience higher demoralization, but sense-making buffers this effect.


The solution NMR structure of a blue-green algae hepatotoxin, microcystin-RR--a comparison with the structure of microcystin-LR.
The microcystin-RR structures are compared with the structures of microcystin-LR in solution as well as in the crystal structure of the complex with protein phosphatase. The gross structures of the two peptides are similar, but with a more accentuated and compact saddle structure for microcystin-RR. The structural differences affect the hydrogen-bond pattern in the peptides and the location of the side chain of N-methyldehydroalanine, both of which are important for the ability of the peptide to form a tight complex with protein phosphatase. These structural differences may contribute to the observed differences in toxicity of microcystin-RR and microcystin-LR.


Statins in cardiometabolic disease: what makes pitavastatin different?
The term cardiometabolic disease encompasses a range of lifestyle-related conditions, including Metabolic syndrome (MetS) and type 2 diabetes (T2D), that are characterized by different combinations of cardiovascular (CV) risk factors, including dyslipidemia, abdominal obesity, hypertension, hyperglycemia/insulin resistance, and vascular inflammation. These risk factors individually and interdependently increase the risk of CV and cerebrovascular events, and represent one of the biggest health challenges worldwide today. CV diseases account for almost 50% of all deaths in Europe and around 30% of all deaths worldwide. Furthermore, the risk of CV death is increased twofold to fourfold in people with T2D. Whilst the clinical management of CV disease has improved in Western Europe, the pandemic of obesity and T2D reduces the impact of these gains. This, together with the growing, aging population, means the number of CV deaths is predicted to increase from 17.1 million worldwide in 2004 to 23.6 million in 2030. The recommended treatment for MetS is lifestyle change followed by treatment for the individual risk factors. Numerous studies have shown that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D or MetS. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one-third, which leaves substantial residual risk. Recent studies suggest that low high-density lipoprotein-cholesterol (HDL-C) (<1 .0 mmol/l; 40 mg/dl) and high triglyceride levels (≥1.7 mmol/l; 150 mg/dl) are independent risk factors for CV disease and that the relationship between HDL-C and CV risk persists even when on-treatment LDL-C levels are low (<1.7 mmol/l; 70 mg/dl). European guidelines highlight the importance of reducing residual risk by targeting these risk factors in addition to LDL-C. This is particularly important in patients with T2D and MetS because obesity and high levels of glycated hemoglobin are directly related to low levels of HDL-C and high triglyceride. Although most statins have a similar low-density lipoprotein-lowering efficacy, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects (for example, high-density lipoprotein-elevating efficacy), adverse event profiles, and drug-drug interactions. The choice of statin should therefore depend on the needs of the individual patient. The following reviews will discuss the potential benefits of pitavastatin versus other statins in the treatment of patients with dyslipidemia and MetS or T2D, focusing on its effects on HDL-C quantity and quality, its potential impact on atherosclerosis and CV risk, and its metabolic characteristics that reduce the risk of drug interactions. Recent controversies surrounding the potentially diabetogenic effects of statins will also be discussed.


Large-scale spatial population databases in infectious disease research.
Modelling studies on the spatial distribution and spread of infectious diseases are becoming increasingly detailed and sophisticated, with global risk mapping and epidemic modelling studies now popular. Yet, in deriving populations at risk of disease estimates, these spatial models must rely on existing global and regional datasets on population distribution, which are often based on outdated and coarse resolution data. Moreover, a variety of different methods have been used to model population distribution at large spatial scales. In this review we describe the main global gridded population datasets that are freely available for health researchers and compare their construction methods, and highlight the uncertainties inherent in these population datasets. We review their application in past studies on disease risk and dynamics, and discuss how the choice of dataset can affect results. Moreover, we highlight how the lack of contemporary, detailed and reliable data on human population distribution in low income countries is proving a barrier to obtaining accurate large-scale estimates of population at risk and constructing reliable models of disease spread, and suggest research directions required to further reduce these barriers.


Computerised training improves cognitive performance in chronic pain: a participant-blinded randomised active-controlled trial with remote supervision.
Chronic pain is associated with reduced efficiency of cognitive performance, and few studies have investigated methods of remediation. We trialled a computerised cognitive training protocol to determine whether it could attenuate cognitive difficulties in a chronic pain sample. Thirty-nine adults with chronic pain (mean age = 43.3, 61.5% females) were randomised to an 8-week online course (3 sessions/week from home) of game-like cognitive training exercises, or an active control involving watching documentary videos. Participants received weekly supervision by video call. Primary outcomes were a global neurocognitive composite (tests of attention, speed, and executive function) and self-reported cognition. Secondary outcomes were pain (intensity; interference), mood symptoms (depression; anxiety), and coping with pain (catastrophising; self-efficacy). Thirty participants (15 training and 15 control) completed the trial. Mixed model intention-to-treat analyses revealed significant effects of training on the global neurocognitive composite (net effect size [ES] = 0.43, P = 0.017), driven by improved executive function performance (attention switching and working memory). The control group reported improvement in pain intensity (net ES = 0.65, P = 0.022). Both groups reported subjective improvements in cognition (ES = 0.28, P = 0.033) and catastrophising (ES = 0.55, P = 0.006). Depression, anxiety, self-efficacy, and pain interference showed no change in either group. This study provides preliminary evidence that supervised cognitive training may be a viable method for enhancing cognitive skills in persons with chronic pain, but transfer to functional and clinical outcomes remains to be demonstrated. Active control results suggest that activities perceived as relaxing or enjoyable contribute to improved perception of well-being. Weekly contact was pivotal to successful program completion.


Placental Microbiome and Its Role in Preterm Birth.
Despite the well-known fact that the placenta has long-term effects on maternal and fetal health, the placenta remains a poorly understood and understudied organ. Not only is the placenta a site of exchange of nutrients and blood and gases between the fetal and maternal systems, but it also performs critical metabolic functions for supporting fetal development and maintaining maternal-fetal tolerance. It is also abundantly clear that impairment of placental function leads to severe pregnancy complications, including preterm birth (PTB), a significant cause of perinatal mortality and morbidity worldwide. Understanding the causes of PTB and other adverse outcomes is clearly essential for the development of effective methods of prevention and treatment. We focus our review of one major known cause of PTB, namely, infection. We also introduce a new and somewhat unexpected factor(s) that may well affect PTB and every aspect of placental biology and function: the placental microbiome. We discuss the implications of the placenta housing a microbial biomass for PTB and the effect of maternal microbiomes at various niches for fetal colonization and health outcomes. We suggest that the placenta is an integral part of the pipeline for microbe-powered driver of fetal destiny.


Augmentation of Primary ACL Reconstruction With a Modified Ellison Lateral Extra-articular Tenodesis in High-Risk Patients: A Pilot Study.
Lateral extra-articular tenodesis (LET) has been used to augment primary anterior cruciate ligament (ACL) reconstruction to reduce the risk of reinjury. Most LET procedures result in a construct that is fixed to both the femur and the tibia. In a modified Ellison procedure, the construct is only fixed distally, reducing the risk of inadvertently overconstraining the lateral compartment. To evaluate the use of the modified Ellison procedure in a cohort of patients deemed to be at a high risk of further ACL injury after primary ACL reconstruction. Case series; Level of evidence, 4. Included were 25 consecutive patients with at least 2 of the following risk factors: age <20 years at the time of surgery, previous contralateral ACL reconstruction, positive family history of ACL rupture (parent or sibling), generalized ligamentous laxity (Beighton ≥4), grade 3 pivot shift in the consulting room, a desire to return to a pivoting sport, and an elite or professional status. All patients underwent primary ACL reconstruction with an additional modified Ellison procedure. Postoperatively, patients completed the IKDC subjective knee evaluation form (International Knee Documentation Committee), KOOS Quality of Life subscale (Knee injury and Osteoarthritis Outcome Score), ACL-Return to Sport After Injury Scale, Marx Activity Rating Scale, and SANE score (Single Assessment Numeric Evaluation). At 12-month follow-up, the mean outcome scores were as follows: SANE, 94/100; IKDC, 92/100; Marx, 13/16; ACL-Return to Sport, 85/100; and KOOS, 77/100. At 24 months, return-to-sport data were available for 23 of 25 patients; 17 (74%) were playing at the same level or higher than preinjury and 2 at a lower level. One patient (4%) sustained a contact mechanism graft rupture at 12 months. There were 2 (9%) contralateral ACL injuries, including 1 ACL graft rupture, at 11 and 22 months postoperatively. There was a further contralateral ACL graft rupture at 26 months. The use of the modified Ellison procedure as a LET augmentation of a primary ACL reconstruction to produce a low graft rupture rate appeared to be safe in a cohort considered to be at a high risk of reinjury. The procedure showed promise in terms of reducing further graft injuries.


Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting.
Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML.


Medial gastrocnemius myoelectric control of a robotic ankle exoskeleton.
A previous study from our laboratory showed that when soleus electromyography was used to control the amount of plantar flexion assistance from a robotic ankle exoskeleton, subjects significantly reduced their soleus activity to quickly return to normal gait kinematics. We speculated that subjects were primarily responding to the local mechanical assistance of the exoskeleton rather than directly attempting to reduce exoskeleton mechanical power via decreases in soleus activity. To test this observation we studied ten healthy subjects walking on a treadmill at 1.25 m/s while wearing a robotic exoskeleton proportionally controlled by medial gastrocnemius activation. We hypothesized that subjects would primarily decrease soleus activity due to its synergistic mechanics with the exoskeleton. Subjects decreased medial gastrocnemius recruitment by 12% ( p < 0.05 ) but decreased soleus recruitment by 27% ( p < 0.05). In agreement with our hypothesis, the primary reduction in muscle activity was not for the control muscle (medial gastrocnemius) but for the anatomical synergist to the exoskeleton (soleus). These findings indicate that anatomical morphology needs to be considered carefully when designing software and hardware for robotic exoskeletons.


Comparing the lexical similarity of the triarchic model of psychopathy to contemporary models of psychopathy.
The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009) posits that psychopathic personality comprises three domains: boldness, meanness, and disinhibition. The present study aimed to clarify conceptual overlap between contemporary definitions of psychopathy, with particular emphasis given to the relevance of boldness (i.e., social dominance, venturesomeness, emotional resiliency)-a topic of recent debate. Undergraduate students (N = 439) compared the lexical similarity of triarchic domains with two contemporary models of psychopathy: the Comprehensive Assessment of Psychopathic Personality (CAPP; Cooke, Hart, Logan, & Michie, 2012) and the Five-Factor Model of psychopathy (FFM; Widiger & Lynam, 1998). From a content validity perspective, meanness and disinhibition were lexically similar to both the CAPP and FFM psychopathy, whereas boldness was less strongly associated with these models. Meanness showed the strongest lexical similarity in comparison with past prototypicality ratings of the CAPP and FFM psychopathy. These findings bear implications for defining and comparing conceptualizations of psychopathy that underpin its assessment.


Outcomes of pulmonary rehabilitation after lung resection in patients with lung cancer.
In this study, we aimed to examine the effectiveness of pulmonary rehabilitation applied after resection in patients with lung cancer. Between October 2017 and December 2019, a total of 66 patients (53 males, 13 females; median age: 65 years; range, 58 to 70 years) who underwent lung resection for non-small cell lung cancer and who were not administered any chemotherapy or radiotherapy regimen were included in the study. An eight-week comprehensive outpatient pulmonary rehabilitation program was applied to half of the patients, while the other half received respiratory exercise training. After the intervention, the results of both groups were compared. In the pulmonary rehabilitation group, forced vital capacity value (p=0.011), six-minute walking distance (p<0.001), and Short Form-36 physical function, mental health, vitality scores increased significantly, while all scores of St. George's Respiratory Questionnaire, dyspnea (p<0.001) and anxiety score (p=0.041) significantly decreased. In the group given breathing exercise training, only dyspnea (p=0.046) and St. George's Respiratory Questionnaire symptom scores (p=0.038) were decreased. When the changes in the groups after pulmonary rehabilitation were compared, the decrease in dyspnea perception was significantly higher in the pulmonary rehabilitation group (p<0.001). Pulmonary rehabilitation program applied after lung resection in patients with non-small cell lung cancer reduces dyspnea and psychological symptoms, increases exercise capacity, and improves quality of life. It should be ensured that patients with lung cancer who have undergone lung resection are directed to the pulmonary rehabilitation program and benefit from this program.


Mutation in internode length affects wheat plant-type.
A mutant form was found in an M(2) population of wheat Triticum aestivum L. em. Thell. (aestivum group) 'Seneca'. The population was derived from soaked grains treated with 3.2 kilorads of gamma rays. The first and second internodes below the spike were reduced in length 33 and 15 percent, respectively, and the total height was 18 percent shorter than the prototype. The flag leaf sheath was normal in length resulting in spike placement below the flag leaf lamina. Segregation data suggest that one dominant gene controls this character. The canopy structure of a population of mutant plants is different from that of the normal type; therefore, this mutant can be used to evaluate light interception and physiological aspects of crop productivity.


Metastatic hepatocellular carcinoma to the parotid gland: A diagnostic dilemma with review of the literature.
Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a leading cause of cancer-related death worldwide. It has a very aggressive clinical course, with a mean survival rate of much less than a year if left untreated. Here, we present a case of a 68-year-old male with progressively enlarging painful right facial swelling, involving the ramus and condyle of mandible on contrast-enhanced computed tomography mimicking an osteosarcoma. Eventually, the final diagnosis of HCC metastatic to the right parotid gland was made. We report a case of a rare metastasis of HCC to the parotid gland. Furthermore, the present case demonstrates the importance of tissue biopsy and immunohistochemistry for obtaining an accurate final diagnosis.


Morphosyntactic but not lexical corpus-based probabilities can substitute for cloze probabilities in reading experiments.
During reading or listening, people can generate predictions about the lexical and morphosyntactic properties of upcoming input based on available context. Psycholinguistic experiments that study predictability or control for it conventionally rely on a human-based approach and estimate predictability via the cloze task. Our study investigated an alternative corpus-based approach for estimating predictability via language predictability models. We obtained cloze and corpus-based probabilities for all words in 144 Russian sentences, correlated the two measures, and found a strong correlation between them. Importantly, we estimated how much variance in eye movements registered while reading the same sentences was explained by each of the two probabilities and whether the two probabilities explain the same variance. Along with lexical predictability (the activation of a particular word form), we analyzed morphosyntactic predictability (the activation of morphological features of words) and its effect on reading times over and above lexical predictability. We found that for predicting reading times, cloze and corpus-based measures of both lexical and morphosyntactic predictability explained the same amount of variance. However, cloze and corpus-based lexical probabilities both independently contributed to a better model fit, whereas for morphosyntactic probabilities, the contributions of cloze and corpus-based measures were interchangeable. Therefore, morphosyntactic but not lexical corpus-based probabilities can substitute for cloze probabilities in reading experiments. Our results also indicate that in languages with rich inflectional morphology, such as Russian, when people engage in prediction, they are much more successful in predicting isolated morphosyntactic features than predicting the particular lexeme and its full morphosyntactic markup.


Regulation of retinol uptake and esterification in MCF-7 and HepG2 cells by exogenous fatty acids.
The influence of extracellular fatty acids on the uptake and esterification of [3H]retinol bound to human retinol-binding protein (RBP), to RBP-transthyretin (TTR), or in dispersed form by the human hepatoma, HepG2, and human mammary epithelial carcinoma, MCF-7, cell lines was studied. The esterification of [3H]retinol was significantly increased in cells incubated with myristic, palmitic, stearic oleic, or linoleic acid-albumin complexes and was observed for all forms of [3H]retinol. Enhancement of [3H]retinol uptake was also observed in cells incubated with these fatty acids, but this increase was relatively small for the dispersed form as compared to that observed for [3H]retinol bound to RBP or RBP-TTR. Comparing equal concentrations of the [3H]retinol donors, cell uptake and esterification was greatest from the dispersed form and least from that bound to RBP-TTR. After preincubation of cells with oleate, uptake and esterification of [3H]retinol was increased but not to the extent observed when oleate and [3H]retinol donor were co-incubated. Incubation of cells with oleate resulted in rapid and correlated increases in the rates of [3H]retinol uptake and esterification which persisted until the steady state for [3H]retinol uptake was achieved. Beyond this time, net esterification of [3H]retinol continued in the presence of oleate. This kinetic pattern was observed for all [3H]retinol donors. These effects on [3H]retinol uptake and esterification were dose-dependent as the oleate to albumin ratio was varied from 0.5 to 3.0 and were observed across a physiological concentration range of RBP-3H-retinol. The data indicate that: 1) the fatty acid status of cells is a determinant of retinol uptake and esterification; and 2) the form of retinol presentation to cells is not qualitatively important for these processes.


The relationship between folding and activity in UreG, an intrinsically disordered enzyme.
A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease. The effect of denaturants and osmolytes on protein structure and activity was analyzed using circular dichroism (CD), Site-Directed Spin Labeling (SDSL) coupled to EPR spectroscopy, and enzymatic assays. Our data show that SpUreG needs a "flexibility window" to be catalytically competent, with both too low and too high mobility being detrimental for its activity.


Automatic knowledge extraction in sequencing analysis with multiagent system and grid computing.
Advances in bioinformatics have contributed towards a significant increase in available information. Information analysis requires the use of distributed computing systems to best engage the process of data analysis. This study proposes a multiagent system that incorporates grid technology to facilitate distributed data analysis by dynamically incorporating the roles associated to each specific case study. The system was applied to genetic sequencing data to extract relevant information about insertions, deletions or polymorphisms.


Association of Nursing Overtime, Nurse Staffing, and Unit Occupancy with Health Care-Associated Infections in the NICU.
Objective This study aims to assess the association of nursing overtime, nurse staffing, and unit occupancy with health care-associated infections (HCAIs) in the neonatal intensive care unit (NICU). Study Design A 2-year retrospective cohort study was conducted for 2,236 infants admitted in a Canadian tertiary care, 51-bed NICU. Daily administrative data were obtained from the database "Logibec" and combined to the patient outcomes database. Median values for the nursing overtime hours/total hours worked ratio, the available to recommended nurse staffing ratio, and the unit occupancy rate over 3-day periods before HCAI were compared with days that did not precede infections. Adjusted odds ratios (aOR) that control for the latter factors and unit risk factors were also computed. Results A total of 122 (5%) infants developed a HCAI. The odds of having HCAI were higher on days that were preceded by a high nursing overtime ratio (aOR, 1.70; 95% confidence interval [95% CI], 1.05-2.75, quartile [Q]4 vs. Q1). High unit occupancy rates were not associated with increased odds of infection (aOR, 0.85; 95% CI, 0.47-1.51, Q4 vs. Q1) nor were higher available/recommended nurse ratios (aOR, 1.16; 95% CI, 0.67-1.99, Q4 vs. Q1). Conclusion Nursing overtime is associated with higher odds of HCAI in the NICU.


Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats.
To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-like1 receptor (ORL1 receptor) in the estrus cycle of female rats. Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphe1]Nociceptin(1-13)NH2, that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohistochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat. Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreatment with 20 nmol NC13. The OFQ mRNA level in the POA on pro-estrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreactive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and estrus (P<0.05). The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on pro-estrus suggests that it might play a negative modulatory role in the estrus cycle.


Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization.
New types of protein sources will enter our diet in a near future, reinforcing the need for a straightforward in vitro (cell-based) screening model to test and predict the safety of these novel proteins, in particular their potential risk for de novo allergic sensitization. The Adverse Outcome Pathway (AOP) for allergen sensitization describes the current knowledge of key events underlying the complex cellular interactions that proceed allergic food sensitization. Currently, there is no consensus on the in vitro model to study the intestinal translocation of proteins as well as the epithelial activation, which comprise the first molecular initiation events (ME1-3) and the first key event of the AOP, respectively. As members of INFOGEST, we have highlighted several critical features that should be considered for any proposed in vitro model to study epithelial protein transport in the context of allergic sensitization. In addition, we defined which intestinal cell types are indispensable in a consensus model of the first steps of the AOP, and which cell types are optional or desired when there is the possibility to create a more complex cell model. A model of these first key aspects of the AOP can be used to study the gut epithelial translocation behavior of known hypo- and hyperallergens, juxtaposed to the transport behavior of novel proteins as a first screen for risk management of dietary proteins. Indeed, this disquisition forms a basis for the development of a future consensus model of the allergic sensitization cascade, comprising also the other key events (KE2-5).


Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission.
The role of seated immobility at work in the pathogenesis of venous thromboembolism (VTE) is uncertain. In this case series, 61 patients aged <65 years with a recent admission for deep venous thrombosis and/or pulmonary embolism completed an interviewer-administered questionnaire to obtain information regarding risk factors. Prolonged seated immobility at work in the 4 weeks before the VTE event was defined as being seated at least 8 h in a 24-h period and at least 3 h at a time without getting up, at least 10 h in a 24-h period and at least 2 h at a time without getting up or at least 12 h in a 24-h period and at least 1 h at a time without getting up. The most commonly identified risk factors were family history of VTE (21 of 61, 34%), seated immobility at work (21 of 61, 34%) and a thrombophilic state (19 of 61, 31%). We conclude that prolonged seated immobility at work may represent a common and important risk factor for VTE.


Saturation of the free carrier absorption in ZnTe crystals.
This study systematically investigates the influence of free carriers on the generation of THz in ZnTe crystals, over a wide range of pumping fluences. As the pumping fluence is increased (< 6.36 mJ/cm(2)), the concentration of free carriers gradually increases and the THz output power is saturated, as clearly demonstrated by the time delay in the THz temporal waveforms, the changes in the THz spectral weight and the red-shift in the PL spectra. For high pumping fluences (> 6.36 mJ/cm(2)), spectacularly, there is a significant quadratic increase in the THz output power when the pumping fluence is increased, as well as at low pumping fluences of < 0.58 mJ/cm(2), because of the saturation of free carriers.


Purification of Chlamydia trachomatis lymphogranuloma venereum elementary bodies and their interaction with HeLa cells.
A procedure has been developed to yield infectious elementary bodies of the lymphogranuloma venereum strains LGV 434 and 404 of Chlamydia trachomatis, labelled during intracellular growth in HeLa 229 cells. The final preparation, obtained after velocity sedimentation of a polycarbonate membrane-filtered sample through a sucrose gradient, is free of host proteins and, more importantly, of chlamydial reticulate bodies. Using such purified preparations, it was found that the association of LGV 434 elementary bodies with HeLa 229 cultures was unaffected by the pretreatment of the host cells with a variety of lectins or with neuraminidases from Clostridium perfringens and Vibrio cholerae. The association was inhibited by dextran sulphate and by mild trypsin treatment of HeLa cultures. Treatment of purified elementary bodies with trypsin, chymotrypsin, neuraminidases and a variety of carbohydrates and lectins did not produce any change in the rate of association with HeLa cultures. Heat-inactivated elementary bodies were significantly less able to associate with the host cells.


Does dilation and curettage affect future pregnancy outcomes?
The purpose of this study was to determine if dilation and curettage has an effect on future pregnancy outcome. Retrospective review of the electronic medical records of all patients who underwent D&C between January 1, 2002, and December 31, 2006, was performed. Patients who had one or more subsequent pregnancies were selected and evaluated for pregnancy outcome. Frequency and incidence of subsequent pregnancy complications were determined by Chi square and Fisher's exact tests and compared to reported statistics. The incidence of postpartum hemorrhage was significantly higher than previously reported averages (p < 0.0004). We found no difference in the incidence of preterm delivery, preeclampsia, placental abruption, malpresentation, cervical incompetence, first trimester bleeding, and miscarriage when compared with previously reported data. Pregnancy outcomes among patients with a history of cervical dilation and those without were not significantly different. The current study suggests that dilation and curettage may predispose to postpartum hemorrhage. It is important to consider the effects of surgical management for miscarriage on future pregnancy outcomes.


The relationship between plasma levels of immunoreactive atrial natriuretic hormone and hemodynamic function in man.
To evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p greater than .001) or femoral vein IR-ANH levels (r = .52, p less than .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p less than .002) and with femoral vein IR-ANH levels (r = .58, p less than .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 +/- 40 vs 90 +/- 20 pmol/liter; r = .90, p less than .001). Right ventricular and left ventricular levels were almost identical (155 +/- 46 vs 146 +/- 43 pmol/liter; r = .99, p less than .001). Patients with volume overload states had elevated IR-ANH levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Sedentary lifestyle and precocious puberty in girls during the COVID-19 pandemic: an Italian experience.
This retrospective study aimed to evaluate children observed for suspected precocious puberty in five Italian centers of Pediatric Endocrinology during the first wave of coronavirus disease 2019 pandemic (March-September 2020), compared to subjects observed in the same period of the previous year. The study population (490 children) was divided according to the year of observation and final diagnosis: transient thelarche, non-progressive precocious puberty, central precocious puberty (CPP), or early puberty. Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+122%). The increase was observed in girls (328 subjects in 2020 vs 140 in 2019, P < 0.05), especially during the second half of the period considered (92 girls from March to May vs 236 girls from June to September); while no difference was observed in boys (10 subjects in 2020 vs 12 in 2019). The percentage of girls with confirmed CPP was higher in 2020, compared to 2019 (135/328 girls (41%) vs 37/140 (26%), P < 0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 CPP girls showed more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population. The present findings corroborate the recently reported association between the complex lifestyle changes related to the lockdown and a higher incidence of CPP in Italian girls.


Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative Campath-1H exposure.
A number of recent reports in clinical and experimental intestinal transplantation have suggested that the donor lymphocytes present in and around the gastrointestinal system are potent mediators of graft-versus-host (GvH) reactivity and that GvH responses may contribute to posttransplant morbidity. Therefore, we have tested the proliferative and cytotoxic capabilities of gut-associated lymphocytes from cadaveric donors obtained prerevascularization (pre-r) and about 6 hours postrevascularization (post-r) in recipients pretreated with Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the recipient and third-party alloantigenic stimulating cells. However, similar preparations from the post-r samples responded in MLR at significantly lower levels (P < .01). This post-r decrease in responsiveness was not observed in similar lymphocyte samples obtained from donors of recipients not treated with Campath-1H. Both the pre-r and post-r samples had similar flow cytometric profiles, suggesting that there was no receptor loss in these lymphoid tissues by the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely, in preliminary experiments where the donor were treated with Campath-1H, it was observed that very few lymphocytes could be obtained from intestinal tissues (n = 3). These results suggested that Campath-1H treatment of the recipient could bring about a drastic reduction in an otherwise strong GvH reactivity by the donor intestinal immune cells.


Potential protective effects of alpha-pinene against cytotoxicity caused by aspirin in the IEC-6 cells.
Alpha-pinene is a key compound of the essential oils extracted from many species of coniferous trees. It is known for its biological activities. The aim of the present study was to determine the preventive effect of alpha-pinene on aspirin-induced toxicity in vitro, using IEC-6 cells, and to investigate its antioxidant activities. The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). The cytotoxicity and oxidative stress were detected by cell viability, antioxidant enzyme activity, malondialdehyde (MDA) and GSH production, and the activation of MAPK pathways. The results indicated that alpha-pinene revealed an important antioxidant activity. It was evaluated by DPPH test (EC50=310±10μg/mL) and FRAP test (EC50=238±18.92μg/mL). The co-exposure of alpha-pinene with aspirin on cells significantly increased the survival of cells and the level of GSH, and decreased the levels of MDA and total SOD and the activity of Mn-SOD. In addition, the activation of p38 and JNK was blocked by alpha-pinene. Therefore, these findings suggest that alpha-pinene can protect IEC-6 cells against aspirin-induced oxidative stress.