Volatile fatty acids production via mixed culture fermentation: Revealing the link between pH, inoculum type and bacterial composition.
The aim of the study was to investigate the effects of operational parameters, inoculum type and bacterial community on mixed culture fermentation to produce one dominant acid type in the mixture of volatile fatty acids (VFA). The study was performed using three different inocula (large&small granular and slurry) with glucose under various initial pH. The VFA production efficiency reached to 0,97 (gCOD/gSCOD) by granular sludge. VFA composition was changed by initial pH: in neutral conditions, acetic acid; in acidic conditions, acetic and butyric acids, in alkali conditions butyric acid were dominated, respectively. The VFA production was positively affected by the high relative abundance of Firmicutes. On the contrary, a negative correlation was seen between VFA production and the relative abundance of Chloroflexi. The results revealed the physical sludge structure of inoculum was the key factor for production efficiency, whereas, pH was the most important parameter to affect VFA composition.


van der Waals Interactions in Hadron Resonance Gas: From Nuclear Matter to Lattice QCD.
An extension of the ideal hadron resonance gas (HRG) model is constructed which includes the attractive and repulsive van der Waals (VDW) interactions between baryons. This VDW-HRG model yields the nuclear liquid-gas transition at low temperatures and high baryon densities. The VDW parameters a and b are fixed by the ground state properties of nuclear matter, and the temperature dependence of various thermodynamic observables at zero chemical potential are calculated within the VDW-HRG model. Compared to the ideal HRG model, the inclusion of VDW interactions between baryons leads to a qualitatively different behavior of second and higher moments of fluctuations of conserved charges, in particular in the so-called crossover region T∼140-190 MeV. For many observables this behavior resembles closely the results obtained from lattice QCD simulations. This hadronic model also predicts nontrivial behavior of net-baryon fluctuations in the region of phase diagram probed by heavy-ion collision experiments. These results imply that VDW interactions play a crucial role in the thermodynamics of hadron gas. Thus, the commonly performed comparisons of the ideal HRG model with the lattice and heavy-ion data may lead to misconceptions and misleading conclusions.


Dissecting seed pigmentation-associated genomic loci and genes by employing dual approaches of reference-based and k-mer-based GWAS with 438 Glycine accessions.
The soybean is agro-economically the most important among all cultivated legume crops, and its seed color is considered one of the most attractive factors in the selection-by-breeders. Thus, genome-wide identification of genes and loci associated with seed colors is critical for the precision breeding of crop soybeans. To dissect seed pigmentation-associated genomic loci and genes, we employed dual approaches by combining reference-based genome-wide association study (rbGWAS) and k-mer-based reference-free GWAS (rfGWAS) with 438 Glycine accessions. The dual analytical strategy allowed us to identify four major genomic loci (designated as SP1-SP4 in this study) associated with the seed colors of soybeans. The k-mer analysis enabled us to find an important recombination event that occurred between subtilisin and I-cluster B in the soybean genome, which could describe a special structural feature of ii allele within the I locus (SP3). Importantly, mapping analyses of both mRNAs and small RNAs allowed us to reveal that the subtilisin-CHS1/CHS3 chimeric transcripts generate and act as an initiator towards 'mirtron (i.e., intron-harboring miRNA precursor)'-triggered silencing of chalcone synthase (CHS) genes. Consequently, the results led us to propose a working model of 'mirtron-triggered gene silencing (MTGS)' to elucidate a long-standing puzzle in the genome-wide CHS gene silencing mechanism. In summary, our study reports four major genomic loci, lists of key genes and genome-wide variations that are associated with seed pigmentation in soybeans. In addition, we propose that the MTGS mechanism plays a crucial role in the genome-wide silencing of CHS genes, thereby suggesting a clue to currently predominant soybean cultivars with the yellow seed coat. Finally, this study will provide a broad insight into the interactions and correlations among seed color-associated genes and loci within the context of anthocyanin biosynthetic pathways.


[Typical sonographic findings in hemihepatectomized or partially hepatectomized patients].
The frequency of postoperative complications following immediately and at intervals after hepatic surgery, is evaluated by ultrasonography in 29 patients. In addition, the following sonographic findings--not mentioned upto now in literature--are pointed out: Enlargement of the typical cross-section of the vena cava and especially pseudotumorous vault of the parenchyma of the liver versus lumen of the vena cava; the latter may produce difficulties in discriminating local relapses in paracaval liver segments. Sclerosis of great liver veins with wall-like echoes in portal veins. After right hemihepatectomy, the portal vein could be identified by ultrasonography in only 50% of the cases. Transient oedema of the gallbladder wall and periportal fields. Tortuosity of intrahepatic vessels in the immediate postoperative course; especially after resection of great tumours of more than 7.5 cm diameter.


Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L.
Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited. To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts. We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed. We identified 2 DMPs with epigenome-wide significant (P < 2.4E-7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E-10) and cg04173586 in DOT1L (P = 2.09E-16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH. This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.


An Analysis of Malpractice Litigation of Vascular Surgeons in Cases Involving Aortic Pathologies.
The aim of this study was to analyze malpractice claims for aortic pathologies and to assess if there has been a change in rate of malpractice lawsuits with evolution of endovascular therapy. Malpractice lawsuits were individually screened and compiled from the Westlaw database from 2000 to 2017 through use of relevant search terms. Data were collected of allegations, diagnoses, and outcomes of each case and compared. 268 unique cases were included in this study, with aneurysms (54%, n = 145) and dissection (35%, n = 94) making up the majority. There was a defendant verdict in 53% (n = 141), plaintiff verdict in 24% (n = 65), and settlements in 23% (n = 62) of lawsuits. Litigation was higher in the Midwest and Northeast. There was a gradual decline in litigation overall, however endovascular case numbers remained constant. There was negligible difference in the primary allegation underlying the litigation for various aortic pathologies, time to litigation and award between open and endovascular procedures. The proportion of litigation for clinical negligence in endovascular cases amongst all vascular surgical lawsuits is increasing. As novel methods of endovascular therapy emerge, it is imperative that physicians remain vigilant to legal considerations to minimize malpractice risk.


Primary care and communication in shared cancer care: a qualitative study.
To explore perceptions of primary care physicians' (PCPs') and oncologists' roles, responsibilities, and patterns of communication related to shared cancer care in 3 integrated health systems that used electronic health records. Qualitative study. We conducted semistructured interviews with 10 patients having early-stage colorectal cancer and with 14 oncologists and PCPs. Sample sizes were determined by thematic saturation. Dominant themes and codes were identified and subsequently applied to all transcripts. Physicians reported that electronic health records improved communication within integrated systems but that communication with physicians outside of their system was still difficult. Primary care physicians expressed uncertainty about their role during cancer care, although medical oncologists emphasized the importance of comorbidity control during cancer treatment. Patients and physicians described additional roles for PCPs, including psychological distress support and behavior modification counseling. Integrated systems that use electronic health records likely facilitate shared cancer care through improved PCP-oncologist communication. However, strategies to promote a more active role for PCPs in managing comorbidities, psychological distress, and behavior modification, as well as to overcome communication challenges between physicians not practicing within the same integrated system, are still needed to improve shared cancer care.


[Treatment of Hodgkin's disease, clinical stage I and II. Results obtained in 100 patients by combination of 1 or 2 cycles of chemotherapy with radiotherapy].
The results obtained by chemo+radiotherapy in 100 patients with Hodgkin's disease at stage I or II as defined by clinical and radiological staging are analysed. All patients were treated by chemotherapy followed by radiotherapy; 74 received a complement chemotherapy after the radiotherapy. Statistical analysis emphasizes the usefulness of associating two cycles of chemotherapy with the classical radiotherapy. With this treatment which gives a constant remission rate of about 90% a long-term chemotherapy is no longer necessary and the interest of exploratory laparotomy becomes negligible.


Hepatic resection is associated with reduced postoperative opioid requirement.
Postoperative pain can significantly affect surgical outcomes. As opioid metabolism is liver-dependent, any reduction in hepatic volume can lead to increased opioid concentrations in the blood. The hypothesis of this retrospective study was that patients undergoing open hepatic resection would require less opioid for pain management than those undergoing open pancreaticoduodenectomy. Data from 79 adult patients who underwent open liver resection and eighty patients who underwent open pancreaticoduodenectomy at our medical center between January 01, 2010 and June 30, 2013 were analyzed. All patients received both general and neuraxial anesthesia. Postoperatively, patients were managed with a combination of epidural and patient-controlled analgesia. Pain scores and amount of opioids administered (morphine equivalents) were compared. A multivariate lineal regression was performed to determine predictors of opioid requirement. No significant differences in pain scores were found at any time point between groups. Significantly more opioid was administered to patients having pancreaticoduodenectomy than those having a hepatic resection at time points: Intraoperative (P = 0.006), first 48 h postoperatively (P = 0.001), and the entire length of stay (LOS) (P = 0.002). Statistical significance was confirmed after controlling for age, sex, body mass index, and American Society of Anesthesiologists physical status classification (adjusted P = 0.006). Total hospital LOS was significantly longer after pancreaticoduodenectomy (P = 0.03). A multivariate lineal regression demonstrated a lower opioid consumption in the hepatic resection group (P = 0.03), but there was no difference in opioid use based on the type of hepatic resection. Patients undergoing open hepatic resection had a significantly lower opioid requirement in comparison with patients undergoing open pancreaticoduodenectomy. A multicenter prospective evaluation should be performed to confirm these findings.


[Sensitivity of neurones of the limbic structure, hypothalamus and cerebral cortex of rabbits to microiontophoretic administration of corticotropin].
Reactions of the neurons of the hypothalamus, septum, amygdala of the hyppocampus, and of the brain cortex of rabbits to microionophoretic application of adrenocorticotropic hormone (ACTH) of the hypophysis, noradrenaline and acetylcholine were investigated. About half of the cells in all the brain areas under study changed the frequency of their discharges during the hormone application. The septal and the hyppocampus neurons mostly responded to ACTH by the excitation reactions, whereas neurons of the medial hypothalamus--by the inhibtion reactions. Comparison of the number of cells responding unidirectionally to the hormone and to each of the mediator agents studied, with the number of neurons responding multidirectionally showed no definite significant differences.


A new technique for correction of distal penile hypospadias.
The major aims of correction of hypospadias include construction of a neourethra, removal of the chordee, and reduction of the probability of postoperative fistulization. Here, we describe a new technique that can be easily used in cases with subcoronal distal penile hypospadias (even those with chordee) for the construction of the urethra using meatus-based transverse flaps. This new technique was used in 10 patients (mean age, 4.6 years). There were no complications such as fistula formation, chordee recurrence, hematoma formation, or flap necrosis during the follow-up period (mean follow-up period, 13.4 months). We believe that this surgical technique can be used in cases with chordee, carries a low risk of fistula formation, has the advantage of the use of richly vascular flaps for construction of the urethra, and yields a better cosmetic result. Hence, it can safely be used for surgical correction of distal hypospadias.


Two-color far-field fluorescence nanoscopy.
We demonstrate two-color fluorescence microscopy with nanoscale spatial resolution by applying stimulated emission depletion on fluorophores differing in their absorption and emission spectra. Green- and red-emitting fluorophores are selectively excited and quenched using dedicated beam pairs. The stimulated emission depletion beams deliver a lateral resolution of <30 nm and 65 nm for the green and the red color channel, respectively. The approximately 5 nm alignment accuracy of the two images establishes the precision with which differently labeled proteins are correlated in space. Colocalized nanoscopy is demonstrated with endosomal protein patterns and by resolving nanoclusters of a mitochondrial outer membrane protein, Tom20, in relation with the F(1)F(0)ATP synthase. The joint improvement of resolution and colocalization demonstrates the emerging potential of far-field fluorescence nanoscopy to study the spatial organization of macromolecules in cells.


Biventricular ICD Placement Percutaneously Via the Iliac Vein: Case Reports and a Review.
Cardiac resynchronization therapy (CRT) has been demonstrated to improve symptoms of heart failure. As a result, it has become the standard of care in selected patients, and is commonly completed with three leads placed via an upper-extremity vein. However, in rare situations, such as in the case of superior vena cava occlusion, venous access is not possible via the upper extremity. It is in such instances that alternative means must be sought. Here, two patients who received a CRT defibrillator via an iliac vein approach with a mid-abdominal generator are introduced, and a review of the techniques used is presented. Technical aspects to this approach are discussed, including iliac venous access, defibrillation electrode positioning, coronary sinus access, and lead tunneling to an abdominal generator for patient comfort. This approach should be considered when vascular access is compromised, at least until combined leadless CRT pacing and subcutaneous implantable cardioverter-defibrillator devices become available and feasible for use.


Corrigendum Supports Therapeutic Contribution of Acupoint Tapping to EFTs' Observed Effects: Response to Spielmans (2021).
We published a meta-analysis of studies that examined the various components of an evidence-based therapy called emotional freedom techniques (EFTs). EFT uses elements of conventional therapies such as exposure and cognitive processing but includes the unique ingredient of acupoint stimulation using fingertip tapping. Six studies were identified, and three of these met the quality control criteria of the American Psychological Association's Division 12 Task Force for Empirically Validated Therapies. Meta-analysis found that the acupoint component of EFT was not an inert ingredient or inactive placebo but made an active contribution to the therapeutic effects noted in a research literature that now numbers over 100 clinical trials of EFT. Subsequent to publication, errors in the original analysis were identified, primarily incorrect standard deviations. A new analysis was performed by an independent statistician and found slightly greater effects than the original investigation. The results were published as a corrigendum, which was subsequently challenged by Spielmans. Here we examine the critiques of the corrigendum and original article. We find that although they may be of academic interest, they are irrelevant to the central research question of whether the acupoint component of EFT is inert or active. We reaffirm that the evidence clearly validates the contribution made by acupoint tapping to EFT's observed clinical effects.


Lower Back Pain Imaging: A Readability Analysis.
The internet provides access to a myriad of educational health-related resources which are an invaluable source of information for patients. Lower back pain is a common complaint that is discussed extensively online. In this article, we aim to determine if the most commonly accessed articles about lower back pain imaging use language that can be understood by most patients. According to the American Medical Association (AMA) and National Institute of Health (NIH), this corresponds to a sixth-grade reading level. Online searches were conducted from the most commonly used search engine, Google, to assess the present state of readability on radiograph imaging for LBP. Then the top 20 populated URL links from each search were utilized based on "health & fitness" search trends and click-through rates (CTRs). The readability of various websites was evaluated with WebFX online software that analyzed the unique websites' text when put into reader view on Firefox web browser version 116.0.3 (64-bit). Evaluation occurred via five common readability indices: the Automated Readability Index (ARI), the Coleman Liau Index (CLI), the SMOG index, the Gunning Fog Score Index (GFSI), and the Flesch Kincaid Grade Level Index (FKGLI). In addition, the Flesch Kincaid Reading Ease Index (FKREI) was also used but was excluded from the calculation due to its measuring scale outside of US grade levels. The number of samples was analyzed via health and fitness-specific CTR from an open-access database from July 2022 to July 2023. This was used to calculate the number of persons clicking and visiting positional URLs (first URL to the 20th URL) from each unique keyword search and the rational criteria for selecting the first 20 websites for each query. Online material that included LBP imaging information was calculated to have an overall readability score of 10.745 out of the 23 websites obtained from unique searches. The range was a mean readability score of 8 to 14. Notably, 17 websites were excluded from a total of 40 websites due to duplication of the same data (URLs that resulted from both unique searches) and accessibility requiring payment (specifically, an UpToDate link). A readability score of 10.745 refers to an 11th-grade reading level. That is to say, the most commonly visited sites on Google that contain information about lower back pain imaging are, on average, five grade levels higher than the sixth-grade reading level recommended by the AMA and the NIH. Most internet content regarding lower back pain imaging is written at a reading level that is above the recommended limit defined by the AMA and NIH. To improve education about lower back pain imaging and the patient-physician relationship, we recommend guiding patients to online material that contains a reading level at the sixth-grade level as suggested by the AMA and NIH.


Mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115.
The mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115 (SC115) maintained in castrated DS mice by low doses of androgen (10 micrograms of testosterone propionate or 4 micrograms of 5 alpha-dihydrotestosterone/mouse/day) is reported. Although the low androgen treatment slightly but significantly (P less than 0.05) stimulated tumor growth, concomitant estrogen (4 micrograms of 17 beta-estradiol/mouse/day) significantly (P less than 0.01) enhanced the tumor growth. The high growth rate, histological type (medullary carcinoma), androgen dependency, and high androgen receptor content of the tumor grown during estrogen plus low androgen treatment did not differ significantly from those of the original SC115 tumor grown in normal males or in castrated mice treated with high doses of androgen. On the other hand, the treatment with low doses of androgen alone induced the development of slowly growing spindle-shaped cells from the medullary SC115 cells. The spindle-shaped cells containing low levels of androgen receptor were shown to be androgen independent and were also induced from the SC115 cells in nontreated castrated mice. These findings demonstrated that low doses of androgen and estrogen synergize to maintain and increase the growth of SC115 cells, whereas low doses of androgen alone fail to maintain the SC115 cells.


Detection of Reduced Retinal Vessel Density in Eyes with Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Projection-Resolved Optical Coherence Tomography Angiography.
To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes by using projection-resolved optical coherence tomography angiography (PR-OCTA). Prospective cross-sectional study. Study participants underwent macular 3- × 3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500-μm GA rim regions, and non-GA regions to similar macular locations in control eyes. Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8 ± 2.4% vs. 60.8 ± 3.1%; P < 0.001), ICP (34.0 ± 1.5% vs. 37.3 ± 1.7%; P = 0.003) and DCP (24.4 ± 2.3% vs. 28.0 ± 2.3%; P < 0.001) than control eyes. Retinal vessel density within the GA region decreased significantly in SVC, ICP, and DCP. Retinal vessel density in the GA rim region decreased in SVC and ICP but not in DCP. The non-GA region did not significantly deviate from normal controls. Eyes with GA had significantly reduced photoreceptor layer thickness; but similar nerve fiber layer, ganglion cell complex, inner nuclear layer, and outer plexiform layer thickness. Eyes with GA have reduced retinal vessel density in SVC, ICP, and DCP compared to those in controls. Loss is greatest within regions of GA. Vessel density may be more sensitive than retinal layer thickness measurement in the detection of inner retinal change in eyes with GA.


EEG power spectral responses to wind farm compared with road traffic noise during sleep: A laboratory study.
Wind turbine noise is dominated by low frequencies for which effects on sleep relative to more common environmental noise sources such as road traffic noise remain unknown. This study examined the effect of wind turbine noise compared with road traffic noise on sleep using quantitative electroencephalogram power spectral analysis. Twenty-three participants were exposed to 3-min samples of wind turbine noise and road traffic noise at three sound pressure levels (33, 38 and 43 dBA) in randomised order during established sleep. Acute (0-30 s) and more sustained (30-180 s) effects of noise presentations during N2 and N3 sleep were examined using spectral analysis of changes in electroencephalogram power frequency ranges across time in 5-s intervals. Both noise types produced time- and sound pressure level-dependent increases in electroencephalogram power, but with significant noise type by sound pressure level interactions in beta, alpha, theta and delta frequency bands (all p < 0.05). Wind turbine noise showed significantly lower delta, theta and beta activity immediately following noise onset compared with road traffic noise (all p < 0.05). However, alpha activity was higher for wind turbine noise played at lower sound pressure levels (33 dBA [p = 0.001] and 38 dBA [p = 0.003]) compared with traffic noise during N2 sleep. These findings support that spectral analyses show subtle effects of noise on sleep and that electroencephalogram changes following wind turbine noise and road traffic noise onset differ depending on sound pressure levels; however, these effects were mostly transient and had little impact on conventionally scored sleep. Further studies are needed to establish if electroencephalogram changes associated with modest environmental noise exposures have significant impacts on sleep quality and next-day functioning.


Light adaption of the cyclic GMP phosphodiesterase of frog photoreceptor membranes mediated by ATP and calcium ions.
The light-activated guanosine 3',5'-cyclic monophosphate (cyclic GMP) phosphodiesterase (PDE) of frog photoreceptor membranes has been assayed by measuring the evolution of protons that accompanies cyclic GMP hydrolysis. The validity of this assay has been confirmed by comparison with an isotope assay used in previous studies (Robinson et al. 1980. J. Gen. Physiol. 76: 631-645). The PDE activity elicited by either flash or continuous dim illumination is reduced if ATP is added to outer segment suspensions. This desensitization is most pronounced at low calcium levels. In 10(-9) M Ca++, with 0.5 mM ATP and 0.5 mM GTP present, PDE activity remains almost constant as dim illumination and rhodopsin bleaching continue. At intermediate Ca++ levels (10-7-10-5M) the activity slowly increases during illumination. Finally, in 10(-4) and PDE activity is more a reflection of the total number of rhodopsin molecules bleached than of the rate of the rhodopsin bleaching. At intermediate or low calcium levels a short-lived inhibitory process is revealed by observing a nonlinear summation of responses of the enzyme to closely spaced flashes of light. Each flash makes PDE activity less responsive to successive flashes, and a steady state is obtained in which activation and inactivation are balanced. It is suggested that calcium and ATP regulation of PDE play a role in the normal light adaption processes of frog photoreceptor membranes.


Integrating multiple criteria for the characterization of Psammotettix populations in European cereal fields.
The wheat dwarf disease is among the most damaging diseases in cereals. Its aetiological agent is the Wheat dwarf virus (WDV), which is exclusively transmitted from plant to plant by leafhoppers from the genus Psammotettix (Hemiptera, Cicadellidae). The parameters linked to the WDV/Psammotettix pathosystem are still poorly understood. We studied Psammotettix individuals collected in wheat and barley fields in France and, as a comparison, from grassland at agroecological interface in West Slovenia. Species identity of males and females has been determined using multiple criteria. In the first step, the characterization of the collected individuals included recordings of vibrational signals used in mating behaviour and morphometric analyses. In addition, a 442 nt sequence of the mitochondrial cytochrome oxydase I (COI) gene was obtained for some individuals and compared to COI sequences of the Psammotettix leafhoppers available in public databases. In the cereal fields in France, P sammotettix alienus was the most numerous species; however, it sometimes occurred together with Psammotettix confinis, while in the grasslands in Slovenia, the third syntopic species in Psammotettix community was Psammotettix helvolus. The temporal parameters of the P. alienus male calling song that were measured in this study were very similar to those measured in a previous study. The local biotic and/or abiotic parameters most likely influence the life history of Psammotettix leafhoppers, and the proportion of viruliferous individuals collected in cereal fields was 14.9%, while leafhoppers collected in Slovenia were virus-free. Taken together, results show that more detailed information on population structure of Psammotettix leafhoppers is crucial for providing an insight into the epidemiology of wheat dwarf disease.


Detection of pathogens from venous or arterial blood of patients with left-sided infective endocarditis by metagenomic next-generation sequencing: A prospective study.
Infective endocarditis is a life-threatening uncommon infectious disease, and we aimed to explore the clinical utility of venous or arterial blood-based metagenomic next-generation sequencing (mNGS) approaches to diagnose left-sided infective endocarditis (LSIE). We prospectively studied 79 LSIE patients who received valvular surgery in our hospital. Results of blood culture, valve culture, venous blood-based mNGS, arterial blood-based mNGS, venous blood-based mNGS plus blood culture, and arterial blood-based mNGS plus blood culture were evaluated and compared. Both venous blood- and arterial blood-based mNGS methods displayed significantly higher positive detection rates than blood culture and valve culture (43.0 %, 49.4 % vs. 32.9 %, 19.0 %; P < 0.001). Strikingly, when combining blood-based mNGS and blood culture, the positive rate could be further improved to more than 60 %. Moreover, we found mNGS LSIE detection was closely associated with preoperative leukocyte (P = 0.027), neutrophil value (P = 0.018), vegetation ≥ 14 mm (P = 0.043), and vegetations in aortic valve (P = 0.048). In addition, we discovered that blood-based mNGS had a superir capacity over blood culture to detect gram-negative bacteria, fungi, Bartonella Quintana, and mixed infections than blood culture. This study indicates that venous blood- and arterial blood-based mNGS displayed high positive rate in the rapid detection of pathogens in high-risk LSIE patients.


Ready for shared decision making: Pretesting a training module for health professionals on sharing decisions with their patients.
While shared decision-making (SDM) training programmes for health professionals have been developed in several countries, few have been evaluated. In Norway, a comprehensive curriculum, "klar for samvalg" (ready for SDM), for interprofessional health-care teams was created using generic didactic methods and guidance to tailor training to various contexts. The programmes adapted didactic methods from an evidence-based German training programmes (doktormitSDM). The overall aim was to evaluate two particular SDM modules on facilitating SDM implementation into clinical practice. A descriptive mixed methods study using questionnaires and a focus group guided by the Medical Research Council Complex Interventions Framework. The training was provided as two different applications (module AB [introduction and SDM-basics] and module ABC [introduction, SDM-basics and interactive training]) with differing learning objectives, extent of interactivity, and duration (1 vs 2 hours). Groups of participants were recruited consecutively based on requests for health professional SDM training in university/college- and hospital-settings. By a focus group and a self-administered questionnaire comprehensibility, relevance and acceptance were assessed and qualitative feedback collected after the training. Data passed descriptive and content analysis, respectively. Knowledge was assessed twice using five multiple-choice items and analysed using paired t-tests. In 11 (six AB and five ABC) training sessions, 357/429 (296 AB and 133 ABC) eligible nurses, physicians and health professional students with varying clinical backgrounds and previous levels of SDM-knowledge participated. SDM-knowledge increased from 25-78% (range pretest) to 85-95% (range post-test) (P ≤ .001). The training was rated easy to understand, acceptable and relevant for practice. Findings to improve the education suggest higher emphasis on interprofessional teaching methods. The two SDM training modules met the basic requirements for use in a broader SDM implementation strategy and can even improve knowledge.


A reproducible accelerated in vitro release testing method for PLGA microspheres.
The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures).


[Change of circadian pattern of arterial pressure in patients with congestive heart failure treated with perindopril, an inhibitor of angiotensin-converting enzyme (ACE)].
The 24-h profile of blood pressure (BP) was studied in 28 patients (21 males and 7 females) with congenital heart failure (CHF) of NYHA class II-III (ejection fraction < 45%). The patients were 46 to 76 years of age and had postinfarction cardiosclerosis. They had not received ACE inhibitors before. Two groups were formed basing on the presence of hypertension. Perindopril was administered in a single daily dose of 2 mg or higher if demanded to reduce symptoms of CHF and/or to normalize BP. The treatment continued for 3 months. The 24-h BP profile was assessed using portable device SpaceLabs 90207 (USA). In CHF patients with hypertension perindopril significantly lowered mean 24-h, day and night BP and its loads, reestablished two-phase circadian rhythm of AP and corrected BP variability. In CHF patients free of hypertension significant changes of the profile were not registered. It is evident that unwanted changes in the BP 24-h profile due to perindopril were absent in CHF normotensives.


Hip fractures and pain following proton therapy for management of prostate cancer.
Proton therapy (PT) for prostate cancer reduces rectal and bladder dose, but increases dose to the femoral necks. We assessed the risk of hip fracture and pain in men treated with PT for prostate cancer. From 2006 to 2008, 382 men were treated for prostate cancer and evaluated at six-month intervals after PT for toxicities at University of Florida Proton Therapy Institute (UFPTI). The WHO Fracture Risk Assessment Tool (FRAX) generated annual hip-fracture risk for the cohort. The WHO FRAX tool was utilized to generate the expected number of patients with hip fractures and the observed-to-expected ratio; confidence intervals and p-value were generated with the mid-P exact test. Univariate analysis of hip pain as a function of several prognostic factors was accomplished with Fisher's exact test. Median follow-up was four years (range, 0.1-5.5 years). Per FRAX, 3.02 patients were expected to develop a hip fracture without PT. Three PT patients actually developed fractures for a rate of 0.21 fractures per 100 person-years of follow-up. There was an observed-expected ratio of 0.99 (p-value not significant). Forty-eight patients (13%) reported new pain in the hip during follow-up; three required prescription analgesics. PT for prostate cancer did not increase hip-fractures in the first four years after PT compared to expected rates in untreated men.


Interpretable artificial intelligence-assisted embryo selection improved single-blastocyst transfer outcomes: a prospective cohort study.
What is the pregnancy and neonatal outcomes of an interpretable artificial intelligence (AI) model for embryo selection in a prospective clinical trial? This single-centre prospective cohort study was carried out from October 2021 to March 2022. A total of 330 eligible patients were assigned to their preferred groups, with 250 patients undergoing a fresh single-blastocyst transfer cycle after the exclusion criteria had been applied. For the AI-assisted group (AAG), embryologists selected the embryos for transfer based on the ranking recommendations provided by an interpretable AI system, while with the manual group, embryologists used the Gardner grading system to make their decisions. The implantation rate was significantly higher in the AAG than the manual group (80.87% versus 68.15%, P = 0.022). No significant difference was found in terms of monozygotic twin rate, miscarriage rate, live birth rate and ectopic pregnancy rate between the groups. Furthermore, there was no significant difference in terms of neonatal outcomes, including gestational weeks, premature birth rate, birth height, birthweight, sex ratio at birth and newborn malformation rate. The consensus rate between the AI and retrospective analysis by the embryologists was significantly higher for good-quality embryos (i.e. grade 4BB or higher) versus poor-quality embryos (i.e. less than 4BB) (84.71% versus 25%, P < 0.001). These prospective trial results suggest that the proposed AI system could effectively help embryologists to improve the implantation rate with single-blastocyst transfer compared with traditional manual evaluation methods.


Multiple inositol polyphosphate phosphatase: evolution as a distinct group within the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19.
Multiple inositol polyphosphate phosphatase is the only enzyme known to hydrolyze the abundant metabolites inositol pentakisphosphate and inositol hexakisphosphate. We have previously demonstrated that the chick homolog of multiple inositol polyphosphate phosphatase, designated HiPER1, has a role in growth plate chondrocyte differentiation. The relationship of these enzymes to intracellular signaling is obscure, and as part of our investigation we have examined the murine ((MMU)Minpp1) and human ((HSA)MINPP1) homologs. Northern blot analysis demonstrated expression of ((MMU)Minpp1 in a variety of mouse tissues, comparable to the expression of other mammalian homologs, but less restricted than the expression of HiPER1 in chick. A purified (MMU)Minpp1 fusion protein cleaved phosphate from inositol (1,3,4,5)-tetrakisphosphate and para-nitrophenyl phosphate. When the presumptive active site histidine was altered to alanine by site-directed mutagenesis, enzyme activity was abolished, confirming the classification of (MMU)Minpp1 as a histidine phosphatase. The amino acid sequences of the murine and human MINPP proteins share >80% identity with the rat enzyme and >56% identity with HiPER1, with conservation of the C-terminal consensus sequence that retains proteins in the endoplasmic reticulum. The intron/exon structure of the mammalian (MMU)Minpp1 and (HSA)MINPP1 genes is also conserved compared to the chick HiPER1 gene. Sequence analysis of plant and fruit fly MINPP homologs supports the hypothesis that the MINPP enzymes constitute a distinct evolutionary group within the histidine phosphatase family. We have mapped (HSA)MINPP1 to human chromosome 10q23 by fluorescence in situ hybridization, YAC screening, and radiation hybrid mapping. This assignment places (HSA)MINPP1 in a region of chromosome 10 that is frequently mutated in human cancers and places (HSA)MINPP1 proximal to the tumor suppressor PTEN, which maps to 10q23.3. Using a radiation hybrid panel, we localized (MMU)Minpp1 to a region of mouse chromosome 19 that includes the murine homolog of Pten. The evolutionary conservation of this novel enzyme within the inositol polyphosphate pathway suggests a significant role for multiple inositol polyphosphate phosphatase throughout higher eukaryotes.


The long winding road of opioid substitution therapy implementation in South-East Asia: challenges to scale up.
The South-East Asia Region contains an estimated 400,000-500,000 people who inject drugs (PWID). HIV prevalence among PWID is commonly 20% or higher in Indonesia, Thailand, Myanmar and some regions of India. Opioid substitution therapy (OST) is an important HIV prevention intervention in this part of the world. However, key challenges and barriers to scale up of OST exist, including: pervasive stigma and discrimination towards PWID; criminalisation of drug use overshadowing a public health response; lack of political will and national commitment; low financial investment; focus towards traditional treatment models of detoxification and rehabilitation; inadequate dosing of OST; and poor monitoring and evaluation of programmes. Our review of local evidence highlights that OST can be successful within the Asian context. Such evidence should be utilised more widely to advocate for policy change and increased political commitment to ensure OST reaches substantially more drug users. Significance for public healthSeveral countries in the World Health Organization South-East Asia Region can be commended for introducing opioid substitution therapy (OST) to address the ongoing HIV epidemic among people who inject drugs (PWID). Local evidence shows OST is an effective drug treatment approach in the Asian context given sufficient technical and institutional support. However, despite much progress, the number of OST dispensing sites and recipients remains totally inadequate in terms of impact upon the current HIV epidemic among PWID. Ongoing advocacy is needed if countries are to achieve the WHO's target of 40% of PWID being dosed with OST. Greater political commitment a strengthened policy environment, capacity building for OST clinics, lessening the criminalisation of drug use and promoting a public health response will give many more PWID access to OST and slow the advance of the HIV epidemic.


[Functional indices in assessment of gonarthrosis treatment efficacy with structum and chondrolon].
The trial included 50 patients aged from 40 to 67 years with osteoarthrosis (OA) stage I and II by Kellgren-Lawrence. Patients of group 1 (n=30) received chondrolon, of group 2 (n=20)--structum. Treatment efficacy was assessed by WOMAC scale, Leken's functional index, VAS pain at rest, walking, goniometry findings, time of 30 m walking. A positive clinical effect was achieved in both groups by all the indices. The improvement was significant in VAS pain, functional tests, Leken's index, WOMAC scale. A positive trend in clinical symptoms and tests developed more quickly in the treatment with chondrolon than with structum (in 8 vs. 12 months, respectively). Treatment with different chondroitin sulphate drugs raised quality of life in gonarthrosis patients assessed by WOMAC scale, the effect being comparable. Structum and chondrolon can be used for OA stage I-II with moderate dysfunction of knee joints. The treatment course should be long, at least 3 months, 3-6 months for structum.


Evaluation of algal active compounds as potent antibiofilm agent.
Biofilm is the syntrophic association of microbial colonies that remain adhered to the biotic and abiotic surfaces with the help of self-secreted polymeric substances also termed extracellular polymeric substances. Chronic pathogenicity caused by biofilm-associated pathogenic microorganisms becomes a significant threat in biomedical research. An extensive search is being made for the antibiofilm agents made from natural sources or their biogenic derivatives due to their effectivity and nontoxicity. Algae being the producer of various biogenic substances are found capable of disintegrating biofilm matrix and eradication of biofilm without exerting any deterrent effect on other biotas in the ecosystem. The current trend in phycological studies includes the exploration of antifouling efficacy among various algal groups. The extracts prepared from about 225 microalgae and cyanobacteria species are found to have antibiofilm activity. Polyunsaturated fatty acids are the most important component in the algal extract with antibacterial and antibiofilm properties. The antibiofilm activity of the sulfated polysaccharides extracted from a marine alga could be effectively used to remove dental biofilm. Algal extracts are also being used for the preparation of different biogenically synthesized nanoparticles, which are being used as potent antibiofilm agents. Genome editing of algal species by CRISPR/Cas9 may make precise modifications in the algal DNA for improving the algal strains and production of a more effective antibiofouling agent.


The Cellvibrio japonicus mannanase CjMan26C displays a unique exo-mode of action that is conferred by subtle changes to the distal region of the active site.
The microbial degradation of the plant cell wall is a pivotal biological process that is of increasing industrial significance. One of the major plant structural polysaccharides is mannan, a beta-1,4-linked d-mannose polymer, which is hydrolyzed by endo- and exo-acting mannanases. The mechanisms by which the exo-acting enzymes target the chain ends of mannan and how galactose decorations influence activity are poorly understood. Here we report the crystal structure and biochemical properties of CjMan26C, a Cellvibrio japonicus GH26 mannanase. The exo-acting enzyme releases the disaccharide mannobiose from the nonreducing end of mannan and mannooligosaccharides, harnessing four mannose-binding subsites extending from -2 to +2. The structure of CjMan26C is very similar to that of the endo-acting C. japonicus mannanase CjMan26A. The exo-activity displayed by CjMan26C, however, reflects a subtle change in surface topography in which a four-residue extension of surface loop creates a steric block at the distal glycone -2 subsite. endo-Activity can be introduced into enzyme variants through truncation of an aspartate side chain, a component of a surface loop, or by removing both the aspartate and its flanking residues. The structure of catalytically competent CjMan26C, in complex with a decorated manno-oligosaccharide, reveals a predominantly unhydrolyzed substrate in an approximate (1)S(5) conformation. The complex structure helps to explain how the substrate "side chain" decorations greatly reduce the activity of the enzyme; the galactose side chain at the -1 subsite makes polar interactions with the aglycone mannose, possibly leading to suboptimal binding and impaired leaving group departure. This report reveals how subtle differences in the loops surrounding the active site of a glycoside hydrolase can lead to a change in the mode of action of the enzyme.


The DNA of Bacteria of the World Ocean and the Earth in Cosmic Dust at the International Space Station.
Cosmic dust samples from the surface of the illuminator of the International Space Station (ISS) were collected by a crew member during his spacewalk. The sampler with tampon in a vacuum container was delivered to the Earth. Washouts from the tampon's material and the tampon itself were analyzed for the presence of bacterial DNA by the method of nested PCR with primers specific to DNA of the genus Mycobacteria, DNA of the strains of capsular bacteria Bacillus, and DNA encoding 16S ribosomal RNA. The results of amplification followed by sequencing and phylogenetic analysis indicated the presence of the bacteria of the genus Mycobacteria and the extreme bacterium of the genus Delftia in the samples of cosmic dust. It was shown that the DNA sequence of one of the bacteria of the genus Mycobacteria was genetically similar to that previously observed in superficial micro layer at the Barents and Kara seas' coastal zones. The presence of the wild land and marine bacteria DNA on the ISS suggests their possible transfer from the stratosphere into the ionosphere with the ascending branch of the global electric circuit. Alternatively, the wild land and marine bacteria as well as the ISS bacteria may all have an ultimate space origin.


The community and consumer food environment and children's diet: a systematic review.
While there is a growing body of research on food environments for children, there has not been a published comprehensive review to date evaluating food environments outside the home and school and their relationship with diet in children. The purpose of this paper is to review evidence on the influence of the community and consumer nutrition environments on the diet of children under the age of 18 years. Our search strategy included a combination of both subject heading searching as well as natural language, free-text searching. We searched nine databases (MEDLINE, Web of Science, CINAHL, Embase, Scopus, ProQuest Public Health, PsycINFO, Sociological Abstracts, and GEOBASE) for papers published between 1995 and July 2013. Study designs were included if they were empirically-based, published scholarly research articles, were focused on children as the population of interest, fit within the previously mentioned date range, included at least one diet outcome, and exposures within the community nutrition environment (e.g., location and accessibility of food outlets), and consumer nutrition environment (e.g., price, promotion, and placement of food choices). After applying exclusion and inclusion criteria, a total of 26 articles were included in our review. The vast majority of the studies were cross-sectional in design, except for two articles reporting on longitudinal studies. The food environment exposure(s) included aspects of the community nutrition environments, except for three that focused on the consumer nutrition environment. The community nutrition environment characterization most often used Geographic Information Systems to geolocate participants' homes (and/or schools) and then one or more types of food outlets in relation to these. The children included were all of school age. Twenty-two out of 26 studies showed at least one positive association between the food environment exposure and diet outcome. Four studies reported only null associations. This review found moderate evidence of the relationship between the community and consumer nutrition environments and dietary intake in children up to 18 years of age. There is wide variation in measures used to characterize both the community and consumer nutrition environments and diet, and future research should work to decrease this heterogeneity.


Impact of construal level manipulations on delay discounting.
Construal Level Theory states that psychologically proximal outcomes are construed concretely while psychologically distal outcomes are construed abstractly. Previous research suggests that the principles of Construal Level Theory can be applied to enhance self-control, as measured by delay discounting. The present studies replicate and expand on this work by examining whether theory-informed priming manipulations lead to delay discounting reductions in a repeated-measures design. Study 1 conceptually replicated previous work, with reduced delay discounting observed as a function of thinking abstractly. Studies 2 and 3 expanded on this work by reinterpreting (a) preference for immediate outcomes as preference for outcomes that are construed concretely, and (b) dispreference for delayed outcomes as dispreference for outcomes that are construed abstractly. Study 2 provided support for the first interpretation, as reduced delay discounting was observed as a function of thinking concretely about the future. Study 3 provided support for the second interpretation, as reduced delay discounting was observed as a function of thinking abstractly about the present. In studies 1 and 3, significant condition × order interactions were observed. In all three studies, the same impact of order of exposure to priming manipulation was observed, indicating specific carryover effects.


Solvent exposure from liquid sampling media.
Use of a personal sampling method using a toluene-based solution in a midget impinger led to the suspicion that it would result in toluene exposure to the worker. Field data from three workplaces indicate that in open environments, 8-hour TWA toluene exposures range from 3.6 - 20.1 mg/m3 with a mean of 8.9 mg/m3. However, sampling in semi-confined spaces resulted in 8-hour TWA concentrations up to 189 mg/m3, or 50% of the NIOSH-recommended exposure limit (375 mg/m3). Use of this and similar wet sampling methods in confined spaces requires investigators to be aware of the degree of ventilation in the space; and suggests the need to predict potential exposures before sampling. The vapor pressure method is a rapid, safe and simple way to predict this potential exposure.


Cervical ectopy in adolescent girls with and without human immunodeficiency virus infection.
The objective of this study was to examine factors, including human immunodeficiency virus (HIV) infection, associated with ectopy among adolescent girls aged 12-20 years who were participating in an ongoing study of HIV infection in adolescents. Samples for detection of bacterial vaginosis, Chlamydia trachomatis, and Neisseria gonorrhoeae and a high-resolution photograph of the cervix for ectopy measurement were collected. Ectopy data for 189 and 92 HIV-positive and -negative adolescents, respectively, were examined. Although univariate analysis found HIV infection and oral contraceptive use to be associated with the amount of ectopy, multivariate logistic regression analysis showed that only number of lifetime sex partners was a significant predictor, with more partners associated with less ectopy (odds ratio, 0.47; 95% confidence interval, 0.22-1.00; P=.05). In summary, adolescent girls with greater numbers of lifetime sex partners were more likely to have mature cervixes (less ectopy). HIV infection was not independently associated with ectopy.


Is familial hyperparathyroidism a unique disease?
Familial hyperparathyroidism is a rare condition reported to behave more aggressively than sporadic hyperparathyroidism. A retrospective (1975 to 1995) analysis was performed on 30 such patients. All patients had at least one first-degree relative with surgically treated hyperparathyroidism and no personal or family history of multiple endocrine neoplasia. There were 19 women and 11 men with a mean age of 39 years (range, 13 to 78 years). Fourteen patients (47%) had nephrolithiasis. The mean serum calcium level was 11.6 mg/dl (range, 10.5 to 15.3 mg/dl). Twenty-three primary and 15 repeat explorations (eight recurrent and seven persistent disease) were performed during the study period. Follow-up was obtained on all patients and ranged from 1 to 21 years (mean, 12 years). At the conclusion of the study, hypercalcemia (five recurrent and one persistent) was present in six patients (20%). Familial hyperparathyroidism is a distinct and unique entity. Patients are diagnosed at a young age and have a high incidence of nephrolithiasis. Long-term follow-up is mandatory because of the high incidence of both recurrent and persistent hyperparathyroidism. Surgical treatment should include subtotal parathyroidectomy and routine transcervical thymectomy performed in centers with experience in the management of multiple-gland parathyroid disease.


Preoperative management of the pheochromocytoma patient.
Pheochromocytomas are rare neuroendocrine tumors with a highly variable clinical presentation, but they most commonly present as spells of headaches, sweating, palpitations, and hypertension. Patients with pheochromocytoma may develop complicated and potentially lethal cardiovascular and other complications, especially in the setting of diagnostic or interventional procedures (e.g. upon induction of anesthesia or during surgery). The serious and potentially lethal nature of such complications is due to the potent effect of paroxysmal release of catecholamines. Because this warrants prompt diagnosis and treatment, the physician should be aware of the clinical manifestations and complications of catecholamine excess and be able to provide proper preoperative management to minimize catecholamine-related pre-, intra-, and postoperative adverse events. The following clinical scenario and discussion aim to enhance the knowledge of the physician regarding the behavior of pheochromocytoma and to outline current approaches to comprehensive preoperative management of patients suffering from this tumor.


Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition.
Exosomes are nanovesicles released by different cell types including dendritic cells (DCs). The fact that exosomes express surface MHC-peptide complexes suggests that they could function as Ag-presenting vesicles or as vehicles to spread allogeneic Ags for priming of anti-donor T cells during elicitation of graft rejection or induction/maintenance of transplant tolerance. We demonstrate that circulating exosomes transporting alloantigens are captured by splenic DCs of different lineages. Internalization of host-derived exosomes transporting allopeptides by splenic DCs leads to activation of anti-donor CD4 T cells by the indirect pathway of allorecognition, a phenomenon that requires DC-derived, instead of exosome-derived, MHC class II molecules. By contrast, allogeneic exosomes are unable to stimulate direct-pathway T cells in vivo. We demonstrate in mice that although graft-infiltrating leukocytes release exosomes ex vivo, they do not secrete enough concentrations of exosomes into circulation to stimulate donor-reactive T cells in secondary lymphoid organs. Instead, our findings indicate that migrating DCs (generated in vitro or isolated from allografts), once they home in the spleen, they transfer exosomes expressing the reporter marker GFP to spleen-resident DCs. Our results suggest that exchange of exosomes between DCs in lymphoid organs might constitute a potential mechanism by which passenger leukocytes transfer alloantigens to recipient's APCs and amplify generation of donor-reactive T cells following transplantation.


Leydig cell aging and hypogonadism.
Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences.


Preterm appropriate for gestational age infants: size at birth explains subsequent growth.
The aim was to evaluate growth and breastfeeding up to 18 months corrected age (CA) among preterm appropriate for gestational age (AGA) infants whose mothers initiated breastfeeding during the infants' hospital stay. One hundred and twenty-seven preterm AGA infants with a median birth weight of 2320 (769-3250) g and gestational age 34.29 (25.00-35.86) weeks were evaluated up to a CA of 18 months. A retrospective, descriptive and comparative design was used. Data were obtained by chart review of hospital medical records and a questionnaire completed by the mothers. The changes in standard deviation scores (SDS) during the infants' hospital stay were -0.9 for weight, -0.3 for length and -0.5 for head circumference (HC). Infants with higher SDS at birth showed more negative changes from birth to discharge. Median increments in SDS from discharge to a CA of 2 months were as high as, or higher than, the loss from birth to discharge. Preterm AGA infants with higher SDS for weight, length and HC at birth are at higher risk of inadequate growth during their hospital stay.


Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials.
Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.


Short- versus long-term responses to changing CO2 in a coastal dinoflagellate bloom: implications for interspecific competitive interactions and community structure.
Increasing pCO2 (partial pressure of CO2 ) in an "acidified" ocean will affect phytoplankton community structure, but manipulation experiments with assemblages briefly acclimated to simulated future conditions may not accurately predict the long-term evolutionary shifts that could affect inter-specific competitive success. We assessed community structure changes in a natural mixed dinoflagellate bloom incubated at three pCO2 levels (230, 433, and 765 ppm) in a short-term experiment (2 weeks). The four dominant species were then isolated from each treatment into clonal cultures, and maintained at all three pCO2 levels for approximately 1 year. Periodically (4, 8, and 12 months), these pCO2 -conditioned clones were recombined into artificial communities, and allowed to compete at their conditioning pCO2 level or at higher and lower levels. The dominant species in these artificial communities of CO2 -conditioned clones differed from those in the original short-term experiment, but individual species relative abundance trends across pCO2 treatments were often similar. Specific growth rates showed no strong evidence for fitness increases attributable to conditioning pCO2 level. Although pCO2 significantly structured our experimental communities, conditioning time and biotic interactions like mixotrophy also had major roles in determining competitive outcomes. New methods of carrying out extended mixed species experiments are needed to accurately predict future long-term phytoplankton community responses to changing pCO2 .


A Global Outlook on Child Sexual Abuse and Sexually Explicit Material Online During COVID-19: Trends and Interdisciplinary Prevention Methods.
This scoping review investigates the impact of COVID-19 on global and national trends in online child sexually explicit material (CSEM) trafficking and production in addition to online child sexual abuse (OCSA). Globally, CSEM consumption increased dramatically during the pandemic, as well as trafficking of self-generated material. The hypothesized reasons for the increase in OCSA and CSEM that guided this review included stay-at-home orders, COVID-19-related precautions, technology use increase, economic instability, and lack of available victim and legal resources. Current global and national law enforcement procedures to prevent the proliferation of online sexual abuse are reviewed with suggestions for preventing further increases in CSEM production, distribution, and consumption at the micro and macro levels.


Elevated ozone reduces photosynthetic carbon gain by accelerating leaf senescence of inbred and hybrid maize in a genotype-specific manner.
Exposure to elevated tropospheric ozone concentration ([O3 ]) accelerates leaf senescence in many C3 crops. However, the effects of elevated [O3 ] on C4 crops including maize (Zea mays L.) are poorly understood in terms of physiological mechanism and genetic variation in sensitivity. Using free air gas concentration enrichment, we investigated the photosynthetic response of 18 diverse maize inbred and hybrid lines to season-long exposure to elevated [O3 ] (~100 nl L-1 ) in the field. Gas exchange was measured on the leaf subtending the ear throughout the grain filling period. On average over the lifetime of the leaf, elevated [O3 ] led to reductions in photosynthetic CO2 assimilation of both inbred (-22%) and hybrid (-33%) genotypes. There was significant variation among both inbred and hybrid lines in the sensitivity of photosynthesis to elevated [O3 ], with some lines showing no change in photosynthesis at elevated [O3 ]. Based on analysis of inbred line B73, the reduced CO2 assimilation at elevated [O3 ] was associated with accelerated senescence decreasing photosynthetic capacity and not altered stomatal limitation. These findings across diverse maize genotypes could advance the development of more O3 tolerant maize and provide experimental data for parameterization and validation of studies modeling how O3 impacts crop performance.


New Development of Biomarkers for Gastrointestinal Cancers: From Neoplastic Cells to Tumor Microenvironment.
Biomarkers refer to a plethora of biological characteristics that can be quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and predict a response to treatment. The identification of objective biomarkers is among the most crucial steps in the realization of individualized cancer care. Several tumor biomarkers for gastrointestinal malignancies have been applied in the clinical setting to help differentiate between cancer and other conditions, facilitate patient selection for targeted therapies, and to monitor treatment response and recurrence. With the coming of the immunotherapy age, the need for a new development of biomarkers that are indicative of the immune response to tumors are unprecedentedly urgent. Biomarkers from the tumor microenvironment, tumor genome, and signatures from liquid biopsies have been explored, but the majority have shown a limited prognostic or predictive value as single biomarkers. Nevertheless, use of multiplex biomarkers has the potential to provide a significantly increased diagnostic accuracy compared to traditional single biomarker. A comprehensive analysis of immune-biomarkers is needed to reveal the dynamic and multifaceted anti-tumor immunity and thus imply for the rational design of assays and combinational strategies.


Pitching single-focus confocal data analysis one photon at a time with Bayesian nonparametrics.
Fluorescence time traces are used to report on dynamical properties of molecules. The basic unit of information in these traces is the arrival time of individual photons, which carry instantaneous information from the molecule, from which they are emitted, to the detector on timescales as fast as microseconds. Thus, it is theoretically possible to monitor molecular dynamics at such timescales from traces containing only a sufficient number of photon arrivals. In practice, however, traces are stochastic and in order to deduce dynamical information through traditional means-such as fluorescence correlation spectroscopy (FCS) and related techniques-they are collected and temporally autocorrelated over several minutes. So far, it has been impossible to analyze dynamical properties of molecules on timescales approaching data acquisition without collecting long traces under the strong assumption of stationarity of the process under observation or assumptions required for the analytic derivation of a correlation function. To avoid these assumptions, we would otherwise need to estimate the instantaneous number of molecules emitting photons and their positions within the confocal volume. As the number of molecules in a typical experiment is unknown, this problem demands that we abandon the conventional analysis paradigm. Here, we exploit Bayesian nonparametrics that allow us to obtain, in a principled fashion, estimates of the same quantities as FCS but from the direct analysis of traces of photon arrivals that are significantly smaller in size, or total duration, than those required by FCS.


Subcutaneous panniculitis-like T-cell lymphoma associated with hemophagocytic lymphohistiocytosis: a systematic review of 63 patients reported in the literature.
To review and summarize the clinical features, treatment strategies, and prognosis of subcutaneous panniculitis-like T-cell lymphoma complicated with hemophagocytic lymphohistiocytosis (SPTCL-HLH). We searched the Web of Science, Embase, Cochrane Library, and PubMed databases. The keywords were subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis or hemophagocytic syndrome. The patients were divided into a mutated group and a wild-type group based on the existence of HAVCR2 gene mutation. A total of 45 reports, including 63 patients with SPTCL-HLH, were included in the systematic review. Twelve patients detected gene mutations, including 11 with the HAVCR2 gene mutation and 1 with the STXBP2 gene mutation. Thirty-one patients were tested for autoantibodies. Compared with the wild-type group, patients in the mutated group were younger (p = 0.017), and the autoantibody-positive rate was higher (p = 0.006). The main treatment target of 17 patients was to control HLH, yielding an ORR of 88.2%. Two cases relapsed, and both were treated with corticosteroid monotherapy. The corticosteroid monotherapy experienced a higher recurrence rate than the corticosteroids plus other immunoregulatory agents therapy (66.7 vs. 0.0%, p = 0.029). Eighteen patients received initial anthracycline-based chemotherapy, and 50.0% reached remission. The ORR of initial chemotherapy aiming at controlling HLH was higher than those of anthracycline-based chemotherapy (p = 0.015). The ORR was higher in patients initially controlled for HLH versus chemotherapy without HLH control first (90.5 vs. 61.5%, p = 0.024). Interestingly, one patient with juvenile idiopathic arthritis developed SPTCL-HLH during tocilizumab therapy, discontinuing tocilizumab led to a remission of the disease spontaneously. Sixteen patients received stem cell transplantation (SCT). Fifteen patients, including 5 with relapsed/refractory SPTCL-HLH, responded well and survived after receiving SCT. One case who received a sibling-identical SCT relapsed. Further analysis revealed a homozygous HAVCR2 mutation with the donor. The 2-year overall survival (OS) was 91.0% ± 4.4%. There was a significant difference in the OS among patients of different age groups, and patients aged 40-60 had the lowest 2-year OS (66.7% ± 19.2%). Patients with HAVCR2 gene mutations are younger and more likely to be misdiagnosed with autoimmune diseases. Initial treatment of corticosteroids plus immunoregulatory agents attaches great significance to avoiding too aggressive therapies. Intensive anthracycline-based chemotherapy such as CHOP or CHOP-like regimens can also induce long-term remission for aggressive disease. SCT is still a reliable strategy currently. In addition, a watch and wait approach is recommended in patients with mild SPTCL-HLH caused by drugs. The occurrence of HLH does not necessarily mean a more rapidly progressive disease and worse prognosis in patients with SPTCL, but older patients with SPTCL-HLH may be associated with a lower survival rate.


Hearing impairment, disability and handicap in elderly people living in residential care and in the community.
This study aimed to compare the prevalence of hearing impairment, disability and handicap in the elderly living in residential care with those living in the community, and to examine the relationship between impairment, disability and handicap in both groups. Fifty community-based and 129 residential subjects were assessed using pure-tone audiometry as a measure of impairment, and a self-assessment questionnaire as a measure of disability and handicap. Community-based subjects were also assessed using a test of speech discrimination as an objective measure of disability. Results indicated 95% of residential subjects and 70% of community-based subjects were hearing-impaired, while 27% of residential subjects and 42% of community-based subjects demonstrated significant disability/handicap. Significant correlations were obtained between impairment, disability and handicap in both subject groups. The implications of the findings for the aural rehabilitation of the elderly are discussed.


Intravenous salbutamol for childhood asthma: evidence-based medicine?
Intravenous salbutamol is commonly used to treat children with severe asthma unresponsive to inhaled β2-agonist therapy. However, in this setting, there is little clinical trial data demonstrating its effectiveness. Additionally, there are significant concerns that intravenous salbutamol-dosing recommendations for children with acute asthma are excessive, and unnecessarily raise the potential for adverse reactions, such as lactic acidosis and tachycardia which, by increasing respiratory workload, exacerbate respiratory failure. Here, we review salbutamol clinical pharmacology and toxicology, evidence relating to its use in acute asthma and highlight gaps in the evidence base.


Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia.
Modafinil, a novel cognitive enhancer, selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder (ADHD). It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission. The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia. Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind, randomized, placebo-controlled crossover study using a 200 mg dose of modafinil. Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. Improvement was seen on short-term verbal memory span, with trends towards improved visual memory and spatial planning. This was accompanied by slowed response latency on the spatial planning task. No effect on stop-signal performance was seen. Importantly, significant improvement in attentional set shifting was seen, despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.


Short-term neuropsychological recovery in clients with substance use disorders.
Cognitive impairments are frequently observed in clients who enter treatment programs for substance abuse. The potential for early recovery of cognitive abilities is suggested by previous research; however, the extent of improvement and risk factors that may help predict individual differences in rates of recovery remain unclear. This study is a 6-week follow-up and retest of an original sample of 197 men and women who had received a broad neuropsychological assessment at addiction treatment entry. The aim was to examine the potential clinical significance of changes in cognitive functioning and the extent to which differential recovery was predictable from client background information. Fifteen neuropsychological tests were readministered to 169 of 197 clients 6 weeks after treatment entry. Structural equation modeling was used to estimate separately the practice effects and recovery in four cognitive domains: executive function, memory, information processing speed, and verbal ability. Client background information included age, sex, education, substance use and consequences, psychopathology, medical problems, familial alcoholism history, and childhood behavior problems. A four-factor model of latent neuropsychological ability that was previously identified at treatment entry was replicated at follow-up. Statistically significant increases in the means of the four latent abilities were found. Memory showed a medium effect size improvement. Executive function, verbal ability, and information processing speed, however, showed only small effect size improvements, suggesting limited clinical significance. Substance use between treatment entry and follow-up, antisocial personality disorder, negative use consequences, less education, and medical problems were modestly predictive of less recovery. Cognitive recovery in the first 6 weeks of treatment is possible, but, with the possible exception of memory, improvement may be minor in terms of clinical relevance.


The quality of preventive health care delivered to adults: results from a cross-sectional study in Southern Italy.
It is assumed that providing clinical preventive services to patients can identify or detect early important causes of adult mortality. The aim of this study was to quantify access to preventive services in Southern Italy and to assess whether and how the provision of preventive care was influenced by any specific characteristics of patients. In a cross-sectional study adults aged 18 years and over attending primary care physician (PCP) offices located in Southern Italy were interviewed from June through December 2007. Quality indicators of preventive health care developed from RAND's Quality Assessment Tools and Behavioral Risk Factor Surveillance System (BRFSS) were used. Multivariate analysis was performed to identify and to assess the role of patients' characteristics on delivery of clinical preventive services. A total of 1467 subjects participated in the study. Excepting blood pressure preventive check (delivered to 64.4% of eligible subjects) and influenza vaccination (recommended to 90.2% of elderly), the rates of delivery of clinical preventive services were low across all measures, particularly for screening and counseling on health habits. Rates for providing cancer screening tests at recommended times were 21.3% for colonoscopy, 51.5% for mammography and 52.4% for Pap smear. Statistical analysis showed clear disparities in the provision of clinical preventive services associated with age, gender, education level, perceived health status, current health conditions and primary care access measures. There is overwhelming need to develop and implement effective interventions to improve delivery of routine clinical preventive services.


Childhood borderline lepromatous leprosy: a case report.
Leprosy in children is a strong indicator of the recent failure of leprosy control and disease transmission programs. For twenty-two years, leprosy has been declared `eliminated as a public health hazard,` yet new cases continue to emerge in endemic areas. The new case detection rate among the child population was recorded at 4.4 per million children. Because of their underdeveloped or neonatal immunity and exposure to intrafamilial contacts, children tend to be the most vulnerable population. We present a case of the borderline lepromatous type of leprosy in a 9-year-old Indonesian male patient with the chief complaint of three stiff fingers on his left hand that began four years ago and hypopigmented patches on the back and buttocks that began five years ago. In this case, there was a history of leprosy in his mother`s sister, who had died. Leprosy in the patient was suspected of possibly being transmitted from his mother`s sister who had intense contact with the patient. The results of bacteriological examination with Ziehl- Neelsen staining of tissue scrapings found acid-fast bacilli. He was treated with a multibacillary multidrug regimen for 12 months. Periodical observations after the patient received the treatment revealed no new spots on the patient`s skin, some of the previous hypopigmented patches seemed to fade, especially those on the back. In the absence of an effective vaccine, early diagnosis and treatment are critical in preventing disability and deformity and reducing the physical, psychosocial, and economic burden of the disease.


Metallothionein as a storage protein for cadmium: its toxicological implications.
Upon exposure to cadmium, the biosynthesis of metallothionein is increased in liver and kidneys. The protein sequesters a large fraction of the tissue cadmium, thereby making it less available for excretion. The primary function of the protein in cadmium metabolism, therefore, appears to be storage of the metal in a less toxic form. Low levels of metallothionein are found in plasma and urine upon cadmium exposure. The protein is cleared from the circulation and is reabsorbed by kidney. There it is rapidly degraded, releasing Cd2+ ions which are the probable cause of the proximal tubular damage. Circulating metallothionein can also induce the autoimmune response, resulting in the formation of soluble immune complexes which may deposit in glomeruli and affect their function as well. Therefore, due to its release into the circulation, the metallothionein-bound storage form of cadmium may in fact be responsible for both tubular and glomerular dysfunction observed after chronic cadmium exposure.


The Benefits and Challenges of Managing Asthma in Hispanic Families in South Texas: A Mixed-Methods Study.
Understanding the experience of Hispanic parents of children diagnosed with asthma can be useful in the delivery of effective and meaningful asthma education. In order to assess the needs of Hispanic families with asthmatic children in South Texas, investigators utilized a combination of qualitative and quantitative research methods. This study aimed (1) to assess the impact of asthma in the quality of life of Hispanic children and their families and (2) to identify barriers and challenges to asthma management as perceived by parents of children diagnosed with asthma. A mixed-methods study included a quality-of-life survey and focus group discussions. The Children's Health Survey for Asthma (CHSA) was completed by 90 parents of children with asthma. Three focus groups were conducted with 15 low-income, Hispanic parents of asthmatic children to assess their needs and experience in managing the disease. Results from the CHSA showed that asthma significantly affects the quality of life of children with asthma and their families, particularly the emotional dimensions and the child's physical health. Fifty-three percent of the children had visited the emergency room, and 51% had been hospitalized due to asthma. One out of five parents had missed work, and 27% of children had missed school in the past 2 weeks due to the child's asthma. In the focus group discussions, the key themes emerging included lack of asthma knowledge, the burden of disease for asthmatic children and their families, and the importance of asthma education and self-management behaviors for asthma control. One of the main challenges faced by Hispanic families with asthmatic children is the lack of asthma-related knowledge to help understand and control their children's disease. Lack of knowledge and self-management skills lead to significant stress and anxiety among children with asthma and their parents. Results highlight that while asthma has an effect on the quality of life of children and their families, particularly on the emotional health domain, a wide dissemination of asthma management education in different settings might help prevent asthma attacks and improve symptom control among those suffering from this disease along the US-Mexico border.


Mental health nursing and stress: maintaining balance.
The recruitment and retention of mental health nurses within acute inpatient mental health facilities continues to be an ongoing issue. Literature and current research highlight an environment fraught with pressure and stress, identifying several key factors contributing to job dissatisfaction. These factors include greater patient acuity, unpredictable and challenging workspaces, violence, increased paperwork, and reduced managerial support. This qualitative, critical, feminist exploration investigated the lived experiences of 13 female mental health nurses working in inpatient services. They were asked about their practice and perceptions of workplace culture, and they shared their thoughts on stress management and professional well-being. Positive workplace practice was highlighted, and the participants revealed an environment they were proud to be a part of. Individual interviews, focus groups, and reflective practice were all used to collect data. The findings from the investigation unanimously support current literature that clearly confirms mental health nursing to be stressful. Interestingly, however, the findings also clearly identified that the way in which the nurse participants managed their stress was intrinsically linked to their job satisfaction. The major theme identified throughout the present study revealed that the female participants' ability to manage an at times complex workspace through the notions of teamwork, diversity, and creativity. All of the participants considered these elements as significant to providing a high standard in patient care. This research might provide an opportunity for others to view mental health nursing from a different perspective, and through the lived experiences of the participants, embrace the positive and rewarding aspects of the role.


United States-Japan workshop on New Rodent Models for the Analysis and Prevention of Carcinogenesis.
In assessing the present status of rodent models for the analysis and prevention of carcinogenesis, the discussion emphasized that models exist for very few of the major cancers occurring in the United States and Japan. Almost without exception, those that do exist were invented for etiological and mechanistic studies of chemical and physical carcinogenesis. Applicability to cancer chemoprevention was not a primary objective in their development. However, they have been adapted and used for identifying and characterizing chemopreventive agents out of necessity. It is therefore not surprising that they generally fail to fulfill most or all of the requisites of "ideal" models enumerated above, and consequently, the validity of data produced through their use has been questioned. Evolution of future mechanistic models may similarly lead to their eventual adaptation to chemoprevention, but advances will be fragmentary, and the rate of progress seems likely to be slow. Animal models discussed at this workshop were designed specifically for this purpose and promise to expedite the accumulation of valuable new information. Nonetheless, recurrent discussion identified the urgent need for institution of a major, dedicated research initiative with the expressed objective of developing rodent models for organ-specific chemoprevention based on current understanding of underlying genetic and cellular processes. No concerted programs with this objective presently exist either in the United States or Japan. In addition to research specifically designed to meet this need, efforts should be made to involve investigators developing mechanistic animal models in the validation of their models through modulating cancer development by chemopreventive agents. Support for such research initiatives will be essential to continued progress toward the overall objective of identifying safe and effective cancer chemopreventive agents.


A signaling loop of REST, TSC2 and β-catenin governs proliferation and function of PC12 neural cells.
The RE-1-specific silencing transcription factor (REST or NRSF) is a transcription repressor that orchestrates differentiation and also operates in differentiated neurons and neurosecretory cells (neural cells). Its role in proliferation has been investigated so far only in rapidly growing tumors, with conflicting results: suppression in non-neural tumors, stimulation in medulloblastomas. Working with two clones of chromaffin-neuronal PC12 cells, which express different levels of REST, and using genetic complementation and knockdown approaches, we show that REST also promotes proliferation in differentiated neural cells. Mechanistically, this occurs by a signaling pathway involving REST, the GTPase-activating protein tuberin (TSC2) and the transcription co-factor β-catenin. In PC12 cells, raised expression of REST correlates with reduced TSC2 levels, nuclear accumulation and co-transcriptional activation of β-catenin, and increased expression of its target oncogenes Myc and Ccnd1, which might account for the proliferation advantage and the distinct morphology. Rest transcription is also increased, unveiling the existence of a self-sustaining, feed-forward REST-TSC2-β-catenin signaling loop that is also operative in another neural cell model, NT2/D1 cells. Transfection of REST, knockdown of TSC2 or forced expression of active β-catenin recapitulated the biochemical, functional and morphological properties of the high-expressing REST clone in wild-type PC12 cells. Upregulation of REST promoted proliferation and phenotypic changes, thus hindering neurosecretion. The new REST-TSC2-β-catenin signaling paradigm might have an important role in various aspects of neural cell physiology and pathology, including the regulation of proliferation and neurosecretion.


An exposed/unexposed cohort study assessing the effectiveness, the safety and the survival of patients established on home non-invasive ventilation after 80 years old.
Little is known about the use of long-term non-invasive ventilation (NIV) in the elderly. We aimed to assess if the effectiveness of long-term NIV of patients ≥ 80 years (older) was not greatly inferior to that of patients < 75 years (younger). This retrospective exposed/unexposed cohort study included all patients established on long-term NIV treated at Rouen University Hospital between 2017 and 2019. Follow-up data were collected at the first visit following NIV initiation. The primary outcome was daytime PaCO2 with a non-inferiority margin of 50% of the improvement of PaCO2 for older patients compared to younger patients. We included 55 older patients and 88 younger patients. After adjustment on the baseline PaCO2, the mean daytime PaCO2 was reduced by 0.95 (95% CI: 0.67; 1.23) kPa in older patients compared to1.03 (95% CI: 0.81; 1.24) kPa in younger patients for a ratio of improvements estimated at 0.95/1.03 = 0.93 (95% CI: 0.59; 1.27, one-sided p = 0.007 for non-inferiority to 0.50). Median (interquartile range) daily use was 6 (4; 8.1) hours in older versus 7.3 (5; 8.4) hours in younger patients. No significant differences were seen in the quality of sleep and NIV safety. The 24-months survival was 63.6% in older and 87.2% in younger patients. effectiveness and safety seemed acceptable in older patients, with a life expectancy long enough to expect a mid-term benefit, suggesting that initiation of long-term NIV should not be refused only based on age. Prospective studies are needed.


The association between socioeconomic status and the 30- and 90-day risk of infection after total hip arthroplasty : a registry-based cohort study of 103,901 patients with osteoarthritis.
The aim of this study was to examine whether socioeconomic status (SES) is associated with a higher risk of infections following total hip arthroplasty (THA) at 30 and 90 days. We obtained individual-based information on SES markers (cohabitation, education, income, and savings) on 103,901 THA patients from Danish health registries between 1 January 1995 and 31 December 2017. The primary outcome measure was any hospital-treated infection (i.e. all infections). The secondary outcomes were further specified to specific hospital-treated infections (pneumonia, urinary tract infection, and periprosthetic joint infection). The primary timepoint was within 90 days. In addition, the outcomes were further evaluated within 30 days. We calculated the cumulative incidence, and used the pseudo-observation method and generalized linear regression to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs) for each marker. The cumulative incidence of any infection at 90 days was highest in patients who lived alone (1.5% (95% CI 1.3 to 1.6)) versus cohabitant (0.7% (95% CI 0.7 to 0.8)), had the lowest educational achievement (1.1% (95% CI 1.0 to 1.2)) versus highest (0.7% (95% CI 0.5 to 0.8)), had the lowest income (1.6% (95% CI 1.5 to 1.70)) versus highest (0.4% (95% CI 0.3 to 0.5)), or had lowest savings (1.3% (95% CI 1.2 to 1.4)) versus highest (0.7% (95% CI 0.6 to 0.8)). Within 90 days, the RRs for any infection were 1.3 (95% CI 1.2 to 1.4) for patients living alone versus cohabiting, 1.2 (95% CI 1.0 to 1.3) for low education achievement versus high, 1.7 (95% CI 1.4 to 2.1) for low income versus high income, and 1.5 (95% CI 1.4 to 1.8) for low savings versus high savings. The same trends were also seen for any infections within the first 30 days. Our study provides evidence that socioeconomic inequality adversely influences the risk of infection after THA, thus contributing to healthcare disparities and inequalities. We found that living alone, low educational achievement, low income, or low savings were associated with higher risks of infections within the first 30 and 90 days after THA. Therefore, the development of targeted intervention strategies with the aim of increasing awareness of patients identified as being at greatest risk is needed to mitigate the impact of SES on the risk of infections following THA. Cite this article: Bone Joint J 2022;104-B(2):221-226.


Taenia solium cysticercosis.
The larval stage of the pork tapeworm (Taenia solium) infects the human nervous system, causing neurocysticercosis. This disease is one of the main causes of epileptic seizures in many less developed countries and is also increasingly seen in more developed countries because of immigration from endemic areas. Little information is available on the natural evolution of taeniasis or cysticercosis. Available therapeutic measures include steroids, treatments for symptoms, surgery, and, more controversially, antiparasitic drugs to kill brain parasites. Efforts to control and eliminate this disease are underway through antiparasitic treatment of endemic populations, development of pig vaccines, and other measures.