Histologic processing and reporting of cutaneous pigmented lesions: recommendations based on a survey of 94 dermatopathologists.
Standard operating procedures for laboratory processing and reporting of margins of cutaneous pigmented lesions do not exist. We conducted a survey of 94 dermatopathologists to evaluate these practices. We sought to: (1) identify dominant practices among dermatopathologists; (2) determine the impact of the procedure, intent to excise, and histologic diagnosis on the process of margin evaluation; and (3) propose guidelines based on these findings. The survey consisted of 44 questions focused on the impact of procedure (punch, shave, or ellipse), intent (excision or biopsy), and histologic diagnosis (common nevus, congenital nevus, atypical nevus, melanoma) on processing and margin reporting. For ellipses, or specimens indicated as excisions, the majority practice (76%-98%) was to ink the specimens. Although more than 90% of observers report the margins on all melanomas and atypical nevi, fewer than 50% of respondents report margins on all nonatypical nevi. The study consists of a survey sample of dermatopathologists and does not represent the practices of those who did not respond to the survey. Based on the results of this survey we have arrived at the following recommendations: (1) ink all specimens that are ellipses or designated as excisions; (2) tips should be evaluated separately if the specimen is an ellipse; (3) obtain levels in cases with tumor in the tip but not at ink if the specimen is an ellipse or excision and the diagnosis is atypical nevus or melanoma; and (4) report margins on all atypical nevi and melanomas.


Anaesthetic Management of a Child with Parapharyngeal Abscess.
Airway management in a case of parapharyngeal abscess is challenging as there can be airway obstruction during anaesthetic induction. We describe airway management in 13-yr-old child with parapharyngeal abscess scheduled for incision and drainage. Informed consent was taken for publishing this case report.


Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice.
Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582. No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compoinds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective. For Ro-07-0582 and metronidazole, several concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min. The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray. Both metronidazole and Ro-07-0582 gave significant enhancement effect at serum concentrations which can be achieved in man.


[Differential diagnosis of epileptic seizures].
The differential diagnoses of epileptic seizures depend on the different semiologies of the respective seizures. Patient history and history of witnesses are of foremost importance in the differentiation. When seizures recur, they are more easily distinguished than single seizures. Diagnostic methods like EEG and eventually EEG video monitoring will help in the differentiation when clinical information and patient history do not allow a clear diagnosis. We present the most common differential diagnoses and their differences compared to epileptic seizures.


Social representations of "non-eating" experienced by patients on exclusive enteral nutrition.
In a scenario where food is absent or restricted, as in the case of enteral nutrition (EN), eating becomes an experience filled with different meanings in the hospitalization process. This study aimed to understand the social representations of "non-eating" experienced by patients receiving EN. This was an empirical, qualitative, cross-sectional study. Hospitalized patients using EN for at least seven days and who were over 18 years of age participated in the study. The sample size was defined using the data saturation criterion. Patients were selected after an active search was conducted through the beds of a university hospital in the state of Minas Gerais, Brazil. The instruments used were (a) a semi-structured interview script and (b) the researcher's field journal. Data analysis was based on the thematic analysis of Braun and Clark, and the theoretical foundation was supported by the theory of social representations. Nine patients were interviewed and four thematic categories were identified: (1) Perceptions related to the body in the experience of enteral nutrition, (2) The place of hunger and cravings in the body, (3) The price of healing, and (4) Communication with the team. The results indicate an experience largely associated with physical sensations, recognized by patients as aversive, with a tendency to a better adaptation to EN with longer use of the tube. Patients did not perceive physical hunger while the presence of "wanting" or "craving for" food, that is, the desire to taste and experience food, was reported by all, equating it to the experience of hunger. The main difficulties experienced by patients involve the absence or loss of communication with the health team and the reduction of autonomy, both in terms of mobility and the power of participation and decision-making regarding the treatment. The experience of patients in EN is complex and permeated by several difficulties, such as the lack of pleasure and symbolism associated with food and eating. On the other hand, even in the face of adversity, those patients undergo treatment, to seek a "cure" for their condition. It is essential to highlight the lack of communication on the part of the health team as an important difficulty listed by the patients. These results are fundamental for the health teams to review and reconstruct the management related to the care of patients to improve their well-being.


Diagnosis of adolescent polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age and is increasingly recognized as a disorder manifesting in the peripubertal and adolescent period. Diagnosis in the adolescent is difficult due to the high background rate of menstrual irregularity, the high prevalence of polycystic ovarian morphology and hyperandrogenic features in this population. Recent guidelines suggest that menstrual irregularity for over two years, reduced reliance on ultrasound diagnosis of polycystic ovarian morphology, and accurate assessment of hyperandrogenic and metabolic features are suitable strategies for the diagnosis of PCOS in the adolescent. Accurate diagnosis is important given the long-term implications of the disorder, with increasing emphasis on metabolic sequelae.


Ontogeny of lymphoid organs and immunoglobulin producing cells in Atlantic cod (Gadus morhua L.).
The ontogeny of lymphoid organs and the development of cells expressing immunoglobulin heavy chain (IgH) mRNA as well as cells containing immunoglobulin (IgM) were studied in Atlantic cod (Gadus morhua L.), a marine teleost. Head kidney and spleen appeared as the first lymphoid organs, present at the time of hatching, whereas thymus was observed in 9 mm larvae. Fully developed lymphoid organs were not achieved until after metamorphosis. Cells expressing IgH mRNA were detected in paraffin sections of larvae and juveniles by in situ hybridization. Positive cells were not detected in fish smaller than 33 mm (58 days after hatching). IgH mRNA expression coincided with the first appearance of immunoglobulin-positive cells as revealed by immunohistochemistry in the same animals.


Depressive symptoms are associated with increased systemic vascular resistance to stress.
The deleterious effects of major depressive disorder on cardiovascular (CV) functioning are well known. However, the etiologic mechanisms underlying this association are incompletely understood. In the current study, subjects with varying degrees of depressive symptoms performed a stress task while CV reactivity was measured. We hypothesized that high levels of depressive symptoms would be associated with altered CV reactivity. Ninety-one healthy volunteer subjects performed reactivity testing while measures of impedance cardiography and autonomic nervous system function were obtained. Subjects completed the Center for Epidemiological Studies Depression Scale (CES-D) and were categorized into either the high depressive (i.e., CES-D > or =16) or low depressive (i.e., CES-D <16) symptoms group. Task performance was associated with increases in systemic vascular resistance (SVR) (p = .001), mean arterial pressure (p = .001), and heart rate (p = .005), and decreases in cardiac output (p = .001), heather index (p = .001), and stroke volume (p = .05). After controlling for screening mean arterial pressure, an interaction effect of stress by mood group on SVR (p = .01) was observed; subjects with high amounts of depressive symptoms manifested significantly greater SVR at baseline and in response to a stressor task than did subjects with low amounts of depressive symptoms. These results suggest a mechanism that may partially explain the increased CV morbidity associated with depressive symptoms. In future studies, it may be useful to examine if treatment of depressive symptoms alters CV reactivity.


Safety and efficacy of golimumab in Chinese patients with active ankylosing spondylitis: 1-year results of a multicentre, randomized, double-blind, placebo-controlled phase III trial.
The aim of this study was to assess the efficacy and safety of golimumab in Chinese patients with active AS. Two hundred and thirteen patients were randomized in a 1:1 ratio to receive either s.c. injections of placebo from weeks 0 to 20 followed by golimumab 50 mg from weeks 24 to 48 (group 1, n = 105) or golimumab 50 mg from weeks 0 to 48 (group 2, n = 108), both every 4 weeks. Placebo crossover occurred at week 24, while early escape was at week 16. The primary endpoint was an improvement of at least 20% in the Assessment of SpondyloArthritis international Society (ASAS20) criteria at week 14. Major secondary endpoints included week 24 ASAS20 response and week 14 change scores for BASFI and BASMI. Golimumab treatment elicited significantly better responses than placebo in week 14 ASAS20 response [49.1% (53/108) vs 24.8% (26/105), respectively, P < 0.001], week 24 ASAS20 response (50.0% vs 22.9%, P < 0.001) and mean improvements in BASFI (-1.26 vs 0.11, P < 0.001) and BASMI (-0.42 vs -0.19, P = 0.021) scores at week 14. Additionally, golimumab treatment led to significant improvements in the mental and physical components of health-related quality of life (HRQoL) and sleep problems at week 24, all of which were further improved through week 52. During the 16-week placebo-controlled study period, 31.4% and 30.6% of patients had adverse events (AEs) in groups 1 and 2, respectively; similar AE reporting rates were observed through week 24 (34.3% and 32.0%) and among the golimumab-treated patients through week 56 (41.2%). Golimumab significantly reduced clinical symptoms/signs and improved physical function, range of motion and HRQoL in Chinese patients with active AS without unexpected safety concerns. ClinicalTrials.gov, NCT01248793.


Pesticide residue intake from fruits and vegetables and alterations in the serum metabolome of women undergoing infertility treatment.
Pesticide exposure is linked to a myriad of negative health effects; however, the mechanisms underlying these associations are less clear. We utilized metabolomics to describe the alterations in the serum metabolome associated with high and low pesticide residue intake from fruits and vegetables (FVs), the most common route of exposure in humans. This analysis included 171 women undergoing in vitro fertilization who completed a validated food frequency questionnaire and provided a serum sample during controlled ovarian stimulation (2007-2015). FVs were categorized as high or low-to-moderate pesticide residue using a validated method based on pesticide surveillance data from the USDA. We conducted untargeted metabolic profiling using liquid chromatography with high-resolution mass spectrometry and two chromatography columns. We used multivariable generalized linear models to identified metabolic features (p < 0.005) associated with high and low-to-moderate pesticide residue FV intake, followed by enriched pathway analysis. We identified 50 and 109 significant features associated with high pesticide residue FV intake in the C18 negative and HILIC positive columns, respectively. Additionally, we identified 90 and 62 significant features associated with low-to-moderate pesticide residue FV intake in the two columns, respectively. Four metabolomic pathways were associated with intake of high pesticide residue FVs including those involved in energy, vitamin, and enzyme metabolism. 12 pathways were associated with intake of low-to-moderate pesticide residue FVs including cellular receptor, energy, intercellular signaling, lipid, vitamin, and xenobiotic metabolism. One energy pathway was associated with both high and low-to-moderate pesticide residue FVs. We identified limited overlap in the pathways associated with intake of high and low-to-moderate pesticide residue FVs, which supports findings of disparate health effects associated with these two exposures. The identified pathways suggest there is a balance between the dietary antioxidant intake associated with FVs intake and heightened oxidative stress as a result of dietary pesticide exposure.


MR imaging of acute cortical venous infarction: preliminary experience with an animal model.
Surgically ligated cortical veins in rabbits produced areas of hemorrhage and infarction. Pathological correlation with serial magnetic resonance (MR) imaging of these surgically created lesions was obtained. Imaging within 4 hours after ligation showed the site of venous infarction to be a focus of low signal intensity on T1-weighted images (T1WI) within a larger overlapping area of high intensity on T2-weighted images (T2WI). The serial imaging showed persistence of T1WI and T2WI changes without alteration of pattern. At 3-day follow-up, both the T1WI and T2WI changes were maximal. At 7- and 14-day follow-up, T1WI and T2WI changes showed regression. There was no identifiable site of paramagnetic influence within the lesions produced. This lack of local paramagnetic effect may be related to the acuteness and minute size of the lesions, partial volume effects, and/or atmospheric exposure of the lesion related to the surgical procedure. Our preliminary results are encouraging not only for trying to image cortical venous infarction but also in trying to define the sensitivity of MRI for small cortical lesions.


Lower GI bleeding: a review of current management, controversies and advances.
Lower gastrointestinal (GI) bleeding is defined as bleeding distal to the ligament of Treitz. In the UK, it represents approximately 3 % of all surgical referrals to the hospital. This review aims to provide review of the current evidence regarding the management of this condition. Literature was searched using Medline, Pubmed, and Cochrane for relevant evidence by two researchers. This was conducted in a manner that enabled a narrative review of the evidence covering the aetiology, clinical assessment and management options of continuously bleeding patients. The majority of patients with acute lower GI bleeding can be treated conservatively. In cases where ongoing bleeding occurs, colonoscopy is still the first line of investigation and treatment. Failure of endoscopy and persistent instability warrant angiography, possibly preceded by CT angiography and proceeding to superselective embolisation. Failure of embolisation warrants surgical intervention. There are still many unanswered questions. In particular, the development of a more reliable predictive tool for mortality, rebleeding and requirement for surgery needs to be the ultimate priority. There are a small number of encouraging developments on combination therapy with regard to angiography, endoscopy and surgery. Additionally, the increasing use of haemostatic agents provides an additional tool for the management of bleeding endoscopically in difficult situations.


Lower level noise exposure that produces only TTS modulates the immune homeostasis of cochlear macrophages.
Noise exposure producing temporary threshold shifts (TTS) has been demonstrated to cause permanent changes to cochlear physiology and hearing function. Several explanations have been purported to underlie these long-term changes in cochlear function, such as damage to sensory cell stereocilia and synaptic connections between sensory cells and their innervation by spiral ganglion neurons, and demyelination of the auditory nerve. Though these structural defects have been implicated in hearing difficulty, cochlear responses to this stress damage remains poorly understood. Here, we report the activation of the cochlear immune system following exposure to lower level noise (LLN) that causes only TTS. Using multiple morphological, molecular and functional parameters, we assessed the responses of macrophages, the primary immune cell population in the cochlea, to the LLN exposure. This study reveals that a LLN that causes only TTS increases the macrophage population in cochlear regions immediately adjacent to sensory cells and their innervations. Many of these cells acquire an activated morphology and express the immune molecules CCL2 and ICAM1 that are important for macrophage inflammatory activity and adhesion. However, LLN exposure reduces macrophage phagocytic ability. While the activated morphology of cochlear macrophages reverses, the complete recovery is not achieved 2 months after the LLN exposure. Taken together, these observations clearly implicate the cochlear immune system in the cochlear response to LLN that causes no permanent threshold change.


Cognitive control and semantics in schizophrenia: an integrated approach.
The authors tested whether decisions about incongruencies in the representation and processing of semantic knowledge, thought to be related to cognitive control, are selectively impaired in schizophrenia. Twenty-four patients with schizophrenia and 24 healthy comparison subjects determined the relative size of paired stimuli as they are in the real world. Stimuli were words or images. Real-world "distance" (size difference between stimuli) was manipulated within pairs, as was "congruency" between real-world and presentation size. Although patients were slower overall, both groups exhibited similar effects of "distance" and "congruency"; the task was easier when the real-world size difference between stimuli was greater and when stimuli were congruent in presentation and real-world size. Some aspects of the representation of semantic knowledge are preserved in schizophrenia, and patients use this information to control cognition in the same manner as healthy individuals.


Purification of the fibroblast growth factor activity from bovine brain.
The purification of the fibroblast growth factor (FGF) from bovine brain has led to the isolation of two peptides. FGF-1 with 128 amino acids and FGF-2 with 107 amino acids. The biological activity of these two peptides is acid- and heat-labile. As indicated by the amino acid composition of FGF-1 and -2, these two peptides are derived from a common precursor and bear no resemblance to pituitary FGF. The brain FGF peptides, like pituitary FGF, are mitogenic in vitro for the same wide variety of mesoderm-derived cells. Since their mitogenic activity is acid- and heat-labile, they are thereby distinguished from the platelet factor isolated from platelets and from the cationic peptide isolated from serum which has been shown to have the same molecular weight and isoelectric point as brain and pituitary FGF.


In Situ Studies of Mitochondrial Translation by Cryo-Electron Tomography.
Cryo-electron tomography (cryo-ET) enables the three-dimensional (3D) visualization of macromolecular complexes in their native environment (in situ). The ability to visualize macromolecules in situ is in particular advantageous for complex, membrane-associated processes, such as mitochondrial translation. Mitochondrial translation occurs almost exclusively associated with the inner mitochondrial membrane, giving rise to the mitochondrial DNA-encoded subunits of oxidative phosphorylation machinery. In cryo-ET, the 3D volume is reconstructed from a set of 2D projections of a frozen-hydrated specimen, which is sequentially tilted and imaged at different angles in a transmission electron microscope. In combination with subtomogram analysis, cryo-ET enables the structure determination of macromolecular complexes and their 3D organization. In this chapter, we summarize all steps required for structural characterization of mitochondrial ribosomes in situ, ranging from data acquisition to tomogram reconstruction and subtomogram analysis.


On Wright's mechanism for intergroup selection.
A haploid model of Wright's (1945) intergroup selection is described. Several approximate analyses as well as Monte Carlo simulation show that Wright's mechanism leads to powerful selection for group advantageous traits in the face of strong local selection against them. Intergroup selection is favored by small local subpopulation size and by high, not low, rates of immigration into local groups, although the dependence on migration rate is not strong. These results and others cast doubt on the primacy of genic selfishness as a tenet of Darwinian theory.


Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study.
Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.


Higher monetary incentives led to a lowered response rate in ambulatory patients: a randomized trial.
Monetary incentives can increase response rate in patient surveys, but calibration of the optimal incentive level is required. Our aim was to assess the effect of different monetary incentives on response rates to calibrate the optimal monetary incentive for ambulatory patients. A patient-randomized trial was performed in which targeted individuals received different gift vouchers (€5.00, €7.50, €10.00, and €12.50) on completion of a survey and interview. Eligible patients (diagnosed type 2 diabetes, over 18 years) were recruited from primary care practices. The response rate for the €12.50 incentive was lower compared with both the €7.50 and the €10.00 incentive [odds ratio (OR) = 0.60 and OR = 0.58]. A nonlinear model yield a better fit than a linear model. Within the observed range of incentive levels, an overall decrease in response rate was found. High monetary incentives are not only inefficient but also less effective.


Unleashing the mechanism among environmental regulation, artificial intelligence, and global value chain leaps: a roadmap toward digital revolution and environmental sustainability.
Strengthening environmental regulation and adhering to the green as well as sustainable development of China's manufacturing industry has become an inevitable trend. Technological innovation leads to industrial transformation, and artificial intelligence becomes a new driving force for core competitiveness and value chain upgrading. Is there a link between environmental regulation, artificial intelligence, and the jump in global value chains? Does AI have a mediating effect? This paper draws the following conclusions through panel estimation: environmental regulation plays a positive role in global value chains, and artificial intelligence has improved the level of global value chains as well. Further analysis of the mediation effect of artificial intelligence finds that artificial intelligence replaces low-end labor, reduces labor costs for enterprises, and promotes the leap of the global value chain. The strengthening of environmental regulation has greatly improved the total factor productivity of enterprises, artificial intelligence has significantly improved production efficiency, and total factor productivity has shown a positive influence on the global value chain as well.


In silico analysis of the association of hsa-miR-16 expression and cell survival in MDA-MB-231 breast cancer cells subjected to photodynamic therapy.
Breast cancer is the most common malignancy effecting women, and the triple-negative breast cancer (TNBC) subtype is particularly aggressive. This study aimed to evaluate the differential expression pattern of microRNAs (miRNAs) between untreated MDA-MB-231 cells (TNBC cell model) and those that survived photodynamic therapy (PDT) to gain insights into cell survival mechanisms. Two PDT cycles were applied to MDA-MB-231 cells, using δ-aminolevulinic acid (ALA) followed by laser light at 635 nm. RNA was obtained from cells surviving PDT and untreated cells. The miRNAs expression profile was analyzed to detect the differences between the two groups. The potential target network of hsa-miR-16 was examined in silico with the integrative database Ingenuity® Pathway Analysis software. After the first and second PDT cycles, 17.8% and 49.6% of the MDA-MB-231 cells were viable. Microarray profiling of miRNAs showed decreased hsa-miR-16 expression (p < 0.05) in MDA-MB-231 cells surviving PDT when compared to the control cells. The predicted downstream targets of hsa-miR-16 were: 1) tumor suppressor protein 53; 2) molecules related to the cell cycle, such as cyclin D1, D3, and E1, and checkpoint kinase 1; 3) cell proliferation molecules, including fibroblast growth factor 1, 2 and 7 and fibroblast growth factor receptor 1; and 4) apoptosis-related molecules, consisting of BCL-2, B-cell leukemia/lymphoma 2, caspase 3, and cytochrome c. The differential expression of hsa-miR-16 between untreated MDA-MB-231 cells and those surviving PDT has not been previously reported. There was a lower expression of hsa-miR-16 in treated cells, which probably altered its downstream target network. In silico analysis predicted, a network related to the cell cycle, proliferation and apoptosis. These results are congruent with previous descriptions of hsa-miR-16 as a tumor suppressor and suggest that the treated population has increased their capacity to survive.


Impact of Checkpoint Inhibitor Immunotherapy, Primarily Pembrolizumab, on Infection Risk in Patients With Advanced Lung Cancer: A Comparative Retrospective Cohort Study.
Checkpoint inhibitor (CPI) immunotherapy has revolutionized cancer treatment. However, immune-related adverse events and the risk of infections are not well studied. To assess the infectious risk of CPIs, we evaluated the incidence of infections in lung cancer patients treated with CPIs plus conventional chemotherapy (CC) vs CC alone. We performed a retrospective comparative study of patients with advanced non-small cell lung cancer who received CPIs combined with CC and those treated with CC alone at our institution during January 2016 to February 2019. We compared clinical characteristics, treatments, and outcomes including infection rate and mortality between the groups. We identified 123 patients for the CPI group and 147 patients for the control (CC) group. Eighteen patients (15%) in the CPI group and 33 patients (22%) in the control group developed infections (P = .1). Pneumonia was the most common infection encountered in both groups. Urinary tract infection was higher in the CC group (40%) than in the CPI group (9%) (P = .01). On multivariable analysis, chronic obstructive pulmonary disease (P = .024), prior use of corticosteroids (P = .021), and neutropenia (P < .001) were independent risk factors for infection and severe infection requiring hospital admission. Chronic kidney disease (P = .02), prior cancer treatment (P = .023), and neutropenia (P < .0001) were identified as independent risk factors for all-cause mortality. Lung cancer patients treated with CPIs combined with CC have a comparable risk of infection to those treated with CC alone, although there is a trend towards fewer infections in those given CPIs, particularly when it comes to urinary tract infections.


Systematic review with meta-analysis: efficacy of balloon-assisted enteroscopy for dilation of small bowel Crohn's disease strictures.
Evidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon-assisted enteroscopy is scarce. To evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon-assisted enteroscopy. Citations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta-analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome-relevant risk factors. In the pooled per-study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short-term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow-up, 48.3% of patients reported symptom recurrence, 38.8% were re-dilated and 27.4% proceeded to surgery. On the per-patient-based multivariable analysis, that patients with disease activity in the small intestine had lower short-term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14-0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09-3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34-2.34, P < 0.001). Balloon-assisted enteroscopy for dilatation of CD-associated small intestinal strictures has high short-term technical and clinical efficacy and low complication rates. However, up to two-thirds of patients need re-dilation or surgery.


Neuropsychiatric manifestations associated with azithromycin in two brothers.
Neurologic adverse events reported in premarketing clinical trials of azithromycin have been mild, occurring in less than 1% of the patients, and include dizziness, headache, vertigo, and somnolence. Serious adverse neuropsychiatric effects of azithromycin have never been reported in the pediatric population and only seldom in adults. We report two brothers aged 6 and 15 years with severe and prolonged complex neuropsychiatric manifestations associated with azithromycin treatment. Both brothers experienced visual and auditory hallucinations, and one brother additionally experienced multiple partial complex seizures, severe headaches, and recurrent cortical blindness. All symptoms commenced within 24 h after the initial dose of azithromycin and resolved slowly, within 2-4 weeks. Possible genetic and environmental explanations are discussed, such as polymorphism in uptake of efflux transporters at different levels, particularly at the blood brain barrier level.


Alice Augusta Ball: The African-American chemist who pioneered the first viable treatment for Hansen's Disease.
Alice Augusta Ball (1892-1916) was a young and dynamic chemist who achieved extraordinary milestones in her short lifespan of 24 years. As an African American and as a woman in the early 20th century, her work and achievements set a benchmark. Her breakthrough work on the extraction of the water-soluble ethyl esters of chaulmoogra oil changed the lives of millions of people affected by Hansen's disease who were socially boycotted and segregated to leprosy colonies and asylums. The chaulmoogra oil esters, which continued to be used for almost two decades, were the first viable treatment of leprosy. Unfortunately, Ball did not receive recognition and honor for her work, and she was forgotten soon after her untimely death.


[Principles and fields of application of screening procedures].
This article explains some important concepts of screening and early detection. It also discusses under which circumstances screening is useful, who can profit from screening and which persons may be at risk from screening procedures. Before the introduction of a screening program, empirical studies on the effectiveness are necessary to evaluate whether a screening program could be successful.


Immunopurification, characterization, and nature of membrane association of human melanoma-associated oncofetal antigen gp87 defined by monoclonal antibody 140.240.
A melanoma-associated oncofetal antigen, gp87 (a p97-like molecule), defined by the monoclonal antibody (MoAb) 140.240 has been purified to homogeneity from the spent medium of cultured melanoma cells by a two-step immunoadsorbent procedure. The first immunoadsorbent step using glutaraldehyde-insolubilized MoAb 140.240 (ascites fluid) resulted in a 13-fold enrichment with 93% recovery in the bound material. In the second immunoadsorbent step constructed by the purified IgG2a of MoAb 140.240 (culture fluid) coupled to CNBr-activated Sepharose 4B the bound material from the first step was further purified resulting in a 330-fold purification with 90% recovery. SDS-polyacrylamide gel electrophoretic analysis of the final purified material revealed a single band migrating as a polypeptide with an approximate molecular weight of 87 Kd, consistent with the size of the molecule immunoprecipitated by MoAb 140.240 from lysates of radiolabelled melanoma cells. Preliminary amino acid analysis indicates a particularly high proportion of phenylalanine in gp87. We have also compared gp87 with two well defined antigens, HLA-A,B,C (integral membrane protein) and "94K" melanoma/carcinoma-associated antigen (peripheral membrane protein) with respect to antigen extractability from melanoma cells using phosphate-buffered saline, 0.1 M urea, 3 M NaCl, or nonionic detergent (NP-40). The results showed that whereas 94K antigen was extractable by each of the four different solutions, gp87, similar to HLA-A,B,C antigens, could only be extracted with NP-40, strongly suggesting that gp87 is an integral melanoma cell component.


KDM2B-Rearranged Soft Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma.
Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval to spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe 3 soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included 1 infant, 1 adolescent, and 1 older patient. All tumors showed histologic findings indistinguishable from those of BCOR-associated sarcomas and were originally diagnosed as such based on the phenotype. However, none of the tumors had BCOR or YWHAE genetic alterations. Instead, targeted RNA sequencing identified in-frame KDM2B::NUTM2B, KDM2B::CREBBP, and KDM2B::DUX4 fusions. KDM2B fusions were validated using reverse-transcription PCR, Sanger sequencing, and in situ hybridization assays. Genome-wide DNA methylation analysis matched all 3 tumors with BCOR-associated sarcomas using the Deutsches Krebsforschungszentrum (DKFZ) classifier and t-distributed stochastic neighbor embedding analysis. One localized tumor showed a flat genome-wide copy number profile, and the patient remained disease-free after treatment. The other tumors showed multiple copy number alterations, including MDM2/CDK4 amplification and/or CDKN2A/B loss, and both tumors metastasized, leading to the patient's death in one of the cases. When tested using KDM2B immunohistochemistry, all 3 KDM2B-rearranged sarcomas showed diffuse strong staining, and all 13 sarcomas with BCOR genetic alterations also demonstrated diffuse, strong, or weak staining. By contrast, among 72 mimicking tumors, only a subset of synovial sarcomas showed focal or diffuse weak KDM2B expression. In conclusion, our study suggests that KDM2B-rearranged soft tissue sarcomas belong to the BCOR-associated sarcoma family and expand its molecular spectrum. This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.


The effect of pH, temperature and concentration on electrooxidation of phenol.
The electrochemical oxidation of phenol on Pt electrode has been investigated in 1M NaOH and 0.5M H2SO4 solutions at different temperature and different phenol concentration. A simplified mechanism for the electrochemical oxidation of phenol is proposed which includes a selective oxidation parallel with PtO(x) formation. Activation energy, which was obtained from the experimental data, was almost same in studied mediums. This means that electrooxidation mechanism for phenol must be same. Other thermodynamic values such as DeltaS, DeltaH were calculated from the experimental data.


Associations of daily walking and television viewing time with liver cancer mortality: findings from the Japan Collaborative Cohort Study.
Several studies have suggested that daily vigorous physical activity reduces the risk of liver cancer, whereas sedentary behavior increases the risk of several cancers. However, the link between liver cancer and low-intensity physical activity (walking) and sedentary behavior is unclear. Therefore, we explored the links between liver cancer mortality and daily walking time/television (TV) viewing time in Japanese adults aged 40-79 years in a large-scale nationwide cohort study. We excluded participants with a history of liver disease, cancer, stroke, or myocardial infarction at baseline (1988-1990) and those who died within the first 5 years of follow-up. A total of 69,752 adults (28,642 men and 41,110 women) were enrolled and followed for a median of 19.4 years. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for liver cancer mortality adjusted for age, sex, and other possible confounding factors. During the study period, 267 participants died of liver cancer. The HRs of participants who walked for >0.5 h/day and watched TV for 2-4 versus <2 h/day were 0.58 (95% CI 0.39-0.89) and 0.58 (95% CI 0.35-0.98), respectively, compared with those who walked for <0.5 h/day and watched TV for >4 h/day. Our findings suggest that longer walking times and shorter TV viewing times may reduce the risk of liver cancer.


[Outpatient Long/Post-COVID Care: Barriers and Desires of Affected Persons to Medical Care].
Persistent and new-onset symptoms after SARS-CoV-2 infection (so-called Long/Post-COVID syndrome) represent a major challenge for our healthcare system. However, there have been limited data on primary outpatient care and care planning, complicating patient flow management and ultimately patient care. Assessing the care reality of patients with Long/Post-COVID-symptoms, as well as their difficulties and desires in receiving medical care, is a necessary first step toward improving outpatient care. The JenUP study (Jena study on the population-based incidence of Post-COVID complaints) is a questionnaire-based survey of all adults in the city of Jena who were registered with RT-PCR-confirmed SARS-CoV-2 infection between March 2020 and September 2021. Part of this study focused on the medical care of the affected persons as well as subjective difficulties of the patients in the context of treatment. A total of 1,008 of the 4,209 individuals responded to the questionnaire; 922 (91,5%) experienced at least one Long/Post-COVID-associated symptom. 85,6% of these individuals (790/922) also provided detailed information about contacts with health care facilities. Three out of four persons (590/790) consulted their general practitioner/family doctor in connection with their complaints and 155/790 (19,6%) specialists in addition (most frequently mentioned were specialists in internal medicine - 7,1% (55/790)). Difficulties in obtaining a subjectively required therapy were mentioned by 22,6% (162/718). The main reasons were the patient's apparent feeling of "not being sick enough" (69/162) and a lack of a specialist consultant (65/162). 27% (247/919) of all subjects with Long/Post-COVID complaints expressed a desire for a specific consultant. Primary care physicians represent a central element of outpatient care for Long/Post-COVID patients. In addition, nationwide structures for interdisciplinary care should be established according to the national S1 guideline. Analysis of wishes for medical care and perceived barriers to accessing it represent a first step in improving outpatient care for Long/Post-COVID patients.


A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles.
To determine the predictive value and define threshold values for basal antral follicle count in patients undergoing IVF. Prospective cohort analysis. Tertiary care center. Two hundred eighty-nine patients. Transvaginal ultrasonography before starting gonadotropin administration. Number of oocytes retrieved, basal hormone levels, and cycle outcomes. Pregnant patients had significantly more antral follicles (13.8 +/- 7.5 vs. 12.4 +/- 10.0). Patients in whom cycles were canceled had significantly fewer antral follicles (7.6 +/- 4.8 vs. 13.7 +/- 8.8). Antral follicle count significantly correlated with most prestimulation and poststimulation IVF variables. Threshold analysis demonstrated a lower pregnancy rate (23.5% vs. 57.6%) and a higher cancellation rate (41% vs. 6.4%) associated with having four or fewer antral follicles. The basal antral follicle count identified patients who responded poorly to IVF stimulation. Having four or fewer antral follicles was associated with a high cancellation rate (41%) and, in patients without a cancelled cycle, a low pregnancy rate (23%). However, no antral follicle count absolutely predicted pregnancy or cycle cancellation.


Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma.
F-box and WD repeat domain-containing 7 (Fbxw7) is a cell cycle regulatory gene that targets for ubiquitination and proteasomal degradation various cell cycle regulators such as c-Myc and cyclin E. Defects in the Fbxw7 gene that lead to cell cycle re-entry and expedite the G1-S transition is thought to be one of the causes of cancer development. However, its expression and clinical importance for hepatocellular carcinoma (HCC) patients remains undetermined. This prompted us to investigate its expression level in HCC patients to establish its clinical significance. Sixty surgically resected paired HCC and normal tumor-adjacent tissues were freshly collected. Fbxw7 expression at both mRNA and protein level was examined by reverse transcription polymerase chain reaction and immunohistochemistry. The protein expression of c-Myc, cyclin E and p53 was evaluated by immunohistochemistry to identify correlations with Fbxw7. The mRNA and protein expression of Fbxw7 was significantly downregulated in the HCC tumor tissues compared to the normal tumor-adjacent tissues (P < 0.01, respectively). Fbxw7 protein was expressed at significantly lower levels in patients with high histological grade and advanced tumor-node-metastasis stage. In HCC tissues, Fbxw7 protein expression was negatively correlated with c-Myc, cyclin E and p53 (r = -0.459, P < 0.05; r = -0.573, P < 0.001; r = -0.579, P < 0.05, respectively). In HCC, reduced Fbxw7 expression closely correlated with clinicopathological characteristics and may have prognostic potential through the enhanced function of cell cycle regulatory proteins.


Exploiting Drosophila genetics to understand microRNA function and regulation.
Although a great deal is known about the identity, biogenesis, and targeting capacity of microRNAs (miRNAs) in animal cells, far less is known about their functional requirements at the organismal level. Much remains to be understood about the necessity of miRNAs for overt phenotypes, the identity of critical miRNA targets, and the control of miRNA transcription. In this review, we provide an overview of genetic strategies to study miRNAs in the Drosophila system, including loss- and gain-of-function techniques, genetic interaction strategies, and transgenic reporters of miRNA expression and activity. As we illustrate the usage of these techniques in intact Drosophila, we see certain recurrent themes for miRNA functions, including energy homeostasis, apoptosis suppression, growth control, and regulation of core cell signaling pathways. Overall, we hope that this exposition of Drosophila genetic techniques, well known to the legions of fly geneticists and used to study all genes, can inform the general miRNA community that focuses on other biochemical, molecular, computational, and structural avenues. Clearly, it is the combination of these myriad techniques that has accelerated miRNA research to its extraordinary pace.


Development of an arginine-based cationic hydrogel platform: Synthesis, characterization and biomedical applications.
A series of biodegradable and biocompatible cationic hybrid hydrogels was developed from water-soluble arginine-based unsaturated polymer (Arg-AG) and poly(ethylene glycol) diacrylate (PEG-DA) by a photocrosslinking method. The physicochemical, mechanical and biological properties of these hydrogels were intensively examined. The hydrogels were characterized in terms of equilibrium swelling ratio (Qeq), compression modulus and interior morphology. The effects of the chemical structure of the two Arg-AG precursors and the feed ratio of these precursors on the properties of resulting hybrid hydrogels were investigated. The crosslinking density and mechanical strength of the hybrid hydrogels increased with an increase in allylglycine (AG) content in the Arg-AG precursor, as the gelation efficiency (Gf) increased from 80% to 90%, but the swelling and pore size of the hybrid hydrogels decreased as the equilibrium swelling weight (Qeq) decreased from 1890% to 1330% and the pore size from 28 to 22 μm. The short-term in vitro biodegradation properties of hydrogels were investigated as a function of Arg-AG chemical structures and enzymes. Hybrid hydrogels showed faster biodegradation in an enzyme solution than in a phosphate-buffered saline solution. Bovine serum albumin and insulin release profiles indicated that this cationic hydrogel system could significantly improve the sustained release of the negatively charged proteins. The cellular response of the hybrid hydrogels was preliminarily evaluated by cell attachment, encapsulation and proliferation tests using live-dead and MTT assay. The results showed that the hybrid hydrogels supported cell attachment well and were nontoxic to the cells.


The equivalence of assays within individual guidelines for the testing of the potential mutagenicity of chemicals: problems associated with battery selection.
Many individual Mutagenicity Guidelines contain suggested test systems with choices of such parameters as strains, cell types and even endpoint assayed. Comparisons have been made of data obtained from variants of yeast assays for the induction of mitotic recombination, in vitro assays for the induction of chromosome aberrations and assays for the induction of cell transformation. Individual test variants included in guidelines of the EEC and OECD show considerable qualitative and quantitative variability of response to potential mutagens and carcinogens. Such variability between assays within the same guideline raises considerable problems in the selection of test batteries chosen from published Mutagenicity Guidelines. Improved battery selection is dependent upon the reduction of choice within guidelines to those assays which produce consistent and reproducible results.


Different apoprotein(a) isoform proportions in serum and carotid plaque.
Cardio- and/or cerebro-vascular risk are associated with high lipoprotein (a) [Lp(a)] levels and low-molecular-weight (LMW) apo(a) isoforms. Aims of this study were to evaluate the deposition of apo(a) isoforms and apoprotein B (apo B) in atherosclerotic plaque from patients (males and females) who had carotid endarterectomy for severe stenosis, and to identify differences between patients classified by gender and divided according to the stability or instability of their plaques. We determined lipids, apo B and Lp(a) in serum and plaque extracts from 55 males and 25 females. Apo(a) was phenotyped and isoforms were classified by number of kringle IV (KIV) repeats. Lp(a) levels were higher in female serum and plaque extracts than in male samples, while apo B levels were lower. More Lp(a) than apo B deposition was observed in plaque after normalization for serum levels. Thirty-one different apo(a) isoforms were detected in our patients, with a double band phenotype in 94% of cases. In both sexes, the low/high (L/H) molecular weight apo(a) isoform expression ratio was significantly higher in plaque than in serum. Females with unstable plaques had higher Lp(a) levels in both serum and tissue extracts, and fewer KIV repeats of the principal apo(a) isoform in the serum than the other female group or males. In both sexes, the same apo(a) isoforms are found in serum and atherosclerotic plaque, but in different proportions: in plaque, LMW apo(a) is almost always more strongly accumulated than HMW apo(a), irrespective of any combination of apo(a) isoforms in double band phenotypes or Lp(a) serum levels. Moreover, serum and tissue Lp(a) levels were higher in females than in males, and particularly in the group with unstable plaques.


Integrated approach of photo-assisted electrochemical oxidation and sequential biodegradation of textile effluent.
Synthetic azo dyes are extensively used in the textile industries, which are being released as textile effluent into the environment presence of azo dyes in the environment is great environmental concern therefore treatment of textile effluent is crucial for proper release of the effluent into the environment. Electrochemical oxidation (EO) is extensively used in the degradation of pollutants because of its high efficiency. In this study, photo-assisted electrooxidation (PEO) followed by biodegradation of the textile effluent was evaluated. The pretreatment of textile effluent was conducted by EO and PEO in a tubular flow cell with TiO2-Ti/IrO2-RuO2 anode and titanium cathode under different current densities (10, 15, and 20 mA cm-2). The chemical oxygen demand level reduced from 3150 mg L-1 to 1300 and 600 mg L-1under EO and PEO, respectively. Furthermore, biodegradation of EO and PEO pretreated textile effluent shows reduction in chemical oxygen demand (COD) from 1300 mg L-1 to 900 mg L-1and 600 mg L-1to 110 mg L-1, respectively. The most abundant genera were identified as Acetobacter, Achromobacter, Acidaminococcus, Actinomyces, and Acetomicrobium from the textile effluent. This study suggests that an integrated approach of PEO and subsequent biodegradation might be an effective and eco-friendly method for the degradation of textile effluent.


Radiosynthesis of 20-[18F]fluoroarachidonic acid for PET-MR imaging: Biological evaluation in ApoE4-TR mice.
Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (APOE4) genotype, the strongest genetic risk factor of late-onset Alzheimer's disease (AD). Visualization of AA uptake and distribution in the brain can offer insight into neuroinflammation and AD pathogenesis. Here we present a novel synthesis and radiosynthesis of 20-[18F]fluoroarachidonic acid ([18F]-FAA) for PET imaging using a convergent route and a one-pot, single-purification radiolabeling procedure, and demonstrate its brain uptake in human ApoE4 targeted replacement (ApoE4-TR) mice. By examining p38 phosphorylation in astrocytes, we found that fluorination of AA at the ω-position did not significantly alter its biochemical role in cells. The brain incorporation coefficient (K*) of [18F]-FAA was estimated via multiple methods by using an image-derived input function from the right ventricle of the heart as a proxy of the arterial input function and brain tracer concentrations assessed by dynamic PET-MR imaging. This new synthetic approach should facilitate the practical [18F]-FAA production and allow its translation into clinical use, making investigations of dysregulation of lipid metabolism more feasible in the study of neurodegenerative diseases.


The protein concentration gradient within eye lens might originate from constant osmotic pressure coupled to differential interactive properties of crystallins.
A protein concentration gradient exists from the center to the periphery of most lenses, the origin of which is still a matter of debate. The gradient, which contributes to the lens optical quality, seems to be accompanied by an uneven distribution of the crystallin classes, with the nucleus usually enriched in gamma- and the cortex in alpha-crystallins. Since the osmotic pressure within the lens seems to be constant and since a rather different interaction behaviour of alpha- and gamma-crystallins was demonstrated in previous studies, we propose that the maintenance of a constant osmotic pressure through the lens is sufficient to induce and stabilize a protein concentration gradient. The theoretical treatment has been worked out and the validity of the hypothesis has been demonstrated with colloidal osmotic pressure measurements of lens cortical and nuclear cytoplasmic extracts as a function of protein concentration. To account for the observed lens concentration gradient, however, a small additional concentration gradient in the opposite direction, involving an ion or small molecule, might be required.


Desorption from Hot Scandate Cathodes: Effects on Vacuum Device Interior Surfaces after Long-Term Operation.
Scandate cathodes have exhibited superior emission properties compared to current state-of-the-art "M-type" thermionic cathodes. However, their integration into vacuum devices is limited in part by a lack of knowledge regarding their functional lifespan and behavior during operation. Here, we consider thermal desorption from scandate cathodes by examining the distribution of material deposited on interior surfaces of a sealed vacuum device after ~26,000 h of cathode operation. XPS, EDS, and TEM analyses indicate that on the order of 1 wt.% of the initial impregnate is desorbed during a cathode's lifetime, Ca does not desorb uniformly with time, and little to no Sc desorbs from the cathode surfaces (or does so at an undetectable rate). Findings from this first-ever study of a scandate cathode after extremely long-time operation yield insight into the utility of scandate cathodes as components in vacuum devices and suggest possible effects on device performance due to deposition of desorption products on interior device surfaces.


A Mild Synthesis of Aryl Triflates Enabling the Late-Stage Modification of Drug Analogs and Complex Peptides.
We report the discovery of a straightforward protocol to convert phenols into the corresponding aryl triflates using 1-methyl-3-((trifluoromethyl)sulfonyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one in the presence of a fluoride source. This novel reagent can be handled without any precautions to exclude air or moisture making this method highly convenient. The reactions generally show very clean conversions within only a few minutes at room temperature. The mild conditions allow the so far unprecedented O-triflation of tyrosine in peptides bearing challenging side chains present for example in arginine and histidine including the late-stage triflation of complex bioactive peptides. We show how aryl triflates - an interesting but so far underutilized group - can be used to optimize physicochemical and in vitro properties of compound series in medicinal chemistry. We believe that this method is highly attractive for applications in peptide functionalization as well as automated and medicinal chemistry.


The TGF-β/Smad2/3 signaling pathway is involved in Musashi2-induced invasion and metastasis of colorectal cancer.
To identify Musashi2 as an effective biomarker regulated by the TGF-β/Smad2/3 signaling pathway for the precise diagnosis and treatment of colorectal cancer (CRC) through bioinformatic tools and experimental verification. The Cancer Genome Atlas, Timer, and Kaplan-Meier analyses were performed to clarify the expression of Musashi2 and its influence on the prognosis of CRC. Transforming growth factor beta 1 (TGF-β1) was used to activate the TGF-β/Smad2/3 signaling pathway to identify whether it could regulate the expression and function of Musashi2. Western blot analysis and quantitative PCR analyses were conducted to verify the expression of Musashi2. Cell counting kit-8 (CCK8), EdU, wound healing, and Transwell assays were conducted to reveal the role of Musashi2 in the proliferation, migration, and invasion of CRC. Musashi2 was upregulated in CRC and promoted proliferation and metastasis. TGF-β1 increased the expression of Musashi2, while the antagonist inducer of type II TGF-β receptor degradation-1 (ITD-1) decreased the expression. CCK8 and EdU assays demonstrated that inhibition of Musashi2 or use of ITD-1 lowered proliferation ability. The Transwell and wound healing assays showed that the migration and invasion abilities of CRC cells could be regulated by Musashi2. The above functions could be enhanced by TGF-β1 by activating the TGF-β/Smad2/3 signaling pathway and reversed by ITD-1. A positive correlation was found between Musashi2 and the TGF-β/Smad2/3 signaling pathway. TGF-β1 activates the TGF-β/Smad2/3 pathway to stimulate the expression of Musashi2, which promotes the progression of CRC. Musashi2 might become a target gene for the development of new antitumor drugs.


Multi-species probiotics improve growth, intestinal microbiota and morphology of Indian major carp mrigal Cirrhinus cirrhosus.
This study aimed to examine the effects of multi-species probiotic on growth, hematological status, intestinal microbes, and intestinal morphology of mrigal (Cirrhinus cirrhosus). The mrigal fries (average weight 0.51 g) were reared for 60 days by supplementing multi-species probiotics containing Bacillus spp. (1 × 109 cfu/mL) and Lactobacillus spp. (1 × 1011 cfu/mL) in the raising water at doses of 0 (control), 0.5, and 1.0 mL/L. The results indicated that fish reared with multi-species probiotics showed significantly higher growth performance and feed efficiency where the survival rate was similar in all cases. Accordingly, significant higher red blood cell (RBC) and white blood cell (WBC) were counted from the fish reared with multi-species probiotic. There was a considerable difference in bacterial microbiota between the experimental and control group. Multi-species probiotics significantly enhanced the length, width, and villus area. Several immune response indicators like fattening of intestinal mucosal fold, width of lamina propria, the width of enterocytes, and abundance of goblet cells were also increased significantly in fish that received multi-species probiotics. This study revealed that multi-species probiotics can significantly contribute to the growth of mrigal through upgrading intestinal microbiota and morphology, which can be suggested as an eco-friendly growth stimulator in mrigal farming.


Increased peak end-expiratory pressure in ventilated preterm lambs changes cerebral microvascular perfusion: direct synchrotron microangiography assessment.
Positive end-expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondarily to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral hemodynamics in the preterm brain are unknown. We aimed to assess the effect of PEEP on microvessels in the preterm brain by using synchrotron radiation (SR) microangiography, which enables in vivo real-time high-resolution imaging of the cerebral vasculature. Preterm lambs (0.8 gestation, n = 4) were delivered via caesarean section, anesthetized, and ventilated. SR microangiography of the right cerebral hemisphere was performed with iodine contrast administered into the right carotid artery during PEEP ventilation of 5 and 10 cmH2O. Carotid blood flow was measured using an ultrasonic flow probe placed around the left carotid artery. An increase of PEEP from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm) in all four lambs. Additionally, the higher PEEP increased the cerebral contrast transit time in three of the four lambs. Carotid blood flow increased in two lambs, which also had increased carbon dioxide levels during PEEP 10. Our results suggest that PEEP of 10 cmH2O alters the preterm cerebral hemodynamics, with prolonged cerebral blood flow transit and engorgement of small cerebral microvessels likely due to the increased intrathoracic pressure. These microvascular changes are generally not reflected in global assessment of cerebral blood flow or oxygenation.NEW & NOTEWORTHY An increase of positive end-expiratory pressure (PEEP) from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm). This suggests increased intrathoracic pressure due to high PEEP can drive microvessel engorgement in the preterm brain, which may play a role in cerebrovascular injury.


Resveratrol and cardiovascular system-the unfulfilled hopes.
Resveratrol is a natural polyphenolic compound with a stilbene structure endowed with multiple health-promoting effects. Among phenolic compounds, resveratrol is assigned a leading role in the health-promoting effects of red wine. The aim of the study was to assess the effect of resveratrol on the cardiovascular system in the experimental and clinical studies conducted so far. Moreover, the paper discusses the results of the most recent meta-analyses assessing resveratrol's therapeutic effect on the cardiovascular system in humans. In animal and preclinical studies, resveratrol has demonstrated a wide physiological and biochemical spectrum of activity, including antioxidant, anti-inflammatory, antiplatelet, and anticoagulant activities, which translated into its health-promoting effects on the cardiovascular system. The performed meta-analyses allow to confirm such an impact, however, after the assessment with the use of the SYRCLE's tool, these studies are burdened with a high risk of bias, and the results are not clearly presented. Despite numerous articles and clinical studies, the convincing beneficial mechanisms of resveratrol as well as its health-promoting effects in cardiovascular diseases have not been clearly confirmed in humans. Therefore, there is a need for further clinical studies, especially randomized, double-blind, placebo-controlled trials to objectively confirm the possible health-promoting effects of this substance and to determine both the efficacy and safety, and possible therapeutic potential.


Prevalence of adverse childhood experiences and associations with personal and professional factors in health and social care workers: A systematic review.
To systematically review papers reporting the prevalence of adverse childhood experiences (ACEs) in health and social care workers, as well as any personal or professional factors they were associated with. CINAHL, EMCARE, PsychInfo, and Medline were searched to find studies utilizing the ACE questionnaire (Felitti et al., 1998) in health and social care worker populations. The initial search returned 1,764 papers, with 17 studies meeting the inclusion criteria to be in the review. ACEs among health and social care workers were frequently reported and occurred more often than in the general population. They were also associated with several personal and professional outcomes, including poor physical and mental health, and workplace stress. Understanding staff ACE characteristics can help organizations to consider ways to support staff, which may be individual or systemic. Trauma-responsive systems may be a possible answer among organizations to improve staff well-being, quality of service, and better outcomes for service users. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Understanding health-related quality of life trajectories among older adults with diabetes mellitus: Mixed methods research.
To examine health-related quality of life trajectories among older adults with diabetes mellitus (DM). A sequential explanatory mixed method study protocol. In the quantitative phase, health-related quality of life trajectory over 5 years, from 2009 to 2013, of a national representative sample (N = 440) of older adults with DM was analysed using group-based modelling. Next, a qualitative multiple case study (N = 10) was conducted between November 2017 and April 2018. In the mixed phase, by linking the quantitative and qualitative data, similarities and differences among the four trajectories were identified. Four distinctive health-related quality of life trajectories could be distinguished: high then decrease, high stable, medium stable and low then increase. These differed in attitude towards DM, self-management of DM-related tasks, comorbidity-related health-related quality of life, coping with DM and financial concerns about medical needs. Our results help illuminate the heterogeneity of health-related quality of life trajectories in older adults with DM. This research may help healthcare providers understand the need to assess the HR-QoL comprehensively and promote HR-QoL for older adults with DM.


Echocardiographic reference ranges for normal cardiac Doppler data in healthy Turkish population: ECHO-DOP-TR Trial.
Doppler echocardiography has become the standard imaging modality for diastolic function and provides pathophysiological insight into systolic and diastolic heart failure. In this study, we aimed to obtain normal echocardiographic Doppler parameters of healthy Turkish population. Among 31 collaborating institutions from all regions of Turkey, 1154 healthy volunteers were enrolled in this study. Predefined protocols were used for all participants during echocardiographic examination and The American Society of Echocardiography and European Association of Cardiovascular Imaging recommendations were used for echocardiographic Doppler measurements. A total of 967 healthy participants were enrolled in this study after applying exclusion criteria. Echocardiographic examination was obtained from all subjects following predefined protocols. Mitral E wave velocity and E/A ratio were higher in females and decreased progressively in advancing ages. E wave deceleration time and A wave velocity were increased with aging. Assessment of tissue Doppler velocities showed that left ventricular lateral e', septal e', and septal s' were higher in younger subjects and in females. E/e' ratio was increased progressively with advancing decades. Right ventricular e' and s' were decreased but a' was increased with increasing age. Septal e' lower than 8 cm/s was 1.9% in the fifth decade and 13.7% in ages older than 50 years. The E/e' ratio greater than 15 (and also 13) was not found. This study, for the first time, provides echocardiographic reference ranges for normal cardiac Doppler data in healthy Turkish population which will be useful in routine clinical practice as well as in future clinical trials.


Risk factors and clinical significances for retropancreatic lymph node metastasis in gastric cancer patients.
The incidence of retropancreatic lymph node metastasis in gastric cancer patients is not negligible. The aim of present study was to determine the risk factors for retropancreatic lymph node (LN) metastasis and to investigate its clinical significance. Clinical pathologic data of 237 patients with gastric cancer between June 2012 and June 2017 were analyzed retrospectively. 14 patients (5.9%) had retropancreatic LN metastases. The median survival of patients with and without retropancreatic LN metastasis was 13.1 and 25.7 months. According to univariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, presence of angiolymphatic invasion, depth of invasion (pT4), N3 stage, No. 3, No. 7, No. 8, No. 9, and No. 12p LN metastasis was found to be associated with retropancreatic LN metastasis. According to multivariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, pT4, N3 stage, No. 9 LN metastasis, and No. 12p LN metastasis were found to be independent prognostic variables for retropancreatic LN metastasis. Retropancreatic LN metastasis is a poor prognostic factor for gastric cancer. Tumor size (≥ 8 cm), Bormann type III/IV, undifferentiated tumor, pT4, N3 stage, and No. 9 and No. 12p LN metastasis are risk factors for metastasis to retropancreatic lymph node.


Delay in the diagnosis and treatment of oral cancer.
Oral and pharyngeal cancer is one of the most mortal cancers; however, its quick diagnosis and referral is a crucial factor in enhancing the survival rate of the patients. The aim of this study was to inspect the referral conditions and the reasons for the delay in curing the patients referred to the educational hospitals in Tehran. In this retrospective -descriptive study, two hundred and fifty six files related to the oral and pharyngeal cancer were inspected. The documents were obtained from 5 educational hospitals specialized in the field of cancers. Eventually data related to the time difference between the first time of attending to lesion and diagnosing the cancer as patient's delay and until the curing as professional's delay were recorded. The majority of cancers were squamous cell carcinoma (SCC). The patient's delay was recorded in 110 files among the whole files. The mean of the time between the patients' first notice of the problem and the time visiting a primary care clinician was 270 days (range, 0-2520 days). The mean of the time from when the patient visited a primary- care clinician to the starting time of definitive treatment was 90 days (range, 0-270 days). In this study, like other studies, SCC was the most common occurring cancer. Delays related to the patients were more than those related to the professionals. And at last, accuracy in recording the files and training the patients were recognized to be the most imperative factors to continue the treatment successfully.


A case report of fatal feline babesiosis caused by Babesia canis in north western Spain.
In Europe, Babesia infections in cats are sporadic and only partial knowledge is currently available since the number of described cases including both the clinical presentation and the molecular identification of the Babesia species involved is limited. In the present case report, the clinical signs, the epidemiological data and the molecular results suggest that this is the first reported fatal case of feline babesiosis caused by Babesia canis. A six month old female European shorthair cat from north-western Spain died after being hospitalized for two days. This animal was pregnant and showed anorexia, lethargy, weakness, jaundice and fever with increased respiratory and heart rates. Haematological analysis revealed haemolytic regenerative anaemia, thrombocytopenia and leukocytosis. The presence of piroplasms was assessed using a PCR targeting the 18S rRNA gene of Babesia spp. and Theileria spp.; the sample resulted positive and B. canis was identified by DNA sequence analysis. The possible existence of co-infections with other vector-borne pathogens such as Anaplasma spp., Bartonella spp., Borrelia burgdorferi s.l., Cytauxzoon spp., Ehrlichia spp., Hepatozoon canis, Mycoplasma spp. or Rickettsia spp. was excluded by qPCR. Our results together with previous reports on Babesia infections in cats from Europe suggest that feline babesiosis should be included in the differential diagnosis of animals with anaemia, thrombocytopenia, anorexia and lethargy, especially in young or immunocompromised animals from endemic areas for canine babesiosis.


High frequency of mitochondrial genome instability in human endometrial carcinomas.
To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer.


Testing Theory-Based Messages to Encourage Women at Average Risk for Breast Cancer to Consider Biennial Mammography Screening.
The US Preventive Services Task Force does not recommend routine annual mammography screening for women aged 40-49 at average risk. Little research has been done to develop theory-based communication interventions to facilitate informed decision-making about reducing potentially low-value mammography screening. Evaluate the effects of theory-based persuasive messages on women's willingness to consider delaying screening mammography until age 50 or have mammograms biennially. We conducted a randomized controlled communication experiment online with a population-based sample of U.S. women aged 40-49 (N = 383) who screened to be at average risk for breast cancer. Women were randomly assigned to the following messaging summaries: annual mammography risks in 40s (Arm 1, n = 124), mammography risks plus family history-based genetic risk (Arm 2, n = 120), and mammography risks, genetic risk, and behavioral alternatives (Arm 3, n = 139). Willingness to delay screening or reduce screening frequency was assessed post-experiment by a set of 5-point Likert scale items. Women in Arm 3 reported significantly greater willingness to delay screening mammography until age 50 (mean = 0.23, SD = 1.26) compared with those in Arm 1 (mean = -0.17, SD = 1.20; p = .04). There were no significant arm differences in willingness to reduce screening frequency. Exposure to the communication messages significantly shifted women's breast cancer-related risk perceptions without increasing unwarranted cancer worry across all three arms. Providing women with screening information and options may help initiate challenging discussions with providers about potentially low-value screening.


A new genus and species of Coenosiini from Costa Rica (Diptera, Muscidae, Coenosiinae).
Palpilongus gen. n. is herein described for one species - Palpilongus bifurcus sp. n., from Costa Rica, based on male and females. The striking morphological characters of the species - palpus very long, about as long as prementum; upper calypter truncate and very short and setae of male sternite 5 bifurcated, confirm that this new species is also a new genus in the tribe Coenosiini. Male and female terminalia were dissected and illustrated.


[Adrenergic mechanisms of changes in the resistance and volume vessels of the small intestine in the presence of a reduced volume of circulating blood].
In humorally isolated small intestine, the 10--20%--decrease in the perfusing blood volume against the background of augmented vascular resistance of the small intestine, induces different shifts of the latter's vascular capacitance. At the blockade of small intestine's beta--adrenoreceptors the decrease does not practically tell on the character of shifts in the intestine's resistance and capacitance while the blockade of alpha--adrenoreceptors abolishes the augmentation of these parameters.


Mutagenicity arising from near-ultraviolet irradiation of N-nitrosomorpholine.
When a mixture of N-nitrosomorpholine and S. typhimurium TA100 in saline was irradiated with near-ultraviolet light, mutagenesis of the bacteria took place. The same observation was made with S. typhimurium TA1535, E. coli WP2 uvrA, pKM101 and uvrA/pKM101. Several other nitrosamines showed ed the same, but weaker, effect. Evidence is presented to indicate that the mutagenicity arises from the cellular phosphate-mediated photochemical formation of direct-acting mutagen from the nitrosamine.


A Rare Location of Osteosarcoma in the Cuboid Bone: A Case Report.
In this case report, we describe a patient with left foot pain whose magnetic resonance imaging revealed a destructive tumor of the left cuboid bone. A biopsy of the tumor confirmed an osteoblastic osteosarcoma of the cuboid, and the patient was treated with chemotherapy followed by a below-the-knee amputation. There are only a handful of cases reporting osteosarcoma of the cuboid bone, and challenges remain in properly diagnosing the lesion to recommend the best course of treatment.


Heavy rainfall provokes anticoagulant rodenticides' release from baited sewer systems and outdoor surfaces into receiving streams.
Prevalent findings of anticoagulant rodenticide (AR) residues in liver tissue of freshwater fish recently emphasized the existence of aquatic exposure pathways. Thus, a comprehensive wastewater treatment plant and surface water monitoring campaign was conducted at two urban catchments in Germany in 2018 and 2019 to investigate potential emission sources of ARs into the aquatic environment. Over several months, the occurrence and fate of all eight ARs authorized in the European Union as well as two pharmaceutical anticoagulants was monitored in a variety of aqueous, solid, and biological environmental matrices during and after widespread sewer baiting with AR-containing bait. As a result, sewer baiting in combined sewer systems, besides outdoor rodent control at the surface, was identified as a substantial contributor of these biocidal active ingredients in the aquatic environment. In conjunction with heavy or prolonged precipitation during bait application in combined sewer systems, a direct link between sewer baiting and AR residues in wastewater treatment plant influent, effluent, and the liver of freshwater fish was established. Moreover, study results confirmed insufficient removal of anticoagulants during conventional wastewater treatment and thus indirect exposure of aquatic organisms in receiving streams via tertiary treated effluents and combined sewer overflows. Nevertheless, further research is required to determine the ecological implications and risks for aquatic organisms as well as fish-eating predators from chronic AR exposure at environmentally relevant concentrations.


Carbon Dioxide Chemically Responsive Switchable Gas Valves with Protonation-Induced Liquid Gating Self-Adaptive Systems.
Carbon dioxide (CO2 ) capture and storage technologies are promising to limit CO2 emission from anthropogenic activities, to achieve carbon neutrality goals. CO2 capture requires one to separate CO2 from other gases, and therefore a gas flow system that exhibits discernible gating behaviors for CO2 would be very useful. Here we propose a self-adaptive CO2 gas valve composed of chemically responsive liquid gating systems. The transmembrane critical pressures of the liquid gate vary upon the presence of CO2 , due to the superamphiphiles assembled by poly(propylene glycol) bis(2-aminopropyl ether) and oleic acid in gating liquids that are protonated specifically by CO2 . It is shown that the valve can perform self-adaptive regulation for specific gases and different concentrations of CO2 . This protonation-induced liquid gating mechanism opens a potential platform for applications of CO2 separators, detectors, sensors and beyond.


Short term Outcomes of Routine Exposure Versus non Exposure of the Recurrent Laryngeal Nerve During Thyroidectomy for Benign Thyroid Diseases.
To evaluate the outcomes of the exposure versus non-exposure of the RLN during thyroidectomy for benign thyroid diseases. A prospective study for patients who underwent thyroidectomy for benign diseases. They were classified into two groups, group 1 (the exposed group) and group 2 (the non-exposed group) of the RLN. History, examination, laboratory and radiological investigations as well as intra and post-operative details were recorded. 97 patients were included in the study, group 1 (63 patients) while group 2 (34 patients). The median age of both groups was 40 (for group 1) and 42 (for group 2) respectively. There was no significant difference regarding the gender of the patients (P = 0.089) and the type of surgery (P = 0.234). The duration of surgery as well as the amount of intraoperative blood loss were equal with no significant difference (P = 0.791) (P = 0.225). Hematoma was detected in three patients in the exposed group while RLN injury was detected in 5 patients in total (2 in group 1 and 3 in group 2) without any significant difference. There was significant hypocalcemia in favor of the non-exposed group (P = 0.001). Regarding the postoperative hospital stay, there was no significant difference between both groups (P = 0.720). Exposure versus non-exposure of the RLN is still considered a matter of debate but precautions during dissection are a very useful maneuver. Meanwhile, it is better to expose the nerve with meticulous dissection and preservation of the parathyroid gland vascularity.


Direct measurement of the voltage sensitivity of second-harmonic generation from a membrane dye in patch-clamped cells.
We report what is to our knowledge the first optical imaging of voltage-clamped cells by second-harmonic generation. For the membrane-staining styryl dye di-4-ANEPPS, we determined the sensitivity of second-harmonic generation to be 18%/100 mV at an excitation wavelength of 850 ns. This sensitivity is significantly better than the optimal 10%/100 mV under fluorescence and further establishes the importance of second-harmonic generation for the functional imaging of membrane potential in living cells.


Electrophysiological signatures: magnetoencephalographic studies of the neural correlates of language impairment in autism spectrum disorders.
While magnetoencephalography (MEG) is of increasing utility in the assessment of pediatric patients with seizure disorders, this reflects only a part of the clinical potential of the technology. Beyond epilepsy, a broad range of developmental psychiatric disorders require the spatial and temporal resolution of brain activity offered by MEG. This article reviews the application of MEG in the study of auditory processing as an aspect of language impairment in children. Specifically, the potential application of MEG is elaborated in autism spectrum disorders (ASD), a devastating disorder with prevalence of 1 in 150. Results demonstrate the sensitivity of MEG for detection of abnormalities of auditory processing in ASD ('electrophysiological signatures') and their clinical correlates. These findings offer promise for the comprehensive assessment of developmental neuropsychiatric disorders.


Structure-Based Identification of HDAC8 Non-histone Substrates.
HDAC8 is a member of the family of histone deacetylases (HDACs) that catalyze the deacetylation of acetyl lysine residues within histone and non-histone proteins. The recent identification of novel non-histone HDAC8 substrates such as SMC3, ERRα, and ARID1A indicates a complex functionality of this enzyme in cellular homeostasis. To discover additional HDAC8 substrates, we developed a comprehensive, structure-based approach based on Rosetta FlexPepBind, a protocol that evaluates peptide-binding ability to a receptor from structural models of this interaction. Here we adapt this protocol to identify HDAC8 substrates using peptide sequences extracted from proteins with known acetylated sites. The many new in vitro HDAC8 peptide substrates identified in this study suggest that numerous cellular proteins are HDAC8 substrates, thus expanding our view of the acetylome and its regulation by HDAC8.


Obstructive sleep apnea and cancer: a complex relationship.
Obstructive sleep apnea (OSA) has been recognized as a risk factor for cancer mainly through hypoxia, based on studies that did not distinguish among cancer types. The purpose of this review is to discuss the most recent data on epidemiology and pathophysiology of the OSA-cancer association. According to epidemiological studies, OSA may have different influences on each type of cancer, either increasing or decreasing its incidence and aggressiveness. Time spent with oxygen saturation below 90% appears the polysomnographic variable most strongly associated with unfavorable effects on cancer. Experimental studies support the role of hypoxia as an important risk factor for cancer growth and aggressiveness, especially when it shows an intermittent pattern. These effects are largely mediated by the hypoxia-inducible factor, which controls the synthesis of molecules with effects on inflammation, immune surveillance and cell proliferation. Sleep fragmentation participates in increasing cancer risk. Modulating effects of age remain controversial. Effects of OSA on cancer may largely vary among neoplastic diseases, both in their magnitude and direction. The worse risk associated with intermittent rather than persistent hypoxia, and the effects of OSA therapy on cancer natural history are still poorly known, and deserve new careful studies.


Plant-microbe interactions: Plant-exuded myo-inositol attracts specific bacterial taxa.
Plants exude a plethora of metabolites that transform the microbiome composition. Initiated from genome-wide association studies of either a plant or a bacterium, two new studies dissect the impact of plant-secreted myo-inositol on recruitment of certain bacterial taxa by Arabidopsis.


Human Milk Fortification Strategies in the Neonatal Intensive Care Unit.
Multicomponent fortification is the standard of care to support short-term growth in preterm infants receiving human milk. There is no consensus regarding the optimal timing, method, or products used to fortify human milk. Both bovine milk-based and human milk-based human milk fortifiers are safe options, though increased fortification and enrichment may be needed to achieve adequate growth. Additional studies are needed to evaluate newer fortifier products and fortification strategies.


(S)-Methyl 2-benzamido-3-(3,4-dimeth-oxy-phen-yl)propano-ate.
The dimethoxypbenzene ring in the title compound, C(19)H(21)NO(5), is gauche to the amide group and anti to the ester group. The chirality was confirmed to be S from two-dimensional NMR spectroscopy. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds and several short-contact inter-actions (2.07-3.45 Å) create chains parallel to [110]. The phenyl ring is disordered over two orientations in a 0.54 (2):0.46 (2) ratio.


ω-O-Acylceramides but not ω-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids.
Epidermal omega-O-acylceramides (ω-O-acylCers) are essential components of a competent skin barrier. These unusual sphingolipids with ultralong N-acyl chains contain linoleic acid esterified to the terminal hydroxyl of the N-acyl, the formation of which requires the transacylase activity of patatin-like phospholipase domain containing 1 (PNPLA1). In ichthyosis with dysfunctional PNPLA1, ω-O-acylCer levels are significantly decreased, and ω-hydroxylated Cers (ω-OHCers) accumulate. Here, we explore the role of the linoleate moiety in ω-O-acylCers in the assembly of the skin lipid barrier. Ultrastructural studies of skin samples from neonatal Pnpla1+/+ and Pnpla1-/- mice showed that the linoleate moiety in ω-O-acylCers is essential for lamellar pairing in lamellar bodies, as well as for stratum corneum lipid assembly into the long periodicity lamellar phase. To further study the molecular details of ω-O-acylCer deficiency on skin barrier lipid assembly, we built in vitro lipid models composed of major stratum corneum lipid subclasses containing either ω-O-acylCer (healthy skin model), ω-OHCer (Pnpla1-/- model), or combination of the two. X-ray diffraction, infrared spectroscopy, and permeability studies indicated that ω-OHCers could not substitute for ω-O-acylCers, although in favorable conditions, they form a medium lamellar phase with a 10.8 nm-repeat distance and permeability barrier properties similar to long periodicity lamellar phase. In the absence of ω-O-acylCers, skin lipids were prone to separation into two phases with diminished barrier properties. The models combining ω-OHCers with ω-O-acylCers indicated that accumulation of ω-OHCers does not prevent ω-O-acylCer-driven lamellar stacking. These data suggest that ω-O-acylCer supplementation may be a viable therapeutic option in patients with PNPLA1 deficiency.


Intestinal helminths of a landlocked ringed seal (Phoca hispida saimensis) population in eastern Finland.
A small, landlocked, endangered ringed seal (Phoca hispida saimensis) population lives as a postglacial relict in Lake Saimaa in eastern Finland. In this study, the intestinal metazoans were examined from a total of 61 Saimaa seals found dead from 1981 to 2001. The helminth fauna was very depauperate. Only one acanthocephalan species, Corynosoma magdaleni, has been able to survive during isolation in the freshwater environment. In addition, only two cestode species were found: Diphyllobothrium ditretum and Schistocephalus sp. However, neither of these larvae developed in the ringed seals. As the newborn pups of Saimaa seals are nursed for about 2 months only one of them was infected by C. magdaleni. At 2-5 months the pups harboured worms; however, the mean intensity did not rise distinctively until the seals were adults. C. magdaleni infection increased with increasing age and the abundances were significantly different between the age groups. There was no correlation between the number of parasites and the adult seal body weight; however, seals weighing 36 kg or more carried the majority of the worms. The distribution of the parasites was aggregated; six seals carried 65% (n=1,182) of all worms (total n=1,809) and 26 seals were uninfected. Variation in the number of worms in individual seals may indicate differences in feeding behaviour and in the diet of seals, and/or variation in the immune status of the seals.


Mild to moderate aortic stenosis and coronary bypass surgery.
Aortic stenosis (AS) is the most common valvular disease in adult cardiac surgery and its incidence continues to rise. Increasingly older patients are being referred for coronary artery bypass grafting (CABG) with mild to moderate AS. Concomitant aortic valve replacement (AVR) for patients with moderate or severe AS undergoing CABG is warranted regardless of symptoms. Concomitant AVR remains contentious in patients with less than moderate severity AS undergoing CABG. We review the contemporary literature aiming to resolve this dilemma in clinical practice. The assessment of these patients is reviewed. Considerations include identifying the rapid progressors, and balancing the risks of concomitant valve surgery against the potential prognostic gains. Pathophysiological links between degenerative calcific AS and coronary artery disease suggest that the disease is an active, progressive process with mutually shared risk factors. Statins, however, offer limited protection against AS, despite its established role in coronary artery disease. Age, atherosclerosis risk, valve morphology, motion, and hemodynamics identify the rapid progressors, whilst the patients' general comorbidities and life expectancy influence the risk-benefit profile of concomitant operations. A precise echocardiographic quantification of the stenotic grade is mandatory before adopting any therapeutic strategy. Concomitant AVR for moderate AS is recommended if surgical risk is not prohibitive. Concomitant AVR for mild AS in 'rapid progressors' (i.e. moderate-severe valve calcification) may be considered, but patients should have reasonable life expectancy exceeding 5 years. Moderately restricted leaflet motions, gradient increase of > 10 mm Hg per year, and aortic jet velocity increase > 0.4 m/s per year further supports intervention. Comorbidities increasing atherosclerotic burden and renal dialysis accelerate AS progression and increase surgical risk. Procedural advances in interventional cardiology and minimally invasive cardiac surgery may further expand the options available for these patients.


In Situ Enzyme Immobilization by Covalent Organic Frameworks.
Enzyme immobilization is a widely reported method to favor the applicability of enzymes by enhancing their stability and re-usability. Among the various existing solid supports and immobilization strategies, the in situ encapsulation of enzymes within crystalline porous matrices is a powerful tool to design biohybrids with a stable and protected catalytic activity. However, to date, only a few metal-organic frameworks (MOFs) and hydrogen-bonded organic frameworks (HOFs) have been reported. Excitingly, for the first time, Y. Chen and co-workers expanded the in situ bio-encapsulation to a new class of crystalline porous materials, namely covalent organic frameworks (COFs). The enzyme@COF materials not only exhibited high enzyme loading with minimal leaching, high catalytic activity and selectivity, chemical and long-term stability and recyclability but could also be scaled up to a few grams. Undoubtedly, this work opens new striking opportunities for enzymatic immobilization and will stimulate new research on COF-based matrices.


Climacteric complaints and their relation to menopausal development--a retrospective analysis.
The present study had two objectives: (1) to register the prevalence of a number of climacteric complaints in a Danish general population cohort and (2) retrospectively to test the validity of an association between climacteric complaints, menopausal development, occurrence of life events and social background. A postal questionnaire sent to the 51-year-old female population living in four Copenhagen suburbs, (N = 597, response rate = 88%) included information on menstrual pattern and change, hormonal treatment, socioeconomic data and a 4-year retrospective annual registration of prevalence of a number of climacteric complaints and life events. Logistic regression analyses performed on a restricted sample (women who experienced a natural menopausal development) revealed prevalence of hot flushes, moodiness and fatigue to be significantly associated with transitions in menopausal status. Fatigue, moodiness and depression were strongly associated with socio-economic variables. Life events were only occasionally associated with prevalence of the studied complaints.