Characteristics of ambient ozone (O3) pollution and health risks in Zhejiang Province.
Troposphere ozone, which is from secondary formation processes, has been increasing dramatically during the last decades in China, inducing high health risks. In this study, temporal and spatial distribution of O3 was studied among 13 sites of three cities during 2014-2016. The objectives were to clarify the characteristics of the ambient pollution of O3 under the influence from other pollutants and meteorological parameters and the health outcomes from exposure to O3. The concentrations of O3 during summer were much higher than those during winter, and the concentrations in downtown areas were higher than in rural or mountain areas. PM2.5, NO2, SO2, and wind speed (WS) were negatively correlated with O3, and CO, temperature (T), and relative humidity (RH) were positively correlated with O3. In multivariable analysis, two separate factors-solar radiation and atmospheric diffusion status, affected the O3 levels. The concentrations of O3 reached the highest level at 15:00 and the lowest value at about 6:00-8:00, with the similar trend to T and WS, and opposite to RH. According to the dose-response model, relative risks (RRs) and population attributable fractions (PAFs) with confidence intervals (CIs) for chronic obstructive pulmonary disease (COPD) from exposure to O3 were 1.0612 (CI 1.0607-1.0616) and 5.32% (CI 5.29-5.36%), respectively, attributable to 2000 deaths in Zhejiang Province in 2014.


Response to commentary on "the middle fossa approach with self-drilling screws: a novel technique for BONEBRIDGE implantation".
The aim of this letter is to respond to a commentary on a published article on the middle fossa approach to BONEBRIDGE implantation with self-drilling screws published by the senior authors.


Toxoplasma gondii: Pig seroprevalence, associated risk factors and viability in fresh pork meat.
This study was conducted on 161 fattening pig farms located in Aragón (Northeast Spain). Serum samples from 1200 pigs were tested for antibodies against T. gondii by indirect immunofluorescence assay (IFA). Antibodies to T. gondii (≥1:20) were detected in 301 pigs (24.52%). The seroprevalence observed in the present study indicates a widespread exposure to T. gondii, as seropositive pigs were found in 96.67% of the farms studied although low pig titers were determined. Risk factors associated with T. gondii seroprevalence were presence of cats in or around the farms, presence of dogs around the facilities, low number of animals in the farms, poor hygiene and bad maintenance of the farms. Finally, it was observed that where rodent baits were used, Toxoplasma prevalence was lower. Risk management measures including control of cats and rodents on the farms, among others, could help to reduce the observed prevalence levels. By mouse bioassay, T. gondii was detected in 73.7% and isolated from 42.1% of seropositive pigs and a significant relation between the titers of pigs and the presence and viability of T. gondii in the tissues was found. The detection of T. gondii is not possible by currently practiced meat inspection. Nevertheless, the increased probability of detecting viable forms of T. gondii in tissues of pigs with titers ≥1: 80 could be used as the cutoff for discriminating higher risk animals, and could be used as an effective control tool for the industry of cured meat products. In practical terms, we propose that this value could be used as a critical limit in the HACCP system.


Granulomatous prostatitis. Special reference to radiologic findings.
Cystourethrography was performed in 2 patients with nonspecific, noneosinophilic granulomatous prostatitis. Lengthening of the prostatic urethra was noted essentially in the inframontane portion, thus differentiating it from benign prostatic hypertrophy. The widening in the prostatic urethra differentiates it from carcinoma of the prostate.


Algorithmic foundation of spectral rarefaction for measuring satellite imagery heterogeneity at multiple spatial scales.
Measuring heterogeneity in satellite imagery is an important task to deal with. Most measures of spectral diversity have been based on Shannon Information theory. However, this approach does not inherently address different scales, ranging from local (hereafter referred to alpha diversity) to global scales (gamma diversity). The aim of this paper is to propose a method for measuring spectral heterogeneity at multiple scales based on rarefaction curves. An algorithmic solution of rarefaction applied to image pixel values (Digital Numbers, DNs) is provided and discussed.


Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells.
Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance. Of 113 circuits analyzed, 109 functioned (96.5%) as intended without optimization. The circuits, which are available through Addgene, include a 3-input, two-output full adder; a 6-input, one-output Boolean logic look-up table; circuits with small-molecule-inducible control; and circuits that incorporate CRISPR-Cas9 to regulate endogenous genes. BLADE enables execution of sophisticated cellular computation in mammalian cells, with applications in cell and tissue engineering.


Endoscopically removed rectal NETs: a nationwide cohort study.
Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this is also safe for NETs up to 20 mm is unclear. We performed a nationwide study to determine the risk of lymph node and distant metastases in endoscopically removed NETs. All endoscopically removed rectal NETs between 1990 and 2010 were identified using the national pathology database (PALGA). Each NET was stratified according to size, grade and resection margin. Follow-up was until February 2016. Between 1990 and 2010, a total of 310 NETs smaller than 20 mm were endoscopically removed. Mean size of NETs was 7.4 mm (SD 3.5). In 49% of NETs (n = 153), no grade (G) could be assessed from the pathology report, 1% was G2 (n = 3), and the remaining NETs were G1. Median follow up was 11.6 years (range 4.9-26.0). During follow-up, 30 patients underwent surgical resection. Lymph node or distant metastasis was seen in 3 patients (1%) which all had a grade 2 NET. Mean time from endoscopic resection to diagnosis of metastases was 6.1 years (95% CI 2.9-9.2). No lymph node or distant metastases were seen in endoscopically removed G1 NETs up to 20 mm during the long follow-up of this nationwide study. This adds evidence to the ENET guideline that endoscopic resection of G1 NETs up to 20 mm appears to be safe.


Maternal smoking during pregnancy affects children's vigilance performance.
Aspects of attentional behaviour in 4--7-year-olds, as assessed by auditory and visual vigilance tasks, were related to prenatal exposure to cigarettes. Data on 76--79 children born to healthy, white, predominantly middle-class women were analyzed using multiple regression techniques controlling for potentially confounding variables including postnatal second hand smoke exposure. Cigarette smoking during pregnancy was related to an increased activity level of the children during the tasks and increased errors of commission in the auditory task and, to a lesser degree, in the visual task. After controlling for confounding factors, the relationship between prenatal smoking and errors of omission did not retain significance. The combination of results suggest that the deficits in attention may reflect impulsive responding and increased overall activity.


Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.
Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.


Obstetric gaslighting and the denial of mothers' realities.
Gaslighting is a type of abuse aimed at making victims question their sanity as well as the veracity and legitimacy of their own perspectives and feelings. In this article, we show how gaslighting can operate as a key, yet underexamined strategy of obstetric violence, or the institutional and interpersonal violation of women's rights during pregnancy, childbirth, and postpartum. We draw on forty-six in-depth, semi-structured interviews with mothers who experienced a traumatic childbirth to examine how obstetric providers gaslight mothers before, during and after childbirth when they deny - and thereby destabilize - mothers' realities. We identify and examine four core types of denials: denials of 1) mothers' humanity, 2) mothers' knowledge as valid, 3) mothers' judgements as rational and 4) mothers' feelings as legitimate. All four denials work to render mothers noncredible and their claims illegible within clinical encounters. In explicitly naming, theorizing, and examining obstetric gaslighting, our aims are threefold: 1) to uncover and theorize an underexamined mechanism of obstetric violence through a sociological lens, 2) to offer a typology of obstetric gaslighting's manifestations to aid scholars and practitioners in recognizing when obstetric gaslighting is occurring and 3) to advance a growing research program on gaslighting in medicine.


Adolescents as partners in the fight against COVID-19.
We report our experience of COVID-19 disease burden among patients aged 0-21 years at two tertiary care institutions in the Northeast and Midwest from New Jersey and Iowa. Our results showed that during the initial surge (March to August 2020) at both geographic locations, majority of COVID-19 disease burden occurred in adolescents and that they were more likely to be hospitalized for COVID-related illnesses, as well as develop severe disease needing intensive care. The study results emphasize the need for providing more targeted interventions toward this group to help prevent disease acquisition and transmission.


Clinical and radiographic evaluation of surgical reconstruction of finger flexion in tetraplegia.
To define the order and frequency of elongation in tendon junctions in extensor carpi radialis longus (ECRL) to flexor digitorum profundus tendon transfer and its correlation to grip strength and lack of finger flexion. Forty-seven tetraplegic patients had surgery involving the reconstruction of finger flexion with the transfer of the ECRL in a total of 62 arms. During surgery metal markers were placed on both sides of the tendon-to-tendon attachment site. After surgery the distance between the markers was measured on radiographs. Any increase in the distance between the markers was judged as elongation. The grip strength and mean pulp-to-palm distance were evaluated a minimum of 6 months after surgery. Three arms had a second surgery because of insufficient functional results. The average final elongation was 9 +/- 10 mm (mean +/- SD). The mean grip strength was 16 +/- 12 kPa (range, 0-50). The lack of flexion (mean value of pulp-to-distal palmar crease of 3 ulnar digits) was 0.8 +/- 1.2 cm on average. Elongation up to 15 to 20 mm still was compatible with good grasp. The tendon junction after a transfer of the ECRL to the finger flexors can be overloaded. Elongation therefore must be considered as one among several possible causes of an unsatisfactory result after this type of tendon transfer but elongation less than 15 mm usually is compatible with excellent function.


Fructose-1,6-diphosphate inhibits platelet activation.
Fructose-1,6-diphosphate (FDP) is a physiological product which exhibits pharmacological properties. This study shows that FDP (1-3 mM) inhibits platelet aggregation induced by the agonists thrombin, vasopressin, platelet activating factor, ADP, adrenaline, arachidonate and the stable thromboxane analogue U 44069. Thrombin-promoted ATP secretion and cytosolic Ca2+ rise are also drastically inhibited by FDP, which decreases, although to a lesser extent, the protein kinase C-dependent phosphorylation of the 47 kDa protein. The inhibition on thrombin-induced aggregation is shared, albeit less efficiently, by glucose-1,6-diphosphate and fructose-2,6-diphosphate but not by other phosphorylated monosaccharides (fructose-1:2 cyclic,6-diphosphate, glucose-1- and glucose-6-phosphate, fructose-1- and fructose-6-phosphate, mannose-6-phosphate and 5-phosphoryl ribose-1-pyrophosphate). FDP does not affect platelet activation induced by the protein kinase C activators dioctanoylglycerol or phorbol 12-myristate 13-acetate. No increase of cAMP concentration is observed in FDP-treated platelets. Altogether, these results indicate that FDP inhibits platelet activation at a level preceding phospholipase C. The data are consistent with a general inhibitory action of FDP on signal transmission.


Negative mood induction and unbalanced nutrition style as possible triggers of binges in binge eating disorder (BED).
To investigate whether negative mood and unbalanced nutrition style (fat rich/carbohydrate low) synergistically trigger binge eating in overweight and obese binge eating disorder (BED) patients. Subsequently to following an unbalanced or a balanced nutrition plan for three days, participants' food intake in a taste test was measured. During the taste test, participants were either in a negative or a neutral mood that was induced through a guided imagery task. Sixty-nine overweight and obese women with BED (mean age: 36.7 years, mean body mass index: 32.8 kg/m2). Eating behavior was assessed by measuring the amount of eaten food during the taste test. Visual analog scales were used to assess negative affect, tension, urge to eat, and hunger before and after the mood induction and after the taste test. Negative mood and unbalanced nutrition had neither a combined synergistic effect nor separate additive effects on the amount of food intake. Negative affect and tension decreased after the taste test in the negative mood group. Negative mood does not invariably enhance the risk of binge-eating behavior. Fat-rich, carbohydrate-low nutrition style did not influence food intake during a taste test. This finding questions the role of this specific nutrition style as a crucial factor in promoting binge eating. If replicated, these findings are important, since they could guide development of treatment protocols.


Chronic Villitis of unknown etiology (VUE): Obstetrical features, outcome and treatment.
Villitis of unknown etiology (VUE) is characterized by lympho-histiocytic infiltrates, which are predominant within the villous stroma. VUE can be of low grade i.e. affecting less than 10 contiguous villi or high grade with either patchy or diffuse subgroups (the later concerning more than 30 % of distal villi). Several other placental lesions could be associated with VUE, in particular in diffuse subgroups, such as diffuse perivillous fibrin deposition and chronic intervillositis. One of the most characteristic features of VUE is the late onset of fetal growth restriction after 32 weeks of gestation, and earlier detection of villitis should first raise an infectious origin. High grade VUE has been associated with fetal growth restriction, prematurity, fetal deaths, recurrent pregnancy loss, central nervous system injury and is characterized by relatively high risk of recurrence (25-50 %). Prospective and well-designed studies are necessary to determine the real prevalence of these adverse pregnancy events associated with VUE. Data about the management of VUE are extremely scarce and thus no recommendation based on the literature review could be actually done.


[Angiography of face and skull base (author's transl)].
The anatomic and technical conditions of the angiography of the face and the skull base are described. The significance of the catheter technique for selective demonstration of branches of the external carotid artery is stressed. The communications between the internal and the external carotid artery are discussed as well as the angiographic problems of arteriovenous fistulae and of hypervascular tumors. The selective angiography of the internal and the external carotid artery is an important tool of neuroradiology. By exact anatomic correlation of individual vessels and pathologic processes of the face and the skull base it is of interest also for oto-rhino-laryngology. Because of pain associated with the injection of contrast material general anaesthesia is deriable for the angiography of the external carotid artery.


Management of papillary breast lesions diagnosed on core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up.
Clinical management of papillary breast lesions (PBLs) remains controversial. The objective of this study was to identify pathologic and radiologic predictors of malignancy from a large cohort of PBLs diagnosed on core-needle biopsy (CNB). Retrospective review of the institutional pathology database identified all PBLs diagnosed from 2001 to 2009 and surgically excised within 6 months of diagnosis. PBLs were divided into intraductal papilloma (IDP) and IDP associated with atypical ductal or lobular hyperplasia (ADH/ALH). Surgical pathology of all lesions was reviewed and upgrade was defined as a change to a lesion of greater clinical significance, including ALH, ADH, lobular, or ductal carcinoma in situ (LCIS or DCIS), and invasive ducal carcinoma (IDC). We identified 276 patients (mean age 56 years; range 23 to 88 years) with PBLs on CNB. Seventy-nine patients (28.6%) upgraded to a lesion of greater clinical significance. Of the 234 (84.7%) had IDP only, 42 (17.9%) upgraded to ADH, and 21 (8.9%) to DCIS or IDC. Of the 42 (15.3%) patients with associated ADH or ALH on CNB, 16 (38.0%) upgraded to DCIS or IDC. The majority of patients (n = 173, 62.6%) had no breast symptoms. All patients had an abnormal mammogram and/or ultrasound that prompted the CNB. Among all clinical and radiographic variables analyzed, older age alone was predictive of upgrade. Frequent upgrade to a high-risk lesion or cancer is observed with IDPs diagnosed on CNB without adequate identifiable clinical and radiographic risk factors. Surgical excision should be performed for all IDPs to delineate subsequent clinical management.


Safety of gadolinium contrast angiography in patients with chronic renal insufficiency.
To prevent iodinated contrast medium-induced nephrotoxicity, gadolinium has been used increasingly for magnetic resonance angiography (MRA) or conventional digital subtraction angiography (DSA) to visualize arterial anatomy in patients undergoing vascular surgery who are considered at high risk because of chronic renal insufficiency. We assessed the safety of gadolinium-based contrast medium as a substitute for iodinated contrast medium-enhanced examinations. We determined the incidence of gadolinium-induced nephrotoxicity in a clinical setting and searched for contributing risk factors. Patients and methods In a single-center retrospective study from December 1999 to January 2001, 218 inpatients underwent MRA and 42 inpatients underwent DSA, with gadolinium as the sole contrast agent. Patient comorbid conditions, indications for vascular imaging, contrast dose, urine output, baseline and post-procedure serum creatinine concentration (SCr), and outcome were recorded for all patients in whom gadolinium-induced renal failure developed. Of 260 patients who received gadolinium-based contrast agents, at a dose of 0.25 mmol/kg or more, 195 patients (75%) had pre-test baseline chronic renal insufficiency. In 7 of 195 patients (3.5%) acute renal failure developed after gadolinium-based contrast medium administration, for MRA (n = 153) in 3 patients (1.9%) and DSA (n = 42) in 4 patients (9.5%). Average baseline SCr in the 195 patients with chronic renal insufficiency was 38.2 +/- 1.6 mL/min/1.73 m(2), and in the 7 patients in whom acute renal failure developed, baseline SCr was 32.5 +/- 7.8 mL/min/1.73 m(2) (P =.33). Respective intravenous and intra-arterial gadolinium doses in these 7 patients ranged from 0.31 to 0.41 mmol/kg for MRA and 0.27 to 0.42 mmol/kg for DSA. Acute renal failure did not develop in any of 65 patients with normal baseline SCr. Despite reports of negligible nephrotoxicity, rarely gadolinium-based contrast agents can cause acute renal failure in patients with underlying chronic renal insufficiency. Estimation of creatinine clearance alone does not enable prediction of which patients are likely to have acute renal failure. Patients at high-risk should be identified, and prophylactic measures should be taken to reduce the risk for nephrotoxicity.


Multiple urethral metastases from prostatic carcinoma causing urinary retention.
A rare case of multiple urethral metastases from adenocarcinoma of prostate causing urinary retention is reported. The unique findings of the urethrogram are described. Transurethral resection provided symptomatic relief. No local recurrence of tumor was observed during the follow-up period of sixteen months.


One drop only. Easy and rapid Raman evaluation of β-carotene in olive oil and its relevance as an index of olive fly attack.
This paper presents, for the first time, a method for the rapid quantification of β-carotene in olive oil by Raman spectroscopy. Using a 532 nm Raman laser source, our procedure requires only one drop (100 µL) of oil, for β-carotene content to be determined. Results show that β-carotene content is associated with the lutein/β-carotene ratio, a parameter whose value describes how healthy the olives were before processing, specifically whether an olive fly attack occurred. Since olive fly attacks are not always visible to the oil producers, this method gives them the means to control the validity of the prevention strategies they adopted.


Trends in cardiovascular engineering: organizing the human heart.
The regulation of heart growth through the interaction of cell types, matrix molecules, and mechanical cues is poorly understood, yet is necessary for the heart to reach its proper size and function. Using mechanical load and vascular cell co-culture in combination with a tissue engineering approach, we have recently been able to generate organized human myocardium in vitro and to modulate cardiomyocyte alignment, proliferation, and hypertrophy within the engineered tissue construct; further, we measured contractile function and the force-length dependence of the engineered tissue as a whole. The goal of these studies has been to characterize in vitro models of human cardiac development and to work towards human therapeutics using organized, vascularized, contractile human cardiac tissue. This review will touch on the current state of knowledge in this field, give an overview of the results of our own recent findings, and present areas of active investigation and new directions for future research.


Impact of the coronavirus pandemic on the patterns of vital signs recording and staff compliance with expected monitoring schedules on general wards.
Coronavirus disease 2019 (COVID-19) placed increased burdens on National Health Service hospitals and necessitated significant adjustments to their structures and processes. This research investigated if and how these changes affected the patterns of vital sign recording and staff compliance with expected monitoring schedules on general wards. We compared the pattern of vital signs and early warning score (EWS) data collected from admissions to a single hospital during the initial phase of the COVID-19 pandemic with those in three control periods from 2018, 2019 and 2020. Main outcome measures were weekly and monthly hospital admissions; daily and hourly patterns of recorded vital signs and EWS values; time to next observation and; proportions of 'on time', 'late' and 'missed' vital signs observations sets. There were large falls in admissions at the beginning of the COVID-19 era. Admissions were older, more unwell on admission and throughout their stay, more often required supplementary oxygen, spent longer in hospital and had a higher in-hospital mortality compared to one or more of the control periods. More daily observation sets were performed during the COVID-19 era than in the control periods. However, there was no clear evidence that COVID-19 affected the pattern of vital signs collection across the 24-h period or the week. The increased burdens of the COVID-19 pandemic, and the alterations in healthcare structures and processes necessary to respond to it, did not adversely affect the hospitals' ability to monitor patients under its care and to comply with expected monitoring schedules.


A dam mutant of Yersinia pestis is attenuated and induces protection against plague.
We have constructed a dam mutant of Yersinia pestis GB. In BALB/c mice inoculated subcutaneously, the median lethal dose of the mutant was at least 2000-fold higher than the wild type. Mice inoculated with sub-lethal doses of the mutant were protected against a subsequent challenge with virulent Y. pestis. The effect of dam inactivation on gene expression was examined using a DNA microarray, which revealed increased expression of a number of genes associated with the SOS response. These results confirm the key role of Dam in the regulation of virulence, and its potential role as a target for the generation of attenuated strains of pathogenic bacteria.


Spatial orientation deficit in children due to cerebellum astrocytoma pediatric tumor obtained by means of the Attentional Network Test.
Cerebellum astrocytomas are the most typical nervous system tumors in children. Several cognitive deficits have been previously described. These deficits are probably produced by cerebellar connection and gray matter damage. The present study examines attentional deficits in children operated on for cerebellum astrocytomas, using an attentional paradigm with theoretical and clinical bases: the Attentional Network Test (ANT). This test was designed considering the attentional network theory proposed by Posner, and its usefulness has been demonstrated in clinical settings. Children operated on for cerebellar astrocytoma showed a mild attentional deficit in the orientation network.


Bioprocess and genetic engineering aspects of ascomycin production: a review.
Ascomycin is a highly valuable multifunctional drug which exhibits numerous biological properties. Being an immunosuppressant, it is known to prevent graft rejection in humans and has potential to treat varying skin ailments. Its derivatives represent a novel class of anti-inflammatory macrolactams. But the biosynthetic machinery of ascomycin is still unclear. Due to the structural complexity, there occurs difficulty in its chemical synthesis; therefore, microbial production has been preferred by using Streptomyces hygroscopicus subsp. ascomyceticus. Through several genetic manipulation and mutagenesis techniques, the yield can be increased by several folds without any difficulties. Genetic engineering has played a significant role in understanding the biosynthetic pathway of ascomycin. Recently, many efforts have been made to utilize the therapeutic effects of ascomycin and its derivatives. This article covers concepts related to the production kinetics of ascomycin including an update of the ongoing yield improvement techniques as well as screening method of novel strains for ascomycin production.


Identification of an archaeal maltooligosyltrehalose trehalohydrolase encoded by an interrupted gene.
Complete genome analysis of the thermoacidophilic Archaeon Sulfolobus tokodaii strain 7 revealed two open reading frames (ORF), namely, ST0926 and ST0927. These ORFs are interrupted by two putative insertions and encode for the N- and C-terminal fragments, respectively, of a putative Sulfolobus sp. maltooligosyltrehalose trehalohydrolase (StMTHase). Two specific deletion mutations, designed on the basis of sequence alignments of the adjacent ORFs and the published Sulfolobus sp. MTHases, allowed soluble expression in Escherichia coli of an active acidic and thermophilic enzyme. The purified enzyme exhibited a maximum amylolytic activity at 70 °C and pH 5.0, which resembled the optimal conditions of the Sulfolobus homologs. Furthermore, we report that these ORFs are actively co-transcribed in vivo, and we confirm the presence of insertions between them at the cDNA level. However, immunization and western blot experiments demonstrated no expression of ST0926 or the putative full-length StMTHase in vivo, indicating that they might exist as nonfunctional pseudogenes.


The applicability of a non-anatomical soft and hard tissue centroid line (S&H centroid) in cephalometrics.
The applicability of a newly introduced non-anatomical soft and hard tissue cephalometric centroid line (S&H centroid) was investigated. The "S&H centroid" line established from 12″ × 14″ lateral cephalometric radiographs of 57 selected adults was used as a base to create a new cephalometric reference line "Centroid-Nasion". The reliability and the use of the newly created "Centroid-Nasion" as a reference line was tested against the conventional "Sella-Nasion" cephalometric reference line to evaluate the sagittal and vertical maxillary and mandibular relationship. Pearson's correlation coefficient, one way ANOVA, and Tukey multiple comparison post Hoc statistical tests were used. The digitization technique was reliable. The "Centroid-Nasion" cephalometric reference line created by utilizing the "S&H centroid" line, was found to be as useful as the conventional "Sella-Nasion" cephalometric plane in establishing and differentiating between sagittal and vertical intermaxillary relationships.


A High-Quality Melon Genome Assembly Provides Insights into Genetic Basis of Fruit Trait Improvement.
Accurate reference genomes have become indispensable tools for characterization of genetic and functional variations. Here we generated a high-quality assembly of the melon Payzawat using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. The final 12 chromosome-level scaffolds cover ∼94.13% of the estimated genome (398.57 Mb). Compared with the published DHL92 genome, our assembly exhibits a 157-fold increase in contig length and remarkable improvements in the assembly of centromeres and telomeres. Six genes within STHQF12.4 on pseudochromosome 12, identified from whole-genome comparison between Payzawat and DHL92, may explain a considerable proportion of the skin thickness. In addition, our population study showed that melon domesticated at multiple times from whole-genome perspective and melons in China are introduced from different routes. Selective sweeps underlying the genes related to desirable traits, haplotypes of alleles associated with agronomic traits, and the variants from resequencing data enable efficient breeding.


[Relationship between vascular endothelial growth factor expression and angiogenesis in osteosarcoma].
To determine the relationship between angiogenesis and vascular endothelial growth factor (VEGF) expression in osteosarcoma. The expression of VEGF was evaluated by immunohistochemical staining of tumor specimens from 33 patients with osteosarcoma. The microvessel density was assessed by immunostaining with CD34 in the most neovascularized area (hot spots). In osteosarcoma, the mean microvessel count of VEGF strong-expression tumors was significantly higher than that of VEGF low-expression tumors (Wilcoxon rank sum test, P < 0.05). The close correlation was found between VEGF expression and microvessel density. In contrast, no association was found between Price's grade of osteosarcoma and VEGF expression, as well as microvessel density. These observations suggest that VEGF is an important angiogenic factor in osteosarcoma.


The structure of two blood group A-active glycosphingolipids with 12 sugars and a branched chain present in the epithelial cells of rat small intestine.
Two blood group A-active dodecaglycosylceramides were earlier reported in a mixed fraction isolated from rat small intestine (Breimer, M. E., Hansson, G. C., Karlsson, K.-A., and Leffler, H. (1982) J. Biol. Chem. 257, 906-912). Treatment of these with alpha-N-acetylgalactosaminidase produced two blood group H-type decaglycosylceramides earlier identified in this tissue (Breimer, M. E., Falk, K.-E., Hansson, G. C. and Karlsson, K.-A. (1982) J. Biol. Chem. 257, 50-59). Proton NMR spectroscopy of the intact dodeca- and decaglycosylceramides and degradation studies established the following two branched-chain species, one (60% of the mixture) with type 1 sequences (Gal beta 1 leads to 3GlcNAc) in all three places, and the second (40% of the mixture) identical with this except for a type 2 sequence (Gal beta 1 leads to 4GlcNAc) in the 6-linked branch.


The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.
The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kvβ) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development.


[Thoracic radiography in intensive care units. Comparison of an asymmetric film-screen-grid combination with an L-film].
Using an asymmetrical screen-film-grid combination with an ITC-VHC special grid (Kodak), the effect of the individual components was evaluated with regard to detail in the lungs and mediastinum as well as patient dose. The system was compared with the Curix Ortho screen film system (Agfa L-film) using phantoms and 62 patients in an intensive care unit. The results were analysed by three independent observers. Dose measurements on phantoms were carried out with a WD 10 (Wellhoefer) dosimeter and with a thermoluminescence dosimeter for patients. Both phantom and patient images showed improved demonstration of mediastinal structures with similar details of lung structure. Details in the peripheral lungs are significantly better shown with the ITC-VHC system with the special grid than they are without the grid. However, there is an increase about three to four times in radiation dose when using the grid. Our trial shows that the use of the ITC-VHC grid system is to be recommended for routine clinical use because of the better demonstration of details, but one must be aware of the increased radiation dose to the patient.


An Evaluation of US Food and Drug Administration's Program to Register HIV Drugs for Use in Resource-Constrained Settings.
The US Food and Drug Administration (FDA) program to review antiretroviral drugs for use in low-resource settings via the US President's Emergency Plan for AIDS Relief (PEPFAR) now supports treatment of more than 14 million patients with HIV. However, an in-depth evaluation of the program has not been undertaken. To conduct a quantitative analysis of the FDA-reviewed antiretroviral drug applications in order to assess the contributions of PEPFAR and to identify areas for improvement. A cross-sectional study was conducted of all PEPFAR applications submitted to the FDA from December 1, 2004, to May 31, 2018. The analyses were conducted between October 2018 and February 2019. Numbers and types of applications reviewed, how long it took for applications to obtain approval or tentative approval (time to registration), how often the FDA issued a complete response letter (CRL) identifying deficiencies precluding application approval or tentative approval and their reasons, and the association between CRLs and time to registration. Overall, 260 PEPFAR applications for 327 antiretroviral therapies were reviewed by FDA, of which 216 applications (83%) for 272 drugs were authorized for use. Of the 216 authorized applications, 184 applications for 231 drugs remain in active status and, thus, are available for use. Twenty-six percent (56 of 216) of the applications were for pediatric-specific formulations or strengths; the remainder were for adults. For all 216 applications, the median (interquartile range) time to registration was 10.0 (7.0-17.5) months. Thirty-seven percent (95 of 260) of the applications received 1 or more CRLs, resulting in a total of 172 CRLs; most applications received 1 CRL, whereas some were issued up to 6 CRLs. Among all CRLs, 264 deficiency reasons were identified; the most common deficiencies were associated with manufacturing processes (155 [44%]), followed by product labeling (62 [23%]), and failing facility inspections (54 [20%]). Complete response letters were associated with an increased time to registration. Applications without CRLs had a median (interquartile range) time to registration of 9.0 (5.5-12.0) months, whereas those with at least 1 CRL took a median (interquartile range) of 22.0 (14.0-38.0) months (P < .001). The FDA's PEPFAR program has made many antiretroviral drugs available for global use. However, FDA and the pharmaceutical companies could take steps to improve the quality of applications submitted to prevent avoidable deficiencies in manufacturing processes and labeling. Further efforts to develop better, easier to use pediatric-specific therapies are needed.


In vitro activity of cefbuperazone compared with that of other new beta-lactam agents against anaerobic gram-negative bacilli and contribution of beta-lactamase to resistance.
Cefbuperazone was compared with other currently available and investigational antibiotics against 278 clinical isolates of anaerobic gram-negative bacilli by an agar dilution method. Cefbuperazone and cefotetan were equally active against Bacteroides fragilis, with 8% of the organisms tested found to be resistant to 32 micrograms of either drug per ml. Cefoperazone, cefotaxime, ceftriaxone, and cefmetazole were less active against these strains; cefoxitin, moxalactam, piperacillin, clindamycin, and metronidazole were more active. None of the agents were consistently active against any of the other anaerobic gram-negative bacilli except imipenem, for which the minimum concentration required to inhibit 90% of all strains tested was 4 micrograms/ml. A 10,000-fold increase in inoculum size caused an increase in the MIC of ceftriaxone, cefotaxime, and cefoperazone but not of cefbuperazone, cefotetan, or cefoxitin. Investigation of the mechanism of resistance to cephalosporin-like agents demonstrated a correlation between the level of resistance and beta-lactamase activity. Cefbuperazone, cefotetan, and cefoxitin were not hydrolyzed, had lower MICs, and were less affected by changes in inoculum size than were cefotaxime, ceftriaxone, and cefoperazone.


Added-value of ancillary imaging features for differentiating hepatocellular carcinoma from intrahepatic mass-forming cholangiocarcinoma on Gd-BOPTA-enhanced MRI in LI-RADS M.
To identify the reliable imaging features and added-value of ancillary imaging features for differentiating hepatocellular carcinoma (HCC) and intrahepatic mass-forming cholangiocarcinoma (IMCC) assigned to LI-RADS M on Gd-BOPTA-enhanced MRI. This retrospective study included 116 liver observations assigned to LI-RADS M, including 82 HCC and 34 IMCC histologically confirmed. Before and after adding ancillary imaging features, all variables with a p-value of < 0.05 in univariable analysis were entered into a multivariable logistic regression analysis to build diagnostic model 1 and model 2 to find reliable predictors of HCC diagnosis. Receiver operating characteristic (ROC) analysis and the DeLong test were used to compare the two models. Forty-nine of 82(59.8%) HCCs had a considerably higher frequency of enhancing "capsule" compared with IMCCs (p < 0.001). Based on LI-RADS major and LR-M features and clinical-pathologic factors, an elevated AFP level (OR = 10.676, 95%CI = 2.125-4.470, p = 0.004) and enhancing "capsule" (OR = 20.558, 95%CI = 4.470-94.550, p < 0.001) were extracted as independent risk factors in Model 1. After adding ancillary imaging features, Male (OR = 23.452, 95%CI = 1.465-375.404, p = 0.026), enhancing "capsule" (OR = 13.161, 95%CI = 1.725-100.400, p = 0.013), septum (OR = 17.983, 95%CI = 1.049-308.181, p = 0.046), small-scale central HBP hyperintensity (OR = 44.386, 95%CI = 1.610-1223.484, p = 0.025) were confirmed as independent significant variables associated with HCC. Model 2 demonstrated significantly superior AUC (0.918 vs 0.845, p = 0.021) compared with Model 1. When any two or more predictors in model 2 were satisfied, sensitivity was 91.46%, and accuracy was at the top (87.93%). Enhancing "capsule" was a reliable imaging feature to help identify HCC. Adding ancillary imaging features improved sensitivity and accuracy for HCC diagnosis with differentiation from IMCC in LR-M.


Acute kidney injury in the context of staged revision arthroplasty and the use of antibiotic-laden cement spacers: a systematic review.
The most common cause of revision arthroplasty is prosthetic joint infection (PJI). Chronic PJI is commonly treated with two-stage exchange arthroplasty involving the placement of antibiotic-laden cement spacers (ACS) in the first stage, often containing nephrotoxic antibiotics. These patients often have significant comorbidity burdens and have higher rates of acute kidney injury (AKI). This systematic review aims to assess the current literature to identify (1) AKI incidence, (2) associated risk factors, and (3) antibiotic concentration thresholds in ACS that increase AKI risk following first-stage revision arthroplasty. An electronic search was performed of the PubMed database of all studies involving patients undergoing ACS placement for chronic PJI. Studies assessing AKI rates and risk factors were screened by two authors independently. Data synthesis was performed when possible. Significant heterogeneity prevented meta-analysis. Eight observational studies consisting of 540 knee PJIs and 943 hip PJIs met inclusion criteria. There were 309 (21%) cases involving AKI. The most commonly reported risk factors included perfusion-related factors (lower preoperative hemoglobin, transfusion requirement, or hypovolemia), older age, increased comorbidity burden, and nonsteroidal anti-inflammatory drug consumption. Only two studies found increased risk with greater ACS antibiotic concentration (> 4 g vancomycin and > 4.8 g tobramycin per spacer in one study, > 3.6 g of vancomycin per batch or > 3.6 g of aminoglycosides per batch in the other); however, these were reported from univariate analyses not accounting for other potential risk factors. Patients undergoing ACS placement for chronic PJI are at an increased risk for AKI. Understanding the risk factors may lead to better multidisciplinary care and safer outcomes for chronic PJI patients.


Bedside case presentations: why patients like them but learners don't.
To determine current attitudes of patients, medical students, housestaff, and clinical faculty toward bedside case presentations. Survey using multiple-choice questionnaire and open comments for students, housestaff, and faculty, and a structured interview of patients. Major teaching hospitals on the campus of a midwestern medical school, staffed by full-time faculty. 136 medical students, 58 housestaff, 66 faculty, and 73 patients. 85% of patients liked the case presentation discussion at the bedside, but 95% of both students and housestaff felt more comfortable with such discussion away from the patient. Attending faculty were about evenly divided in preference, with the younger staff preferring the conference room setting. Most patients (88%) opposed rounds in the hallway. Duration of rounds of one to two hours was felt desirable by most, but 50% of students preferred a duration of less than one hour. For length of new patient case presentation, 60% of learners again favored brevity, less than 5 minutes. Bedside rounds are an opportunity to sharpen diagnostic skills and to demonstrate the art of medicine. They are undervalued by learners and younger faculty but appreciated by patients. The authors recommend that faculty improve bedside rounds by assessing team members' educational needs, by cultivating sensitivity and respect for the needs of all parties, and by assuring pertinence and brevity of bedside discussion.


Differential behavioral profile induced by the injection of dipotassium chlorazepate within brain areas that project to the nucleus accumbens septi.
The effect of the agonism on γ-aminobutyric acid (GABA) receptors was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These structures send glutamatergic projections to the nucleus accumbens septi (NAS), in which interaction and integration between these afferent pathways has been described. In a previous study of our group, blockade of glutamatergic transmission within NAS induced an anxiolytic like effect. Three rat groups received either saline or dipotassium chlorazepate (1 or 2 μg/1 μl solution) 15 min before testing. Time spent in the open arms (TSOA), time per entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and relationship between open- and closed-arms quotient (OCAQ) were recorded. In the AMY injected group TSOA, OAE and EA were increased by the higher doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA, OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p < 0.01) and saline injection showed an increasing significant difference (p < 0.001 in all cases) with the action of guide cannula alone within VH in TSOA, OAE and EA. We conclude that the injection of dipotassium chlorazepate has a differential effect depending of the brain area, leading to facilitatory and inhibitory effects on anxiety processing.


Evaluation of the myotoxicity of bupivacaine in bier blocks--a biochemical and electron microscopic study.
The possible myotoxic effect of bupivacaine in combination with tourniquet ischemia was evaluated in 11 patients who underwent surgery of an arm under intravenous regional anesthesia. Eleven patients with the same kind of surgery and tourniquet who had general anesthesia served as controls. Venous blood bupivacaine concentrations in the anesthetized arm were high at the end of tourniquet time (27.2-202 micrograms/m1) and varied from 2.3 to 12.3 micrograms/ml 10 min after tourniquet release. Changes in blood-gas tensions and plasma potassium and lactate concentrations before and just after tourniquet release correlated with the ischemia time. Changes in creatine phosphokinase, lactate dehydrogenase and aspartate aminotransferase activities, possible indices of loss of integrity of muscle cell membranes, varied considerably and did not correlate with the ischemia time. There were no significant differences between the two groups in any of the parameters. Electron microscopy revealed no evidence of muscle degeneration 24 hr after the use of tourniquet with either bupivacaine intravenous regional (n = 4) or general anesthesia (n = 3).


A genome-wide association analysis of temozolomide response using lymphoblastoid cell lines shows a clinically relevant association with MGMT.
Recently, lymphoblastoid cell lines (LCLs) have emerged as an innovative model system for mapping gene variants that predict the dose response to chemotherapy drugs. In the current study, this strategy was expanded to the in-vitro genome-wide association approach, using 516 LCLs derived from a White cohort to assess the cytotoxic response to temozolomide. Genome-wide association analysis using ∼2.1 million quality-controlled single-nucleotide polymorphisms (SNPs) identified a statistically significant association (P<10(-8)) with SNPs in the O(6)-methylguanine-DNA methyltransferase (MGMT) gene. We also show that the primary SNP in this region is significantly associated with the differential gene expression of MGMT (P<10(-26)) in LCLs and differential methylation in glioblastoma samples from The Cancer Genome Atlas. The previously documented clinical and functional relationships between MGMT and temozolomide response highlight the potential of well-powered genome-wide association studies of the LCL model system to identify meaningful genetic associations.


Cernunnos defect in an Iranian patient with T- B+ NK+ severe combined immunodeficiency: A case report and review of the literature.
Defective Cernunnos gene in nonhomologous end-joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature. The patient was a 6-month-old female born to consanguineous parents. She presented with long-lasting fever, diarrhea, poor feeding, and restlessness. She had suffered from recurrent fever of unknown origin and multiple episodes of oral candidiasis. In the physical examination, microcephaly, failure to thrive, oral candidiasis, pustular rash on fingers, and perianal ulcers, but no dysmorphic feature were observed. The immunologic workup revealed lymphopenia, neutropenia, normocytic anemia, low T- but normal B- and natural killer (NK)- cells, low immunoglobulin (Ig)G, and normal IgA, IgM, and IgE. The T-cell receptor excision circle (TREC) was low and the lymphocyte transformation test (LTT) was abnormal to mitogens and antigens. She was diagnosed with T- B+ NK+ SCID and improved by intravenous immunoglobulin along with antimicrobials. A homozygous splice site variant, c.390 + 1G > T, at the intron 3 of the NHEJ1, was identified and the diagnosis of Cernunnos deficiency was established. However, while a candidate for hematopoietic stem cell transplantation, she developed sepsis and died at 11 months of age. Cernunnos deficiency should be considered as a differential diagnosis in patients with microcephaly, growth retardation, recurrent infections, T-cell defects, and hypogammaglobulinemia. The normal B-cell level in the index patient is an unexpected finding in Cernunnos deficiency which requires further evaluation.


Pathogenicity and immunogenicity in chickens of Newcastle disease viruses isolated from wild ducks. Brief report.
Three Newcastle disease viruses (NDV) isolated from wild ducks in Japan were evaluated for their biological activities, pathogenicity and immunogenicity against one-day-old chickens. One isolate was of the mesogenic type and the other two were of the lentogenic type for chicken. The lentogenic isolates could induce enough immunity in chickens to protect them from challenge with a virulent strain of NDV.


Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism.
Serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), C-terminal immunoreactive PTH (iPTH), calcium and phosphate, and endogenous creatinine clearance (Clcr) were measured in 34 patients with primary hyperparathyroidism. Clcr ranged from 13 to 161 ml/min (mean 72). S-iPTH was elevated in 82% of the patients and correlated positively to serum calcium (r = 0.74, P less than 0.001) and inversely to Clcr (r = -0.50, P less than 0.02). S-25(OH)D3 was reduced in 28% of the patients and depended on regular multivitamin supplementation (P less than 0.005). S-1,25(OH)2D3 was increased in 26% of the patients and decreased in 9%. It was positively correlated to S-25(OH)D3 (r = 0.39, P less than 0.05) and Clcr (r = 0.42, P less than 0.02) and inversely to serum levels of calcium (r = -0.39, P less than 0.05), phosphate (r = -0.42, P less than 0.02) and iPTH (r = -0.40, P less than 0.05). Multiple regression analysis revealed a positive correlation to 25(OH)D3 when Clcr was taken into account and to Clcr when S-25(OH)D3 was taken into account. When both variables were considered no significant partial correlations were found between S-1,25(OH)2D3 and serum calcium, phosphate and PTH, respectively. It is concluded that serum levels of 25(OH)D3 and renal function are the main determinants for S-1,25(OH)2D3 in primary hyperparathyroidism.


Genetical and geographic studies on isoniazid inactivation.
Rapid and slow inactivators of isoniazid are homozygotes, and intermediate inactivators are heterozygotes. There is no dominance between the two alleles. The chasm between Eskimos and Caucasians in isoniazid metabolism is bridged by our investigation of the races in the Far East.


Gender-specific relationship between frequency of food-away-from-home with serum lipid levels and dyslipidemia in chinese rural adults.
Food-away-from-home (FAFH) is one of the leading dietary patterns in Chinese families. However, the relationship between FAFH and dyslipidemia remains unclear, especially in the rural adult population. This study explored the relationship of FAFH frequency with serum lipid levels and dyslipidemia in rural Chinese adults. A total of 12,002 men and 17,477 women aged 18-79 were included from the Henan rural cohort. Serum lipid levels were measured by enzyme colorimetry. Information on FAFH frequency was collected using a validated questionnaire. The associations of FAFH frequency and serum lipid levels were assessed through multiple linear regression modeling. Logistic regression was performed to explore the linkages of the FAFH frequency to dyslipidemia and its four parameter types. Mediation analysis examined whether body mass index (BMI) acted as a mediator between the FAFH frequency and dyslipidemia. After adjusting for potential confounders, the adjusted odds ratio (OR) and 95% confidence interval (CI) of the groups with 8-11 FAFH times/week for dyslipidemia were 1.991 (1.569, 2.526) in men compared with 0-frequency subgroup. Participants who consumed 8-11 FAFH times/week had a higher risk of high total cholesterol (TC), high triglycerides (TG), high LDL-cholesterol (LDL-C), and low HDL-cholesterol (HDL-C) with the OR and 95% CI of 1.928 (1.247, 2.980), 1.723 (1.321, 2.247), 1.875 (1.215, 2.893), and 1.513 (1.168, 1.959), respectively. In addition, the interaction effect between FAFH and gender was significantly associated with dyslipidemia and lipid levels (P < 0.001). BMI played a fully mediating effect between FAFH frequency and dyslipidemia in men, and the Sobel test showed the significance of the mediating effect (z = 4.2158, P < 0.001). In rural Chinese adults, FAFH was significantly associated with a higher risk of dyslipidemia, which indicated the importance of FAFH reduction and dietary intervention in patients with dyslipidemia and cardiovascular disease, especially in clinical practice. The Henan Rural Cohort Study has been registered on the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15,006,699).


Effect of mild hypothermia on lung injury after cardiac arrest in swine based on lung ultrasound.
Lung injury is common in post-cardiac arrest syndrome, and is associated with increased morbidity and mortality. The aim of this study was to evaluate the effect of mild hypothermia on lung injury after cardiac arrest in swine based on lung ultrasound. Twenty-three male domestic swine weighing 36 ± 2 kg were randomly assigned to three groups: therapeutic hypothermia (TH, n = 9), normothermia (NT, n = 9), and sham control (control, n = 5) groups. Sham animals only underwent surgical preparation. The animal model was established with 8 min of ventricular fibrillation followed by 5 min of cardiopulmonary resuscitation. Therapeutic hypothermia was induced and maintained until 24 h post-resuscitation in the TH group by surface blanket cooling, followed by rewarming at a rate of 1 °C/h for 5 h. The extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), PO2/FiO2, and lung ultrasound score (LUS) were measured at baseline and at 1, 3, 6, 12, 24, and 30 h after resuscitation. After euthanizing the swine, their lung tissues were quickly obtained to evaluate inflammation. After resuscitation, ELWI and PVPI in the NT group were higher, and PO2/FiO2 was lower, than in the sham group. However, those measures were significantly better in the TH group than the NT group. The LUS was higher in the NT group than in the sham group at 1, 3, 6, 12, 24, and 30 h after resuscitation. The LUS was significantly better in the TH group compared to the NT group. The lung tissue biopsy revealed that lung injury was more severe in the NT group than in the TH group. Increases in LUS were highly correlated with increases in ELWI (r = 0.613; p < 0.001) and PVPI (r = 0.683; p < 0.001), and decreases in PO2/FiO2 (r = - 0.468; p < 0.001). Mild hypothermia protected against post-resuscitation lung injury in a swine model of cardiac arrest. Lung ultrasound was useful to dynamically evaluate the role of TH in lung protection.


National TB elimination programme - What has changed.
Before the start of Coronavirus (COVID-19) pandemic, TB was the leading cause of death due to a single infectious agent, ranking well above HIV/AIDS. Almost one-fourth of the world's population is infected with M. tuberculosis. TB is curable and preventable. About 85% of people who develop TB can be successfully treated with drug regimens of 6 months. Universal health coverage (UHC) is necessary to ensure that all those with the disease can access these treatments. Research breakthroughs (e.g., newer rapid diagnostic techniques, drugs, newer vaccine) are needed to rapidly reduce the number of new cases each year (TB incidence) worldwide. Changes in the National TB Elimination Programme since its inception. The Government of India launched the "National TB Programme" in 1962 as District TB Centre model involved with BCG vaccination and TB treatment to fight tuberculosis, a major public health problem. The tuberculosis control programme has come a long way since then and has undergone major changes over the past few years The Ministry of Health and Family Welfare has developed the "National Strategic Plan" for Tuberculosis Elimination (2017-25) which encapsulates the bold and innovative steps required to eliminate TB in India by 2025, five years ahead of the global targets. By 2020 it was clear that the NSP- 2017-25 will not be able to meet these objectives, so another new NSP India 2025 had been launched in 2020. India has been actively involved in TB control activities for more than 50 years now. TB still continues to be a severe health problem in India. The country is now better prepared to tackle TB than before. It now has advanced and effective interventions and technologies for diagnosis, treatment and care of TB cases.


"The necessity for better bodies to perpetuate our institutions, insure a higher development of the individual, and advance the conditions of the race." Physical culture and the formation of the self in the late nineteenth and early twentieth century USA.
This article explores the significance of sports and physical exercise in the turn-of-the-century culture and society of the U.S. It depicts how physical fitness became a decisive feature of collective and individual self-perception and was understood as being at the core of a successful shaping of both the self and of the American body politic. I concentrate in particular on paradigms and strategies of human resources management to exemplify the overarching significance of physical fitness as it established itself at the heart of the USA's enterprise culture that began to emerge in the later nineteenth century. American peculiarities will be considered, alongside ties and allusions to European, and particularly British, developments.


Information sources used by parents to learn about medications they are giving their children.
Previous studies have indicated the use of medication by children to be dependent on the attitudes of knowledge of their parents; however, little is known about sources parents might use in driving medication use decisions. The aim of this study was to describe the information sources that parents use regarding their children's medication and their perceptions of the reliability of these information sources. This study is part of a cross-sectional population survey with a random sample of 6000 children younger than 12 years. The response rate of the questionnaire was 67%. Parents were asked about the use of information sources and their perception of reliability with a list of 16 information sources. The information sources that parents reported having used were physicians (72%), patient information leaflets (PILs) (67%), public or school health nurses (52%), and pharmacists (44%). Regardless of the child's age, physicians were the parents' most-used information source. Physicians were the most-used information source also when the child had at least 1 of the 4 most common long-term diseases among children in Finland (asthma, diabetes, epilepsy, and juvenile idiopathic arthritis). Parents considered physicians (50%), PILs (31%), pharmacists (27%), nurses (20%), and public or school health nurses (17%) very reliable information sources. Finnish parents seek information from health care professionals and PILs when looking for information concerning their children's medication. Furthermore, they find health care professionals and PILs to be reliable information sources.


Large sub-pleural air cysts: an extreme form of pulmonary interstitial emphysema.
Pulmonary interstitial emphysema is a well-documented complication of positive-pressure ventilation. However, the occurrence of large sub-pleural air cysts is a less well-known, extreme manifestation of this entity. We present here an infant who developed this complication of pulmonary barotrauma during cardiopulmonary resuscitative efforts.


Promotion of bio-oil production from the microwave pyrolysis of cow dung using pretreated red mud as a bifunctional additive: Parameter optimization, energy efficiency evaluation, and mechanism analysis.
To address the issues of high oxygen content and energy consumption in the microwave-assisted pyrolysis of biomass for biofuel production, this study used high-temperature pretreated red mud (RM) as an additive. The pretreated RM exhibited dual functionalities, namely microwave absorption and catalytic properties, during the microwave-assisted pyrolysis of cow dung (CD). This study also evaluated the optimization potential of energy recovery efficiency. The results showed that the addition of pretreated RM significantly increased the oil yield during the microwave-assisted pyrolysis of CD. The highest oil yield (59.63%) was obtained via the microwave-assisted pyrolysis of CD over catalysis with RM pretreated at 750 °C (RM750). Through the optimization of the RM750-to-CD mixing ratio, optimal oil quality and energy recovery efficiency were achieved. At a mixing ratio of 1:1, the pyrolysis oil featured the highest aromatic hydrocarbon content and lowest acid content. The high-temperature pretreatment of RM increased the Fe2O3 content, which enhanced the dielectric properties and magnetic loss ability of the reactants. This resulted in localized high temperatures and the formation of "hot spots," which can promote the deoxygenation and hydrogenation reactions of oil. Consequently, the lower heating rate of oil increased from 35.12 to 40.11 MJ kg-1. The released oxygen escaped in the form of CO. In addition, pyrolytic char was used as an in situ microwave absorbing material owing to its increased Fe2O3 content and graphitization degree, leading to an increase in energy recovery efficiency from 4.71% to 9.98%. This study provides valuable guidance for the efficient utilization of diversified solid wastes and demonstrates the potential application of microwave-assisted pyrolysis technology in the resource utilization of solid wastes.


[Differential expressions of microRNAs and their predicted targets in liver transplant recipients with long-term stable survival].
To determine whether the miRNA expression profile in peripheral blood mononuclear cells (PBMCs) differs between liver transplant recipients with long-term stable survival and those with acute rejection. Twenty-nine liver transplant recipients with long-term stable survival (STA) group, 10 recipients with acute rejection (RJ group), and 17 healthy subjects (control group) were recruited for genome-wide microarray analysis of miRNA expressions in the PBMCs. The differentially expressed miRNAs among the 3 groups were validated by real-time PCR, and the targets of these miRNAs were predicted. Compared with the RJ group, the STA group showed down-regulation of 13 miRNAs in the PBMCs. Of these down-regulated miRNAs, miRNA-18b, miRNA-340 and miRNA-106b were validated by real-time PCR, and the latter two miRNAs were predicted to target the TGF-β pathway. The differentially expressed miRNAs in liver transplant recipients with long-term stable survival, namely miRNA-18b, miRNA-340 and miRNA-106b, can be potential clinical biomarkers to predict the outcomes of liver transplantation.


De novo peptide sequencing and quantitative profiling of complex protein mixtures using mass-coded abundance tagging.
Proteomic studies require efficient, robust, and practical methods of characterizing proteins present in biological samples. Here we describe an integrated strategy for systematic proteome analysis based on differential guanidination of C-terminal lysine residues on tryptic peptides followed by capillary liquid chromatography-electrospray tandem mass spectrometry. The approach, termed mass-coded abundance tagging (MCAT), facilitates the automated, large-scale, and comprehensive de novo determination of peptide sequence and relative quantitation of proteins in biological samples in a single analysis. MCAT offers marked advantages as compared with previously described methods and is simple, economic, and effective when applied to complex proteomic mixtures. MCAT is used to identify proteins, including polymorphic variants, from complex mixtures and measure variation in protein levels from diverse cell types.


How the 'HIV/TB co-epidemic-HIV stigma-TB stigma' syndemic impacts on the use of occupational health services for TB in South African hospitals: a structural equation modelling analysis of the baseline data from the HaTSaH Study (cluster RCT).
Tuberculosis (TB) has become an occupational health hazard in South African hospitals where healthcare workers (HCWs) are additionally confronted daily with HIV and its associated stigma, causing a syndemic. Early TB diagnosis and treatment are vital, but the uptake of these services through occupational healthcare units (OHUs) is low. The current study hypothesises that (1) the link between HIV and TB and (2) the perceived HIV stigmatisation by colleagues create (3) a double HIV-TB stigma which increases (4) internalised TB stigma and leads to (5) a lower willingness to use OHU services for TB screening and treatment. A cross-sectional study using the baseline data from the HIV and TB Stigma among Healthcare workers Study (HaTSaH Study). Six hospitals in the Free State province of South Africa. 820 HCWs of the six selected hospitals. The study results demonstrate that the co-epidemic (β=0.399 (screening model) and β=0.345 (treatment model)) combined (interaction effect: β=0.133 (screening) and β=0.132 (treatment)) with the persistent stigmatisation of HIV is altering the attitudes towards TB (β=0.345 (screening) and β=0.400 (treatment)), where the stigmatising views of HIV are transferred to TB-illustrating the syndemic impact. Our model demonstrated that this syndemic not only leads to higher levels of internal TB stigma (β=0.421 (screening) and β=0.426 (treatment)), but also to a lower willingness to use the OHU for TB screening (probit coefficient=-0.216) and treatment (probit coefficient=-0.160). Confidentiality consistently emerged as a contextual correlate of OHU use. Theoretically, our results confirm HIV as a 'syndemic generator' which changes the social meaning of TB in the hospital context. Practically, the study demonstrated that the syndemic of TB and HIV in a highly endemic context with stigma impacts the intended use of occupational TB services. Pre-results of the trial registered at the South African National Clinical Trials Register, registration ID: DOH-27-1115-5204.


Carer distress among community living older adults with complex needs in the pre- and post-COVID-19 era: a national population study.
Carer distress is one important negative impact of caregiving and likely exacerbated by the novel coronavirus disease 2019 (COVID-19) pandemic, yet little population-based epidemiological information exists. Using national data from repeated standardized comprehensive geriatric needs assessments, this study aims to: describe the pattern of caregiver distress among those providing informal care to community-living adults aged ≥ 65 years with complex needs in New Zealand over time; estimate the COVID-19 effect on this temporal pattern; and, investigate relationships between participants' sociodemographic and selected health measures on caregiver distress. Fractional polynomial regression and multivariable multilevel mixed-effects models were employed. Overall, 231,277 assessments from 144,358 participants were analysed. At first assessment, average age was 82.0 years (range 65-107 years), and 85,676 (59.4%) were female. Carer distress prevalence increased from 35.1% on 5 July 2012 to a peak of 48.5% on 21 March 2020, when the New Zealand Government announced a national lock-down. However, the population attributional fraction associated with the COVID-19 period was small, estimated at 0.56% (95% CI 0.35%, 0.77%). Carer distress is common and has rapidly increased in recent years. While significant, the COVID-19 impact has been relatively small. Policies and services providing efficacious on-going strategies to support caregivers deserves specific attention.


A novel approach for determination of free fatty acids in vegetable oils by a flow injection system with manual injection.
A non-aqueous flow injection method for determining free fatty acid (FFA) content in corn and sunflower oil samples was developed. A single-line manifold system was built by modification of an HPLC for flow injection analysis (FIA). Without pre-treatment, oil samples were injected into a n-propanol solution containing KOH and phenolphthalein (PHP). The main parameters, such as flow rate of carrier phase, length, geometry, inner diameters of the coils and reagent concentration were all optimized. The proposed FIA method was validated for precision, accuracy, linear region, limit of detection (LOD) and limit of quantification (LOQ). The intra- and inter-day measurements of the precision of the method were found to be within the limits of acceptance criteria (RSD < 1%), and were rugged when the method was performed by a different analyst. The linear concentration range was calculated as 0.09-1.50 and 0.07-1.40 FFA% for corn and sunflower oils, correspondingly. The LOD and LOQ were found to be 7.53 × 10(-4)-2.28 × 10(-3) oleic acid % and 7.11 × 10(-4)-2.23 × 10(-3) oleic acid % for corn and sunflower oils, respectively. The results were compared with those obtained by the AOCS (Ca-5a-40) method using statistical t and F tests, and a significant difference was not observed between the methods at a 95% confidence level. The proposed method is suitable for quality control of routine applications due to its simplicity, high sample throughput, and economy of solvents and sample, offering considerable promise as a low cost analytical system that needs minimum human intervention over long periods of time.


Repeated translocation of a supergene underlying rapid sex chromosome turnover in Takifugu pufferfish.
Recent studies have revealed a surprising diversity of sex chromosomes in vertebrates. However, the detailed mechanism of their turnover is still elusive. To understand this process, it is necessary to compare closely related species in terms of sex-determining genes and the chromosomes harboring them. Here, we explored the genus Takifugu, in which one strong candidate sex-determining gene, Amhr2, has been identified. To trace the processes involved in transitions in the sex-determination system in this genus, we studied 12 species and found that while the Amhr2 locus likely determines sex in the majority of Takifugu species, three species have acquired sex-determining loci at different chromosomal locations. Nevertheless, the generation of genome assemblies for the three species revealed that they share a portion of the male-specific supergene that contains a candidate sex-determining gene, GsdfY, along with genes that potentially play a role in male fitness. The shared supergene spans ∼100 kb and is flanked by two duplicated regions characterized by CACTA transposable elements. These results suggest that the shared supergene has taken over the role of sex-determining locus from Amhr2 in lineages leading to the three species, and repeated translocations of the supergene underlie the turnover of sex chromosomes in these lineages. These findings highlight the underestimated role of a mobile supergene in the turnover of sex chromosomes in vertebrates.


Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.
Acute renal failure has important prognostic implications in critically ill patients, but the effects of acute renal failure on in-hospital mortality in the subset of patients with cardiogenic shock are not known. All consecutive patients who presented with acute coronary syndrome at our cardiovascular intensive care unit from 1993 to 2000 and who were in cardiogenic shock were enrolled. Acute renal failure was defined as a urine volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5 mg/dL or > 50% above the baseline value. There were 118 patients (83 men [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute renal failure within 24 hours after the onset of shock. In-hospital mortality was 87% (34/39) in patients with acute renal failure and 53% (42/79) in patients without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]: 2.1 to 17; P < 0.001). Other significant univariate predictors of mortality included the peak serum lactate level, epinephrine dose, and the maximum serum creatinine level. Multivariate logistic regression analysis identified acute renal failure as the only independent predictor of mortality. Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.


[A unique population in today's paediatric intensive care unit: Immigrant children presenting with infectious diseases].
Despite similar disease severity scores; we found a higher crude death rate in the group of immigrant children compared to the group of native children in a paediatric intensive care unit. Our study aimed to compare descriptive data and standardised mortality ratios (SMR) in order to analyse differences in mortality. We conducted a retrospective study comparing demographic characteristics, diagnostic data, disease severity scores and mortality in immigrant children of Syrian descent and children of Turkish descent. We included data for the medical and surgical patients admitted in 1 year. The sample included 1283 patients. We compared the age and sex distribution, presence of underlying disease, frequency of community-acquired infectious diseases, length of say, PRISM scores, SMR and crude death rates in the 2 groups. There were 1077 patients in the Turkish group and 206 patients in the immigrant group. The proportion of patients with underlying disease was greater in the Turkish group (42% vs. 37.4%). The proportion of patients with a community-acquired infectious disease as the presenting complaint was similar in both groups (52.9% vs. 47.4%). The mortality in patients with infectious disease was higher in the immigrant group (19.3% vs. 9.8%). There was not significant difference in the mean PRISM score between the 2 groups. We found a higher mortality in the immigrant group (16% vs. 11%). The standardised mortality ratio was 0.32 in the total sample group; 0.4 in the immigrant group and 0.24 in the Turkish group. In our study, we found an association between community-acquired infectious disease and increased mortality in the immigrant group. The underlying mechanism for this increase remains to be explained and further research is required to determine whether parameters related to infection should be added to this severity score for its use in this specific population.


Does Obesity Increase the Risk and Severity of Falls in People Aged 60 Years and Older? A Systematic Review and Meta-analysis of Observational Studies.
Recent investigations suggest that obesity may be associated with an increased risk of falls; however, this theory has yet to be definitively confirmed. This systematic review and meta-analysis examined the strength of the association between obesity and falls, multiple falls, fall-related injuries, and fall-related fractures among older adults. MEDLINE, Embase, CINAHL, PsycINFO, SPORTDiscus, LILACS, and Web of Science databases were searched to identify observational studies that assessed the association between obesity and fall-related outcomes in participants aged 60 years and older. Two independent reviewers performed data extraction and quality assessment. Relative risks and 95% confidence intervals (CI) were pooled using random effect meta-analyses. Thirty-one studies including a total of 1,758,694 participants were selected from 7,815 references. Pooled estimates showed that obese older adults have an increased risk of falls compared with nonobese counterparts (24 studies; relative risk: 1.16; 95% CI: 1.07-1.26; I2: 90%). Obesity was also associated with an increased risk of multiple falls (four studies; relative risk: 1.18; 95% CI: 1.08-1.29; I2: 0%). There was no evidence, however, of an association between obesity and fall-related injuries (seven studies; relative risk: 1.04; 95% CI: 0.92-1.18; I2: 65%). Fall-related fractures were reported in only one study, which demonstrated a lower risk of hip fracture with obesity (odds ratio: 0.65; 95% CI: 0.63-0.68). Obesity increases the risk of falls and multiple falls in people aged 60 years and older; however, there is insufficient evidence of an association with fall-related injuries or fractures. Prevention and treatment of obesity may play a role in preventing falls in older age.


The impact of closed incision negative pressure therapy on prevention of median sternotomy infection for high risk cases: a single centre retrospective study.
Sternal wound infection (SWI) following cardiothoracic surgery is a major complication. It may significantly impact patient recovery, treatment cost and mortality rates. No universal guideline exists on SWI management, and more recently the focus has become prevention over treatment. Recent studies report positive outcomes with closed incision negative pressure therapy (ciNPT) on surgical incisions, particularly for patients at risk of poor wound healing. This study aims to assess the effect of ciNPT on SWI incidence in high-risk patients. A retrospective study was performed to investigate the benefit of ciNPT post sternotomy. Patients 3 years before the introduction of ciNPT (Control group) and 3 years after ciNPT availability (ciNPT group) were included. Only patients that had two or more of the risk factors; obesity, Chronic Obstructive Pulmonary Disease, old age and diabetes mellitus in the High Risk ciNPT cohort were given the ciNPT dressing. Patient demographics, EuroSCOREs and length of staywere reported as mean ± standard deviation. The Fisher's exact test (two-tailed) and an unpaired t-test (two-tailed) were used to calculate the p-value for categorical data and continuous data, respectively. The total number of patients was 1859 with 927 in the Control group and 932 in the ciNPT group. No statistical differences were noted between the groups apart from the Logistic EuroSCORE (Control = 6.802 ± 9.7 vs. ciNPT = 8.126 ± 11.3; P = 0.0002). The overall SWI incidence decreased from 8.7 to 4.4% in the overall groups with the introduction of ciNPT (P = 0.0005) demonstrating a 50% reduction. The patients with two and above risk factor in the Control Group (High Risk Control Group) were 162 while there was 158 in the ciNPT Group (High Risk ciNPT Group). The two groups were similar in all characteristics. Although the superficial and deep sternal would infections were higher in the High Risk Control Group versus the High Risk ciNPT group patients (20(12.4%) vs 9(5.6%); P = 0.049 respectively), the length of postoperative stay was similar in both (13.0 ± 15.1 versus 12.2 ± 15.6 days; p + 0.65). However the patients that developed infections in the two High Risk Groups stayed significantly longer than those who did not (25.5 ± 27.7 versus 12.2 ± 15.6 days;P = 0.008). There were 13 deaths in Hospital in the High Risk Control Group versus 10 in the High Risk ciNPT Group (P = 0.66). In this study, ciNPT reduced SWI incidence post sternotomy in patients at risk for developing SWI. This however did not translate into shorter hospital stay or mortality.


[Evolutionary trends in the prokaryotic community and prokaryotic community-phage systems].
The Evolutionary Constructor software has been used for computer simulation of the life and evolution of communities of unicellular haploid organisms (prokaryotic cells). Opposite trends of the community evolution (simplification and complication of the genome) have been studied. It has been demonstrated that species with reduced genomes tend to replace genetically and metabolically rich species under highly favorable environmental conditions. Under unfavorable conditions, the opposite tendency is observed. It has also been shown that introduction of phages capable of killing the cells into the system may radically change the current evolutionary trend.


The etiology, biology, and evolving pathology of premenstrual syndromes.
Menstrually related symptoms and disorders are multidimensional and affect diverse physiologic systems. Elucidation of the pathophysiologic mechanisms of these disorders should allow for a more precise diagnosis, and provide direction for targeted therapeutic interventions. Several biologic mechanisms that underlie menstrually related symptoms have been proposed. They focus mostly on gonadal hormones, their metabolites and interactions with neurotransmitters and neurohormonal systems, such as serotonin, GABA, cholecystokinin, and the renin-angiotensin-aldosterone system. Altered responses of these systems to gonadal hormone's fluctuations during the menstrual cycle, as well as an increased sensitivity to changes in gonadal hormones may contribute to menstrually related symptoms in vulnerable women. Disrupted homeostasis and deficient adaptation may be core underlying mechanisms. Future directions for clinically-relevant progress include identification of specific subgroups of menstrually-related syndromes, assessment of the genetic vulnerability and changes in vulnerability along the life cycle, the diversified mechanisms by which vulnerability is translated into pathophysiology and symptoms, the normalization process as well as syndromes-based and etiology-based clinical trials.


Pest demography critically determines the viability of synthetic gene drives for population control.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.


Hemostasis assessment in Fontan patients using the new thrombodynamics test.
Thromboembolic events are a well-known risk for Fontan patients and often lead to morbidity and mortality in cyanotic patients and patients with a single ventricle. Coagulopathy and thrombophilia, in addition to disturbed Fontan blood flow and endothelial injury, are major contributors to thromboembolic complications. However, there is currently no consensus regarding the optimal medication to prevent or treat these events. Identification of coagulation disorders is therefore crucial for selecting appropriate management strategies and evaluating long-term outcomes in these patients. We present the case of a 35-year-old male who underwent the Fontan procedure with a total cavopulmonary modification during childhood due to tricuspid atresia. He was admitted with complaints of headaches and visual disturbances, but no clear cardiovascular cause was identified. Standard coagulation test parameters were normal, but the thrombodynamics test indicated severe hypercoagulation and spontaneous clot formation. Anticoagulation therapy was initiated, and a subsequent thrombodynamics assay showed normalization of the coagulation parameters. The patient remained asymptomatic during the six-month follow-up period. The thrombodynamics test is a valuable tool for the diagnosis of coagulation disorders, as it can assess coagulation parameters and clot growth in vitro. This method can also aid in the optimization of antithrombotic therapy. The presented clinical case highlights the potential use of the thrombodynamics test in Fontan patients to diagnose coagulation disorders and improve long-term outcomes.


Safety and efficacy of inulin and oligofructose supplementation in infant formula: results from a randomized clinical trial.
The sterile newborn digestive tract is rapidly colonized after birth and feeding type could influence this process. Infant formulas try to mimic the bifidogenic effect of human milk using prebiotic supplementation. The aim of this study was to demonstrate the efficacy, safety and tolerance of a 0.8 g/dL Orafti(®)Synergy1 (oligofructose-enriched inulin) supplemented infant formula during the first 4 months of life. In a double-blind, randomized, placebo-controlled and parallel trial, formula fed healthy term newborns were randomized to receive a control (controls) or SYN1 supplemented infant formula (SYN1). Breastfed newborns (BF) were also followed for comparison. Anthropometry, water balance, blood parameters, adverse events, stool frequency and characteristics and faecal microbiota were assessed. A total of 252 formula fed infants were randomized at birth (n = 124 controls, n = 128 SYN1) and 131 BF infants were recruited; after 4 months 68 controls, 63 SYN1 and 57 BF completed the study. SYN1 infants showed a microbiota composition closer to that of BF infants, with a trend towards higher Bifidobacterium cell counts, softer stools and a higher deposition frequency compared to controls. There were no differences between formulas in anthropometry and relevant adverse events, water balance or blood parameters. A 0.8 g/dL SYN1-supplemented infant formula during the first 4 months of life is safe and effective, promoting a gut microbiota closer to that of breastfeeding. This clinical trial was registered at Clinicaltrials.gov as Study on Fermentable Carbohydrates in Healthy Infants (number NCT00808756).


Positron tomography in cerebral ischemia. A review.
This paper reviews the advances provided by positron emission tomography in the understanding of the pathophysiology of cerebral ischemic disorders in humans. The main focuses are on the evaluation of tissue integrity in recent stroke, distant metabolic effects of circumscribed vascular lesions, and hemodynamic consequences of internal carotid artery occlusion.


Characterizing Gender-Affirming Voice Intervention Discussion on Social Media: A Cross-Platform Analysis.
Gender-affirming voice treatments, such as voice training and surgery, are highly impactful for transgender patients experiencing vocal dysphoria and may be discussed on social media platforms including Twitter and Reddit. Our goal was to characterize the content and sentiment of social media posts pertaining to gender-affirming voice interventions to better understand the needs of this patient population. Retrospective data-mining study. A total of 18,695 Tweets from 2001 to 2021 and 23,742 r/Transvoice Reddit submissions and comments from 2009 to 2020 were extracted via publicly available application programming interfaces and analyzed using language processing and sentiment analysis techniques. One thousand eighty-six highly emotive r/Transvoice posts related to voice modification treatments were manually reviewed for further classification. Online discussion of gender-affirming voice has increased over time and is centered on vocal feminization. Recurrent themes included use of online training resources, singing voice, and barriers to care such as cost and variable experiences with health care providers. Sentiment analysis demonstrated that posts discussing gender-affirming voice training had higher average sentiment scores than those discussing voice surgery, on both Twitter (0.252 vs 0.161; P < 0.001) and Reddit (0.349 vs 0.301; P < 0.001). Frequently appearing themes in highly negative surgery posts included mixed outcomes (9.3%), surgical complications (9.3%), and recovery time (8.5%). Common themes shared by the positive subgroup analysis included peer support, vocal quality, and importance of practice. Gender-diverse patients share various concerns and resources relating to voice intervention in the online communities of Twitter and Reddit. The discussion has been growing over the past decade and is mostly positive, with significant social support and resource-sharing within the community. Aggregated online sentiment toward gender-affirming voice surgery is more negative than voice training, largely due to concerns about surgical outcomes and variability, risks, and recovery period.


Antimicrobial activity of alexidine alone and associated with N-acetylcysteine against Enterococcus faecalis biofilm.
The purpose of this study was to assess the efficacy of alexidine (ALX), alone and combined with N-acetylcysteine (NAC), in eradicating two Enterococcus faecalis strain biofilms. The biofilms of E. faecalis ATCC 29212 and the clinical isolate E. faecalis D1 were grown in the MBEC-high-throughput device for 24 h and were exposed to five twofold dilutions of ALX (2%-0.007 8%) alone and combined with 100 mg⋅mL(-1) NAC, for 1 and 5 min. Eradication was defined as 100% kill of biofilm bacteria. The Student's t-test was used to compare the efficacy of the associations of the two irrigants. After 1-min contact time, ALX eradicated the biofilms at all concentrations except for 0.007 8% and 0.015 6%-0.007 8% with E. faecalis ATCC 29212 and E. faecalis D1, respectively. Similar results for eradication and concentration were obtained when it was combined with 100 mg⋅mL(-1) NAC. After 5 min of contact time, ALX alone and combined with NAC eradicated all enterococci biofilms. ALX showed antimicrobial properties against the two E. faecalis strain biofilms tested at very low concentrations, and its combined use with NAC was not seen to enhance its activity.