An improved phylogeny of the Andean tit-tyrants (Aves, Tyrannidae): more characters trump sophisticated analyses.
The phylogeny of the flycatcher genus Anairetes was previously inferred using short fragments of mitochondrial DNA and parsimony and distance-based methods. The resulting topology spurred taxonomic revision and influenced understanding of Andean biogeography. More than a decade later, we revisit the phylogeny of Anairetes tit-tyrants using more mtDNA characters, seven unlinked loci (three mitochondrial genes, six nuclear loci), more closely related outgroup taxa, partitioned Bayesian analyses, and two coalescent species-tree approaches (Bayesian estimation of species trees, BEST; Bayesian evolutionary analysis by sampling trees, (*)BEAST). Of these improvements in data and analyses, the fourfold increase in mtDNA characters was both necessary and sufficient to incur a major shift in the topology and near-complete resolution. The species-tree analyses, while theoretically preferable to concatenation or single gene approaches, yielded topologies that were compatible with mtDNA but with weaker statistical resolution at nodes. The previous results that had led to taxonomic and biogeographic reappraisal were refuted, and the current results support the resurrection of the genus Uromyias as the sister clade to Anairetes. The sister relationship between these two genera corresponds to an ecological dichotomy between a depauperate humid cloud forest clade and a diverse dry-tolerant clade that has diversified along the latitudinal axis of the Andes. The species-tree results and the concatenation results each reaffirm the primacy of mtDNA to provide phylogenetic signal for avian phylogenies at the species and subspecies level. This is due in part to the abundance of informative characters in mtDNA, and in part to its lower effective population size that causes it to more faithfully track the species tree.


Ex vivo biomechanical comparison of V-LOC 180® absorbable wound closure device and standard polyglyconate suture for diaphragmatic herniorrhaphy in a canine model.
To compare 2-0 polyglyconate barbed suture (V-LOC™ 180 Absorbable Wound Closure Device, Covidien, Mansfield, MA) to standard 2-0 monofilament absorbable polyglyconate suture (Maxon™, Covidien) for maximum load to failure and failure mode when used to appose standardized defects in canine diaphragm muscle. Randomized, cadaveric ex vivo mechanical testing. Canine cadaveric hemi-diaphragmatic specimens (n = 32 pairs). Thirty-two cadaveric diaphragm specimens were collected and divided to obtain 64 muscle specimens (9 cm × 4 cm). Paired specimens were bisected in the midpoint of their 9 cm length in the direction of the muscle fibers and apposed using either 2-0 polyglyconate or 2-0 barbed polyglyconate (V-LOC™ 180 Absorbable Wound Closure Device) in a simple continuous pattern. Increasing tension was applied perpendicular to the suture line until specimen failure. Failure mode and maximum load to failure were recorded for each specimen. Mean ± SD failure load of simulated herniorrhaphies performed with barbed polyglyconate suture (54.5 ± 10.27 N) was not significantly different than repair with polyglyconate (56.9 ± 10.87 N). Failure mode for both construct types was suture tear out rather than suture failure. Clinical application of 2-0 barbed polyglyconate suture can be considered as an alternative to the use of 2-0 polyglyconate for diaphragmatic herniorrhaphy.


A highly potent and cellularly active beta-peptidic inhibitor of the p53/hDM2 interaction.
New and improved: The incorporation of a 6-chlorotryptophan (6-Cl-Trp) into a beta-peptide (M)-3(14) helix leads to a high-affinity hDM2 inhibitor, as demonstrated by fluorescence fluctuation analysis at single molecule resolution. When conjugated to penetratin, the newly derived hDM2 binder specifically inhibits tumour cell growth in vitro.


A generalization of the clonal survival models: equations for the families of curves obtained with fractionated irradiation.
The survival curves obtained when cellular recovery follows various first radiation dose deliveries DI seem, when semi-logarithmically plotted, to be translated from the part of the curve corresponding to an unfractionated irradiation beyond a dose DR. A possible assumption consistent with such experimental observations is proposed which allows the generalization of any survival model S = f (D). The derived equation S = f (DR + D - DI) f (DI)/f (DR) is convenient for the whole family of experimental survival curves involving cellular damage repairs when the first radiation doses vary. All the parameters of the family equation can be simultaneously fitted so that their reliability is increased. The generalized equations are given for the four following models: two-hits targets, Chadwick and Leenhouts, Green and Burki, Wideröe. As an example, the Chadwick and Leenhouts generalized model parameters are fitted to a family of experimental survival curves concerning Chlorella cells exposed to fractionated and continuous gamma irradiation. The fittings are presented with their confidence limits and are briefly discussed.


Scanning electron microscopy of the nephrotic kidney.
Scanning electron microscopy (SEMy), supplemented with light microscopy and transmission electron microscopy, was used to study aminonucleoside nephrosis in rats. The visceral epithelium undergoes dramatic restructing in response to aminonucleoside nephrosis. Due in part to an accumulation of intracellular vacuoles, kidney podocytes swell in size. Podocyte major processes lose their many pedicles and slit pores and form close junctions (80 A) with adjacent podocytes. Although no prominant pores opening into the urinary space are found in the visceral epithelium, there is evidence that podocyte vacuoles may rupture and thereby release protein into the urinary space. Many parietal cells also increase in size, accumulate intracellular vacuoles and come into very cose proximity to the visceral epithelium. Casts of PAS-positive, electron-dense material fill the lumina of many uriniferous tubules. Although most proximal tubules exhibit an extensive loss of brush border, no significant changes in other kidney microprojections or cilia were noted. Transmission electron and light microscopy of nephrotic kidneys reveal considerable changes in proximal and distal tubules including a reduction in mitochondria, in cell height, in electron density of the cytoplasmic matrix, in lateral and basal plasmalemma infolds, enlarged euchromatic nuclei, dilated lumens, and accumulation of PAS-positive cytoplasmic granules. SEMy of kidney needle biopsies from patients with proteinuria reveal that SEMy is useful for evaluating glomerular changes in man.


H-Y antigen expression in a case of XX true hermaphroditism.
Cells from an XX true hermaphrodite expressed a reduced amount of H-Y antigen when compared with normal XY cells and with cells from his father, who had an XY/XX chromosomal constitution. His mother had a normal karyotype and was H-Y negative. The four brothers of the patient were clinically and karyotypically normal. An X-Y interchange followed by random inactivation of the X chromosome is proposed to explain the H-Y antigen titer found in the patient.


High potency of a new bombesin antagonist (RC-3095) in inhibiting serum gastrin levels; comparison of different routes of administration.
This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist D-Tpi6,Leu13 psi (CH2NH)Leu14-bombesin (6-14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing-peptide (GRP(14-27))-stimulated gastrin release in rats. First, we showed that GRP(14-27) itself was highly active when administered by different routes. GRP(14-27), given to rats at a dose of 25 micrograms/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 micrograms/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 micrograms GRP(14-27). RC-3095 administered 2 min prior to GRP(14-27) decreased the gastrin response to GRP(14-27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14-27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14-27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the bioavailability of RC-3095 given by the pulmonary inhalation route was about 69% of the s.c. route.(ABSTRACT TRUNCATED AT 250 WORDS)


Phosphatidylserine synthase from yeast.
Whereas mammalian cells produce PS by a base exchange reaction from preexisting phospholipids, yeast cells synthesize PS from CDP-diacylglycerol and serine by the PS synthase reaction. Yeast PS synthase was purified to homogeneity and shown to have a molecular mass of 23 kDa. The activity is dependent on either Mg2+ or Mn2+ and Triton X-100. The enzyme specifically transfers the phosphatidyl group from CDP-diacylglycerol or dCDP-diacylglycerol to L-serine, but not to threonine, cysteine and ethanolamine. The PSS/CHO1 gene encoding the enzyme was cloned by the complementation of the choline auxotrophic pss/cho1 mutant. The deduced protein comprises 279 amino acids with a calculated molecular mass of 30,804. The primary translate undergoes proteolytic processing to the enzymatically more active 23-kDa enzyme. The deduced amino acid sequence contains several putative membrane-spanning regions and resembles that of the Bacillus subtilis enzyme, but not those of the E. coli and Haemophilus influenzae enzymes. The sequence also contains the local, conserved region found in enzymes catalyzing the transfer of the phosphoalcohol moiety from CDP-alcohol, such as PI synthase, cholinephosphotransferase and phosphatidylglycerolphosphate synthase. The activity of PS synthase is maximal in the exponential phase, but decreases when cells enter the stationary phase. The enzyme is phosphorylated at a single serine residue by cyclic AMP-dependent protein kinase with a 60-70% decrease in enzymatic activity, but the primary translation product is not phosphorylated. PS synthase is inhibited by CTP, probably due to the chelation of the divalent cations, Mg2+ and Mn2+, and also by sphingoid bases, such as sphinganine and phytosphingosine. Phosphatidate, phosphatidylcholine and phosphatidylinositol are stimulatory, whereas cardiolipin and diacylglycerol are inhibitory. The expression of yeast PS synthase is transcriptionally repressed by myo-inositol and choline in a coordinate manner with other phospholipid-synthesizing enzymes. The upstream regulatory region of the PSS/CHO1 gene responsible for the myo-inositol-choline regulation was identified. An octameric sequence, CATRTGAA (R = A or G), plays an important role in the conferral of the myo-inositol-choline transcriptional regulation.


Clearance of indomethacin occurs predominantly by renal glucuronidation.
In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indomethacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to glucuronidation in the human kidney. These glucuronides may be converted to isomeric glucuronides and/or the parent compound indomethacin during the residence time in the bladder.


Long-term results of intrapericardial chemotherapeutic treatment of malignant pericardial effusions with thiotepa.
Pericardial involvement is a common feature in different neoplastic diseases, having a strong influence on the natural history of the disease and on the quality of life of the patients. This study was performed in order to investigate the long-term effects of intracavitary treatment with thiotepa in the reduction of pericardial effusion (PE) recurrences. Prospective controlled intervention study. European Institute of Oncology, Milan, Italy. We studied 33 patients, 15 men and 18 women, with malignant PE, who were affected by breast cancer (11 patients), lung cancer (16 patients), microcytoma (4 patients), endometrial cancer (1 patients), and melanoma (1 patient). All patients with large PE, with or without cardiac tamponade, underwent percutaneous pericardiocentesis (PC) under echocardiographic monitoring. Patients with neoplastic cells in drained fluid were considered to be eligible for treatment. After drainage, the catheter was maintained in the pericardial sac for the instillation of a sclerosing, alkylating antiblastic agent (thiotepa) on days 1, 3, and 5 after the PC (15 mg at each step). No procedure-related complications or side effects were observed. Two patients died because of disease progression, without PE evidence. No PE occurred in the remaining patients during the first month. Three recurrences occurred (9.1%), requiring additional PC and intrapericardial treatment. The median survival time was 115 days (range, 22 to 1,108 days) in the overall population, and 272 days in patients with breast cancer. Intrapericardial treatment with thiotepa carries a minimal risk and is a repeatable procedure that can dramatically increase quality of life, or even can improve survival and the natural history of disease in cancer patients.


How We Escalate Vasopressor and Corticosteroid Therapy in Patients With Septic Shock.
Septic shock is defined by the need for vasopressor agents to correct hypotension and lactic acidosis resulting from infection, with 30%-40% case fatality rates. The care of patients with worsening septic shock involves multiple treatment decisions involving vasopressor choices and adjunctive treatments. In this edition of "How I Do It", we provide a case-based discussion of common clinical decisions regarding choice of first-line vasopressor, BP targets, route of vasopressor delivery, use of secondary vasopressors, and adjunctive medications. We also consider diagnostic approaches, treatment, and monitoring strategies for the patient with worsening shock, as well as approaches to difficult weaning of vasopressors.


Duration of sexual intercourse related to satisfaction: survey of Japanese married couples.
Inappropriate intromission time causes sexual problems for couples, and therefore it is important for the couple to set treatment targets. We investigated appropriate intromission times by conducting a questionnaire survey of the interval from initiation of insertion to just before ejaculation in Japanese married couples. A questionnaire survey of 300 married couples was conducted by mail. The estimated mean intromission times were 14.5 min (median: 10 min) for male subjects and 13.6 min (median: 10 min) for female subjects. The mean desired intromission time for female subjects was 15.7 min (median: 15 min). Regarding the difference between the actual and desired intromission times, the desired time was longer, the same, and shorter for 43.0%, 38.7%, and 18.3% of all the female subjects. It seems that female subjects may consider a wide variety of intravaginal insertion times to be desirable. Accordingly, married couples need to improve communication regarding the desired duration of intromission and other related issues.


Influence of ovarian cysts on the results of in vitro fertilization.
To determine if ovarian cysts are associated with a particular basal endocrine profile and impair follicular growth. Retrospective study. In Vitro Fertilization (IVF) Center. Nine hundred fourteen stimulation cycles stimulated with a combination of luteinizing hormone-releasing hormone analogues (LH-RH-a) and human menopausal gonadotropins (hMG) in a long protocol in an IVF program. After 15 days of LH-RH-a therapy, ovarian cysts (> or = 20 mm) were observed in 8% of cases. These cysts were not related to a particular basal endocrine profile and did not impair follicular growth and IVF results. However, puncturing these cysts enhanced the quality of subsequent follicular growth. On the contrary, cysts appearing during hMG treatment (> or = 25 mm) were related with a lower LH:follicle-stimulating hormone ratio (0.79 +/- 0.52 versus 0.92 +/- 0.74 in absence of cyst) and to a lower ovarian response as assessed by the maximal estradiol level to the total number of hMG ampules ratio (51.6 +/- 36.5 versus 65.9 +/- 47.9 in absence of cyst). However, this difference had no influence on the pregnancy per stimulation rate (18% versus 16% in absence of cyst; not significant). Results show that the pathogens of ovarian cysts appearing during the blockage phase and during the stimulation phase are different. However, they do not impair the results of IVF, and thus it is not necessary to cancel the attempt in case of ovarian cyst.


Approaches to modelling the human immune response in transition of candidates from research to development.
This review considers the steps required to evaluate a candidate biodefense vaccine or therapy as it emerges from the research phase, in order to transition it to development. The options for preclinical modelling of efficacy are considered in the context of the FDA's Animal Rule.


A worldwide map of swine short tandem repeats and their associations with evolutionary and environmental adaptations.
Short tandem repeats (STRs) are genetic markers with a greater mutation rate than single nucleotide polymorphisms (SNPs) and are widely used in genetic studies and forensics. However, most studies in pigs have focused only on SNPs or on a limited number of STRs. This study screened 394 deep-sequenced genomes from 22 domesticated pig breeds/populations worldwide, wild boars from both Europe and Asia, and numerous outgroup Suidaes, and identified a set of 878,967 polymorphic STRs (pSTRs), which represents the largest repository of pSTRs in pigs to date. We found multiple lines of evidence that pSTRs in coding regions were affected by purifying selection. The enrichment of trinucleotide pSTRs in coding sequences (CDS), 5'UTR and H3K4me3 regions suggests that trinucleotide STRs serve as important components in the exons and promoters of the corresponding genes. We demonstrated that, compared to SNPs, pSTRs provide comparable or even greater accuracy in determining the breed identity of individuals. We identified pSTRs that showed significant population differentiation between domestic pigs and wild boars in Asia and Europe. We also observed that some pSTRs were significantly associated with environmental variables, such as average annual temperature or altitude of the originating sites of Chinese indigenous breeds, among which we identified loss-of-function and/or expanded STRs overlapping with genes such as AHR, LAS1L and PDK1. Finally, our results revealed that several pSTRs show stronger signals in domestic pig-wild boar differentiation or association with the analysed environmental variables than the flanking SNPs within a 100-kb window. This study provides a genome-wide high-density map of pSTRs in diverse pig populations based on genome sequencing data, enabling a more comprehensive characterization of their roles in evolutionary and environmental adaptation.


Color Doppler hysterosalpingography in the diagnosis of tubal patency.
To assess tubal patency by color Doppler hysterosalpingography (HSG). Comparative study of color Doppler HSG with roentgenogram HSG and chromolaparoscopy in infertile women of childbearing age. Clinical environment. Sixty female patients (22 to 39 years) with long-lasting infertility problems. Sterile saline was transcervically injected into the uterine cavity through a catheter and color Doppler HSG was performed. All the patients were submitted to roentgenogram HSG and chromolaparoscopy. The diagnostic efficacy of color Doppler HSG and its concordance with "gold standard" chromolaparoscopy were analyzed. Correlation between color Doppler HSG and roentgenogram HSG with chromolaparoscopy occurred in 86% versus 93% of all women studied. Color Doppler HSG with its accuracy and safety results a promising alternative technique to roentgenogram HSG in diagnosing tubal status in infertile patients.


Cystoid macular edema following secondary lens implantation.
We reviewed 224 cases that had undergone secondary lens implantation. Cystoid macular edema occurred in 16 (7.1%) cases; edema was transient in 14 (6.3%) cases and permanent in two (0.8%) cases. Three factors seem to affect the incidence of CME: time lapse between cataract extraction and lens implantation; a positive preoperative fluorescein angiogram; and vitreous loss during lens implantation--if implantation is performed within a year of cataract extraction. Two eyes with pre-existing CME and a functional vision of 20/100 or better deteriorated to 20/200 or less after secondary lens implantation due to permanent macula edema. However, the incidence of postoperative CME can be as low as 1.3% if the macula is clear on the preoperative fluorescein angiogram and if surgery is performed no sooner than one year after cataract extraction.


Periodic charge distributions in the myosin rod amino acid sequence match cross-bridge spacings in muscle.
The amino acid sequence of the rod portion of nematode myosin, deduced for the sequence of the unc-54 heavy chain gene of Caenorhabditis elegans, is highly repetitive and has the characteristics of an alpha-helical coiled coil. The molecular surface contains alternate clusters of positive and negative charge. Interactions between charge clusters on adjacent molecules could account for the observed spacing of the myosin cross-bridges in muscle. Calculations also suggest that the N-terminal third of the rod is only loosely associated with the thick filament backbone. Bending of the rod near the end of this region could allow the N-terminal section to act as a hinged arm during muscle contraction.


Wheat germ agglutinin-ricin A-chain conjugate is neuronotoxic after vagal injection.
'Suicide transport' is a term coined to describe the use of retrogradely axonally transported toxin to produce anatomically selective neural lesions. As a first step in developing neuron type-selective, systemically non-toxic suicide transport agents, a prototype hybrid toxin consisting of ricin A-chain (RTA) disulfide coupled to wheat germ agglutinin (WGA) was synthesized by first derivatizing WGA by reaction with N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP) in the presence of N-acetylglucosamine and then formation of WGA-SS-RTA by mixing the derivatized WGA with reduced RTA. The ability of this conjugate to inhibit protein synthesis was tested on two cell lines in vitro; the ID50 was 0.2 nM using the K562 hematopoietic stem cell line and 0.02 nM for the 2a neuroblastoma cell line. Suicide transport activity was assessed by microinjection of hybrid into the cervical vagus nerve of rats. Intact WGA-SS-RTA, but not hybrid that was pretreated with dithiothreitol to uncouple RTA from the WGA carrier, reliably killed vagal motor neurons. Both intact and reduced hybrid killed vagal sensory neurons. Indirect peroxidase immunohistochemistry demonstrated transport of RTA to vagal sensory neurons and WGA to both vagal sensory and motor neurons. These results are the first evidence that a hybrid toxin can be active as a suicide transport agent.


Gene for A-type inclusion body protein is useful for a polymerase chain reaction assay to differentiate orthopoxviruses.
Orthopoxvirus species were identified and differentiated by polymerase chain reaction amplification of genome DNA using a single primer-pair based on sequences coding for the major protein component of the cowpox virus acidophilic-type inclusion body (ATI). DNA available for 6 of 8 Old World (cowpox, variola, monkeypox, camelpox, ectromelia and vaccinia viruses) and 3 New World (skunkpox, volepox, and raccoonpox) resulted in amplicons that ranged in size from 510 to 1673 base pairs depending on the species, except for raccoonpox virus DNA which did not amplify. XbaI digest gel electrophoresis profiles of the amplicons improved resolution of the differences.


[Mobbing at work in Italy: a need for legislation on a growing problem].
Mobbing at work is defined as the presence of violent behaviors, including physical and emotional abuse, by co-workers, subordinates or superiors to force someone out of the workplace through rumor, innuendo, intimidation, humiliation, discrediting, and isolation. According to recent Italian data, it has been estimated that about 1 million and 404 thousand women have been victims of mobbing or sexual abuse. Unfortunately, to date, a specific legislation for mobbing is lacking, and judge's sentences are based only on personal interpretations/applications on current Italian laws on violence and work-stress, as well as on the growing Supreme Court sentences regarding this hot issue. This perspective paper aims to better define the mobbing phenomenon, highlighting the main concerns and offering potential solutions.


A microwave-induced plasma jet for efficient degradation of methomyl in aqueous solution.
As a typical carbamate pesticide, methomyl was once widely used in agriculture for its excellent broad-spectrum insecticidal effect. However, due to its high toxicity, long half-life, and difficult degradation properties, it poses a serious challenge to water environment pollution. In this study, an electrode-free discharge microwave-induced plasma technology was used to rapidly and efficiently degrade methomyl in aqueous solution. In this experiment, the statistical design of experiments (DOE) was adopted to optimize the plasma degradation parameters. Under the optimized parameters (P = 140 W, D = 0 mm, R = 0.5 L/min), 78.4% removal of 50 mg/L of methomyl was achieved after 8 min. The optical emission spectrometry and free radical detection experiments showed that the active substances generated by the collision reaction between plasma and water molecules occurring at the gas-liquid interface were the key factors to exert the degradation effect. The degradation rate of methomyl decreased by 73.2% after the addition of tert-butanol (OH burster), while it decreased by only about 12.0% after the addition of peroxidase. These implied that ∙OH was largely responsible for methomyl degradation. In addition, based on the detected intermediates, possible degradation mechanisms and pathways were analyzed.


Predictors of recurrence of cancer-associated venous thromboembolism after discontinuation of anticoagulant therapy: a multicenter cohort study.
Data on recurrence after the end of anticoagulation for a first event of cancer-associated venous thromboembolism (VTE) are scarce. Our aim was to assess predictors of VTE recurrence during a 1-year follow-up period. This study is an analysis of RIETE, an international, multicenter, prospective cohort study of patients diagnosed with VTE. Patients had to have active cancer at the time of VTE and to have withdrawn from anticoagulation after 3 months of full treatment. Analyses were performed using Fine and Gray models, with death as a competing risk, and multiple imputation of missing data was performed by chained equations. Among 14 318 patients with cancer-associated VTE, 3414 had undergone time-limited anticoagulation for at least 3 months. The cumulative incidence function for recurrent VTE was 10.2% (95% CI, 9.1-11.5) at 1 year. Chronic kidney disease (a subhazard ratio [sHR] of 1.08 for 10-mL/min decrease in glomerular filtration rate; 95% CI, 1.02-1.14); cancer of the lung, brain, stomach, esophagus, liver, or ovary (sHR, 3.56; 95% CI, 1.07-11.80; compared with cancer of the oropharynx, larynx, or melanoma); cancer of the pancreas, the biliary tract, or of unknown origin (sHR, 6.86; 95% CI, 1.89-24.85); inferior vena cava filter (sHR, 3.16; 95% CI, 1.75-5.71); postthrombotic syndrome (sHR, 2.09; 95% CI, 1.06-4.15); and residual pulmonary thrombotic obstruction (sHR, 2.58; 95% CI, 1.38-4.82) were predictive of recurrence. Surgery during the 2 months before VTE was predictive of absence of recurrence (sHR, 0.60; 95% CI, 0.40-0.92). One year after anticoagulant cessation for cancer-associated VTE, approximately 10% of patients experienced recurrence. Discontinuing anticoagulant therapy seems safe, mainly in surgery-associated VTE.


Short-Course Versus Prolonged-Course Antimicrobial Therapy in Adults With Catheter-Related Septic Thrombosis: A Propensity-Weighted Retrospective Study.
Optimal duration of antimicrobial therapy (AT) for catheter-related septic deep venous thrombosis (DVT) is unknown. We aimed to compare the outcomes of patients receiving short-course AT (≤21 days) versus prolonged-course AT (>21 days). This was a monocentric retrospective study comparing adults with catheter-related septic DVT from 2015 to 2020 treated with short- or prolonged-course AT. A propensity score-weighted analysis was used to mitigate potential bias. The primary outcome was a composite of all-cause mortality or recurrent bloodstream infection 30 days after AT discontinuation. Of 172 patients with catheter-related septic DVT, 104 were treated with prolonged-course AT and 68 with short-course AT. In the propensity score analysis, we found no significant difference in 30-day all-cause mortality or relapse between the 2 groups (inverse probability of treatment weighted hazard ratio [wHR], 2.16 [95% confidence interval {CI}, .68-6.88]; P = .192). No differences in 90-day all-cause mortality and 90-day relapse were observed between the treatment groups (wHR, 1.01 [95% CI, .49-2.05], P = .987 and 1.13 [95% CI, .08-15.62], P = .928, respectively). A 21-day AT could be an effective and safe option to treat catheter-related septic DVT. Further randomized studies are needed to establish the optimal duration of AT for patients with catheter-related septic DVT.


LMO3 reprograms visceral adipocyte metabolism during obesity.
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. KEY MESSAGES: LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.


Elemental formula associated hypophosphataemic rickets.
Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.


Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.
Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting. From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR). Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median OS was 4.5 months (95%CI: 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%). Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer. AHEAD-G202 (NCT02668380).


Fertility preservation for boys with cancer.
Childhood cancer is a curable disease due to the development of chemo- and radiation therapies, but long-term survivors suffer late side-effects including infertility. Cytotoxic agents and radiation impair spermatogenesis and cause oligospermia or azoospermia as well as genetic damage in sperm. To date, the only established option to preserve fertility is cryopreservation of sperm before treatment and artificial reproduction techniques, if men with cancer can ejaculate, but only a quarter of men have banked sperm. Lack of information is the most common reason for failing to bank sperm. However, prepubertal patients who have only spermatogonia and spermatocytes in their testes do not benefit from cryopreservation of their sperm and assisted reproductive techniques. Thus, the only available option is to harvest testicular tissues before treatment for cryopreservation, from which immature germ cells can somehow be maturated. Autotransplantation of germ cells into the testis holds promise for fertility restoration, but contamination by malignant cells may induce relapse. Fluorescence-activated cell sorting (FACS) with two surface markers could exclude contaminated leukemic cells from murine germ cells, and transplantation of sorted germ cells successfully restored fertility without transmission of leukemia. Human germ cells could be also isolated from human leukemia and lymphoma cell lines by FACS using surface markers. Before autotransplantation can be applied clinically, some issues, including the risk of contamination by malignant cells and in vitro propagation of spermatogonial stem cells, should be resolved.


A Different and Novel Alternative (ADANA) Renal Access Technique when CT or USG Guidance Is Inadequate in Case of Retro-Renal Colon.
Computed tomography (CT) or ultrasonography (USG)-guided renal access for percutaneous nephrolithotomy (PNL) is not suitable in all cases with retro-renal colon (RRC) due to anatomical and technical restrictions. We would like to describe our novel technique that permits standard subcostal renal access with a small incision for these patients. This method was performed on adult patients with severe RRC and complex renal stones who were not suitable for renal access with CT or USG guidance. Time from skin incision to puncture needle insertion, incision length, stone-free rate (SFR), and complications were evaluated. The appropriate renal calyx for renal access was identified with retrograde pyelography. The skin closest to the identified calyx was incised and retroperitoneum visualized. The RRC was swept laterally by blunt dissection to obtain a safe puncture line. The retractors were placed to keep the colon away from the incision. Then, the puncture needle was placed over Gerota's fascia. After this, the puncture needle was inserted into the targeted calyx under fluoroscopic guidance. The insertion of guidewire and the rest of the procedure such as dilatation and insertion of Amplatz sheath were performed under same maneuver. A total of 1,348 patients were treated with PNL between January 2016 and November 2019. Our group consisted of 16 adult patients with a median age of 44.8 years (7 females and 9 males) who underwent PNL with our new access technique. SFR and clinically insignificant residual fragment (CIRF) rate were 72.5 and 14.2%, respectively. The median access time was 22.2 min (range: 15-30 min). The median skin incision length was 3.7 (range: 3.0-4.5) cm. The average skin incision length was 3.7 cm. The SFR and CIRF rate were 72.5 and 14.2%, respectively. We did not observe any complication related to our access technique. Our novel access technique created a safe anatomical route for standard subcostal renal access with acceptable incision length and very low complication rate.


Prediction model of laparoendoscopic single-site surgery in gynecology using machine learning algorithm.
Minimally invasive surgery has been widely used in gynecology. The laparoendoscopic single-site surgery (LESS) risk prediction model can provide evidence-based references for preoperative surgical procedure selection. To determine whether the patients are suitable for LESS and to provide guidance for the clinical operation plan, we aimed to compare the clinical outcomes of LESS and conventional laparoscopic surgery (CLS) in gynecology. We constructed a LESS risk prediction model and predicted surgical conditions for the preoperative evaluation system. A retrospective analysis was carried out among patients undergoing LESS (n = 1019) and CLS (n = 1055). Various clinical indicators were compared. Multiple machine model algorithms were evaluated. The optimal results were chosen as the model to form the risk prediction model. The LESS group showed advantages in the postoperative 12/24 h visual analog scale and Vancouver scar score compared with the CLS group (p < 0.05). The comparisons in other clinical indicators between the two groups showed that each group had advantages and the difference was statistically significant (p < 0.05), including operative time, estimated blood loss, and hospital stay. We evaluated the predictive value for various models using AUC values of 0.77, 0.77, 0.76, and 0.67 for XGBoost, random forest, GBDT, and logistic regression, respectively. The decision tree model was shown to be the optimal model. LESS can reduce postoperative pain, shorten hospital stay and make scars acceptable. The risk prediction model based on a machine learning algorithm has manifested a high degree of accuracy and can satisfy the doctors' demand for individualized preoperative evaluation and surgical safety in LESS.


Diversity and complexity of ceramide generation after exposure of jurkat leukemia cells to irradiation.
To define which intracellular pools of sphingomyelin and ceramide are involved in the triggering of apoptosis of Jurkat leukemia cells in response to gamma-ray exposure. We examined the kinetics of ceramide generation at the whole-cell level and in different subcellular compartments (plasma membrane rafts, mitochondria, and endoplasmic reticulum) after irradiation with photons. Ceramide was measured by high-performance liquid chromatography or after pulse labeling experiments, and the presence of sphingomyelinase within mitochondria was assessed by electron microscopy. Irradiation of Jurkat leukemia cells resulted in the sequential triggering of sphingomyelin hydrolysis, followed by de novo synthesis that led to a late ceramide response (from 24 h) correlated with the triggering of apoptosis. At the subcellular level, pulse-label experiments, using [(3)H]-palmitate as a precursor, strengthened the involvement of the radiation-induced sphingomyelin breakdown and revealed a very early peak (15 min) of ceramide in plasma membrane rafts. A second peak in mitochondria was measured 4 h after irradiation, resulting from an increase of the sphingomyelin content relating to the targeting of acid sphingomyelinase toward this organelle. These data confirm that ceramide is a major determinant in the triggering of radiation-induced apoptosis and highlight the complexity of the sequential compartment-specific ceramide-mediated response of Jurkat leukemia cells to gamma-rays.


Assessment of pronuclear formation following in vitro fertilization with bovine spermatozoa obtained after thermal insulation of the testis.
This study was conducted to follow the chronology of pronuclear formation in bovine zygotes after in vitro insemination with a population of spermatozoa having abnormal morphology. Semen samples were obtained and cryopreserved from four Holstein bulls before and after a scrotal insulation period of 48 h (Day 0). A pre-insult (Day 5) and a Day 20 post-insult semen sample were evaluated for morphology and used for IVF after standard swim-up sperm separation protocols. Pronuclear formation was scored on subpopulations of presumptive zygotes after they were fixed and stained at 3-h time intervals from 6 to 18 h post in vitro insemination (hpi). Post-thaw morphological evaluation of semen samples revealed a decrease in the percentages of normal spermatozoa in the post-insult samples compared with the pre-insult samples for Bull I (74-22%) and Bull III (68-1%). The sperm penetration rate decreased (P<0.05) between the pre- and post-insult samples for Bulls I (90-76%) and III (92-70%), but was not different for Bulls II (92-90%) and IV (78-85%). The pronuclear formation rates for post-insult zygotes for Bulls II and IV had comparable increases in development over time, whereas there was no increase in the pronuclear development for the zygotes from the post-insult samples for Bulls I and III, and generally a condensed sperm head was observed in the oolemma. At 18 hpi the fertilization rate between the pre- and post-insult samples for Bulls I (51-4%), II (88-75%) and III (94-2%) decreased (P<0.01), but there was no change for Bull IV (66%). In conclusion, we inferred that the failure in normal pronuclear formation was associated with an absence of normal decondensation of the penetrating spermatozoon; this suggested that the effect of morphologically abnormal spermatozoa occurred prior to cleavage, thus limiting early development.


Effect of aerobic exercise intensity on health-related quality of life in severe obesity: a randomized controlled trial.
Aerobic exercise is an important part of obesity treatment and may improve health-related quality of life (HRQOL). The objective of this study was to compare the effect of two different exercise programs on health-related quality of life in patients with severe obesity. This was a single-center, open-label, randomized, parallel-group study comparing the effects of a 24-week moderate-intensity continuous training (MICT) program and a combined high-intensity interval training program with MICT (HIIT/MICT). The primary objective (specified secondary outcome) was to assess HRQOL by using the general health dimension of the Short Form Health Survey (SF-36). The secondary objectives were to assess other dimensional SF-36 scores, the impact of weight on the physical and psychosocial aspects of quality of life (IWQOL-Lite), and the burden of obesity-specific weight symptoms (WRSM). 73 patients were enrolled and reported patient reported outcome measures, with 71 patients (55% females) allocated to either MICT (n = 34) or HIIT/MICT (n = 37). In the intention-to-treat analysis, general health scores increased between baseline and 24-week follow-up in both the HIIT/MICT group and the MICT group, with a mean change of 13 (95% CI 6-21) points and 11 (95% CI 5-17) points, respectively, with no difference between the groups. The effect sizes of these changes were moderate. The vitality and social functioning scores of SF-36, and the physical function and self-esteem scores of IWQOL-Lite increased moderately in both groups, with no difference between groups. The tiredness, back pain, and physical stamina scores based on WRSM showed moderate to strong changes in both the groups. Patients who had completed a combined HIIT/MICT program did not experience larger improvements in general health compared with those completing a clean 24-week MICT program. Exercise may confer general health benefits independent of intensity. Regional Committees for Medical and Health Research Ethics south east, Norway, October 23, 2013 (identifier: 2013/1849) and ClinicalTrials.gov December 8, 2014 (identifier: NCT02311738).


Antenatal care service utilization in tribal and rural areas in a South Indian district: an evaluation through mixed methods approach.
Maternal and child healthcare is one of the eight basic components of primary healthcare. Poor access and utilization of antenatal care (ANC) services continue to contribute to high maternal mortality and morbidity; and the services of primary healthcare are amenable for evaluation. To report the utilization of ANC services by women living in tribal and rural areas in the district of Visakhapatnam, Andhra Pradesh, India. Both qualitative and quantitative methods were used in the study. Quantitative data on ANC were collected from women having a child aged less than a year (n=380) through a structured interview schedule. The qualitative data were collected through indepth interviews with key informants in the villages (n=12). The study reports higher utilization of ANC compared with the national average of India. A greater proportion of women living in tribal areas utilize the services from governmental sources (92%), whereas approximately 54% of the rural women seek services (paid services) from private practitioners. Health workers' visits match with the utilization of government health services. The study showed relatively higher utilization of ANC services than the national average, but at the same time, child deliveries at home, which were mostly conducted by untrained elderly women, were also high. This gap is indicative of the target-oriented approach where quantity rather than the quality takes priority. In addition, the literacy levels of women, socioeconomic conditions and distance to the health facilities also played a role. To improve utilization and access, community health needs assessment has to be made, along with attempts to develop community participation.


Climatically promoted taxonomic homogenization of macroinvertebrates in unaffected streams varies along the river continuum.
Biotic homogenization appears to be a global consequence of anthropogenic change. However, the underlying environmental factors contributing to homogenization are difficult to identify because their effects usually interact and confound each other. This can be the reason why there is very little evidence on the role of climate warming in homogenization. By analysing macroinvertebrate assemblages in 65 streams that were as close to natural conditions as possible, we avoided the confounding effects of common anthropogenic stressors. This approach resulted in revealing a significant effect of increased temperature (both summer and winter) on changes in macroinvertebrate compositional over the past two decades. However, homogenization was significant only at opposite ends of the river continuum (submontane brooks, low-altitude rivers). Surprisingly, species of native origin predominated overall, increasing in frequency and abundance ("winners"), while only a minority of species declined or disappeared ("losers"). We hypothesise that undisturbed conditions mitigate species declines and thus homogenization, and that the temperature increase has so far been beneficial to most native species. Although we may have only captured a transitional state due to extinction debt, this underscores the importance of maintaining ecological conditions in stream to prevent species loss due to climate change.


Variation of lung density corrections in a typical patient population.
The correction factors to allow for the excess transmission through the lung were worked out for 25 patients who underwent radiation treatment of lesions in thorax. The geometrical arrangements of the beams used for the treatments were reconstructed on the CT scans to identify the amount of lung that intervened. The lung transmission correction factors were worked out for four possible photon energies Cobalt-60, 6 MV, 10 MV, and 20 MV. Isocentric treatment was considered throughout and the isocenter was regarded as the point of dose prescription as is done in normal practice. Correction factors were based on published experimental data for situations that had the isocenter inside the lung. Ratio of TAR (or TMR) method and Batho's power law of TAR (or TMR) method were used if the isocenter was behind the lung. It was observed that the average increase in the total dose after lung corrections were 11.5 +/- 6%, 8.5 +/- 5%, 5.5 +/- 3%, and 4.0 +/- 2% at the energies of Cobalt-60, 6 MV, 10 MV, and 20 MV, respectively. This proves the importance of carrying out the lung transmission corrections to achieve a greater consistency in the doses delivered between groups of patients treated with different photon energies.


Usability of Fag e 2 ImmunoCAP in the diagnosis of buckwheat allergy.
Currently, the detection of crude buckwheat extract-specific IgE by ImmunoCAP (f11) (Phadia AB, Uppsala, Sweden) is widely used to diagnose buckwheat allergy. However, the results of this test do not always correlate with the development of allergic symptoms. This study aimed to evaluate the diagnostic usefulness of specific IgE antibody titers for the major buckwheat allergens Fag e 1 and Fag e 2. Specific IgE antibodies were determined using the ImmunoCAP method for native Fag e 1 and Fag e 2, recombinant Fag e 1 and Fag e 2, and crude buckwheat extract (f11) in 10 buckwheat allergy patients, 14 atopic dermatitis patients, and 15 healthy subjects. All buckwheat allergy patients showed positive results for native Fag e 1- and Fag e 2-specific IgE tests and for ImmunoCAP (f11). In contrast, the rates of atopic dermatitis patients with positive results for native Fag e 1- and Fag e 2-specific IgE tests were 64.2% (9/14) and 57.1% (8/14), respectively. The sensitivities of the test using recombinant proteins were lower than those of the test using native proteins. The area under the curve (AUC) as determined by receiver operating characteristic (ROC) curve analysis was the largest for the native Fag e 2-specific IgE test (0.967), with a sensitivity of 90% and a specificity of 89.6% (cut-off: 2.74 kUa/L). Thus, the native Fag e 2-specific IgE antibody titer obtained using the ImmunoCAP method is more reliable than the buckwheat ImmunoCAP (f11) value for predicting buckwheat allergy.


An enzymatic assay for acetate in spent bacterial culture supernatants.
A method is presented for the rapid enzymatic determination of acetate in spent bacterial culture supernatants. The assay is based on a previously published assay for acetate kinase [Bergmeyer et al. (1974) in Methods of Enzymatic Analysis (Bergmeyer, H. V., ed.), Vol. 1, pp. 425-426, Verlag Chemie-Academic Press, New York/London], and is sufficiently sensitive to detect acetate levels of 50 microM. The assay is cheaper than commercially available assays and is particularly useful for occasional use by laboratories not equipped for routine acetate analysis using gas chromatography. The application of the assay to the measurement of acetate in bacterial cultures is described, though it should also be applicable to other biological fluids and foodstuffs.


Changes in intestinal microbiota and correlation with TLRs in ulcerative colitis in the coastal area of northern China.
To investigate the communities of fecal microbiota and the role of Toll-like receptors in patients with ulcerative colitis in the coastal area of northern China. Stool samples from 31 patients with ulcerative colitis and 12 healthy individuals were collected. The total bacterial genomic DNA was extracted, and the V3+V4 hypervariable region in the bacterial 16S rRNA gene sequence was amplified by polymerase chain reaction (PCR). High-throughput sequencing analysis was performed on the Illumina Hiseq platform. The expression of TLR2, TLR4, Tollip, PPAR-γ, IL-6, and TNF-α in the colonic mucosa was measured by Western blots. The diversity of the fecal microbiota in patients with ulcerative colitis was significantly less than that in healthy control individuals (p < 0.05). The proportion of Bacteroidetes was significantly reduced (p < 0.01), whereas Proteobacteria was prevalent (p < 0.01) in patients with ulcerative colitis. At the genus level, the relative abundance of Streptococcus and Anaerostipes was significantly increased (p < 0.05), whereas the proportion of Bacteroides, Lachnospira, Ruminococcus, Phascolarctobacterium, and Coprococcus was significantly decreased in patients with ulcerative colitis (p < 0.05). The diversity indexes of fecal microbiota in patients with ulcerative colitis were negatively correlated with disease severity (p < 0.05). The relative abundance of Enterobacteriaceae was positively correlated with disease severity, and the relative abundance of Phascolarctobacterium, Anaerostipes, Fusobacterium, Parabacteroides, Oscillospira, and Ochrobactrum were negatively correlated with disease severity. The expression levels of TLR2 and TLR4 in the intestinal mucosa were positively correlated with the relative abundance of Streptococcus and Enterobacteriaceae, respectively (r = 0.481, p = 0.007; r = 0.455, p = 0.017). There were significant changes in the diversity and composition of the fecal microbiota in patients with ulcerative colitis compared to healthy individuals. The dysbiosis of gut microbiota and correlation with TLRs might play important roles in the pathogenesis and progression of ulcerative colitis.


Heart innervation after ligation of the left anterior descending coronary artery (LAD).
Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.


Low-Level Brain Somatic Mutations Are Implicated in Schizophrenia.
Somatic mutations arising from the brain have recently emerged as significant contributors to neurodevelopmental disorders, including childhood intractable epilepsy and cortical malformations. However, whether brain somatic mutations are implicated in schizophrenia (SCZ) is not well established. We performed deep whole exome sequencing (average read depth > 550×) of matched dorsolateral prefrontal cortex and peripheral tissues from 27 patients with SCZ and 31 age-matched control individuals, followed by comprehensive and strict analysis of somatic mutations, including mutagenesis signature, substitution patterns, and involved pathways. In particular, we explored the impact of deleterious mutations in GRIN2B through primary neural culture. We identified an average of 4.9 and 5.6 somatic mutations per exome per brain in patients with SCZ and control individuals, respectively. These mutations presented with average variant allele frequencies of 8.0% in patients with SCZ and 7.6% in control individuals. Although mutational profiles, such as the number and type of mutations, showed no significant difference between patients with SCZ and control individuals, somatic mutations in SCZ brains were significantly enriched for SCZ-related pathways, including dopamine receptor, glutamate receptor, and long-term potentiation pathways. Furthermore, we showed that brain somatic mutations in GRIN2B (encoding glutamate ionotropic NMDA receptor subunit 2B), which were found in two patients with SCZ, disrupted the location of GRIN2B across the surface of dendrites among primary cultured neurons. Taken together, this study shows that brain somatic mutations are associated with the pathogenesis of SCZ.


Observed Progression of Parents' Understanding of Preterm Infants' Behavioral Signs at 33 to 35 Weeks Corrected Age.
Interventions aimed at improving parental understanding of preterm infants' behavioral signs have drawn increased attention in recent years. However, there are limited data regarding parents' actual perceptions of infants' behavior during parent-infant interactions while infants are in a light-sleep state. (1) To describe parental perceptions of infants' behavior at 33 to 35 weeks' corrected age during light-sleep and (2) to identify changes in parental perceptions of preterm infants' behavior over time. This study used a qualitative, longitudinal design based on observations and interviews. Three sets of parents and their infants born between 29 and 30 weeks' gestational age were observed up to 3 times during light sleep states when the infants were 33 to 35 weeks' corrected age. Parents were interviewed regarding their perceptions of infant behavior/growth once at the time of observation and once more within 2 weeks of the final observation. The findings are based on the observation of parents' perception-driven interactions with infants. Four themes emerged describing the transition of parental perception that progresses to gain a better understanding of their infant's behavior through repeated interaction. The findings of this study inform caregivers in neonatal intensive care units regarding the unique experience of parent-infant dyads. This knowledge can help promote family-centered developmental care efforts in neonatal intensive care units. Further research should focus on studying a larger sample group to confirm the findings and refining strategies to incorporate the findings to enhance neonatal intensive care unit care.


Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.
Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease.


Strategies for peak-purity assessment in liquid chromatography.
One of the key requirements for the validation of chromatographic methods is to determine the purity of a chromatographic peak. Statistical modelling of the chromatographic process suggests that overlapping components are highly probable in a chromatogram. Hence extensive efforts have been directed at the development of sensitive, reliable and robust methods to assess peak purity. This is especially the case in the pharmaceutical industry, where liquid chromatography (LC) is widely utilized and the demands on method validation are justifiably high. On-line multiwavelength absorptiometric detection is often used to generate the additional data required to facilitate peak-purity assessment in LC. This approach, using photodiode-array technology, is directly compatible with the aqueous-based reversed-phase LC solvents used extensively in drug analysis. Consequently, this work highlights many of the peak-purity algorithms, which may be applied using LC with diode-array detection. The relative merits of the individual techniques are discussed, and a rationale is developed for their application.


Dual-signaling amplification strategy for glutathione sensing by using single gold nanoelectrodes.
A new nanosensor for glutathione (GSH) detection by use of single nanoelectrodes has been developed through a dual-signaling ratiometric amplification strategy. Ag nanoparticles (Ag NPs) metalized DNA1 was modified on an Au nanoelectrode surface. Due to the strong affinity between Ag NP and GSH, Ag NPs could be removed by the addition of GSH. The remaining metalized DNA1 could hardly form a double strand, while the de-metalized DNA1 could hybrid with DNA2 and DNA3 to form a complex structure to adsorb methylene blue (MB), and then the electrochemical signal of differential pulse voltammetry (DPV) from MB oxidation could be observed. With the addition of GSH, the peak current of MB oxidation at about -0.27 V (IMB) increases, while the signal of Ag oxidation at about 0.1 V (IAg) decreases. It was found that there had a linear relationship between the ratio of dual-signal (IMB/IAg) and the GSH concentrations, which could be used to detect GSH. The ratiometric nanosensor is label-free, easy to operate, and can eliminate inherent system errors. Considering the advantages of nanoelectrodes, such as low IR drop, fast response, and small overall dimension, this developed nanosensor can be used for GSH detection living systems (e.g., cell lysate).


The impact of electric generation capacity by renewable and non-renewable energy in Brazilian economic growth.
Renewable sources are relevant in a country's energy planning because they are linked to the creation of opportunities for technological, economic, and productive development guided by the principles of sustainability. Thus, the aim of this study was to investigate the relation between electric generation capacity by renewable and non-renewable energies and Brazilian socioeconomic variables. The analysis of the interrelationships between electricity generation capacity and economic growth in Brazil, from April 2009 to March 2017, was carried out by the vector autoregressive and autoregressive distributed lag methodologies. It was verified that the variance of employment is explained by renewable sources: hydroelectric in 7.71%, biomass in 1.99%, wind energy in 3.13%, and solar energy in 10.58%. While, the GDP variance is explained in 3.15% by hydroelectric energy, 0.06% by biomass, 1.70% by wind energy, and 17.38% by solar energy. The export variance is explained by renewable sources: hydroelectric 2.48%, biomass 0.39%, wind energy 2.34%, and solar energy 17.58%. Finally, the variance of the minimum wage is explained by hydroelectric energy in 1.48%, biomass in 5.09%, wind energy in 9.09%, and solar energy in 10.67%. An ARDL (1, 1, 2, 0, 0, 0, 3, 2, 0, 2, 0, 2) model was also adjusted for natural gas, with AIC (13.082) and BIC (13.739), and the ARDL (1, 0, 1, 0, 0, 0, 0, 0, 3, 0, 0, 4) model adjusted for hydroelectric power, with AIC (13.633) and BIC (14.189), considering the variables' order cited above. Through the adjustment of the ARDL model, it was verified that there is a long-term influence of socioeconomic variables on electricity production variables, both renewable and non-renewable ones. The analysis of the impulse response function and the variance decomposition allowed us to verify that the installed capacity for production of electric energy exerts influence on Brazilian socioeconomic variables considered in this study.


Emergency medicine updates: Droperidol.
Droperidol is a butyrophenone that has recently been reintroduced after a United States Food and Drug Administration (US FDA) black box warning in 2001. Evidence demonstrates utility in a variety of clinical conditions. This paper provides evidence-based updates concerning the use of droperidol for the emergency clinician. Droperidol received a black box warning by the US FDA in 2001 due to concerns for QT prolongation and torsades de pointes; however, reevaluation of the available data suggests droperidol is a safe and efficacious medication. It can be used in the emergency department (ED) setting for many conditions, including acute agitation, headaches, vertigo, nausea, and vomiting. Extensive literature supports that the QT-prolonging effects are transient and that the risk of torsades de pointes is rare with doses utilized in the ED. An electrocardiogram does not need to be routinely obtained before droperidol use but should be considered in patients at high risk for QT prolongation. Current evidence suggests that droperidol is a safe and effective medication for treating nausea and vomiting, headache, vertigo, and agitation in the ED setting.


Motion detection is dependent on spatial frequency not size.
The maximum displacement for the detection of apparent motion is measured using stimuli made up of micro-patterns randomly distributed across the stimulus field. The micro-patterns were Gabor functions or half-wave rectified Gabor functions. Dmax is shown to be dependent of the spatial frequency content of the stimulus, and to be largely independent of the size of the stimulus elements or the number of them in the stimulus field (within limits). Evidence is shown for Dmax to be considered a measure of motion detection that reveals properties of low level underlying motion mechanisms.


Geometry-informed irreversible perturbations for accelerated convergence of Langevin dynamics.
We introduce a novel geometry-informed irreversible perturbation that accelerates convergence of the Langevin algorithm for Bayesian computation. It is well documented that there exist perturbations to the Langevin dynamics that preserve its invariant measure while accelerating its convergence. Irreversible perturbations and reversible perturbations (such as Riemannian manifold Langevin dynamics (RMLD)) have separately been shown to improve the performance of Langevin samplers. We consider these two perturbations simultaneously by presenting a novel form of irreversible perturbation for RMLD that is informed by the underlying geometry. Through numerical examples, we show that this new irreversible perturbation can improve estimation performance over irreversible perturbations that do not take the geometry into account. Moreover we demonstrate that irreversible perturbations generally can be implemented in conjunction with the stochastic gradient version of the Langevin algorithm. Lastly, while continuous-time irreversible perturbations cannot impair the performance of a Langevin estimator, the situation can sometimes be more complicated when discretization is considered. To this end, we describe a discrete-time example in which irreversibility increases both the bias and variance of the resulting estimator.


Nano-fertilizers: A sustainable technology for improving crop nutrition and food security.
Excessive use of synthetic fertilizers cause economic burdens, increasing soil, water and atmospheric pollution. Nano-fertilizers have shown great potential for their sustainable uses in soil fertility, crop production and with minimum or no environmental tradeoffs. Nano-fertilizers are of submicroscopic sizes, have a large surface area to volume ratio, can have nutrient encapsulation, and greater mobility hence they may increase plant nutrient access and crop yield. Due to these properties, nano-fertilizers are regarded as deliverable 'smart system of nutrients'. However, the problems in the agroecosystem are broader than existing developments. For example, nutrient delivery in different physicochemical properties of soils, moisture, and other agro-ecological conditions is still a challenge. In this context, the present review provides an overview of various uses of nanotechnology in agriculture, preference of nano-fertilizers over the conventional fertilizers, nano particles formation, mobility, and role in heterogeneous soils, with special emphasis on the development and use of chitosan-based nano-fertilizers.


Atrial natriuretic factor regulates steroidogenic responsiveness and cyclic nucleotide levels in mouse Leydig cells in vitro.
The effects of synthetic atrial natriuretic factor (ANF) on the regulation of mouse Leydig cell steroidogenesis have been studied in vitro. ANF in nanomolar concentration increased testosterone production by more than 30-fold over basal levels. Concomitantly, cyclic guanosine monophosphate levels were increased 35-fold; cyclic adenosine monophosphate levels fell minimally (15-20%). ANF at low concentration (1 X 10(-11) M) inhibited testosterone production by luteinizing hormone-stimulated cells, while at higher concentration (greater than 2 X 10(-9) M) ANF stimulated steroidogenesis beyond the level attained by luteinizing hormone alone. These results indicate that ANF can exert stimulatory effects on testosterone steroidogenesis in vitro, and that the mechanism may involve an intracellular messenger other than cyclic adenosine monophosphate.


Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis.
Infection with coronavirus disease-2019 (COVID-19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID-19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID-19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non-hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID-19 was 3·9% [95% confidence interval (CI): 2·1-7·2] during hospitalisation, 0·9% (95% CI: 0·2-3·1) in the three months after discharge and 0·2% (95% CI: 0·00-1·25) in non-hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.


Ultra-wide-field imaging assessment of small choroidal pigmented lesions using red and green colour channels.
Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma. Retrospective cross-sectional study of patients with small choroidal pigmented lesions up to 3 mm in thickness. All patients underwent clinical and imaging assessment including UWF. Lesions were subcategorized based on thickness and lesion type. A qualitative assessment ensued using the red and green channels feature. A total of 152 patients were included. Melanotic naevi (76/152,50%) and small choroidal melanomas (55/152,36%) were the predominant types. Thickness was <1 mm in 30% (46/152), 1-2 mm in 46% (70/152) and 2-3 mm in 24% (36/152) of cases. Two distinct imaging patterns were noted: dark on RC/undetectable on GC and dark on RC/light on GC. In melanotic naevi the dark on RC/light on GC pattern was significantly associated with increased tumour thickness (p = 0.006) and the presence of lipofuscin (p < 0.001) suggesting a potential prognostic significance. In small melanomas such an association was not established. The majority of small melanomas manifested a dark on RC/undetectable on GC pattern despite the presence of subretinal fluid and lipofuscin. UWF imaging of choroidal pigmented tumours with red-green channels revealed two distinct patterns. The dark on RC/light on GC pattern was more common in suspicious melanotic naevi, but not in small melanomas. The use of red-green channels is not a reliable diagnostic tool in the early detection of small melanomas.


[Autocastration of a young schizophrenic man].
Self-mutilation of the genitals in man is a rare phenomenon mainly occurring in young males. The importance of conflicts about the male role, difficulties with the male identification in childhood and feeling of guilt for sexual offences are discussed in the literature. The influence of developmental crisis on this symbolic form of automutilation will be discussed in our case report. We present a case of a young schizophrenic man whose illness started in adolescence. He committed genital automutilation already in early adolescence, as a young male he autocastrated himself. We demonstrate the connection of specific problems of development in adolescence and psychopathology. Autocastration will be discussed as a "psychotic" solution of the adolescent conflict of dependence. Developmental conflicts may be important pathoplastic factors who may lead to severe psychopathology and misbehavior. Additionally to a psychopharmacological treatment a specific adolescent- and conflictoriented psychotherapy for solving the developmental conflicts in young schizophrenic patients should be established.


Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification.
The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.


Successful pregnancy in ovariectomized mice using a combination of heterotopic autotransplantation of ovarian tissues and embryo transfer.
Aim: The present report is the first to show that, after ovariectomy, female mice with autotransplanted ovarian sections can maintain pregnancy after embryo transfer (ET) independent of the transplantation site. Methods: Three-month-old ICR females were ovariectomized, and sections from their own ovaries were transplanted either under their kidney capsule (KC group) or into a subcutaneous space (SC group) just after ovariectomy. In vitro fertilized blastocysts were transferred into uterine horns of the pseudopregnant mice that had received the transplanted ovarian tissues. Cesarean sections were carried out 17 days after ET to deliver any live fetuses that were present, and the numbers of implantation sites and fetuses were noted. Transplanted ovarian sections were removed and fixed for histological analysis. Results: Of the 10 mice in the KC group that received 107 blastocysts, two females (20%) became pregnant; they showed 12 implantation sites (11.2%) and produced four pups (3.7%). In the SC group, 101 blastocysts were transferred to eight females, and three females (37.5%) became pregnant; there were seven implantation sites (6.9%), and three pups (3.0%) were born. There were no statistically significant differences between the two groups in any of the parameters evaluated. On histological examination, luteinization and vascularization of the ovarian sections that were transplanted in the pregnant SC and KC females were noted. Conclusion: The pregnancy and full-term fetal development were obtained in ovariectomized mice using a combination of heterotopic ovarian tissue autotransplantation and transfer of embryos produced by in vitro fertilization.


Impact factor of medical journals: problems in geriatrics.
The Impact Factor (IF) is one of the most reliable methods for evaluating the quality of scientific journals. To date, no one has studied the IF of geriatric journals over time. Our aims were 1) to evaluate the IF trend of geriatric journals in general, and with respect to internal medicine, which is the nearest discipline, and 2) to assess the proportion of papers on common geriatric topics published in geriatric journals, with respect to other general periodicals. The current literature was studied to define what IF is and describe its good points and deficiencies. We then analyzed the situation regarding geriatric journals. A bibliometric analysis addressed the kind of journal interested in important geriatric themes (syncope, falls, hip fractures, delirium). Geriatric journals have a low IF, but their importance has been growing over the years. Despite this, papers regarding geriatric themes are published mainly in non-specific journals, and the number of publications regarding syncope, falls, hip fractures, and delirium has not increased during the period in question. In conclusion, it is difficult to use the IF for comparisons between different disciplines, in particular when the one under consideration (geriatrics and gerontology) is spread over a wide range of medical fields. The increase in IF of geriatric journals over time is the most important result of our analysis; this finding will encourage geriatric scientists to submit their papers to geriatric periodicals and will increase the specificity of the gerontological discipline.


Retrograde cell changes in medial septum and diagonal band following fimbria-fornix transection: quantitative temporal analysis.
Complete unilateral fimbria-fornix transections, including the overlying cingulate cortex, were administered to female rats. At time points from 1 day to 6 weeks, the septal-diagonal band region was examined using acetylcholinesterase histochemistry, Cresyl Violet cell staining, and choline acetyltransferase biochemistry. As early as 1 day following the transection a decrease in acetylcholinesterase positive cell body staining was observed in the medial septum; however, no loss of Nissl-stained neurons was measured in Cresyl Violet stained sections until 1 week after the lesion. Maximal loss of acetylcholinesterase-positive cells, as visualized after irreversible acetylcholinesterase inhibition, was measured at 1 week, and no further change was observed at time points up to 6 weeks after operation. The loss of acetyltransferase-positive cells was greatest in the medial septal area (-65%) and the vertical limb of the diagonal band (-55%). Little cell loss was measured in the horizontal limb of the diagonal band. This is consistent with the known projections of these cell bodies. Remaining acetylcholinesterase-positive cell bodies in the medial septum had shrunk by about 20% (measured as the diameter along the major axis). A marked neuronal cell loss (about 50%) was demonstrable in the medial septum and vertical limb of the diagonal band in the Cresyl Violet-stained sections, too. A pile-up of acetylcholinesterase-stained material was observed in the dorsal-lateral quadrant of the septal area just proximal to the lesion at 1 day following transection. This pile-up occurred in the medial septum and diagonal band area up to 1 week following the transection, and had nearly disappeared by 2 weeks post-transection. Choline acetyltransferase biochemical activity, measured in samples of whole septum, decreased significantly at 1 day but subsequently returned to control levels. By 2 weeks following transection, an increase in acetylcholinesterase-positive stained fibers was observed in the dorsal-lateral quadrant of the septum, ipsilateral to the lesion relative to the contralateral septum. This response, which was interpreted as sprouting from the lesioned axons proximal to the transection, probably accounted for the rise in choline acetyltransferase biochemical activity in the whole septum following the reduction on the first day.


Differing action potential shapes in rat dorsal root ganglion neurones related to their substance P and calcitonin gene-related peptide immunoreactivity.
Intracellular electrophysiological recordings were made in vitro at 36.5 degrees C from lumbar (L4 to L6) dorsal root ganglion neurones of 6-8-week-old female rats. Electrophysiological properties were recorded prior to intracellular injection with fluorescent dye. The following showed substance P-like immunoreactivity (SP-LI): 8/19 C-fibre cells, 6/26 Adelta cells, and 0/52 Aalpha/beta cells. In C-fibre neurones, there were no significant differences in action potential (AP) characteristics between those with SP-LI and those without. In contrast, the Adelta neurones with SP-LI had significantly deeper and longer afterhyperpolarisations (AHPs), but their AP durations did not differ from those without SP-LI. Both SP-LI and calcitonin gene-related peptide-LI (CGRP-LI) were examined on 18 Adelta and 11 C cells. Most (7/8) neurones with SP-LI also showed CGRP-LI, but only 7/21 neurones without SP-LI showed CGRP-LI. One C cell showed SP-LI but no CGRP-LI. Neurones with neither peptide (-/-), with only CGRP (-/CGRP) or with both peptides (SP/CGRP) were compared (n = 28). The numbers in each group were, respectively, 5, 2, and 3 with C-fibres and 9, 5, and 4 with Adelta-fibres. The peptide content and AP shape were related in Adelta neurones. Most -/- Adelta neurones had short APs and short AHPs; most -/CGRP neurones had long APs and long AHPs, and SP/CGRP neurones had short APs with deep, long AHPs. There was a positive correlation between log10 of the area under the AP (AP area) and log10 AHP duration in Adelta neurones. All SP- and most CGRP-containing Adelta neurones had AP shapes similar to those previously described for nociceptive neurones. However, a few without peptide also showed such properties, raising the possibility that some nociceptive neurones did not express these peptides.


Catering of high-risk foods and potential of stored food menu data for timely outbreak investigations in healthcare facilities, Italy and Germany.
Healthcare-associated foodborne outbreaks (HA-FBOs) can cause significant morbidity and mortality, affecting particularly vulnerable hospital populations. Electronic records of food served in healthcare facilities (HCFs) could be useful for timely investigations of HA-FBOs. We explored the availability and usability of electronic food menu data to support investigations of HA-FBOs through a survey among 35 HCFs in Germany (n = 13) and in Italy (n = 22). Large variability was reported in the storage time of menu data (from no storage up to 10 years) and their formats, including paper, electronic (PDF, Word, Excel), or fully searchable databases (15/22 in Italian HCFs, 3/13 in German HCFs). Food products that may present a risk to vulnerable persons - including deli salads, raw/fermented sausage products, soft cheese, smoked fish or frozen berries - were offered on the menu of all HCFs in Germany, and one-third of the Italian HCFs. The usability of electronic food menu data for the prevention or investigation of HA-FBOs may be suboptimal in a large number of HCFs in Germany, as well as in some HCFs in Italy. Standardised collection for use of electronic food menu data might help discover the association between illnesses and food eaten during outbreak investigations. Hospital hygienists, food safety and public health authorities should collaborate to increase implementation of food safety guidelines.


Overuse of training increases mechanoreceptors in supraspinatus tendon of rats SHR.
The presence of mechanoreceptors in tendon after overuse activities can be a further step to learn about tendinopathy and overuse. Studies of tendons mechanoreceptors in rats are rare. We studied 12 isogenic spontaneous hypertensive rats (SHR), which underwent an overuse protocol consisting of an hour per daily session of treadmill running at a speed of 17 m/min, 5 times/week for 4 months. Supraspinatus tendons were evaluated with immunohistochemistry using S100 protein antibodies and histological protocol. Supraspinatus tendons at the end of 4 months of overuse protocol had a high number of media mechanoreceptors (4.3) than controls (0.6). The overexpression of S100 protein antibody in overuse activities maybe could represent a adaptative effort to tendon before the tear.


Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population.
Melatonin is reported to be an anti-inflammatory agent. No genetic study concerning the association between melatonin and inflammatory disease has yet been reported. Here we performed a polymorphism study on the melatonin receptor type 1B (MTNR1B) in Korean rheumatoid arthritis (RA) patients and controls. The polymorphism of MTNR1B located in 3'-untranslated region (rs 1562444) was selected for its higher rate of heterozygosity among other single nucleotide polymorphisms (SNPs) in both MTNR1A and MTNR1B genes and investigated in RA patients (n = 173) and healthy controls (n = 195) by polymerase chain reaction-restriction fragment length polymorphism assay using NlaIII restriction enzyme. No statistically significant difference in either genotype distribution or allele frequency was observed between RA patients and controls. The genotype distributions and allele frequencies of rheumatoid factor negative [RF(-)] patients were similar to those of controls. However, statistical analysis of genotype revealed a significant association (chi2 = 6.42, P = 0.04) is present between RF(+) and MTNR1B SNP (rs 1562444). Although no statistically significant difference in allele frequency between RF(+) and controls was observed (chi2 = 2.75, P = 0.10), the results might suggest that MTNR1B SNP (rs 1562444) is associated with the presence of RF in RA. This is the first study, to our knowledge, to report a positive genetic relationship between melatonin and RA.


Comparison of the cytotoxic effect of lapachol, alpha-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells.
The pentacyclic 1,4-naphthoquinones 1a-d were cytotoxic (IC(50) approximately 2-7 microM) to human leukemic cell lines K562 (oxidative stress-resistant), Lucena-1 (MDR phenotype) and Daudi. Fresh leukemic cells obtained from patients, some with the MDR phenotype, were also sensitive to these compounds. The pentacyclic 1,4-naphthoquinones 1a and 1c induced apoptotic cell death in cells from leukemic patients as determined by flow cytometry. Conversely, the cell lines were highly insensitive to lapachol (2) and alpha-lapachone (3). Mitomycin-C inhibited cell proliferation at concentrations as low as 0.5 microM. The low toxicity against lymphocytes activated by phytohemagglutinin shows that these compounds are selective for the cancer cells studied. Previous data suggest that these compounds (1a-d) can be bioactivated in situ by reduction followed by rearrangement leading to enones, which are powerful alkylating agents. In contrast, lapachol (2) and beta-lapachone (3), which cannot be bioactivated by reduction, showed little activity against the same cell lines.


The Cupid shuffle: Do enhancers prefer specific promoters?
Two recent reports (Martinez-Ara et al., 2022; Bergman et al., 2022) explore the compatibility between enhancers and promoters and find that enhancers preferentially activate promoters with low intrinsic activity rather than favoring housekeeping or cell-type-specific promoters.


[A Case of Synchronous Multiple Colorectal Cancer with Rectal Neuroendocrine Tumor and Ascending Colon Cancer].
A 43-year-old man who had no previous medical history or family history had positive fecal occult blood test in a local physician. Colonoscopy revealed a type 2 tumor of the ascending colon and a 10 mm submucosal tumor(SMT)of the lower rectum. Biopsy indicated moderately-differentiated adenocarcinoma of the ascending colon and neuroendocrine tumor (NET)of the lower rectum. No metastasis was detected by computed tomography. Therefore, the rectal SMT was resected first by endoscopic submucosal resection. Histopathologically, the lesion was localized in the submucosa and no lymphovascular invasion was found. Vertical margin was also negative. We decided not to perform additional intestinal resection for rectal NET. Thereafter, the patient underwent laparoscopic right hemicolectomy for ascending colon cancer. The histopathological findings were pT3, pN1, pM0, pStage Ⅲb. The patient received adjuvant chemotherapy. No relapse was found 18 months after surgery. We reported a rare case of a lower rectal NET with concomitant ascending colon cancer.


Detection of BCS pairing in neutral fermi fluids via stokes scattering: the Hebel-Slichter effect.
We consider the effects of superfluidity on the light scattering properties of a two component gas of fermionic atoms, demonstrating that the scattered intensities of the Stokes and anti-Stokes lines exhibit a large maximum below the critical temperature when the gas is superfluid. This effect, the light scattering analog of the Hebel-Slichter effect in conventional superconductors, can be used to detect unambiguously the onset of pairing in an atomic gas in the BCS regime.


Endogenous release of metals with dissolved organic carbon from biochar: Effects of pyrolysis temperature, particle size, and solution chemistry.
Metals are released from biochar (BC) in either the free or dissolved organic carbon (DOC)-combined form. The complexation of metals with DOC influences their toxicity and bioavailability in the environment. The endogenous release of metal species with heterogeneous DOC from BC is very complex; this process has been neglected and remains unaddressed in the literature to date. In this study, the yield and chemical properties of labile DOC from BC were characterized, and the release of endogenous metal/metalloid elements (K, Mg, Mn, Fe, Al, Cu, and Si) and their species from BC with various pyrolysis temperatures and particle sizes were systematically investigated under various solution chemistries. The results showed that pyrolysis temperature of BC significantly influenced the yield and composition of DOC and DOC-metal/metalloid complexes, while particle size had lower impact. The yield of BC-derived DOC significantly decreased and the components gradually changed from low-molecular weight and low-aromaticity hydrophilic humic acid-like substances to complex high-molecular weight and high-aromaticity hydrophobic substances as pyrolysis temperature increased from 200 to 700 °C. The release of total dissolved metals decreased with increasing pyrolysis temperature, while the highest total dissolved Si was released from BC with the moderate pyrolysis temperature (500 °C). The metal elements were mainly released in the DOC-combined form, while the released Si was mainly in the free form in the neutral water environment. The release of DOC increased while that of dissolved metals decreased with increasing solution pH. The release of total dissolved metals/metalloids increased but the ratio of the DOC-combined metals/metalloids decreased with increasing solution ionic strength. These results provide new insight into the understanding of endogenous metal/metalloid release from BC in the natural environment.


The COVID-19 pandemic necessitates a shift to a plastic circular economy.
The COVID-19 pandemic is exacerbating plastic pollution. A shift in waste management practices is thus urgently needed to close the plastic loop, requiring governments, researchers and industries working towards intelligent design and sustainable upcycling.


Effect of adjunctive diode laser in the non-surgical periodontal treatment in patients with diabetes mellitus: a systematic review and meta-analysis.
This study aimed to systematically review and analyze the present randomized clinical trials (RCTs) regarding the clinical efficacy of a diode laser (DL) adjuvant to scaling and root planning (SRP) in patients with chronic periodontitis (CP) who have diabetes mellitus (DM). Five databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and Chinese BioMedical Literature Databases) were searched. A meta-analysis was implemented to evaluate periodontal parameters including probing depth (PD) and clinical attachment level (CAL) as primary outcomes. Hemoglobin A1c (HbA1c), plaque index (PI), and the gingival index (GI) were also observed as secondary outcomes. Independent scanning of 239 papers resulted in 9 RCTs. Moderate evidence demonstrated that the test groups showed significant benefits for PD reduction, CAL gain, and HbA1c reduction after 3 and 6 months. Significant differences in PI and GI reduction were not found except for GI reduction within 1 month. The collective evidence suggested that the DL with SRP had significant improvements in clinical results compared to SRP alone. Based on our results, the DL could be a recommended therapy for patients with CP who have DM.