Adjuvant and neo-adjuvant chemotherapy for Ewing's sarcoma family tumors and osteosarcoma of the extremity: further outcome for patients event-free survivors 5 years from the beginning of treatment.
In 326 patients with Ewing's sarcoma family tumor (ESFT) and 628 extremity osteosarcoma (OS) treated with adjuvant and neo-adjuvant chemotherapy and event-free survivors 5 years from the beginning of treatment we evaluated outcome in the following years. Post 5-year follow-up for these patients was 9.7 years (5.5-29 years). Adverse events observed after 5-year follow-up were 73 (7.6%): 38 late relapses, nine leukemia, 14 second solid tumor, seven radioinduced sarcoma, three severe adriamycin-related cardiomyopathy, one suicide and one death by car crash. Of the patients who developed late events, 16 (22.5%) are alive and event free after 8 years from the last treatment (2-22 years). We conclude that the high rate of late adverse events after 5 years in patients with OS and ESFT is noteworthy and indicates that these patients should be followed for >5 years.


A data retrieval system for the eye clinic. II. The programmed system.
The programmed system of a data retrieval system for the eye clinic is described. The system uses an IBM 370/168 computer, involves programmes to minimize the possibility of entering errors and a magnetic tape back-up system to reduce the cost of storing rarely required material and as a safeguard against the accidental erasion of material on disc.


Role of mast cells in acupuncture effect: a pilot study.
To better understand the therapeutic effectiveness of acupuncture, questions about the underlying mechanisms need to be addressed. Here we describe the impact of manual stimulation by an acupuncture needle of zusanli (stomach 36 [ST36]) on analgesia in rats. The analgesic effect was more pronounced after stimulation of ST36 than after stimulation of a sham point near the acupuncture point. At the same time, we determined in tissue slices the density of mast cells in the acupuncture points and nearby points, as well as the degree of degranulation before and after stimulation. We found that the density of mast cells from the ST36 of rats was higher than that from a nearby sham point. In addition, acupuncture resulted in a remarkable increase in degranulation of the mast cells. Pretreatment of the acupuncture point with disodium chromoglycate not only counteracted the phenomenon of degranulation but also reduced analgesic effect of acupuncture. Our experiments on inhibition of degranulation of mast cells in tissue from acupuncture points demonstrates the possible role of mast cells in acupuncture effects.


HLA antigen expression at the single cell level on a K562 X B cell hybrid: an analysis with monoclonal antibodies using bacterial binding assays.
The influence of different genetic environments on the expression of HLA complex-controlled antigens has been investigated using cell lines with various defects in the synthesis of these molecules and a somatic cell hybrid derived from them. A very sensitive bacterial binding assay allowing simultaneous evaluation of the morphology of a given cell and the quantity of a surface molecule has been developed for these studies. The fetal erythroid cell line K562, the Burkitt's lymphoma-derived cell line DAUDI, and their hybrid DUTKO1 have been employed. K562 and the hybrid, but not DAUDI, expressed HLA-A,B,C heavy chains as detected by the monoclonal antibody W6/32.HL, while two monoclonal antibodies (TU48 and 2BC4) against the supertypic specificities HLA-Bw4 and Bw6 showed no reactivity. The presence of human Ia-like antigens on the cell surfaces was investigated with a panel of eight monoclonal antibodies. K562 cells were completely unreactive, and DAUDI cells gave the expected positive reaction, but about 1% or less of the cells in the DUTKO1 population appeared to express these antigens as well. We discuss possible reasons for the failure to detect HLA-B antigens with monoclonal antibodies and the lack of complete "dominance" of the K562 genome in the hybrid cell line.


The use of real-time PCR methods in DNA sequence variation analysis.
Real-time (RT) PCR methods for discovering and genotyping single nucleotide polymorphisms (SNPs) are becoming increasingly important in various fields of biological sciences. SNP genotyping is widely used to perform genetic association studies aimed at characterising the genetic factors underlying inherited traits. The detection and quantification of somatic mutations is an important tool for investigating the genetic causes of tumorigenesis. In infectious disease diagnostics there is an increasing emphasis placed on genotyping variation within the genomes of pathogenic organisms in order to distinguish between strains. There are several platforms and methods available to the researcher wishing to undertake SNP analysis using real-time PCR methods. These use fluorescent technologies for discriminating between the alternate alleles of a polymorphism. There are several real-time PCR platforms currently on the market. Two of the key technical challenges are allele discrimination and allele quantification. Applications of this technology include SNP genotyping, the sensitive detection of somatic mutations and infectious disease subtyping.


Aqueous enantioselective organocatalytic Diels-Alder reactions employing hydrazide catalysts. A new scaffold for organic acceleration.
[reaction: see text] Cyclic hydrazides function as asymmetric organocatalysts in aqueous Diels-Alder reactions. The hydrazide is employed as the catalytic machinery in a compact camphor-derived framework that imparts facial selectivity to the cycloadditions. Kinetic evidence suggests the reaction involves rapid iminium formation.


Family delivery from the standpoint of fathers--can stereotypes of participant or non-participant father be fully justified?
Family delivery is an important aspect of modern obstetrics. The aim of this study was to estimate the phenomenon of family delivery from the standpoint of participating and non-participating fathers. Two types of questionnaires were used in the study. Five hundred and five men were divided into two groups: (A) delivery participants and (B) delivery non-participants. The participants were significantly younger than non-participants. Better educated men dominated in group (A), whereas men with trade education were the majority in group (B). Low birth classes attendance among women in group (B) was noticed. All men in group (B) knew about the possibility of taking part in the delivery. Almost 100% of participants declared their satisfaction with family delivery. For non-participants, wife and media were the main source of knowledge, while for participants it was the medical staff and labor schools. Family labor is commonly accepted by both partners and is generally connected with positive emotions. This phenomenon is generally approved by couples with higher economical status. Family labor resignation, common among pairs with lower economical status, is caused generally by fear and lack of proper knowledge. Health care providers, through labor schools and outpatients visits, should concentrate on getting to couples, whose attitude towards family labor is negative. Educational programs and popular press articles should be prepared more thoroughly, focusing on the whole population of potential fathers.


Treatment and follow up of children with chronic hepatitis C in Albania.
Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained.


Increase in nuclease activity as a possible means for detecting tumor cell sensitivity to anticancer agents.
Histochemical activity of nucleases was investigated in sensitive and resistant rat tumors at several periods after a single dose of cyclophosphamide and was compared with that in a control group of untreated tumors. Intense increase of nuclease activity(mainly that of acid DNAse) appeared only in the cells of the sensitive tumors at 12 hours, reaching its maximum three days after drug administration. Untreated malignant tumors usually have variable amounts of spontaneous necrosis with high nuclease activity. Not the absolute values of high nuclease activity but only the increase of such activity from the basal level of untreated tumors to that measured at frequent periods after trial treatment may be suggested as an early marker of therapeutically induced tumor cell necrosis. However, more investigation is needed before such a marker might be applied as a test for tumor sensitivity to therapeutic agents.


Inflammatory responses of a macrophage/epithelial cell co-culture model to mono and mixed infections with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia.
Accumulated evidence points to Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia as three major etiologic agents of chronic periodontitis. Epithelial cells and macrophages play a major role in the host response to periodontopathogens, and the secretion of inflammatory mediators and matrix metalloproteinases (MMPs) by these host cells is believed to contribute to periodontal tissue destruction. The aim of this study was to investigate the inflammatory response of a macrophage/epithelial cell co-culture model following mono or mixed infections with the above three periodontopathogens. An in vitro co-culture model composed of epithelial-like transformed cells (HeLa cell line) and macrophage-like cells (phorbol myristic acid-differentiated U937 monocytic cell line) was challenged with whole cells or lipopolysaccharides (LPS) of P. gingivalis, T. denticola, and T. forsythia, individually and in combination. Following stimulation, the production of interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), regulated on activation normal T cell expressed and secreted (RANTES), prostaglandin E2 (PGE2), and MMP-9 were quantified by enzyme-linked immunoassays. We observed that mono or mixed infections of the co-culture model induced the secretion of IL-1beta, IL-6, IL-8, PGE2, and MMP-9. P. gingivalis and T. forsythia induced an increase in RANTES secretion, whereas T. denticola alone or in combination resulted in a significant decrease in RANTES levels. All LPS challenges induced an increase in chemokine, MMP-9, and PGE2 production. No synergistic effect on the production of cytokines, chemokines, PGE2, and MMP-9 was observed for any of the bacterial or LPS mixtures tested. This study supports the view that P. gingivalis, T. denticola, and T. forsythia may induce high levels of pro-inflammatory mediators and MMP-9 in periodontal lesions, thus contributing to the progression of periodontitis.


Covid-19 in Israel: socio-demographic characteristics of first wave morbidity in Jewish and Arab communities.
The first wave of the Covid-19 pandemic hit Israel in late February 2020. The present study examines patterns of the first wave of Covid-19 morbidity in Israel at the macro level, during the period of late February to early June 2020, when the first wave has faded out. The analysis focuses on the significance of four sociodemographic variables: socioeconomic status, population density, rate of elderly population and minority status (Jewish / Arab identity) of the population in cities with 5000 residents or more. Additionally, we take a closer look into the association between morbidity rates and one SES component - home Internet access. The article is a cross sectional study of morbidity rates, investigated on a residential community basis. Following the descriptive statistics, we move on to present multivariate analysis to explore associations between these variables and Covid-19 morbidity in Israel. Both the descriptive statistics and regressions show morbidity rates to be positively associated with population density. Socioeconomic status as well as the size of elderly population were both significantly related to morbidity, but only in Jewish communities. Interestingly, the association was inverse in both cases. i.e., the higher the SES the lower the morbidity and the larger the elderly population, the lower the community's morbidity. Another interesting result is that overall, morbidity rates in Jewish cities were consistently higher than in Arab communities. We attribute the low morbidity rates in communities with relatively small elderly populations to the exceptionally high fertility rates in ultra-orthodox communities that sustained increased rates of morbidity; the lower morbidity in Arab communities is attributed to several factors, including the spatial Jewish-Arab segregation.


Death wishes in the very elderly: data from a 3-year follow-up study.
The aim of this study was to study the 3-year outcome of death wishes in an elderly population. 1099 very elderly people were examined extensively by physicians, including a structured psychiatric interview. Three years later those who had survived were re-examined (n = 683) using a similar procedure. Of the sample, 11.6% (n = 128) had death wishes at the first examination and 8.9% (n = 54) at the follow-up. Of the 54, 17 have had death wishes persistently during the 3-year period; all of them had psychiatric diagnoses. Of those having death wishes at one of the examinations 70% had psychiatric diagnoses. Attrition was more common in the group with death wishes than in the group without when age, gender, somatic disorders including dementia and disability in daily living were taken into account. This study shows that there is a need for a psychiatric examination when elderly people express death wishes.


Tyrosol Ameliorates the Symptoms of Obesity, Promotes Adipose Thermogenesis, and Modulates the Composition of Gut Microbiota in HFD Fed Mice.
Tyrosol is one of the main polyphenolic compounds in extra virgin olive oil (EVOO) and its role in combating obesity is unknown. Thus, this study is designed to investigate the effect of tyrosol consumption on obesity and its underlying mechanisms in high-fat diet (HFD)-induced mice. After supplementation with 0.2% (wt/wt) tyrosol for 16 weeks, the final body weight, and the levels of plasma triacylglycerol (TG), total cholesterol (TC), and fasting glucose are significantly decreased when compared with HFD group. Furthermore, tyrosol may act as a ligand which binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα). Uncoupling protein 1 (UCP1), iodothyronine deiodinase 2 (DIO2), PPAR-γ coactivator-1α (PGC-1α), and PR domain containing 16 (PRDM16), the downstream genes of PPARα which are related to thermogenic function of adipocytes, are significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after tyrosol administration. In addition, tyrosol changes the community composition of gut microbiota, including decreasing the ratio of Firmicutes to Bacteroidetes, and increasing the relative abundance of family muribaculaceae, genus Blautia and Lachnospiraceae_bacterium_28_4. Tyrosol consumption attenuates obesity and related symptoms in HFD-fed mice probably via the modulation of PPARα-thermogenesis and gut microbiota.


Clinical and MRI findings after high dosage medical exercise therapy in patients with long lasting subacromial pain syndrome: a case series on six patients.
SUMMARY BACKGROUND AND PURPOSE: The primary aim of this case series was to investigate the effect of a high dosage medical exercise therapy program on shoulder pain in patients with subacromial pain syndrome. Six subjects were assigned to a medical exercise therapy group. They received three treatments a week over three months. Outcome measures were descriptions of the subacromial space including supraspinatus tendon diameter, function, pain, and active range of motion in the shoulder girdle. The subjects showed improvement posttest compared to pretest with respect to pain, function, range of motion, and isometric strength. An MRI demonstrated no change in tendon thickness after the treatment. Inflammatory signs such as fluid in the subacromial bursa decreased in some patients. In patients with uncomplicated subacromial pain syndrome, high dosage medical exercise therapy might be an efficient treatment approach. The clinical effects might be explained by morphological changes in the subacromial space.


Immunopurification of gastric parietal cell tubulovesicles.
1. The tubulovesicles of hog and rabbit gastric parietal cells were immunopurified from microsomes using monoclonal antibodies against the (H+, K+)-ATPase. 2. The best yields of immunoprecipitation were obtained with an ATPase/mAb molar ratio of 0.3: the immunoprecipitate contained 79 and 90% of the hog and rabbit microsomal PNPPase activity respectively and K(+)-stimulated ATPase specific activity was 221 +/- 29 mumoles Pi per hr and per mg of membrane protein. 3. The immunoprecipitate contained vesicles that were 85% cytoplasmic-side out, like tubulovesicles in vivo, demonstrating that the epitopes were cytoplasmic. 4. The alpha-beta protomer of (H+, K+)-ATPase accounted for 80 +/- 12% of the immunopurified proteins. 5. The major other proteins ran at 80, 75, 69, 57, 47, 44, 39, 34 and 32 kDa on the SDS-PAGE. 6. Comparative analysis between sucrose-gradient purified fractions and immunopurified tubulovesicles demonstrated that carbonic anhydrase and actin were contaminants and that the 53 kDa and presumably the 50 kDa bands of the gradient fraction were alpha and beta subunits of F1 ATPase.


Unusual endolaryngeal extension of a large thyroglossal duct cyst.
Thyroglossal duct cysts account for approximately 70% of congenital neck abnormalities. Hoarseness of voice and the extension of the cyst into the larynx are very uncommon. We present a patient with a long history of a large thyroglossal cyst who developed progressive hoarseness of voice. The cyst had protruded into the larynx producing the appearance of a laryngeal neoplasm. Computed tomography (CT) clearly demonstrated the nature of the cyst and its encroachment into the larynx. This was safely excised with a Sistrunk procedure and a temporary tracheostomy to maintain a secure airway, in view of the possibility of postoperative supraglottic oedema. Endolaryngeal extension of the thyroglossal duct cyst is rare. Evaluation of unusual large midline neck masses should include a CT scan. The intralaryngeal component of the cyst can be easily dissected off from the neighbouring structures during dissection in the Sistrunk procedure. A tracheostomy may be needed.


Measuring water exchange on a preclinical MRI system using filter exchange and diffusion time dependent kurtosis imaging.
Filter exchange imaging (FEXI) and diffusion time (t)-dependent diffusion kurtosis imaging (DKI(t)) are both sensitive to water exchange between tissue compartments. The restrictive effects of tissue microstructure, however, introduce bias to the exchange rate obtained by these two methods, as their interpretation conventionally rely on the Kärger model of barrier limited exchange between Gaussian compartments. Here, we investigated whether FEXI and DKI(t) can provide comparable exchange rates in ex vivo mouse brains. FEXI and DKI(t) data were acquired from ex vivo mouse brains on a preclinical MRI system. Phase cycling and negative slice prewinder gradients were used to minimize the interferences from imaging gradients. In the corpus callosum, apparent exchange rate (AXR) from FEXI correlated with the exchange rate (the inverse of exchange time, 1/τex ) from DKI(t) along the radial direction. In comparison, discrepancies between FEXI and DKI(t) were found in the cortex due to low filter efficiency and confounding effects from tissue microstructure. The results suggest that FEXI and DKI(t) are sensitive to the same exchange processes in white matter when separated from restrictive effects of microstructure. The complex microstructure in gray matter, with potential exchange among multiple compartments and confounding effects of microstructure, still pose a challenge for FEXI and DKI(t).


The 5% Lidocaine Patch for Decreasing Postoperative Pain and Rescue Opioid Use in Sternotomy: A Prospective, Randomized, Double-blind Trial.
Poststernotomy pain (PSP), a primary concern after sternotomy, can negatively affect patients' satisfaction with surgery and quality of life. Many clinical trials have been conducted to examine the usefulness of lidocaine patches (LPs) for postoperative pain control for multiple types of surgery; however, the results of these trials are inconsistent. In addition, little is known about the use of LPs after cardiac procedures that require sternotomy. This prospective, double-blind, placebo-controlled trial aimed to determine the efficacy of the 5% LP application at the sternotomy site for reducing PSP and rescue opioid consumption. The patients were randomly assigned to receive either the 5% LP or the placebo patch on each side of the incision site immediately after the surgery. The intensity of pain at 6, 12, 24, and 48 h after the patch application; the total dose of rescue opioids; incidence of nausea, vomiting, and sleep disturbance; and use of antiemetics were compared between the 2 groups. Fifty-seven (31 in the LP group and 26 in the placebo group) patients were included. The pain intensity was significantly lower in the LP group at each time point (66%-68% pain reduction, P < 0.001, interaction of time × treatment P = 0.69). In addition, the total dose of rescue opioids used for 48 h was significantly lower in the L group (27.2% reduction, P = 0.008). No significant differences were found in other outcome variables between the 2 groups. The application of a 5% LP on each side of the sternotomy site can reduce PSP and additional opioid use without significant adverse effects in patients undergoing sternotomy. Thus, it can be considered as a standard and routine modality along with other analgesic medications for the management of PSP. Clinical Trial Registry in South Korea identifier: KCT0000476.


Cancer causes and prevention: a condensed appraisal in Europe in 2008.
The rising cancer burden in Europe, mainly due to a rapidly ageing population, demands a clear and coordinated response from researchers, oncologists and other physicians, public health professionals and policy-makers. Primary and secondary prevention is the front line in the complex battle against cancer in Europe. To formulate the best strategies in this fight, the major determinants of cancer are summarised in the order of their relative importance in Europe, including tobacco smoking, alcohol, diet, physical activity, occupational factors, environmental factors, infectious agents and genetic and hormonal factors. Furthermore, this paper offers explicit recommendations on individual behaviour modification and possible public policies. It also details the numerous examples of European policies and programmes already in effect which aim to reduce the impact of these risk factors on cancer. Although there are still pending questions, which need further epidemiologic research, it is also true that we have more operational knowledge for cancer prevention than ever before. The prompt implementation of prevention programmes such as those detailed here should be applied with determination to maximise the prevention results.


[Primary cancer of the gallbladder. Analysis of a surgical series of 24 cases. Attempted anatomical classification of its prognosis. Proposal of a preventive approach].
This analysis of 24 cases of primary carcinoma of the gall bladder is compared with series in the literature. The extremely poor prognosis of this carcinoma, recognised by all authors, may be explained by the unfavourable background, delay in diagnosis at all stages, early regional spread, difficulty in laying down the therapeutic indications. A Pathological classification for prognosis has been proposed for the surgeon with stages: O, I, II, II a and b, IV a and b, in relation to the spread of the gall bladder carcinoma and reflexions inspired by analysis of the operative results in the literature. Even with better knowledge of predisposing factors, and if new methods of treatment gave greater hope in the future, more frequent use of cholecystectomy seems the best prevention of bladder carcinoma in any case of cholelithiasis whether symptomatic or not, in the absence of any contra-indication.


Acceptability, Feasibility, Drug Safety, and Effectiveness of a Pilot Mass Drug Administration with a Single Round of Sulfadoxine-Pyrimethamine Plus Primaquine and Indoor Residual Spraying in Communities with Malaria Transmission in Haiti, 2018.
For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.


Non-fatal overdose risk associated with prescribing opioid agonists concurrently with other medication: Cohort study conducted using linked primary care, secondary care and mortality records.
An apparently protective effect of opioid agonist treatment (OAT) on all-cause and cause-specific mortality risk has been widely reported. Non-fatal overdose (NFO) often precedes subsequent drug-poisoning deaths. We hypothesized that benzodiazepines, gabapentinoids, antipsychotics, antidepressants, Z-drugs or opioids increase the NFO risk when co-prescribed with OAT. We conducted a cohort study using the Clinical Practice Research Datalink GOLD and Aurum databases. The cohort was linked to Hospital Episode Statistics admitted patient care data (HES-APC), neighbourhood- and practice-level Index of Multiple Deprivation quintiles and mortality records from the Office for National Statistics. Primary care in England. We studied patients with opioid use disorder, aged 18-64 years, who were prescribed OAT (15155 methadone and 5743 buprenorphine recipients) between Jan 1, 1998, and Dec 31, 2017. The main outcome examined was NFO risk during co-prescription of OAT with benzodiazepines, antipsychotics, gabapentinoids, antidepressants, Z-drugs or opioids. Overdose was defined according to International Classification of Diseases codes from the HES-APC data set. Negative binomial regression models were used to estimate weighted rate ratios (wRR) for NFO during co-prescription of OAT and benzodiazepines, antipsychotics, gabapentinoids, antidepressants, Z-drugs or opioids with periods of exclusive OAT usage. Among 20 898 patients observed over 83 856 person-years, we found an elevated overdose risk that resulted in hospital admission during co-prescription of OAT with benzodiazepines [wRR: 1.45; 95% confidence interval (CI) = 1.26-1.67], gabapentinoids (wRR = 2.22; 95% CI = 1.77-2.79), Z-drugs (wRR = 1.60; 95% CI = 1.31-1.96), antipsychotics (wRR = 1.85; 95% CI = 1.53-2.25) and opioids (wRR = 1.28; 95% CI = 1.02-1.60). The risk ratio for antidepressant co-prescriptions was below unity (wRR = 0.90; 95% CI = 0.79-1.02) but this result was not statistically significant. Elevated risk of non-fatal overdose among opioid agonist treatment recipients is associated with concurrent use of medication prescribed for other reasons.


Preparative separation of isomeric caffeoylquinic acids from Flos Lonicerae by pH-zone-refining counter-current chromatography.
This work concentrates on pH-zone-refining counter-current chromatography of two isomeric dicaffeoylquinic acids, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid along with 3-caffeoylquinic acid, from crude extracts of Flos Lonicerae. The elution sequence of the isomeric dicaffeoylquinic acids, the mixing zone and mechanism of separation are discussed. The separation of 2.136g of the crude sample from Flos Lonicerae yielded two isomeric compounds: 0.289g 3,5-dicaffeoylquinic acid and 0.106g 3,4-dicaffeoylquinic acid plus 0.690g 3-caffeoylquinic acid at a high purity of over 92.9%, 94.2% and 97.5%, respectively.


PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction.
IV hydration before and after cardiac catheterization is effective in preventing contrast-associated renal dysfunction for patients with mild-to-moderate renal insufficiency, but necessitates overnight hospital admission. We tested an outpatient oral precatheterization hydration strategy in comparison with overnight IV hydration. We randomized 36 patients with renal dysfunction (serum creatinine > or = 1.4 mg/dL) undergoing elective cardiac catheterization to receive either overnight IV hydration (0.45 normal saline solution at 75 mL/h for both 12 h precatheterization and postcatheterization; n = 18) or an outpatient hydration protocol including precatheterization oral hydration (1,000 mL clear liquid over 10 h) followed by 6 h of IV hydration (0.45 normal saline solution at 300 mL/h) beginning just before contrast exposure. The predefined primary end point was the maximal change in creatinine up to 48 h after cardiac catheterization. The inpatient and outpatient groups were well matched for baseline characteristics and contrast volume. By protocol design, the outpatient group received a greater volume of hydration, although the net volume changes were comparable in the two groups. The maximal changes in serum creatinine in the inpatient (0.21+/-0.38 mg/dL; 95% confidence interval [CI], 0.02 to 0.39 mg/dL) and outpatient groups (0.12+/-0.23 mg/dL; 95% CI, 0.01 to 0.24 mg/dL) were comparable (p = not significant). There were no instances of protocol intolerance. A hydration strategy compatible with outpatient cardiac catheterization is comparable to precatheterization and postcatheterization IV hydration in preventing contrast-associated changes in serum creatinine. Hospital admission for IV hydration is unnecessary before elective cardiac catheterization in the setting of mild-to-moderate renal dysfunction.


Arthroscopic management of elbow stiffness.
The elbow is particularly prone to stiffness. Loss of elbow motion is very limiting, and can be the result of trauma, primary osteoarthritis, heterotopic ossification and other conditions. Several exposures have been described for open elbow contracture release. Although a few decades ago elbow arthroscopy was considered only for diagnosis and removal of loose bodies, contemporary arthroscopic techniques allow successful management of the majority of conditions leading to elbow stiffness. Careful patient evaluation, use of advanced imaging studies, and acquisition of appropriate surgical skills are essential for the successful arthroscopic management of the stiff elbow. This expert opinion reviews some fundamentals of elbow stiffness as well as principles for the evaluation and arthroscopic management of the stiff elbow.


Draft Genome Sequence of Mariprofundus ferrooxydans Strain JV-1, Isolated from Loihi Seamount, Hawaii.
Mariprofundus ferrooxydans strain JV-1 was isolated in 1998 from Loihi Seamount, Hawaii. Here, we present the draft genome of strain JV-1, which shows similarity to other sequenced Mariprofundus isolates, strains PV-1 and M34.


MOSPD2 is an endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis.
Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER-anchored proteins, such as MOSPD2, that function as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER-lipid droplet (LD) contacts, thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein-membrane interaction. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.


Distal effects in a model of proximal axonopathy: 3,3'-iminodipropionitrile causes specific loss of neurofilaments in rat vestibular afferent endings.
3,3'-Iminodipropionitrile (IDPN) is a neurotoxic compound that causes both a proximal neurofilamentous axonopathy and loss of the vestibular sensory hair cells. We used immunocytochemistry to examine changes in the expression of heavy, medium and light neurofilament (NF-H, NF-M, NF-L) proteins in the afferent terminals of vestibular sensory epithelia after IDPN exposure in rats. Acute, repeated and subchronic IDPN exposure induced a marked loss of NFs in the nerve terminals. The effect of subchronic IDPN was specific, as demonstrated by comparison with the synaptic membrane protein SNAP-25. In addition, Western blot analysis indicated specific loss of NFs in the vestibular receptors. Ultrastructural analysis revealed that afferent endings in the vestibular receptors were significantly preserved in animals exposed to subchronic IDPN, but that these endings showed NF segregation from microtubules followed by NF loss. These effects were closely paralleled by ultrastructural changes in the nerve terminals, particularly in the afferent contacts with the hair cells, and preceded hair cell loss. Thus, distal NF loss and nerve terminal pathology occur in the IDPN model of proximal neurofilamentous axonopathy. Similar distal pathology could also occur in human diseases characterized by proximal axonal swellings, particularly in amyotrophic lateral sclerosis.


Substernal goiter.
The literature on substernal goiter from the seventeenth century to the present is reviewed. Substernal goiter may be defined as any thyroid enlargement that has its greater mass inferior to the thoracic inlet. Truly ectopic mediastinal goiters are rare, and most substernal goiters arise from and maintain some attachment to the cervical thyroid gland. Patients are generally in the fifth decade of life, and women predominate. Most patients experience dyspnea, stridor, or dysphagia, but 15 to 50% are asymptomatic; symptoms are often positional, and acute stridor may occur. Ten to twenty percent have no cervical mass or tracheal deviation on examination, and virtually all patients are euthyroid. Standard chest roentgenograms are often diagnostic, but computed tomographic or radioactive iodine scans may be helpful. The presence of a substernal goiter in all but the highest-risk patients is an indication for resection, usually through a cervical collar incision; an occasional patient will require sternotomy or thoracotomy. Death or major complications should be rare postoperatively. Substernal goiters are adenomatous and benign, but carcinoma occurs in 2 to 3% and may be occult. Patients should be followed closely, as these goiters may recur.


Cardiopulmonary and sedative effects of the peripheral α2-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs.
To evaluate the cardiopulmonary and sedative effects of the peripheral α(2)-adrenoceptor antagonist MK 0467 when administered IM or IV concurrently with medetomidine in dogs. 8 adult dogs. Dogs received 20 μg of medetomidine/kg, IM, alone or concurrently with MK 0467 (0.4 mg/kg, IM), and 10 μg of medetomidine/kg, IV, alone or concurrently with MK 0467 (0.2 mg/kg, IV), in a randomized crossover study. Sedation characteristics were scored and hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained before (time 0; baseline) and for 90 minutes after treatment. Heart rate (HR), mixed-venous partial pressure of oxygen (Pvo(2)), and cardiac index (CI) were significantly lower and mean arterial blood pressure (MAP), systemic vascular resistance (SVR), and oxygen extraction ratio (ER) were significantly higher after administration of medetomidine IM or IV, compared with baseline values. Administration of medetomidine and MK 0467 IM caused a significantly higher heart rate, CI, and Pvo(2) and significantly lower MAP, SVR, and ER for 60 to 90 minutes than did IM administration of medetomidine alone. Administration of medetomidine and MK 0467 IV caused a significantly higher CI and Pvo(2) and significantly lower MAP, SVR, and ER for 45 to 90 minutes than did IV administration of medetomidine alone. There was no significant difference in sedation scores among treatments. In dogs, MK 0467 administered concurrently with medetomidine IV or IM reduced the cardiovascular effects of medetomidine but had no detectable effect on sedation scores.


Does the high-intensity zone (HIZ) of lumbar Intervertebral discs always represent an annular fissure?
The aim of this study was to examine high-intensity zone (HIZ) characteristics on both T1- and T2-weighted sagittal magnetic resonance (MR) images, and to reveal their exact nature. Seventy-three patients with low back pain and HIZs (identified on T2-weighted images) were included. Patients, aged 25-80 years (mean 51), were divided into two groups: the 'single-HIZ' group exhibited HIZs only on T2-weighted images, while the 'dual-HIZ' group exhibited HIZs on both T2-weighted and T1-weighted images. Tissue corresponding to the HIZ was harvested from surgery for analysis. Eighty-two discs were studied, from 39 patients with single HIZs, 30 with dual HIZs, and four with both in the posterior annulus. HIZ volume, volume ratio, and signal intensity on T2-weighted images from the dual-HIZ group were significantly greater. Surgery was able to successfully restore patients' ability in both groups, while conservative treatments were less effective for patients with dual HIZs. Histology revealed outer annular fissures invaded by granulation tissue in the single-HIZ group. In dual-HIZ discs, Von Kossa staining and CT scans showed more calcified or ossified lesions (94.1 vs. 0 %, P<0.001), and chemical analysis showed significantly higher calcium content. HIZs on both T2- and T1-weighted images represent calcified tissue, possibly from a vertebral endplate. A new concept of dual HIZ should be defined. • Conventional definition of an HIZ refers to T2-weighted images only. • Dual HIZs have greater HIZ volume, volume ratio, and signal intensity. • HIZs on both T2- and T1-weighted images represent calcified tissue. • Conservative treatments are less likely to be effective for patients with dual HIZs.


Attention-deficit/hyperactivity disorder in children with hearing loss.
To evaluate rates of Attention-Deficit/Hyperactivity Disorder (AD/HD) diagnosis among pediatric patients with normal hearing (NH) and hearing loss (HL) with and without comorbidities. Retrospective cohort study of NH and HL patients following chart review of all pediatric patients with a history of tympanostomy tube placement treated at the Cleveland Clinic Foundation between 2019 and 2022. Patient demographic information, hearing status (type of HL, laterality, severity), and comorbidities including prematurity, genetic syndromes, disorders with neurological impairment, and autism spectrum disorder (ASD) were collected. Rate of AD/HD amongst HL and NH cohorts with and without comorbidities were compared using Fisher's exact test. Covariate-adjusted analysis was also completed (sex, current age, age at tube placement, and OSA). The primary outcome of interest was rates of AD/HD among children with NH and HL, and the secondary outcome of interest was the impact of comorbidities on rates of AD/HD diagnosis in these cohorts. Of the 919 screened patients between 2019 and 2022, there were 778 NH patients and 141 HL patients (80 bilateral, 61 unilateral). HL ranged from mild (n = 110) to moderate (n = 21) to severe/profound (n = 9). Overall, the rate of AD/HD was significantly higher in HL children (12.1% HL vs 3.6% NH, p < 0.001). Of the 919 patients, 157 had comorbidities. In children without comorbidities, HL children still had significantly higher rates of AD/HD compared to NH children (8.0% vs 1.9%, p = 0.02), but there was loss of significance after covariate adjustment (p = 0.72). The rate of AD/HD among children with HL (12.1%) is higher than the rate of AD/HD in NH children (3.6%), consistent with previous findings. After excluding patients with comorbidities and adjusting for covariates, there are similar rates of AD/HD between HL and NH patients. Given high rates of comorbidities and AD/HD in HL patients and potential for augmented developmental challenges, clinicians should have a low threshold to refer children with HL for neurocognitive testing, particularly those with any of the comorbidities or covariates described in this study.


Early Detection of Respiratory Diseases in Calves by Use of an Ear-Attached Accelerometer.
Accelerometers (ACL) can identify behavioral and activity changes in calves. In the present study, we examined the association between bovine respiratory disease (BRD) and behavioral changes detected by an ear-tag based ACL system in weaned dairy calves. Accelerometer data were analyzed from 7 d before to 1 d after clinical diagnosis of BRD. All calves in the study (n = 508) were checked daily by an adapted University of Wisconsin Calf Scoring System. Calves with a score ≥ 4 and fever for at least two consecutive days were categorized as diseased (DIS). The day of clinical diagnosis of BRD was defined as d 0. The data analysis showed a significant difference in high active times between DIS and healthy control calves (CON), with CON showing more high active times on every day, except d -3. Diseased calves showed significantly more inactive times on d -4, -2, and 0, as well as longer lying times on d -5, -2, and +1. These results indicate the potential of the ACL to detect BRD prior to a clinical diagnosis in group-housed calves. Furthermore, in this study, we described the 'normal' behavior in 428 clinically healthy weaned dairy calves obtained by the ACL system.


Dengzhan Shengmai capsule attenuates cardiac fibrosis in post-myocardial infarction rats by regulating LTBP2 and TGF-β1/Smad3 pathway.
Cardiac fibrosis contributes to myocardial remodeling after myocardial infarction (MI), which may facilitate the progression to end-stage heart failure. Dengzhan Shengmai capsule (DZSMC), a traditional Chinese formula derived from Shen-mai powder, has shown remarkable therapeutic effects against cardiovascular diseases. However, the effect of DZSMC on cardiac fibrosis and its potential mechanism are ill-defined. To evaluate the effects of DZSMC on cardiac fibrosis after myocardial infarction (MI) and investigate its underlying mechanism. In vivo, MI rat models were established by permanently ligation of left anterior descending coronary arteries (LAD) and then were intragastrically treated with DZSMC or captopril for 5 weeks. Ex vivo, an everted intestinal sac model was used to study the intestinal absorption components of DZSMC, which were further identified through an ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. In vitro, a myocardium fibrotic model was constructed by stimulating primary cardiac fibroblasts (CFs) with 1 μM Ang II. Subsequently, the absorbent solution of DZSMC from the intestinal sac was performed on the cell models to further elucidate its anti-fibrotic effects and underling mechanism. In vivo results showed that DZSMC significantly improved cardiac function and inhibited pathological myocardial fibrosis in post-MI rats in a dose dependent manner. Histological analysis and western blot results demonstrated that DZSMC treatment significantly reduced the expression of extracellular matrix (ECM)-related proteins, including LTBP2, TGF-βR1, Smad3 and pSmad3, in myocardial tissue of MI rats. Ex vivo results showed that 18 absorbed components were identified, mainly consisting of phenolic acids, flavonoids and lignans, which may be responsible for the anti-fibrotic effects. Further in vitro results validated that DZSMC attenuated myocardial fibrosis by suppressing the expression of LTBP2, TGF-β1 and pSmad3. DZSMC ameliorates cardiac function and alleviates cardiac fibrosis, which may be mediated by inhibition of CFs activation and reduction of excessive ECM deposition via LTBP2 and TGF-β1/Smad3 pathways.


Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.
To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available.


Low power interstitial Nd YAG laser photocoagulation: studies in a transplantable fibrosarcoma.
The effects of interstitial delivery of low power (1.2-2 W), long exposure (600-1200 s) Nd YAG laser light on a transplantable fibrosarcoma in rats have been studied. Three cohorts of ten animals were treated either by 1.2 W for 600 s, 1.2 W for 1200 s or 2 W for 600 s to each tumour nodule. An additional untreated cohort served as controls and a further cohort was treated by radical surgical resection. A partial response as evidenced by ulceration was seen in all laser-treated tumours. In the cohort treated by 2 W for 600 s there was complete loss of palpable tumour, and in five out of the ten animals there was no evidence of local recurrence following a prolonged period of observation. Three of these eventually died from metastatic disease and two were cured. There was a significant prolongation of survival in this cohort compared with the controls (median 70 days versus 30 days, P less than 0.05), but not in any of the other cohorts. Histological assessment of tumours 2 days after laser treatment showed a central area of degeneration with shrunken and densely staining nuclei and disorganized cytoplasm, the boundary between the degenerate zone and surrounding viable tumour being well defined. The technique might be used to induce necrosis of intrahepatic and other solid organ tumours.


Perspectives and mechanisms for targeting mitotic catastrophe in cancer treatment.
Mitotic catastrophe is distinct from other cell death modes due to unique nuclear alterations characterized as multi and/or micronucleation. Mitotic catastrophe is a common and virtually unavoidable consequence during cancer therapy. However, a comprehensive understanding of mitotic catastrophe remains lacking. Herein, we summarize the anticancer drugs that induce mitotic catastrophe, including microtubule-targeting agents, spindle assembly checkpoint kinase inhibitors, DNA damage agents and DNA damage response inhibitors. Based on the relationships between mitotic catastrophe and other cell death modes, we thoroughly evaluated the roles played by mitotic catastrophe in cancer treatment as well as its advantages and disadvantages. Some strategies for overcoming its shortcomings while fully utilizing its advantages are summarized and proposed in this review. We also review how mitotic catastrophe regulates cancer immunotherapy. These summarized findings suggest that the induction of mitotic catastrophe can serve as a promising new therapeutic approach for overcoming apoptosis resistance and strengthening cancer immunotherapy.


A single carboxy-terminal arginine determines the amino-terminal helix conformation of an alanine-based peptide.
Arginine is a stabilizing element in both thermophilic and low molecular weight proteins. Similarly Lys+-->Arg+ substitutions increase the helix content of designed helical peptides. Here we explore this 'arginine effect' by examining how Lys+-->Arg+ substitutions influence the 3(10)-helix-->alpha-helix equilibrium in the helical peptide Ac-(AAAAK)3A-NH2. The unsubstituted sequence contains a significant amount of 3(10)-helix, however, single Lys+-->Arg+ substitutions shift the peptide conformation toward alpha-helix in a position-dependent fashion. The single substitution closest to the carboxy terminus induces the largest conformational change at the helix amino terminus. These findings suggest that a single strategically-placed arginine can exert long range control on helix structure.


Protamine use during peripheral vascular surgery: a prospective randomized trial.
One hundred twenty patients undergoing aortic reconstruction (40), infrainguinal bypass (49), and carotid endarterectomy (31) were prospectively enrolled into a double-blind randomized trial to investigate the utility of routine heparin reversal with protamine. All patients underwent systemic heparinization with 90 U/kg body weight during operation and after revascularization were randomized to receive either protamine or saline solution for heparin reversal. Blood loss was measured throughout the surgical procedure, and indexes of coagulation and the requirement for blood and blood products were documented during operation and the first 24 hours after operation. Plasma heparin concentration, partial thromboplastin time, and activated clotting time were significantly higher (p < 0.05) in those receiving saline solution at 20 minutes and 1 hour after administration. Total surgical blood loss was not significantly different between study groups. No significant differences were found in blood product requirement, intravenous fluid administered, hematocrit, or wound hematomas between groups at 24 hours. In addition, no difference was seen in the surgeon's subjective intraoperative assessment of hemostasis after administration of either study drug. Furthermore, after study drug administration protamine was associated with a deleterious effect on subsequent intraoperative blood loss (318 +/- 33 ml vs 195 +/- 18 ml, p < 0.05). Although protamine effectively reverses heparin anticoagulation, its routine use after elective peripheral vascular surgical reconstruction does not appear to provide any clinical benefit.


Titanium for Orthopedic Applications: An Overview of Surface Modification to Improve Biocompatibility and Prevent Bacterial Biofilm Formation.
Titanium and its alloys have emerged as excellent candidates for use as orthopedic biomaterials. Nevertheless, there are often complications arising after implantation of orthopedic devices, most notably prosthetic joint infection and aseptic loosening. To ensure that implanted devices remain functional in situ, innovation in surface modification has attracted much attention in the effort to develop orthopedic materials with optimal characteristics at the biomaterial-tissue interface. This review will draw together metallurgy, surface engineering, biofilm microbiology, and biomaterial science. It will serve to appreciate why titanium and its alloys are frequently used orthopedic biomaterials and address some of the challenges facing these biomaterials currently, including the significant problem of device-associated infection. Finally, the authors shall consolidate and evaluate surface modification techniques employed to overcome some of these issues by offering a unique perspective as to the direction in which research is headed from a broad, interdisciplinary point of view.


Diet spectra and resource partitioning in the larvae and juveniles of three species and six cohorts of cyprinids from a subalpine lake.
Diet composition based on gut analyses was studied in larvae and juveniles belonging to six (out of eight) age groups (cohorts) of three species of cyprinids (Rutilus rutilus L., Leuciscus cephalus L., Scardinius erythrophthalmus L.) from a small meso-oligotrophic lake in Tyrol, Austria.A basic pattern of ontogenetic shifts of resource use is postulated for the first weeks after hatching, consisting of the sequence: phytoplankton-rotifers-crustaceans-chironomid larvae. However, there are several variations to this general theme.Diet overlap is of about the same magnitude between representatives of different species or different cohorts, and between members of schools belonging to one cohort. This points to the importance of random food selection in all larvae and juveniles during this phase of life.Prey size is a very poor predictor of food choice by young cyprinids, but there is greater similarity in diet between the larger juveniles than between the smaller larvae, irrespective of whether the fish compared represent different species, different cohorts or are members of homogeneous groups.The lack of correlation between prey size and predator size may be explained by assuming that out of a limited range of available prey size the fish always "try" to include in their diet also the largest items they are able to swallow. This would be a good strategy considering that growth rates are positively correlated with food size.One clearcut interspecific difference in resource use may be noted: The larvae of L. cephalus are distinguished from those of the other two species by the absence of rotifers and nauplii in their diet, and by their greater ability to handle both adult copepods and chironomid larvae.


Socioeconomic conditions and children's mental health and quality of life during the COVID-19 pandemic: An intersectional analysis.
Children and adolescents are highly vulnerable to the impact of sustained stressors during developmentally sensitive times. We investigated how demographic characteristics intersect with socioeconomic dimensions to shape the social patterning of quality of life and mental health in children and adolescents, two years into the COVID-19 pandemic. We used data from the prospective SEROCoV-KIDS cohort study of children and adolescents living in Geneva (Switzerland, 2022). We conducted an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy by nesting participants within 48 social strata defined by intersecting sex, age, immigrant background, parental education and financial hardship in Bayesian multilevel logistic models for poor health-related quality of life (HRQoL, measured with PedsQL) and mental health difficulties (measured with the Strengths and Difficulties Questionnaire). Among participants aged 2-17 years, 240/2096 (11.5%, 95%CI 10.1-12.9) had poor HRQoL and 105/2135 (4.9%, 95%CI 4.0-5.9) had mental health difficulties. The predicted proportion of poor HRQoL ranged from 3.4% for 6-11 years old Swiss girls with highly educated parents and no financial hardship to 34.6% for 12-17 years old non-Swiss girls with highly educated parents and financial hardship. Intersectional strata involving adolescents and financial hardship showed substantially worse HRQoL than their counterparts. Between-stratum variations in the predicted frequency of mental health difficulties were limited (range 4.4%-6.5%). We found considerable differences in adverse outcomes across social strata. Our results suggest that, post-pandemic, interventions to address social inequities in HRQoL should focus on specific intersectional strata involving adolescents and families experiencing financial hardship, while those aiming to improve mental health should target all children and adolescents.


Small Molecule NIR-II Dyes for Switchable Photoluminescence via Host -Guest Complexation and Supramolecular Assembly with Carbon Dots.
Small molecular NIR-II dyes are highly desirable for various biomedical applications. However, NIR-II probes are still limited due to the complex synthetic processes and inadequate availability of fluorescent core. Herein, the design and synthesis of three small molecular NIR-II dyes are reported. These dyes can be excited at 850-915 nm and emitted at 1280-1290 nm with a large stokes shift (≈375 nm). Experimental and computational results indicate a 2:1 preferable host-guest assembly between the cucurbit[8]uril (CB) and dye molecules. Interestingly, the dyes when self-assembled in presence of CB leads to the formation of nanocubes (≈200 nm) and exhibits marked enhancement in fluorescence emission intensity (Switch-On). However, the addition of red carbon dots (rCDots, ≈10 nm) quenches the fluorescence of these host-guest complexes (Switch-Off) providing flexibility in the user-defined tuning of photoluminescence. The turn-ON complex found to have comparable quantum yield to the commercially available near-infrared fluorophore, IR-26. The aqueous dispersibility, cellular and blood compatibility, and NIR-II bioimaging capability of the inclusion complexes is also explored. Thus, a switchable fluorescence behavior, driven by host-guest complexation and supramolecular self-assembly, is demonstrated here for three new NIR-II dyes.


Topographic localization of the motor branch of the median nerve.
To redefine the localization of the thenar branch (TB) of the median nerve in relation to the surface landmarks that are in routine use. The study was performed in 37 hands of 34 patients who had carpal tunnel release. All of the patients were women and the mean age was 50 years (range, 35-67 y). A radiologic marking technique was used to determine the localization of the TB, the middle finger radial side line, and Kaplan's cardinal line. The TB was marked by circumscribing with a soft radiopaque yarn and the surface landmark lines were shown by taping a K-wire to the hand for each line. An image-intensifier-printed image was obtained for each case and the distances between the markers of the TB and the wires were measured. The TB had a mean ulnar offset of 12.6 mm (range, 4.0-19.7 mm) from the middle finger radial side line and was located 4.4 mm (range, 0-9.5 mm) proximal to the cardinal line. During carpal tunnel release surgery the surgeon must pay more attention to the localization of the TB of the median nerve because it was found to be 12.6 mm more ulnar than the location described in the literature.


Cerebral white matter correlates of delay discounting in adolescents.
The adolescent brain undergoes extensive structural white matter (WM) changes. Adolescence is also a critical time period during which cognitive, emotional and social maturation occurs in transition into adulthood. Compared to adults, adolescents are generally more impulsive with increased risk-taking behaviors. The goal of this study is to examine whether adolescent impulsivity may be related to cerebral WM maturation. In 89 healthy adolescents, we assessed impulsivity using the delay discounting task, and MRI WM volumes in brain regions previously implicated in delay discounting behaviors. We found that smaller delay discounting AUC (area under the curve) was associated with larger WM volumes in orbitofrontal, dorsolateral and medial prefrontal cortices (PFC) and motor cortex. There were no significant effects of AUC on WM volumes within somatosensory brain regions. In our sample, younger age was significantly associated with greater WM volumes in orbitofrontal and dorsolateral PFC subregions. Even after accounting for age-related effects, preference for immediate rewards (or greater impulsivity) still correlated with larger WM volumes in prefrontal regions known to mediate cognitive control. Our findings lend further support to the notion that reduced brain WM maturity may limit the ability in adolescents to forgo immediate rewards leading to greater impulsivity.


Traumatic Orthopaedic Injury Is Not an Independent Risk Factor for High Postdischarge Opioid Consumption.
The purpose of this study was to quantify how opioid use in patients with traumatic injury compared with opioid use in patients undergoing elective arthroplasty. In a retrospective review, 235 adult trauma patients treated surgically for fracture were compared with 98 patients undergoing elective total hip or knee arthroplasty. Inpatient, discharge, and postdischarge opioid use were recorded in oral morphine equivalents (OMEs). There were no differences between trauma and elective arthroplasty patients for inpatient opioid use (OME/day: 70.2 vs. 67.3; P = 0.53), discharge prescription (OME: 542 vs. 594; P = 0.13), or postdischarge opioid use (OME: 986 vs. 1,147; P = 0.29). Postdischarge opioid use was positively correlated with Caucasian race, intensive care unit admission, baseline alcohol or opioid use, and higher discharge prescriptions (P < 0.0001; adjusted R2 = 0.127). Discharge prescription amount was the most significant predictor. Traumatic injury is not a predictor of high post-discharge opioid use. Demographic, social, and physician prescribing behaviors contribute to higher postdischarge opioid consumption.


From theory to practice: the inclusion of hospitalized children's families in painful procedures.
To understand nursing team professionals' strategies to include the family in painful procedures performed on hospitalized children. An exploratory-descriptive, qualitative study, carried out with nursing professionals. Data were collected through semi-structured interviews, guided by a script of topics, transcribed and submitted to thematic content analysis, in the light of Symbolic Interactionism, discussed considering the Family-Centered Care philosophy assumptions. Two central categories emerged, "Theoretical perspective: the family as a care agent in painful procedures" and "Practical perspective: experiences, challenges and strategies in painful procedures for family inclusion", with their respective subcategories. Nursing professionals have theoretical knowledge about family inclusion in painful procedures based on the assumptions: Family-Centered Care: dignity and respect; information sharing; joint participation; and family collaboration. However, knowledge is not applied in clinical practice; consequence of the interaction between beliefs and attitudes unfavorable to family presence.


[Is microembolism present and is it important element of COPD exacerbation?].
Pulmonary embolism often coexists with chronic obstructive pulmonary disease (COPD) and it is difficult to diagnose because of similar clinical symptoms. IN OUR STUDY: To try to answer the question if basic laboratory investigations reveal hypercoagulability and if so, if it has any impact on the course of COPD exacerbation. 28 patients (11F, 17M) with COPD exacerbation were enrolled to the study. Hematocrit, hemoglobin concentration, platelet count, the level of fibrinogen and D-dimers and arterial blood gases were investigated. Lung function was assessed by spirometry. Risk factors of pulmonary embolism, the number of COPD exacerbation in the past 12 months and the exacerbation triggering factors were established with the help of a questionnaire. On admission, abnormalities of the analysed parameters were found in 18 patients. This group was compared with the rest of the study group. There were no statistically significant differences in arterial blood gases and spirometrical values. There was a differences in the level of fibrinogen and D-domers. The data suggest that in some patients COPD may be accompanied by intravascular coagulation but the influence of this process on the course of the exacerbation is unclear. Further studies on hemostasis impairment and its impact on exacerbation in patients with COPD are required.


Optimizing door-to-balloon times for STEMI interventions - Results from the SINCERE database.
Primary angioplasty decreases mortality and improves long-term outcomes for patients with STEMI. To be most effective, it needs to be performed expediently, with door-to-balloon times (D2B) less than 90 min. From January 2005 to presently, 420 short D2B STEMI interventions were performed at 5 community hospitals by a single experienced operator creating the SINCERE (Single INdividual Community Experience REgistry) database. Median D2B time was 78 min, median procedure time (local anesthesia to recanalization) was 13 min; 85.2% of procedures had D2B time <90 min; 95% of the procedures were successful - relief of chest pain, >70% ST segment resolution, TIMI 3 flow and Myocardial Perfusion Grade 3. Primary PCI with high success rates and predictable short D2B times can be performed with standardized techniques in community hospitals.


Upregulation of TGF-beta1 expression may be necessary but is not sufficient for excessive scarring.
Transforming growth factor beta 1 (TGF-beta1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. In this study, we overexpressed TGF-beta1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta1 secretion was measured, as were the effects of TGF-beta1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted approximately 20 times the TGF-beta1 released by control cells, but only cells expressing mutant TGF-beta1 secreted it in the active form. Fibroblasts expressing the active TGF-beta1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta1 formed "keloid-like" nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta1 and prolong cell persistence.


Trans-ACPD selectively inhibits excitability of hippocampal CA1 neurones.
The selective agonist of metabotropic glutamate receptors, t-ACPD (trans-1-aminocyclopentyl-1,3-dicarboxylic acid) (100-250 microM), reversibly inhibited extracellularly recorded EPSP (excitatory postsynaptic potentials) in the CA1 layer of rat hippocampus. This effect was accompanied by depression of electrical excitability of CA1 neurons as revealed by their antidromic stimulation. The excitability of CA3 neurons remained uneffected. Peculiarly, excitatory postsynaptic currents recorded in voltage clamped, internally perfused CA1 cells remained unaltered. Selective depolarization of CA1 neurons may account for the phenomena described.


Comprehensive analysis of resistance mechanisms to EGFR-TKIs and establishment and validation of prognostic model.
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with lung adenocarcinoma (LUAD) harboring activating EGFR mutations. However, the emergence of drug resistance to EGFR-TKIs remains a critical obstacle for successful treatment and is associated with poor patient outcomes. The overarching objective of this study is to apply bioinformatics tools to gain insights into the mechanisms underlying resistance to EGFR-TKIs and develop a robust predictive model. The genes associated with gefitinib resistance in the LUAD cell Gene Expression Omnibus (GEO) database were identified using gene chip expression data. Functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed to comprehensively explore the mechanism of gefitinib resistance. Furthermore, a GRRG_score was constructed by integrating genes related to LUAD prognosis from The Cancer Genome Atlas (TCGA) database with the screened Gefitinib Resistant Related differentially expressed genes (GRRDEGs) using the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. Furthermore, we conducted an in-depth analysis of the tumor microenvironment (TME) features and their association with immune infiltration between different GRRG_score groups. A prognostic model for LUAD was developed based on the GRRG_score and validated. The HPA database was used to validate protein expression. The CTR-DB database was utilized to validate the results of drug therapy prediction based on the relevant genes. A total of 110 differentially expression genes were identified. Pathway enrichment analysis of DEGs showed that the differentially expressed genes were mainly enriched in Mucin type O-glycan biosynthesis, Cytokine-cytokine receptor interaction, Sphingolipid metabolism. Gene set enrichment analysis showed that biological processes strongly correlated with gefitinib resistance were cell proliferation and immune-related pathways, EPITHELIAL_MESENCHYMAL_TRANSITION, APICAL_SURFACE, and APICAL_JUNCTION were highly expressed in the drug-resistant group; KRAS_SIGNALING_DN, HYPOXIA, and HEDGEHOG_SIGNALING were highly expressed in the drug-resistant group. The GRRG_score was constructed based on the expression levels of 13 genes, including HSPA2, ATP8B3, SPOCK1, EIF6, NUP62CL, BCAR3, PCSK9, NT5E, FLNC, KRT8, FSCN1, ANGPTL4, and ID1. We further screened and validated two key genes, namely, NUP62CL and KRT8, which exhibited predictive value for both prognosis and drug resistance. Our study identified several novel GRRDEGs and provided insight into the underlying mechanisms of gefitinib resistance in LUAD. Our results have implications for developing more effective treatment strategies and prognostic models for LUAD patients.


PCR-based assays for the detection of monoclonality in non-Hodgkin's lymphoma: application to formalin-fixed, paraffin-embedded tissue and decalcified bone marrow samples.
In crucial cases the diagnosis of non-Hodgkin's lymphoma (NHL) still represents a challenge to the pathologist since morphological criteria do not always help to distinguish between reactive and malignant lymphoproliferations. Clonality assays are a useful supplement since monoclonal cell proliferation is strong evidence for malignancy. The polymerase chain reaction (PCR) can be utilized to establish the clonal origin of B- or T-cell lymphocyte populations by amplification of rearranged immunoglobulin and T-cell receptor (TCR) genes. In the present study DNA was isolated from a variety of neoplastic and nonneoplastic formalin-fixed, paraffin-embedded lymph nodes (n = 62), cutaneous tissue (n = 9), samples of miscellaneous origin (n = 11), and reported here for the first time, decalcified bone marrow samples (n = 35). These samples were submitted to PCR-based assays directed against the immunoglobulin heavy-chain (IgH), immunoglobulin kappa light-chain (IgL kappa), and TCR gamma chain genes. The impact of various decalcifying agents on the ability to amplify DNA was investigated by PCR-based amplification of a single copy gene. Buffered and nonbuffered EDTA was found not to impede amplification of DNA fragments up to 300 bp in length. In lymph node and cutaneous specimens monoclonality was detected in 83% of B-NHL cases using a seminested PCR approach for the amplification of IgH, whereas the same approach gave rise to monoclonal bands in 80% of bone marrow samples. The subsequent amplification of IgL kappa helped to raise the sensitivity of detection to 94%. Monoclonality was detected in seven of nine T-cell NHLs by amplification of TCR gamma.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of genetic defects in the apelin-AGTRL1 system with myocardial infarction risk in Han Chinese.
We aimed to test the hypothesis that apelin (APLN) and its receptor AGTRL1 (APLNR) genes may contribute to the pathogenesis of myocardial infarction in Han Chinese. This is a hospital-based, case-control association study, involving 1067 patients with myocardial infarction and 942 healthy controls. Myocardial infarction is diagnosed by electrocardiogram or anatomopathological examination. Eight polymorphisms in APLN gene and 5 in APLNR gene were genotyped using the TaqMan assay. Risk was summarized as odds ratio (OR) and 95% confidence interval (CI). In males, rs56204867-G allele (adjusted OR, 95% CI, p: 0.21, 0.08-0.55, 0.002) and rs2235309-T allele (0.60, 0.42-0.84, 0.004) was associated with a significantly reduced risk of myocardial infarction, and the mutations of rs2235310 was associated with an increased risk (1.41, 1.06-2.52, 0.021), as well as for rs948847-GG genotype (1.85, 1.23-2.91, 0.007). In females, the presence of rs56204867-AG and -GG genotypes was significantly associated with 44% and 50% reduced risk (0.56 and 0.50, 0.40-8.04 and 0.29-0.86, 0.007 and 0.036), respectively; for rs2235310, CC genotype was associated with 72% increased risk (1.72, 1.09-3.22, 0.016), and the odds of myocardial infarction was 3.47 for rs9943582-TT genotype (95% CI: 1.53-7.57, 0.009). The gender-specific association of APLN and APLNR genes with myocardial infarction was reinforced by further linkage and haplotype analyses. Finally, nomograms based on significant polymorphisms are satisfactory, with the C-indexes over 80% for both genders. Taken together, our findings indicate that APLN and APLNR genes are potential candidates in the pathogenesis of myocardial infarction in Han Chinese, and importantly their contribution is gender-dependent.


A microporous scandium terephthalate, Sc2(O2CC6H4CO2)3, with high thermal stability.
A scandium terephthalate with isolated ScO6 octahedra and fully-linked carboxylate groups is prepared hydrothermally and possesses a novel hybrid framework structure with high thermal stability and a pore volume for N2 adsorption of 0.26 cm(3) g(-1) at 77 K.


Twenty-four-hour growth hormone profiling in the assessment of acromegaly.
Recent guidelines recommend insulin-like growth factor (IGF-1), random growth hormone (GH) and nadir GH on an oral glucose tolerance test (OGTT) for assessment of acromegaly. At this Regional Centre, the 24-hour GH profile has also been used. We evaluated 57 GH profiles from 34 patients from 2008 to 2012. Samples were drawn every 2 hour and matched with 0800 GH, nadir GH after OGTT and IGF-1. Correlations between the mean 13-point profiles and mean 5-point profile, OGTT nadir and 0800 GH were as follows: r = .99, .99 and .90, respectively (P < .01 for all). The correlation between the mean 13-point profiles and IGF-1 was r = .32 P = .02.Of 5 patients with very high 0800 GH preoperatively (≥20 μg/L), mean 13-point GH reduced by 88%-99% postoperatively. IGF-1 did not normalize in these patients, and all required extra treatment. Preoperatively, all patients had concordant 0800 GH and IGF-1. Postoperatively, 6 patients had 0800 GH <1 μg/L and high IGF-1; only 2 of these had a 13-point mean >1 μg/L, but 5 required further treatment. Growth hormone profiling is not necessary for assessing the majority of patients with acromegaly if there is confidence in the local IGF-1 assay. When undertaken, a 5-point profile is adequate. In patients with very high 0800 GH, 24-hour profiling was useful in demonstrating partial therapeutic success but did not alter management. Further work is needed to explore the possible role of GH profiling in stratifying patients with discordant IGF-1 and GH results.


Coat color inheritance in American mink.
Understanding the genetic mechanisms underlying coat color inheritance has always been intriguing irrespective of the animal species including American mink (Neogale vison). The study of color inheritance in American mink is imperative since fur color is a deterministic factor for the success of mink industry. However, there have been no studies during the past few decades using in-depth pedigree for analyzing the inheritance pattern of colors in American mink. In this study, we analyzed the pedigree of 23,282 mink extending up to 16 generations. All animals that were raised at the Canadian Center for Fur Animal Research (CCFAR) from 2003 to 2021 were used in this study. We utilized the Mendelian ratio and Chi-square test to investigate the inheritance of Dark (9,100), Pastel (5,161), Demi (4,312), and Mahogany (3,358) colors in American mink. The Mendelian inheritance ratios of 1:1 and 3:1 indicated heterozygous allelic pairs responsible for all studied colors. Mating sire and dam of the same color resulted in the production of offspring with the same color most of the time. Overall, the results suggested that color inheritance was complex and subjected to a high degree of diversity in American mink as the genes responsible for all four colors were found to be heterozygous.


Increasing resiliency: A focus for clinical conferencing / group debriefing in nursing education.
High attrition rates of novice nurses partly reflect how well nursing education programs are preparing students for the physical, mental, and emotional demands of nursing practice. Resilience is a positive adaptation to stress that improves the ability of nurses to effectively navigate complex challenges, and adversity without losing personal balance and the desire to stay in the profession. Resiliency is both a process and an outcome that is modifiable through education and practice. Clinical conferences, or group debriefings, are an underdeveloped component of nursing education that provide timely opportunities to focus on building aspects of resiliency and prepare students for a sustainable transition into practice.


Expression of transforming growth factor beta isoforms and their roles in tendon healing.
Transforming growth factor beta (TGF-beta) plays active roles in tendon healing. However, the differential effects of TGF-beta isoforms on tendon healing have not been investigated. In cultured tendon fibroblasts, we tested the effects of TGF-beta1, beta2, and beta3 on the mRNA levels of COL1A1 and COL3A1 by quantitative real-time polymerase chain reaction. We also investigated the expression of TGF-beta isoforms, TGF-beta receptors, procollagen Type I and Type III in a rat model of tendon healing. We found that TGF-beta3 exhibited the highest potency in stimulating COL1A1 and COL3A1. TGF-beta1 exerted antagonistic effects to TGF-beta2 and beta3. All TGF-beta isoforms and procollagen Type I were confined to the edges of the healing tendon at day 28 postinjury. Our results indicated that interaction of TGF-beta isoforms exist in the regulation of collagen synthesis in tendon fibroblasts. Their effects may be further complicated by uneven spatial distribution of TGF-beta and TGF-beta receptors in healing tendons.


Prevalence and determinants of refractive error and related ocular morbidities among Saudi adolescence population in Riyadh, Saudi Arabia.
The purpose of this study was to determine the magnitude and determinants of refractive error (RE) and related ocular morbidities among preparatory and secondary Saudi students in Riyadh. This study was conducted in 2017-2018 at preparatory (12-14 years) and secondary (15-18 years) schools. A "Spot Screener" was used to determine if the child passed or failed a refraction test. Fail test meant RE ≥ ± 0.50 D. Data were collected on refractive status in each eye, anisometropia, and strabismus. The type of RE was estimated and analysis was performed for an association to gender, age, and education levels. The use of spectacle while screening defined the compliance of spectacle wear. The study sample was comprised of 708 Saudi students. There were 59.5% of boys. The prevalence of RE was 43.6% (95% confidence interval [CI]: 40.0, 47.3). The prevalence of RE in preparatory and secondary students was 44.5% and 43.2%, respectively. The proportion of myopia (≥ -0.5 D) and hyperopia (≥ +0.5 D) among students with RE was 82.2% and 17.8%, respectively. Family history of RE was positively associated to RE in students (odds ratio: 1.8 [95% CI: 1.3, 2.5]). The current screening initiative identified 45 (6.4%) new cases of RE who required spectacles. The compliance rate for using visual aid among students with RE was 74.6%. The prevalence of anisometropia and strabismus was 3.0% and 4.1%, respectively. A high proportion of Saudi adolescence in Riyadh have RE. Periodic ophthalmic assessment and refractive services are recommended as part of school health screening initiatives.


Reproductive ecology of the coral Astrangia lajollaensis: Sexual and asexual patterns in a kelp forest habitat.
The temperate water coral, Astrangia lajollaensis broadcasts a large number of small eggs. It propagates asexually by budding and regeneration, and forms two-dimensional colonies on hard rocky substrate. Sexual recruitment was absent and asexual propagation was slow during this study. I conclude that budding at the borders of colonies is not slowed by the presence of adjacent space competitors nor is it enhanced by their absence. A model of colony growth is presented and ages of colonies at the study site are predicted. The ecological roles of sexual and asexual reproduction in the kelp forest habitat of A. lajollaensis are discussed. The occurrence of A. lajollaensis population at a study site in Pacific Grove, California extends the northern range for the species. The nearest conspecifics are 200-300 km to the south. Establishment of this northern population probably occurred by settlement of planktonic planulae but the long-term persistence of the population may be possible only by the strategy of asexual propagation and regeneration.


[Energy expenditure in workers who install plastic and metal pipes for water supplies and sewage].
The mounting of plastic and metallic water and sewage tubes is the type of work that requires a very high energy expenditure: 45 kJ/min, 9631 kJ for eight working hours and about 17,000 kJ for a working day. Working conditions involve a very demanding working posture, carrying of heavy loads and poor weather conditions. The work is considered to be very heavy physical work.


A multicentre comparison of the dosimetric impact of inter- and intra-fractional anatomical variations in fractionated cervix cancer brachytherapy.
To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes. DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1-6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D(2cm(3)) for the bladder, rectum and sigmoid and D(90) for HR CTV were recorded. For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D(2cm(3)), were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D(2cm(3)) variations (mean±1SD) were 0.6±19.5%, 4.1±21.7% and 1.6±26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be -1.1±13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3-7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4-8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV. Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery.


Optimization of the Maillard reaction of xylose with cysteine for modulating aroma compound formation in fermented tilapia fish head hydrolysate using response surface methodology.
Aroma defects limit the application of fish protein hydrolysates as flavourings. This study aimed to develop a flavour concentrate from fermented tilapia fish head hydrolysate bymaximising the Maillard reaction production of meaty and roasted aroma associated compounds. We studied the optimal conditions of the Maillard reaction of xylose with cysteine to form meat-like odorants using response surface methodology. A 3-factored and 3-leveled Box Behnken design was employed, where the independent variables were cysteine concentration (A, w/v, %), heating temperature (B, °C) and heating time (C, min). 2-Methyl-3-furanthiol and 2-furfurylthiol were used as response factors. The optimal conditions were obtained as follows: A, 0.80%; B, 183.80 °C; C, 89.34 min. Compared with the controls, Maillard reaction products enriched the meaty and roasted aroma associated compounds in the treated hydrolysate. In conclusion, the treated tilapia fish head hydrolysate may be used as a base in development of new fish-based flavourings.


Modeling noisy time-series data of crime with stochastic differential equations.
We develop and calibrate stochastic continuous models that capture crime dynamics in the city of Valencia, Spain. From the emergency phone, data corresponding to three crime events, aggressions, stealing and women alarms, are available from the year 2010 until 2020. As the resulting time series, with monthly counts, are highly noisy, we decompose them into trend and seasonality parts. The former is modeled by geometric Brownian motions, both uncorrelated and correlated, and the latter is accommodated by randomly perturbed sine-cosine waves. Albeit simple, the models exhibit high ability to simulate the real data and show promising for crimes-interaction identification and short-term predictive policing.


Genital HPV infection and related lesions in men.
Human papillomavirus (HPV) is highly prevalent in men and there is an interest in further understanding the relationship between HPV infection and disease in men, including the development of genital warts, penile intraepithelial neoplasia and invasive penile carcinomas. Genital warts are caused by HPV 6/11 and are the most common clinical manifestation of HPV in men. Though they are benign and not associated with mortality, they are a source of psychosocial distress and physical discomfort. HPV infection can also develop into invasive penile carcinoma which is associated with morbidity and mortality. Approximately 40% of invasive penile carcinomas are attributable to HPV with HPV 16, 18, and 6/11 being the genotypes most commonly detected in penile tumors. Penile carcinomas of the basaloid and warty histologic subtypes are most likely to test positive for HPV. In addition to HPV infection, the risk factors most strongly associated with penile cancer are lack of neonatal circumcision, phimosis (the inability of uncircumcised men to fully retract the foreskin), and anogenital warts. Male vaccination with the quadrivalent HPV vaccine that protects against HPV 6/11/16/18 has been shown to significantly reduce HPV-associated anogenital infection and disease in men. If the quadrivalent vaccine is successfully disseminated to large segments of the young male population, there is the potential for substantial reduction in genital HPV infection and related lesions in men.


Deriving the indications for laparoscopic appendectomy from a comparison of the outcomes of laparoscopic and open appendectomy.
Indications for laparoscopic appendectomy (LA) remain controversial and poorly defined. We sought to identify indications for LA through a comparison of LA and open appendectomies (OA). We reviewed demographics, coexisting medical conditions, radiology and pathology data, hospital course, and complications from charts on all LA patients and a comparison group of OA done from 1991 to 1998. The following were significantly associated with LA: female sex, higher mean body mass index (BMI), coexisting medical problems, private insurance, and daytime surgery. The OA group was significantly more likely to have: a radiology report suggesting the diagnosis of acute appendicitis, perforation of the appendix, intensive care unit admission, and complications in their hospital course. Forty-one percent of the LA patients did not have appendicitis, compared with 20% of the OA patients. Daytime surgery, women, private insurance, coexisting medical problems, prior abdominal surgery, higher BMI, and less severe disease appear to be used by surgeons as indicators for LA. The threshold for surgical exploration appears to be lower for LA.


Ethical arguments for and against sperm sorting for non-medical sex selection: a review.
Much has been written about the ethics of sex selection. This article thoroughly explores the ethical arguments put forth in the literature both for and against non-medical sex selection using sperm sorting. While most of these arguments come from philosophers, feminist scholars, social scientists and members of the healthcare community, they are often echoed in empirical studies that have explored community values. This review is timely because the first efficacious method for sex selection via sperm sorting, MicroSort, is currently in clinical trials and moving closer to FDA approval for marketing in the USA. While the clinical trials are currently focused on the use of MicroSort to avoid X-linked genetic diseases, MicroSort can also be used to satisfy parental preferences.


The main organizational changes in dermatological practice in the Lombardy Region, Italy, from 2001 to 2009.
Changes in financing health care delivery, including the adoption of diagnosis-related groups (DRG), has deeply influenced dermatological practice across Europe. To define the current status of dermatological care in the Lombardy Region, Italy, and compare the status of 2009 to that of 2001. Data were analysed from the annual reports of the Healthcare General Department of the Lombardy Region; legislative and administrative data were taken into consideration. Beds for inpatients in Dermatologic Wards decreased from 251.7 (2001) to 49.07 (2009). In 2009, a large proportion of inpatients with skin diseases were admitted to non-dermatological departments. Beds for day-hospital activities increased from 55.9 (2001) to 61.0 (2009), and the proportion of admissions for surgical purposes progressively increased. In addition, the complexity and quality of surgical procedures increased, in view of the need to justify a day-hospital admission. The total number of services for outpatients increased from 1,090,052 (2001) to 1,503,692 (2009); in addition, the weighted numbers (an indicator of complexity) increased from 2,117,000 (2001) to 3,644,032 (2009). The number of dermatologists with unlimited contracts decreased, and the number of low paid scholarship recipients and external consultants increased. Three of six medical faculties currently do not have a university department of Dermatology. Over the last decade, the number of patients hospitalized in Dermatological Departments has declined; moreover, patients hospitalized with dermatological disorders have been increasingly admitted to wards with a non-dermatologist attending physician.


Stereotactic Ablative Radiotherapy for ≥T1b Primary Renal Cell Carcinoma: A Report From the International Radiosurgery Oncology Consortium for Kidney (IROCK).
Patients with larger (T1b, >4 cm) renal cell carcinoma (RCC) not suitable for surgery have few treatment options because thermal ablation is less effective in this setting. We hypothesize that SABR represents an effective, safe, and nephron-sparing alternative for large RCC. Individual patient data from 9 institutions in Germany, Australia, USA, Canada, and Japan were pooled. Patients with T1a tumors, M1 disease, and/or upper tract urothelial carcinoma were excluded. Demographics, treatment, oncologic, and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes. Ninety-five patients were included. Median follow-up was 2.7 years. Median age was 76 years, median tumor diameter was 4.9 cm, and 81.1% had Eastern Cooperative Oncology Group performance status of 0 to 1 (or Karnofsky performance status ≥70%). In patients for whom operability details were reported, 77.6% were defined as inoperable as determined by the referring urologist. Mean baseline estimated glomerular filtration rate (eGFR) was 57.2 mL/min (mild-to-moderate dysfunction), with 30% of the cohort having moderate-to-severe dysfunction (eGFR <45mL/min). After SABR, eGFR decreased by 7.9 mL/min. Three patients (3.2%) required dialysis. Thirty-eight patients (40%) had a grade 1 to 2 toxicity. No grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at 2 years and 91.4%, 69.2%, 64.9% at 4 years, respectively. Local, distant, and any failure at 4 years were 2.9%, 11.1%, and 12.1% (cumulative incidence function with death as competing event). On multivariable analysis, increasing tumor size was associated with inferior cancer-specific survival (hazard ratio per 1 cm increase: 1.30; P < .001). SABR for larger RCC in this older, largely medically inoperable cohort, demonstrated efficacy and tolerability and had modest impact on renal function. SABR appears to be a viable treatment option in this patient population.


A mechanistic study on the nuclease activities of some hydroxystilbenes.
The nuclease activities of a series of hydroxystilbeneoids have been studied so as to establish a structure-activity correlation and deduce the mechanistic pathway of the process. Although the test compounds could nick plasmid DNA, only three of these including resveratrol produced double strand breaks in DNA. Amongst these new stilbenes, compound 2e containing a partially methylated catechol and a C-4 hydroxy moieties was equally potent as resveratrol. The activities of the unprotected catechol-derivatives were less than those of the resorcinol-derivatives, which were, however, compensated by partial methylation of the former. The presence of Cu(2+) and O(2) and the participation of a Cu(+)-oxo intermediate were obligatory in the process which did not require addition of any external reducing agent. Overall, the differential nuclease activities of the compounds could be explained primarily with their superoxide anion generation abilities, and to a lesser extent with their DNA binding and Cu(2+) reducing capacities. The amount of superoxide anion produced by the compounds depended strongly on their Cu(+)-complexation abilities, which again, was decided by the pattern and nature of the oxygenated substituents in the aromatic rings.