Identification of inflammatory biomarkers for pediatric malarial anemia severity using novel statistical methods.
Areas where Plasmodium falciparum transmission is holoendemic are characterized by high rates of pediatric severe malarial anemia (SMA) and associated mortality. Although the etiology of SMA is complex and multifactorial, perturbations in inflammatory mediator production play an important role in the pathogenic process. As such, the current study focused on identification of inflammatory biomarkers in children with malarial anemia. Febrile children (3 to 30 months of age) presenting at Siaya District Hospital in western Kenya underwent a complete clinical and hematological evaluation. Children with falciparum malaria and no additional identifiable anemia-promoting coinfections were stratified into three groups: uncomplicated malaria (hemoglobin [Hb] levels of ≥11.0 g/dl; n = 31), non-SMA (Hb levels of 6.0 to 10.9 g/dl; n = 37), and SMA (Hb levels of <6.0 g/dl; n = 80). A Luminex hu25-plex array was used to determine potential biomarkers (i.e., interleukin 1β [IL-1β], IL-1 receptor antagonist [IL-1Ra], IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, tumor necrosis factor alpha [TNF-α], alpha interferon [IFN-α], IFN-γ, granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage inflammatory protein 1 alpha [MIP-1α], MIP-1β, IFN-inducible protein of 10 kDa [IP-10], monokine induced by IFN-γ [MIG], eotaxin, RANTES, and monocyte chemoattractant protein 1 [MCP-1]) in samples obtained prior to any treatment interventions. To determine the strongest biomarkers of anemia, a parsimonious set of predictor variables for Hb was generated by least-angle regression (LAR) analysis, controlling for the confounding effects of age, gender, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and sickle cell trait, followed by multiple linear regression analyses. IL-12p70 and IFN-γ emerged as positive predictors of Hb, while IL-2R, IL-13, and eotaxin were negatively associated with Hb. The results presented here demonstrate that the IL-12p70/IFN-γ pathway represents a set of biomarkers that predicts elevated Hb levels in children with falciparum malaria, while activation of the IL-13/eotaxin pathway favors more profound anemia.


Advanced glycation: implications in tissue damage and disease.
Advanced glycation end products (AGEs) are formed from the non-enzymatic reaction between reducing sugars and amine residues on proteins, lipoproteins or nucleic acids. AGEs are found on long-lived proteins and their tissue accumulation is associated with normal ageing. The formation of AGEs can be accelerated in certain pathological conditions such as diabetes where hyperglycaemia is present. AGE modification of proteins can lead to alterations of normal function by binding to intracellular or extracellular cell components, or through receptor binding. This consequently can initiate a cascade of events, which includes the activation of signal transduction pathways, which activate inflammatory responses causing tissue damage. Such tissue injury contributes to the development of microvascular complications and is of particular relevance in diabetes where interventions to reduce the accumulation of AGEs is desirable.


Long-term potentiation phenomena in the rat limbic forebrain.
Long-term potentiation (LTP) phenomena were investigated in several limbic forebrain pathways. With the possible exception of the lateral olfactory tract, LTP could be produced in all pathways tested. LTP effects tended to increase as the stimulation site moved caudally along the pyriform lobe. The largest effects were produced by stimulation of pathways into and out of the hippocampus. Target sites also differed, with the hippocampal sites showing the strongest and longest lasting LTP effects. The time course of LTP appeared to be best fitted by the sum of two exponential curves with time constants of about 1.5 h and 5 days respectively. We also looked at the potentiation effects produced by repeated epileptogenic (kindling) stimulations, and the effect of this potentiation on subsequent tests of short-term and long-term potentiation. In most cases, the short-term effects, and the first component of the LTP effect, were still intact after kindling. The longest lasting component, however, could no longer be produced with either amygdala or perforant path stimulation. This result indicates that the potentiation produced by kindling may be based upon the same mechanism as the LTP effect.


Attenuation of equine influenza viruses through truncations of the NS1 protein.
Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.


Effect of Citrullus colocynthis Extract on Glycated Hemoglobin Formation (In Vitro).
Diabetes mellitus (DM) is typically a disorder of carbohydrate, fat, and protein metabolism. It develops due to a lack of or loss associated with insulin and/or resistance to insulin. Regarding complications of chemical substance use, drugs with few complications and high-reliability tannins are needed. This study aimed to determine the effect and mechanism of action of Citrullus colocynthis extract on the formation of glycated hemoglobin (HbA1c). A solution containing hemoglobin and glucose was incubated for 1, 2, 3, 4, 30, and 60 days by adding Citrullus colocynthis extract or glutathione. Quantitative measurement of HbA1c was performed using ion-exchange chromatography. Data were analyzed using ANOVA and two-way repeated measures test. A p<0.05 was considered statistically significant. The Citrullus colocynthis extract in hyperglycemic conditions and with increasing time reduced the formation of HbA1c and thus inhibited the production of glycated proteins. By increasing the time and after initiation of reaction of extract concentrations (0, 0.1, 0.3, 0.5, and 1 g/dL), presently, there was a significant decrease in the formation of HbA1C compared to those in the control group (p<0.05). The decrease in glycation has been dose dependent. Therefore, Citrullus colocynthis could directly reduce the formation of HbA1c.


Research Gaps in Diet and Nutrition in Inflammatory Bowel Disease. A Topical Review by D-ECCO Working Group [Dietitians of ECCO].
Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD.


Including adolescents of childbearing potential in clinical trials with possible exposure to teratogenic medication: a challenge for paediatricians and researchers.
The issue of contraception and pregnancy tests among minor adolescent women participating in clinical trials, whether healthy or suffering from a disease, represents a challenging issue for paediatricians and researchers, given the potential harmful effect of various therapeutic procedures being tested. First, they need to gauge at what age or developmental stage they need to impose pregnancy tests and contraception. Second, if the adolescent denies any sexual activity, it may be ethically questionable to impose such procedures. Third, these professionals must deal with the issue of confidentiality, taking into account the fact that some adolescents engage in penetrative sexual intercourse without their parents or caregivers knowing. Fourth, in such cases, they must assess the extent to which a minor adolescent can be considered as competent (capable of making autonomous decisions) and deserves privacy and confidentiality. There is indeed a legal obligation for the provider to check that sexual experiences and intercourse take place within a safe relationship. Fifth, if the prescription of contraception is warranted, they have to decide who should assist the adolescent in choosing the method. Finally, with the occurrence of a positive pregnancy test, they may face the rare instance of a competent minor adolescent who refuses to inform her parents. This article has been developed by a group of experts under the auspices of swissethics, the Swiss Association of Research Ethics Committees and SwissPedNet, the umbrella organisation that coordinates the paediatric research in Switzerland. The paper reviews how to address practical and ethical questions regarding minor adolescents of childbearing potential enrolled in a clinical trial that may involve teratogenic medication and offers a series of concrete advice and tools for dealing with problematic situations. Most paediatric protocols stipulate that adolescents included in clinical trials involving potentially teratogenic drugs should undergo pregnancy tests and use contraception. The circumstances in which such requirements are undertaken, however, has not been sufficiently addressed. The recommendations presented in this article will assist researchers in assessing which circumstances apply when considering minor adolescents as individuals with childbearing potentials. It also offers concrete suggestions for tackling such situations.


Isolated echogenic foci in the fetal heart as marker of chromosomal abnormality.
To assess the effect of echogenic foci in the fetal heart on the risk for Down's syndrome. Prospective evaluation of fetal echocardiograms at a fetal cardiology referral center and systematic postnatal follow-up. A relative risk was calculated from the prevalence of echogenic foci in fetuses subsequently demonstrated to have trisomy 21 divided by that in normal fetuses. For a subgroup of 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the expected number of trisomy 21 fetuses calculated from maternal age risks was compared with the observed number to derive a relative risk for isolated echogenic foci. Echogenic foci occurred in 905 of 6904 fetuses scanned, but after excluding those referred specifically because of an echogenic focus and those with heart defects, the incidence was 9.5%. Overall, echogenic foci were more frequent in fetuses with trisomy 21 than those without by a factor of 2.93. For the 548 fetuses with echogenic foci but otherwise normal detailed anomaly scans, the actual number of trisomy 21 fetuses exceeded that expected on the basis of maternal age risks by a factor of 5.54. Combination with data from several previous studies suggests a consensus relative risk of about 3.0. Echogenic foci are associated with increased risk of trisomy 21 even when present as an isolated finding. Their significance in an individual should be interpreted in the light of prior risk assessment based on maternal age and results of any first-trimester screening tests. We suggest that the prior risk is increased by a factor of 3.0.


Factor analysis of the Swedish version of the Dark Triad Dirty Dozen.
The aim of this study was to test the proposed three-factor structure of the Swedish version of the Dark Triad Dirty Dozen measure. A confirmatory factor analysis showed mixed evidence for model fit. In contrast to expectations, men did not score significantly higher than women in Machiavellianism and narcissism. Nevertheless, men scored higher than women in psychopathy.


LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5.
Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR-family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes.


Lifetime marijuana use in relation to insulin resistance in lean, overweight, and obese US adults.
Obese individuals are more likely to show insulin resistance (IR). However, limited population studies on marijuana use with markers of IR have yielded mixed results. The aim of this study was to examine the association of marijuana use with IR in US adults with different body mass index (BMI) status. Data from the 2009 to 2016 National Health and Nutrition Examination Survey (NHANES) were abstracted. Minimal lifetime marijuana use was estimated using the duration of regular exposure and frequency of use. The association of marijuana use with both fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) was determined in lean, overweight, and obese individuals separately using generalized linear models. Interview weight years of data were used to account for the unequal probability of sampling and non-response. Of all 129 509 adults aged 18 to 59 years, 50.3% were women. In current obese marijuana consumers, mean FINS in those with less than four uses per month was 52% (95% confidence interval [CI] 19%-71%) lower than in never users. In former obese consumers with eight or more uses per month and who stopped marijuana use <12 months ago, mean FINS was 47% (95% CI 18%-66%) lower than in never users. Mean FINS in those who quit marijuana 12 to 119 and 120 months and more prior the survey was 36% (95% CI 7%-57%) and 36% (95% CI 10%-54%) lower, respectively. Marijuana use is associated with lower FINS and HOMA-IR in obese but not non-obese adults, even at low frequency of less than four uses per month. Former marijuana consumers with high lifetime use had significantly lower FINS levels that persisted, independent of the duration of time since last use.


Risk of serious adverse events associated with non-steroidal anti-inflammatory drugs in orthopaedic surgery. A protocol for a systematic review.
Postoperative pain is a common condition following orthopaedic surgeries and causes prolonged hospitalisation, delayed rehabilitation and hamper the quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics and anti-inflammatory mediators in the treatment of postoperative pain. The association of NSAIDs with serious adverse events may however keep some clinicians and clinical decision makers from using NSAIDs perioperatively. The evidence regarding the risks of serious adverse events following perioperative use of NSAIDs in orthopaedic surgery is sparse and needs to be assessed in a systematic review. This is a protocol for a systematic review that aims to identify the risks of serious adverse events from perioperative use of NSAIDs in orthopaedic patients. Our methodology is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the eight-step assessment procedure suggested by Jakobsen and colleagues. We wish to assess if NSAIDs versus placebo, usual care or no intervention, will influence the risks of serious adverse events in patients undergoing orthopaedic surgery. We will include all randomised trials assessing the use of NSAIDs perioperatively. To identify trials we will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cochrane Central Register, Science Citation Index Expanded on Web of Science and BIOSIS. Two authors will screen the literature and extract data. We will use the 'Risk of Bias 2 tool' to assess trials. Extracted data will be analysed using RStudio and Trial Sequential Analysis. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes. We will assess the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). This systematic review can potentially aid clinicians and clinical decision makers in the use of NSAIDs for treatment of postoperative pain following orthopaedic surgeries.


Evaluation and treatment of community-acquired Staphylococcus aureus infections in term and late-preterm previously healthy neonates.
We describe the evaluation and treatment of neonatal community-acquired Staphylococcus aureus disease in the era of community-acquired methicillin-resistant S. aureus. We retrospectively reviewed the evaluation and treatment of 126 community-acquired S. aureus infections of term and late-preterm previously healthy neonates who were < or = 30 days of age between August 2001 and July 2006 at Texas Children's Hospital. S. aureus infections included 43 pustulosis, 68 cellulitis/abscess, and 15 invasive infections. We found 84 methicillin-resistant and 42 methicillin-susceptible S. aureus isolates. Twenty-one patients received outpatient antibiotics before hospital presentation. Systemic infection evaluation included urine, blood, and cerebrospinal fluid cultures in 79, 102, and 84 neonates, respectively. Culture revealed S. aureus urinary tract infections in 1, S. aureus bacteremias in 6, and aseptic cerebrospinal fluid pleocytosis of unclear cause in 11 neonates. Physicians admitted 106, transferred 5 to other hospitals, and discharged 15 afebrile patients with topical or oral antibiotics. Clindamycin was the predominant antistaphylococcal intravenous and oral antibiotic for pustulosis and cellulitis/abscess infections. One patient with systemic S. aureus and herpes simplex virus infection died. At discharge after inpatient treatment, physicians prescribed no antibiotics for 43 patients and oral or topical antibiotics for 62 patients. Outpatient treatment failed for 1 patient who was discharged after intravenous therapy and was readmitted. Eighty percent (16 of 20) of patients with mastitis alone completed treatment with outpatient oral antibiotics. Evaluation and treatment strategies for neonatal community-acquired S. aureus disease are varied at our hospital. Prospective studies are needed to determine optimal management strategies.


Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial.
Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. The primary end point was overall survival. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. clinicaltrials.gov identifier: NCT00849615.


EM-Navigated Catheter Placement for Gynecologic Brachytherapy: An Accuracy Study.
Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and/or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.


Migration of thoracic aorta after the anterior correction of thoracic idiopathic scoliosis without parietal pleura closure.
To compare the preoperative and postoperative relative position of the thoracic aorta to the vertebrae in patients with idiopathic scoliosis (IS) after anterior corrective surgery without parietal pleura closure. To investigate the impact of unrepaired parietal pleura on thoracic aorta migration after anterior correction of right thoracic IS. Vascular injuries caused by vertebral screws have been reported in several studies. Recent studies showed an anteromedial shift of thoracic aorta after anterior curve correction with closure of the parietal pleura in thoracic IS. Migration of the aorta in patients with nonclosed parietal pleura has not been studied before, although it has been speculated in benefiting the transposition of the aorta and thus reduces the risk of vascular injury. Fifteen IS patients with predominant right thoracic scoliosis who underwent anterior instrumentation without parietal pleura closure were recruited for the study. There were 10 female and 5 male patients with an average age of 15.9 years. The following parameters were measured on preoperative and postoperative computed tomographic scans: angle α: aorta-vertebral angle; distance a: distance between the aorta and the left rib head; distance b: distance from aorta to vertebral body cortex. From computed tomographic measurements, the angle α from T5 to T12 ranged from 28.9 to 68.3 degrees before surgery and 18.8 to 63.2 degrees after surgery. The distance a ranged from 5.6 mm to 28.1 mm before surgery and 2.3 mm to 24.3 mm after surgery. The distance b ranged from 1.7 mm to 4.3 mm before surgery and 2.3 mm to 8.0 mm after surgery. These changes in all the parameters reached statistically significant difference at all the levels except in upper and lower end vertebrae (P<0.05). The thoracic aorta in patients with predominant right thoracic IS migrated posterolaterally relative to the vertebral body after anterior surgery without parietal pleura closure.


Long-term use of disodium cromoglycate in bronchial asthma.
For many patients disodium cromoglycate will retain its usefulness and safety in long-term use. Care should be exercised in employing disodium cromoglycate in chronic corticosteroid users who develop respiratory infection to avoid the development of pneumonia. Disodium cromoglycate may be expected to regain its usefulness following non-use of the drug for varying periods of time.


The non-sagittal knee moment vector identifies 'at risk' individuals that the knee abduction moment alone does not.
Multi-planar forces and moments are known to injure the anterior cruciate ligament (ACL). In ACL injury risk studies, however, the uni-planar frontal plane external knee abduction moment is frequently studied in isolation. This study aimed to determine if the frontal plane knee moment (KM-Y) could classify all individuals crossing a risk threshold compared to those classified by a multi-planar non-sagittal knee moment vector (KM-YZ). Recreationally active females completed three sports tasks-drop vertical jumps, single-leg drop vertical jumps and planned sidesteps. Peak knee abduction moments and peak non-sagittal resultant knee moments were obtained for each task, and a risk threshold of the sample mean plus 1.6 standard deviations was used for classification. A sensitivity analysis of the threshold from 1-2 standard deviations was also conducted. KM-Y did not identify all participants who crossed the risk threshold as the non-sagittal moment identified unique individuals. This result was consistent across tasks and threshold sensitivities. Analysing the peak uni-planar knee abduction moment alone is therefore likely overly reductionist, as this study demonstrates that a KM-YZ threshold identifies 'at risk' individuals that a KM-Y threshold does not. Multi-planar moment metrics such as KM-YZ may help facilitate the development of screening protocols across multiple tasks.


Soy Isoflavones Improve the Spermatogenic Defects in Diet-Induced Obesity Rats through Nrf2/HO-1 Pathway.
Soy isoflavones (SIF) are biologically active compounds of non-steroidal and phenolic properties that are richly present in soybeans, which can reduce the body weight and blood lipids of obese animals. Recently, SIF have been reported to affect reproductive ability in obese male rats. However, the specific mechanism has not been well defined. The aim of the current study was to study the possible mechanisms for the effect of SIF administration on obesity induced spermatogenic defects. Obese rats model induced by high-fat diets were established and gavage treated with 0, 50,150 or 450 mg of SIF/kg body weight/day for 4 weeks. Here, our research shows that obesity resulted in spermatogenic degeneration, imbalance of reproductive hormone, testicular oxidative stress and germ cell apoptosis, whereas evidently recovery effects were observed at 150 and 450 mg/kg SIF. We also have discovered that 150 and 450 mg/kg SIF can activate Nrf2/HO-1 pathway in control of Bcl-2, BAX and cleaved caspase-3 expression with implications in antioxidant protection. Our study indicates the potential mechanism of SIF regulating spermatogenic function in obese rats, and provides a scientific experimental basis for the regulation of biological function of obese male reproductive system by SIF.


IL-33 Is a Cell-Intrinsic Regulator of Fitness during Early B Cell Development.
IL-33 is an IL-1 family member protein that is a potent driver of inflammatory responses in both allergic and nonallergic disease. This proinflammatory effect is mediated primarily by extracellular release of IL-33 from stromal cells and binding of the C-terminal domain of IL-33 to its receptor ST2 on targets such as CD4+ Th2 cells, ILC2, and mast cells. Notably, IL-33 has a distinct N-terminal domain that mediates nuclear localization and chromatin binding. However, a defined in vivo cell-intrinsic role for IL-33 has not been established. We identified IL-33 expression in the nucleus of progenitor B (pro-B) and large precursor B cells in the bone marrow, an expression pattern unique to B cells among developing lymphocytes. The IL-33 receptor ST2 was not expressed within the developing B cell lineage at either the transcript or protein level. RNA sequencing analysis of wild-type and IL-33-deficient pro-B and large precursor B cells revealed a unique, IL-33-dependent transcriptional profile wherein IL-33 deficiency led to an increase in E2F targets, cell cycle genes, and DNA replication and a decrease in the p53 pathway. Using mixed bone marrow chimeric mice, we demonstrated that IL-33 deficiency resulted in an increased frequency of developing B cells via a cell-intrinsic mechanism starting at the pro-B cell stage paralleling IL-33 expression. Finally, IL-33 was detectable during early B cell development in humans and IL33 mRNA expression was decreased in B cell chronic lymphocytic leukemia samples compared with healthy controls. Collectively, these data establish a cell-intrinsic, ST2-independent role for IL-33 in early B cell development.


Exercise for osteoarthritis of the hip.
Current international treatment guidelines recommending therapeutic exercise for people with symptomatic hip osteoarthritis (OA) report are based on limited evidence. To determine whether land-based therapeutic exercise is beneficial for people with hip OA in terms of reduced joint pain and improved physical function and quality of life. We searched five databases from inception up to February 2013. All randomised controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in water) with a non-exercise group. Four review authors independently selected studies for inclusion. We resolved disagreements through consensus. Two review authors independently extracted data, assessed risk of bias and the quality of the body of evidence for each outcome using the GRADE approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) and dichotomous outcomes (proportion of study withdrawals). We considered that seven of the 10 included RCTs had a low risk of bias. However, the results may be vulnerable to performance and detection bias as none of the RCTs were able to blind participants to treatment allocation and, while most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self reported. One of the 10 RCTs was only reported as a conference abstract and did not provide sufficient data for the evaluation of bias risk.High-quality evidence from nine trials (549 participants) indicated that exercise reduced pain (standardised mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.20) and improved physical function (SMD -0.38, 95% CI -0.54 to -0.05) immediately after treatment. Pain and physical function were estimated to be 29 points on a 0- to 100-point scale (0 was no pain or loss of physical function) in the control group; exercise reduced pain by an equivalent of 8 points (95% CI 4 to 11 points; number needed to treat for an additional beneficial outcome (NNTB) 6) and improved physical function by an equivalent of 7 points (95% CI 1 to 12 points; NNTB 6). Only three small studies (183 participants) evaluated quality of life, with overall low quality evidence, with no benefit of exercise demonstrated (SMD -0.07, 95% CI -0.23 to 0.36). Quality of life was estimated to be 50 points on a norm-based mean (standard deviation (SD)) score of 50 (10) in the general population in the control group; exercise improved quality of life by 0 points. Moderate-quality evidence from seven trials (715 participants) indicated an increased likelihood of withdrawal from the exercise allocation (event rate 6%) compared with the control group (event rate 3%), but this difference was not significant (risk difference 1%; 95% CI -1% to 4%). Of the five studies reporting adverse events, each study reported only one or two events and all were related to increased pain attributed to the exercise programme.The reduction in pain was sustained at least three to six months after ceasing monitored treatment (five RCTs, 391 participants): pain (SMD -0.38, 95% CI -0.58 to -0.18). Pain was estimated to be 29 points on a 0- to 100-point scale (0 was no pain) in the control group, the improvement in pain translated to a sustained reduction in pain intensity of 8 points (95% CI 4 to 12 points) compared with the control group (0 to 100 scale). The improvement in physical function was also sustained (five RCTs, 367 participants): physical function (SMD -0.37, 95% CI -0.57 to -0.16). Physical function was estimated to be 24 points on a 0- to 100-point scale (0 was no loss of physical function) in the control group, the improvement translated to a mean of 7 points (95% CI 4 to 13) compared with the control group.Only five of the 10 RCTs exclusively recruited people with symptomatic hip OA (419 participants). There was no significant difference in pain or physical function outcomes compared with five studies recruiting participants with hip or knee OA (130 participants). Pooling the results of these 10 RCTs demonstrated that land-based therapeutic exercise programmes can reduce pain and improve physical function among people with symptomatic hip OA.


Cardiotoxicity of Senna occidentalis in sheep (Ovis aries).
The cardiotoxicity of Coffee senna (Senna occidentalis) was investigated in sheep that were fed diets containing its seeds, which are recognized as the most poisonous part of such weed. Dianthrone, the main toxic component of S. occidentalis, is known to impair mitochondrial oxidative phosphorylation, leading to myofiber degeneration. In this study, fifteen ewes were fed 0%, 2% or 4% of seeds of S. occidentalis for 63 days. Non-specific markers of myocyte injury and electrocardiograms were undertaken at baseline, and at 14, 35, and 63 days after the animals were first fed the diets, while histopathology of heart samples was performed at the very end of the study. Our results showed an increase in serum AST and LDH over time, while CK-MB did not change significantly. Changes that could be ascribed to myocardial damage were not documented in the electrocardiograms. Cardiac histopathology demonstrated only mild-to-moderate vacuolar degeneration, myofiber edema and disarray, structural disorganization, and cellular necrosis. In conclusion, S. occidentalis caused myocardial fiber degeneration in a dose-dependent fashion, but the electrocardiogram was not able to identify these lesions non-invasively. Because the markers of myofiber injury used in this study lack specificity, they may not be used to support cardiac impairment objectively, despite some of them did change over time.


Calcium inactivation in skeletal muscle fibres of the stick insect, Carausius morosus.
1. Inactivation of Ca currents in skeletal muscle fibres of the stick insect, Carausius morosus, was studied using a three-electrode voltage-clamp method. 2. The extent of inactivation showed a voltage-dependence similar to that of the Ca current, inactivation being absent in the absence of a Ca current, maximal at potentials where Ca currents are largest, and reduced at potentials close to ECa. 3. Ca currents inactivated along a double exponential time course, both when measured from the decline of Ca current during a single pulse and when measured using a two pulse protocol. In 20 mM-Ca-Ringer the fast time constant of inactivation had a mean value of 27 msec and that of the slow time constant was 134 msec, at O mV and 5 degrees C. 4. The rate of inactivation was slowed, and its extent reduced, in low [Ca]o, where Ca currents are smaller. Similarly, inactivation was faster and more complete in high-Ca-Ringer. 5. The rate of recovery from inactivation also followed a double exponential time course, with time constants of 638 msec and 4 sec following a 500 msec inactivating pulse in 20 mM-Ca-Ringer at 5 degrees C. Recovery appeared to be related to the amount of Ca entry during the inactivating pulse, being slower in high [Ca]o and following longer inactivating pulses. 6. Inactivation was slowed and reduced in extent when Ba2+ or Sr2+ carried current. Inactivation in Ba solutions may be due to depletion of Ba2+ from the lumen of the transverse tubules. 7. Ba2+ does not compete with Ca2+ for the inactivation mechanism. 8. It is concluded that inactivation of Ca currents in stick insect muscle fibres is primarily mediated by Ca2+ entry.


Relationship between Caregiver Health Literacy and Caregiver Burden.
This study was conducted in order to examine the relationship between caregiver health literacy and caregiver burden. A cross sectional and descriptive design was used. The research was carried out at the state hospital from November 2017 to January 2018. The study sample consisted of 215 caregivers. Data were collected through face-to-face interviews with a health literacy scale and a burden interview. The research found that the participating caregivers had a high level of health literacy and a moderate level of care burden. There was a moderately negative relationship between health literacy and caregiver burden (r = -.310; p = .000). It was found that as a caregiver's level of health literacy increased, that individual's burden decreased. It is important for individuals who are caring for chronic patients and need assistance in this tough process to stay healthy in terms of decreasing the care burden. Caregivers must be adequately health literate so that they will be able to understand basic health information and develop the proper self-care behavior that will enable them to maintain and even improve their own health status.


A prospective study of eating away-from-home meals and weight gain in a Mediterranean population: the SUN (Seguimiento Universidad de Navarra) cohort.
The traditional Mediterranean food pattern is more easily preserved when meals are eaten at home; however, as a result of recent socio-economic changes, away-from-home meal consumption has increased rapidly in Mediterranean countries. Little research has been conducted so far to investigate the long-term health effects of these changes in the Mediterranean area. In a prospective Spanish dynamic cohort of 9182 university graduates (the SUN Study; Seguimiento Universidad de Navarra, University of Navarra Follow-up) with a mean age of 37 years, followed up for an average of 4.4 years, we assessed the association between the frequency of eating out of home and weight gain or incident overweight/obesity. Dietary habits were assessed with an FFQ previously validated in Spain. During follow-up, eating-out consumers (two times or more per week) had higher average adjusted weight gain (+129 g/year, P < 0.001) and higher adjusted risk of gaining 2 kg or more per year (OR = 1.36; 95 % CI 1.13, 1.63) than non-eating-out consumers. Among participants with baseline BMI < 25 kg/m2, we observed 855 new cases of overweight/obesity. Eating away-from-home meals was significantly associated with a higher risk of becoming overweight/obese (hazard ratio = 1.33; 95 % CI 1.13, 1.57). A higher frequency of meals eaten out of home may play a role in the current obesity epidemic observed in some Mediterranean countries.


Systematic spectral shifts in the mid-infrared spectroscopy of aerosols.
Infrared spectroscopy in the spectral fingerprint region from 6.5 to 20 µm has been applied for decades to identify vapor- and condensed-phase chemicals with high confidence. By employing a unique broadband laser operating from 7.2- to 11.5-µm we show that, in this region, wavelength-dependent Mie-scattering effects substantially modulate the underlying chemical absorption signature, undermining the ability of conventional infrared absorption spectroscopy to identify aerosolized liquids and solids. In the aerosol studied, Mie theory predicts that the positions of spectroscopic features will blue-shift by up to 200 nm, and this behavior is confirmed by experiment, illustrating the critical importance of considering Mie contributions to aerosol spectroscopy in the mid infrared. By examining the spectroscopy of light scattered from an aerosol of the chemical diethyl phthalate, we demonstrate excellent agreement with a Mie-scattering model informed by direct measurements of the particle-size-distribution and complex refractive index.


Atypical chemokine receptor ACKR2 mediates chemokine scavenging by primary human trophoblasts and can regulate fetal growth, placental structure, and neonatal mortality in mice.
Inflammatory chemokines produced in the placenta can direct the migration of placental leukocytes using chemokine receptors that decorate the surface of these cells. Fetal trophoblasts can also express receptors for inflammatory chemokines, and they are one of the few cell types that express atypical chemokine receptor 2 (ACKR2), previously known as D6. ACKR2 binds many inflammatory CC chemokines but cannot stimulate cell migration or activate signaling pathways used by conventional chemokine receptors. Existing evidence suggests that ACKR2 is a specialized chemokine scavenger, but its function in primary human trophoblasts has not been explored. In mice, ACKR2 is thought to be dispensable for the reproductive success of unchallenged females that have conceived naturally, but it can suppress inflammation-induced abortion and aid the survival of implanted allogeneic embryos. In this article, we demonstrate that cultured primary human trophoblasts express ACKR2 far more strongly than genes encoding conventional receptors for inflammatory CC chemokines. Moreover, these cells are capable of the rapid internalization and efficient scavenging of extracellular chemokine, and this is mediated by ACKR2. We also report that in unchallenged DBA/1j mice, Ackr2 deficiency increases the incidence of stillbirth and neonatal death, leads to structural defects in the placenta, and can decrease fetal weight. Loss of Ackr2 specifically from fetal cells makes a key contribution to the placental defects. Thus, primary human trophoblasts use ACKR2 to scavenge chemokines, and ACKR2 deficiency can cause abnormal placental structure and reduced neonatal survival.


Preoperative multivariable prognostic model for prediction of nonorgan confined urothelial carcinoma of the upper urinary tract.
We created a prognostic tool for the accurate preoperative prediction of nonorgan confined upper tract urothelial carcinoma. A computerized data bank containing comprehensive information on 1,453 patients who underwent radical nephroureterectomy at 13 academic institutions was generated and continuously updated. This study comprised a subset of 659 patients in whom all appropriate preoperative prognostic variables (age, gender, race, symptoms, Eastern Cooperative Oncology Group performance status, primary tumor location, tumor architecture, tumor grade and history of previous bladder cancer) were available for statistical analysis. A multivariable logistic regression model containing relevant clinicopathological variables addressed the prediction of nonorgan confined stage disease (T3-4 and/or N+) at radical nephroureterectomy. A backward step-down selection process was applied to achieve the most informative and parsimonious model. Internal validation was performed using 200 bootstrap resamples. Pathological nonorgan confined urothelial carcinoma was found in 40% of patients. Grade, architecture and location of the tumor were independently associated with nonorgan confined disease. A nomogram including these 3 variables achieved 76.6% accuracy in predicting nonorgan confined upper tract urothelial cancer. We developed a simple and accurate prognostic tool for the prediction of locally advanced upper tract urothelial cancer. This preoperative prediction model can be used for designing clinical trials, selecting patients for preoperative systemic therapy and guiding the extent of concomitant lymph node dissection at nephroureterectomy.


[Amyloid beta: functional protein or biological junk?].
During a decade there was a dogma that Alzheimer's amyloid beta (Ap) is produced only upon the disease, and that this protein is neurotoxic for neurons and brain tissue. Current scientific evidence demonstrate that AP is an essential molecule in synaptic plasticity that underlie learning and memory. Therefore, it was hypothesized that the change of AP biology in Alzheimer's disease (as well as in a number of other human pathologies, including cardiovascular disease, Niemann-Pick type C disease and Down syndrome) represents a physiological mechanism serving to compensate the impaired brain structure or function. This review summarizes experimental evidence on Abeta as functional player in synaptic plasticity and neurochemical pathways.


Effects of paternal and maternal undernutrition on growth of offspring in rats.
In adult males, undernutrition is associated with altered spermatogenesis. The present study was performed to evaluate the possible role of paternal undernutrition on growth and development of rat offspring and to compare those effects with undernutrition in pregnant animals. Male rats were fed 100%, 80% or 60% of their ad lib food intake for eight weeks and were then bred to untreated females. Pregnant rats were mated with untreated males and received their food allotments throughout pregnancy. Although male body weights and rate of successful matings were decreased by paternal undernutrition, offspring litter size, birth weights, and weights at 21 days were not significantly altered. By contrast, maternal undernutrition was associated with decreased maternal weight gain, lower offspring birth weights and body weights at weaning.


Compounding Parenteral Products in Pediatric Wards-Effect of Environment and Aseptic Technique on Product Sterility.
Parenteral products must be compounded using an aseptic technique to ensure sterility of the medicine. We compared the effect of three clinical environments as compounding areas as well as different aseptic techniques on the sterility of the compounded parenteral product. Clinical pharmacists and pediatric nurses compounded 220 samples in total in three clinical environments: a patient room, a medicine room and biological safety cabinet. The study combined four methods: observation, environmental monitoring (settle plates), monitoring of personnel (finger dab plates) and sterility testing (membrane filtration). Of the compounded samples, 99% were sterile and no significant differences emerged between the clinical environments. Based on the settle plates, the biological safety cabinet was the only area that fulfilled the requirements for eliminating microbial contamination. Most of the steps on the observation form for aseptic techniques were followed. All participants disinfected their hands, wore gloves and disinfected the septum of the vial. Non-contaminated finger dab plates were mostly detected after compounding in the biological safety cabinet. Aseptic techniques were followed relatively well in all environments. However, these results emphasize the importance of good aseptic techniques and support the recommendation of compounding parenteral products in biological safety cabinets in clinical environments.


"Psyche is extended": from Kant to Freud.
This paper is inspired by one of Freud's last notes, which is famous for its astonishing conclusion: "Psyche is extended; knows nothing about it," which describes the perception of space as a product of the extension of the psychic apparatus, and compares it with Kant's a priori categories. The Author reconstructs the historical background of this idea as part of a long discussion between Freud and his pupil Marie Bonaparte in the second half of 1938, and shows how the relationship between body and psychic functions in Freud's thought was influenced by his intellectual debt to Kant. Through an outline of the influence of Kantian philosophy on the emerging Naturphilosophie in fin de siècle Vienna, the Author aims to show the profound influence of Kantian philosophy on the development of Freud's thought. By committing to a modern and non-dualistic conception of the relationship between body and mind, Freud conceives an indissoluble bond between the mind and, not only the brain, but the whole body and its spatial extension. The Author concludes by identifying a close link between the aphorism of 1938 and Kantian pre-Critique thought, and, more generally, highlighting the influence of the Königsberg philosopher on the relationship between mind and body and on the perception of time and space in Freudian thought.


Evaluating the contribution of soil properties to modifying lead phytoavailability and phytotoxicity.
Soil properties affect Pb bioavailability to human and ecological receptors and should be considered during ecological risk assessment of contaminated soil. We used path analysis (PA) to determine the relative contribution of soil properties (pH, organic C [OC], amorphous Fe and Al oxides [FEAL], and cation-exchange capacity [CEC]) in modifying Pb bioavailability. The response of biological endpoints (bioaccumulation and dry matter growth [DMG]) of lettuce (Lactuca sativa) grown on 21 Pb-spiked (2,000 mg/kg) soils were determined. Lettuce tissue Pb ranged from 3.22 to 233 mg/kg, and relative DMG ranged from 2.5 to 88.5% of their respective controls. Simple correlation showed strong relationships between CEC and OC (p < 0.01) and weaker relationships between pH and FEAL (p < 0.05) and Pb bioaccumulation. Results of PA suggest that soil pH increased the negative surface charge of organic matter and clay, thereby increasing CEC and decreasing Pb bioaccumulation. Also, the direct effect of OC on tissue Pb can be attributed to formation of surface Pb complexes by organic matter functional group ligands. Increased OC and/or CEC reduced Pb solubility and bioavailability in the 21 soils in the present study. The relative importance of soil properties likely will vary between studies employing different soils. Soil properties should be considered during the ecological risk assessment of metal in contaminated soils. Path analysis is useful for ecological studies involving soils with a wide range of physicochemical properties and can assist in site risk assessment of metals and remediation decisions on contaminated sites.


Comparison of arterial wall mechanics using ring and cylindrical segments.
Thin rings and intact cylindrical segments of canine carotid and iliac arteries were used to determine wall mechanics. Measurements of force and length were obtained from the ring segments, whereas measurements of pressure and diameter were obtained from the cylindrical segments under conditions of active (147 mM K+) and passive smooth muscle (Ca2+ free and 2 mM ethyleneglycolbis (beta-aminoethylether)-N,N'-tetraacetic acid). These measurements were normalized to values of segment stress and strain. Under passive conditions stress-strain relations for the rings appeared to be stiffer than those obtained using cylindrical segments. Pressure-diameter curves computed using force-length data from the rings were shifted to higher values of diameter compared with values from the intact segments at all pressure levels. Passive mechanics derived from measurements on ring segments yielded poor estimates of mechanics derived from intact segments. Despite this finding, values of active force development from the two sample geometries were similar. No statistically significant differences were found in values of maximum force development expressed in terms of sample cross-sectional area. Some differences in values of active force development at low values of muscle length were found. The latter were probably related to the differences in passive mechanics and the procedure used to normalize muscle length. Reasonable values of active force development can be obtained from ring segments.


Sexually transmitted diseases and anorectum.
Sexually transmitted diseases (STD) are a major public health problem because their incidence is increasing worldwide despite prevention campaigns and because they raise the risk of HIV infection. Anorectal localisations of STD are common among men who have sex with men (MSM) but can also be seen among heterosexuals (men or women). Transmission of such infections is due to anal sex or to other sexual behaviours like "fisting". Although some pathogens (like Human Papillomavirus-HPV) are common in gastroenterologist/proctologist consultations, others are not so well-known. Furthermore during the last years, sexual risky behaviours have led to resurgence of old affections (like syphilis) or to emergence of unknown diseases (like lymphogranuloma venereum) in our countries. This presentation tends to focus on clinical manifestation, diagnosis and treatment of different STD: HPV, Herpes Simplex Virus, Neisseria gonorrhoeae, Chlamydia trachomatis (in particularly lymphogranuloma venereum) and Treponema pallidum.


The equine neck and its function during movement and locomotion.
During both locomotion and body movements at stance, the head and neck of the horse are a major craniocaudal and lateral balancing mechanism employing input from the visual, vestibular and proprioceptive systems. The function of the equine neck has recently become the focus of several research groups; this is probably also feeding on an increase of interest in the equine neck in equestrian sports, with a controversial discussion of specific neck positions such as maximum head and neck flexion. The aim of this review is to offer an overview of new findings on the structures and functions of the equine neck, illustrating their interplay. The movement of the neck is based on intervertebral motion, but it is also an integral part of locomotion; this is illustrated by the different neck conformations in the breeds of horses used for various types of work. The considerable effect of the neck movement and posture onto the whole trunk and even the limbs is transmitted via bony, ligamentous and muscular structures. Also, the fact that the neck position can easily be influenced by the rider and/or by the employment of training aids makes it an important avenue for training of new movements of the neck as well as the whole horse. Additionally, the neck position also affects the cervical spinal cord as well as the roots of the spinal nerves; besides the commonly encountered long-term neurological effects of cervical vertebral disorders, short-term changes of neural and muscular function have also been identified in the maximum flexion of the cranial neck and head position. During locomotion, the neck stores elastic energy within the passive tissues such as ligaments, joint capsules and fasciae. For adequate stabilisation, additional muscle activity is necessary; this is learned and requires constant muscle training as it is essential to prevent excessive wear and tear on the vertebral joints and also repetitive or single trauma to the spinal nerves and the spinal cord. The capability for this stabilisation decreases with age in the majority of horses due to changes in muscle tissue, muscle coordination and consequently muscle strength.


Altering preferences for suicide crisis resources using the decoy nudge: Evidence of context-dependent effects in suicide prevention decision making.
Suicide is the 10th leading cause of death in the United States. There are several important decisions that could confer later risk to a suicide attempt (e.g., how to store lethal means). Therefore, understanding how people make decisions that are relevant for suicide risk is an important area of study for suicidology. Human behavior diverges from perfectly rational economic decision making according to observable patterns based on predictable cognitive processes. Nudges attempt to diminish, leverage, or circumvent these deviations to increase the probability of a desired choice being selected or behavior being performed. One deviation from rationality is that human choice is context dependent. This deviation can be observed by introducing an objectively inferior alternative option (a decoy) into a choice array that alters an individual's preference. Using decoys could be one way to nudge people toward best practices in suicide prevention work. This study examined if decoys could reliably alter participant preferences for suicide prevention resources using a hypothetical scenario in three separate online samples (i.e., general population, participants with recent suicidal thoughts, gun owners). Our results found that introducing a slightly (but objectively) worse version of an existing suicide prevention resource increased the preference toward the slightly better option. These findings indicate that using decoys could be an effective nudge for influencing people's preference toward best practices. Most important, these findings highlight the importance of context effects on choice preference in suicide research and prevention efforts, as well as suggest irrational decision-making processes in suicide-relevant decision making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Intrinsic Bauschinger effect and recoverable plasticity in pentatwinned silver nanowires tested in tension.
Silver nanowires are promising components of flexible electronics such as interconnects and touch displays. Despite the expected cyclic loading in these applications, characterization of the cyclic mechanical behavior of chemically synthesized high-quality nanowires has not been reported. Here, we combine in situ TEM tensile tests and atomistic simulations to characterize the cyclic stress-strain behavior and plasticity mechanisms of pentatwinned silver nanowires with diameters thinner than 120 nm. The experimental measurements were enabled by a novel system allowing displacement-controlled tensile testing of nanowires, which also affords higher resolution for capturing stress-strain curves. We observe the Bauschinger effect, that is, asymmetric plastic flow, and partial recovery of the plastic deformation upon unloading. TEM observations and atomistic simulations reveal that these processes occur due to the pentatwinned structure and emerge from reversible dislocation activity. While the incipient plastic mechanism through the nucleation of stacking fault decahedrons (SFDs) is fully reversible, plasticity becomes only partially reversible as intersecting SFDs lead to dislocation reactions and entanglements. The observed plastic recovery is expected to have implications to the fatigue life and the application of silver nanowires to flexible electronics.


Longitudinal machine learning uncouples healthy aging factors from chronic disease risks.
To understand human longevity, inherent aging processes must be distinguished from known etiologies leading to age-related chronic diseases. Such deconvolution is difficult to achieve because it requires tracking patients throughout their entire lives. Here, we used machine learning to infer health trajectories over the entire adulthood age range using extrapolation from electronic medical records with partial longitudinal coverage. Using this approach, our model tracked the state of patients who were healthy and free from known chronic disease risk and distinguished individuals with higher or lower longevity potential using a multivariate score. We showed that the model and the markers it uses performed consistently on data from Israeli, British and US populations. For example, mildly low neutrophil counts and alkaline phosphatase levels serve as early indicators of healthy aging that are independent of risk for major chronic diseases. We characterize the heritability and genetic associations of our longevity score and demonstrate at least 1 year of extended lifespan for parents of high-scoring patients compared to matched controls. Longitudinal modeling of healthy individuals is thereby established as a tool for understanding healthy aging and longevity.


The unintended consequences of cervical screening: distress in women undergoing cytologic surveillance.
It is well known that receipt of an initial abnormal cervical cytology test can trigger considerable anxiety among women. Less is known about the impact of follow-up by repeat cytology tests. We quantified prevalence, and identified predictors, of distress after repeat cytologic testing in women with a single low-grade test. Within the framework of the TOMBOLA randomized controlled trial of alternative managements, 844 women aged 20 to 59 years with a single routine cytology test showing borderline nuclear abnormalities (BNA; broadly equivalent to atypical squamous cells of undetermined significance) were assigned to follow-up by repeat cytology in primary care (the first test was due 6 months after the initial BNA result). Women completed sociodemographic and psychosocial questionnaires at recruitment and the Impact of Event Scale (IES) 6 weeks after their first follow-up cytology test. Factors associated with significant psychologic distress (IES ≥ 9) were identified using logistic regression. The response rate was 74% (n = 621/844). Of all the respondents, 39% scored in the range for significant distress. Distress varied by follow-up cytology result: negative, 36%; BNA or mild dyskaryosis, 42%; other (including high grade and inadequate), 55%. After adjusting for the cytology result, risk of distress was significantly raised in women who had significant anxiety at recruitment, reported experiencing pain after the follow-up cytology, had children, or were dissatisfied with support they had received after their initial BNA test. Substantial proportions of women experience surveillance-related psychologic distress after a follow-up cytology test, even when the result is negative. This is an important, albeit unintended, consequence of cervical screening. Strategies to alleviate this distress merit attention.


[Legg-Calvé-Perthes disease].
Legg-Calvé-Perthes disease is characterized by avascular necrosis of the head of the femur. This article deals with the epidemiology, possible causes, treatment and prognostic factors connected with the disease. The article is based on a non-systematic literature search and own clinical practice, with special emphasis on a Norwegian countrywide study of children with Legg-Calvé-Perthes disease. The incidence of Legg-Calvé-Perthes disease varies in different countries and regions. Those who are older than six years at the time of diagnosis and have over 50% femoral head necrosis have a worse prognosis than younger children where the necrosis is less extensive. Treatment has been discussed extensively over the past 100 years, and still varies considerably. The Norwegian countrywide investigation showed that the results in children who were over six years at the time of diagnosis and had more than 50% femoral head necrosis were significantly better after varus femoral osteotomy than after physiotherapy or orthosis. This agrees with the only other prospective study that has been published. Operative treatment should be considered in children who are six years old or older and have over 50% femoral head necrosis when the diagnosis Legg-Calvé-Perthes disease is made. Those who are younger than six years at the time of diagnosis or who have less than 50% femoral head necrosis should be treated symptomatically. Abduction orthosis has no place in the treatment of Legg-Calvé-Perthes disease.


How far can we go with structural mass spectrometry of protein complexes?
Physical interactions between proteins and the formation of stable complexes form the basis of most biological functions. Therefore, a critical step toward understanding the integrated workings of the cell is to determine the structure of protein complexes, and reveal how their structural organization dictates function. Studying the three-dimensional organization of protein assemblies, however, represents a major challenge for structural biologists, due to the large size of the complexes, their heterogeneous composition, their flexibility, and their asymmetric structure. In the last decade, mass spectrometry has proven to be a valuable tool for analyzing such noncovalent complexes. Here, I illustrate the breadth of structural information that can be obtained from this approach, and the steps taken to elucidate the stoichiometry, topology, packing, dynamics, and shape of protein complexes. In addition, I illustrate the challenges that lie ahead, and the future directions toward which the field might be heading.


Clinical and microbiological efficacy and toxicity of colistin in patients infected with multidrug-resistant gram-negative pathogens.
Polymyxins have recently again become important because of multidrug-resistant (MDR) gram-negative pathogens. The aim of this study was to evaluate the clinical and microbiological efficacy and toxicity of different dosages of colistin in patients infected with MDR microorganisms that were sensitive only to colistin. The study was conducted in the 1,200-bed Ankara Numune Training and Research Hospital. Patients with normal renal function who received colistin for 48 h or more were retrospectively evaluated. Clinical response was defined as resolution of fever and clinical and laboratory findings. Microbiological response was defined as bacteriological eradication from the infection site. Nephrotoxicity was defined as at least two consecutive serum creatinine measurements with an increase of 0.5 mg/dl from baseline at least 24 h apart after 2 or more days of colistin therapy. Twenty-four patients were included in the study: total clinical response was obtained in 17 of 24 (70.8 %) patients and microbiological response in 15 of 24 (62.5 %) patients. Patients were grouped according to colistin dosage of 3 × 1 million units (MU) versus 3 × 2 MU. Clinical response rates were 69.2 % and 72.7 %, respectively (p = 0.65). Microbiological response rate was similar (p = 0.62). Nephrotoxicity was revealed in 1 of 13 patients (7.7 %) for the 3 × 1 MU group and 2 of 11 patients (18.2 %) in the 3 × 2 MU group (p = 0.57). The nephrotoxicity rate was greater with higher dosages of colistin, but the difference was not statistically significant. Renal function of patients receiving higher dosages of colistin should be more closely monitored.


Compression of Cerebellar Functional Gradients in Schizophrenia.
Our understanding of cerebellar involvement in brain disorders has evolved from motor processing to high-level cognitive and affective processing. Recent neuroscience progress has highlighted hierarchy as a fundamental principle for the brain organization. Despite substantial research on cerebellar dysfunction in schizophrenia, there is a need to establish a neurobiological framework to better understand the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellum in schizophrenia. To help to establish such a framework, we investigated the abnormalities in the distribution of sensorimotor-supramodal hierarchical processing topography in the cerebellum and cerebellar-cerebral circuits in schizophrenia using a novel gradient-based resting-state functional connectivity (FC) analysis (96 patients with schizophrenia vs 120 healthy controls). We found schizophrenia patients showed a compression of the principal motor-to-supramodal gradient. Specifically, there were increased gradient values in sensorimotor regions and decreased gradient values in supramodal regions, resulting in a shorter distance (compression) between the sensorimotor and supramodal poles of this gradient. This pattern was observed in intra-cerebellar, cerebellar-cerebral, and cerebral-cerebellar FC. Further investigation revealed hyper-connectivity between sensorimotor and cognition areas within cerebellum, between cerebellar sensorimotor and cerebral cognition areas, and between cerebellar cognition and cerebral sensorimotor areas, possibly contributing to the observed compressed pattern. These findings present a novel mechanism that may underlie the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellar and cerebro-cerebellar circuits in schizophrenia. Within this framework of abnormal motor-to-supramodal organization, a cascade of impairments stemming from disrupted low-level sensorimotor system may in part account for high-level cognitive cerebellar dysfunction in schizophrenia.


Possibility for Combination of Human rIFN-alpha and rIFN-beta in Complex Immune Therapy of Multiple Sclerosis.
Six patients with an evident multiple sclerosis (MS) were observed in dynamics of long term immune therapy based on administration of rIFN preparations. One half of them received the therapy with rIFN-alpha. Three other patients received rIFN-beta administration that was interrupted, when sensitivity of blood cells to in vitro IFN-beta action was decreased; the trial was continued by rIFN-alpha courses. Production of IFN-alpha and IFN-gamma by stimulated peripheral blood leukocytes (PBL) of the patients was tested simultaneously with detection of in vitro PBL response to IFN-alpha, IFN-beta and IFN-gamma priming action every 10th day of observation. It has been shown that positive clinical effect of rIFN-alpha therapy following rIFN-beta administration was comparable or even surpassed neurological effects of rIFN-alpha and rIFN-beta applied alone. Similarly rIFN-alpha and rIFN-beta therapy caused a partial restoration of initially decreased IFN-alpha and IFN-gamma production by PBL. It has been also accompanied by the dissociation appearance between IFN-alpha and IFN-gamma production by PBL, when in accordance with physiological IFN system state restoration the IFN-alpha production was augmented while IFN-gamma synthesis was reduced. Such a dissociation was paralleled by decrease in PBL response to IFN-alpha treatment, by increase in blood cell sensitivity to IFN-beta action, and by keeping IFN-gamma response at lower level than during rIFN-alpha or rIFN-beta caused dissociation. The data obtained allowed to confirm the possibility to combine rIFN-beta pathogenetical therapy with rIFN-alpha administration in patients with MS when sensitivity of blood cells to IFN-beta action displayed a tendency to a fall.


Serial administration of adrenergic antagonist and agonist ("pulsatile therapy") reduces the incidence of long-term drift to timolol in humans.
To test whether the incidence of long-term drift to timolol can be reduced by a "pulsatile" treatment (6 months timolol-2 months dipivefrin). In a randomized clinical trial, 100 consecutive subjects with ocular hypertension or high-tension primary open-angle glaucoma in at least one eye were randomly assigned to either group A, which was administered timolol 0.5% twice a day (b.i.d.), or to group B, which was administered timolol 0.5% b.i.d. (6 months) alternated with 0.1% dipivefrin b.i.d. (2 months). Diurnal intraocular pressure (IOP) was measured at recruitment, 1 month later during timolol administration ("reference value"), and every 6 months in group A or at the end of each pulse in group B. In bilateral cases, the right eye only was considered for the analysis. Length of follow-up was 54 months. Long-term drift was diagnosed if the IOP on timolol increased by at least 5 mm Hg over the reference value and was followed by a </ = 2mm Hg increase after withdrawing timolol for 2 weeks. Reference values were comparable in both groups (16.4+/-1.2 mm Hg in group A, 15.9+/-1.7 mm Hg in group B). Eleven subjects (four in group A and seven in group B) did not complete follow-up because IOP increased >5 mm Hg in the study eye without detectable drift to the beta-blocker. The actual 54-month incidence of long-term drift was 45% (21/46) in group A versus 7% (3/43) in group B (P<0.01). In group B, IOP was always higher during dipivefrin pulse than on timolol (paired samples t-test, P<0.01). However, dipivefrin proved more effective through follow-up; IOP was 21.1+/-1.2 mm Hg at month 8 (first "pulse") and 18.6+/-0.95 mm Hg at month 48 (last "pulse") (paired samples t-test, P<0.01). Serial administration of adrenergic antagonist and agonist can reduce the incidence of long-term drift to the beta-blockade in ocular hypertension and primary open angle glaucoma.


Targeted Radiation Delivery Before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-Term Survivors.
Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase 1/2 study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML and ALL), or myelodysplastic syndrome (MDS) [ClinicalTrials.gov, NCT00589316]. Patients received a tracer diagnostic dose before a therapeutic infusion of 131I-anti-CD45 to deliver escalating doses (12 to 26 Gy) to the dose-limiting organ. Patients subsequently received fludarabine, cyclophosphamide (CY), and 2 Gy TBI conditioning before haploidentical marrow HCT. GVHD prophylaxis was post-transplant CY plus tacrolimus and mycophenolate mofetil. Twenty-five patients (20 with AML, 4 ALL and 1 high-risk MDS) were treated; 8 had ≥ 5% blasts by morphology (range 9-20 %), and 7 had previously failed HCT. All 25 patients achieved a morphologic remission 28 days after HCT, with only two patients showing minimal residual disease (0.002 -1.8%) by flow cytometry. Median time to engraftment was 15 days for neutrophils and 23 days for platelets. Point estimates for overall survival and progression-free survival were 40% and 32% at 1 year, and 24% and 24% at 2 years, respectively. Point estimates of relapse and non-relapse mortality at 1 year were 56% and 12%, respectively. 131l-anti-CD45 radioimmunotherapy prior to haploidentical HCT is feasible and can be curative in some patients, including those with disease, without additional toxicity.


The role of ferroelectric domain structure in second harmonic generation in random quadratic media.
We study theoretically and numerically the second harmonic generation in a nonlinear crystal with random distribution of ferroelectric domains. We show that the specific features of disordered domain structure greatly affect the emission pattern of the generated harmonics. This phenomena can be used to characterize the degree of disorder in nonlinear photonic structures.


Methods for detecting indole production by gram-negative nonsporeforming anaerobes.
To help select the most appropriate method for detecting indole production with anaerobic gram-negative bacilli, several recommended methods were compared. Indole was measured both quantitatively and qualitatively after varying periods of incubation. Studies evaluated the results obtained in different media, the effect of adding glucose and/or tryptophan, the requirement for strict anaerobiasis, and the effects of reducing the total volume of broth. A 1-ml amount of thioglycolate broth without glucose but with 0.02% tryptophan gave optimal results after 2 to 7 days of incubation in anaerobic (Gas-Pak) jars. The majority of clinical isolates will give strong positive tests after 1 to 2 days but a few require 3 to 7 days of incubation. Prolonged incubation was required more frequently with conventional methods.


Self-Efficacy for Adoption and Maintenance of Exercise Among Fibromyalgia Patients: A Pilot Study.
Objective. While multimodal treatment approaches for fibromyalgia (FM), incorporating exercise, have been found most effective, information about factors associated with exercise adoption and maintenance is lacking. Design, Setting, and Methods. Women veterans with FM (N = 19) completed an anonymous Internet survey measuring FM impact (FI), adoption of exercise behavior, and self-efficacy for exercise. Using classifications of behavior specified by the transtheoretical model, the self-efficacy of participants classified in the action or maintenance (AM) stages was compared with those in earlier stages (precontemplation through preparation) of exercise readiness. Multivariate analysis of variance analyses examined differences in FI domains by stage of change. Analysis of covariance examined whether exercise self-efficacy differed by stage of change while controlling for FI. Results. Higher levels of self-efficacy were detected among participants in the AM stages. Participants in the AM stages also reported higher levels of FI symptoms. After controlling for FI, self-efficacy did not differ significantly between the 2 groups; however the effect size was large (η2 = .11). Conclusions. Findings of this pilot study suggest a role for self-efficacy in exercise adoption and maintenance, even in the setting of higher FM symptoms. Replication of this study with a larger sample size is warranted.


[Role of compression of the vessels of the gastrocnemius muscle in changes in its blood supply during stretching].
In the m. gastrocnemius of anesthetized cats, the pressure of tissue resistance balancing was 5 mm Hg initially and developed a 7-fold increase in longitudinal stretch of the muscle by 10-20% when the total mechanical tension increased 20-fold (from 2400 to 47 662 H/m2) and the blood flow reduced from 5.0 to 3.0 ml . min-1 (100 r)-1. Decrease of the blood flow in stretching and the postelongation hyperemia could not be reproduced in external compression of the muscle equal to the balancing pressure at a given stretching. Only the external pressure 50 and 100 mm Hg decelerated the blood flow and developed a hyperemia even though a lesser one than the postelongation hyperemia. The effect of longitudinal muscle stretch on its vessels is not limited by their compression with the "intramuscular pressure".


Co-administration of SARS-CoV-2 and influenza vaccines in healthcare workers: Results of two vaccination campaigns in a large teaching hospital in Rome.
The concurrent administration of COVID-19 and influenza vaccines has arisen as a promising approach to bolster protection against respiratory pathogens and improve vaccination rates. However, there remains a lack of data regarding the prevalence of co-administration across several vaccination campaigns, especially among healthcare workers (HCWs). Therefore, this study aims to shed light on the acceptance of co-administration strategies among HCWs during the two campaigns following the introduction of the anti-SARS-CoV-2 vaccine. A retrospective cohort study was conducted among the HCWs of the Fondazione Policlinico Universitario "A. Gemelli" IRCCS, a research hospital in Rome. Hospital administrative databases were accessed to gather information about vaccination for SARS-CoV-2 and influenza during the 2021/2022 and 2022/2023 vaccination campaigns. The study included 7399 HCWs. The co-administration of anti-SARS-CoV-2 and influenza vaccines presented a significant rise in 2022/2023 compared to the previous vaccination campaign (+38%): this was confirmed for every professional category, with the largest increases among resident doctors (+47%) and physicians (+44%), and also for every age category, but it was particularly evident for the youngest health professionals. The probability of co-administration uptake during the 2022/2023 campaign was significantly higher for males, and for those that received co-administration during the 2021/2022 campaign, while the probability was lower for nurses and administrative staff. This study highlights the co-administration procedure as a valuable and effective tool in annual vaccination campaigns for SARS-CoV-2 and influenza. The procedure's safety and streamlined logistics make it increasingly attractive for implementation, particularly among HCWs.


Protocol for systematic review of ethical declarations made in clinical publications concerning COVID-19.
COVID-19 is a respiratory disease caused by a coronavirus, designated SARS-CoV-2, which is responsible for a global pandemic in 2020. Public interest in this disease has led to the publication of thousands of articles in the medical literature in a very short timeframe. It is imperative that medical research into COVID-19 is conducted quickly and safely, and that due reference is given to the ethical considerations enshrined in the ICH GCP guidelines, according to the Declaration of Helsinki. In order to review the reporting of ethical considerations in these papers, we hereby propose a protocol for a systematic review of COVID-19 papers up to April 14 th 2020. The search criteria proposed for the review are based upon what would be a reasonable search conducted by a lay member of the public with access to PubMed.gov. It is proposed to publish the findings of the review with a summary of the institutional Research Ethics Committee response to the challenges of reviewing and approving clinical research proposals in the time of a pandemic.


Acute and Long-Term Impact of High-Protein Diets on Endocrine and Metabolic Function, Body Composition, and Exercise-Induced Adaptations.
High-protein diets have been shown to improve body composition through alterations in satiety, muscle protein synthesis, and the thermic effect of food. Given these findings, the purpose of this review is to discuss the integration of the specific hormonal and metabolic effects of high-protein diets following both acute and long-term usage, especially with regard to body composition. Full-text articles were obtained through PubMed by using the terms "high-protein diet and body composition," "high-protein diet and exercise," "high-protein diet risk," "high-protein diet side effects," "protein quality PDCAAS," "RDA for protein," and "daily protein recommendation." Articles were initially screened according to their title and abstract; careful evaluation of the full manuscripts was then used to identify relevant articles. The higher satiety exerted by high-protein diets is generated through increments in anorexigenic, as well as decrements in orexigenic hormones. Improvements in muscle mass are achieved by activation of muscle protein synthesis acting through the mTOR pathway. High thermic effect of food is caused due to necessary deamination, gluconeogenesis, and urea synthesis caused by high-protein diets. Interestingly, high-protein diets in both hypo- and normocaloric conditions have shown to improve body composition, whereas in combination with hypercaloric conditions does not seem to increase fat mass, when the excess energy comes from protein. High protein diets effectively improve body composition by acting through different pathways.


A super stable assembled P nanowire with variant structural and magnetic/electronic properties via transition metal adsorption.
By means of first-principles calculations, we systematically investigated the structure, stability and magnetic and electronic properties of one-dimensional P nanowire (1D-P10 NW) assembled by Pn subunits (n = 2, 8) and transition metal doped 1D-P10 NW. Our calculations showed that the assembled 1D-P10 NW is super stable in thermodynamic, dynamic, thermal and chemical perspectives. Moreover, when the assembled 1D-P10 NW is decorated with transition metals (TM = Ti ∼ Zn, Zr ∼ Mo), structural transformation occurs (to sandwich or quasi-sandwich chains), and various magnetic and electronic characteristics are introduced to the nanowire. Particularly, the sandwich chains 1D-Mn2@P10 and 1D-V1@P5 are a ferromagnetic semiconductor and a ferromagnetic half-metal, respectively, and the magnetic anisotropy energies are both ∼0.3 meV per Mn/V atom. Our theoretical studies proposed a super stable 1D P nanowire and also offer a feasible approach to reach P5-TM-P5-TM chains with diverse magnetic and electronic properties, as well as ferromagnetic vdW-type 2D systems, which are promising in nanoelectronic devices and spintronics.


Determination of drug resistance of Mycobacterium tuberculosis cultures.
A total of 3,303 strains of Mycobacterium tuberculosis were tested for sensitivity to streptomycin (SM), isoniazid (INH), and p-aminosalicylic acid (PAS) by the Steenken modified minimal inhibitory concentration (MIC) test. A simultaneous double blind comparison was carried out on 277 selected strains by the Steenken MIC test and the Canetti proportion method. Agreement between the results for the two tests was 82% for SM, 95% for INH, and 89% for PAS. A small number of strains appeared to be sensitive when tested by one method but resistant by the other. MIC determinations were carried out on 83 strains by using Steenken-Smith, Lowenstein-Jensen, and Middlebrook 7H10 media containing a more extended range of concentrations of the test drugs. The MIC values for both SM and dihydrostreptomycin increased on Steenken-Smith medium compared with the other two. INH did not show any medium effect, whereas PAS showed increased MIC values in 7H10 agar. The significance of the comparisons of the MIC values on the various media is discussed in terms of possible changes in the drug sensitivity testing methods used at present in this laboratory.


Health-related quality of life and emotional distress in patients with dizziness: a cross-sectional approach to disentangle their relationship.
Dizziness is frequently encountered in medical practice, often takes a chronic course and can impair the health related quality of life (HRQoL). However results on the extent of this impairment of HRQoL are mixed. Furthermore, the relationship between dizziness and the HRQoL is only partially understood. The role of clinical symptoms of dizziness and psychosocial factors such as emotional distress on this relationship is for the most part unknown. The cross-sectional study evaluated the HRQoL in 203 patients suffering from dizziness, using the Medical Outcomes Studies 36-Item Short-Form Health-Survey (SF-36). The results were correlated with the severity of dizziness, using the Dizziness Handicap-Inventory (DHI), with emotional distress, using the Hospital Anxiety and Depression-Scale (HADS) and with further clinical symptoms and psychosocial parameters. In a multivariate hierarchical regression analysis associated variables which explain significant variance of the mental and physical HRQoL (MCS-36, PCS-36) were identified. Patients suffering from dizziness showed a markedly reduced mental and physical HRQoL. Higher DHI and HADS scores were correlated with lower MCS-36 and PCS-36 scores. Taken together DHI and vertigo characteristics of dizziness explained 38% of the variance of PCS-36. Overall explained variance of PCS-36 was 45%. HADS and living with a significant other explained 66% of the variance of MCS-36 (overall variance explained: 69%). Both the physical and mental HRQoL are significantly impaired in patients with dizziness. While the impairment in PCS-36 can be explained by clinical symptoms of the dizziness, MCS-36 impairment is largely associated with psychosocial factors. To improve the patient's overall well-being significantly and permanently doctors have to keep in mind both, the clinical symptoms and the psychosocial factors. Therefore, in addition to the physical examination doctors should integrate a basic psychological examination into the daily routine with dizziness patients.


Strategies for navigating the healthcare credit market.
Not-for-profit healthcare organizations are experiencing a tightened credit market due to financial stresses on the healthcare industry such as declining payments, effects of the Balanced Budget Act of 1997, and the shift to outpatient care. In the future, healthcare organizations wanting to access the capital market will be expected to preserve cash as an "insurance policy," offer greater security and stricter covenants, and report financial information on a quarterly basis. To meet these requirements and navigate today's tighter credit market, healthcare financial managers will need to focus on the organization's most reliably profitable areas of business, link strategic and financial issues, and carefully monitor the balance sheet.


Trends in general practitioners/family doctors workload in Croatia in period 1995-2012.
This research aimed to present public data describing the Croatian family doctors (FDs) workload, presented as the average number of patients on the lists, and annual and daily number of consultations per one FD team during the period 1995-2012. Croatian Health Service Yearbook for consecutive years was used as basis for data collection. Impressive increase number of persons on FD lists and significant increase of rate of persons per FD team were observed. Average number of contact to FD team also showed constant increase, starting at level of 5.9 per year in 1995 and reaching 9.6 per year in 2012. However, average number of direct consultation (including physical examination) to FD showed modest increase from level of 4.1 per year in 1995 till level of 5.8 per year in 2005. The number of referrals per one visit remain stable, but the number of referrals per one direct consultation decreased. The data stress problem of discrepancy of increasing number of persons on FD lists and stagnation trend of number of FD teams in Croatian primary health care. Results suggested problem of increasing workload of FD teams, but further research are needed for deeper amylases of the FDs workload.


4-nitrophenyl phosphate--characterization of high-purity materials for measuring alkaline phosphatase activity in human serum.
We studied 53 lots of 4-nitrophenyl phosphate (I), obtained from 20 different commercial suppliers, and used this information to set specifications for it. Using these well-defined specifications, we classified 21 lots of I as "unacceptable," 26 lots as "borderline," and six as "acceptable." All lots were shown to contain some 4-nitrophenol and inorganic phosphate. However, "acceptable" I had < 0.3 mmol of 4-nitrophenol and < 10 mmol of inorganic phosphate per mole of I. The mole concentration of I (based on disodium hexahydrate, formula weight 371) was determined by enzymic conversion to 4-nitrophenol in five lots of "acceptable" materials. The mole fraction of I ranged from 0.982 to 0.998. From these measurements and from estimates of impurities that absorb at 311 nm, as determined by liquid chromatography and spectrophotometry at other wavelengths, our best estimate of the molar absorptivity of I at 311 nm in 10 mmol/L NaOH at 25 degrees C was 9867 L x mol-1 x cm-1, with a total uncertainty of 76 L x mol-1 x cm-1. We recommend that I used in clinical laboratories for measurement of alkaline phosphatase activity in serum meet the specifications given in this paper: I content > 98%, maximum activity > 98% in comparative testing with other "acceptable" lots of I, and impurities not to exceed the values cited above.


Fertility desire and intention of people living with HIV/AIDS in Tanzania: a call for restructuring care and treatment services.
Scaling up of antiretroviral therapy (ART) is currently underway in sub-Saharan Africa including, Tanzania, increasing survival of people living with HIV/AIDS (PLWHA). Programmes pay little attention to PLWHA's reproductive health needs. Information on fertility desire and intention would assist in the integration of sexual and reproductive health in routine care and treatment clinics. A cross-sectional study of all PLWHA aged 15-49 residing in Kahe ward in rural Kilimanjaro Tanzania was conducted. Participants were recruited from the community and a local counselling centre located in the ward. Data on socio-demographic, medical and reproductive characteristics were collected through face-to-face interviews. Data were entered and analysed using STATA statistical software. A total of 410 PLWHA with a mean age of 34.2 and constituting 264 (64.4%) females participated. Fifty-one per cent reported to be married/cohabiting, 73.9% lived with their partners and 60.5% were sexually active. The rate of unprotected sex was 69.0% with 12.5% of women reporting to be pregnant at the time of the survey. Further biological children were desired by 37.1% of the participants and lifetime fertility intention was 2.4 children. Increased fertility desire was associated with living and having sex with a partner, HIV disclosure, good perceived health status and CD4 count ≥200 cells for both sexes. Reduced desire was associated with havingmore than 2 children among females, divorce or separation, and having a child with the current partner among both males and females. Fertility desire and intention of PLWHA was substantially high though lower than that of the general population in Tanzania. Practice of unprotected sexual intercourse with higher pregnancy rate was observed. Fertility desire was determined by individual perceived health and socio-family related factors. With increasing ART coverage and subsequent improved quality of life of PLWHA, these findings underscore the importance of integrating reproductive health services in the routine care and treatment of HIV/AIDS worldwide. The results also highlight a group of PLWHA with potentially high desire for children who need to be targeted during care.


Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI.
Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to a dysregulated host response to infection. Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome. The pathophysiology of sepsis-associated AKI (sepsis-AKI) remains incompletely understood, but mitochondria have emerged as key players in the pathogenesis. Therefore, our aim was to identify mitochondrial damage in patients with sepsis-AKI. We conducted a clinical laboratory study using "warm" postmortem biopsies from sepsis-associated AKI patients from a university teaching hospital. Biopsies were taken from adult patients (n = 14) who died of sepsis with AKI at the intensive care unit (ICU) and control patients (n = 12) undergoing tumor nephrectomy. To define the mechanisms of the mitochondrial contribution to the pathogenesis of sepsis-AKI, we explored mRNA and DNA expression of mitochondrial quality mechanism pathways, DNA oxidation and mitochondrial DNA (mtDNA) integrity in renal biopsies from sepsis-AKI patients and control subjects. Next, we induced human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS) for 48 h to mimic sepsis and validate our results in vitro. Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass. Sepsis-AKI patients had lower mRNA expression of mitochondrial quality markers TFAM, PINK1 and PARKIN, but not of MFN2 and DRP1. Oxidative DNA damage was present in the cytosol of tubular epithelial cells in the kidney of sepsis-AKI patients, whereas it was almost absent in biopsies from control subjects. Oxidative DNA damage co-localized with both the nuclei and mitochondria. Accordingly, HUVECs induced with LPS for 48 h showed an increased mnSOD expression, a decreased TFAM expression and higher mtDNA damage levels. Sepsis-AKI induces mitochondrial DNA damage in the human kidney, without upregulation of mitochondrial quality control mechanisms, which likely resulted in a reduction in mitochondrial mass.