[The socio-hygienic monitoring as an integral system for health risk assessment and risk management at the regional level].
The information and analytical framework for the introduction of health risk assessment and risk management methodologies in the Sverdlovsk Region is the system of socio-hygienic monitoring. Techniques of risk management that take into account the choice of most cost-effective and efficient actions for improvement of the sanitary and epidemiologic situation at the level of the region, municipality, or a business entity of the Russian Federation, have been developed and proposed. To assess the efficiency of planning and activities for health risk management common method approaches and economic methods of "cost-effectiveness" and "cost-benefit" analyses provided in method recommendations and introduced in the Russian Federation are applied.


Dose prescription and treatment planning based on FMISO-PET hypoxia.
The study presents the implementation of a novel method for incorporating hypoxia information from PET-CT imaging into treatment planning and estimates the efficiency of various optimization approaches. Its focuses on the feasibility of optimizing treatment plans based on the non-linear conversion of PET hypoxia images into radiosensitivity maps from the uptake properties of the tracers used. PET hypoxia images of seven head-and-neck cancer patients were used to determine optimal dose distributions needed to counteract the radiation resistance associated with tumor hypoxia assuming various scenarios regarding the evolution of the hypoxic compartment during the treatment. A research planning system for advanced studies has been used to optimize IMRT plans based on hypoxia information from patient PET images. These resulting plans were compared in terms of target coverage for the same fulfilled constraints regarding the organs at risk. The results of a planning study indicated the clinical feasibility of the proposed method for treatment planning based on PET hypoxia. Antihypoxic strategies would lead to small improvements in all the patients, but higher effects are expected for the fraction of patients with hypoxic tumors. For these, individualization of the treatment based on hypoxia PET imaging could lead to improved treatment outcome while creating the premises for limiting the irradiation of the surrounding normal tissues. The proposed approach offers the possibility of improved treatment results as it takes into consideration the heterogeneity and the dynamics of the hypoxic regions. It also provides early identification of the clinical cases that might benefit from dose escalation as well as the cases that could benefit from other counter-hypoxic measures.


Is the canadian health care system suffering from abuse? A commentary.
The authors suggest that more attention must be paid to acting on information about the effectiveness of diagnostic and therapeutic procedures, their cost-effectiveness, and their net benefit to Canadians. Canadian health professionals and policy-makers must translate information on ineffective procedures, poor use of effective procedures, and the relative cost of services delivered in different settings by different personnel into changes in use levels and patterns. Another challenge, which involves the general public as well, is to achieve an informed social consensus about the level of health care spending and its distribution across types of services. Education of Canadians, including health professionals, is needed so that they can contribute responsibly and effectively to this change.


Cryptic genetic variation in natural populations: a predictive framework.
Understanding how populations respond to rapid environmental change is critical both for preserving biodiversity and for human health. An increasing number of studies have shown that genetic variation that has no discernable effect under common ecological conditions can become amplified under stressful or novel conditions, suggesting that environmental change per se can provide the raw materials for adaptation. Indeed, the release of such hidden, or "cryptic," genetic variants has been increasingly viewed as playing a general and important role in allowing populations to respond to rapid environmental change. However, additional studies have suggested that there is a balance between cryptic genetic variants that are potentially adaptive in future environments and genetic variants that are deleterious. In this article, we begin by discussing how population and environmental parameters-such as effective population size and the historical frequency and strength of selection under inducing conditions-influence relative amounts of cryptic genetic variation among populations and the overall phenotypic effects of such variation. The amount and distribution of cryptic genetic variation will, in turn, determine the likelihood that cryptic variants, once expressed, will be adaptive or maladaptive during environmental transitions. We then present specific approaches for measuring these parameters in natural populations. Finally, we discuss one natural system that will be conducive to testing whether populations that vary in these parameters harbor different amounts, or types, of cryptic genetic variation. Generally, teasing apart how population and environmental parameters influence the accumulation of cryptic genetic variation will help us to understand how populations endure and adapt (or fail to adapt) to natural environmental change and anthropogenic disturbance.


Comparative radiologic identification with standardized single CT images of the paranasal sinuses-Evaluation of inter-rater reliability.
The aim of this study was to assess the reproducibility of a standardized image for personal identification (SIPI), used in the comparative analysis of paranasal sinuses, and test the effect of inaccurate reformation of the SIPI on suitability for comparative identification. Five raters with different professional backgrounds independently reformatted SIPIs from ten post-mortem head CTs. Inter-rater, intra-rater agreement as well angular deviations between reformatted SIPI images and reference SIPI images were calculated. Second, raters assessed the suitability of 70 accurately and inaccurately reformatted SIPIs for identification with a 4-point Likert scale. Inter-rater agreement as well as levels of significance regarding image suitability were calculated. Inter-rater agreement regarding reproducibility of SIPI reformation was excellent (inter-rater correlation coefficient (ICC) 0.9995, intra-rater ICC 0.9983). Deviation between the angular dimensions of the reformatted SIPIs and the reference SIPIs was ≤1° in 94% of all 300 measurements. Inter-rater agreement regarding the effect of inaccurate SIPI reformation on suitability for comparative identification was fair (ICC 0.6809). There was no statistically significant difference between raters' evaluation of image suitability (p=0.9755). This study shows that the standardized image for personal identification can be accurately reformatted by different raters with varying professional backgrounds. In addition, raters agree that inaccurately reformatted SIPIs are still suitable for comparative identification in the majority of cases.


Quantitative facial muscle ultrasound: feasibility and reproducibility.
In this study we describe a protocol for quantitative ultrasound of facial muscles (procerus, zygomaticus major, levator labii superior, depressor anguli oris, mentalis, orbicularis oris pars labialis, orbicularis oris pars marginalis). Muscle thickness (MT) and echo intensity (EI) were measured in 12 healthy subjects and a myotonic dystrophy type 1 patient. MTs ranged from 0.15 to 0.30 mm, except for the procerus muscle (0.06 mm). EIs ranged from 1 to 34, except for the procerus muscle. MT reproducibility was fair for the orbicularis oris pars labialis, excellent for the procerus and levator labii, and good for the other muscles. The myotonic dystrophy type 1 patient showed high EIs, outside the range in healthy subjects in 6 of the 7 muscles. MT was lower than the range seen in healthy subjects in 4 muscles. Quantitative muscle ultrasound of the facial muscles is feasible and shows moderate to excellent reproducibility.


Economic crisis and inequalities in health systems in the countries of Southern Europe.
The current article addresses the issue of health system inequalities in the countries of Southern Europe, specifically Spain, Greece, Italy, and Portugal. The study resulted from a non-systematic literature review, based on the scoping review proposal. We begin by presenting a brief contextualization of the social welfare state systems in these European countries, highlighting the principal specificities and differences in relation to other European welfare state systems. Next, we describe the health systems in the four countries, emphasizing the respective reform processes and the main health inequalities that have characterized them before and during the economic crisis. The crisis and austerity policies have greatly increased the level of dissatisfaction with healthcare provision in these countries, particularly in Greece and Portugal. In this sense, we conduct a comparative discussion of the health inequalities, identifying both common trends and differences. In the four countries, the social gradient (particularly in education, income, and labor) represents the principal determinant of health inequalities, while not ruling out geographic inequalities in access to health services as the result of different levels of economic development in the various regions. Finally, we discuss the recent debate in the international literature on the relationship between different welfare state systems and health inequalities, and precisely the critique of the use of welfare state typologies as a determinant of health and health inequalities.


Low-power 808-nm laser irradiation inhibits cell proliferation of a human-derived glioblastoma cell line in vitro.
It has been reported that low-power laser irradiation (LLI) can modulate various biological processes including cell proliferation. Some reports suggest that LLI interferes with the cell cycle and inhibits cell proliferation, while others suggest that LLI has a stimulatory effect. Mechanisms underlying the effects of LLI remain unclear. Since the effects of LLI on cancer cells are not well understood, with the aim of developing an LLI therapy for malignant glioblastoma, we investigated the effects of LLI on the cell proliferation of the human-derived glioblastoma cell line A-172. Glioblastoma cell cultures were irradiated with a diode laser at a wavelength of 808 nm and the effects on cell viability and proliferation were examined. Cell counting at 24 and 48 h after irradiation showed that LLI (at 18, 36 and 54 J/cm(2)) suppressed proliferation of A-172 cells in a fluence-dependent manner (irradiation for 20, 40 and 60 min). A reduction in the number of viable cells was also demonstrated by a fluorescent marker for viable cells, calcein acetoxymethylester (calcein-AM). The reduction in cell viability was not associated with morphological changes in the cells or with necrotic cell death as demonstrated by propidium iodide staining. LLI also had little effect on cell proliferation as shown by 5-bromo-2'-deoxyuridine staining. We discuss possible mechanisms underlying the suppressive effect of 808-nm LLI on the viability of human-derived glioblastoma A-172 cells.


Bullying among school children: a case report.
The case study shows an example of peer violence, a physical attack on a high school student. The attacker was a child his own age attending the same school. Immediately after the attack the victim visited his chosen family doctor accompanying by mother. After interviewing in calm and safe environment and physical examination he was referred to the hospital emergency, because of evident trauma. During the follow up, it was obvious that the patient is interested in talking about the event but is uncomfortable to do so in front of his mother. Having obtained the mother's permission the conversation was carried out alone and the patient revealed all the details regarding the assault as well as his own feelings. The case study contains a description of the incident, the basic information regarding types of abuse amongst children, information on how to approach a victim as well as the obligation to report every type of abuse.


Plant circadian networks and responses to the environment.
There are regular, and therefore predictable, environmental changes on Earth due to the rotation of the planet on its axis and its orbit around the sun. Thus organisms have adapted their metabolism, physiology and behaviour to minimise stresses caused by unfavourable conditions and maximise efficiency of growth. Additionally, most organisms are able to anticipate these changes and accordingly maximise metabolic efficiency and growth, because they have a complex biological time-keeping system commonly referred to as the circadian clock. Multiple pathways in plants are organised in a temporal manner through circadian clock-regulation of gene transcription and post-translational modifications. What is becoming more apparent is the bidirectional nature of interactions between the clock and stress response pathways. Until recently, the focus of many studies had been on the unidirectional, hierarchical control of biological processes by the circadian clock, and impacts on the clock in response to environmental stress had been largely ignored. Studies of interactions of the circadian clock with the environment have primarily been to understand mechanisms of entrainment. We review the evidence and implications of the reciprocal interactions between the clock and the environment.


Incidence of acute kidney injury following total joint arthroplasty: a retrospective review by RIFLE criteria.
Total joint arthroplasty (TJA) is a common procedure with demand for arthroplasties expected to increase exponentially. Incidence of acute kidney injury (AKI) following TJA is reportedly low, with most studies finding an incidence of <2%, increasing to 9% when emergency orthopaedic patients are included. Retrospective medical record review of consecutive primary, elective TJA procedures was undertaken at a large tertiary hospital (Alfred). Demographic, peri-operative and post-operative data were recorded. Factors associated with AKI (based on RIFLE criteria) were determined using multiple logistic regression. Between January 2011 and June 2013, 425 patients underwent TJA; 252 total knee replacements (TKR) and 173 total hip replacements (THR). Sixty-seven patients (14.8%) developed AKI, including 51 TKR. Factors associated with AKI (adjusting for known confounders) include increasing body mass index [adjusted odds ratio (AOR) 1.14; 95% CI: 1.07, 1.21], older age (AOR 1.07; 95% CI 1.02, 1.13) and lower pre-operative glomerular filtration rate (AOR 0.97; 95% CI 0.96, 0.99) and taking angiotensin-converting enzyme inhibitors (AOR 2.70; 95% CI 1.12, 6.48) and angiotensin-II receptor blockers (AOR 2.64; 95% CI 1.18, 5.93). In most patients, AKI resolved by discharge, however, only 62% of patients had renal function tests after discharge. This study showed a rate of AKI of nearly 15% in our TJA population, substantially higher than previously reported. Given that AKI and long-term complications are associated, prospective research is needed to further understand the associated factors and predict those at risk of AKI. There may be opportunities to maximize the pre-operative medical management and mitigate risk.


The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis.
B23 is a major phosphoprotein in the interphasic nucleolus where it is involved in the assembly of pre-ribosomes. Using several cultured animal cells, we report that, in addition to the known redistribution of the protein during mitosis, B23 also becomes associated with mitotic spindle poles starting from early prometaphase onwards. Colocalization of B23 with the protein NuMA (Nuclear Mitotic Apparatus protein) was studied in mitotic cells and taxol-arrested cells. During the onset of mitosis, we observed that a fraction of B23 associates with, and dissociates from, the poles later than NuMA. At metaphase, both proteins are colocalized at the poles. The polar redistribution of both B23 and NuMA is mediated by microtubules. In taxol-treated cells, B23 is associated with the microtubule minus ends in the center of mitotic asters together with NuMA. Association of B23 with microtubule minus ends of mitotic asters was further confirmed with an in vitro assay, where B23 was found by western blotting to co-sediment with taxol-induced microtubule asters formed in a mitotic cell extract. Immunolabeling demonstrated that B23 and NuMA were both present at the center of the asters. Furthermore, an additional hyperphosphorylated form of B23 appeared when microtubule asters formed and associated with the asters. Immunodepletion of B23 from the mitotic extract revealed that taxol-induced microtubule asters were still observed in B23-immunodepleted mitotic extract, indicating that the presence of B23 at the poles is unlikely to be essential for spindle formation or stabilisation.


What are the situational and behavioral factors associated with condomless anal sex without pre-exposure prophylaxis in MSM?
This study aimed to identify situational and behavioral factors associated with condomless anal sex without on-demand PrEP in the open-label extension (OLE) study of the ANRS-IPERGAY trial. Univariable and multivariable modified Poisson regressions with a generalized estimating equation (GEE) were used. The attributable risk percentage for each explanatory variable and for condomless anal sex without PrEP was calculated. In the OLE, 19% of anal intercourses were unprotected (i.e. no PrEP or condom). Of these, 85% were attributable to sexual intercourse with main partners and 47% with HIV-negative partners. The following factors were positively associated with condomless anal sex without PrEP: a depressive episode in the previous 12 months [aR (95% CI), P-value: 1.49 (1.02--2.17), 0.039], a higher number of sexual intercourses during the previous 4 weeks [1.01 [1.002--1.02], 0.014], and sexual intercourses under the influence of alcohol [1.45 (1.10--1.92), 0.008]. By contrast, condomless anal sex without PrEP was less frequent during sexual intercourses with known casual, unknown casual and multiple partners [0.20 (0.14--0.30), <0.001; 0.10 (0.05--0.20), <0.001; 0.11 (0.05--0.29), <0.001, respectively], as well as with HIV+ partners with an undetectable viral load and HIV+ partners with a detectable/unknown viral load or unknown serology status [0.57 (0.38--0.86), 0.007; 0.52 (0.32--0.87), 0.012, respectively]. Choosing to have condomless anal sex without PrEP depends primarily on the sexual partner's characteristics (level of intimacy, serological status). This reflects a form of rationality in HIV risk management. However, our results raise questions about the true efficacy of managing HIV risk using this approach.


[Usefulness of endoscopic ultrasound guided elastography in the assessment of solid pancreatic lesions].
endoscopic ultrasonography (EUS) elastography is considered a useful tool for the evaluation of solid pancreatic lesions (SPL). The aim of our study was to evaluate the diagnostic performance of elastography in patients with SPL. A prospective, cross-sectional study was performed at the Rebagliati Hospital between July 2017 and June 2018. Patients with a diagnosis of SPL and echoendoscopic study, elastography and FNA were included. Qualitative and quantitative elastography: strain ratio (SR) and strain histogram, were performed and analyzed with histopathological results. The diagnostic accuracy of EUS elastography in detecting malignancy was calculated using receiver operating curve analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the detection of malignancy were calculated. Out of 832 EUS examinations performed, 46 patients with SPL (mean age, 64.6 years; 29 women) were included in the study. Pancreatic adenocarcinoma was diagnosed in 36 cases. In qualitative elastography, score 3 was most frequent (n = 39, 84.8%) with sensitivity, specificity and accuracy of 88.9%, 30% and 76.1%, respectively, for predict adenocarcinoma. A strain ratio of 15 or higher (100% sensitivity, 66.7% specificity and 97.8% accuracy) and a histogram of less than 49 (66.7% sensitivity, 97.6% specificity and 95.6% accuracy) predicts malignancy in SPL, with area under a ROC curve of 0.941 (95% CI, 0.82 - 1.0). EUS elastography provides information to predict the malignant nature of the pancreatic lesion. In our study, the elastographic detection of a score 3, SR≥15 or a histogram <49 predicts the presence of malignancy in LSP.


An outbreak of serotype 1 Streptococcus pneumoniae meningitis in northern Ghana with features that are characteristic of Neisseria meningitidis meningitis epidemics.
The Kassena-Nankana District (KND) of northern Ghana lies in the African meningitis belt, where epidemics of bacterial meningitis have been reoccurring every 8-12 years. These epidemics are generally caused by Neisseria meningitidis, an organism that is considered to be uniquely capable of causing meningitis epidemics. We recruited all patients with suspected meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were collected and analyzed by standard microbiological techniques. Bacterial isolates were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic-resistance testing. A continual increase in the incidence of pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited strong seasonality, a broad host age range, and clonal dominance, all of which are characteristic of meningococcal meningitis epidemics in the African meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%; the majority of pneumococcal isolates were antibiotic sensitive and expressed the serotype 1 capsule. MLST revealed that these isolates belonged to a clonal complex dominated by sequence type (ST) 217 and its 2 single-locus variants, ST303 and ST612. The S. pneumoniae ST217 clonal complex represents a hypervirulent lineage with a high propensity to cause meningitis, and our results suggest that this lineage might have the potential to cause an epidemic. Serotype 1 is not included in the currently licensed pediatric heptavalent pneumococcal vaccine. Mass vaccination with a less complex conjugate vaccine that targets hypervirulent serotypes should, therefore, be considered.


Zone I retinopathy of prematurity.
Two (5.4%) of 37 patients with retinopathy of prematurity were noted to have zone I vascularization of the retina in at least one eye. Three eyes in the two patients showed plus disease with nonflorid stage 3 ridge formation and extraretinal fibrovascular proliferation. Two of the three eyes were not treated and rapidly progressed to total retinal detachment and blindness. The third eye was treated with cryotherapy and this was followed by resolution of the plus disease. Although the treated eye did not develop dragging of the retinal vessels or retinal detachment, it is unfortunately blind.


A Word on Words in Words: How Do Embedded Words Affect Reading?
A surprisingly small portion of reading research has been dedicated to investigating how the visual word recognition process is influenced by embedded words (e.g., 'arm' in 'charm'), and no research has yet investigated embedded words in a natural reading setting. Covering this issue, the present work reports analyses of eye-tracking data from the GECO bilingual book reading corpus. Word viewing times were analyzed as a function of the number, frequency and proportional length of embedded words. We anticipated two scenarios: embedded words would either facilitate processing due to increased word-letter feedback, or inhibit processing due to increased lexical competition. A main facilitatory effect of embedded words on the recognition process was established, with an increasing number of embedded words resulting in shorter word viewing times and fewer fixations. This pattern was depicted by readers of Dutch as well as readers of English. Long, high-frequency embedded words formed an exception however, as these led to inhibition (Dutch participants) or a null-effect (English participants). The present results indicate that both scenarios outlined above are at play, but with a theoretical constraint on the role of word-to-word inhibitory connections. Specifically, such connections may predominantly exist among words of similar length. Hence, embedded words generally facilitate processing through word-letter feedback, but this facilitatory effect is countered by word-to-word inhibition if the embedded word's length approximates that of its superset.


Solitary rectal cap polyp: Case report and review of the literature.
Rectal bleeding combined with the presence of a rectal mass has been traditionally associated with the presence of malignant disease. Cap polyposis is a relatively young and still undefined rare entity which mainly involves the rectosigmoid. It is characterized by the presence of inflammatory polyps. In this case report, we present a patient who was diagnosed with a solitary cap polyp of the rectum during the investigation of a bleeding rectal mass. The patient's age and the absence of family history were not in favor of malignancy, despite the strong initial clinical impression. After confirmation of the diagnosis, the patient underwent a snare excision and remains asymptomatic. Cap polyposis, although rare, should be suspected and, when diagnosed, should be treated according to location, number of polyps and severity of symptoms.


Whose depression relates to discrepancies? Testing relations between informant characteristics and informant discrepancies from both informants' perspectives.
This study examined whether mothers' and children's depressive symptoms were each uniquely related to mother-child rating discrepancies on a multidimensional dyadic construct: domains associated with parental monitoring (i.e., Child Disclosure, Parental Knowledge, and Parental Solicitation). Participants included a community sample of 335 mother/female-caregiver and child dyads (182 girls, 153 boys; 9-16 years old). Children's depressive symptoms were consistently related to each of the three domains of mother-child discrepancies. Mothers' depressive symptoms were related to perceived discrepancies in two domains (Child Disclosure and Parental Knowledge). Furthermore, these relations could not be accounted for by other informant characteristics (maternal stress, child age, child gender, child ethnicity). Findings provide important empirical support for theory suggesting that both informants' perspectives meaningfully contribute to their discrepancies in perceived behavior. Consideration of both informants' perspectives leads to valuable information as to whether any particular characteristic is an important correlate of discrepancies.


Aerobic Capacity is Related to Repeated Sprint Ability with Sprint Distances Less Than 40 Meters.
Research is inconclusive regarding the association between aerobic fitness (objectively measured VO2max) and repeated sprint performance when the sprints are less than 40 meters. Soccer athletes must be able to repeat sprints without significant decreases in speed and strength and conditioning coaches need to better understand if aerobic fitness is related to repeated sprint ability (RSA). Twenty (10 male, 10 female) Division I soccer athletes first completed a graded maximal treadmill test to measure VO2max. Then on a separate day, athletes completed the RSA test. The RSA test consisted of 10, 30-meter sprints which athletes repeated every 30 seconds. There were significant negative correlations (r ≤ -0.69, P < 0.001) between VO2max and all 10-sprint times and average sprint time. More aerobically fit Division I soccer athletes were faster at all time points during the RSA test. Aerobic fitness is associated with faster sprint times during a more anaerobic RSA test when sprint distances are less than 40 meters.


Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs.
We examined the interaction of graded hypoxia and hypercapnia on stimulation of vasopressin (AVP), ACTH, and corticosteroids in nonsurgically stressed, pentobarbital-anesthetized, gallamine-paralyzed ventilated dogs. Partial pressure of O2 in arterial blood (PaO2) levels of approximately 26-29, 38-41, 54-57, and 83-88 Torr were achieved by altering the fractional concentration of O2 in dry inspired gas with a normocapnic (PaCO2, 35 Torr) and hypercapnic (PaCO2, 59 Torr) background. Normocapnic hypoxia produced a PaO2-dependent increase in AVP, ACTH, and corticosteroids. The threshold PaO2 for AVP was lower (approximately 35 Torr) than for ACTH (approximately 45 Torr). AVP, ACTH, and corticosteroids at all PaO2 levels were higher during hypercapnia. In addition, an ACTH and corticosteroid dose-response correlation estimated the threshhold ACTH to be 20-30 pg/ml. The PaO2-dependent hormone increases and the augmentation of these relationships by hypercapnia are consistent with a peripheral chemoreceptor-mediated reflex. In addition, hypoxia and hypercapnia did not seem to alter the high sensitivity of the adrenal cortex for ACTH.


Cap-Gly proteins at microtubule plus ends: is EB1 detyrosination involved?
Localization of CAP-Gly proteins such as CLIP170 at microtubule+ends results from their dual interaction with α-tubulin and EB1 through their C-terminal amino acids -EEY. Detyrosination (cleavage of the terminal tyrosine) of α-tubulin by tubulin-carboxypeptidase abolishes CLIP170 binding. Can detyrosination affect EB1 and thus regulate the presence of CLIP170 at microtubule+ends as well? We developed specific antibodies to discriminate tyrosinated vs detyrosinated forms of EB1 and detected only tyrosinated EB1 in fibroblasts, astrocytes, and total brain tissue. Over-expressed EB1 was not detyrosinated in cells and chimeric EB1 with the eight C-terminal amino acids of α-tubulin was only barely detyrosinated. Our results indicate that detyrosination regulates CLIPs interaction with α-tubulin, but not with EB1. They highlight the specificity of carboxypeptidase toward tubulin.


Chemotherapeutic activity of 5-fluorocytosine and amphotericin B against Candida albicans in mice.
The effect of treatment with combinations of the two antifungal agents, 5-fluorocytosine (5-FC) and amphotericin B (AB), against systemic Candida albicans infections in mice was investigated. Graded doses of the single substances and of combinations of the drugs were administered daily for 21 days. The 50% curative dose (CD(50)) values were calculated on the basis of the presence or absence of C. albicans in cultures prepared from the kidneys of animals that succumbed during the experimental period or were sacrificed at the termination of the experiments. Overall, when graded doses of AB were administered in the presence of a constant, inactive dose of 5-FC (approximately one-half to one-fourth the CD(50) of 5-FC), the CD(50) values for AB were lower than those for amphotericin B alone. Similarly, the CD(50)s for 5-FC were reduced when AB was administered at a constant dose equal to one-half to one-fourth the CD(50) of AB alone. In no instance was there evidence of antagonism.


Tenascin-C mRNA and tenascin-C protein immunoreactivity increase in astrocytes after activation by bFGF.
Tenascin-C is an extracellular matrix glycoprotein with trophic and repulsive properties, involved in migratory processes in CNS. Previous reports demonstrated that this molecule is produced and secreted by astrocytes. Preliminary data on fibroblasts and astrocytes have suggested that bFGF may modulate tenascin-C expression. bFGF is a mitogenic growth factor, involved in cell differentiation and neovascularization. In the present study, we examined whether bFGF modulates the expression of tenascin-C in hippocampal astrocytes from newborn rats. Our results suggest that bFGF increases the production of tenascin-C by cultured hippocampal astrocytes. We found that both tenascin-C mRNA and protein immunoreactivity were increased after bFGF treatment. Our results also demonstrated that tenascin-C polypeptides were secreted into the extracellular medium. In agreement with previous studies, we suggest that secreted tenascin-C is mainly the high molecular weight form. In addition, our results suggest that a cleavage of the high molecular weight form. In addition, our results suggest that a cleavage of the high molecular weight form may occur in the extracellular medium causing production of proteolytic fragments, that may modify the biological properties of tenascin-C. The present results may be relevant to the understanding of lesion scarring and regeneration process.


[An end to smearing! Detecting and treating rectal rectal and anal prolapse].
Rectal prolapse is defined as the invagination of the entire wall of the rectum into or through the lumen of the anal canal. In the main it is a disorder of elderly women. The leading symptom is a sensation of incomplete defecation. Patients commonly complain of incontinence of varying severity, tenesmus, unsuccessful straining, and the passage of blood and mucus in the stools. The diagnosis is based on the history and physical examination. Equipment-based diagnostic procedures serve treatment planning. For therapy, a range of possibilities are available. Anal prolapse is categorized as third-degree hemorrhoidal disease, and the diagnosis can be made by simple inspection. Reduction may be attempted during digital examination of the rectum. Treatment is determined by the clinical presentation.


CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development.
Nuclear architecture has never been carefully examined during early mammalian development at the stages leading to establishment of the embryonic and extra-embryonic lineages. Heterogeneous activity of the methyltransferase CARM1 during these stages results in differential methylation of histone H3R26 to modulate establishment of these two lineages. Here we show that CARM1 accumulates in nuclear granules at the 2- to 4-cell stage transition in the mouse embryo, with the majority corresponding to paraspeckles. The paraspeckle component Neat1 and its partner p54nrb are required for CARM1's association with paraspeckles and for H3R26 methylation. Conversely, CARM1 also influences paraspeckle organization. Depletion of Neat1 or p54nrb results in arrest at the 16- to 32-cell stage, with elevated expression of transcription factor Cdx2, promoting differentiation into the extra-embryonic lineage. This developmental arrest occurs at an earlier stage than following CARM1 depletion, indicating that paraspeckles act upstream of CARM1 but also have additional earlier roles in fate choice.


Automated structuring of gait data for analysis purposes - A deep learning pilot example.
Clinical gait analysis can help diagnose ambulatory children with cerebral palsy and provide treatment recommendations. This group represents the largest group of children with gait problems. Currently, the workflow for 3D gait analysis involves a complex process of collecting motion capture data and other types of data, analyzing the collected data, and creating an expert knowledge-based assessment. With this in mind, a data pipeline is essential for efficiently and effectively structuring data and reducing the time and effort required for data annotation and organization.A novel data pipeline has been developed to help structure, anonymize and automate parts of the annotation process of the data. In this sense, a pilot experiment was conducted using a simple convolutional neural network to classify between hemi-plegic and diplegic gait. This experiment included preprocessing the data, training the model and testing it.The data pipeline was used to create a semi-automated annotated data set. The neural network was trained on the data set and achieved an accuracy of 0.78 and a median of 1.0 on a holdout test set.


Volunteering in the care of people with severe mental illness: a systematic review.
Much of the literature to date concerning public attitudes towards people with severe mental illness (SMI) has focused on negative stereotypes and discriminatory behaviour. However, there also exists a tradition of volunteering with these people, implying a more positive attitude. Groups with positive attitudes and behaviours towards people with SMI have received relatively little attention in research. They merit further attention, as evidence on characteristics and experiences of volunteers may help to promote volunteering. The present paper aims to systematically review the literature reporting characteristics, motivations, experiences, and benefits of volunteers in the care of people with SMI. In November 2010, a systematic electronic search was carried out in BNI, CINAHL, Embase, Medline, PsycINFO, Cochrane Registers and Web of Science databases, using a combination of 'volunteer', 'mental health' and 'outcome' search terms. A secondary hand search was performed in relevant psychiatric journals, grey literature and references. 14 papers met the inclusion criteria for the review, with data on a total of 540 volunteers. The results suggest that volunteers are a mostly female, but otherwise heterogeneous group. Motivations for volunteering are a combination of what they can 'give' to others and what they can 'get' for themselves. Overall volunteers report positive experiences. The main benefit to persons with a psychiatric illness is the gaining of a companion, who is non-stigmatizing and proactive in increasing their social-community involvement. The evidence base for volunteers in care of people with SMI is small and inconsistent. However there are potential implications for both current and future volunteering programmes from the data. As the data suggests that there is no 'typical' volunteer, volunteering programmes should recruit individuals from a variety of backgrounds. The act of volunteering can not only benefit people with SMI, but also the volunteers. Further research may specify methods of recruiting, training, supervising and using volunteers to maximise the benefit for all involved.


Carboxyhaemoglobin levels in infants with hypoxic ischaemic encephalopathy.
Hypoxic ischaemic encephalopathy (HIE) is associated with oxidative stress. A potential marker of oxidative damage is carboxyhaemoglobin (COHb) which is the product of the reaction between carbon monoxide and haemoglobin and is routinely assessed on blood gas analysis. Our objective was to test the hypothesis that higher COHb levels would be associated with worse outcomes in infants treated for HIE. A retrospective, observational study was performed of all infants who received whole body hypothermia for HIE at a tertiary neonatal intensive care unit between January 2018 and August 2021. For each participating infant, the highest COHb level per day was recorded for days one, three and five after birth. During the study period, 67 infants with a median (IQR) gestational age of 40 (38-41) weeks underwent therapeutic hypothermia for HIE. The median (IQR) COHb level on day three was higher in infants without electroencephalographic seizures (1.4 [1.1-1.4] %) compared with infants with seizures (1.1 [0.9-1.3] %, p=0.024). The median (IQR) COHb on day five was higher in infants without MRI brain abnormalities (1.4 [1.2-1.7] %) compared with infants with MRI abnormalities (1.2 [1.0-1.4] %, p=0.032). The COHb level was not significantly different between the nine infants who died compared to the infants who survived. COHb levels were higher in infants with HIE without seizures and in those with normal MRI brain examinations. We suggest that carbon monoxide has a potential protective role in HIE.


In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India.
The in vitro activity of root-tuber-peel extract of Flemingia vestita, an indigenous plant consumed by the natives in Northeast India, was tested against helminth parasites. Live parasites (nematode: Ascaris suum from pigs, A. lumbricoides from humans, Ascaridia galli and Heterakis gallinarum from domestic fowl; cestode: Raillietina echinobothrida from domestic fowl; trematode: Paramphistomum sp. from cattle) were collected in 0.9 % physiological buffered saline (PBS) and maintained at 37 +/- 1 degrees C. In vitro treatment of the parasites with the crude extract (50 mg/ml) in PBS revealed complete immobilization of the trematode and cestode in about 43 and 20 min, respectively. However, the cuticle-covered nematodes did not show any change in physical activity and remained viable even after a long period of exposure to the extract. Exposure of R. echinobothrida to genistein (0.5 mg/ml), an active principle isolated from the root-tuber peel, caused spontaneous loss of movement (paralysis) in 4.5 h, which was slower than the time required for praziquantel, the reference flukicide and cestodicide. The treated parasites showed structural alteration in their tegumental architecture. This study suggests the vermifugal activity of this plant extract against trematodes and cestodes.


Neurofilament proteins are co-expressed with desmin in heart conduction system myocytes.
We have recently shown that specialized myocytes of the rabbit heart express a cytoskeletal protein similar to the M subunit of neurofilaments (NF). Since this result was obtained using a single anti-NF-M monoclonal antibody, we tested on conduction myocytes a panel of five anti-NF antibodies, specific for each of the three NF subunits and for phosphorylated and non-phosphorylated epitopes. Two antibodies, one specific for the L subunit and one for phosphorylated M subunit of NF, reacted with specialized myocytes in immunohistochemistry. In immunoblots on conduction tissue homogenates the two antibodies recognized two polypeptides with electrophoretic mobility and solubility properties identical to those of NF-L and NF-M in the sciatic nerve. The subcellular distribution of NF immunoreactivity in specialized myocytes was very similar to desmin localization; namely, it was distributed on large filamentous bundles and on fine filaments localized transversely at the level of the Z line. At the ultrastructural level, immunoreactive filaments were localized in the intermyofibrillar space and connected myofibrils with mitochondria. Co-expression of NF proteins and desmin was also observed in vitro in a minor population of cardiac myocytes cultured from embryonic rabbit heart. In most cases NF immunoreactivity co-localized with desmin, especially where filaments were well organized, but in some cells anti-NF and anti-desmin antibodies labelled different filamentous structures. These results indicate that NF proteins are structural components of the cytoskeleton of specialized myocytes and show a subcellular distribution very similar to desmin. Such a composition of intermediate filaments indicates that in these cardiac cells muscle differentiation is compatible with the expression of neuronal proteins.


Transcriptional Profiling of Porcine HCC Xenografts Provides Insights Into Tumor Cell Microenvironment Signaling.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model-a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRAS G12D and TP53 R167H driver mutations-has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.


Medicinal and injection therapies for mechanical neck disorders.
Controversy persists regarding medicinal therapies and injections. To determine the effects of medication and injections on primary outcomes (e.g. pain) for adults with mechanical neck disorders and whiplash. We searched CENTRAL, MANTIS, CINAHL from their start to May 2006; MEDLINE and EMBASE to December 2006. We scrutinised reference lists for other trials. We included randomised controlled trials with adults with neck disorders, with or without associated headache or radicular findings. We considered medicinal and injection therapies, regardless of route of administration. Two authors independently selected articles, abstracted data and assessed methodological quality. When clinical heterogeneity was absent, we combined studies using random-effects models. We found 36 trials that examined the effects of oral NSAIDs, psychotropic agents, steroid injections, and anaesthetic agents. Trials had a mean of 3.1 on the Jadad Scale for methodological quality; 70% were high quality. For acute whiplash, administering intravenous methylprednisolone within eight hours of injury reduced pain at one week (SMD -0.90, 95% CI -1.57 to -0.24), and sick leave but not pain at six months compared to placebo in one trial. For chronic neck disorders at short-term follow-up, intramuscular injection of lidocaine was superior to placebo (SMD -1.36, 95% CI -1.93 to -0.80); NNT 3, treatment advantage 45% and dry needling, but similar to ultrasound in one trial each. In chronic neck disorders with radicular findings, epidural methylprednisolone and lidocaine reduced neck pain and improved function more than when given by intramuscular route at one-year follow-up, in one trial. In subacute and chronic neck disorders, muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits. In participants with chronic neck disorders with or without radicular findings or headache, there was moderate evidence from five high quality trials that Botulinum toxin A intramuscular injections had similar effects to saline in improving pain (pooled SMD: -0.39, 95%CI -1.25 to 0.47), disability or global perceived effect. The major limitations are the lack of replication of the findings and sufficiently large trials. There is moderate evidence for the benefit of intravenous methylprednisolone given within eight hours of acute whiplash, from a single trial. Lidocaine injection into myofascial trigger points appears effective in two trials. There is moderate evidence that Botulinum toxin A is not superior to saline injection for chronic MND. Muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.


Transcatheter aortic valve implantation in patients with bicuspid aortic valve: A patient level multi-center analysis.
We sought to evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve (BiAV). BiAV remains a relative contraindication to TAVI resulting in exclusion from TAVI trials and thus limiting data on the clinical performance of transcatheter valves in these patients. We conducted an international patient level multicenter analysis on outcomes in patients with BiAV undergoing TAVI. The primary outcome of the study was the combined early safety endpoint--a composite of 30 day mortality, stroke, life-threatening bleeding, acute kidney injury, coronary artery obstruction, major vascular complication and valve related dysfunction. Secondary endpoints included the individual components of the primary endpoint as well as post-TAVI paravalvular leak (PVL), rehospitalization, new pacemaker insertion and device success rates at 30 days and 1 year. A total of 108 patients with BiAV were identified in 21 centers in Canada, Spain, Italy, Poland and Singapore who underwent TAVI between January 2005 and March 2014. The composite primary outcome occurred in one quarter of patients (26.9%)--mainly driven by re-intervention for valve malposition (9.3%). The 30-day and 1 year mortality rates were 8.3% and 16.9% respectively with AR ≥ 3+ occurring in 9.6% of patients. Device success was achieved in 85.2% of cases with pacemaker insertion in 19.4%. While PVL was not associated with an increased risk of 30 day or 1 year mortality--Type I BiAV anatomy with left and right cusp fusion had significantly better outcomes than other valve variants. In selected patients with BiAV and severe aortic stenosis, TAVI appears both safe and feasible with acceptable clinical outcomes. Clinical studies of TAVI in this patient population are warranted.


Probabilistic learning vector quantization on manifold of symmetric positive definite matrices.
In this paper, we develop a new classification method for manifold-valued data in the framework of probabilistic learning vector quantization. In many classification scenarios, the data can be naturally represented by symmetric positive definite matrices, which are inherently points that live on a curved Riemannian manifold. Due to the non-Euclidean geometry of Riemannian manifolds, traditional Euclidean machine learning algorithms yield poor results on such data. In this paper, we generalize the probabilistic learning vector quantization algorithm for data points living on the manifold of symmetric positive definite matrices equipped with Riemannian natural metric (affine-invariant metric). By exploiting the induced Riemannian distance, we derive the probabilistic learning Riemannian space quantization algorithm, obtaining the learning rule through Riemannian gradient descent. Empirical investigations on synthetic data, image data , and motor imagery electroencephalogram (EEG) data demonstrate the superior performance of the proposed method.


Metformin monotherapy for type 2 diabetes mellitus.
Metformin is an anti-hyperglycaemic agent used for the treatment of type 2 diabetes mellitus. Type 2 diabetes may present long-term complications: micro- (retinopathy, nephropathy and neuropathy) and macrovascular (stroke, myocardial infarction and peripheral vascular disease). Two meta-analyses have been published before, although only secondary outcomes were assessed. To assess the effects of metformin monotherapy on mortality, morbidity, quality of life, glycaemic control, body weight, lipid levels, blood pressure, insulinaemia, and albuminuria in patients with type 2 diabetes mellitus. Studies were obtained from computerised searches of multiple electronic databases and hand searches of reference lists of relevant trials identified. Date of last search: September 2003. Trials fulfilling the following inclusion criteria: Diabetes mellitus type 2, metformin versus any other oral intervention, assessment of relevant clinical outcome measures, use of random allocation. Two reviewers extracted data, using a standard data extraction form. Data were summarised under a random effects model. Dichotomous data were expressed as relative risk. We calculated the risk difference (RD), and the Number Needed to Treat, when it was possible. We collected data of mean and standard deviation from changes to baseline. However many trials reported end point data. This limitation lead to the expression of the results as standardised mean differences (SMD) and an overall SMD was calculated. Heterogeneity was tested for using the Z score and the I-squared statistic. Subgroup, sensitivity analysis and meta-regression were used to explore heterogeneity. We included for analysis 29 trials with 37 arms (5259 participants), comparing metformin (37 arms and 2007 participants) with sulphonylureas (13 and 1167), placebo (12 and 702), diet (three and 493), thiazolidinediones (three and 132), insulin (two and 439), meglitinides (two and 208), and glucosidase inhibitors (two and 111). Nine studies reported data on primary outcomes. Obese patients allocated to intensive blood glucose control with metformin showed a greater benefit than chlorpropamide, glibenclamide, or insulin for any diabetes-related outcomes (P = 0.009), and for all-cause mortality (P = 0.03). Obese participants assigned to intensive blood glucose control with metformin showed a greater benefit than overweight patients on conventional treatment for any diabetes-related outcomes (P = 0.004), diabetes-related death (P = 0.03), all-cause mortality (P = 0.01), and myocardial infarction (P = 0.02). Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control, weight, dyslipidaemia, and diastolic blood pressure. Metformin presents a strong benefit for HbA1c when compared with placebo and diet; and a moderated benefit for: glycaemia control, LDL cholesterol, and BMI or weight when compared with sulphonylureas. Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Metformin produces beneficial changes in glycaemia control, and moderated in weight, lipids, insulinaemia and diastolic blood pressure. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.


[HIV infection. Immunopathology and pathogenesis].
More recent knowledge on pathogenesis and immunopathology of HIV-infection permit more hope for progress in prevention and treatment. The important steps of viral replication and persistence are restated. The considerable magnitude of HIV plasma viremia during all disease stages implies relevant conclusions concerning diagnosis, therapy and virulence. Variable pathogenesis of HIV-infection is based on viral features, cofactors and immunopathological events.


Green imine synthesis from amines using transition metal and micellar catalysis.
Imines are a versatile class of chemicals with applications in pharmaceuticals and as synthetic intermediates. While imines are conventionally synthesized via aldehyde-amine condensation, their direct preparation from amines can avoid the need for the independent preparation of the aldehyde coupling partner and associated constraints with regard to aldehyde storage and purification. The direct preparation of imines from amines typically utilizes transition metal catalysis and is often well-aligned with green chemistry principles. This review provides a comprehensive overview of transition metal catalysed imine synthesis, with a particular focus on the copper-catalyzed oxidative coupling of amines. The emerging application of micellar catalysis for imine synthesis is also surveyed due to its potential to avoid the use of hazardous solvents and intensify these reactions through reduced catalyst loadings and locally increased reactant concentrations. Future directions relating to the confluence of these two areas are proposed towards the more sustainable preparation of imines.


[Circadian rhythms of urinary parameters in children with glomerulonephritis].
Circadian rhythms of urinary parameters were studied in healthy children and those with glomerulonephritis. In healthy children, urinary excretion of many substances rhythmically varied during a day. Variations were related to the volume and specific gravity of urine, to the levels of creatinine, MDA, and SOD activities. Children with glomerulonephritis showed changes in values of circadian rhythm of urine parameters. These disorders included changes in circadian variations and mean daily values, inversion of group and individual excretion patterns, which indicates that there is an external and internal disagreement of biological rhythms in children with glomerulonephritis.


Implementation of a Nurse-driven Educational Program Improves Management of Sorafenib's Toxicities in Hepatocellular Carcinoma.
Sorafenib is the standard treatment of advanced hepatocellular carcinoma. Because of its unique toxicities, improving patients' tolerance merits close follow-up. Nurses can play a crucial role by leading a patient educational program (EP). The aim of this study was to assess whether adding EP to usual care (UC) improves patient's care. Since 2011, oncologists referred patients treated by sorafenib to the EP led by clinical nurses. The EP included a visit before the first administration, weekly telephone calls, and a visit with the nurse before each oncologist consultation. We retrospectively compared patients in the EP with those in UC followed by an oncologist and patients included in a clinical trial. Since 2005, 129 patients were treated with sorafenib for hepatocellular carcinoma: 31 in the EP (24%), 22 in a clinical trial (17%), and 76 with UC (59%). Seventy-one percent of the patients in the EP had toxicities identified during a telephone call, which prompted symptomatic measures in 65% of the patients, leading to treatment modification before the planned on-site visit in 29% of the patients. Educational program patients required fewer dose reductions (39% vs 61% for UC, P = .04), and median time to first dose reduction was shorter with EP than with UC (25 vs 45 days, P = .036). This study suggests a clinical benefit of EP related to improved toxicity management of sorafenib that resulted in fewer dose reductions. Patients treated with sorafenib may benefit from an EP. Different types of EP should be compared prospectively, focusing on patients' quality of life.


Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C proteases.
The enteroviruses poliovirus (PV), Coxsackie B virus (CVB) and rhinovirus (HRV) are members of Picornaviridae that inhibit host cell translation early in infection. Enterovirus translation soon predominates in infected cells, but eventually also shuts off. This complex pattern of modulation of translation suggests regulation by a multifactorial mechanism. We report here that eIF5B is proteolytically cleaved during PV and CVB infection of cultured cells, beginning at 3 hours post-infection and increasing thereafter. Recombinant PV, CVB and HRV 3Cpro cleaved purified native rabbit eukaryotic initiation factor (eIF) 5B in vitro at a single site (VVEQG, equivalent to VMEQG479 in human eIF5B) that is consistent with the cleavage specificity of enterovirus 3C proteases. Cleavage separates the N-terminal domain of eIF5B from its essential conserved central GTPase and C-terminal domains. 3Cpro-mediated cleavage of eIF5B may thus play an accessory role in the shutoff of translation that occurs in enterovirus-infected cells.


A novel index for assessing treatment plan quality in stereotactic radiosurgery.
OBJECTIVEStereotactic radiosurgery (SRS) is characterized by high levels of conformity and steep dose gradients from the periphery of the target to surrounding tissue. Clinical studies have backed up the importance of these factors through evidence of symptomatic complications. Available data suggest that there are threshold doses above which the risk of symptomatic radionecrosis increases with the volume irradiated. Therefore, radiosurgical treatment plans should be optimized by minimizing dose to the surrounding tissue while maximizing dose to the target volume. Several metrics have been proposed to quantify radiosurgical plan quality, but all present certain weaknesses. To overcome limitations of the currently used metrics, a novel metric is proposed, the efficiency index (η50%), which is based on the principle of calculating integral doses: η50% = integral doseTV/integral dosePIV50%.METHODSThe value of η50% can be easily calculated by dividing the integral dose (mean dose × volume) to the target volume (TV) by the integral dose to the volume of 50% of the prescription isodose (PIV50%). Alternatively, differential dose-volume histograms (DVHs) of the TV and PIV50% can be used. The resulting η50% value is effectively the proportion of energy within the PIV50% that falls into the target. This value has theoretical limits of 0 and 1, with 1 being perfect. The index combines conformity, gradient, and mean dose to the target into a single value. The value of η50% was retrospectively calculated for 100 clinical SRS plans.RESULTSThe value of η50% for the 100 clinical SRS plans ranged from 37.7% to 58.0% with a mean value of 49.0%. This study also showed that the same principles used for the calculation of η50% can be adapted to produce an index suitable for multiple-target plans (Gη12Gy). Furthermore, the authors present another adaptation of the index that may play a role in plan optimization by calculating and minimizing the proportion of energy delivered to surrounding organs at risk (OARη50%).CONCLUSIONSThe proposed efficiency index is a novel approach in quantifying plan quality by combining conformity, gradient, and mean dose into a single value. It quantifies the ratio of the dose "doing good" versus the dose "doing harm," and its adaptations can be used for multiple-target plan optimization and OAR sparing.


Inspection of additive-manufactured layered components.
Laser powder deposition (LPD) is a rapid additive manufacturing process to produce, layer upon layer, 3D geometries or to repair high-value components. Currently there is no nondestructive technique that can guarantee absence of flaws in LPD products during manufacturing. In this paper a laser ultrasonic technique for in-line inspection of LPD components is proposed. Reference samples were manufactured from Inconel and machined flaws were created to establish the sensitivity of the technique. Numerical models of laser-generated ultrasonic waves have been created to gain a deeper understanding of physics, to optimize the set-up and to verify the experimental measurements. Results obtained on two sets of reference samples are shown. A proof-of-concept prototype has been demonstrated on some specific deposition samples with induced flaws, that were confirmed by an ultra-high sensitivity X-ray technique. Experimental outcomes prove that typical micro-defects due to the layer-by-layer deposition process, such as near-surface and surface flaws in a single layer deposit, can be detected.


Diabetes mellitus in Mexico.
Diabetes in Mexico is a public health problem with considerable medical, social, and economic consequences. Although detailed data on the prevalence of diabetes and its complications are not available, health services utilization data of the Social Security organization (Instituto Mexicano del Seguro Social) indicate increasing use of primary and tertiary care for diabetes over a recent 10-yr period. A health interview survey conducted in 1988 indicated that, in different areas, from 3.5 to 12.7% of people aged greater than or equal to 65 yr are believed to have diabetes, and that rates are higher in many of the states bordering the United States. Diabetes ranks among the leading 10 causes of death throughout the country. Although the ranking varies from state to state and the diagnosis may not appear on the death certificate when death results from a complication of the disease, in 1983 diabetes was the leading cause of death in Mexico and the first or second leading cause in many of the states bordering the U.S. Gestational diabetes contributes to perinatal mortality, and in view of the high birth rates, represents an important facet of the disease in Mexico. The impact of specific complications of diabetes on morbidity and mortality in Mexico are not well delineated. The relative frequency and impact of insulin-dependent and non-insulin-dependent diabetes in Mexico are not known.


Patient safety and professional practice across European borders.
Patient safety issues have increasingly become an issue of concern by the European Union (EU). This paper explores some recent EU proposals in the area of patient safety. It suggests that these proposals may have broad implications at member state level and ultimately may impact on professional practice standards in the UK.


Development and evaluation of different normalization strategies for gene expression studies in Candida albicans biofilms by real-time PCR.
Candida albicans biofilms are commonly found on indwelling medical devices. However, the molecular basis of biofilm formation and development is not completely understood. Expression analysis of genes potentially involved in these processes, such as the ALS (Agglutinine Like Sequence) gene family can be performed using quantitative PCR (qPCR). In the present study, we investigated the expression stability of eight housekeeping genes potentially useful as reference genes to study gene expression in Candida albicans (C. albicans) biofilms, using the geNorm Visual Basic Application (VBA) for Microsoft Excel. To validate our normalization strategies we determined differences in ALS1 and ALS3 expression levels between C. albicans biofilm cells and their planktonic counterparts. The eight genes tested in this study are ranked according to their expression stability (from most stable to least stable) as follows: ACT1 (beta-actin)/PMA1 (adenosine triphosphatase), RIP (ubiquinol cytochrome-c reductase complex component), RPP2B (cytosolic ribosomal acidic protein P2B), LSC2 (succinyl-CoA synthetase beta-subunit fragment), IMH3 (inosine-5'-monophosphate dehydrogenase fragment), CPA1 (carbamoyl-phosphate synthethase small subunit) and GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Our data indicate that five genes are necessary for accurate and reliable normalization of gene expression data in C. albicans biofilms. Using different normalization strategies, we found a significant upregulation of the ALS1 gene and downregulation of the ALS3 gene in C. albicans biofilms grown on silicone disks in a continous flow system, the CDC reactor (Centre for Disease Control), for 24 hours. In conclusion, we recommend the use of the geometric mean of the relative expression values from the five housekeeping genes (ACT1, PMA1, RIP, RPP2B and LSC2) for normalization, when analysing differences in gene expression levels between C. albicans biofilm cells and planktonic cells. Validation of the normalization strategies described above showed that the ALS1 gene is overexpressed and the ALS3 gene is underexpressed in C. albicans biofilms grown on silicone in the CDC reactor for 24 hours.


Authenticity and quality evaluation of different Rhodiola species and commercial products based on NMR-spectroscopy and HPLC.
The main concern regarding the authenticity and quality of Rhodiola rosea L. (Sedum rosea (L.) Scop.) products is their adulteration with other Rhodiola species. The aim of the study was the development of a reliable and practical analytical platform for quality and quantity assessment of the characteristic molecules in three Rhodiola species (R. rosea, R. kirilowii (Regel) Maxim and R. crenulata (Hook. f. & Thomson) H. Ohba), commercial products and their possible application as markers for the authentication of R. rosea based products. The major molecules were identified by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR)-based metabolomics and quantitatively determined by high-performance liquid chromatography ultraviolet (HPLC-UV) analysis. The orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed the specific patterns in the metabolite profiles of R. rosea and R. crenulata. The coumarin crenulatin was only identified in R. crenulata and can be used as a marker to detect potential adulteration of the commercial products. Crenulatin was identified in two of the four analysed products by NMR-spectroscopy. According to the HPLC data, in less than a quarter of all products, the labelled amounts of salidroside and total rosavins were confirmed. The developed analytical platform was found to be useful in the investigations of the phytochemical diversity of different Rhodiola species, the recognition of the unique metabolites between them and the identification of adulterated products. Therefore, this approach could be applied from the earliest to the latest stages of the value chain in the manufacturing of R. rosea based products.


Serotonin transporter (SERT) polymorphisms, personality and problem-solving in urban great tits.
Understanding underlying genetic variation can elucidate how diversity in behavioral phenotypes evolves and is maintained. Genes in the serotonergic signaling pathway, including the serotonin transporter gene (SERT), are candidates for affecting animal personality, cognition and fitness. In a model species, the great tit (Parus major), we reevaluated previous findings suggesting relationships between SERT polymorphisms, neophobia, exploratory behavior and fitness parameters, and performed a first test of the relationship between single nucleotide polymorphisms (SNPs) in SERT and problem-solving in birds. We found some evidence for associations between SERT SNPs and neophobia, exploratory behavior and laying date. Furthermore, several SNPs were associated with behavioral patterns and success rates during obstacle removal problem-solving tests performed at nest boxes. In females, minor allele homozygotes (AA) for nonsynonymous SNP226 in exon 1 made fewer incorrect attempts and were more likely to problem-solve. In both sexes, there was some evidence that minor allele homozygotes (CC) for SNP84 in exon 9 were more likely to problem-solve. Only one SNP-behavior relationship was statistically significant after correcting for multiple comparisons, but several were associated with substantial effect sizes. Our study provides a foundation for future research on the genetic basis of behavioral and cognitive variation in wild animal populations.


Autoradiographic localization of cholecystokinin receptors in rodent brain.
Cholecystokinin (CCK) receptor binding sites have been localized by autoradiography in the guinea pig and rat central nervous system. [125I]CCK-triacontatriapeptide labeled the sites in brain slices with an observed association constant equal to 0.041 min-1 and a dissociation constant equal to 0.008 min-1. CCK-triacontatriapeptide (CCK-33) and the C-terminal octapeptide of CCK-33 (CCK-8) potently inhibited [125I]CCK-33 binding with Ki's of 2 nM, whereas desulfated CCK-8 (CCK8-ds) and the C-terminal tetrapeptide of CCK-33 (CCK-4) were much weaker. Receptors were concentrated in the olfactory bulb, in the superficial laminae of the primary olfactory cortex, in the deep laminae of the cerebral cortex, and in the pretectal area. Substantial numbers of sites were also found in the basal ganglia, in the amygdala, and in the hippocampal formation. [125I]CCK-33 binding sites appear to be located on fibers of the optic tract and probably on olfactory tract fibers as well. These results are discussed in terms of physiological functions associated with CCK, presynaptic receptors, and axonal flow of CCK receptors.


Implementation of facial recognition with Microsoft Kinect v2 sensor for patient verification.
The aim of this study was to present a straightforward implementation of facial recognition using the Microsoft Kinect v2 sensor for patient identification in a radiotherapy setting. A facial recognition system was created with the Microsoft Kinect v2 using a facial mapping library distributed with the Kinect v2 SDK as a basis for the algorithm. The system extracts 31 fiducial points representing various facial landmarks which are used in both the creation of a reference data set and subsequent evaluations of real-time sensor data in the matching algorithm. To test the algorithm, a database of 39 faces was created, each with 465 vectors derived from the fiducial points, and a one-to-one matching procedure was performed to obtain sensitivity and specificity data of the facial identification system. ROC curves were plotted to display system performance and identify thresholds for match determination. In addition, system performance as a function of ambient light intensity was tested. Using optimized parameters in the matching algorithm, the sensitivity of the system for 5299 trials was 96.5% and the specificity was 96.7%. The results indicate a fairly robust methodology for verifying, in real-time, a specific face through comparison from a precollected reference data set. In its current implementation, the process of data collection for each face and subsequent matching session averaged approximately 30 s, which may be too onerous to provide a realistic supplement to patient identification in a clinical setting. Despite the time commitment, the data collection process was well tolerated by all participants and most robust when consistent ambient light conditions were maintained across both the reference recording session and subsequent real-time identification sessions. A facial recognition system can be implemented for patient identification using the Microsoft Kinect v2 sensor and the distributed SDK. In its present form, the system is accurate-if time consuming-and further iterations of the method could provide a robust, easy to implement, and cost-effective supplement to traditional patient identification methods.


Patient and Physician Satisfaction with Analgesic Treatment: Findings from the Analgesic Treatment for Cancer Pain in Southeast Asia (ACE) Study.
The aim of this study was to examine patients' and physicians' satisfaction, and concordance of patient-physician satisfaction with patients' pain control status. This cross-sectional observational study involved 465 adults prescribed analgesics for cancer-related pain from 22 sites across Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Pain intensity, pain control satisfaction, and adequacy of analgesics for pain control were documented using questionnaires. Most patients (84.4%) had stage III or IV cancer. On a scale of 0 (no pain) to 10 (worse pain), patients' mean worst pain intensity over 24 hours was 4.76 (SD 2.47). More physicians (19.0%) than patients (8.0%) reported dissatisfaction with patient's pain control. Concordance of patient-physician satisfaction was low (weighted kappa 0.36; 95% CI 0.03-0.24). Most physicians (71.2%) found analgesics to be adequate for pain control. Patients' and physicians' satisfaction with pain control and physician-assessed analgesic adequacy were significantly different across countries (P < 0.001 for all). Despite pain-related problems with sleep and quality of life, patients were generally satisfied with their pain control status. Interestingly, physicians were more likely to be dissatisfied with patients' pain control. Enhanced patient-physician communication, physicians' proactivity in managing opioid-induced adverse effects, and accessibility of analgesics have been identified to be crucial for successful cancer pain management. This study was registered at ClinicalTrials.gov (identifier NCT02664987).


Rapid behavioral responses of an invertebrate larva to dissolved settlement cue.
Larvae of the nudibranch Phestilla sibogae were used to study whether a natural dissolved settlement cue (from their prey, Porites compressa, an abundant coral on Hawaiian reefs) induces behavioral responses that can affect larval transport to suitable settlement sites. As cue and larvae are mixed in the turbulent flow over a reef, cue is distributed in fine-scale filaments that the larva experiences as rapid (seconds) on/off encounters. To examine larval responses in this setting, individual larvae were tethered in a small flume with flow simulating water velocity relative to a freely swimming larva, and their responses to realistic temporal patterns of cue encounter were videotaped. Competent larvae quickly ceased swimming in cue filaments and resumed swimming after exiting filaments. The threshold cue concentration eliciting a response was 3%-17% of concentrations within heads of P. compressa in nature. When moving freely in filtered seawater, competent larvae swam along straight paths in all directions at approximately 0.2 cm s(-1), whereas in water conditioned by P. compressa, most ceased swimming and sank at approximately 0.1 cm s(-1). The ability of larvae to rapidly respond (by sinking) to brief encounters with dissolved settlement cues can enhance their rapid transport to the substratum, even in wave-driven turbulent flow.


Decision making for breast lesions initially detected at contrast-enhanced breast MRI.
The purpose of this study was to assess the clinical significance of breast lesions initially detected at contrast-enhanced breast MRI and to consider how to manage those lesions in accordance with the imaging findings and the indication for MRI. A retrospective study of 4260 consecutive breast MRI examinations was performed to identify MRI-detected enhancing lesions. In 4260 studies, 554 MRI-detected lesions were found in 417 patients, and 134 (24%) of the lesions were malignant. Pathologic confirmation was obtained for 319 (58%) lesions. Results of the subsequent imaging workup, biopsy, surgery, and imaging follow-up were reviewed. The median size of the lesions was 89 mm (malignant, 15.45 mm; benign, 7.48 mm). Irregular shape, irregular or spiculated margins, and heterogeneous or rim enhancement were seen significantly more often in malignant mass lesions (p < 0.001). Malignant lesions were more likely to exhibit rapid enhancement (p < 0.001). Benign lesions were more likely to have persistent kinetics (p < 0.001). There was a statistically significant difference (p < 0.001) between malignant (58/87, 67%) and benign lesions (128/287, 45%) with respect to sonographic detection at second-look ultrasound examinations. Malignant lesions were most often detected in patients with metastatic axillary lymph nodes with an unknown primary tumor (8/8, 100%), followed by patients with positive or close margins in recent breast cancer surgery (45/76, 59%), and patients with newly diagnosed breast cancer (44/115, 38%). Management of MRI-detected lesions should be based on both MRI findings and the patient's indication for MRI.


Selective migration from Samoa: a longitudinal study of pre-migration differences in social and psychological characteristics.
In 1981 extensive questionnaire and interview data were collected on some 100 young Samoan adults. Five years later in 1986 we determined their whereabouts and divided the data in accordance with migration status. The answers of the 35 who had migrated in the intervening period were contrasted to those 65 who remained in Samoa. The migrants differed in several distinct areas. Migrants reported a higher degree of peer-reliance as a personal adaptive strategy. Migrants also reported larger numbers of individuals in social support networks, a higher quality of support and more community involvement. They also report less expressive display of anger. Those who did not migrate reported a slightly better view of life in Samoa and abroad, as well as better relations with their friends and neighbors. These findings support a hypothesis that migrants are pre-selected to fit into migrant communities and do not appear to be misfits who are unhappy with life in Samoa.


The prevalence of hopelessness among adults: disability and other related factors.
Hopelessness has become an important issue in the fields of health and social care. This study aims to determine the prevalence of hopelessness and its association with the current health condition, disability, and other socio-demographic characteristics. The cross-sectional study sampled a population of 501 adults in Bolu, Turkey. Questionnaires included the Household Questionnaire, the Health Condition Questionnaire, Beck Hopelessness Scale, and Brief Disability Questionnaire. Data were collected through face-to-face home interviews between September 29 and October 11, 2003. The prevalence of hopelessness was 30.9%. It was higher among the literate (60.0%) (p < 0.05), males (35.0%) (p > 0.05), and agricultural workers and peasants (50.0%, 41.9%) (p < 0.05). Almost half of the participants were disabled, and 44.6% of the subjects with disabilities were hopeless (p < 0.05). Being without hope was statistically significant with gender, social class, perceived health, and disability (p < 0.05). The risk of hopelessness increased in subjects with perceived bad health, lowered social class, and disability, compared with the reference groups. In this study, hopelessness prevalence was high and it was also associated with the current state of health, perceived health, disability, and some socio-demographic variables. It will be important to increase the number of studies related to hopelessness and associated factors for improved mental health services planning at population level.


Dynamic immune landscape in vaccinated-BA.5-XBB.1.9.1 reinfections revealed a 5-month protection-duration against XBB infection and a shift in immune imprinting.
The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. This study was supported by R&D Program of Guangzhou National Laboratory (SRPG23-005), National Key Research and Development Program of China (2022YFC2604104, 2019YFC0810900), S&T Program of Guangzhou Laboratory (SRPG22-006), and National Natural Science Foundation of China (81971485, 82271801, 81970038), Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013), and State Key Laboratory of Respiratory Disease (J19112006202304).


Progression of cartilage damage and meniscal pathology over 30 months is associated with an increase in radiographic tibiofemoral joint space narrowing in persons with knee OA--the MOST study.
To determine the association of MRI-assessed worsening of tibiofemoral cartilage damage, meniscal damage, meniscal extrusion, separately and together, with progression of radiographic joint space narrowing (JSN). The Multicenter Osteoarthitis Study (MOST) Study is a cohort study of subjects with or at risk for knee osteoarthritis (OA). Knees with radiographic OA Kellgren-Lawrence grade 2 at baseline and with baseline and 30-month 1.0 T MRIs were selected for reading using the WORMS system for cartilage damage, meniscal damage, and meniscal extrusion. The association of worsening of cartilage damage, meniscal damage, and/or meniscal extrusion with increases in the JSN was performed using logistic regression. A total of 276 knees (one per subject) were included (women 68.5%, mean age 62.9 ± 7.8, mean body mass index (BMI) 30.2 ± 5.0). Worsening of each MRI feature was associated with any increase in JSN (P < 0.01). Worsening of cartilage damage was more frequently observed than worsening of meniscal damage and extrusion, and was significantly associated with both slow and fast progression of JSN. An increasing risk of JSN worsening was associated with increasing number of worsening MRI features (P for trend < 0.0001). Worsening of tibiofemoral cartilage damage, meniscal damage, and meniscal extrusion are independent predictors of JSN progression in the same compartment. Worsening of cartilage damage is more frequently observed in JSN when compared to meniscal worsening. A strong cumulative effect on JSN progression is observed for worsening of more than one MRI feature.


The Effects of Major Depressive Disorder on the Sequential Organization of Information Processing Stages: An Event-Related Potential Study.
The adverse effects of depression on patients' life have been reported but information about its effects on the sequential organization of the information processing stages remains poorly understood as previous studies focused only on distinct stages. This study adds to existing knowledge by examining the effect of major depressive disorder (MDD) on the sequential organization of information processing, executive and community functioning. Fifty-seven participants with 19 participants each for first episode depression (FMDD), recurrent episodes depression (RMDD), and healthy controls (HCs) participated in this study. They completed assessments on executive and community functioning measures, and choice reaction time task (CRTT) for the event-related potential (ERP) data. Findings revealed no significant between-group difference in executive functioning but participants with depression (FMDD and RMDD) were found to be more depressed, with FMDD participants having worse community functioning skills compared with HCs. There was no significant between-group main effect on behavioral data. ERP data showed significantly less positive-going P3b among RMDD participants compared with HCs. FMDD participants used a different information processing strategy at P1, while HCs and RMDD participants used a different processing strategy at N2b compared with the other group(s), respectively. The results suggest the use of multifaceted assessment to get a holistic view of the health status of people with MDD in order to inform clinicians on the appropriate interventional strategies needed for the patient.


Differential roles of depressive and anxious symptoms and gender in defensiveness.
Among a sample of Air Force cadets facing the prospect of basic training (N= 1,190; 1,005 men and 185 women), the influence of a defensive test-taking style on measures of depressive and anxious symptoms was examined. Participants completed the Beck Depression Inventory (Beck & Steer, 1987) and the Beck Anxiety Inventory (Beck, Epstein, Brown, & Steer, 1988), as well as the MMPI (Hathaway & McKinley, 1943) L scale. Results supported hypotheses that defensiveness would affect a self-report measure of depression but not a self-report measure of anxiety and would do so more among men than women. Applied implications of the results are discussed.


The relationship between anogenital distance and benign prostate hyperplasia-related lower urinary tract symptoms.
Anogenital distance (AGD) is the length between the genitals and anus which shows an androgenic activity in the evolution of the reproductive system in the uterine life. For prostatic evolution and development during the embryological stage, androgen exposure is required. In this study, we aimed to investigate the relationship between AGD and benign prostate hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). A total of 70 patients who were admitted to our urology clinics with LUTS due to BPH (LUTS group) and 70 patients without LUTS (control group) were included. All patients were administered an International Prostate Symptom Score form. Data including height, weight, body mass index, total prostate-specific antigen, prostate volume and uroflowmetry Qmax values of all patients were evaluated. The AGD of the LUTS and control groups was measured. The mean AGDAS values of the LUTS group were significantly lower than the control group (p = .013). There was no statistically significant difference between the two groups in terms of the mean adjusted AGDAP values (p = .241). However, the mean adjusted AGDAS values were significantly lower in the LUTS group than the control group (p = .002). Our study results suggest that AGD may be a useful marker in BPH-related LUTS.


Survival and hospitalization for intensive home hemodialysis compared with kidney transplantation.
Canadian patients receiving intensive home hemodialysis (IHHD; ≥16 hours per week) have survival comparable to that of deceased donor kidney transplant recipients in the United States, but a comparison with Canadian kidney transplant recipients has not been conducted. We conducted a retrospective cohort study of consecutive, adult IHHD patients and kidney transplant recipients between 2000 and 2011 at a large Canadian tertiary care center. The primary outcome was time-to-treatment failure or death for IHHD patients compared with expanded criteria, standard criteria, and living donor recipients, and secondary outcomes included hospitalization rate. Treatment failure was defined as a permanent switch to an alternative dialysis modality for IHHD patients, and graft failure for transplant recipients. The cohort comprised 173 IHHD patients and 202 expanded criteria, 642 standard criteria, and 673 living donor recipients. There were 285 events in the primary analysis. Transplant recipients had a reduced risk of treatment failure/death compared with IHHD patients, with relative hazards of 0.45 (95% confidence interval [95% CI], 0.31 to 0.67) for living donor recipients, 0.39 (95% CI, 0.26 to 0.59) for standard criteria donor recipients, and 0.42 (95% CI, 0.26 to 0.67) for expanded criteria donor recipients. IHHD patients had a lower hospitalization rate in the first year of treatment compared with standard criteria donor recipients and in the first 3 months of treatment compared with living donor and expanded criteria donor recipients. In this cohort, kidney transplantation was associated with superior treatment and patient survival, but higher early rates of hospitalization, compared with IHHD.


Shigella outer membrane protein PSSP-1 is broadly protective against Shigella infection.
In developing countries, Shigella is a primary cause of diarrhea in infants and young children. Although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. Thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. We have identified several conserved protein antigens that are shared by multiple Shigella serotypes and species. Among these, one antigen induced cross-protection against experimental shigellosis, and we have named it pan-Shigella surface protein 1 (PSSP-1). PSSP-1-induced protection requires a mucosal administration route and coadministration of an adjuvant. When PSSP-1 was administered intranasally, it induced cross-protection against Shigella flexneri serotypes 2a, 5a, and 6, Shigella boydii, Shigella sonnei, and Shigella dysenteriae serotype 1. Intradermally administered PSSP-1 induced strong serum antibody responses but failed to induce protection in the mouse lung pneumonia model. In contrast, intranasal administration elicited efficient local and systemic antibody responses and production of interleukin 17A and gamma interferon. Interestingly, blood samples from patients with recent-onset shigellosis showed variable but significant mucosal antibody responses to other conserved Shigella protein antigens but not to PSSP-1. We suggest that PSSP-1 is a promising antigen for a broadly protective vaccine against Shigella.


[Movement disorders in David Copperfield].
Charles Dickens' novels are a source of vivid neurological descriptions. Besides Pickwickian syndrome, many other neurological descriptions can be found in Dickens' novels. David Copperfield contains several characters with movement disorders including generalized dystonia (Mr. Uriah Heep), restless legs syndrome (the waiter), cervical dystonia (Mr. Sharp) and spasmodic dysphonia (Mr. Creakle). These neurological descriptions an probably based on the observation of actual patients.


Strategy nursing in children with compromised ventilation: Umbrella review.
Changes in the ventilation demand nursing interventions duly adapted to the management of said impairment and to the adaptability of the child/parents. This revision aimed to investigate the evidence behind the interventions performed on children with impaired ventilation.' Systematic reviews of literature in English, Spanish, French, and Portuguese from studies on nursing interventions related to children with impaired ventilation in all contexts of the clinical practice. The Joanna Briggs Institute recommendations were followed. We conducted a comprehensive search as of January 2022 and updated as of June 2023. The following electronic databases were searched: SCOPUS, Web of Science, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, MEDLINE (via PubMed), CINAHL (via EBSCO), MedicLatina (via EBSCO), The Cochrane Database of Systematic Reviews (via EBSCO), and Database of Abstracts of Reviews of Effects (DARE). Nineteen articles published between 2012 and 2022 were included in this review. Nineteen studies investigated the efficacy of respiratory exercises (Breathing Control - relaxed breathing, pursed lip breathing, Diaphragmatic breathing exercises, respiratory expansion exercise - deep breathing exercise, thoracic expansion exercises (with device), exercises for respiratory muscle strengthening and position to optimize ventilation. In the majority of the studies, it was not possible to evaluate the interventions separately. Thirteen studies evidenced the efficacy of respiratory exercises, BIPAP, and oxygen therapy. Seven articles demonstrated the effectiveness of respiratory muscle-strengthening exercises, and only three mentioned the efficacy of positioning regarding impaired ventilation. Interventions based on respiratory exercises and respiratory muscle training were the most common ones. The results suggest that nursing interventions to optimize ventilation are efficient. Nevertheless, the same present a low to moderate evidence degree, justified by the population characteristics (small and heterogeneous). There is proof of evidence for the studied interventions. However, the lack of methodological robustness points to future research to duly describe interventions, data, and comparable results, using reliable samples in which the focus of the study is clear.


Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis.
We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B - 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of - 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B - 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD.