Antibody immunoglobulin G1 and immunoglobulin G2a responses against some cystic fluid proteins of Cysticercus bovis in Balb/c mice.
Immunoglobulin (Ig) G1 and IgG2a are the surrogate markers respectively for humoral and cellular immune responses of hosts against antigens including cystic fluid proteins of Cysticercus bovis. A study was conducted to investigate the IgG1 and IgG2a responses of Balb/c mice against some individual cystic fluid proteins of C. bovis in an effort to determine the roles of each protein in inducing the humoral and cellular immune responses in host. Individual p71, p31, and p14 proteins of C. bovis were purified by separation of the proteins using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and elution of individual proteins from the gel. Six female Balb/c mice were immunized 4 times at 10-day intervals with the crude cystic fluid proteins, and sera were collected for the measurement of IgG1 and IgG2a levels against the individual proteins. Sera samples collected before the first immunization were used as negative antibody control, sera samples collected after the fourth immunization were used as positive antibody control, and crude cystic fluid protein was used as positive antigen control. All immunized mice were immune to p71, p31, p14, and crude cystic fluid proteins of C. bovis. The crude cystic fluid proteins of C. bovis induced a higher IgG2a than IgG1 level following the first and the second immunizations but switched into a higher IgG1 than IgG2a level following the fourth immunization. Protein 71 kDa (p71) induced a higher IgG2a than IgG1 level following the fourth immunization. In contrast, p14 induced a higher IgG1 than IgG2a level following the fourth immunization. Low and balance IgG1 and IgG2a levels against p31 were observed following the first to the fourth immunizations. Using IgG1 and IgG2a levels as the surrogate markers, it appears that cystic fluid antigens of C. bovis induce both humoral and cellular immune responses in Balb/c mice. The p71 appears to be a better inducer of cellular immune response, whereas p14 is a better inducer of humoral immune response of mice.


Automated Shoulder Implant Manufacturer Detection using Encoder Decoder based Classifier from X-ray Images.
Total shoulder arthroplasty is the process of replacing the damaged ball and socket joint in the shoulder with a prosthesis made with polyethylene and metal components. The prosthesis helps to restore the normal range of motion and reduce pain, enabling the patient to return to their daily activities. These implants may need to be replaced over the years due to damage or wear and tear. It is a tedious and time-consuming process to identify the type of implant if medical records are not properly maintained. Artificial intelligence systems can speed up the treatment process by classifying the manufacturer and model of the prosthesis. We have proposed an encoder-decoder based classifier along with the supervised contrastive loss function that can identify the implant manufacturer effectively with increased accuracy of 92% from X-ray images overcoming the class imbalance problem.


Evaluation of Serum Adenosine Deaminase and Inflammatory Markers in Psoriatic Patients.
Adenosine deaminase (ADA) is an enzyme involved in purine metabolism and it is a marker of nonspecific T-cell activation. Few studies have shown high levels of ADA in the epidermis and sera of psoriatic patients. Other inflammatory markers such as high-sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and serum uric acid (SUA) have shown correlations with psoriasis area severity index (PASI) score. The correlation between ADA and PASI score is still a matter of debate. The aim of this study was to evaluate serum ADA, hsCRP, SUA, and ESR in psoriatic patients and their correlation with PASI score. This study included 60 psoriatic patients divided according to PASI score into three groups (mild, moderate, and severe) each containing 20 patients. PASI score <10 was defined as mild, (10-20) moderate, and >20 severe. Twenty healthy subjects of matched age and sex were included as control. Serum ADA, hsCRP, SUA, and ESR were evaluated for patients and controls. Correlations of ADA, hsCRP, SUA, and ESR with PASI scores were done. While ADA, hsCRP, SUA, and ESR showed a significant increase in psoriatic patients compared with that of the controls (P<001), they showed no significant difference between different psoriatic groups (P>0.05) and no correlations with PASI score (P>0.05). The frequency of joint affection increased with increasing severity of psoriasis (5%, 10%, and 25% in mild, moderate, and severe psoriasis, respectively). Serum ADA, hsCRP, SUA, and ESR showed higher levels among psoriatic patients than in controls. The increased ADA in psoriatic patients supports the role of T-cell activation and proliferative disorder in the pathogenesis of psoriasis. No significant correlations were found between these biomarkers and PASI score. Further studies are needed to validate these biomarkers as diagnostic and prognostic factors in psoriasis.


Innervation of reconstructed bladder above the level of spinal cord injury for inducing micturition by contractions of the abdomen-to-bladder reflex arc.
To establish an artificial bladder reflex arc in dogs via an abdominal reflex pathway above the level of spinal cord injury to reinnervate the neurogenic bladder and restore controllable micturition. Ten beagles were used in the experiment. We anastomosed the proximal end of the right T12 ventral root and distal end of the right S2 ventral root by performing autogenous nerve grafting to build an abdomen-to-bladder reflex, whereas the right T12 dorsal root was kept intact. The early function of the reflex arc was evaluated by performing electrophysiological studies as well as by the measurement of intravesicular pressure and histological examination. Single focal stimulation of the right T12 intercostal nerves elicited evoked action potentials at the right vesicular plexus before and after horizontal spinal cord transaction between the L4 and S3 levels. Bladder contraction was successfully initiated by trains of stimuli targeting the right T12 intercostal nerves. The bladder pressures and amplitude of the complex action potentials at the bladder smooth muscles were unchanged after paraplegia was induced; they were comparable to those of the control. Prominent axonal sprouting was observed in the distal part of the nerve graft. Our data showed the effectiveness of bladder innervation above the level of spinal cord injury in inducing micturition by abdomen-to-bladder reflex contractions and, therefore, might provide a new clinical approach for restoring bladder function in individuals with paraplegia.


Fast and scalable approximate spectral matching for higher order graph matching.
This paper presents a fast and efficient computational approach to higher order spectral graph matching. Exploiting the redundancy in a tensor representing the affinity between feature points, we approximate the affinity tensor with the linear combination of Kronecker products between bases and index tensors. The bases and index tensors are highly compressed representations of the approximated affinity tensor, requiring much smaller memory than in previous methods, which store the full affinity tensor. We compute the principal eigenvector of the approximated affinity tensor using the small bases and index tensors without explicitly storing the approximated tensor. To compensate for the loss of matching accuracy by the approximation, we also adopt and incorporate a marginalization scheme that maps a higher order tensor to matrix as well as a one-to-one mapping constraint into the eigenvector computation process. The experimental results show that the proposed method is faster and requires smaller memory than the existing methods with little or no loss of accuracy.


Statistical methods to model and evaluate physical activity programs, using step counts: A systematic review.
Physical activity reduces the risk of noncommunicable diseases and is therefore an essential component of a healthy lifestyle. Regular engagement in physical activity can produce immediate and long term health benefits. However, physical activity levels are not as high as might be expected. For example, according to the global World Health Organization (WHO) 2017 statistics, more than 80% of the world's adolescents are insufficiently physically active. In response to this problem, physical activity programs have become popular, with step counts commonly used to measure program performance. Analysing step count data and the statistical modeling of this data is therefore important for evaluating individual and program performance. This study reviews the statistical methods that are used to model and evaluate physical activity programs, using step counts. Adhering to PRISMA guidelines, this review systematically searched for relevant journal articles which were published between January 2000 and August 2017 in any of three databases (PubMed, PsycINFO and Web of Science). Only the journal articles which used a statistical model in analysing step counts for a healthy sample of participants, enrolled in an intervention involving physical exercise or a physical activity program, were included in this study. In these programs the activities considered were natural elements of everyday life rather than special activity interventions. This systematic review was able to identify 78 unique articles describing statistical models for analysing step counts obtained through physical activity programs. General linear models and generalized linear models were the most popular methods used followed by multilevel models, while structural equation modeling was only used for measuring the personal and psychological factors related to step counts. Surprisingly no use was made of time series analysis for analysing step count data. The review also suggested several strategies for the personalisation of physical activity programs. Overall, it appears that the physical activity levels of people involved in such programs vary across individuals depending on psychosocial, demographic, weather and climatic factors. Statistical models can provide a better understanding of the impact of these factors, allowing for the provision of more personalised physical activity programs, which are expected to produce better immediate and long-term outcomes for participants. It is hoped that this review will identify the statistical methods which are most suitable for this purpose.


Report from the Advisory Committee on Immunization Practices (ACIP): decision not to recommend routine vaccination of all children aged 2-10 years with quadrivalent meningococcal conjugate vaccine (MCV4).
At its February 2008 meeting, the Advisory Committee on Immunization Practices (ACIP) decided not to recommend routine vaccination of children aged 2-10 years against meningococcal disease unless the child is at increased risk for the disease. This report summarizes the deliberations of ACIP and the rationale for its decision and restates existing recommendations for meningococcal vaccination among children aged 2-10 years at increased risk for meningococcal disease. ACIP continues to recommend routine vaccination against meningococcal disease for all persons aged 11-18 years and those persons aged 2-55 years who are at increased risk for meningococcal disease.


[Classical actions of vitamin D: insights from human genetics and from mouse models on calcium and phosphate homeostasis].
At the beginning of the 20th century, the discovery of vitamin D by Sir EV McCollum allowed a better comprehension of its origin and its role, and made it possible to cure rickets, a largely prevalent disease at that time. The main role of vitamin D3 is to maintain calcium and phosphate homeostasis through the action of 1,25-dihydroxyvitamin D3, its active form. This underlies physiological functions related to calcium and phosphate, such as bone mineralization or muscle function. Progress in basic research for the last 40 years led to the discovery of the main hydroxylation steps that produce and catabolize the active form of vitamin D. It also uncovered the molecular aspects of vitamin D action, from its nuclear receptor, VDR, to the various target genes of this hormone. Recent progress in human genetics pointed out mutations in genes involved in vitamin D metabolism and 1,25-dihydroxyvitamin D3 actions. It also helped to understand the role of the major actors that control vitamin D production and effects, through 1,25-dihydroxyvitamin D3 actions on phosphate and calcium homeostasis, and on bone biology. Genetical engineering targeting the whole animal or defined tissues or cell types have yielded many mouse models in the past decades. When targeted to tissues important for vitamin D metabolism and activity, these models allowed a more detailed comprehension of vitamin effects on calcium and phosphorus homeostasis.


Glial cells stabilize axonal protoglomeruli in the developing olfactory lobe of the moth Manduca sexta.
Odor information is processed in spherical structures called glomeruli, which in all animals with differentiated olfactory systems are sites of densely spaced synaptic contacts between olfactory sensory axons and target central nervous system (CNS) neurons. Glomerulus development in the antennal (olfactory) lobe of the moth brain, which is initiated by the arrival of antennal receptor axons, requires interaction among three elements: glial cells, receptor axons, and their targets, the antennal-lobe neurons. Receptor axons form an array of protoglomeruli that become surrounded by glia and serve as a template for mature glomeruli. Previous experiments showed that when the number of glial cells is sharply reduced during development either by irradiation or by an anti-mitotic agent, receptor axons form protoglomeruli, but in the mature lobes, glomeruli are absent and central neurons lack the characteristic glomerular tufting of their arbors. The current investigation was conducted to determine which cellular events in the process of glomerulus formation are disrupted by severe reduction in glial-cell number. The branching patterns of receptor axons and antennal-lobe neurons were examined in animals that had been irradiated to produce glia-deficient antennal lobes at stages during which glomeruli normally would develop. We found that the receptor axons did form protoglomeruli, but that the protoglomeruli quickly disintegrated in glia-deficient antennal lobes; the receptor axons branched diffusely, except where several neighboring glia survived irradiation and together formed a wall of processes that appeared to block the passage of neuronal processes. Multi-glomerular antennal-lobe neurons never developed tufted arbors even at early stages. These results suggest that maintenance of protoglomeruli depends on the border of glia that forms around each protoglomerulus and that the subsequent tufting of antennal-lobe neurons depends on maintenance of the protoglomerular template during the period of dendritic growth.


RanBP9 overexpression accelerates loss of pre and postsynaptic proteins in the APΔE9 transgenic mouse brain.
There is now compelling evidence that the neurodegenerative process in Alzheimer's disease (AD) begins in synapses. Loss of synaptic proteins and functional synapses in the amyloid precursor protein (APP) transgenic mouse models of AD is well established. However, what is the earliest age at which such loss of synapses occurs, and whether known markers of AD progression accelerate functional deficits is completely unknown. We previously showed that RanBP9 overexpression leads to robustly increased amyloid β peptide (Aβ) generation leading to enhanced amyloid plaque burden in a mouse model of AD. In this study we compared synaptic protein levels among four genotypes of mice, i.e., RanBP9 single transgenic (Ran), APΔE9 double transgenic (Dbl), APΔE9/RanBP9 triple transgenic (Tpl) and wild-type (WT) controls. We found significant reductions in the levels of synaptic proteins in both cortex and hippocampus of 5- and 6-months-old but not 3- or 4-months-old mice. Specifically, at 5-months of age, rab3A was reduced in the triple transgenic mice only in the cortex by 25% (p<0.05) and gap43 levels were reduced only in the hippocampus by 44% (p<0.01) compared to wild-type (WT) controls. Interestingly, RanBP9 overexpression in the Tpl mice reduced gap43 levels by a further 31% (p<0.05) compared to APΔE9 mice. RanBP9 also further decreased the levels of drebrin in the hippocampus by 32% (p<0.01) and chromogranin in the cortex by 24% (p<0.05) compared to APΔE9 mice. At 6-months of age, RanBP9 expression in the cortex led to further reduction of rab3A by 30% (p<0.05) and drebrin by 38% (p<0.01) compared to APΔE9 mice. RanBP9 also increased Aβ oligomers in the cortex at 6 months. Similarly, in the hippocampus, RanBP9 expression further reduced rab3A levels by 36% (p<0.01) and drebrin levels by 33% (p<0.01). Taken together these data suggest that RanBP9 overexpression accelerates loss of synaptic proteins in the mouse brain.


Integrin α3β1-CD151 complex regulates dimerization of ErbB2 via RhoA.
Integrin α3β1 regulates adhesive interactions of cells with laminins and have a critical role in adhesion-dependent cellular responses. Here, we examined the role of α3β1-integrin in ErbB2-dependent proliferation of breast cancer cells in three-dimensional laminin-rich extracellular matrix (3D lr-ECM). Depletion of α3β1 in ErbB2-overexpressing breast cancer cells suppressed growth and restore cell polarity in 3D lr-ECM. The phenotype of α3β1-depleted cells was reproduced upon depletion of tetraspanin CD151 and mirrored that of the cells treated with Herceptin, an established ErbB2 antagonist. Breast cancer cells expressing the α3β1-CD151 complex have higher steady-state phosphorylation of ErbB2 and show enhanced dimerization of the protein when compared with α3β1-/CD151-depleted cells. Furthermore, Herceptin-dependent dephosphorylation of ErbB2 was only observed in α3β1-CD151-expressing cells. Importantly, the inhibitory activity of Herceptin was more pronounced when cells expressed both α3β1 and CD151. We also found that the level of active RhoA was increased in α3β1- and CD151-depleted cells and that Rho controls dimerization of ErbB2. Expression of α3β1 alone did not have significant prognostic value in patients with invasive ductal carcinoma of the breast. However, expression of α3β1 in combination with CD151 represented a more stringent indicator of poor survival than CD151 alone. Taken together, these results demonstrate that the α3β1-CD151 complex has a critical regulatory role in ErbB2-dependent signalling and thereby may be involved in breast cancer progression.


Plasma oxalate: comparison of methodologies.
Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial.


Use, knowledge, and perception of the scientific contribution of Sci-Hub in medical students: Study in six countries in Latin America.
Sci-Hub is a useful web portal for people working in science as it provides access to millions of free scientific articles. Satisfaction and usage should be explored in the Latino student population. The objective of this study was to evaluate the use, knowledge, and perception of the scientific contribution of Sci-Hub in medical students from Latin America. A multicenter, observational, analytical study was conducted in 6632 medical students from 6 countries in Latin America. We surveyed from a previously validated instrument, delving into knowledge, monthly average usage, satisfaction level, and perception of the scientific contributions provided by Sci-Hub. Frequencies and percentages are described, and generalized linear models were used to establish statistical associations. Only 19.2% of study participants knew of Sci-Hub and its function, while the median use was twice a month. 29.9% of Sci-Hub-aware participants claimed they always find the desired scientific information in their Sci-Hub search; 62.5% of participants affirmed that Sci-Hub contributes to scientific investigation; only 2.2% reported that Sci-Hub does not contribute to science. The majority of Latino students are not aware of Sci-Hub.


Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis.
To conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens. We searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles. We included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence. Data abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis. The estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures. The meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used. This analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it.


Staged surgery with neoadjuvant 90Y-DOTATOC therapy for down-sizing synchronous bilobular hepatic metastases from a neuroendocrine pancreatic tumor.
Treatment with DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), labeled with beta-emitting radioisotope yttrium-90 ((90)Y-DOTATOC), has successfully been used for the palliative treatment of patients with advanced somatostatin receptor-expressing neuroendocrine tumors (NETs). However, controversy persists as to whether patients with metastatic NETs of the pancreas should undergo radical (salvage) surgery or receive palliative therapy. We proposed that (90)Y-DOTATOC could be used in a neoadjuvant intention for improving therapy of hepatic NET metastases. We investigated a novel therapy concept in a 49-year-old patient presenting with a neuroendocrine tumor of the pancreatic tail and synchronous multiple bilobular hepatic metastases. After surgical removal of the large primary tumor by extended left en bloc resection of the pancreatic tail, the patient received neoadjuvant (90)Y-DOTATOC for therapy of primarily non-resectable bilobular hepatic metastases. The (90)Y-DOTATOC therapy resulted in an impressive regression of hepatic lesions, thus facilitating surgical removal of all remaining liver metastases in a second operation (staged surgery). In addition, one lesion was ablated using radiofrequency ablation (RFA). At 1-year of follow-up after hepatic R0 resection/RFA, there was no evidence of tumor recurrence or extrahepatic metastasis. The neoadjuvant use of (90)Y-DOTATOC therapy could prove valuable for treatment of advanced pancreatic NETs metastatic to the liver in terms of facilitating R0 resection by applying staged surgery concepts.


A silicate inclusion in Puente del Zacate, a IIIA iron meteorite.
The IIIA and IIIB iron meteorites are considered to have formed in the cores of asteroids. A silicate inclusion within the IIIA meteorite Puente del Zacate consisting of olivine (Fa4), low-calcium pyroxene (Fs6Wo1), chromium diopside (Fs3Wo47), plagioclase (An14Or4), graphite, troilite, chromite, daubreelite, and iron metal resembles inclusions in IAB iron meteorites. The oxygen isotopic composition of the Puente del Zacate inclusion is like chromite and phosphate inclusions in other IIIA and IIIB irons. The Puente del Zacate inclusion may have been derived from the lower mantle of the IIIAB parent asteroid.


The role of the environment in eliciting phantom-like sensations in non-amputees.
Following the amputation of a limb, many amputees report that they can still vividly perceive its presence despite conscious knowledge that it is not physically there. However, our ability to probe the mental representation of this experience is limited by the intractable and often distressing pain associated with amputation. Here, we present a method for eliciting phantom-like experiences in non-amputees using a variation of the rubber hand illusion in which a finger has been removed from the rubber hand. An interpretative phenomenological analysis revealed that the structure of this experience shares a wide range of sensory attributes with subjective reports of phantom limb experience. For example, when the space where the ring finger should have been on the rubber hand was stroked, 93% of participants (i.e., 28/30) reported the vivid presence of a finger that they could not see and a total of 57% (16/28) of participants who felt that the finger was present reported one or more additional sensory qualities such as tingling or numbness (25%; 7/28) and alteration in the perceived size of the finger (50%; 14/28). These experiences indicate the adaptability of body experience and share some characteristics of the way that phantom limbs are described. Participants attributed changes to the shape and size of their "missing" finger to the way in which the experimenter mimed stroking in the area occupied by the missing finger. This alteration of body perception is similar to the phenomenon of telescoping experienced by people with phantom limbs and suggests that our sense of embodiment not only depends on internal body representations but on perceptual information coming from peripersonal space.


Visual disturbances with clomiphene.
Clomiphene is a widely prescribed drug for the treatment of infertility. Visual symptoms that occur as a side effect of this drug are uncommon. Some doctors may neglect to mention this side effect when prescribing clomiphene. Thus these visual disturbances can be very alarming to the patient and may also pose a hazard if the patient is doing activities such as driving or operating machinery. The patient should be told to stop taking clomiphene and ophthalmologic evaluation should be performed. Although visual disturbances generally cease on stopping clomiphene, some women may experience persistent visual disturbances.


Grading of Oral Leukoplakia: Can It be Improvised Using Immunohistochemical Markers p63 and CD31.
Oral squamous cell carcinoma is usually preceded by potentially malignant disorders (PMDs), the most common being oral leukoplakia. A conservative management protocol is followed for milder dysplastic cases, while severe dysplastic lesions are surgically excised. Several classification systems have been developed based mainly on histopathological features with a lot of inter-observer variations. The present study was done to assess the use of immunohistochemical (IHC) markers in grading leukoplakic lesions in addition to histopathological grading. To grade leukoplakia using different grading systems and assess if IHC markers can aid in categorizing leukoplakia. Thirty-five cases of leukoplakia were graded using Ljubljana, 2005 World Health Organization (WHO), and Binary System followed by IHC staining with p63 and CD31. Variation was noted in 12 cases while using WHO, 11 using Ljubljana, and 7 using Binary System and was significant on Cohen-Kappa statistics, with the least significant variation noted on Binary System. p63 staining assisted to group doubtful cases and even identify variation in cases graded positively on histopathology. In total, 17 cases stained one-third (mild/low), while 15 cases stained one-half or more (higher grade) epithelial thickness. A weak correlation was observed between all grading systems and p63 on Kendall's Tau-b analysis and the weak correlation was significant for the WHO and binary grading systems. Analyzing p63 and CD31 using Kruskal-Wallis test, an increase in mean vessel density (MVD) was noted for mild/moderate cases but decreased for severe cases. Addressing histological categorization of PMDs assisted by IHC markers to understand the biological behavior of the tissues is currently essential with studies on more markers to assist in the management protocol.


Corrosion-induced release of Cu and Zn into rainwater from brass, bronze and their pure metals. A 2-year field study.
A 2-year field study has been conducted in an urban environment to provide annual release rates of copper and zinc from brass (20 wt% Zn) and copper and tin from bronze (6 wt% Sn) compared to sheets of their pure alloy constituents, copper and zinc. Despite relatively low nominal bulk alloy content, substantially more zinc was released from brass compared to copper. Both metals were released at a significantly slower rate from the brass alloy, compared to the pure metals. The proportion of release rates of copper and zinc from the alloy differed significantly from their proportions in the bulk alloy. Bronze showed relatively constant release rates of copper, being similar to that of pure copper sheet. The release of tin from bronze was negligible. The results clearly show that alloys and the pure metals behave very differently when exposed to rainwater. Accordingly, release rates from pure metals cannot be used to predict release rates of individual constituents from their alloys. Generated data are of importance within REACH, the new chemical policy of the European commission, where metal alloys erroneously are being treated as mixtures of chemical substances.


Trajectories of psychological distress among low-income, female survivors of Hurricane Katrina.
The purpose of this study was to investigate trajectories of psychological distress among low-income, primarily unmarried and African American women who survived Hurricane Katrina (N = 386). Data were collected in the year prior to the hurricane as well as approximately 1 and 3 years thereafter. Using Latent Class Growth Analysis (LCGA), we detected 6 distinct trajectory groups. Over half of the participants fit into a trajectory consistent with resilience; that is, they maintained low levels of psychological distress over the course of the study, but experienced an elevation in symptoms at the first predisaster time point followed by a return to predisaster levels. The other trajectories reflected a range of psychological responses to disasters and indicated that predisaster functioning had a major influence on postdisaster psychological outcomes. Degree of exposure to hurricane-related stressors, experiences of human and pet bereavement, perceived social support, and socioeconomic status were significant predictors of trajectory group membership. Implications for research and policy are discussed.


[Significance of biotechnology in reproductive biology and veterinary medicine].
In the last decade a good number of biotechnical methods have been developed. They are available in medical, biological, and ecological fields of work as well as techniques that can replace animal experiments. These methods have been developed on the basis of researchwork in andrology (AI and cryoconservation of spermatozoa), endocrinology (hormonal control of reproduction) and the availability of industrial produced hormones and their analog. On the other hand practical clinical techniques for examination like the availability of sonography advice and clinical practical techniques for non-surgical recovery and transplantation of gamets and embryos have been the prerequisites for a successful work in this field of action. These fields of action are extended from breeding aspects (genetical progress) over the control of epidemics to the exportation of genetic material (especially developing countries to overcome hygienic and adaptation problems), the creation of gen-pools (conservation of breeds-species) and as well as the elimination of genetic defects like BLAD or DUMPS by help of PCR-techniques or the identification of positive characters like milk components and sexing of embryos. The industrial use of bioproducts produced by especially designed biosystems is in work but in Germany not possible by reasons of legislative restrictions. In the light of these developments the veterinary fields of work should be discussed and focussed towards an understanding that the veterinarian should be active and in a polposition in the processing of reproduction and production and presentation of food of animal origin by using these new technologies.


Endovascular stent placement for right ventricle to pulmonary artery conduit stenosis in the Norwood with Sano modification.
Conduit obstruction is increasingly recognized as a complication of the Sano modified Norwood procedure. We report our experience with stent placement to ameliorate conduit stenoses and prevent premature surgical intervention. Records for all patients having undergone a Sano modified Norwood between September 2003 and December 2006 were reviewed. All patients with Sano conduit obstruction requiring stent placement were included. Sites of obstruction, method of stenting, pre- and poststent oxygen saturations, reinterventions, age at next surgery, and complications were collected and reviewed. Forty-one patients underwent a Sano modified Norwood procedure, and 9 patients had stents deployed for conduit stenoses. The patients presented a median of 52 days following Norwood palliation. Twelve stents were successfully placed in 9 patients. In 8 patients, saturations improved from a median of 67.5% to 81% after stent placement (P = .0005). Arterial saturations were unavailable in 1 patient requiring extracorporeal membrane oxygenation. No patients required reintervention after stent placement. The median age at their next surgery was 144 days. Seven patients underwent a successful bidirectional Glenn, 1 patient underwent a modified Blalock-Taussig shunt, and 1 expired. Complications included hypotension during stent deployment and 1 episode of transient complete heart block. Transcatheter treatment of Sano conduit obstruction can be performed safely and results in immediate improvement in oxygenation, thereby allowing substantial delay of the cavo-pulmonary shunt.


Diagnosis and successful treatment of fusariosis in the compromised host.
We present six cases of fusariosis caused by Fusarium solani that were diagnosed over a three-year period in 166 adult patients undergoing chemotherapy for acute leukemia. Necrotic skin lesions were evident in four patients, fungemia in three, and a deep cellulitis around a great toe nail at the time of a febrile illness in two. The mean minimal inhibitory concentration (MIC) of amphotericin B was 3.3 micrograms/mL and of miconazole, 5.3 micrograms/mL; all isolates were resistant to 5-fluorocytosine. All patients received amphotericin B (1.0-1.5 mg/kg per d) plus 5-fluorocytosine. In contrast to results found in the literature, five patients had resolution of their infections, and the one patient who died had necropsy evidence of disseminated fusariosis. Review of our cases and of the literature did not reveal a definitive source for the organism or its portal of entry. Fusarium spp. must be recognized as opportunistic pathogens that cause a potentially fatal infection in compromised patients.


Clinical significance of cytokeratin 20-positive circulating tumor cells detected by a refined immunomagnetic enrichment assay in colorectal cancer patients.
Current immunomagnetic enrichment method can only detect general epithelial antigens of circulating tumor cells (CTC). Further characterization of the CTCs to provide specific information on the tumor type is not possible. We attempted to overcome this drawback by developing the methodology for using a gastrointestinal-specific anti-cytokeratin (CK) 20 antibody to detect CTCs in colorectal cancer patients' blood. The protocol was validated using a colorectal cancer SW480 cell line. The clinical significance of findings in colorectal cancer was investigated by detecting CK20-positive CTCs (pCTC) in patients with colorectal cancer, other common cancers, colorectal adenoma, benign colorectal diseases, and normal subjects. Moreover, the malignant nature of CK20 pCTCs was examined by comparing chromosome 17 aberration patterns with those from the corresponding primary tumors. The assay successfully showed CK20-positive SW480 cells. When applied in patient samples, the detection rates were 62% (132 colorectal cancer patients; median number = 11 CTCs), 0% (120 patients with other common cancers), 6% (50 colorectal adenoma patients), 0% (120 patients with benign colorectal diseases), and 0% (40 normal subjects). Furthermore, statistical analysis showed that CK20 pCTC numbers were associated with tumor-node-metastasis stage and lymph node status. Using the median CK20 pCTC numbers as the cutoff points, stratified groups of colorectal cancer patients had significant differences in their recurrence, metastasis, and survival. Finally, chromosome 17 aneusomy in 90% of colorectal cancer patients with CK20 pCTCs matched with those from the primary tumors. Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.


The impact of a pre-loaded multi-ingredient performance supplement on muscle soreness and performance following downhill running.
The effects of multi-ingredient performance supplements (MIPS) on perceived soreness, strength, flexibility and vertical jump performance following eccentric exercise are unknown. The purpose of this study was to determine the impact of MIPS (NO-Shotgun®) pre-loaded 4 weeks prior to a single bout of downhill running (DHR) on muscle soreness and performance. Trained male runners (n = 20) were stratified by VO2max, strength, and lean mass into two groups; MIPS (n = 10) ingested one serving daily of NO-Shotgun® for 28 days and 30 min prior to all post-testing visits, Control (CON; n = 10) consumed an isocaloric maltodextrin placebo in an identical manner as MIPS. Perceived soreness and performance measurements (strength, flexibility, and jump height) were tested on 6 occasions; 28 days prior to DHR, immediately before DHR (PRE), immediately post (POST) DHR, 24, 48, and 72 hr post-DHR. Perceived soreness significantly increased (p < 0.05) post DHR compared to PRE at all time-points, with no difference between groups. Creatine kinase (CK) and lactate dehydrogenase (LDH) increased over time (p < 0.001) with no group x time interactions (p = 0.236 and p = 0.535, respectively). Significant time effects were measured for strength (p = 0.001), flexibility (p = 0.025) and vertical jump (p < 0.001). There were no group x time interactions for any performance measurements. Consumption of MIPS for 4 weeks prior to a single bout of DHR did not affect perceived soreness, muscle damage, strength, flexibility, or jump performance compared to an isocaloric placebo in trained male runners following a single bout of DHR.


The importance of mitosis as a factor for predicting sentinel lymph node biopsy for thin melanoma.
23-year-old female patient, with superficial spreading melanoma (SSM) on the back, Breslow 0.35 mm, Clark II, without ulceration and with 2 mitosis/mm². Patient was submitted to margin enlargement and sentinel biopsy of 2 lymph nodes (left armpit). Histopathology revealed micrometastasis in the subcapsular sinus of both. Following the recommendation of the 2009 American Joint Committee on Cancer Melanoma Staging (AJCC), the patient underwent complete axillary lymphadenectomy. No other lymph nodes were metastatic. The clinical application of dermoscopy has enabled more accurate diagnosis of cutaneous melanoma, probably contributing to a greater proportion of thin melanomas at diagnosis. The mitotic rate was included as an important prognostic factor for thin melanomas by the AJCC, suggesting biopsy for these patients.


Topological characterisation and identification of critical domains within glucosyltransferase IV (GtrIV) of Shigella flexneri.
The three bacteriophage genes gtrA, gtrB and gtr((type)) are responsible for O-antigen glucosylation in Shigella flexneri. Both gtrA and gtrB have been demonstrated to be highly conserved and interchangeable among serotypes while gtr((type)) was found to be specific to each serotype, leading to the hypothesis that the Gtr((type)) proteins are responsible for attaching glucosyl groups to the O-antigen in a site- and serotype- specific manner. Based on the confirmed topologies of GtrI, GtrII and GtrV, such interaction and attachment of the glucosyl groups to the O-antigen has been postulated to occur in the periplasm. In this study, the topology of GtrIV was experimentally determined by creating different fusions between GtrIV and a dual-reporter protein, PhoA/LacZ. This study shows that GtrIV consists of 8 transmembrane helices, 2 large periplasmic loops, 2 small cytoplasmic N- and C- terminal ends and a re-entrant loop that occurs between transmembrane helices III and IV. Though this topology differs from that of GtrI, GtrII, GtrV and GtrX, it is very similar to that of GtrIc. Furthermore, both the N-terminal periplasmic and the C-terminal periplasmic loops are important for GtrIV function as shown via a series of loop deletion experiments and the creation of chimeric proteins between GtrIV and its closest structural homologue, GtrIc. The current study provides the basis for elucidating the structure and mechanism of action of this important O-antigen modifying glucosyltransferase.


The Effects of Anterolateral Tenodesis on Tibiofemoral Contact Pressures and Kinematics.
Anterolateral tenodeses are increasingly popular in combination with intra-articular anterior cruciate ligament reconstructions. Despite the perception of risk of overconstraint and lateral osteoarthritis, evidence is lacking regarding the effect of graft tensioning on knee kinematics and intra-articular compartmental joint pressures. To investigate tibiofemoral joint contact pressures and kinematics related to an anterolateral lesion and the effectiveness of a MacIntosh tenodesis in restoring these when varying (1) graft tension and (2) tibial rotation during graft fixation. Controlled laboratory study. Eight fresh-frozen cadaveric knees were tested in a customized rig with femur fixed and tibia free to move from 0° to 90° of flexion. The quadriceps and iliotibial band were loaded by means of a weighted pulley system. At 30° intervals of knee flexion, tibiofemoral contact pressures were measured with a Tekscan sensor and tibiofemoral kinematics were recorded by use of an optical tracking system. The knee was tested intact and then with an anterolateral soft tissue transection. MacIntosh tenodeses were then tested in a randomized order with 20 N or 80 N of graft tension, each with the tibia held in neutral intact alignment or free to rotate. Tibial anterior translation and internal rotation were significantly increased and lateral contact pressures significantly reduced compared with the intact knee following anterolateral soft tissue cutting ( P < .05). Contact pressures were restored with fixed neutral tibial rotation combined with 20 N or 80 N of graft tension or by a free-hanging tibia with 20 N of graft tension (all P values > .5). Grafts tensioned with 80 N caused significant overconstraint both when the tibia was fixed and free hanging (all P values < .05). Increases in the lateral tibiofemoral contact pressures were also seen when the tibia was free hanging and 80 N was used for graft tension ( P < .05). Anterolateral soft tissue injury caused reduced lateral tibiofemoral contact pressures and altered tibiofemoral kinematics; these were restored with a MacIntosh procedure performed with 20 N of graft tension. If 80 N of graft tension was used, increased lateral contact pressures and overconstraint in internal rotation were seen. With the tibia free hanging, intact contact biomechanics were restored when 20 N of graft tension was applied, but 80 N of graft tension significantly increased lateral tibiofemoral pressures and overconstrained internal rotation. The kinematic and contact pressure effects were significantly correlated: Changes in tibial rotation caused by increased graft tension correlated with elevated lateral articular contact pressure. Controlling tibial position appears important when tensioning anterolateral tenodeses. However, the identified changes were subtle and may not be clinically significant in a fully loaded knee.


Recent advances of biomaterials in stem cell therapies.
Stem cells have been utilized as 'living drugs' in clinics for decades. Their self-renewal, differentiation, and immunomodulating properties provide potential solutions for a variety of malignant diseases and disorders. However, the pathological environment may diminish the therapeutic functions and survival of the transplanted stem cells, causing failure in clinical translation. To overcome these challenges, researchers have developed biomaterial-based strategies that facilitatein vivotracking, functional engineering, and protective delivery of stem cells, paving the way for next-generation stem cell therapies. In this perspective, we briefly overview different types of stem cells and the major clinical challenges and summarize recent progress of biomaterials applied to boost stem cell therapies.


Detection of prokaryotic signal peptidase in an Escherichia coli membrane fraction: endoproteolytic cleavage of nascent f1 pre-coat protein.
An inverted membrane vesicle fraction isolated from uninfected Escherichia coli and largely derived from the inner membrane has been shown to contain an endoproteolytic activity that cleaves nascent bacteriophage f1 pre-coat protein into two identifiable products. The electrophoretic mobility on sodium dodecyl sulfate/urea/polyacrylamide gels and the partial amino-terminal sequence of the larger fragment were indistinguishable from those of the mature phage coat protein. Partial amino-terminal sequence analysis showed that the smaller fragment corresponds to the amino-terminal "signal peptide" of f1 pre-coat protein. Cleavage occurred only if the membrane fraction was present during in vitro synthesis, and was not observed if it was added after completion of pre-coat protein synthesis. The cleavage reaction was strongly stimulated when the membrane fraction was present together with the nonionic detergent Nikkol. These results are consistent with and discussed in terms of the signal hyothesis.


Exploring general practitioners' perceptions about the primary care gatekeeper role in Indonesia.
In the current healthcare delivery system funded by National Health Insurance (NHI) in Indonesia, the gatekeeper role of primary care services is critical to ensuring equal healthcare access for the population. To be effective, gatekeeping relies on the performance of general practitioners (GPs). However, the perceptions held by Indonesian GPs about their gatekeeper role are not yet well documented. This study describes the self-perceived knowledge, attitudes and performance of Indonesian GPs with respect to the gatekeeper role and explores associated factors. We conducted a cross-sectional study of all primary care facilities (N = 75) contracted by the regional NHI office in the Banyumas district. The 73 participating GPs completed a written questionnaire that assessed their knowledge, attitudes and performance in relation to the gatekeeper role. Personal and facility characteristics were analysed in a generalised linear model as possible associating factors, as well as for the association between GPs' knowledge and attitude with performance as gatekeepers. GPs scored relatively high in the domains of knowledge and performance but scored lower in their attitudes towards the gatekeeper role of primary care. In the full-adjusted model, no factors were significantly associated with the knowledge score. Work experience as GPs, private or civil service employment status and rural or urban location of the primary care facility were linked to attitude scores. Full- or part-time employment and type of facility were factors associated with the performance score. Attitude scores were positively associated with performance score. GPs in Indonesia are knowledgeable and report that they adequately perform their function as gatekeepers in primary care. However, their attitudes towards the gatekeeper function are less positive. Attitudes and performance with respect to the primary care gatekeeper role are likely influenced more by contextual factors such as location and type of facility than by personal factors. Efforts to address contextual issues could include improvements in practice standards for privately practising physicians and public information campaigns about gatekeeping regulations. Such efforts will be crucial to improving the gatekeeper role of primary care in Indonesia and assuring efficient access to high-quality care for all.


Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle.
Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, and fatigability) occur frequently. We hypothesized that the iatrogenic effects of statins could result from alterations in Ca(2+) homeostasis. Acute applications of simvastatin on human skeletal muscle fibers triggered a Ca(2+) wave of intra-cellular Ca(2+) that mostly originates from sarcoplasmic reticulum (SR) Ca(2+)-release. In addition, simvastatin increased mitochondrial NADH content and induced mitochondrial membrane depolarization (EC(50)=1.96 microM) suggesting an altered mitochondrial function. Consequently on simvastatin application, a weak mitochondrial Ca(2+) efflux (EC(50)=7.8 microM) through permeability transient pore and Na(+)/Ca(2+) exchanger was triggered, preceding the large SR-Ca(2+) release. Increased SR Ca(2+) content after acute application of statin is also suggested by the increased Ca(2+) spark amplitude and by the effect of cyclopiazonic acid. We thus conclude that simvastatin induced alterations in mitochondrial function which lead to an increase in cytoplasmic Ca(2+), SR-Ca(2+) overload, and Ca(2+) waves. Taken together, these statin-induced muscle dysregulations may contribute to myotoxicity.


Schwann cell and epineural fibroblast expression of serine racemase.
D-serine appears to be a natural agonist at the "glycine site" of the NMDA receptor and is created by conversion from L-serine by serine racemase. This racemase has been localized to protoplasmic astrocytes that ensheath synapses and modulate neuronal activity in the CNS, but serine racemase expression in the PNS has not been reported. Immunofluorescence indicated that Schwann cells and other endoneurial components of rat spinal nerve contain serine racemase, and western blot analysis detected the enzyme in lysates of sciatic nerve. Cultures from sciatic nerve contained Schwann cells and fibroblasts, and both cell types showed serine racemase expression by immunofluorescence and Western blot; the quantities per unit of total protein appeared slightly lower than that expressed in cultured astrocytes. Cultures enriched for each cell type were subjected to reverse transcriptase polymerase chain reaction, further confirming serine racemase mRNA in Schwann cells and fibroblasts. Finally, immunodetection of D-serine itself was observed in cultured Schwann cells and fibroblasts. These expression patterns of serine racemase may indicate roles for D-serine in peripheral nerve transduction.


Epidemiology of foot and ankle fractures in the United States: an analysis of the National Trauma Data Bank (2007 to 2011).
Understanding the epidemiology of foot and ankle trauma could be useful in health services research and for policy makers. It can also define practice patterns. Using the National Trauma Data Bank data set from 2007 to 2011, we analyzed the frequency and proportion of each fracture in the foot and ankle in major trauma hospitals in the United States. A total of 280,933 foot and/or ankle fractures or dislocations were identified. Although oversampling of more severe trauma in younger patients might have occurred owing to the nature of the data set, we found that the most common fractures in the foot and ankle were ankle fractures. Midfoot fractures were the least common among all the foot and ankle fractures when categorized by anatomic location. Approximately 20% of all foot and ankle fractures were open.


Photo-induced conjugation of tetrazoles to modified and native proteins.
Bio-orthogonal chemistry has been widely used for conjugation of polymer molecules to proteins. Here, we demonstrate the conjugation of polyethylene glycol (PEG) to bovine beta-lactoglobulin (BLG) by photo-induced cyclo-addition of tetrazole-appended PEG and allyl-modified BLG. During the course of the investigation, a significant side-reaction was found to occur for the conjugation of PEG-tetrazole to native BLG. Further exploration of the underlying chemistry reveals that the presence of a tryptophan residue is sufficient for conjugation of tetrazole-modified molecules.


Learned pacing for adults with chronic pain: A randomised controlled trial feasibility study.
Chronic pain can significantly impact on an individual's occupational performance and quality of life. Pacing is a pain management strategy regularly used in occupational therapy practice; however, evidence for its effectiveness has not been established. To determine the feasibility of a future randomised controlled trial to investigate the effectiveness of a learned pacing intervention on occupational performance and satisfaction for adults with chronic pain. A randomised controlled trial feasibility study was conducted with participants randomly assigned to a learned pacing intervention or a waitlist control group. The primary outcome measure was the Canadian Occupational Performance Measure. One hundred and twenty-eight people were screened for eligibility over 36 weeks, with 74 people invited to participate. Twelve were randomly assigned, eight to the learned pacing group and four to the control group. Those receiving the learned pacing intervention had clinically important changes in occupational performance and occupational satisfaction. Participants in the waitlist control group also had clinically important changes in occupational satisfaction. The method design was deemed feasible; however, several improvements would increase the rate of participant recruitment and reduce attrition. Recruitment from multiple sites is required to obtain an adequate sample size of 60. Undertaking a future randomised controlled trial is feasible and warranted to establish the effectiveness of a learned pacing intervention on occupational performance and satisfaction for adults with chronic pain.


[The gestational age label].
Recent follow-up data on babies born at > 24 weeks' gestation in the Netherlands has shown encouraging results; these outcomes reflect policy in national guidelines to limit treatment in babies born at < 24 weeks' gestation. The use of gestational age as a cut-off point for active treatment in extremely premature infants is, however, scientifically and ethically questionable. As an alternative we should consider a tailor-made approach by well-informed, ethically trained doctors who feel comfortable with complex decision-making, irrespective of the gestational age label.


Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation.
Treatment of brain tumors is challenging since the blood-brain tumor barrier prevents chemotherapy drugs from reaching the tumor site in sufficient concentrations. Nanomedicines have great potential for therapy of brain disorders but are still uncommon in clinical use despite decades of research and development. Here, we provide an update on nano-carrier strategies for improving brain drug delivery for treatment of brain tumors, focusing on liposomes, extracellular vesicles and biomimetic strategies as the most clinically feasible strategies. Finally, we describe the obstacles in translation of these technologies including pre-clinical models, analytical methods and regulatory issues.


Dielectric properties of low-water-content tissues.
The dielectric properties of two low-water-content tissues, bone marrow and adipose tissue, were measured from 1 kHz to 1 GHz. From 1 kHz to 13 MHz, the measurements were performed using a parallel-plate capacitor method. From 10 MHz to 1 GHz, a reflection coefficient technique using an open-ended coaxial transmission line was employed. The tissue water contents ranged from 1 to almost 70% by weight. The dielectric properties correlate well with the values predicted by mixture theory. Comparison with previous results from high-water-content tissues suggests that bone marrow and adipose tissues contain less motionally altered water per unit dry volume than do the previously studied tissues with lower lipid fractions. The high degree of structural heterogeneity of these tissues was reflected in the large scatter of the data, a source of uncertainty that should be considered in practical applications of the present data.


A proton spin-lattice relaxation rate study of methyl and t-butyl group reorientation in the solid state.
We have measured the solid state nuclear magnetic resonance (NMR) 1H spin-lattice relaxation rate from 93 to 340 K at NMR frequencies of 8.5 and 53 MHz in 5-t-butyl-4-hydroxy-2-methylphenyl sulfide. We have also determined the molecular and crystal structures from X-ray diffraction experiments. The relaxation is caused by methyl and t-butyl group rotation modulating the spin-spin interactions and we relate the NMR dynamical parameters to the structure. A successful fit of the data requires that the 2-methyl groups are rotating fast (on the NMR time scale) even at the lowest temperatures employed. The rotational barrier for the two out-of-plane methyl groups in the t-butyl groups is 14.3+/-2.7 kJ mol(-1) and the rotational barrier for the t-butyl groups and their in-plane methyl groups is 24.0+/-4.6 kJ mol(-1). The uncertainties account for the uncertainties associated with the relationship between the observed NMR activation energy and a model-independent barrier, as well as the experimental uncertainties.


Chondroitin sulfate and growth factor signaling in the skeleton: Possible links to MPS VI.
Mucopolysaccharidosis type VI (MPS VI), also called Maroteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficiency of a specific enzyme required for glycosaminoglycan catabolism. Deficiency in the N-acetylgalactosamine-4-sulfatase (4S) enzyme, also called arylsulfatase B (ARSB), may have profound skeletal consequences. In MPS VI, partially degraded glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate accumulate within lysosomes. Through mechanisms that remain unclear, the abnormal GAG metabolism impacts several aspects of cellular function, particularly in the growth plate. This article explores the hypothesis that accrued partially degraded GAGs may contribute to deregulation of signaling pathways that normally orchestrate skeletal development, with a focus on members of the transforming growth factor-β (TGF-β) family. Understanding the molecular mechanisms disrupted by MPS VI may yield insight to improve the efficacy of MPS VI therapies, including bone marrow transplantation and enzyme replacement therapies.


[Phenotype of antibiotic resistance in clinical strains of staphylococci isolated from patients with staphylococcal destructive pneumonia].
The results of the study on the dynamics of changes in antibiotic sensitivity of staphylococci isolated from 38 patients with destructive pneumonia were presented. Most of the strains were characterized by multiple resistance to the main antibiotics with high resistance levels. Aminoglycosides, fusidin and rifampicin were the most active against the clinical strains. Repeated determinations of the antibiotic sensitivity revealed changes in the structure of the antibiotic resistance with inclusion of new resistance markers.


Seasonal variations in injury rates in U.S. Army ordnance training.
This study assessed the effects of seasons and temperature on injury rates during U.S. Army ordnance advanced individual training. Injury data were collected each week at two clinics serving two geographically separated military training units. Weekly injury rates were calculated as the number of injured soldiers in each battalion (numerator) divided by the total number of soldiers in each battalion (denominator). A two-way analysis of variance examined weekly injury rates according to training unit and season of the year. Correlations between injury rates and average maximal temperatures were also examined. Analysis of variance indicated significant differences in injury rates according to training unit (p = 0.04) and season (p < 0.01) but no significant interaction between unit and season (p = 0.16). Injury rates in the summer were higher than injury rates in the winter or autumn. Coefficients for correlations between weekly injury rates and weekly average maximal temperatures were 0.71 and 0.88 for the two training units. These data support previous work in U.S. Army basic combat training indicating a seasonal effect on injury rates. Higher environmental temperatures were associated with higher injury rates.


Precise nanofiltration in a fouling-resistant self-assembled membrane with water-continuous transport pathways.
Self-assembled materials are attractive for next-generation membranes. However, the need to align self-assembled nanostructures (e.g. cylinders, lamellae) and the narrow stability windows for ordered bicontinuous systems present serious challenges. We propose and demonstrate a novel approach that circumvents these challenges by exploiting size-selective transport in the water-continuous medium of a nanostructured polymer templated from a self-assembled lyotropic H1 mesophase. Optimization of the mesophase composition enables high-fidelity retention of the H1 structure on photoinduced cross-linking. The resulting material is a mechanically robust nanostructured polymer possessing internally and externally cross-linked nanofibrils surrounded by a continuous aqueous medium. Fabricated membranes show size selectivity at the 1- to 2-nm length scale and water permeabilities of ~10 liters m-2 hour-1 bar-1 μm. Moreover, the membranes display excellent antimicrobial properties due to the quaternary ammonium groups on the nanofibril surfaces. These results represent a breakthrough for the potential use of polymerized lyotropic mesophase membranes in practical water purification applications.


Neonatal near miss in the Birth in Brazil survey.
This study used data from the Birth in Brazil survey, a nationwide hospital-based study of 24,197 postpartum women and their newborns, collected between February 2011 and July 2012. A three-stage cluster sampling design (hospitals, days, women) was used consisting of stratification by geographic region, type of municipality (capital or non-capital), and type of hospital financing. Logistic regression was used to identify variables that were potential predictors of neonatal mortality and neonatal near miss indicators. After testing nineteen variables, five were chosen to compose a set of neonatal near miss indicators (birth weight of less than 1,500 g, Apgar score of less than 7 in the 5th minute of life, use of mechanical ventilation, gestational age of less than 32 weeks and congenital malformations). The neonatal near miss rate in the Birth in Brazil survey was 39.2 per thousand live births, three and a half times higher than the neonatal mortality rate (11.1 per thousand). These neonatal near miss indicators were able to identify situations with a high risk of neonatal death.


Sex Differences in the Speech of Persons With and Without Parkinson's Disease.
Sex differences are apparent in the prevalence and the clinical presentation of Parkinson's disease (PD), but their effects on speech have been less studied. Speech acoustics of persons with (34 females and 34 males) and without (age- and sex-matched) PD were examined, assessing the effects of PD diagnosis and sex on ratings of dysarthria severity and acoustic measures of phonation (fundamental frequency standard deviation, smoothed cepstral peak prominence), speech rate (net syllables per second, percent pause ratio), and articulation (articulatory-acoustic vowel space, release burst precision). Most measures were affected by PD (dysarthria severity, fundamental frequency standard deviation) and sex (smoothed cepstral peak prominence, net syllables per second, percent pause ratio, articulatory-acoustic vowel space), but without interactions between them. Release burst precision was differentially affected by sex in PD. Relative to those without PD, persons with PD produced fewer plosives with a single burst: females more frequently produced multiple bursts, whereas males more frequently produced no burst at all. Most metrics did not indicate that speech production is differentially affected by sex in PD. Sex was, however, associated with disparate effects on release burst precision in PD, which deserves further study. https://doi.org/10.23641/asha.24388666.


Effectiveness in Regular Practice of Collaborative Care for Depression Among Adolescents: A Retrospective Cohort Study.
Depression is common among adolescents, but many lack ready access to mental health services. Integrated models of care for depression are needed, along with evidence to support their use in regular practice. The authors examined the effectiveness of an ongoing collaborative care program for depressed adolescents embedded in a busy primary care practice. This retrospective cohort study assessed EMERALD (Early Management and Evidence-based Recognition of Adolescents Living with Depression), a collaborative care program. All patients ages 12-17 and age 18 and still in high school with a score of ≥10 on the nine-item Patient Health Questionnaire for Adolescents (PHQ-9A) and without a diagnosis of bipolar disorder were eligible. The sample included 162 EMERALD participants and 499 similarly eligible non-EMERALD patients. Outcomes were six-month remission of depression (score <5) and six-month treatment response (>50% reduction from baseline) as measured by the PHQ-9A. Analyses included logistic regression and propensity score matching to adjust for differences in demographic factors and number of contacts-observations. After propensity score matching, EMERALD patients had better adjusted rates of depression remission (11 percentage points higher, p=.035) and treatment response (14 percentage points higher, p<.001) than comparison patients. Results from primary analyses were as conservative as or more conservative than results from all sensitivity analyses tested. Collaborative care for adolescents in regular practice led to better remission and treatment response than usual care. Future studies could examine which groups might benefit most and flexible payment models to support these services.


Tn502 and Tn512 are res site hunters that provide evidence of resolvase-independent transposition to random sites.
In this study, we report on the transposition behavior of the mercury(II) resistance transposons Tn502 and Tn512, which are members of the Tn5053 family. These transposons exhibit targeted and oriented insertion in the par region of plasmid RP1, since par-encoded components, namely, the ParA resolvase and its cognate res region, are essential for such transposition. Tn502 and, under some circumstances, Tn512 can transpose when par is absent, providing evidence for an alternative, par-independent pathway of transposition. We show that the alternative pathway proceeds by a two-step replicative process involving random target selection and orientation of insertion, leading to the formation of cointegrates as the predominant product of the first stage of transposition. Cointegrates remain unresolved because the transposon-encoded (TniR) recombination system is relatively inefficient, as is the host-encoded (RecA) system. In the presence of the res-ParA recombination system, TniR-mediated (and RecA-mediated) cointegrate resolution is highly efficient, enabling resolution both of cointegrates involving functional transposons (Tn502 and Tn512) and of defective elements (In0 and In2). These findings implicate the target-encoded accessory functions in the second stage of transposition as well as in the first. We also show that the par-independent pathway enables the formation of deletions in the target molecule.


B cells induce tolerance by presenting endogenous peptide-IgG on MHC class II molecules via an IFN-gamma-inducible lysosomal thiol reductase-dependent pathway.
We have previously demonstrated that splenic B cells, transduced with peptide-IgG fusion proteins, are efficient tolerogenic APCs in vivo. Specific hyporesponsiveness to epitopes encoded in the peptide-IgG fusion protein has been achieved to over one dozen Ags, and clinical efficacy has been established in animal models for several autoimmune diseases and hemophilia. Previous studies also demonstrated that tolerance in this system requires MHC class II expression by the transduced B cells. Yet, the mechanisms of this B cell tolerogenic processing pathway remain unclear. In this study, we show that MHC class II molecules on tolerogenic B cells present epitopes derived from endogenous, but not exogenous (secreted), peptide-IgG fusion protein. These class II epitopes from the IgG fusion protein are processed in lysosomes/endosomes in an IFN-gamma-inducible lysosomal thiol reductase-dependent manner. We suggest that the MHC class II presentation of endogenously produced fusion protein epitopes represents a novel mechanism for tolerance induced by peptide-IgG-transduced B cells. An understanding of this process might provide insights into central and peripheral tolerance induced by other professional and nonprofessional APCs.


Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.
This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy. Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met. In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention. In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.


Force Estimation on the Contact of Poly(l,l-lactide) and Poly(d,d-lactide) Surfaces Regarding Stereocomplex Formation.
The stereocomplex formation of poly(l,l-lactide) (PLLA) and poly(d,d-lactide) (PDLA) was selected in order to investigate the interaction of the two surfaces including hydrogen bonding and van der Waals interaction. Adhesion force measurement using surface force apparatus (SFA) equipped with an optical microscope was conducted on the PLLA and PDLA spin-coated films. The adhesion forces, Fad, phenomenologically followed the linear relation with the applied normal load, L. For the force Fad between PLLA and PDLA films with low molecular weights (PLLA, Mn = 2800; PDLA, : Mn = 2100), the slope of linear fitting of Fad vs L was significantly larger for the heterointerface (PLLA/PLDA) compared with that for the homointerface (PLLA/PLLA and PDLA/PDLA). However, when polymers with higher molecular weights (PLLA, Mn = 8500; PDLA, Mn = 8300) were measured, the slopes of linear fitting lines were almost the same for hetero- and homointerfaces. This indicated that the mobility of the lower molecular weight PLLA/PDLA films promoted the selective interaction of PLLA and PDLA under the applied normal loads. The adhesion between the outermost PLLA layer and PDLA layer prepared by layer-by-layer (LbL) assembly was also measured. It is interesting that the adhesion force was very weak in this case. This weak adhesion could be explained by the much less mobility of the polymer chain due to the stereocomplex formation within the LbL layers. This study demonstrated that the adhesion force due to the selective interaction of PLLA and PDLA between PLLA/PDLA films could be directly measured, and depended on the mobility of the outermost polymer chains, which reflected the different structures of polymer chains in the organized complex films.


[Nutritional education: from ignorance to social representations in post-graduation by Rio de Janeiro (1980-98)].
Tbe present article aims at analyzing the of nutrition teaching in post-graduation programs from 1980 to 1998. As the maine cause for nutrition as an academic subject, nutritional ignorance is the basic focus of dissertations from the 1980's up to 1990, showing that the beginning of researchers' education was marked by a technical and intervening approach whose subject scope followed an outside logic. After 1990, dissertations began to criticize nutrition curriculum and practice and to introduce the concept of social representations. On doing so, they kept structural concepts when relating representations and practices. Tracing back the relevant chronological facts of nutrition, as a science and as a profession, ends up to empty informers' statements, revealing that nutritionists represent their education and practice more as a result of external idealized views than as a group of meaningful representations rendered by their practice, in which relational experiences among individuals and with their social environment take place.


The effect of corticosteroid usage on the bacterial killing, clearance and nerve damage in leprosy: a prospective cohort study: part 1--study design and baseline findings of 400 untreated multibacillary patients.
To investigate possible adverse effects of therapeutic usage of corticosteroids on the killing and clearance of M. leprae and the clearance of granuloma, in patients with multibacillary (MB) leprosy. A cohort of 400 untreated MB patients were sub-grouped into those to be treated with corticosteroids (prednisolone 40 mg daily tapered to 5 mg over 12 weeks) along with MB-MDT for reaction and/or neuritis or silent neuropathy (SN) of <6 months duration (group A), and those with no reaction and to be treated with MDT only (group B). Clinical, bacteriological, histopathological and neurological test findings at fixed time points were compared. Analysis was performed using SPSS version 10.0. The significance of association was tested using Chi-square test. In the current report, we describe the study design and baseline findings of 400 untreated MB patients, with special emphasis on differences between patients in groups A and B. At baseline, applying Ridley-Jopling classification, 39% patients were BT, 20% BB, 24% BL, 12% sub-polar LL and 5% pure neural (PN). Overall, 60% patients were slit skin smear (SSS) negative and 33% presented with disability either grades 1 or 2. Overall 140/400 (35%) patients presented with reaction and/or neuritis and 11/400 (3%) presented with SN of <6 months duration. Comparing groups A and B, the percentage of patients presenting with DG2 was significantly higher in group A (43%). By clinical tests, monofilaments (MF) and voluntary muscle testing (VMT), the percentage of patients and nerves showing functional impairment was also significantly higher in group A. However, in the more sensitive nerve conduction velocity (NCV) test, the percentage of patients that showed nerve abnormalities was closely comparable; 94% and 91% in groups A and B respectively while number of affected nerves was higher in group A. At baseline, as recorded by NCV, peripheral nerve function abnormality was observed in almost all the MB patients regardless of reaction; but among those presenting with reaction or neuritis, the nerve damage was more severe and extensive.


Enhanced deficits in long-term potentiation in the adult dentate gyrus with 2nd trimester ethanol consumption.
Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st) or 3(rd) trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd) trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.


Unexpected cardiac arrest in patients after surgical correction of tetralogy of Fallot.
Four of 220 patients without bifasicular block (complete right bundle branch block and left anterior hemiblock) or transient complete heart block immediately after surgery had an unexpected cardiac arrest one to 15 years after satisfactory surgical repair of tetralogy of Fallot. The postoperative electrocardiograms (ECG) revealed complete right bundle branch block in two patients and no intraventricle conduction abnormality in two patients. Each of the four patients had premature ventricular contractions on previous postoperative ECG. The cardiac arrest occurred during normal activity in three patients and mild exercise in one. Following the cardiac arrest, three patients died and one patient survived. Eighteen months before the cardiac arrest, the survivor had a stress test which revealed multifocal premature ventricular contractions with short bursts of ventricular tachycardia after exercise. This ventricular arrhythmia was suppressed with quinidine therapy. Although complete heart block cannot be excluded in these four patients, we reasoned that the cardiac arrests were probably preceded by ventricular tachyarrhythmia. Because of this experience, we believe that any patient who has had intraventricular surgery should be evaluated for ventricular arrhythmia. If frequent premature ventricular contractions or serious ventricular arrhythmias are documented, we seriously consider antiarrhythmic therapy in an attempt to prevent ventricular tachyarrhythmias and sudden death.


Operationalizing the Population Health Framework: Clinical Characteristics, Social Context, and the Built Environment.
As a framework, population health emphasizes health outcomes for entire populations, the broad range of determinants of these outcomes, and the comparative effectiveness of medical and public health interventions. In practice, however, many contemporary population health programs instead focus on small subsets of patients who account for a disproportionate share of health care utilization, often with disappointing results. The authors proposed a new approach to operationalize population health in clinical settings, with the example of tobacco use. Electronic health record (EHR) data from a mid-Atlantic health system were used to: (1) define and describe a hospital-based population of current smokers, (2) analyze the demographic characteristics of the population to consider how the social context may impact treatment, and (3) join EHR data with public licensing data on tobacco retail locations to assess the relationship between the built environment and smoking status. Out of a total of 20,310 unique adult admissions to the health system, 3749 (18.5%) were current smokers. Compared to never smokers, current smokers were significantly younger, more likely to be male, more likely to be Black/African American, less likely to be Hispanic/Latino/a, and more likely to be on Medicaid or be self-pay. Current vs. former smokers had significantly higher exposure to tobacco retail locations, even after adjusting for demographic and other covariates. By defining populations around leading modifiable medical determinants of health, and accounting for the larger context of sociodemographic factors and the built environment, health systems can invest in comprehensive programs designed to produce the greatest population health returns.


Staphylococcal Protein A column: correlation of mitogenicity of perfused plasma with clinical response.
Eleven patients with advanced breast cancer and four with astrocytoma were treated with plasma perfused over columns containing staphylococcal Protein A (SPA). Doses of 5 to 20 mg of SPA were bound to collodion charcoal particles, and this treatment resulted in partial remissions in one patient with astrocytoma and in two patients with breast cancer. Remission duration was 6 wk to 6 mo. Resolution of lymphadenopathy and a decrease in carcinoembryonic antigen were noted in an additional two breast cancer patients. Systemic reactions to infused plasma consisted of fever, chills, and rigors. In brain cancer patients, increased intracranial pressure was also noted. A mitogenic substance was generated in plasma of 11 patients after it was perfused over the SPA charcoal matrix. The mitogenic material induced lymphoproliferation comparable to concanavalin A and required the presence of SPA on the collodion charcoal but was not due to leakage of SPA from the column during plasma perfusion. Of considerable significance was that only patients whose column perfused plasma contained this mitogenic activity exhibited systemic reactions, and five of these patients obtained antitumor responses. This striking correlation implies that the mitogenic factor is an active component of SPA therapy. The ability to demonstrate mitogenicity in column perfused plasma might also be useful for selecting patients amenable to SPA therapy. These findings attest to the therapeutic value of this mode of treatment and provide an initial definition of a mediator of SPA antitumor activity.


An evaluation of embryo, zygote and oocyte cryopreservation in assisted reproductive technology.
The study compared (i) the outcome between cryopreserved ICSI fertilized embryo and cryopreserved ICSI fertilized pronuclear stage zygotes and (ii) the outcome between cryopreserved fertilized mature oocytes with cryopreserved immature oocytes, fertilized by ICSI following thawing. Comparative retrospective review of relevant studies satisfying study criteria. Studies were identified through MEDLINE literature search. Study outcomes were cryosurvival, fertilization, implantation, pregnancy, and delivery rates. Pronucleate zygotes had better cryosurvival rates than the cleaving embryo (90.7% versus 59.9%) and almost double the clinical pregnancy rates for cleaving embryo (12.8% versus 7.0%). There was an almost three-fold higher delivery rate for the pronucleate zygote compared with cleaving embryo (11.6% versus 4.3%). Immature oocytes had lower cryosurvival rates than mature oocytes (34.5% versus 52.3%). Mature and immature oocytes showed good fertilization rates (59.3% versus 50%) and satisfactory embryonic development (90.3% versus 100.0%). Immature oocytes had higher delivery rate per embryo transferred than the mature oocyte (40.0% versus 2.7%). Pronucleate zygote cryopreservation has an advantage over the cleaving embryo. The low survival rate following thawing is still an obstacle to the integration of oocyte cryopreservation into ART.


Reductive dechlorination of 2-chlorophenol by Anaeromyxobacter dehalogenans with an electrode serving as the electron donor.
Electrodes poised at potentials low enough to serve as an electron donor for microbial respiration, but high enough to avoid the production of hydrogen, have been proposed as an alternative to the use of soluble electron donors for stimulating the bioremediation of chlorinated contaminants and/or metals. However, this form of respiration using pure cultures of microorganisms has only been reported in Geobacter species. To further evaluate this bioremediation strategy studies were conducted with Anaeromyxobacter dehalogenans, which has previously been reported to reductively dechlorinate 2-chlorophenol to phenol with acetate as the electron donor. Anaeromyxobacter dehalogenans could oxidize acetate with electron transfer to a graphite electrode poised at a positive potential, demonstrating its ability to directly exchange electrons with electrodes. Anaeromyxobacter dehalogenans attached to electrodes poised at -300 mV versus standard hydrogen electrode reductively dechlorinated 2-chlorophenol to phenol. There was no dechlorination in the absence of A. dehalogenans and electrode-driven dechlorination stopped when the supply of electrons to the electrode was disrupted. The findings that microorganisms other than Geobacter species can accept electrons from electrodes for anaerobic respiration and that chlorinated aromatic compounds can be dechlorinated in this manner suggest that there may be substantial potential for treating a diversity of contaminants with microbe-electrode interactions.


Chemiluminescent Probes for Imaging H2S in Living Animals.
Hydrogen sulphide (H2S) is an endogenous mediator of human health and disease, but precise measurement in living cells and animals remains a considerable challenge. We report the total chemical synthesis and characterization of three 1,2-dioxetane chemiluminescent reaction-based H2S probes, CHS-1, CHS-2, and CHS-3. Upon treatment with H2S at physiological pH, these probes display instantaneous light emission that is sustained for over an hour with high selectivity against other reactive sulphur, oxygen, and nitrogen species. Analysis of the phenol/phenolate equilibrium and atomic charges has provided a generally applicable predictive model to design improved chemiluminescent probes. The utility of these chemiluminescent reagents was demonstrated by applying CHS-3 to detect cellularly generated H2S using a multi-well plate reader and to image H2S in living mice using CCD camera technology.


Persistent use of nitrous oxide for anaesthesia in European hospitals despite its harmfulness to the climate - how emission taxation can achieve the coupling of cost-effectiveness and climate protection: observational study.
Health care has the intrinsic obligation to preserve health. This concept is also applicable to planetary health. Nitrous oxide (N2O) lacks clinical indications in modern anaesthesia, while it is a high-potential greenhouse gas. Its seemingly low cost contrasts with the consequential externalised socio-economic costs due to its contribution to the climate crisis, which is approximately €698 per emitted ton of CO2 equivalent. This difference can be internalised through emission taxation. In this study, we aim to evaluate how much N2O - total amount and converted to CO2 equivalent - is used at a German university hospital and compare this amount to that used at European hospitals. Furthermore, how the cost of N2O usage changes under different emission taxation scenarios is calculated. This trial was a retrospective observational study at a German university hospital with approximately 1,250 beds between 2016 and 2020. Additionally, five European hospitals from the Health Care Without Harm Network were used for comparison from a European perspective. The main outcome parameters were the amount of N2O used, in total and converted to CO2 equivalent, and the total cost at emission taxation of €0, €25, €55 and €698 per ton CO2 equivalent. At the peak, 2,104 tCO2 equivalent in N2O was emitted in 2019. The actual cost was €14,040 in this year, while the corresponding socio-economic damage due to the climate crisis was almost €1.5 million. Other European hospitals showed comparable amounts of emissions. The annual peak amount of emitted N2O corresponded to the total annual greenhouse gas emission of 188 people in Germany. To achieve a drastic reduction in use, the abandonment of recommendations by anaesthesiologic societies appears necessary, in addition to an internalisation of future costs via emission taxation, which will cause inadequate cost for a medication without relevant benefit or indication. To that end, the inclusion of health sector emissions within national or international greenhouse gas taxation, for example, the European Union Emissions Trading System, appears necessary and expedient in view of the urgent need to address the ecological transformation. The trial was registered with the German Clinical Trials Register, identifier DRKS00024973 on 12/04/2021.


Unusual case of hemoptysis 13 years after bilobectomy.
We describe a 68-year-old man with recurrent episodes of hemoptysis. The patient had undergone right upper and middle lobectomies for a benign cystic lesion 13 years ago and coronary artery bypass grafting for ischemic heart disease immediately before the onset of hemoptysis. Diagnostic work-up revealed that pulmonary arterial flow to the remaining right lower lobe had been inadvertently compromised by prior ligation of the right main pulmonary artery during the time of his bilobectomy, with the development of a robust collateral blood supply derived from bronchial and intercostals arteries. Successful treatment required percutaneous embolization of the dominant bronchial collaterals, followed by completion pneumonectomy.


[The therapist in group psychotherapy].
Nowadays, group psychotherapy designates a broad range of procedures based on different theoretical frameworks, applied to several contexts. The purpose of this study is to understand the group therapist's role, delineating some strategies and necessary abilities for group psychotherapy practice. The authors emphasize the technical-scientific level in which the work with groups is developed and the influence of the therapist's personality on the participants. They conclude that, in order to preserve their role without loosing the specificity of his function due to his involvement in multiple patients' experiences, therapists must have a stable professional identity. Therefore, the therapists' preparation, based on a process of continuing formation, is a necessary condition to enable them to face peculiar situations that occur in the group context and also to assure the singular therapeutic potential of group psychotherapy.


Comparison of Clinical Characteristics and Outcome of Critically Ill Patients Admitted to Tertiary Care Intensive Care Units in India during the Peak Months of First and Second Waves of COVID-19 Pandemic: A Retrospective Analysis.
Coronavirus disease-2019 (COVID-19) continues to pose serious challenges to healthcare systems globally with the disease progressing over time in crest-trough pattern of waves. We compared the patient characteristics and outcomes of critically ill patients admitted during the first and second waves of COVID-19 pandemic. We did a retrospective analysis of medical records of critically ill patients admitted to intensive care unit (ICU) at the peak period of both waves. The data on demographics, symptoms, treatment received, and outcomes of patients were recorded. Compared to first wave, significantly more females, younger age group, and those without underlying comorbidities required ICU admission during the second wave. The treatments received during both periods were similar except for preferential use of methylprednisolone over dexamethasone and proclivity of bilevel positive airway pressure (BiPAP) ventilation over high-flow nasal cannula (HFNC). There was no significant difference in the duration of ICU stay and mortality of patients. During the first wave, the factors associated with nonsurvival of patients were advanced age, comorbidities, severe disease, and a lesser number of days on HFNC. All these factors along with higher Sequential Organ Failure Assessment (SOFA) score were observed to be linked with patient nonsurvival during the second wave. In India, the second wave of COVID-19 significantly influenced ICU demographics with a predominance of females and young adults requiring critical care. During both time periods, patients received similar treatment except for the propensity to use methylprednisolone and BiPAP as opposed to dexamethasone and HFNC in second wave. No significant difference in ICU mortality was noted. Kerai S, Singh R, Dutta S, Mahajan A, Agarwal M. Comparison of Clinical Characteristics and Outcome of Critically Ill Patients Admitted to Tertiary Care Intensive Care Units in India during the Peak Months of First and Second Waves of COVID-19 Pandemic: A Retrospective Analysis. Indian J Crit Care Med 2021;25(12):1349-1356.


Stereotypies and other abnormal repetitive behaviors: potential impact on validity, reliability, and replicability of scientific outcomes.
Normal behavior plays a key role in facilitating homeostasis, especially by allowing the animal to control and modify its environment. Captive environments may interfere with these behavioral responses, and the resulting stress may alter many physiological parameters. Abnormal behaviors indicate that an animal is unable to adjust behaviorally to the captive environment and, hence, may be expressing abnormal physiology. Therefore, captive environments may affect the following aspects of an experiment: validity, by introducing abnormal animals into experiments; reliability, by increasing interindividual variation through the introduction of such individuals; and replicability, by altering the number and type of such individuals between laboratories. Thus, far from increasing variability, enrichment may actually improve validity, reliability, and replicability by reducing the number of abnormal animals introduced into experiments. In this article, the specific example of abnormal repetitive behaviors (ARBs) is explored. ARBs in captive animals appear to involve the same mechanisms as ARBs in human psychiatry, which reflect underlying abnormalities of brain function. ARBs are also correlated with a wide range of behavioral changes that affect experimental outcomes. Thus, ARBs in laboratory animals may compromise validity, reliability, and replicability, especially in behavioral experiments; and enrichments that prevent ARB may enhance validity, reliability, and replicability. Although many links in this argument have been tested experimentally, key issues still remain in the interpretation of these data. In particular, it is currently unclear (1) whether or not the differences in brain function seen in animals performing ARB are abnormal, (2) which common behavioral paradigms are affected by ARB, and (3) whether enrichment does indeed improve the quality of behavioral data. Ongoing and future work addressing these issues is outlined.