AO Spine Adult Spinal Deformity Patient Profile: A Paradigm Shift in Comprehensive Patient Evaluation in Order to Optimize Treatment and Improve Patient Care.
Modified Delphi study. Adult spinal deformity (ASD) is an increasingly recognized condition, comprising a spectrum of pathologies considerably impacting patients' health and functional status. Patients present with a combination of pain, disability, comorbidities and radiological deformity. The study aims to propose a systematic approach of gathering information on the factors that drive decision-making by developing a patient profile. The present study comprises of 3 parts. Part 1: Development of prototype of patient profile: The data from the Core Outcome Study on SCOlisis (COSSCO) by Scoliosis Research Society (SRS) was categorized into a conceptual framework. Part 2: Modified Delphi study: Items reaching >70% agreement were included in a 4 round iterative process with 51 panellists across the globe. Part 3: Pilot testing-feasibility: Content validity and usability were evaluated quantitatively. The profile consisted of 4 domains. 1. General health with demographics and comorbidities, 2.Spine-specific health with spine related health and neurological status, 3. Imaging with radiographic and MRI parameters and 4. Deformity type. Each domain consisted of 1 or 2 components with various factors and their measuring instruments. Profile was found to have an excellent content validity (I-CVIr 0.78-1.00; Ave-CVI 0.92) appropriateness, relevance and usefulness. The present study, is first to provide a universally applicable multimodal ASD patient profile to methodically describe patients. Physicians are encouraged to assess ASD patients holistically using this profile and not just based on radiographic findings.


A framework to support the progressive implementation of integrated team-based care for the management of COPD: a collective case study.
In Canada, there is widespread agreement about the need for integrated models of team-based care. However, there is less agreement on how to support the scale-up and spread of successful models, and there is limited empirical evidence to support this process in chronic disease management. We studied the supporting and mitigating factors required to successfully implement and scale-up an integrated model of team-based care in primary care. We conducted a collective case study using multiple methods of data collection including interviews, document analysis, living documents, and a focus group. Our study explored a team-based model of care for chronic obstructive pulmonary disease (COPD) known as Best Care COPD (BCC) that has been implemented in primary care settings across Southwestern Ontario. BCC is a quality improvement initiative that was developed to enhance the quality of care for patients with COPD. Participants included healthcare providers involved in the delivery of the BCC program. We identified several mechanisms influencing the scale-up and spread of BCC and categorized them as Foundational (e.g., evidence-based program, readiness to implement, peer-led implementation team), Transformative (adaptive process, empowerment and collaboration, embedded evaluation), and Enabling Mechanisms (provider training, administrative support, role clarity, patient outcomes). Based on these results, we developed a framework to inform the progressive implementation of integrated, team-based care for chronic disease management. Our framework builds off our empirical work and is framed by local contextual factors. This study explores the implementation and spread of integrated team-based care in a primary care setting. Despite the study's focus on COPD, we believe the findings can be applied in other chronic disease contexts. We provide a framework to support the progressive implementation of integrated team-based care for chronic disease management.


Dendrimers for cancer immunotherapy: Avidity-based drug delivery vehicles for effective anti-tumor immune response.
Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti-tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well-defined architecture. This review offers a comprehensive overview of dendrimer-based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune-suppressive responses (immune checkpoint inhibitors). On-going works and prospects of dendrimer-based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer-based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Varicella zoster meningitis following COVID-19 vaccination: a report of two cases.
Most of the adverse effects reported in patients who have received COVID-19 vaccines have been mild. However, possible serious adverse effects are being monitored cautiously. There have also been a number of case reports of reactivation of varicella zoster infection within 28 days after immunization with mRNA COVID-19 vaccines. A few cases have also been reported after viral vector and inactivated COVID-19 vaccination. The incidence of meningitis following varicella zoster virus infection is rare. In the current study, we report two cases of male patients who received two different types of COVID-19 vaccine (inactivated and viral vector) and developed varicella zoster meningitis within 10 days after vaccination.


Pathogenesis and therapeutics of interstitial lung disease in systemic sclerosis.
Interstitial lung disease is a common manifestation in systemic sclerosis and is considered as one of the two main causes of death among these patients. Although the pathogenesis of interstitial lung disease related to systemic sclerosis (SSc-ILD) is very complex and not yet fully understood, diverse mechanisms such as vascular injury, altered immunological response and inflammatory activation have been proposed. Vascular injury is considered as the earliest event in the pathogenesis of this disease and has been associated with an excessive formation of alveolar capillaries, circulating endothelial cells, and increased expression of endothelin-1. Different cells like myofibroblasts, fibroblasts, endothelial cells and T lymphocytes are involved in the inflammatory activation. Meanwhile, lymphocyte activation, release of several cytokines and autoantibody production play an important role in the immunological response. To date, the treatment of SSc-ILD is not totally defined, as studies have shown mixed results. Given the high progression of the disease, it is difficult to enroll patients for clinical trials. Therefore, there is lack of evidence to guide therapeutic approaches. Throughout this paper, we present evidence supporting that the combination of glucocorticoids and cyclophosphamide is considered the best regimen for patients with SSc-ILD. In addition, we present data regarding the use of azathioprine, mycophenolate, anti-fibrosing agents, bosentan, rituximab, and imatinib mesylate as alternative therapies. Finally, for patients who are unresponsive to pharmacologic interventions, we present data regarding the efficacy of highdose immunosuppression with autologous transplantation of hematopoietic stem cells, and lung transplantation.


Targeted social care for highly vulnerable pregnant women: protocol of the Mothers of Rotterdam cohort study.
Social vulnerability is known to be related to ill health. When a pregnant woman is socially vulnerable, the ill health does not only affect herself, but also the health and development of her (unborn) child. To optimise care for highly vulnerable pregnant women, in Rotterdam, a holistic programme was developed in close collaboration between the university hospital, the local government and a non-profit organisation. This programme aims to organise social and medical care from pregnancy until the second birthday of the child, while targeting adult and child issues simultaneously. In 2014, a pilot in the municipality of Rotterdam demonstrated the significance of this holistic approach for highly vulnerable pregnant women. In the 'Mothers of Rotterdam' study, we aim to prospectively evaluate the effectiveness of the holistic approach, referred to as targeted social care. The Mothers of Rotterdam study is a pragmatic prospective cohort study planning to include 1200 highly vulnerable pregnant women for the comparison between targeted social care and care as usual. Effectiveness will be compared on the following outcomes: (1) child development (does the child show adaptive development at year 1?) and (2) maternal mental health (is maternal distress reduced at the end of the social care programme?). Propensity scores will be used to correct for baseline differences between both social care programmes. The prospective cohort study was approved by the Erasmus Medical Centre Ethics Committee (ref. no. MEC-2016-012) and the first results of the study are expected to be available in the second half of 2019 through publication in peer-reviewed international journals. NTR6271; Pre-results.


Community psychological stressor-induced secondary sex ratio decline after a seismic sequence in the Greek island of Zakynthos.
The secondary sex ratio (the ratio of boys to girls at birth) may demonstrate a decline following community stress-inducing major destructive events. This study aims to investigate whether or not moderate adverse life events, in conjunction with endogenous psychological characteristics, can induce sufficient community stress to affect the sex ratio. From April 3rd to May 8th 2006 a moderate sized earthquake sequence occurred offshore the Greek island of Zakynthos, which had been hit by a destructive earthquake half a century earlier. The monthly sex ratio after the earthquake sequence was estimated and compared with that of previous and following years. Eleven months after the onset of the earthquakes the sex ratio fell to 1.000, and during the next two months (March and April) it declined further to 0.612. The sex ratio one year before its decline was 1.158 and over a total 6-year period, 3 years before and 3 years after the sequence, it was 1.063; the March-April decline in male births is significant (OR=0.53, 95% CI=0.32-0.86, p=0.013, and OR=0.57, 95% CI=0.36-0.91, p=0.023, respectively). Also, the number of boys relative to girls in March-April 2007 was significantly lower than during the same months 3 years before and after the sequence (OR=0.50, 95% CI=0.31-0.82, p=0.007). The findings suggest that basic biological characteristics, such as the sex ratio, can be affected by psychological stressors interwoven with the pertaining psychology of the population.


Unresolved problems of pancreatic pseudocysts.
The treatment of 54 patients with pancreatic pseudocysts was reviewed. The operative mortality was 11% and after an average followup of 3 years the recurrence rate was 3.8%. Hemorrhage was the most significant complication of pseudocysts and occurred in 4 patients preoperatively and three patients postoperatively. The patients who developed recurrence or died had been operated within one day after the diagnoses of pseudocysts were made. The deaths were due to the conditions that necessitated the emergency operations rather than to the fact that the cyst wall had not adequately matured. Ideally, operation should be performed when the patient has reached an optimal clinical condition and the walls of the cyst are sufficiently thick. Currently there is no guide for estimation of the state of cyst maturation, although this may develop with the use of ultrasound. Since complications can develop during a prolonged observation period it was our policy to proceed with surgery as soon after diagnosis as the patient was in satisfactory clinical condition. It is evident from this study that internal drainage can be performed safely in less time than the 6 weeks frequently recommended. Morbidity and mortality were not adversely affected by a short interval between diagnosis and operation if the timing was a matter of election rather than a condition of emergency.


A review and analysis of cryptosporidiosis outbreaks in New Zealand.
Cryptosporidium is a leading global cause of diarrhoea with many reported outbreaks related to water and zoonotic transmission. This study summarizes data from Public Health Surveillance reports since 2010 in New Zealand to describe exposures associated with human diarrhoea outbreaks caused by Cryptosporidium. We investigate the species and subtypes of cases involved in some of the outbreaks to elucidate transmission routes and the predominant aetiological agents of cryptosporidiosis. For the period 2010–2017, 318 cryptosporidiosis outbreaks were reported in New Zealand resulting in 1634 cases and 20 hospitalizations. The most important mode of transmission was person-to-person (primary infections and secondary or close contacts infections), relating to 260 outbreaks and 1320 cases, followed by 113 outbreaks associated with animals, resulting in 436 human cases. From 2018 to 2021, there were 37 cryptosporidiosis outbreaks associated with 324 cases. We identified the subtypes by using polymerase chain reaction targeting the gp60 gene and the likelihood of mixed subtype infections with the Tracking of Indels by DEcomposition (TIDE) algorithm. Subtype families Ib and Ig of Cryptosporidium hominis and IIa and IId of Cryptosporidium parvum were found among cases; however, C. hominis subtypes occurred in 8 of the 11 outbreaks reviewed where molecular data were available. Examination of the chromatograms showed no mixed subtype infections in the samples assessed. Subtyping data need to be routinely incorporated into national surveillance programmes to better understand the epidemiology, sources, transmission and extent of cryptosporidiosis outbreaks in New Zealand. Our study highlights the value of integrating epidemiological information and molecular typing to investigate and manage clusters of cryptosporidiosis cases.


Quantum free energy landscapes from ab initio path integral metadynamics: Double proton transfer in the formic acid dimer is concerted but not correlated.
With the goal of computing quantum free energy landscapes of reactive (bio)chemical systems in multi-dimensional space, we combine the metadynamics technique for sampling potential energy surfaces with the ab initio path integral approach to treating nuclear quantum motion. This unified method is applied to the double proton transfer process in the formic acid dimer (FAD), in order to study the nuclear quantum effects at finite temperatures without imposing a one-dimensional reaction coordinate or reducing the dimensionality. Importantly, the ab initio path integral metadynamics technique allows one to treat the hydrogen bonds and concomitant proton transfers in FAD strictly independently and thus provides direct access to the much discussed issue of whether the double proton transfer proceeds via a stepwise or concerted mechanism. The quantum free energy landscape we compute for this H-bonded molecular complex reveals that the two protons move in a concerted fashion from initial to product state, yet world-line analysis of the quantum correlations demonstrates that the protons are as quantum-uncorrelated at the transition state as they are when close to the equilibrium structure.


Production of piglets after cryopreservation of embryos using a centrifugation-based method for delipation without micromanipulation.
It is still difficult to successfully cryopreserve in vitro-produced (IVP) swine embryos, as they are sensitive to chilling due to the abundance of intracellular lipids. Mechanical delipation through micromanipulation is successful, but this method increases the potential of pathogen transmission because of the damage inflicted upon the zona pellucida during micromanipulation, and it is labor intensive. Reported here is a method to remove the lipid of IVP porcine embryos, without significantly compromising the zona pellucida, by trypsin treating the embryos or exposing the embryo to a high-osmolality solution to enlarge the perivitelline space so that the lipid could be polarized and separated completely after subsequent centrifugation without micromanipulation. The procedures work both for nuclear transfer-derived embryos and in vitro-fertilized embryos. Both methods provide a high-throughput process that leaves the zona pellucida intact (or relatively intact for the trypsin treatment) to aid in preventing disease transmission. It is also demonstrated that this procedure results in viable piglets, a claim that could not be made in many previous reports. Although the efficiencies of cryopreservation have not been dramatically improved, these procedures allow a single person to process very large numbers of embryos without the necessity of manipulating each individual embryo on a micromanipulator. Such high-throughput processing overcomes the lack of high efficiency (i.e., the system can be overloaded with embryos for transfer to surrogates).


[Pellagra--a forgotten disease].
In the civilized world the traditional causes of pellagra such as hunger, malnutrition are disappeared, but the disease has not disappeared after all. In the well developed countries the current etiologic causes are the following: alcoholism, psychiatric disorders, diseases causing cachexy, malabsorption and some drugs. In the case reported by the authors the malnutrition, accompanying the chronic alcoholism was the cause of the diarrhoea, dementia and dermatitis. The correct diagnosis was established after four years of repeated psychiatrical and medical treatment.


Effects of various doses of selenite on stinging nettle (Urtica dioica L.).
The aim of this study was to investigate the effects of selenium (Se) on the growth, accumulation and possible mechanisms of Se transport in certain parts (roots, leaves, stamp and apex) of nettle (Urtica dioica L.) plants. Se was supplemented by one-shot and two repeated doses to the soil (2.0 and 4.0 mg Se per kg of substrate). Selenium content in roots increased linearly with dose and was significantly higher compared to other plant parts of interest. However, growth of the above-ground parts of plant as well as roots was slightly inhibited with increasing selenium concentration in comparison to the untreated plants. The content of phytochelatin2, a low molecular mass peptide containing a sulfhydryl group, correlated well with the Se content. This suggests a possible stimulation of synthesis of this plant peptide by Se.


Anionic sites of human erythrocyte membranes. I. Effects of trypsin, phospholipase C, and pH on the topography of bound positively charged colloidal particles.
The effects of pH, trypsin, and phospholipase C on the topographic distribution of acidic anionic residues on human erythrocytes was investigated using colloidal iron hydroxide labeling of mounted, fixed ghost membranes. After glutaraldehyde fixation at pH 6.5-7.5, the positively charged colloidal particles were bound to the membranes in small randomly distributed clusters. The clusters of anionic sites were reversibly aggregated by incubation at pH 5.5 before fixation at the same pH. These results correlate with the distribution of intramembranous particles found by Pinto da Silva (J. Cell Biol.53:777), with the exception that the distribution of anionic sites on a majority of the fixed ghosts at pH 4.5 was aggregated instead of dispersed. The randomly distributed clusters could be nonreversibly aggregated by trypsin or phospholipase C treatment of intact ghosts before glutaraldehyde fixation. Previous glutaraldehyde fixation prevented trypsin and pH induced aggregation of the colloidal iron sites. Evidence that N-acetylneuraminic acid groups are the principal acidic residues binding colloidal iron was the elimination of greater than 85% of the colloidal iron labeling to neuraminidase-treated cell membranes. Colloidal iron binding N-acetylneuraminic acid residues may reside on membrane molecules such as glycophorin, a sialoglycoprotein which contains the majority of the N-acetylneuraminic acid found on the human erythrocyte membrane.


Range of Hip Joint Motion Is Correlated With MRI-Verified Cam Deformity in Adolescent Elite Skiers.
Radiologically verified cam-type femoroacetabular impingement (FAI) has been shown to correlate with reduced internal rotation, reduced passive hip flexion, and a positive anterior impingement test. To validate how a clinical examination of the hip joint correlates with magnetic resonance imaging (MRI)-verified cam deformity in adolescents. Cross-sectional study; Level of evidence, 3. The sample group consisted of 102 adolescents with the mean age 17.7 ± 1.4 years. The hip joints were examined using MRI for measurements of the presence of cam (α-angle ≥55°) and clinically for range of motion (ROM) in both supine and sitting positions. The participants were divided into a cam and a noncam group based on the results of the MRI examination. Passive hip flexion, internal rotation, anterior impingement, and the FABER (flexion, abduction, and external rotation) test were used to test both hips in the supine position. With the participant sitting, the internal/external rotation of the hip joint was measured in 3 different positions of the pelvis (neutral, maximum anteversion, and retroversion) and lumbar spine (neutral, maximum extension, and flexion). Differences were found between the cam and noncam groups in terms of the anterior impingement test (right, P = .010; left, P = .006), passive supine hip flexion (right: mean, 5°; cam, 117°; noncam, 122° [P = .05]; and left: mean, 8.5°; cam, 116°; noncam, 124.5° [P = .001]), supine internal rotation (right: mean, 4.9°; cam, 24°; noncam, 29° [P = .022]; and left: mean, 4.8°; cam, 26°; noncam, 31° [P = .028]), sitting internal rotation with the pelvis and lumbar spine in neutral (right: mean, 7.95°; cam, 29°; noncam, 37° [P = .001]; and left: mean, 6.5°; cam, 31.5°; noncam, 38° [P = .006]), maximum anteversion of the pelvis and extension of the lumbar spine (right: mean, 5.2°; cam, 20°; noncam, 25° [P = .004]; and left: mean, 5.85°; cam, 20.5; noncam, 26.4° [P = .004]), and maximum retroversion of the pelvis and flexion of the spine (right: mean, 8.4°; cam, 32.5°; noncam, 41° [P = .001]; and left: mean, 6.2°; cam, 36°; noncam, 42.3° [P = .012]). The cam group had reduced ROM compared with the noncam group in all clinical ROM measures. The presence of cam deformity on MRI correlates with reduced internal rotation in the supine and sitting positions, passive supine hip flexion, and the impingement test in adolescents.


The leaf-order-dependent enhancement of freezing tolerance in cold-acclimated Arabidopsis rosettes is not correlated with the transcript levels of the cold-inducible transcription factors of CBF/DREB1.
The central part of cold-acclimated rosettes of Arabidopsis thaliana L. (ecotype Columbia) survived freezing at lower temperatures better than did those at the rosette periphery. Electrolyte-leakage tests with detached leaves verified that freezing tolerance in central (or young) leaves increased faster and to a greater extent than in peripheral (or aged and mature) leaves at 2 degrees C. Cold-induced accumulation of sugars could partly account for the leaf-order-dependent enhancement of freezing tolerance after 1 d at 2 degrees C, whereas the role of proline remains to be determined. Cold-induced accumulation of the transcripts of stress-inducible CBF/DREB1 transcription factors apparently disagreed with the observed difference in the freezing tolerance in different leaf orders. However, the levels of COR78/RD29A transcripts were almost the same between different leaf orders after 1-3 d at 2 degrees C, and COR78/RD29A content per total leaf protein was similar between different leaf orders after 7 d at 2 degrees C. Thus, cold-induced accumulation of COR78/RD29A does not seem to account for the observed difference in freezing tolerance in different leaf orders. Although further studies are required for comprehensive understanding of the phenomenon, the present work does provide an important and interesting physiological aspect in our understanding of the freezing tolerance in plants.


Favorable influence of dopamine on left ventricular performance in patients refractory to discontinuation of cardiopulmonary bypass.
Of 410 consecutive patients undergoing cardiopulmonary bypass, 13 (3.2%) required pressor and inotropic support beyond volume replacement with whole blood and administration of CaCl2 to discontinue bypass. In 4 patients, isoproterenol was ineffective in maintaining cardiac output and systemic arterial pressure. In 12 patients addition and/or substitution of dopamine permitted discontinuation of cardiopulmonary bypass. In 7 patients who had serial hemodynamic measurements, mean systemic arterial pressure increased by 26%; cardiac index increased by 36%; stroke volume increased by 31%; and stroke work index increased by 83% (all p less than 0.005). There were no significant changes in central venous and mean pulmonary arterial wedge pressures, heart rate, or pulmonary and peripheral vascular resistances. Eleven of the 13 patients survived. We conclude that dopamine is an effective pressor and inotropic agent in the management of left ventricular dysfunction immediately after cardiopulmonary bypass.


[Influence of genetic polymorphisms and non-genetic factors on the maintenance dose of warfarin].
OBJECTIVE To assess the influence of genetic polymorphisms and non-genetic factors on warfarin maintenance dose variations in order to provide guidance for personalized use of warfarin. METHODS Two hundred patients from outpatient and inpatient with stable international normalized ratio(INR) were recruited. Clinical data and blood samples were collected. Genotypes of 4 genes involved in warfarin metabolic pathways were determined with Sanger sequencing. Based on statistical analysis of warfarin maintenance dosage, a mathematical model was established. RESULTS Among non-genetic factors, the age and height have significant influence in warfarin dosage. The dosage is negatively correlated with age but positively correlated with height. The difference in dosage for between the 20-year-old group and 60-year-old group has reached 1.81 mg/day, and that for between the 140 cm in height and 180 cm in height groups has reached 1.06 mg/day. VKORC1 -1639G/A, CYP2C9 430C/T, CYP2C9 1075A/C and CYP4F2 V433M polymorphisms have significant influence on stable warfarin dosage. The dosage for patients with wild type and mutant genotypes has varied from 0.35 mg/day to 0.84 mg/day. CONCLUSION Non-genetic factors and genetic polymorphisms play important roles in personalized variations of warfarin maintenance dose. The establishment of mathematical models considering multiple factors is helpful in evaluating the safety and effectiveness of warfarin dosage.


Predicative values of serum microRNA-22 and microRNA-126 levels for non-small cell lung cancer development and metastasis: a case-control study.
Presented study aims to explore the predictive values of serum microRNA-22 (miR-22) and miR-126 levels for non-small cell lung cancer (NSCLC) development and metastasis.A total of 127 NSCLC patients who were admitted in the First People's Hospital of Yancheng City from May, 2013 to May, 2015 were selected as the case group, including 71 cases of adenocarcinoma and 56 cases of squamous cell carcinoma. There were 112 healthy individuals selected as the control group. The qRT-PCR was performed to testify the serum miR-22 and miR-126 levels. Logistic regression analysis was conducted to analyze independent factors influencing NSCLC metastasis and receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of serum miR-22 and miR-126 levels in predicting NSCLC developments and metastasis.The serum miR-22 level was significantly higher in the case group than that in the control group, while the serum miR-126 level was lower in the case group as compared with that in the control group. Compared with squamous cell carcinoma patients, serum miR-22 level significantly increased, while serum miR-126 level decreased in patients with adenocarcinoma. Patients at III + IV stage showed increased serum miR-22 level and relatively decreased serum miR-126 level as compared to patients at I + II stage. Serum miR-22 level elevated in patients with metastasis; in contrast serum miR-126 level reduced in comparison to those without metastasis. In patients with familial inheritance, serum miR-22 level increased but serum miR-126 level decreased as compared to those without familial inheritance. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC development were 99.11%, 84.30%, 82.68% and 96.40%, respectively. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC metastasis were 59.74%, 96.00%, 84.00% and 62.30%, respectively.Results indicated that serum miR-22 and miR-126 levels may be used as the predicative biomarkers for NSCLC development and metastasis.


Vulvar and perianal condyloma superimposed inflammatory linear verrucous epidermal nevus: a case report and review of the literature.
Inflammatory linear verrucous epidermal nevus (ILVEN) is a benign cutaneous hamartoma characterized by intensely erythematous, pruritic, and inflammatory papules that occur as linear bands along the lines of Blaschko. There is a considerable clinical and histological resemblance between ILVEN and linear psoriasis, lichen striatus, linear lichen planus, and invasion of epidermal nevus by psoriasis. The pathogenesis of ILVEN is unknown. It is regarded as a genetic dyskeratotic disease reflecting genetic mosaicism. Here, a case of vulvar and perianal condyloma superimposed ILVEN is presented.


Pediatric nonrhabdomyosarcoma soft tissue sarcomas.
The nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) are a heterogeneous group of mesenchymal cell neoplasms that account for about 4% of childhood cancers. Because each histologic subtype of NRSTS is rare, they have been poorly studied and little is known about their biology, natural history, or optimal treatment. Data from adults with soft tissue sarcomas provide some helpful insight, but adult and childhood NRSTSs differ considerably in the distribution of their histologic subtypes, and certain entities are known to behave differently in young children. The greater risks posed to children by treatment, particularly by radiotherapy, also must be considered in treatment planning for children. This article summarizes what is known to date about childhood NRSTS, including the epidemiology, pathogenesis, and clinical approach to diagnosis and treatment of these tumors.


Novel approaches to the patient with massive hemoptysis.
Massive hemoptysis is a life-threatening condition with a high mortality when treated conservatively. Several modalities have been described in the treatment of hemoptysis with varying results. Endobronchial therapy has traditionally been performed with rigid bronchoscopy. This requires both specialized training and equipment that is not readily available in many centers. The role of fiberoptic bronchoscopy (FOB) is unclear in these situations but is more widely accessible. We describe three cases of the successful treatment of hemoptysis with FOB. These patients were treated with a combination of techniques described previously in the literature; however, these methods failed to result in cessation of the bleeding. Therefore, we employed alternative strategies not described in the literature, using oxidized regenerated cellulose with FOB alone as well as in conjunction with endobronchial placement of vascular embolization coils. These additional techniques may offer other options when rigid bronchoscopy or other modalities are not readily available.


Oxidative Stress Function in Women over 40 Years of Age, Considering Their Lifestyle.
Aging is dependent on biological processes that determine the aging of the organism at the cellular level. The Oxidative Stress Theory of Aging might explain some of the age-related changes in cell macromolecules. Moreover, exposome and lifestyle may also induce changes in cell damage induced by oxidative stress. The aim of the present study was to analyze the related redox changes in lymphocyte function of healthy women over 40 years old. Three groups: younger (YG: 40-49 years), middle aged (MAG: 50-59 years), and older (OG: ≥60 years) were evaluated on anthropometric variables, blood pressure, cardiovascular fitness, lifestyle habits, perceived stress, DNA damage, malondialdehyde, catalase activity, and total antioxidant capacity. Physical activity and cardiovascular fitness were significantly higher in YG and MAG as compared to the OG. Systolic blood pressure increased significantly with group age. Frequency and total amount of alcohol intake were lower in the OG and higher in the MAG. No significant differences were observed between the three groups in oxidative stress parameters. Only alcohol consumption was associated with the higher DNA FPG-sensitive sites, and only in the YG (p < 0.05). Healthy lifestyle is critical to avoiding major ailments associated with aging. This may be inferred from the lack of significant differences in the various oxidative stress parameters measured in the healthy women over the age of 40 who took part in the study. Conscious lifestyle behaviors (decrease in alcohol and smoking habits) could have impaired the expected age-related oxidative stress increase.


Lactate in a laubenpieper.
Acid-base disorders seldom kill; however, the mechanisms and associated complications certainly do. We recently encountered a patient with a mysterious lactic acidosis. The patient proved to be a most capable teacher of important lessons.


Unemployment and health: the healthcare system's role.
Experts from the South Western Sydney Area Health Service and the University of New South Wales say there are few reports of healthcare interventions to address the impact of unemployment on health. They outline possible strategies, which include providing accessible and appropriate healthcare; developing the healthcare system's capacity to deal with the health problems of unemployed people; collaborating with other agencies and sectors working on this issue; acting as an advocate for unemployed people; undertaking research; and providing training, work experience and employment opportunities within the healthcare system. Long term solutions lie in increasing employment and training opportunities. Nevertheless, there is a clear role for the healthcare system in reducing the health impacts of unemployment and ensuring that poor health does not act as a barrier to returning to work.


Repeat length variations in ATXN1 and AR modify disease expression in Alzheimer's disease.
Genomewide association studies (GWASs) have contributed greatly to unraveling the genetic basis of Alzheimer's disease (AD). However, a large amount of "missing heritability" remains. In this exploratory study, we investigated the effect of cytosine-adenine-guanine (CAG) repeats in polyglutamine disease-associated genes (PDAGs) on the risk of AD and its expression. In a cohort of 959 patients diagnosed with AD (Amsterdam Dementia cohort) and 4106 cognitively healthy participants (Leiden 85-plus Study and the Prospective Study of Pravastatin in the Elderly at Risk), we determined the CAG repeat sequences in ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, ATN1, and AR. We did not find a significant association between the risk of AD and variations in CAG repeat numbers of PDAGs. However, we found that differences in CAG repeat numbers in ATXN1, ATXN2, and AR were significantly associated with several clinical and imaging features in AD patients. Specifically, the association between memory performance in patients with AD and the CAG repeat size in the longer ATXN1 allele, and the association between atrophy in the medial temporal lobes and the CAG repeat number in the longer AR allele remained significant after correction for multiple testing. Our findings suggest that repeat polymorphisms in ATXN1 and AR can act as important genetic modifiers of AD, warranting further scrutiny of their role in its missing heritability and pathogenesis.


Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome).
A mother and her son with albinism and sensorineural deafness compatible with Tietz syndrome (MIM 103500) are reported. An in-frame deletion of the MITF gene that is identical at the molecular level to the mouse mi mutant allele has been found in this family. MITF gene mutations account for 20% of Waardenburg syndrome (WS) type II. These data, together with the wide spectrum of mutant alleles reported in mi mice (which have pigmentary disorders), suggest that MITF could be regarded as a candidate gene in various pigmentation disorders in man.


Temperature rise during photo-polymerization under ceramic restorations.
The aim of this study was to measure the temperature increase induced by various light-curing units during photo-polymerization beneath ceramic restorations. Three light-curing units were used; a high intensity QTH unit Elipar 2500 and two LED units: Translux Power Blue and Excelled 1400. The 15 ceramic specimens (CEREC Blocks) used in this study were of 2.5 mm thickness, 5 mm wide and 6 mm long and made using a slow speed saw. Using the same slow speed saw the occlusal enamel portion of 15 mandibular third molars was removed and 15 dentin discs of 1 mm height were prepared. The thickness of the luting cement was delimited to 0.5 mm, using a Teflon mold and then brought into contact with the dentin disc. Light-curing time for all the groups was 20 sec. The temperature rise was measured placing underneath the dentin disc a K-type thermocouple wire connected to a data logger. Five measurements were carried out for each group. Statistical analysis was performed using ANOVA (a=0.05). The results indicated that there was a lower temperature rise induced from Translux Power Blue than from the other two light-curing units, which did not present statistically significant difference (p<0.05). However, temperature rise from the light-curing units used in this study is lower than 5.5°C, which is the limit of pulpal damage. Within the limitations of this study, although the type and characteristics of light-curing units may affect temperature rise under ceramic restorations, this influence is possibly not of clinical significance.


Traditional Chinese medicine to improve rural health in South Africa: A case study for Gauteng.
Rural health is a global crisis across different continents. Most of Africa is predominantly rural and is experiencing financial constraints. Medical support and supplies are a dire need in rural Africa. An alternative option to support the rural population is through traditional Chinese medicine (TCM). Studies have highlighted the efficacy and cost-effectiveness of Chinese medicine in improving health. This article aims to investigate how rural health can be improved through alternative medicine options, focusing primarily on TCM. An identified TCM practice in Gauteng province was selected as the research setting. This study adopted a qualitative case study design to explore 10 participants' views on TCM to improve rural health. The health belief model was used as a theoretical framework, and thematic analysis was used for this study. Findings revealed that most participants accepted TCM as an alternative medical health care option as it resonated with African herbal medicine. Participants agreed that TCM is cheaper and has no side effects. There is a lack of appropriate medical service providers in most rural areas, and often, people depend on traditional medicines as a quick remedy. As TCM is cost-effective and has proven to treat numerous ailments successfully, it is recommended that it be further explored as a health care option available to rural populations. This was the first study on South African patients' views on TCM in the South African context.


Giant Cell Arteritis - Who to Refer to?
Giant cell arteritis is a systemic immune-mediated vasculitis affecting the medium and large arteries. Typical symptoms include new headache, jaw claudication, tender temporal artery, polymyalgia rheumatica, fever and anorexia. Visual loss resulting from giant cell arteritis is an ophthalmic emergency and requires immediate assessment and referral to the ophthalmologist for prompt treatment with steroids. This article provides a systematic approach to the diagnosis and management of giant cell arteritis.


Anterior transposition of the inferior oblique muscle for a snapped inferior rectus muscle following functional endoscopic sinus surgery.
A 55-year-old woman was referred with a 4-month history of diplopia following functional endoscopic ethmoidectomy for chronic sinusitis. She had right hypertropia of 14 prism diopters in the primary position that increased to 30 prism diopters in down gaze. Her right eye showed a moderate limitation of motion in down gaze. Orbital imaging demonstrated a snapped right inferior rectus muscle. The inferior oblique muscle was transposed as an initial treatment for the snapped inferior rectus muscle. After surgery, the patient was orthophoric and obtained fusion in the primary position.


Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression.
Recent data indicate a major role for IL-10 in suppressing immune and inflammatory reactions. To date, expression of human IL-10 has been attributed primarily to helper T lymphocytes, activated monocytes, and neoplastic B cells, and was often found to be associated with IL-6 expression. In this study we sought to determine whether non-hematopoietic human tumor cell lines produce IL-10 and, if so, what is the relationship between IL-10 and IL-6. Using ELISA, we determined IL-10 and IL-6 levels in culture supernatants of 48 cell lines established from carcinomas of the kidney, colon, breast and pancreas, malignant melanomas and neuroblastomas. IL-6 protein was secreted by 28 of the tumor cell lines; IL-10 was measurable in 15 cell lines. IL-6 secretion was maximal and most frequent in renal-cancer cell lines, while IL-10 production was found to be highest and most common among cell lines derived from colon carcinomas. IL-10 in conditioned medium of one of the colon carcinoma cell lines (CCL222) was bio-active, as demonstrated in the mouse MC/9 mast-cell-line assay and in human mixed-lymphocyte reactions. In both assays, IL-10 bio-activity was neutralized by an anti-IL-10 monoclonal antibody. Expression of IL-6 and IL-10 was confirmed by RNA analysis using message amplification by PCR and sequencing of amplified cDNA. LPS, IL-1 alpha, and TNF-alpha strongly enhanced the release of IL-6 by RCC cells, but only marginally affected IL-10 production in colon-carcinoma cells. IL-10 secretion by colon-carcinoma cells was moderately stimulated by IFN-gamma and IL-4. Dexamethasone suppressed the release of IL-6, but had no inhibitory effect on IL-10 secretion. Our results demonstrate that tumor cell lines established from certain types of human carcinomas are capable of expressing and releasing IL-6 and/or IL-10, suggesting a role of these cytokines in solid-tumor development and anti-tumor immunity.


Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts.
RNA virus populations within samples are highly heterogeneous, containing a large number of minority sequence variants which can potentially be transmitted to other susceptible hosts. Consequently, consensus genome sequences provide an incomplete picture of the within- and between-host viral evolutionary dynamics during transmission. Foot-and-mouth disease virus (FMDV) is an RNA virus that can spread from primary sites of replication, via the systemic circulation, to found distinct sites of local infection at epithelial surfaces. Viral evolution in these different tissues occurs independently, each of them potentially providing a source of virus to seed subsequent transmission events. This study employed the Illumina Genome Analyzer platform to sequence 18 FMDV samples collected from a chain of sequentially infected cattle. These data generated snap-shots of the evolving viral population structures within different animals and tissues. Analyses of the mutation spectra revealed polymorphisms at frequencies >0.5% at between 21 and 146 sites across the genome for these samples, while 13 sites acquired mutations in excess of consensus frequency (50%). Analysis of polymorphism frequency revealed that a number of minority variants were transmitted during host-to-host infection events, while the size of the intra-host founder populations appeared to be smaller. These data indicate that viral population complexity is influenced by small intra-host bottlenecks and relatively large inter-host bottlenecks. The dynamics of minority variants are consistent with the actions of genetic drift rather than strong selection. These results provide novel insights into the evolution of FMDV that can be applied to reconstruct both intra- and inter-host transmission routes.


Distributed delays facilitate amplitude death of coupled oscillators.
Coupled oscillators are shown to experience amplitude death for a much larger set of parameter values when they are connected with time delays distributed over an interval rather than concentrated at a point. Distributed delays enlarge and merge death islands in the parameter space. Furthermore, when the variance of the distribution is larger than a threshold, the death region becomes unbounded and amplitude death can occur for any average value of delay. These phenomena are observed even with a small spread of delays, for different distribution functions, and an arbitrary number of oscillators.


A case of pachydermoperiostosis associated with arthritis.
Abstract Pachydermoperiostosis (PDP) is characterized by clubbing fingers, furrowing of the facial skin, and perio-steal hypertrophy. We report a case of a patient with PDP associated with severe arthritis of the knee and ankle joints. His serum C-reactive protein (CRP) levels were increased, and an analysis of serum and synovial fluid showed high levels of interleukin-6. These findings mean that there is some difficulty in distinguishing the disease from rheumatoid arthritis. While treatments such as nonsteroidal anti-inflammatory drugs, steroids, and colchicine were not particularly effective, the severe arthralgia was gradually relieved over a few years.


Periodic health examinations and the provision of cancer prevention services.
To learn about cancer prevention services in primary care practices and to understand physician factors that affect the provision of these services. Survey of physicians and their patients in 1992. Cooperating physicians (n = 72) of a random selection of community general internist and family physician practices in New Hampshire and Vermont. Patients (n = 2775) of the study physicians for at least 1 year, aged 42 years or older, with no life-threatening threatening illness, who recently visited the physician. Proportion of sample patients per practice provided age- and sex-appropriate cancer prevention services in the previous year. In this primary care population, a high proportion of patients received appropriate services in 1992. A periodic health examination within the past year was an important predictor for the receipt of many cancer prevention services. Female physicians provided more periodic health examinations than male physicians; internists provided more than family physicians. The strongest determinant of receiving preventive services is having a periodic health examination. If clinicians and policymakers decrease emphasis on the periodic health examination as a major opportunity to provide indicated preventive services, they should ensure that a satisfactory alternative strategy is in place.


EGFR Trafficking in Physiology and Cancer.
Signaling from the epidermal growth factor receptor (EGFR) elicits multiple biological responses, including cell proliferation, migration, and survival. Receptor endocytosis and trafficking are critical physiological processes that control the strength, duration, diversification, and spatial restriction of EGFR signaling through multiple mechanisms, which we review in this chapter. These mechanisms include: (i) regulation of receptor density and activation at the cell surface; (ii) concentration of receptors into distinct nascent endocytic structures; (iii) commitment of the receptor to different endocytic routes; (iv) endosomal sorting and postendocytic trafficking of the receptor through distinct pathways, and (v) recycling to restricted regions of the cell surface. We also highlight how communication between organelles controls EGFR activity along the endocytic route. Finally, we illustrate how abnormal trafficking of EGFR oncogenic mutants, as well as alterations of the endocytic machinery, contributes to aberrant EGFR signaling in cancer.


The pregnancy outcomes of day-5 poor-quality and day-6 high-quality blastocysts in single blastocyst transfer cycles.
This study compared the outcomes of single blastocyst transfer cycles, using day- 5 poor-quality blastocysts and day-6 high-quality blastocysts. We analyzed 462 frozen-thawed embryo transfer (FET) cycles performed at our center from January 2014 to December 2019. The cycles were divided into two groups: a day-5 poor-quality blastocyst transfer group (group A) and a day-6 high-quality blastocyst transfer group (group B). The clinical outcomes were tested. In groups A and B, respectively, the clinical pregnancy rate (CPR; 61.65% vs. 67.17%, p=0.258), implantation rate (IR; 61.65% vs. 67.17%, p=0.258), and live birth rate (LBR; 69.51% vs. 77.83%, p=0.134) showed no significant differences. Moreover, when day-3 embryo quality was considered, the CPR, IR, and LBR were also similar in group A and group B (p>0.05). The clinical outcomes of day-5 poor-quality blastocysts and day-6 high-quality blastocysts were similar, suggesting that the developmental speed of the embryo might be more important than embryo quality for the clinical outcomes of single blastocyst transfer in FET cycles.


Initial Public Health Laboratory Response After Hurricane Maria - Puerto Rico, 2017.
Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.


MRI-guided stereotactic neurosurgical procedures in a diagnostic MRI suite: Background and safe practice recommendations.
The development of navigation technology facilitating MRI-guided stereotactic neurosurgery has enabled neurosurgeons to perform a variety of procedures ranging from deep brain stimulation to laser ablation entirely within an intraoperative or diagnostic MRI suite while having real-time visualization of brain anatomy. Prior to this technology, some of these procedures required multisite workflow patterns that presented significant risk to the patient during transport. For those facilities with access to this technology, safe practice guidelines exist only for procedures performed within an intraoperative MRI. There are currently no safe practice guidelines or parameters available for facilities looking to integrate this technology into practice in conventional MRI suites. Performing neurosurgical procedures in a diagnostic MRI suite does require precautionary measures. The relative novelty of technology and workflows for direct MRI-guided procedures requires consideration of safe practice recommendations, including those pertaining to infection control and magnet safety issues. This article proposes a framework of safe practice recommendations designed for assessing readiness and optimization of MRI-guided neurosurgical interventions in the diagnostic MRI suite in an effort to mitigate patient risk. The framework is based on existing clinical evidence, recommendations, and guidelines related to infection control and prevention, health care-associated infections, and magnet safety, as well as the clinical and practical experience of neurosurgeons utilizing this technology.


Misuse of psychotropic substances: outline and recommendations of a conference held in London in March 1980.
A conference was held in London in March 1980 on the use and misuse of psychotropic substances. The conference noted that there was a preponderance of medical practitioners who prescribed psychotropic substances. The topics covered ranged from the extent of use of psychotropic substances to the effects of their use in producing different types of morbidity. Consideration was given to controls of psychotropic substances, including steps to reduce their misuse without restricting their legitimate use.


Response to plasmapheresis in myasthenia gravis patients: 22 cases report.
Plasmapheresis means elimination of plasma and replacement of it with other liquids. Effect of this treatment is confirmed in more than 50 diseases like myasthenia gravis, Guillain-Barre syndrome and TTP. This cross sectional study was done on 25 myasthenia gravis patients referred to Shahid Sadoughi hospital, Yazd, Iran 2004-2007. We report 22 myasthenia gravis patients' response to plasmapheresis.


Piezotronic Effect Modulated Heterojunction Electron Gas in AlGaN/AlN/GaN Heterostructure Microwire.
The piezotronic effect is applied to modulate the physical properties of heterojunction electron gas and thus tune the electric transport in AlGaN/AlN/GaN heterostructure microwires. At room temperature, the conductance is increased by 165% under -1.78% compressive strains, and reduced by 48% under 1.78% tensile strains; at 77 K, this modulating effect is further improved by 890% and 940% under compressive and tensile strains, respectively.


Modulation by Trace Amine-Associated Receptor 1 of Experimental Parkinsonism, L-DOPA Responsivity, and Glutamatergic Neurotransmission.
Parkinson's disease (PD) is a movement disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Restoration of dopamine transmission by l-DOPA relieves symptoms of PD but causes dyskinesia. Trace Amine-Associated Receptor 1 (TAAR1) modulates dopaminergic transmission, but its role in experimental Parkinsonism and l-DOPA responses has been neglected. Here, we report that TAAR1 knock-out (KO) mice show a reduced loss of dopaminergic markers in response to intrastriatal 6-OHDA administration compared with wild-type (WT) littermates. In contrast, the TAAR1 agonist RO5166017 aggravated degeneration induced by intrastriatal 6-OHDA in WT mice. Subchronic l-DOPA treatment of TAAR1 KO mice unilaterally lesioned with 6-OHDA in the medial forebrain bundle resulted in more pronounced rotational behavior and dyskinesia than in their WT counterparts. The enhanced behavioral sensitization to l-DOPA in TAAR1 KO mice was paralleled by increased phosphorylation of striatal GluA1 subunits of AMPA receptors. Conversely, RO5166017 counteracted both l-DOPA-induced rotation and dyskinesia as well as AMPA receptor phosphorylation. Underpinning a role for TAAR1 receptors in modulating glutamate neurotransmission, intrastriatal application of RO5166017 prevented the increase of evoked corticostriatal glutamate release provoked by dopamine deficiency after 6-OHDA-lesions or conditional KO of Nurr1. Finally, inhibition of corticostriatal glutamate release by TAAR1 showed mechanistic similarities to that effected by activation of dopamine D2 receptors. These data unveil a role for TAAR1 in modulating the degeneration of dopaminergic neurons, the behavioral response to l-DOPA, and presynaptic and postsynaptic glutamate neurotransmission in the striatum, supporting their relevance to the pathophysiology and, potentially, management of PD. Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Restoration of dopamine transmission by l-DOPA relieves symptoms of PD but causes severe side effects. Trace Amine-Associated Receptor 1 (TAAR1) modulates dopaminergic transmission, but its role in PD and l-DOPA responses has been neglected. Here, we report that TAAR1 potentiates the degeneration of dopaminergic neurons and attenuates the behavioral response to l-DOPA and presynaptic and postsynaptic glutamate neurotransmission in the striatum, supporting the relevance of TAAR1 to the pathophysiology and, potentially, management of PD.


[Lung diseases caused by non-tuberculous mycobacteria in East Germany and Hungary].
Despite the decrease of new cases of pulmonary tuberculosis also between 1982 and 1986 an increase in nontuberculous mycobacteriosis can be seen especially in the GDR and also in Hungary. In 1986 the ratio of recognized lung diseases caused by nontuberculous mycobacteria to all newly diagnosed bacillary cases was 4.1% in the GDR and 2.2% in Hungary. In Hungary, M. xenopi was the most important potential pathogenic species of nontuberculous mycobacteria during the whole period, followed by M. kansasii. In the GDR at the beginning most cases of nontuberculous mycobacteriosis were caused by M. kansasii later, M. xenopi was most frequent. Most of the patients with nontuberculous mycobacteriosis were men older than 50 years of age.


Sharps injuries and job burnout: a cross-sectional study among nurses in China.
The present study investigated the relationship between sharps injuries and job burnout in nurses. Sharps injury questionnaires and the Maslach Burnout Inventory (MBI) questionnaires were used to investigate and analyze job burnout among 468 nurses, of which 458 effective questionnaires were collected, for a response rate of 97.86%. A total of 292 nurses had at least one sharps injury (63.76% of the 458 nurses). The dimension scores were higher for injured nurses compared with non-injured nurses. The difference between the dimensions of emotional exhaustion and depersonalization for nurses with sharps injuries was statistically significant (P < 0.05). A rank correlation analysis showed that these two dimensions had a positive correlation with sharps injuries (r = 0.69-0.78). The prevalence of sharps injuries in nursing is associated with depersonalization, as measured by the MBI. Nursing administrators should pay more attention to clinically burned-out nurses, and provide more opportunity to nurses for training and education to reduce the prevalence of sharps injuries.


Immunological characteristics of amniotic epithelium.
We review recent experimental evidence of the immunosuppressive and immunogenic potential of amniotic epithelial cells. Since cryopreserved amniotic membrane (AM) has been used in clinical applications, much research has focused on the beneficial effects of amniotic stromal matrix rather than on the function of viable amniotic cells. However, viable human amniotic epithelial cells (HAECs) have been shown to elicit beneficial effects on secretion of anti-inflammatory factors. Topical application of culture supernatant from HAECs leads to profound suppression of suture-induced neovascularization in cornea and fewer major histocompatibility complex (MHC) class II antigen-presenting cells (APCs) in inflamed cornea after thermal cautery. Furthermore, expression of interleukin (IL)-1beta mRNA was suppressed in cauterized cornea. These results suggest that HAECs are a source of soluble anti-inflammatory factors that suppress corneal inflammation. However, viable amniotic epithelial cells display antigenicity and immunogenicity as allografts. Fresh allogeneic amniotic epithelium (AE) expresses MHC class I antigens and sensitizes recipients when placed in the eye, although long-term memory of allo-specific delayed hypersensitivity (DH) was not acquired. Allogeneic AE was clearly vulnerable to acute immune rejection in specifically sensitized recipients and recipients of repeated AE transplantation. We therefore suggest that immunogenicity of AE should not be ignored, and use of AM from different donor placentas should be emphasized when repeated AM transplantation is required in patients clinically.


Patients with cancer and their relatives beliefs, information needs and information-seeking behavior about cancer and treatment.
To identify cancer patient and relatives beliefs, information needs, information-seeking behavior and information sources about cancer and treatment. This research was conducted at two hospitals of a university. Data was collected via questionnaires and the Turkish version of the Miller Behavioral Style Scale (MBSS) to assess information-seeking behavior. The sample included 82 patients and 54 relatives. Patients were receiving treatment mostly for breast, gynecologic, lung cancer and leukemia/ lymphoma. All of them indicated that they want to be informed by a doctor about their diagnosis and treatment first. Other information sources were internet, media and nurses. The majority of the patients and half of their relatives agreed that "cancer is curable and preventable disease". Only 2.5% of patients agreed with the statement "I don't want to get information about disease which disturbs me". According the data obtained from MBSS; the mean patients MBSS score (6.41±3.2) was higher than their relatives (5.46±3.1). Respondents with higher education and younger age indicated more information-seeking behavior. Patients and their relatives differ in some of their information-seeking behavior. Patients beliefs and their strategies for coping with their illness can constrain their wish for information and their efforts to obtain it. Healthcare professionals need to assess and be sensitive to the information-seeking behavior of cancer patients and their relatives.


Preoperative serum C-reactive protein and its prognostic significance in patients with stage III-IV colorectal cancer.
The molecular mechanism underlying the development of colorectal cancer (CRC) is not yet fully-understood, but there is evidence that inflammation plays a key role. Several circulating tumor and inflammatory markers can be useful for studying patients with CRC. It has been suggested that high serum levels of C-reactive protein (CRP) are associated with elevated risk of various malignancies and that CRP may affect survival of patients with CRC. We analyzed the relationship existing between the stage of the disease and baseline CRP serum levels in a group of 91 patients undergoing surgery for stage III (N=72, 79.1%) and IVa (N=19, 20.9%) CRC. There were 51 (56%) men and 40 (44%) women, with a median age of 66 years. Prior to surgery, all patients underwent quantitative serum CRP measurement. The overall 5-year survival was 37.1 ± 13.0 months. Patients with stage III disease and the sub-group with CRP<3 mg/l (N=43, 47.3%) had a longer survival (p<0.01) than patients with stage IVa and the sub-group with CRP ≥ 3 mg/l (N=48, 52.7%). No relationship between the age of the patients and CRP levels was found (R=-0.005, p=0.96), whilst there was a significant inverse relationship between survival and CRP level (R=-0.37, y=37.5343-0.5868x, p=0.0003). Using multivariate Cox model analysis (forward stepwise method), adjusted for age, CRP and CRC stage were independent parameters related to survival, with a relative risk of 3.5 (95% confidence interval=1.5-8.2) and 8.1 (95% confidence interval=3.0-21.3), respectively. In conclusion, CRP is a sensitive and easily detectable serum marker that can be useful in patients with CRC, allowing their better clinical stratification.


Central hypogonadism: distinguishing idiopathic low testosterone from pituitary tumors.
To attempt to determine clinical or hormonal characteristics that could help distinguish benign idiopathic low testosterone (ILT) from pituitary tumor. On retrospective review of medical records of patients encountered by Johns Hopkins endocrine staff between 1985 and July 1995, 64 patients who fulfilled our enrollment criteria--27 men with ILT and 37 patients with imaging-proven pituitary tumor--were identified. Men 21 years of age or older needed to have had serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels measured before hormonal replacement therapy or pituitary tumor extirpation (or both) and a high-quality imaging scan (computed tomography or magnetic resonance imaging) done and interpreted by the Johns Hopkins radiology staff. In comparison with men who had ILT, men with pituitary tumors had similar serum testosterone levels and significantly higher serum levels of LH, FSH, and prolactin. In addition, significantly more men with pituitary tumors had visual field abnormalities, headaches, and symptoms of hypothyroidism in comparison with the men with ILT. In contrast, the group with ILT complained significantly more of impotence, erectile dysfunction, and depression than did the group with pituitary tumors. The age at initial assessment was comparable in both study groups. Although age at initial manifestation did not predict the presence of pituitary tumor, the group of men with tumors were more likely than those with ILT to have serum testosterone levels <150 ng/dL, higher serum gonadotropin and prolactin levels, and visual field abnormalities and less likely to have sexual dysfunction. Therefore, on the basis of our data, we recommend that men with these findings should be referred for a magnetic resonance image to exclude the presence of a tumor.


Immunological Responses of Arsenicum album 30CH to Combat COVID-19: Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial in the Pathanamthitta District of Kerala.
COVID-19 is a recent major public health concern caused by the SARS-CoV-2 virus, with approximately 44.6 million COVID-19-positive cases and 530,000 deaths in India (as of February 1, 2023). The COVID-19 vaccination drive in India was initiated in January 2021; however, an effective preventive strategy with high efficacy and immunological safety remains elusive. The aim of this study is to assess the immunogenic responses of Arsenicum album 30CH (AA30CH) as COVID-19 prophylaxis, including assessment of immunological markers, innate and acquired immune responses, COVID-19 symptoms, and its associated antibody responses. This randomized controlled clinical trial (RCT) will include two parallel comparator groups of AA30CH and placebo with an allocation ratio of 1:1 conducted in the Pathanamthitta district of Kerala, India. The placebo or AA30CH will be administered in three intervention schedules and blood samples will be collected before and after each of the intervention schedules. Based on the inclusion and exclusion criteria, 112 participants per arm (with an expected dropout of 20%) will be screened. Immunogenic responses will be evaluated by determining the antigen density and modulation in immunological markers and lymphocyte subsets CD3, CD4, CD8, CD24, CD27, CD38, CD4 interferon-γ, CD4 CD17, CD4 CD25 (activated T lymphocytes), T cells, B cells, dendritic cells (mature and immature), and natural killer cells on days 1, 5, 23,27, 45, 49, and 66. The innate and acquired immune responses will also be evaluated by a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) array profiler (84-gene set) before and after the study interventions. The toxicity status of AA30CH in study participants will be evaluated through hepatic, renal, and hematological parameters and peripheral smears on days 1, 5, 23, 27, 45, 49, and 66. The number of participants developing COVID-19-like symptoms per National Centre for Disease Control guidelines and the number of participants testing positive for COVID-19 in RT-PCR during follow-ups in any of the three intervention schedules will be identified. Moreover, a subgroup analysis will be used to assess the COVID-19 antibody responses between vaccinated and unvaccinated participants. This RCT protocol has been approved by various committees and funded by the Central Council for Research in Homoeopathy, Ministry of Ayush, Government of India. The project has been implemented in collaboration with the Department of Homoeopathy, Government of Kerala. The RCT was rolled out on January 25, 2023, and enrollment was completed April 3, 2023. The immunological assays will be conducted at the Department of Biotechnology-Translational Health Science and Technology Institute, Faridabad, India. This study will represent the first evaluation of the immunological efficacy and safety of AA30CH in an RCT, which may significantly impact the use of homeopathy as an evidence-based medicine approach. Clinical Trials Registry-India CTRI/2022/08/045089; https://tinyurl.com/mryrpkvk. DERR1-10.2196/48479.


A new experimental device for the measurement of moisture emission and heat release from respiratory organs and body surface.
A new experimental device was developed to investigate respiratory diseases. The moisture and heat released from respiratory organs and the body surface of a rat were determined by means of this device as well as the rectal temperature. The high recovery of results was statistically confirmed, and the measured values at various environmental temperatures were significantly different from each other. Some standard drugs, such as ephedrine, aminophylline and chlorpromazine, were examined. Their stimulant or depressant actions were clearly observed. The results of some traditional medicines for the treatment of rhinitis and bronchial asthma from this measuring system were consistent with their clinical applications. These results suggest that this new experimental system is not only effective in the experimental understanding of cold-hot syndrome, but also contributes to the evaluation of the effects of traditional medicines.


Effects of excessive noradrenaline on cardiac mitochondrial calcium transport and oxidative phosphorylation.
Mitochondrial oxidative phosphorylation, calcium transport activity and calcium content were investigated in dog hearts injured by excessive noradrenaline (NA). Diffuse cardiac injury was produced by a 5-hour infusion of NA (2 or 5 micrograms/kg/min), and the injury was evaluated based on ECG and hemodynamic changes. Mitochondrial calcium uptake and binding activities measured in the presence of ATP showed no significant differences between the control and NA groups. However, the calcium content of heart mitochondria isolated from the NA groups, state 3 respiration and the respiratory control index were significantly depressed without any change in the ADP/O ratio. These results suggest that excessive NA causes the intracellular calcium overload and the depression of mitochondrial respiration, and the both of these changes may play a key role in the pathogenesis of myocardial injury through the insufficient control of cytosolic calcium levels.


Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells.
Alpha-amanitin is a known cytotoxic substance found in some mushroom species including Amanita phalloides. Its main mechanism of action is to block the transcription, which can lead to cell death. Lack of reports on the genotoxicity of this toxin was an inspiration for undertaking this experiment. Genotoxic effect of α-amanitin on balb/c mice bone marrow cells was tested using: comet assay and chromosomal aberration test. The tested substance was given once by intraperitoneal administration to animals at doses: 0.1 mg/kg, 0.15 mg/kg and 0.25 mg/kg (LD50) body weight with 48 h exposure. The comet assay demonstrated a statistically significant increase in DNA damage for all the investigated α-amanitin doses compared to the negative control (p < 0.0001). The exposure to 0.15 and 0.25 mg/kg doses of α-amanitin also generated a statistically significant increase in the frequency of chromosomal aberrations in bone marrow cells of mice compared to the negative control (p < 0.05). The genotoxic effect induced by α-amanitin in mammalian cells can result in genome instability and its functional consequences.


Empowering Patients One App at a Time: An Introduction to Digital Therapeutics.
The growth of digital health has led to more app-based solutions entering the market which aim to provide therapeutic outcomes for a variety of diseases. This column explores the emerging field of digital therapeutics (DTx) as evidence-based and FDA-cleared digital interventions - setting them apart from the majority of commercially available solutions. In an effort to identify high quality and evidence-based options, medical and health science librarians can benefit from recognizing the qualifications of DTx, types of available DTx, and use cases for their patrons.


Novel effect of CP55,940, a CB1/CB2 cannabinoid receptor agonist, on intracellular free Ca2+ levels in bladder cancer cells.
The study was undertaken to explore the effect of CP55,940 ((-)-cis-3-[2-Hydroxy4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol), a drug commonly used as a CB1/CB2 cannabinoid receptor agonist, on intracellular free Ca2+ levels ([Ca2+]i) in several cell types [Ca2+]i was measured in suspended cells by using the fluorescent dye fura-2 as an indicator. At concentrations between 1-50 microM, CP55,940 increased [Ca2+]i in a concentration-dependent manner with an EC50 of 8 microM. The [Ca2+]i signal comprised an initial rise, a slow decay, and a sustained phase. CP55940 (10 microM)-induced (Ca2+]i signal was not altered by 5 microM of two cannabinoid receptor antagonists (AM-251, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; AM-281, 1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-m3thyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide). Extracellular Ca2+ removal decreased the maximum value of the Ca2+ signals by 50%. CPS5,940 (10 microM)-induced [Ca2+]i increase in Ca2+-free medium was inhibited by 80% by pretreatment with 1 microM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 10 microM CP55,940 in Ca2+-free medium for 6 min abolished thapsigargin-induced [Ca2+]i increase. Nifedipine (10 microM) and verapamil (10 microM) did not alter CP55,940 (10 microM)-induced [Ca2+]i increase. CP55, 940 (10 microM)-induced Ca2+ release was not affected when phospholipase C was inhibited by 2 microM U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione). CP55,940 (5 microM) also increased [Ca22+] in Madin-Darby canine kidney cells, MG63 human osteosarcoma cells, and IMR-32 neuroblastoma cells. Collectively, CP,55940 induced significant [Ca2+]i increases in several cell types by releasing store Ca2+ from thapsigargin-sensitive pools and by causing Ca2+ entry. The CP55,940's action appears to be dissociated from stimulation of cannabinoid receptors


Cardiopulmonary resuscitation on a moving boat.
A study has found that surf lifeguards can deliver good-quality cardiopulmonary resuscitation (CPR) on moving inflatable rescue boats, but that it is less effective than when delivered onshore.


From ribosome to ribotoxins: understanding the toxicity of deoxynivalenol and Shiga toxin, two food borne toxins.
Ribosomes that synthesize proteins are among the most central and evolutionarily conserved organelles. Given the key role of proteins in cellular functions, prokaryotic and eukaryotic pathogens have evolved potent toxins to inhibit ribosomal functions and weaken their host. Many of these ribotoxin-producing pathogens are associated with food. For example, food can be contaminated with bacterial pathogens that produce the ribotoxin Shiga toxin, but also with the fungal ribotoxin deoxynivalenol. Shiga toxin cleaves ribosomal RNA, while deoxynivalenol binds to and inhibits the peptidyl transferase center. Despite their distinct modes of action, both groups of ribotoxins hinder protein translation, but also trigger other comparable toxic effects, which depend or not on the activation of the ribotoxic stress response. Ribotoxic stress response-dependent effects include inflammation and apoptosis, whereas ribotoxic stress response-independent effects include endoplasmic reticulum stress, oxidative stress, and autophagy. For other effects, such as cell cycle arrest and cytoskeleton modulation, the involvement of the ribotoxic stress response is still controversial. Ribotoxins affect one organelle yet induce multiple toxic effects with multiple consequences for the cell. The ribosome can therefore be considered as the cellular "Achilles heel" targeted by food borne ribotoxins. Considering the high toxicity of ribotoxins, they pose a substantial health risk, as humans are highly susceptible to widespread exposure to these toxins through contaminated food sources.


Cardiac Sympathetic Dominance and Systemic Inflammation in COPD.
Cardiac autonomic dysfunction is an independent determinant of adverse outcomes in many diseases. The available literature on the relative changes in sympathetic and parasympathetic components in chronic obstructive pulmonary disease (COPD) is equivocal, the clinical and physiological correlates are poorly defined and association with markers of systemic inflammation has not been explored. As both autonomic dysfunction and systemic inflammation may contribute to cardiovascular morbidity in COPD, we hypothesized that these may be associated. Sixty three stable patients of COPD and 36 controls underwent spirometry, estimation of diffusion capacity, six-minute walk test and measurements of serum interleukin-6 (IL-6) and high-sensitivity C-Reactive protein. Cardiac autonomic activity was evaluated by standard five-minute heart rate variability (HRV) recordings to obtain time- and frequency-domain indices and the averaged heart rate. We observed that HRV indices of overall autonomic modulation, the standard deviation of time intervals between consecutive normal beats (SDNN) and total power, were greater in patients with higher levels of indices of both parasympathetic and sympathetic activity. The heart rate was significantly higher in patients indicating an overall sympathetic dominance and was inversely correlated with diffusion capacity. Serum IL-6 was inversely correlated with pNN50, an index of parasympathetic activity, and positively with LF/HF ratio, a measure of sympathetic: parasympathetic balance. None of the HRV indices was significantly correlated with physiological measures of severity. It was concluded that patients with COPD have increased cardiac autonomic modulation with sympathetic dominance. This is associated with decreased lung diffusion capacity and systemic inflammation.


The role of MR imaging in detecting nodal disease in thyroidectomy patients with rising thyroglobulin levels.
One of the dilemmas facing clinicians treating patients with thyroid cancer is the evaluation of postthyroidectomy patients with rising serum thyroglobulin levels and indeterminate or normal findings on neck sonography. In this study, we examine the role of MR imaging in this subgroup of patients. We retrospectively reviewed MR images of patients with thyroid cancer with abnormal lymph nodes in the retropharyngeal and parapharyngeal spaces and determined the size and signal-intensity characteristics of these nodes. We reviewed patient charts for the following history: 1) thyroidectomy, 2) rising thyroglobulin levels, 3) iodine-131 radiation therapy, 4) neck dissection, and 5) pathology on neck sonography and chest CT. We reviewed pathology findings to determine if thyroid cancer metastases were present in these lymph nodes. Eight patients had abnormal retropharyngeal space nodes, and 1 patient had a parapharyngeal space mass. Lymph nodes ranged from 7 to 25 mm. On MR imaging, 1 patient had a cystic node, 2 had complex nodes, and 6 had solid nodes. Eight patients had rising serum thyroglobulin levels and a history of thyroidectomy, radioiodine therapy, and neck dissection. Two of these patients had no pathologic nodes on sonography and normal findings on chest CT. Six patients had tissue sampling of their skull base node, and metastatic thyroid cancer was present in 5. MR imaging of the neck should be considered in thyroidectomy patients with rising serum thyroglobulin levels and a history of radioiodine therapy and neck dissection. Radiologists should carefully examine the retropharyngeal and parapharyngeal spaces in these patients because nodal metastases may occur there more commonly than realized.


Irritation and cytotoxic potential of denture adhesives.
The present study aimed to examine the in vitro biocompatibility of denture adhesives. Denture adhesives absorb water to become viscous and sticky, and by this process, other constituents like colouring, flavouring, wetting and preserving agents may be released. Some of these constituents may induce adverse reactions among users of denture adhesives. Five commercially available denture adhesives; three different creams, a powder, and a cushion were included in the study. The irritation and cytotoxic potential was evaluated using the Hen's Egg Test Chorioallantoic Membrane (HET-CAM) method and three cell culture methods; filter diffusion, dimethylthiazol diphenyltetrazolium bromide (MTT) assay and agar diffusion. None of the tested denture adhesives showed a noteworthy acute irritation as evaluated by the HET-CAM method. None of the tested denture adhesives induced cytotoxicity in the filter diffusion test. One of the denture adhesives induced a severe cytotoxic reaction in both the MTT and agar diffusion assays. These tests employ longer exposure times than in both the filter diffusion and the HET-CAM test. Denture adhesives are commonly used throughout the day, and our results raise the concern that denture adhesives may contribute to mucosal inflammation in denture wearers.


Beyond sensitivity, specificity and statistical independence.
Sensitivity and specificity have clear definitions when there is a single test for one disease, and the test is either positive or negative. This paper presents a unified approach for obtaining posterior probabilities (predictive values) when there are more than two test outcomes and/or more than one disease state. In these cases, sensitivity and specificity do not have clear definitions. Three examples from the literature demonstrate how this approach simplifies the presentation of Bayesian revision of prior probabilities. Use of proper care in data collection for the purpose of estimating conditional probabilities can avoid assumptions of statistical independence.


Role of Ca2+ in drought stress signaling in wheat seedlings.
Plants use complex signal transduction pathways to perceive and react to various biotic and/or abiotic stresses. As a consequence of this signaling, plants can modify their metabolism to adapt themselves to new conditions. One such change is the accumulation of proline in response to drought and salinity stresses. We have studied drought and salinity induced proline accumulation and the roles of Ca2+ (10 mM) and indoleacetic acid (IAA, 0.3 mM) in this response. Subjecting seedlings to both drought (6% polyethylene glycol, PEG) and salinity (150 mM NaCl) stress resulted in a dramatic increase in proline accumulation (7-fold higher than control level). However, the application of Ca2+ along with these stress factors had different effects. Unlike the salinity stress, Ca2+ prevented the drought induced proline accumulation indicating that these stress factors use distinct signaling pathways to induce similar responses. Experiments with IAA and EGTA (10 mM) supported this interpretation and suggested that Ca2+ and auxin participate in signaling mechanisms of drought-induced proline accumulation. Drought and salt stress-induced proline accumulation was compared on salt resistant (cv. Gerek 79) and salt sensitive (cv. Bezostaya) wheat varieties. Although proline level of the first was twofold lower than that of the second in control, relative proline accumulation was dramatically higher in the case of the salt resistant wheat variety under stress conditions.


Lymphocyte subpopulations at the site of "piecemeal" necrosis in end stage chronic liver diseases and rejecting liver allografts in cyclosporine-treated patients.
Mononuclear cells in the areas of "piecemeal" necrosis in hepatic tissues from patients with different liver diseases were subtyped using monoclonal antibodies and the avidin-biotin-peroxidase complex method. T lymphocytes were the predominant infiltrating cell type in this lesion (greater than 75% of mononuclear cells) regardless of the etiology of the liver disease. M1-positive cells represented about 20% of the infiltrate. B cells were absent and rare Leu-7-positive cells (killer, natural killer) showed random tissue distribution in both the periportal areas and the parenchyma. In contrast, the T8+ (suppressor-cytotoxic) lymphocytes accumulated selectively in the areas of piecemeal necrosis, where the tissue T4/T8 ratios were consistently less than 1. T8+ lymphocytes were also more numerous than T4+ cells around the hepatitis B surface antigen-positive hepatocytes in piecemeal necrotic areas of livers from patients with hepatitis B surface antigen-positive chronic active hepatitis. In liver tissues of patients with primary biliary cirrhosis, alcoholic cirrhosis, chronic active hepatitis, and rejecting liver allografts, selective accumulations of T8+ lymphocytes at the sites of hepatocyte necrosis were a characteristic and uniform finding. This subpopulation of lymphocytes may be an important part of the immunologically mediated destruction of hepatocytes that occurs in chronic active liver diseases and is characterized by piecemeal necrosis.


Assessment of accuracy and efficiency of atlas-based autosegmentation for prostate radiotherapy in a variety of clinical conditions.
The goal of the current study was to evaluate the commercially available atlas-based autosegmentation software for clinical use in prostate radiotherapy. The accuracy was benchmarked against interobserver variability. A total of 20 planning computed tomographs (CTs) and 10 cone-beam CTs (CBCTs) were selected for prostate, rectum, and bladder delineation. The images varied regarding to individual (age, body mass index) and setup parameters (contrast agent, rectal balloon, implanted markers). Automatically created contours with ABAS(®) and iPlan(®) were compared to an expert's delineation by calculating the Dice similarity coefficient (DSC) and conformity index. Demo-atlases of both systems showed different results for bladder (DSC(ABAS) 0.86 ± 0.17, DSC(iPlan) 0.51 ± 0.30) and prostate (DSC(ABAS) 0.71 ± 0.14, DSC(iPlan) 0.57 ± 0.19). Rectum delineation (DSC(ABAS) 0.78 ± 0.11, DSC(iPlan) 0.84 ± 0.08) demonstrated differences between the systems but better correlation of the automatically drawn volumes. ABAS(®) was closest to the interobserver benchmark. Autosegmentation with iPlan(®), ABAS(®) and manual segmentation took 0.5, 4 and 15-20 min, respectively. Automatic contouring on CBCT showed high dependence on image quality (DSC bladder 0.54, rectum 0.42, prostate 0.34). For clinical routine, efforts are still necessary to either redesign algorithms implemented in autosegmentation or to optimize image quality for CBCT to guarantee required accuracy and time savings for adaptive radiotherapy.


Comparative studies of interferon and three antiviral agents on neurotropic and oncogenic herpesviruses.
The antiviral effects of four compounds, phosphonoacetate, phosphonoformate, acycloguanosine, and purified human lymphoblastic interferon, were tested against two neurotropic herpesviruses, herpesvirus platyrrhine and herpes simplex virus, and two oncogenic herpesviruses, herpesvirus saimiri and herpesvirus ateles. All four compounds induced different degrees of inhibition of these herpesviruses. Phosphonoacetate and phosphonoformate at concentrations of 50 micrograms/ml or greater showed powerful antiviral activities. Interferon was more effective against herpesvirus saimiri and herpesvirus ateles, the two oncogenic viruses. Herpes simplex virus and the oncogenic herpesviruses were effectively inhibited by acycloguanosine, whereas herpesvirus platyrrhine proved to be resistant. The simian herpesviruses required a higher concentration of phosphonoformate, phosphonoacetate, and acycloguanosine for antiviral action. The antiviral action of all four compounds was contingent on the continued presence of the compounds in the infected cell culture medium.


T lymphocytes in allergen-induced late-phase reactions and asthma.
We have studied a number of aspects of the interrelationship between T lymphocytes and allergic inflammation. Using monoclonal antibodies and immunocytochemistry we have observed significant infiltration by CD3+/CD4+ T lymphocytes together with evidence of T cell activation in the allergen-induced late-phase skin reaction in human atopic subjects. These changes were accompanied by eosinophil infiltration and activation. Activated T cells were also detected in the blood of patients with acute severe asthma. The role of T lymphocytes in granulocyte chemotaxis and activation was also explored, using recombinant human lymphokines, and we have identified and characterized two lymphokines which have specific effects upon neutrophils.


Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.
Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.


[Lens biomaterials for cataract surgery].
The first lens implantations were performed by Sir Harold Ridley in 1949 using rigid poly-methyl-methacrylate (PMMA) lenses. This biomaterial was used exclusively for more than 30 years. In the early 1970s, Charles Kelman introduced phacoemulsification, reducing the incision size and beginning biomaterial diversification, including foldable materials. More than 50 years after the introduction of PMMA, the range of biomaterials used for intraocular lenses remains extremely limited. Among the materials tested, acrylic polymers and silicon elastomeres are the only remaining materials used for optics. In vivo tolerance is no longer the sole criterion in choosing biomaterials: clinical performance now plays a major role, including injection abilities, optical qualities, and long-term postoperative intraocular behavior. Together with lens design, the analysis of the physical and chemical characteristics of biomaterials will contribute to the choice of the best intraocular lens.


Dysphagia and associated respiratory considerations in cervical spinal cord injury.
Dysphagia is a relatively common secondary complication that occurs after acute cervical spinal cord injury (SCI). The detrimental consequences of dysphagia in SCI include transient hypoxemia, chemical pneumonitis, atelectasis, bronchospasm, and pneumonia. The expedient diagnosis of dysphagia is imperative to reduce the risk of the development of life-threatening complications. The objective of this study was to identify risk factors for dysphagia after SCI and associated respiratory considerations in acute cervical SCI. Bedside swallow evaluation (BSE) was conducted in 68 individuals with acute cervical SCI who were admitted to an SCI specialty unit. Videofluroscopy swallow study was conducted within 72 hours of BSE when possible. This prospective study found dysphagia in 30.9% (21 out of 68) of individuals with acute cervical SCI. Tracheostomy (P = .028), ventilator use (P = .012), and nasogastric tube (P = .049) were found to be significant associated factors for dysphagia. Furthermore, individuals with dysphagia had statistically higher occurrences of pneumonia when compared with persons without dysphagia (P < .001). There was also a trend for individuals with dysphagia to have longer length of stay (P = .087). The role of respiratory care practitioners in the care of individuals with SCI who have dysphagia needs to be recognized. Aggressive respiratory care enables individuals with potential dysphagia to be evaluated by a speech pathologist in a timely manner. Early evaluation and intervention for dysphagia could decrease morbidity and improve overall clinical outcomes.


Emergency management of bleeding associated with old and new oral anticoagulants.
As major prescribers of oral anticoagulants, cardiologists must be familiar with strategies to manage bleeding, the principal complication associated with all anticoagulants, and to reverse anticoagulant effects in acute-care settings. The purpose of this manuscript is to review currently available information regarding dabigatran and rivaroxaban, the 2 novel oral anticoagulants approved to date in the United States. Further, we suggest reasonable interventions for the clinician faced with a patient who suffers a major bleeding event while receiving one of these agents. Data sources were peer-reviewed publications, US Food and Drug Administration documents in the public domain, and approved US prescribing information for dabigatran (Pradaxa) and rivaroxaban (Xarelto). Strategies for management of bleeding and reversal of anticoagulant effects from warfarin include vitamin K, fresh frozen plasma, and prothrombin complex concentrates. For rivaroxaban and dabigatran, appropriate therapies include support and observation, which are likely to be effective for the majority of patients because of the short half-lives of these agents. In severe life-threatening hemorrhage, clotting-factor substitutes may be appropriate in certain situations. Validated protocols specific to each agent remain to be developed.


A Novel Method for Estimating Monocular Depth Using Cycle GAN and Segmentation.
Modern image processing techniques use three-dimensional (3D) images, which contain spatial information such as depth and scale, in addition to visual information. These images are indispensable in virtual reality, augmented reality (AR), and autonomous driving applications. We propose a novel method to estimate monocular depth using a cycle generative adversarial network (GAN) and segmentation. In this paper, we propose a method for estimating depth information by combining segmentation. It uses three processes: segmentation and depth estimation, adversarial loss calculations, and cycle consistency loss calculations. The cycle consistency loss calculation process evaluates the similarity of two images when they are restored to their original forms after being estimated separately from two adversarial losses. To evaluate the objective reliability of the proposed method, we compared our proposed method with other monocular depth estimation (MDE) methods using the NYU Depth Dataset V2. Our results show that the benchmark value for our proposed method is better than other methods. Therefore, we demonstrated that our proposed method is more efficient in determining depth estimation.