Evaluation and Comparison of Left Ventricular Functions by Cardiac MRI and 2D Transthoracic Echocardiography.
It is important to measure left ventricular function (LVF) accurately in the diagnosis and follow-up of cardiovascular diseases. Different imaging algorithms and mathematical calculations have been developed for the evaluation of LVF in cardiac magnetic resonance imaging (MRI), and numerous studies are still being carried on this. In our study, LVF was calculated by two different measurement methods in MRI and were compared with transthoracic echocardiography (TTE) to assess the correlation and the consistency of these with TTE. In this study, 31 patients with left ventricular dysfunction due to different etiologies were evaluated with simultaneous TTE and MRI. In the Cine MR images, LVF parameters of ejection fraction, end-diastolic volume, end-systolic volume, and myocardial mass were measured using short axis images (short axis method) and short axis plus four chamber and two chamber images (combined method). The results were compared with the results from TTE. We found that the combined and the short axis-based calculations of ejection fraction, end-diastolic volume, end-systolic volume, and myocardial mass in cardiac MRI showed correlation and consistency with those calculated via echocardiography. We also determined that the short axis-based calculations in cardiac MRI showed better correlation with the echocardiography compared with the combined method. Because our results revealed that the cardiac MRI results obtained from the short axis method better correlate with the TTE, we recommend using short axis-based measurements in the evaluation left ventricular dysfunction.


Management of shoulder dystocia: trends in incidence and maternal and neonatal morbidity.
To investigate trends in the incidence of shoulder dystocia, methods used to overcome the obstruction, and rates of maternal and neonatal morbidity. Cases of shoulder dystocia and of neonatal brachial plexus injury occurring from 1991 to 2005 in our unit were identified. The obstetric notes of cases were examined, and the management of the shoulder dystocia was recorded. Demographic data, labor management with outcome, and neonatal outcome were also recorded for all vaginal deliveries over the same period. Incidence rates of shoulder dystocia and associated morbidity related to the methods used for overcoming the obstruction to labor were determined. There were 514 cases of shoulder dystocia among 79,781 (0.6%) vaginal deliveries with 44 cases of neonatal brachial plexus injury and 36 asphyxiated neonates; two neonates with cerebral palsy died. The McRoberts' maneuver was used increasingly to overcome the obstruction, from 3% during the first 5 years to 91% during the last 5 years. The incidence of shoulder dystocia, brachial plexus injury, and neonatal asphyxia all increased over the study period without change in maternal morbidity frequency. The explanation for the increase in shoulder dystocia is unclear but the introduction of the McRoberts' maneuver has not improved outcomes compared with the earlier results. II.


Participation of glyceraldehyde-3-phosphate dehydrogenase in the regulation of 2,3-diphosphoglycerate level in erythrocytes.
Data are presented concerning the possible participation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in regulation of the glycolytic pathway and the level of 2,3-diphosphoglycerate in erythrocytes. Experimental support has been obtained for the hypothesis according to which a mild oxidation of GAPDH must result in acceleration of glycolysis and in decrease in the level of 2, 3-diphosphoglycerate due to the acyl phosphatase activity of the mildly oxidized enzyme. Incubation of erythrocytes in the presence of 1 mM hydrogen peroxide decreases 2,3-diphosphoglycerate concentration and causes accumulation of 3-phosphoglycerate. It is assumed that the acceleration of glycolysis in the presence of oxidative agents described previously by a number of authors could be attributed to the acyl phosphatase activity of GAPDH. A pH-dependent complexing of GAPDH and 3-phosphoglycerate kinase or 2, 3-diphosphoglycerate mutase is found to determine the fate of 1,3-diphosphoglycerate that serves as a substrate for the synthesis of 2,3-diphosphoglycerate as well as for the 3-phosphoglycerate kinase reaction in glycolysis. A withdrawal of the two-enzyme complexes from the erythrocyte lysates using Sepharose-bound anti-GAPDH antibodies prevents the pH-dependent accumulation of the metabolites. The role of GAPDH in the regulation of glycolysis and the level of 2,3-diphosphoglycerate in erythrocytes is discussed.


[Non-diethylstilbestrol-induced adenosis of the vagina].
A case of spontaneous vaginal adenosis in a 39-year old patient is reported. This entity is infrequently observed in comparison to the larger number of vaginal adenosis due to intrauterine DES exposure. The literature concerning the origin of these spontaneous proliferations is controversial: remnants of Wolffian or Müllerian ducts are thought to be the source, as well as metaplastic or prosoplastic changes. According to stage and extent of the disease, the individual case can be categorised into the following subgroups: cystic, florid, adenomatous and carcinomatous adenosis. Benign courses are far more frequent. Symptoms are observed only in advanced cases; therapy depends on histology, extent, and symptoms.


Mechanism of atopic cataract caused by eosinophil granule major basic protein.
Atopic cataracts develop under the ages of 40 years, after which visual acuity rapidly declines. However, the mechanism underlying the development of atopic cataracts is not yet clear. We focused on the eosinophil granule major basic protein (MBP), which was detected in the aqueous humor of atopic cataracts previously, and which was cytotoxic. Specifically, we investigated its origin in this fluid and its effects on lens epithelial cells (LECs). MBP immunostaining was positive in atopic cataract-derived LECs, but negative in age-related cataract-derived LECs. MBP mRNA was not detected in either type of cataract, but protein was detected in the aqueous humor. Furthermore, the flare values associated with atopic cataracts were higher than those with age-related cataracts. When MBP was purified from eosinophils or recombinant MBP was added to LEC culture medium, cell viability decreased in a concentration-dependent manner, but an MBP antibody neutralized the cytotoxic effect of this protein towards these cells. These results were consistent with the flow of MBP into the aqueous humor from the blood due to a compromised blood-aqueous barrier. Thus, MBP could further penetrate the lens capsule and adhere to LECs, resulting in decreased cell viability and the development of atopic cataracts.


Acute atraumatic compartment syndrome in an athlete: a case report.
To present the case of a college football player with acute, atraumatic, exercise-induced compartment syndrome in the leg. Acute, atraumatic, exercise-induced compartment syndrome is an infrequently reported cause of leg pain in the athlete. If left untreated, acute compartment syndrome can cause muscle necrosis. Chronic exertional compartment syndrome, medial tibial syndrome, stress fracture. Treatment consists of compartment fasciotomy. This previously healthy, but unconditioned, athlete developed severe anterolateral left leg pain after two days of fall practice in which he was unable to run a mile in 7.5 minutes. Physical examination by the team physician revealed acute compartment syndrome, and an emergency anterolateral compartment fasciotomy was performed. Second-look débridement performed 48 hours later revealed no significant change in the necrotic appearance of the anterior compartment soft tissue. Therefore, the dead muscle was completely débrided, and a free-flap latissumus dorsi graft was used for coverage of the wound. With recovery, strength returned to normal in the lateral compartment but remained 0/5 in the anterior compartment. The patient had persistent sensory loss in the distributions of the superficial and deep peroneal nerves. Although much less common than the more frequent causes of leg pain (ie, chronic exertional compartment syndrome, medial tibial syndrome, stress fracture), acute compartment syndrome is potentially more devastating. When the increased intracompartmental pressure within a closed tissue space exceeds capillary perfusion pressure, tissue perfusion is decreased, the soft tissue becomes ischemic, and cells die. The most important clinical diagnostic signs of compartment syndrome are pain with passive stretching of the compartment and pain out of proportion to the results of the physical examination.


Endoscopic decompression of the retrocalcaneal space.
Pain in the retrocalcaneal space can be incapacitating. Patients who do not respond to nonoperative treatment may seek a surgical solution. The first purpose of this paper was to describe and evaluate the efficacy of a minimally invasive procedure to address retrocalcaneal pain caused by retrocalcaneal bursitis, a Haglund spur, and impingement. The second purpose was to compare the endoscopic technique with a standard open technique. Our prospective study included thirty-three heels in thirty consecutive patients with chronic pain in the retrocalcaneal space for which nonoperative treatment had failed and endoscopic decompression was performed. The mean age was forty-nine years (range, nineteen to seventy-nine years). This group was compared with a group of seventeen heels in fourteen patients with the same diagnostic criteria who were treated with an open technique. Both groups of patients were evaluated preoperatively and postoperatively with the AOFAS (American Orthopaedic Foot and Ankle Society) Ankle-Hindfoot Scale, and the patients treated with the endoscopic procedure were also evaluated postoperatively with the University of Maryland 100-point Painful Foot Center Scoring System. In the endoscopic group, the AOFAS scores averaged 61.8 points preoperatively and 87.5 points postoperatively (p < 0.001). The endoscopic procedures yielded nineteen excellent, five good, three fair, and three poor results at an average of twenty-two months postoperatively. (Three patients were excluded from the study.) In the open-treatment group, the AOFAS scores averaged 58.1 points preoperatively and 79.3 points at an average of forty-two months postoperatively (p = 0.006). The scores after the endoscopic procedures were numerically, but not significantly (p = 0.115), better than those after the open procedures. The time to recovery was the same in the two groups. The endoscopic procedures were performed more quickly than the open procedures (forty-four compared with fifty-six minutes) and were associated with fewer complications (a 3% compared with a 12% rate of infection, a 10% compared with an 18% rate of altered sensation, and a 7% compared with an 18% rate of scar tenderness). Endoscopic decompression is a feasible and efficient procedure for the treatment of retrocalcaneal disorders. It produces final results equal to or better than those of an open technique, with a similar recovery time, fewer complications, and a better cosmetic appearance.


Aging impairs transcriptional regulation of vascular endothelial growth factor in human microvascular endothelial cells: implications for angiogenesis and cell survival.
In some tissues, aging impairs angiogenesis and reduces expression of vascular endothelial growth factor A (VEGF), a fundamental regulator of angiogenesis. We previously examined angiogenesis in aging and young gastric mucosa in vivo and in vitro and showed that an imbalance between expressions of VEGF (pro-angiogenic factor) and endostatin (anti-angiogenic protein) results in an aging-related impairment of angiogenesis in rats. However, the human relevance of these findings, and whether these mechanisms apply to endothelial cells derived from other tissues, is not clear. Since P-STAT3 and P-CREB are transcription factors that, in association with HIF-1α, can activate VEGF gene expression in some cells (e.g., liver cancer cells, vascular smooth muscle cells), we examined the expression of these two proteins in human dermal microvascular endothelial cells (HMVECs) derived from aging and neonatal individuals. We examined and quantified in vitro angiogenesis, expression of VEGF, P-STAT3, P-CREB and importin-α in HMVECs isolated from neonates (neonatal) and a 66 year old subject (aging). We also examined the effects of treatment with exogenous VEGF and endostatin on in vitro angiogenesis in these cells. Endothelial cells isolated from aging individuals had impaired angiogenesis (vs. neonatal endothelial cells) and reduced expression of VEGF mRNA and protein. Aged HMVECs also had reduced importin-α expression, and reduced expression and nuclear translocation of P-STAT3 and P-CREB. Reduced VEGF gene expression in aged HMVECs strongly correlated with the decreased levels of P-STAT3, P-CREB and importin-α in these cells. Our study clearly demonstrates that endothelial cells from aging individuals have impaired angiogenesis and reduced expression of VEGF likely due to impaired nuclear transport of P-STAT3 and P-CREB transcription factors in these cells.


Does multilingualism act as a protective factor (cognitive reserve) against cognitive impairment in multiple sclerosis?: A retrospective cohort study.
Cognitive impairment (CI) is common in multiple sclerosis (MS), affecting half of persons with MS (PwMS). Cognitive reserve has been associated with delaying the onset and slowing the progression of CI in PwMS. Multilingualism has been demonstrated to be a protective factor against CI in Alzheimer's disease (AD) but has never been studied in PwMS. To explore if multilingualism is a protective factor against CI in PwMS. This is a retrospective cohort study of PwMS aged 18-59, with a confirmed diagnosis of relapsing MS, fluent in English, who completed the Minimal Assessment of Cognitive Function in MS (MACFIMS) at the London (ON) MS Clinic. Any PwMS with a history of dementia or developmental delay, daily marijuana use, a major psychiatric disorder, or less than grade 9 education was excluded. We focused on the Brief Visuospatial Memory Test (BVMTR), immediate recall (-IR) and delayed recall (-DR) as it would be the least affected by language, as well as the Symbol Digit Modalities Test (SDMT), as information processing speed is the most commonly affected domain in PwMS. One-way ANOVA was used to compare raw scores on the BVMTR and SDMT between groups (uni- vs. multillingual), while chi-square was used to compare impairment on BVMTR and SDMT between groups. The cohort consisted of 678 subjects. The mean age was 39.7 (± 9.6) years with 501 (73.9 %) females (sex at birth), the mean duration of disease of 5.9 (± 6.9) years, and mean years of education was 13.9 (±2.2). The majority of subjects (563, 83 %) were unilingual and (115, 17 %) were multilingual; 102 subjects were bilingual and 13 subjects fluent in ≥ three languages. English was the first language was in most of subjects (614, 90.6 %). There was no significant difference on the BVMTR-IR scores (p = 0.189) or BVMTR-DR (p = 0.096) between groups. Similarly, there was no difference in the number of subjects impaired on the BVMTR-IR (X2 (1, N = 678) = 3.167, p = 0.057) or BVMT-DR between groups (X2 (1, N = 678) = 2.996, p = 0.083). Further, there was no significant difference on the SDMT (p = 0.506) between groups, or in number of subjects impaired on the SDMT between groups (X2 (1, N = 678) = 1.023, p = 0.312). This study shows that multilingualism does not have a protective effect against CI in PwMS and does not play a role in enriching the cognitive reserve, in contrast to studies in AD. This difference may be explained by a different underlying pathological mechanism in these diseases and warrants further study.


Acetaminophen interacts with human hemoglobin: optical, physical and molecular modeling studies.
Acetaminophen, a widely used analgesic and antipyretic drug has ample affinity to bind globular proteins. Here, we have illustrated a substantive study pertaining to the interaction of acetaminophen with human hemoglobin (HHb). Different spectroscopic (absorption, fluorescence, and circular dichroism (CD) spectroscopy), calorimetric, and molecular docking techniques have been employed in this study. Acetaminophen-induced graded alterations in absorbance and fluorescence of HHb confirm their interaction. Analysis of fluorescence quenching at different temperature and data obtained from isothermal titration calorimetry indicate that the interaction is static and the HHb has one binding site for the drug. The negative values of Gibbs energy change (ΔG0) and enthalpy changes (ΔH0) and positive value of entropy change (ΔS0) strongly suggest that it is entropy-driven spontaneous and exothermic reaction. The reaction involves hydrophobic pocket of the protein which is further stabilized by hydrogen bonding as evidenced from ANS and sucrose binding studies. These findings were also supported by molecular docking simulation study using AutoDock 4.2. The interaction influences structural integrity as well as functional properties of HHb as evidenced by CD spectroscopy, increased rate of co-oxidation and decreased esterase activity of HHb. So, from these findings, we may conclude that acetaminophen interacts with HHb through hydrophobic and hydrogen bonding, and the interaction perturbs the structural and functional properties of HHb.


Detection of Adverse Drug Reactions using Medical Named Entities on Twitter.
Adverse Drug Reactions (ADRs) are unintentional reactions caused by a drug or combination of drugs taken by a patient. The current ADR reporting systems inevitably have delays in reporting such events. The broad scope of social media conversations on sites such as Twitter means that inevitably health-related topics will be covered. This means that these sites could then be used to detect potentially novel ADRs with less latency for subsequent further investigation. In this work, we investigate ADR surveillance using a large corpus of Twitter data, containing around 50 billion tweets spanning 3 years (2012-2014), and evaluate against over 3000 drugs reported in the FAERS database. This is both a larger corpus and broader selection of drugs than previous work in the domain. We compare the ADRs identified using our method to the FDA Adverse Event Reporting System (FAERS) database of ADRs reported using more traditional techniques, and find that Twitter is a useful resource for ADR detection up to 72% micro-averaged precision. Micro-averaged recall of 6% is achievable using only 10% of Twitter, indicating that with a higher-volume or targeted feed it would be possible to detect a large percentage of ADRs.


Asthma in Hispanics. An 8-year update.
This review provides an update on asthma in Hispanics, a diverse group tracing their ancestry to countries previously under Spanish rule. A marked variability in the prevalence and morbidity from asthma remains among Hispanic subgroups in the United States and Hispanic America. In the United States, Puerto Ricans and Mexican Americans have high and low burdens of asthma, respectively (the "Hispanic Paradox"). This wide divergence in asthma morbidity among Hispanic subgroups is multifactorial, likely reflecting the effects of known (secondhand tobacco smoke, air pollution, psychosocial stress, obesity, inadequate treatment) and potential (genetic variants, urbanization, vitamin D insufficiency, and eradication of parasitic infections) risk factors. Barriers to adequate asthma management in Hispanics include economic and educational disadvantages, lack of health insurance, and no access to or poor adherence with controller medications such as inhaled corticosteroids. Although considerable progress has been made in our understanding of asthma in Hispanic subgroups, many questions remain. Studies of asthma in Hispanic America should focus on environmental or lifestyle factors that are more relevant to asthma in this region (e.g., urbanization, air pollution, parasitism, and stress). In the United States, research studies should focus on risk factors that are known to or may diverge among Hispanic subgroups, including but not limited to epigenetic variation, prematurity, vitamin D level, diet, and stress. Clinical trials of culturally appropriate interventions that address multiple aspects of asthma management in Hispanic subgroups should be prioritized for funding. Ensuring high-quality healthcare for all remains a pillar of eliminating asthma disparities.


Score-based resampling method for evolutionary algorithms.
In this paper, a gene-handling method for evolutionary algorithms (EAs) is proposed. Such algorithms are characterized by a nonanalytic optimization process when dealing with complex systems as multiple behavioral responses occur in the realization of intelligent tasks. In generic EAs which optimize internal parameters of a given system, evaluation and selection are performed at the chromosome level. When a survived chromosome includes noneffective genes, the solution can be trapped in a local optimum during evolution, which causes an increase in the uncertainty of the results and reduces the quality of the overall system. This phenomenon also results in an unbalanced performance of partial behaviors. To alleviate this problem, a score-based resampling method is proposed, where a score function of a gene is introduced as a criterion of handling genes in each allele. The proposed method was empirically evaluated with various test functions, and the results show its effectiveness.


Community trust of government and non-governmental organizations during the 2014-16 Ebola epidemic in Liberia.
The West African Ebola Virus Disease epidemic of 2014-16 cost more than 11,000 lives. Interventions targeting key behaviors to curb transmission, such as safe funeral practices and reporting and isolating the ill, were initially unsuccessful in a climate of fear, mistrust, and denial. Building trust was eventually recognized as essential to epidemic response and prioritized, and trust was seen to improve toward the end of the epidemic as incidence fell. However, little is understood about how and why trust changed during Ebola, what factors were most influential to community trust, and how different institutions might have been perceived under different levels of exposure to the outbreak. In this large-N household survey conducted in Liberia in 2018, we measured self-reported trust over time retrospectively in three different communities with different exposures to Ebola. We found trust was consistently higher for non-governmental organizations than for the government of Liberia across all time periods. Trust reportedly decreased significantly from the start to the peak of the epidemic in the study site of highest Ebola incidence. This finding, in combination with a negative association found between knowing someone infected and trust of both iNGOs and the government, indicates the experience of Ebola may have itself caused a decline of trust in the community. These results suggest that national governments should aim to establish trust when engaging communities to change behavior during epidemics. Further research on the relationship between trust and epidemics may serve to improve epidemic response efficacy and behavior uptake.


Statistical algorithm for nonuniformity correction in focal-plane arrays.
A statistical algorithm has been developed to compensate for the fixed-pattern noise associated with spatial nonuniformity and temporal drift in the response of focal-plane array infrared imaging systems. The algorithm uses initial scene data to generate initial estimates of the gain, the offset, and the variance of the additive electronic noise of each detector element. The algorithm then updates these parameters by use of subsequent frames and uses the updated parameters to restore the true image by use of a least-mean-square error finite-impulse-response filter. The algorithm is applied to infrared data, and the restored images compare favorably with those restored by use of a multiple-point calibration technique.


Ratiometric fluorescence immunoassay based on silver nanoclusters and calcein-Ce3+ for detecting ochratoxin A.
Ochratoxin A (OTA), a dangerous mycotoxin, is found in many crops. It is essential to create sensitive OTA detection techniques to ensure food safety. Based on the principle of p-nitrophenol (PNP) quenched the fluorescence of bovine serum albumin silver nanocluster (BSA-AgNCs) through an internal filtering effect, and phosphate activated fluorescence of calcein-Ce3+ system, a ratiometric fluorescence immunoassay for OTA detection was developed. In this strategy, the value of F518/F640 was used as a signal for response of OTA concentration. The detection range of this strategy was 0.625-25 ng/mL, the limit of detection (LOD) was 0.04 ng/mL. This new immunoassay offered a brand-new platform for detecting OTA.


Graft Subsidence and Revision Rates Following Anterior Cervical Corpectomy: A Clinical Study Comparing Different Interbody Cages.
Retrospective cohort study. To assess the subsidence and revision rates associated with different interbody cages following anterior cervical corpectomy and reconstruction. Different interbody cages are currently used for surgical reconstruction of the anterior and middle columns of the spine following anterior cervical corpectomy. However, subsidence and delayed union/nonunion associated with allograft and cage reconstruction are common complications, which may require revision with instrumentation. We reviewed the cases of 75 patients who underwent cervical corpectomy and compared the radiographic graft subsidence and revision rates for fibula allograft, titanium mesh cage, titanium expandable cage, and carbon fiber cages. Subsidence was calculated by comparing the immediate postoperative lateral x-ray films to those obtained during follow-up visits. The average graft subsidence was 3 mm and revision rate was 25% for fibula allograft versus 2.9 mm and 11.1%, 2.9 mm and 18.8% for titanium mesh cages and titanium expandable cages, respectively. The average graft subsidence for carbon fiber cages was 0.7 mm with no revision surgery in this subset. Our findings suggest that subsidence and revision rates following anterior corpectomy and interbody fusion could be minimized with the use of a carbon fiber cage.


Achieving the millennium development goal for under-five mortality in Bangladesh: current status and lessons for issues and challenges for further improvements.
The study assessed the achievements in, critically reviewed the relevant issues of, and put forward recommendations for achieving the target of the Millennium Development Goal relating to mortality of children aged less than five years (under-five mortality) in Bangladesh within 2015. To materialize the study objectives, a thorough literature review was done. Mortality of under-five children and infants decreased respectively to 65 from 151 and to 52 from 94 per 1,000 livebirths during 1990-2006. The immunization coverage increased from 54% to 81.9% during the same period. The projection shows that Bangladesh will achieve targeted reduction in under-five mortality and infant mortality within the time limit, except immunization coverage. Neonatal mortality contributed to the majority of childhood deaths. Contribution of neonatal mortality to child mortality was the highest. There were remarkable differences in child mortality by sex, division, and residence. To progress further for achieving the target of MDG relating to child mortality, some issues, such as lower use of maternal healthcare services, hazardous environmental effects on childhood illness, high malnutrition among children, shorter duration of exclusive breastfeeding practices, various child injuries leading to death, low healthcare-use of children, probable future threat of financial shortage, and strategies lacking area-wise focus on child mortality, need to be considered. Without these, the achievement of MDG relating to child mortality may not be possible within 2015.


Immunological alterations associated with Plasmodium vivax malaria in South Korea.
Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemto-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3-/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.


Nicotinamide Increases Intracellular NAD+ Content to Enhance Autophagy-Mediated Group A Streptococcal Clearance in Endothelial Cells.
Group A streptococcus (GAS) is a versatile pathogen that causes a wide spectrum of diseases in humans. Invading host cells is a known strategy for GAS to avoid antibiotic killing and immune recognition. However, the underlying mechanisms of GAS resistance to intracellular killing need to be explored. Endothelial HMEC-1 cells were infected with GAS, methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella Typhimurium under nicotinamide (NAM)-supplemented conditions. The intracellular NAD+ level and cell viability were respectively measured by NAD+ quantification kit and protease-based cytotoxicity assay. Moreover, the intracellular bacteria were analyzed by colony-forming assay, transmission electron microscopy, and confocal microscopy. We found that supplementation with exogenous nicotinamide during infection significantly inhibited the growth of intracellular GAS in endothelial cells. Moreover, the NAD+ content and NAD+/NADH ratio of GAS-infected endothelial cells were dramatically increased, whereas the cell cytotoxicity was decreased by exogenous nicotinamide treatment. After knockdown of the autophagy-related ATG9A, the intracellular bacterial load was increased in nicotinamide-treated endothelial cells. The results of Western blot and transmission electron microscopy also revealed that cells treated with nicotinamide can increase autophagy-associated LC3 conversion and double-membrane formation during GAS infection. Confocal microscopy images further showed that more GAS-containing vacuoles were colocalized with lysosome under nicotinamide-supplemented conditions than without nicotinamide treatment. In contrast to GAS, supplementation with exogenous nicotinamide did not effectively inhibit the growth of MRSA or S. Typhimurium in endothelial cells. These results indicate that intracellular NAD+ homeostasis is crucial for controlling intracellular GAS infection in endothelial cells. In addition, nicotinamide may be a potential new therapeutic agent to overcome persistent infections of GAS.


GP120: target for neutralizing HIV-1 antibodies.
The glycoprotein (gp) 120 subunit is an important part of the envelope spikes that decorate the surface of HIV-1 and a major target for neutralizing antibodies. However, immunization with recombinant gp120 does not elicit neutralizing antibodies against multiple HIV-1 isolates (broadly neutralizing antibodies), and gp120 failed to demonstrate vaccine efficacy in recent clinical trials. Ongoing crystallographic studies of gp120 molecules from HIV-1 and SIV increasingly reveal how conserved regions, which are the targets of broadly neutralizing antibodies, are concealed from immune recognition. Based on this structural insight and that from studies of antibody structures, a number of strategies are being pursued to design immunogens that can elicit broadly neutralizing antibodies to gp120. These include (a) the construction of mimics of the viral envelope spike and (b) the design of antigens specifically tailored to induce broadly neutralizing antibodies.


Immune responses of eastern fence lizards (Sceloporus undulatus) to repeated acute elevation of corticosterone.
Prolonged elevations of glucocorticoids due to long-duration (chronic) stress can suppress immune function. It is unclear, however, how natural stressors that result in repeated short-duration (acute) stress, such as frequent agonistic social encounters or predator attacks, fit into our current understanding of the immune consequences of stress. Since these types of stressors may activate the immune system due to increased risk of injury, immune suppression may be reduced at sites where individuals are repeatedly exposed to potentially damaging stressors. We tested whether repeated acute elevation of corticosterone (CORT, a glucocorticoid) suppresses immune function in eastern fence lizards (Sceloporus undulatus), and whether this effect varies between lizards from high-stress (high baseline CORT, invaded by predatory fire ants) and low-stress (low baseline CORT, uninvaded) sites. Lizards treated daily with exogenous CORT showed higher hemagglutination of novel proteins by their plasma (a test of constitutive humoral immunity) than control lizards, a pattern that was consistent across sites. There was no significant effect of CORT treatment on bacterial killing ability of plasma. These results suggest that repeated elevations of CORT, which are common in nature, produce immune effects more typical of those expected at the acute end of the acute-chronic spectrum and provide no evidence of modulated consequences of elevated CORT in animals from high-stress sites.


Validity of self-reported height and weight for measuring prevalence of obesity.
To examine the validity of self-reported body mass index (BMI) in estimating the prevalence of obesity in the Canadian population, and to suggest a model for predicting actual BMI from self-reported data. This analysis is based on 1131 participants with both self-reported and measured height and weight from the Canadian Community Health Survey, Cycle 2.2 dataset. We estimated the prevalence of obesity as well as the mean and standard deviation (SD) of BMI according to sex, age group, and measured weight classification. Multiple regression analysis was used to build a model to assess the relation between actual BMI and variables of age, sex, and self-reported BMI. The overall prevalence of obesity was 23.0% based on measured BMI, and 15.6% based on self-reported BMI. Estimated mean (SD) for self-reported and measured BMI were 25.8 (4.8) and 26.9 (5.0) kg/m(2), respectively. Only 74.3% of obese men and 56.2% of obese women were correctly classified as obese on the basis of self-reported measures. Females and heavier respondents showed more BMI under-reporting than others. To estimate overweight and obesity in etiological and disease relationship studies, the use of measured height and weight in BMI estimation is preferable to the use of self-reported values. However, if self-reported height and weight are used in population studies, our proposed model can be used to reliably predict the actual BMI with a narrow 95% confidence interval.


Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?
The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype.


Organization of translocon complexes in ER membranes.
Protein translocation in the ER (endoplasmic reticulum) and N-glycosylation are fundamental processes essential for the normal functioning of eukaryotic cells. They are the initial steps in the intracellular pathway that are followed by secretory proteins and membrane proteins of the endomembrane system and the plasma membrane. The translocation and concurrent N-glycosylation of these proteins take place on a large molecular machine, the TC (translocon complex), which is associated with membrane-bound polysomes. Segregation of TCs into a differentiated domain of the ER, the rough ER, may increase the efficiency of protein synthesis on membrane-bound polysomes. Our research is concerned with the assembly, functional organization and dynamics of the TCs in the ER, and their contribution to the functioning and the morphological appearance of this organelle. We hypothesize that the TCs form higher-order structures defining the rough domain of the ER. These structures, which are immobilized or diffuse slowly in the plain of the ER membrane, may be formed and stabilized by mRNAs interconnecting the TCs, by cytoskeletal elements and/or by hypothetical proteins that form links between the TCs. We have established the M3/18 cell line, which expresses the GFP (green fluorescent protein)-Dad1 fusion protein quantitatively and functionally incorporated into the OST (oligosaccharyltransferase). GFP-Dad1 can be used as a reporter molecule for the lateral mobility of the TCs since the OST is tightly associated with the complex. As determined by FRAP (fluorescence recovery after photobleaching), the lateral mobility of GFP-Dad1-tagged TCs was much more restricted than expected from the estimated size of the TC and can be affected by the functional state of the TCs. Currently, we are studying the possible involvement of cytoskeletal elements in the organization of the TCs. Our data suggest that microtubules also play a role in the immobilization of the TCs.


Mental health among men who have sex with men in Cambodia: Implications for integration of mental health services within HIV programmes.
Poor mental health contributes to poor HIV prevention, treatment and care outcomes. This paper documents factors associated with psychological distress among men who have sex with men (MSM) in Cambodia and discusses potential ways in which routine mental health management could be integrated into HIV services. A cross-sectional study was conducted in 2014 among 394 MSM randomly selected from two provinces using a two-stage cluster sampling method. A structured questionnaire was used to assess psychological distress, sexual behaviors, substance use, adverse childhood experiences and family dysfunction. Multivariate logistic regression analysis was performed to explore factors associated with levels of psychological distress. In total, 10.7 % of the respondents reported having suicidal thoughts and 6.6 % reported having attempted to commit suicide in the past three months, while 38.8 % had a higher level of psychological distress (GHQ-12 > 3), which indicates poor mental health. Higher levels of psychological distress were independently associated with older age (AOR = 1.09, 95 % CI 1.03-1.14), alcohol use (AOR = 3.3, 95 % CI 1.36-7.83), illicit drug use (AOR = 3.53, 95 % CI 1.12-11.18), poor self-reported quality of life (AOR = 7.45, 95 % CI 1.79-3.04), and reduced condom use at last sex (AOR = 0.40, 95 % CI 0.21-0.73). MSM with higher levels of psychological distress were significantly more likely to report that a family member said hurtful things to them (AOR = 1.80, 95 % CI 1.10-2.97), a parent or guardian had been physically abused (AOR = 3.51, 95 % CI 1.86-6.62), and a family member had been mentally ill (AOR = 4.01, 95 % CI 2.06-7.81) when they were growing up. In order to mitigate psychological distress among MSM in Cambodia, integration of mental health interventions within HIV programmes should be strengthened. To achieve optimal impact, these interventions should also address alcohol and other substance use, and low condom use among distressed MSM. In addition, training of clinical and non-clinical HIV service providers to screen for mental health symptoms, and subsequent provision of peer-based outreach and social support for MSM identified with psychological distress is required.


Orthopaedic literature and MeSH.
Since 1916 there has been a recognized demand for a method of classification of orthopaedic literature inclusive enough to permit the proper collection and retrieval of all literature on the subject. Today, MEDLINE, available through the PubMed interface, has become the de facto standard for organization and retrieval of medical literature. The Medical Subject Headings (MeSH), used to provide indexing and assist in searching, are partly responsible for this standard. Understanding how MeSH is built and maintained may lead the user to a better understanding of how to use MEDLINE, and what to expect from the indexing of an article. The purpose of this review is to provide an understanding of the organization of large quantities of indexed material, the indexing process and the considerations involved in developing an indexing vocabulary. WHERE ARE WE NOW?: Successful terminology development and use, a prerequisite for any sharing of information by electronic means, depends on both user (how the user is expected to use the system) and information (how the information is organized) models. MEDLINE has a simple user model and a simpler information model. The user is expected to determine what is relevant and which MeSH descriptors are appropriate. WHERE DO WE NEED TO GO?: While MEDLINE through PubMed is a success as viewed by the number of hits, further improvements will depend on better, faster indexing with a controlled terminology. Terminology development requires careful consideration of the nature of the subject, how users employ the terminology, the overall purpose of the terminology, and the framework of the systems in which it is used. HOW DO WE GET THERE?: For the future, understanding terminology development might enable the user to comprehend some of the issues involved in sharing of other information by electronic means. Further improvements in the availability and accessibility of medical literature will depend on continued maintenance and development of MeSH, as well as on refinement of the indexing process.


Risk-cost-benefit analysis for transportation corridors with interval uncertainties of heterogeneous data.
Access management, which systematically limits opportunities for egress and ingress of vehicles to highway lanes, is critical to protect trillions of dollars of current investment in transportation. This article addresses allocating resources for access management with incomplete and partially relevant data on crash rates, travel speeds, and other factors. While access management can be effective to avoid crashes, reduce travel times, and increase route capacities, the literature suggests a need for performance metrics to guide investments in resource allocation across large corridor networks and several time horizons. In this article, we describe a quantitative decision model to support an access management program via risk-cost-benefit analysis under data uncertainties from diverse sources of data and expertise. The approach quantifies potential benefits, including safety improvement and travel time savings, and costs of access management through functional relationships of input parameters including crash rates, corridor access point densities, and traffic volumes. Parameter uncertainties, which vary across locales and experts, are addressed via numerical interval analyses. This approach is demonstrated at several geographic scales across 7,000 kilometers of highways in a geographic region and several subregions. The demonstration prioritizes route segments that would benefit from risk management, including (i) additional data or elicitation, (ii) right-of-way purchases, (iii) restriction or closing of access points, (iv) new alignments, (v) developer proffers, and (vi) etc. The approach ought to be of wide interest to analysts, planners, policymakers, and stakeholders who rely on heterogeneous data and expertise for risk management.


Analysing heart rate variability in preterm infants: the effect of temporal adjustment of NN peaks and missing data.
The measurement of heart rate variability (HRV) in preterm infants provides important information on function to clinicians. Measuring the underlying electrocardiogram (ECG) in the neonatal intensive care unit is a challenge and there is a trade off between extracting accurate measurements of the HRV and the amount of ECG processed due to contamination. Knowledge on the effects of 1) quantization in the time domain and 2) missing data on the calculation of HRV features will inform clinical implementation. In this paper, we studied multiple 5 minute epochs from 148 ECG recordings on 56 extremely preterm infants. We found that temporal adjustment of NN peaks improves the estimate of the NN interval resulting in HRV features (m = 9) that are better correlated with age (median percentage increase in correlation of individual features: 0.2%, IQR: 0.0 to 5.6%; correlation with age predictor and age from 0.721 to 0.787). Improved (sub-sample) quantization of the NN intervals (via interpolation) reduced the overall value of HRV features (median percentage reduction in feature value: -1.3%, IQR: -18.8 to 0.0; m = 9), primarily through a reduction in the energy of high-frequency oscillations. HRV features were also robust to missing data, with measures such as mean NN, fractal dimension and the smoothed nonlinear energy operator (SNEO) less susceptible to missing data than features such as VLF, LF, and HF. Furthermore, age predictions derived from a combination of HRV measures were more robust to missing data than individual HRV measures.Clinical Relevance-Poor quantization in time when estimating the NN peak and the presence of missing data confound HRV measures, particularly spectral measures.


The Role of Physical Cues in Co-located and Remote Casework.
Across the world, large swaths of society closed in response to the COVID-19 (C-19) pandemic, transforming the provision of government services, including welfare. The shift to remote work afforded a glimpse of what a future digitized public sector might look like. In Denmark, employment assistance went fully remote in spring 2020 to prevent the spread of C-19. Caseworkers assessed unemployed individuals' needs for welfare benefits over the phone instead of at the physical job center. With this change, caseworkers could no longer rely on nonverbal communication, such as physical cues (e.g., the appearance of an unemployed individual), in their assessment practice. Although they are not explicitly described in the formal work process, caseworkers report that such cues influence their assessment of an individual's challenges related to their unemployment. Taking a qualitative approach, we conducted 60 telephone interviews with 6 caseworkers across 3 Danish job centers during the first wave of the pandemic. Later, during the second wave of the pandemic (August 2020-June 2021), we conducted observational studies (22.5 h) including on-site interviews in two job centers where caseworkers had returned to work having consultations with unemployed individuals both remotely and co-located. During this second-wave period we also conducted new interviews (n = 18) with the caseworkers from the first part of the study. The contribution of this paper is an empirical description of how casework changes when it shifts from co-located to remote consultations, focused on two factors: (1) the role of physical cues and how caseworkers rely on these cues to communicate with and assess the individual, and (2) documentation practices, and how earlier documentation became more important when caseworkers lacked access to physical cues. We contribute to CSCW research by showing that although implicit information about the individual is valuable for caseworkers, it is not problem-free, and therefore we argue that there is a need to find new ways to assess individuals, in particular interpreting implicit or un-spoken information, as the complicated use of physical cues can tip over to become a matter of bias.


Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine.
Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[22.214.171.124(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[126.96.36.199(2,7)]tridecane] (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[188.8.131.52(2,7)]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[126.96.36.199(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[184.108.40.206(2,7)]tridecane is the first successful (+)-sparteine surrogate.


Drawing the battle lines: tracing the "Science War" in the construction of the chloroform and human health risks debate.
The United States Environmental Protection Agency (US EPA) and the Chlorine Chemistry Council, the Chemical Manufacturers Association, and others have been embroiled in a legal challenge concerning the US EPA's "reversal" regarding the scientific assessment of chloroform's carcinogenicity. This issue arose during the US EPA's November 1998 promulgation of a Maximum Contaminant Level Goal for chloroform in the Stage 1 Final Rules for Disinfectants and Disinfection Byproducts in drinking water. In this paper we adopt a claimsmaking approach: to trace the development and outcome of the chloroform court challenge in the USA, to examine the construction of scientific knowledge claims concerning chloroform risk assessments, and to investigate how different interpretations of scientific uncertainties regarding the evidence are contested when such uncertainties are brought into a regulatory and judicial arena. This "science war" (Chlorine Chemistry Council and others v. US EPA and others) took place in the US Court of Appeals for the District of Columbia Circuit. The scientific "authority" in the construction of scientific claims in this dispute is based on the International Life Sciences Institute expert panel report on chloroform. Examining these science wars is important because they signal critical shifts in science policy agendas. The regulatory outcome of the chloroform science war in the United States can have profound implications for the construction and acceptance of scientific claims regarding drinking water in other jurisdictions (e.g., Canada). In this challenge, we argue that the actors involved in the dispute constructed "boundaries" around accepted and credible scientific claims.


Effect of topical administration of 1% morphine sulfate solution on signs of pain and corneal wound healing in dogs.
To evaluate the effect of topical application of a 1% morphine sulfate solution (MSS) on signs of pain and wound healing in dogs with corneal ulcers and examine normal corneas immunohistochemically for the presence of mu and delta opioid receptors. 12 dogs. A 7-mm superficial corneal ulcer was surgically created in the right eye (OD) of 10 dogs, after which gentamicin solution and 1% MSS (n = 6) or saline solution (4) was administered topically OD 3 times daily. Blepharospasm, tearing, conjunctival hyperemia, aqueous flare, esthesiometer readings, and pupil size were recorded before and 30 minutes after treatment in all dogs. Ulcer size and days to completion of healing were recorded. Corneas from 4 treated and 3 control dogs were evaluated histologically. Normal canine corneas from 2 dogs not used in the study were evaluated immunohistochemically for the presence of mu and delta opioid receptors. Dogs treated with MSS had significantly less blepharospasm and lower esthesiometer readings than did control dogs. Duration of ulcer healing and findings of histologic evaluation of corneas did not differ between groups. Numerous delta and infrequent mu opioid receptors were identified in the corneal epithelium and anterior stroma of normal corneas. Topical use of 1% MSS in dogs with corneal ulcers provided analgesia and did not interfere with normal wound healing. Both mu and delta opioid receptors were identified in normal corneas of dogs, although the mu receptors were present only in small numbers.


Evaluating a Web-Based Health-Promoting Dialogue Tool in School Health Services: Feasibility and User Experiences.
Adolescence is a sensitive period in life and a time to redefine and learn new skills. In Norway, school health services provide individual health-promoting consultations with all eighth-grade students. As an aid to support these consultations, a dialogue tool called SchoolHealth was developed using a co-creation approach. SchoolHealth consists of a web-based health information form designed to be completed by the students and generates individual feedback reports to help the school nurses to prepare for the consultation and tailor it to the individual student's need. Our aims were to evaluate the feasibility and user experiences of SchoolHealth among students and school nurses using a mixed methods approach. A total of 79 eighth-grade students (69% of those invited) and four school nurses from three schools participated. Analyses indicated that SchoolHealth was feasible, promoted reflection among students, and helped prepare students and school nurses for the consultation.


Dysphagia in Huntington's Disease: Correlation with Clinical Features.
Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by motor impairment, cognitive decline and psychiatric disorders. Dysphagia is a pathologic condition that increases morbidity and mortality of the affected people. Our aim was to evaluate dysphagia in a group of HD patients in view of motor, cognitive and functional decline. Thirty-seven genetically confirmed HD patients were submitted to clinical evaluations of swallowing. Bedside Swallowing Assessment Scale (BSAS) was used. Dysphagia Outcome and Severity Scale (DOSS) was applied for a preliminary classification of swallowing difficulties. All patients were also evaluated by the Unified Huntington's Disease Rating Scale (UHDRS). A group of 39 controls comparable for sex and age were recruited for BSAS scores normalisation. The BSAS scores indicated that in our HD cohort, 32.4% presented relevant or severe dysphagia. The DOSS levels were significantly correlated with main clinical features, such as age, disease duration and motor impairment, with special regard to lingual protrusion ability, dysarthria and bradykinesia. The total functional capacity (TFC) and cognitive scales did not show significant correlation with DOSS levels. The results of clinical examination of swallowing indicated that dysphagia is a prevalent motor symptom of HD.


[Why and how to correct hypermetropia?].
How and why to prescribe an optical correction in hyperopia is described. The reasons for prescribing are closely related to the visual risk of not doing so (amblyopia, lack of stereopsy, strabismus), to the patient's complains and history as well as to his ophthalmological examination. How to correct hyperopia depends on the presence or absence of squint and on the amount of ametropia.


Pedicled arterial grafts in coronary surgery: postoperative echo color-Doppler study.
In 1994 a mid-term postoperative echo color-Doppler ultrasound was performed to check the pedicled arterial conduits used in coronary surgery, such as the left and right internal mammary arteries (LIMA, RIMA) and the right gastroepiploic artery (RGEA). This evaluation was made in 31 patients with a previous nonemergent complete arterial myocardial revascularization. The pedicled arterial grafts studied were 71 (31 LIMA, 15 RIMA and 25 RGEA). The Doppler spectrum (combined systolic/diastolic waveform), the diameter and the flow of every arterial graft was always identified (100% of detection) and there was a statistical significative difference between mean RGEA flow versus mean LIMA and RIMA flow (p<0.05). All the conduits studied were characterized by a good diastolic and end-diastolic velocity, evidence of normal graft patency. The postoperative angiogram of the LIMA, RIMA and RGEA conduits was performed in 27/31 (87.1%) patients and it showed 100% patency of arterial grafts used and of anastomoses. The echo color-Doppler data were compared to postoperative angiographic results. The echo color-Doppler imaging of the pedicled arterial grafts used in coronary surgery seems to be a promising technique for the postoperative serial assessment of the LIMA, RIMA and RGEA conduit function, because it is noninvasive, safe, easy, quick to perform and the preliminary results of echo color-Doppler ultrasound versus angiography are satisfactory.


Association of cardiac and non-cardiac chronic disease comorbidity on glycaemic control in a multi-ethnic population with type 1 and type 2 diabetes.
To determine the prevalence of chronic disease comorbidity in south Asians (SAs) and white Europeans (WEs) with diabetes and to quantify the relationship of cardiac disease comorbidity (CDCM) and non-cardiac disease comorbidity (NCCM) to glycaemic control in SAs and WEs with type 1 and type 2 diabetes mellitus. A cross-sectional study using a database of patients of SA (25.5%) and WE (74.5%) origin attending a specialist diabetes clinic in the UK between 2003 and 2005 (n=5664). The prevalence of SAs and WEs with type 1 diabetes was 12% and 88%, respectively; for those with type 2 diabetes the prevalence was 30% and 70%, respectively. Overall, the prevalence of comorbidity in people with type 1 diabetes was 25.5% and with type 2 diabetes was 47%. NCCM was more prevalent in WEs than SAs (17.6% vs 12.8%, p<0.001). In type 2 diabetes, the prevalence of suboptimal glycaemic control was significantly greater in SAs compared to WEs with NCCM and CDCM (79% vs 62%, p<0.001; 78% vs 65%, p<0.001, respectively). SAs with type 2 diabetes and comorbidity had excess odds of suboptimal glycaemic control compared to WEs: OR 2.27 (95% CI 1.50 to 3.43) for those with NCCM and OR 1.91 (95% CI 1.49 to 2.44) for those with CDCM. The prevalence of CDCM is higher in SAs compared to WEs with type 2 diabetes, whereas the prevalence of NCCM is higher in WEs compared to SAs. Taking into account comorbidities, SAs (compared to WEs) with type 2 diabetes had an excess risk of having HbA1c ≥7% ranging from 1.86- to 2.27-fold. Further research is needed to identify the reasons for unfavourable metabolic conditions in SAs and also develop and evaluate interventions.


The Metro-Manila Developmental Screening Test: a normative study.
This study aimed to establish Metro-Manila (Philippines) norms for the Denver Developmental Screening Test and to determine the characteristics of children whose scores are normal and those whose scores are abnormal or questionable on the test. The subjects were 6,006 children from 4,846 households of Metro-Manila. Probit analysis established the ages at which 25%, 50%, 75%, and 90% of the sample passed each of the 105 test items. Discriminant analysis showed four clusters of factors that were significantly associated with children's performance. These were a substitute-care-giver variable cluster, a mother variable cluster, a child-situational variable cluster, and an age variable cluster.


Kalpha yields from Ti foils irradiated with ultrashort laser pulses.
We have studied the emission of Kalpha radiation from Ti foils irradiated with ultrashort (45 fs) laser pulses. We utilized the fundamental (800 nm) light from a Ti:sapphire laser on bare foils and foils coated with a thin layer of parylene E (CH). The focusing was varied widely to give a range of intensities from approximately 10(15) - 10(19) W cm(-2). Our results show a conversion efficiency of laser to Kalpha energy of approximately 10(-4) at tight focus for both types of targets. In addition, the coated targets exhibited strong secondary peaks of conversion at large defocus, which we believe are due to modification of the extent of preformed plasma due to the dielectric nature of the plastic layer. This in turn affects the level of resonance absorption. A simple model of Kalpha production predicts a much higher conversion than seen experimentally and possible reasons for this are discussed.


Modulation of DNA damage by pentoxifylline and alpha-tocopherol in skin fibroblasts exposed to Gamma rays.
Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha-tocopherol was highly efficient in reducing late radiation-induced skin damage. The present work aimed at investigating the molecular and cellular mechanisms involved in the effects of this combination. Primary cultures of confluent dermal fibroblasts were gamma-irradiated in the presence of PTX and trolox (Tx), the water-soluble analogue of alpha-tocopherol. Drugs were added either before or after radiation exposure and were maintained over time. Their antioxidant capacity and their effect on radiation-induced ROS production was assessed together with cell viability and clonogenicity. DNA damage formation was assessed by the alkaline comet assay and by the micronucleus (MN) test. Cell cycle distribution was also determined. The combination of PTX/ Tx was shown to reduce both immediate and late ROS formation observed in cells after irradiation. Surprisingly, decrease in DNA strand breaks measured by the comet assay was observed any time drugs were added. In addition, the micronucleus test revealed that for cells irradiated with 10 Gy, a late significant increase in MN formation occurred. The combination of PTX/Tx was shown to be antioxidant and to decrease radiation-induced ROS production. The observed effects on DNA damage at any time the drugs were added suggest that PTX/Tx could interfere with the DNA repair process.


Differntiation of primary from secondary varicose veins by Doppler ultrasound and strain gauge plethysmography.
The Doppler ultrasonic velocity detector and the strain gauge plethysmograph were used to differentiate qualitatively and quantitatively primary from secondary varicose veins. Studies were performed in 21 limbs of 14 normal persons, nine limbs of eight patients with varices secondary to deep venous disease. The latter group of patients was identified by ultrasonic evidence of venous reflux through imcompetent deep venous valves. There was no significant difference in the maximum venous outflow of the limbs of the three groups of persons as determined by plethysmography. The primary hemodynamic abnormality in patients with varicose veins was significant venous reflux through imcompetent venous valves. This reflux was obliterated by tourniquet compression of the varices in patients with primary varicose veins. However, secondary varicose veins are distinguished by persistent abnormal deep venous reflux after compression of the varices. These diagnostic techniques not only provide accurate noninvasive diagnostic information but also may facilitate determination of prognosis and therapy of patients with varicose veins.


Dynamic Monitoring of Probiotics Effect in Parkinson's Disease Patients via Swarm Decomposition and Bispectral Analysis of Electrogastrograms.
People with Parkinson's Disease (PwP) experience a significant deterioration of their daily life quality due to non-motor symptoms, with gastrointestinal dysfunctions manifesting as a vanguard of the latter. Electrogastrography (EGG) is a noninvasive diagnostic tool that can potentially provide biomarkers for the monitoring of dynamic gastric alterations that are related to daily lifestyle and treatment regimens. In this work, a robust analysis of EGG dynamics is introduced to evaluate the effect of probiotic treatment on PwP. The proposed framework, namely biSEGG, introduces a Swarm Decomposition-based enhancement of the EGG, combined with Bispectral feature engineering to model the underlying Quadratic Phase Coupling interactions between the gastric activity oscillatory components of EGG. The biSEGG features are benchmarked against the conventional Power Spectrum-based ones and evaluated through machine learning classifiers. The experimental results, when biSEGG was applied on data epochs from 11 PwP (probiotic vs placebo, AUROC: 0.67, Sensitivity/Specificity: 75/58%), indicate the superiority of biSEGG over Power Spectrum-based approaches and justify the efficiency of biSEGG in capturing and explaining intervention- and meal consumption-related alterations of the gastric activity in PwP.Clinical relevance- biSEGG holds potential for dynamic monitoring of gastrointestinal dysfunction and health status of PwP across diverse daily life scenarios.


Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update.
To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; alpha-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include approximately 82% simple mutations and approximately 18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson-plus syndromes, indicating that mutation screening is recommendable in these patient groups.


Multiple bowel stenosis and perforation as long-term complications of chemoradiotherapy for advanced cervical cancer in a young woman: case report.
Although combined treatment (chemoradiotherapy) appears to improve the overall and progression-free survival of patients wih locally advanced cervical cancer, some acute toxicity is increased (hematological toxicity, nausea, vomiting) while the long-term side effects are unclear. A 35-year-old Caucasian woman with a diagnosis of advanced cervical cancer (FIGO stage IIIB) was treated with neoadjuvant chemoradiotherapy not followed by radical surgery. She underwent whole pelvic radiation therapy for a total of 40 Gy in fractions of 2.5 Gy given 4 times per week for 4 consecutive weeks followed by 2 sessions of intracavitary brachytherapy starting within 7 days of completion of external beam radiotherapy (3500 mg/h and 2500-3000 mg/h). Cis-DDP IV was administered at a dose of 25 mg/m2 on day 1 and then weekly until completion of the radiotherapeutic protocol. After several months the patient presented persistent gastrointestinal symptoms and an X-ray showed findings consistent with bowel occlusion. The patient underwent emergency surgery and multiple bowel stenosis with perforation was diagnosed. This is the first report in which neoadjuvant chemoradiotherapy is associated with the late complication of multiple stenosis and bowel perforation in a young woman with advanced cervical cancer. Considering that despite the large number of studies about non-cisplatin agents there is not enough evidence to justify treatment with alternative agents, this case report might provide new important data regarding the late morbidity of cisplatin-based concurrent chemoradiation.


Impact of a short, culturally relevant training course on cancer knowledge and confidence in Western Australia's Aboriginal Health Professionals.
To develop, deliver and evaluate a cancer education course for Indigenous Health Professionals. The cancer education course combines expert presentations, interactive sessions and visits to local cancer treatment centres. Three four-day courses have been run, in both metropolitan and regional Western Australia (WA). Cancer knowledge and confidence were measured at baseline, course completion and at follow-up (six to eight months). Data were analysed within subject. Thirty-five Aboriginal Health Professionals have completed the program, most from rural or remote WA. All confidence items significantly improved at course completion (p<0.005), but improvements for only two items, 'I know what cancer is' and 'I can describe the different common cancers', were sustained at follow-up (p<0.05). Knowledge of treatment (p<0.05), screening (p<0.05) and the most common cancers in women (p<0.005) were significantly greater after course completion, but increased knowledge was not sustained at follow-up. Demand for places suggests that Aboriginal Health Professionals are interested in developing knowledge, skills and confidence in cancer control. Attendance increased understanding of cancer and improved cancer knowledge however this was not maintained. A short, culturally relevant training course increases cancer knowledge and confidence, however, ongoing education is needed to maintain this.


Evaluation of a stepwise surgical approach to camptodactyly.
Camptodactyly is common, but its treatment remains controversial. Multiple deforming forces have been implicated in its pathogenesis. This study evaluates a logical clinical assessment and corresponding stepwise surgical plan. Eighteen consecutive fingers (12 children) had surgery to treat camptodactyly of the proximal interphalangeal joint at a mean age of 8 years (range, 9 months to 15 years). The little (n = 13), ring (n = 2), and middle fingers (n = 3) were involved. Mean preoperative flexion contracture was 57 degrees (range, 35 to 75 degrees). All digits had moderate to severe contracture with functional impairment and were offered surgery. Preoperative and postoperative active range of motion was recorded. The sequential treatment steps correspond to the clinical examination and potentially involve volar skin release with flap, fascial release, flexor digitorum superficialis tenotomy, sliding volar plate release, extension lag correction, and Fowler extensor tenotomy. Mean postoperative flexion contracture resolved to 3 degrees (range, 0 to 25 degrees) at a mean follow-up of 11 months (range, 3 to 32 months). Mean proximal interphalangeal joint flexion was 88 degrees (range, 50 to 100 degrees). Fifteen of 18 fingers achieved full active proximal interphalangeal joint extension. The remaining digits had residual contractures of 5, 20, and 25 degrees. All digits had soft-tissue release with flap and flexor digitorum superficialis tenotomy, 16 had volar plate release, two had intrinsic transfers, and three had Fowler tenotomy release performed. This stepwise surgical approach effectively treats severe camptodactyly and appears to confirm the authors' suspected pathogenesis of the disorder. Lumbricals and interossei were not involved. Therapeutic, IV.


A significant pool of amino acids is adsorbed on blood cell membranes.
It is well known that the amino acids in the blood are distributed between the plasma and inside the cells. This study was conducted to determine whether amino acids can be located adsorbed on blood cell membranes. The amino acid concentration in the deproteinized haemolysed blood was higher than that in the fraction of blood after removal of the blood cell membranes by centrifugation. These results showed that a pool of amino acids representing 21.1% of the whole blood cell amino acids was adsorbed on the blood cell membranes of adult Wistar rats. The non-polar amino acids showed high adsorption on the membrane, whereas out of the polar amino acid group, only the non-ionic amino acids did adsorb.


Diabetes management in the primary care setting: a comparison of physicians' performance by gender.
A major shift in the gender of the medical-doctor workforce is now underway, and all over the world it is expected that an average 65% of the medical workforce will be women by 2030. In addition, an aging population means that chronic diseases, such as diabetes, are becoming more prevalent and the demand for care is rising. There is growing evidence of female physicians performing better than male physicians.AimOur study aimed to investigate whether any differences in diabetes process indicators are associated with gender, and/or the interaction between gender and different organizational models.Design and settingA population-based cross-sectional analysis was conducted on a large data set obtained by processing the public health administration databases of seven Italian local health units (LHUs). The seven LHUs, distributed all over the Italian peninsula in seven different regions, took part in a national project called MEDINA, with the focus on chronic disease management in primary care (PC). A total score was calculated for the average performance in the previously listed five indicators, representing global adherence to a quality management of patients with diabetes. A multilevel analysis was applied to see how LHUs affected the outcome. A quantile regression model was also fitted. Our study included 2287 Italian general practitioners (586 of them female) caring for a total of 2 646 059 patients. Analyzing the performance scores confirmed that female general practitioners obtained better results than males. The differences between males and females were stronger on the 25th and 75th percentiles of the score than on the median values. The interaction between gender and LHU was not significant. Our study evidenced that female physicians perform better than males in providing PC for diabetes independently by the different organizational models. Further research to understand the reasons for these gender differences is needed.


Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia.
Remarkable progress has occurred in understanding the pathophysiology and in developing improved personalized therapies in adult acute lymphoblastic leukemia (ALL). We searched MEDLINE (1990-2018), the American Society of Clinical Oncology, and American Society of Hematology websites (2010-2018). We used the search terms "acute lymphoblastic or lymphocytic leukemia" or "ALL." We largely selected publications in the past 5 years but did not exclude commonly referenced and highly regarded older publications. Target therapies toward specific transcripts (eg, BCR-ABL1 tyrosine kinase oncoprotein by tyrosine kinase inhibitors) and specific leukemic cell surface antigens (eg, CD20, CD22, and CD19 monoclonal antibodies) are major breakthroughs. Current treatments produce long-term survival in 50% of patients with precursor B-cell ALL including 50% to 70% with Philadelphia chromosome (Ph)-positive ALL, 50% to 60% with T-cell ALL, and 80% with mature B-cell ALL. Next-generation sequencing and genomic profiling in ALL have identified new prognostic markers, targets, and ALL subtypes (eg, Ph-like ALL). Monoclonal antibodies, bispecific antibody constructs, and chimeric antigen receptor T cellular therapies developed in the past 5 to 7 years have revolutionized the treatment of ALL and resulted in US Food and Drug Administration approvals of blinatumomab in 2014, as well as inotuzumab and tisagenlecleucel in 2017 as ALL salvage strategies. Their use in combined modalities as salvage and frontline therapies is currently under investigation. Therapies targeting specific transcripts or leukemic cell surface antigens are major breakthroughs in the treatment of adults with ALL. The incorporation of new monoclonal antibodies and other targeted approaches into frontline regimens is showing promising results. If confirmed, such strategies may increase the cure rates in adults to levels achieved in pediatric ALL and reduce the need for intensive and prolonged chemotherapy.


Testing for epistasis between deleterious mutations in a parasitoid wasp.
Determining the way in which deleterious mutations interact to effect fitness is crucial to numerous areas in evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last, termed synergistic epistasis, then sex and recombination provide an advantage because they enable deleterious mutations to be eliminated more efficiently. However, there is a severe shortage of relevant empirical data, especially of the form that can help test mutational explanations for the widespread occurrence of sex. Here, we test for epistasis in the parasitic wasp Nasonia vitripennis, examining the fitness consequences of chemically induced deleterious mutations. We examine two components of fitness, both of which are thought to be important in natural populations of parasitic wasps: longevity and egg production. Our results show synergistic epistasis for longevity, but not for egg production.


Cannabis use in HIV for pain and other medical symptoms.
Despite the major benefits of antiretroviral therapy on survival during HIV infection, there is an increasing need to manage symptoms and side effects during long-term drug therapy. Cannabis has been reported anecdotally as being beneficial for a number of common symptoms and complications in HIV infections, for example, poor appetite and neuropathy. This study aimed to investigate symptom management with cannabis. Following Ethics Committee approval, HIV-positive individuals attending a large clinic were recruited into an anonymous cross-sectional questionnaire study. Up to one-third (27%, 143/523) reported using cannabis for treating symptoms. Patients reported improved appetite (97%), muscle pain (94%), nausea (93%), anxiety (93%), nerve pain (90%), depression (86%), and paresthesia (85%). Many cannabis users (47%) reported associated memory deterioration. Symptom control using cannabis is widespread in HIV outpatients. A large number of patients reported that cannabis improved symptom control.


[Temporary mechanical left heart support. Recovery of heart function in patients with end-stage idiopathic dilated cardiomyopathy].
Implantation of a mechanical cardiac support system (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. Our experience now includes 13 patients who have been "weaned" from MCSS and we report about the overall results of this treatment as well as the effects of ventricular unloading on cardiac function, anti-beta 1-adrenoceptor-autoantibody (A-beta 1-AAB) level and the degree of myocardial fibrosis. 13 patients with non-ischemic IDC who had been admitted here in cardiogenic shock (CI < 1.61.min-1.m2, left ventricular ejection fraction [LVEF] < 16% and left ventricular internal diameter in diastole [LVIDd] > 68 mm) and who all tested positive for A-beta 1-AABs were implanted with an uni-(12 patients) or a biventricular (1 patient) mechanical assist device. Echocardiographic evaluation and A-beta 1-AAB-level-monitoring was routinely performed after implantation and explantation of the MCSS and the degree of myocardial fibrosis was assessed at the time of implantation and after explantation. During a mean duration of mechanical support of 236 +/- 201 days (range: 30 to 794 days), LV-EF improved to a mean of 46% and LVIDd decreased to a mean value of 56 mm in these 13 patients. A-beta 1-AABs decreased and disappeared 11.7 weeks after implantation of the device and did not reincrease thereafter. The highly pathologic degree of fibrosis at the time of implantation diminished to normal values about 1 year after explantation. One patient died of anesthesiologic complications and another patient shortly presented with a new episode of cardiac insufficiency 6 months after explantation. He was implanted again with an univentricular assist device was successfully transplanted 3 weeks later. Mean observation period of the remaining 11 patients now amounts to 12.6 +/- 9.77 (range: 3 to 26) months after explantation of the device--as of May, 31, 1997--with a cumulative observation period of 139 patient months. Temporary implantation of a MCSS may normalize cardiac function in selected patients with IDC. The striking degree of myocardial fibrosis can reduce to normal values after explantation of the device. A-beta 1-AABs disappear during ventricular unloading and do not increase thereafter. "Weaning" from mechanical device may constitute an alternative treatment to cardiac transplantation in selected patients.


Psychosocial perspectives among cancer patients during the coronavirus disease 2019 (COVID-19) crisis: An observational longitudinal study.
The coronavirus disease 2019 (COVID-19) crisis and consequent changes in medical practice have engendered feelings of distress in diverse populations, potentially adversely affecting the psychological well-being of cancer patients. The purpose of this observational longitudinal study was to evaluate psychosocial perspectives among patients with cancer on intravenous treatment during the COVID-19 pandemic. The study recruited 164 cancer patients undergoing intravenous anti-neoplastic therapy in a tertiary cancer center. Psychosocial indices were assessed at two points in time, corresponding with the beginning of the first wave of COVID-19 pandemic in Israel (March 2020) and the time of easing of restrictions implemented to curtail spread of infection (May 2020). At Time 1 (T1), elevated COVID-19 distress levels (score 1 and 2 on 5-point scale) were observed in 44% of patients, and associated with pre-existing hypertension and lung disease in multivariate analyses but no demographic or cancer related factors. At Time 2 (T2), 10% had elevated anxiety and 24% depression as indicated by Hospital Anxiety and Depression Scale (HADS-A/D). COVID-19 distress at T1 was related to higher levels of HADS-A at T2 (Spearman 0.33 p < .01), but not HADS-D. Patients with breast cancer expressed greater COVID-19 distress compared with other cancer types (p < .01), while both HADS-A and HADS-D were highest for patients with GI cancer. Patient report of loneliness and decreased support from relatives were factors associated with HADS-A (p = .03 and p < .01, respectively), while HADS-D was not similarly related to the factors evaluated. Patients with cancer undergoing intravenous treatment may be vulnerable to acute adverse psychological ramifications of COVID-19, specifically exhibiting high levels of anxiety. These appear unrelated to patient age or disease stage. Those with underlying comorbidities, breast cancer or reduced social support may be at higher risk.


The Effect of Educational Intervention Regarding the Knowledge of Mothers on Prevention of Accidents in Childhood.
Early guidance emphasizes the provision of information to families about growth and normal development in childhood such as specific information about security at home. This research aimed to analyze mothers' knowledge about the prevention of accidents in childhood before and after an educational intervention. It was conducted as a quasi-experimental study with 155 mothers in a Basic Health Unit in northeastern of Brazil in April and May of 2015. The data were collected in two stages through a self-report questionnaire performed before and after the educational intervention by the subjects. The results revealed a significant increase in knowledge about prevention of accidents in childhood in all the self-applied questions (p<0.05). After the educational intervention, there seemed to be a significant difference with the questions regarding the knowledge on preventing fall (p=0.000), drowning (p=0.000), and intoxication (p=0.007). The authors concluded that the educational intervention performed in this study increased the subjects' knowledge on prevention of accidents in childhood.


Quantitative evaluation of binary digital region asymmetry with application to skin lesion detection.
The performance of Computer Aided Diagnosis Systems for early melanoma detection relies mainly on quantitative evaluation of the geometric features corresponding to skin lesions. In these systems, diagnosis is carried out by analyzing four geometric characteristics: asymmetry (A), border (B), color (C) and dimension (D). The main objective of this study is to establish an algorithm for the measurement of asymmetry in biological entities. Binary digital images corresponding to lesions are divided into 8 segments from their centroid. For each segment, the discrete compactness value is calculated using Normalized E-Factor (NEF). The asymmetry value is obtained from the sum of the square difference of each NEF value and corresponding value of its opposite by the vertex. Two public skin cancer databases were used. 1) Lee's database with 40 digital regions evaluated by fourteen dermatologists. 2) The PH2 database which consists of 200 images in an 8-bit RGB format. This database provides a pre-classification of asymmetry carried out by experts, and it also indicates if the lesion is a melanoma. The measure was applied using two skin lesion image databases. 1) In Lee's database, Spearman test provided a value of 0.82 between diagnosis of dermatologists and asymmetry values. For the 12 binary images most likely to be melanoma, the correlation between the measurement and dermatologists was 0.98. 2) In the PH2 database a label is provided for each binary image where the type of asymmetry is indicated. Class 0-1 corresponds to symmetry and one axis of symmetry shapes, the completely asymmetrical were assigned to Class 2, the values of sensitivity and specificity were 59.62 and 85.8% respectively between the asymmetry measured by a group of dermatologists and the proposed algorithm. Simple image digital features such as compactness can be used to quantify the asymmetry of a skin lesion using its digital binary image representation. This measure is stable taking into account translations, rotations, scale changes and can be applied to non-convex regions, including areas with holes.


The use of VP-16 plus cisplatin during induction chemotherapy for small-cell lung cancer.
In an attempt to circumvent innate or acquired tumor-cell resistance to chemotherapy, patients with small-cell lung cancer (SCLC) were treated with induction therapy that incorporated two active and potentially non-cross-resistant chemotherapy regimens on two National Cancer Institute of Canada (NCI-C) trials. Patients with limited disease (LD) SCLC were treated with cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) and vincristine (CAV) and VP-16 plus cisplatin in two different sequences. One arm was randomized to receive CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles, and the other arm received three courses of CAV followed by three courses of VP-16 plus cisplatin. Both treatment strategies produced similar response rates and survival curves, and each treatment group has a projected 2-year survival of 20%. Patients with extensive disease (ED) were treated with either six cycles of CAV (standard regimen) or CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles. In this study, the alternating regimen produced a higher complete response (CR) rate (40% v 27%) and overall response rate (61% v 39%; P less than .01). The progression-free survival was also superior for the alternating arm (P = .001), as was overall survival (P less than .05). The frequency of thrombocytopenia and severe gastrointestinal toxicity was slightly greater in the alternating arm, but the frequency of neutropenia and infection was less. The alternation of CAV and VP-16 plus cisplatin during induction therapy is an effective treatment strategy in the management of SCLC and superior to CAV alone in extensive SCLC.


Palliative and end-of-life care for patients with severe COPD.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. For many patients, maximal therapy for COPD produces only modest or incomplete relief of disabling symptoms and these symptoms result in a significantly reduced quality of life. Despite the high morbidity and mortality associated with severe COPD, many patients receive inadequate palliative care. There are several reasons for this. First, patient-physician communication about palliative and end-of-life care is infrequent and often of poor quality. Secondly, the uncertainty in predicting prognosis for patients with COPD makes communication about end-of-life care more difficult. Consequently, patients and their families frequently do not understand that severe COPD is often a progressive and terminal illness. The purpose of the present review is to summarise recent research regarding palliative and end-of-life care for patients with COPD. Recent studies provide insight and guidance into ways to improve communication about end-of-life care and thereby improve the quality of palliative and end-of-life care the patients receive. Two areas that may influence the quality of care are also highlighted: 1) the role of anxiety and depression, common problems for patients with COPD; and 2) the importance of advance care planning. Improving communication represents an important opportunity for the improvement of the quality of palliative and end-of-life care received by these patients.


Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean.
Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6-6.2). The median age at ART initiation was 36 years (IQR: 30-44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60-251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5-18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47-1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63-2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29-1.69) for 50 vs. 30 years at ART initiation; p<0.001). In this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa.


Measurement of cardiac output in small laboratory animals using recordings of blood conductivity.
No method exists which enables easy, frequent, and, at the same time, reliable cardiac output (CO) measurements in mice. To validate a simple indicator-dilution method suitable for frequent measurements of CO in small laboratory animals, a 5% glucose solution was injected as a bolus into femoral veins of mice and rats. The corresponding blood conductivity was measured continuously between an intra-aortic and a rectal electrode. The resulting conductivity-dilution curves were used to calculate CO in mice during hypervolemia and hypovolemia and in conscious as well as halothane-anesthetized mice and rats. In rats, conductivity-dilution curves and time courses of plasma glucose concentration were recorded simultaneously. Compared with CO in awake animals, CO in both species was slightly, but not significantly, reduced during halothane anesthesia. CO was significantly and gradually reduced in hypovolemic mice (up to 58 ml blood/kg body wt), whereas hypervolemia (23 ml saline/kg body wt) had no significant effect. Simultaneous recordings of conductivity-dilution curves and time courses of plasma glucose concentration yielded corresponding values of CO (P < 0.001). Measurement of blood conductivity appears to be a reliable, simple, and convenient method for quantification of CO in small animals.


A prospective controlled assessment of microdermabrasion for damaged skin and fine rhytides.
Aged skin is characterized by rhytides but also by epidermal and dermal atrophy, rough skin texture, irregular pigmentation, telangiectasias, and laxity. Microdermabrasion is an office-based mechanical resurfacing technique alternative to traditional dermabrasion. It has been used in Europe since 1992 with great acceptance. The purpose of this study was to evaluate and quantify the degree of visible improvement in photodamaged skin and fine rhytides following a series of microdermabrasion treatments. A single operator treated 20 patients with varying degrees of photodamage and rhytides with a series of eight microdermabrasion treatments at 1-week intervals; 17 subjects completed the entire study protocol. Standardized photographic documentation was performed before and after each treatment, and a survey questionnaire was completed by each subject. Punch biopsy specimens (3 mm) were collected on treated and matched nontreated control sites and evaluated for histological characteristics. Preprocedure and postprocedure photographs were rated on a 5-point scale by independent blinded observers. A total of 30 blinded observers (16 plastic surgeons and 14 laypersons) rated all photographs. The results showed that all observers rated a significant improvement of hyperchromic discoloration (p = 0.004), while only nonmedical observers observed improvement in fine rhytides. All patients were very satisfied with the results. Common side effects were mild to moderate discomfort occurring on bony areas during the treatment and an itching and tingling sensation for 2 days after treatment. No infections or scars were observed postoperatively. The average epidermal thickness in the untreated samples was 103 +/- 23 microM (mean +/- SD) before treatment compared with 148 +/- 41 microM after treatment (p < 0.001). Histologic analysis of the matched punch biopsy specimens showed an increase in organized collagen in treated versus nontreated sites. Treatment of aged skin using a series of microdermabrasion treatments is an effective, noninvasive method of skin rejuvenation with minimal risk and patient downtime. It is safe and improves skin quality by minimizing certain hyperchromic pigmentations.