In COVID-19 Patients, the Identified Gastrointestinal Symptoms in Tertiary Care Center of India.
This study aimed to assess the demographic details of coronavirus disease-2019 (COVID-19) patients, their comorbid conditions, preexisting illnesses such as tuberculosis (TB), the prevalence of gastrointestinal (GI) symptoms, duration of GI symptoms, gender-wise distribution of GI symptoms, age-wise distribution of GI symptoms, lab investigation, and computed tomography (CT) scanning was done to record the grading. In total, 956 COVID-19 patients admitted to an isolation ward of a tertiary care center were screened for 3 months. Patients were confirmed positive for SARS-CoV-2 virus by real-time polymerase chain reaction (RT-PCR) test with a throat swab. Patient's age, demographic details, preexisting illness, and GI symptoms such as fever, impairment of appetite, loss of taste, loss of smell, hiccups, nausea, vomiting, diarrhea, abdominal pain, symptom's duration, history of chronic drug intake, biological markers, CT scanning, and comorbidities were recorded. Based on the provided protocol, standard care management was given to the admitted COVID-19 patients.Statistical analysis was performed using SPSS version 20.0. Frequencies with percentages, median (min, max), Chi-square test, and Mann-Whitney U test were used to test the statistical significance, and a p-value of <0.05 was considered statistically significant. In our prospective study of 956 COVID-19 hospitalized patients, details were analyzed and the results are: the median age was 45 years, 70% of male, 60% were above 35 years, comorbidities like diabetes present in 42%, hypertension in 36%, asthma in 8%, cardiovascular diseases (CVD) in 5%, and history of chronic drug intake in 21%.Among 956 COVID-19 patients, GI symptoms were loss of smell (29.2%), loss of taste (26.4%) for 3 days; nausea (10%), vomiting (7.1%), abdominal pain (12.7%), and fever (42.5%) were observed for 2 days among the 36-45 years of age-group; and the loss of appetite (19%) for 3 days among the age-group of 46-55 years.The loss of appetite (23.7 vs 16.9%) (p= 0.014), taste (32.4 vs 23.8%) (p = 0.005), nausea (14.6 vs 8.2%) (p = 0.003), and vomiting (10.8 vs 5.5%) (p = 0.004) were higher in females than in males. No gender difference was observed in loss of smell (p = 0.057), abdominal pain (12 vs 14.3%) (p = 0.491), hiccups (4 vs 2.1%) (p = 0.132), and fever (41.3 vs 45.3%) (p = 0.329).Females had significantly higher levels of C-reactive protein (CRP) than males (6.1 vs 3.8) (p = 0.002). No gender difference was observed in neutrophil/lymphocyte ratio (NLR) (p = 0.772), ferritin, and lactate dehydrogenase (LDH). CT-grade IV was higher in males than in females (1.7 vs 1.5%), but the rest of the CT grades were higher in females than in males. In conclusion, GI symptoms are the onset of symptoms that are first expressed after being infected with the SARS-CoV-2 virus. Several studies showed the GI symptoms but did not analyze the age and gender that are risk factors for any disease, but our study showed all GI symptoms and their association with age and gender, which will shed light for our clinicians for early symptom identification, diagnosis, and appropriate treatment. Murugesan M, Govindarajan R, Prakash L, et al. In COVID-19 Patients, the Identified Gastrointestinal Symptoms in Tertiary Care Center of India. Euroasian J Hepato-Gastroenterol 2022;12(1):24-30.


Combining chemotherapy and targeted therapies in metastatic colorectal cancer.
Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, erbitux and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.


Importance of bladder radioactivity for radiation safety in nuclear medicine.
Most of the radiopharmaceuticals used in nuclear medicine are excreted via the urinary system. This study evaluated the importance of a reduction in bladder radioactivity for radiation safety. The study group of 135 patients underwent several organ scintigraphies [40/135; thyroid scintigraphy (TS), 30/135; whole body bone scintigraphy (WBS), 35/135; myocardial perfusion scintigraphy (MPS) and 30/135; renal scintigraphy (RS)] by a technologist within 1 month. In full and empty conditions, static bladder images and external dose rate measurements at 0.25, 0.50, 1, 1.5 and 2 m distances were obtained and decline ratios were calculated from these two data sets. External radiation dose rates were highest in patients undergoing MPS. External dose rates at 0.25 m distance for TS, TKS, MPS and BS were measured to be 56, 106, 191 and 72 μSv h-1 for full bladder and 29, 55, 103 and 37 μSv h-1 for empty bladder, respectively. For TS, WBS, MPS and RS, respectively, average decline ratios were calculated to be 52%, 55%, 53% and 54% in the scintigraphic assessment and 49%, 51%, 49%, 50% and 50% in the assessment with Geiger counter. Decline in bladder radioactivity is important in terms of radiation safety. Patients should be encouraged for micturition after each scintigraphic test. Spending time together with radioactive patients at distances less than 1 m should be kept to a minimum where possible. None declared.


Proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds, which is part of generalized microangiopathy.
OBJECTIVE We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS Thirty-three patients with proliferative diabetic retinopathy (PDR+), 34 patients without proliferative diabetic retinopathy, and 33 controls underwent magnetic resonance imaging to assess cerebral microangiopathy (cerebral microbleeds) and ischemic damage (white matter hyperintensities and lacunes). Peripheral microvascular function, i.e., skin capillary density and capillary recruitment, was assessed by capillary microscopy. RESULTS Cerebral microbleeds, but not ischemic damage, were more prevalent in PDR+ patients versus the other groups (P < 0.05). A trend was found across groups for the lowest baseline capillary density in PDR+ patients (P for trend = 0.05). In individuals with microbleeds, capillary recruitment was impaired compared with those without microbleeds (P = 0.04). CONCLUSIONS In PDR+ patients, cerebral microbleed prevalence was higher and seems part of generalized microangiopathy that may affect the skin and the brain.


Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model.
Recent investigations have demonstrated that adenoviral and lentiviral vectors encoding HER-2 can be utilized in cancer immunotherapy. However, it is not known whether both viral systems elicit a similar immune response. Here, we compare the immune response in mice induced by dendritic cells (DCs) infected with either recombinant adenovirus or lentivirus encoding rat HER-2 (rHER-2). Both vaccine types yielded similar control of tumor growth, but we found clear differences in their immune responses 10 days after DC immunization. Adenovirus rHER-2-transduced DCs elicited locally and systemically high frequencies of CD4+ and CD8+ T cells, while lentivirus rHER-2-transduced DCs predominantly led to CD4+ T-cell infiltration at the tumor site. Splenocytes from mice immunized with lentivirus rHER-2-transduced DCs secreted higher levels of interferon (IFN)-γ, mainly by CD4+ T cells, following stimulation by RM-1-mHER-2 tumors. In contrast, the adenovirus vaccinated group exhibited CD4+ and CD8+ T cells that both contributed to IFN-γ production. Besides an established cellular immune response, the rHER-2/DC vaccine elicited a significant humoral response that was highest in the adenovirus group. DC subsets and regulatory T cells in the spleen were also differentially modulated in the two vaccine systems. Finally, adoptive transfer of splenocytes from both groups of immunized mice strongly inhibited in vivo tumor growth. Our results suggest that not only the target antigen but also the virus system may determine the nature and magnitude of antitumor immunity by DC vaccination.


Deciphering the distribution of the savanna biome.
• We aimed to identify the limits of savanna across Africa, Australia and South America. We based our investigation on the rich history of hypotheses previously examined: that the limits of savanna are variously determined by rainfall, rainfall seasonality, soil fertility and disturbance. • We categorized vegetation on all continents as 'savanna' (open habitats with a C(4) grass layer) or 'not-savanna' (closed habitats with no C(4) grass layer) and used a combination of statistical approaches to examine how the presence of savanna varied as a function of five environmental correlates. • The presence of savanna is constrained by effective rainfall and rainfall seasonality. Soil fertility is regionally important, although the direction of its effect changes relative to rainfall. We identified three continental divergences in the limits of savanna that could not be explained by environment. • Climate and soils do not have a deterministic effect on the distribution of savanna. Over the range of savanna, some proportion of the land is always 'not-savanna'. We reconciled previous contradictory views of savanna limits by developing a new conceptual framework for understanding these limits by categorizing environmental factors into whether they had a positive or negative effect on woody growth and the frequency of disturbance.


[Long-term drug therapy in ventricular cardiac arrhythmias. Is an improvement of the prognosis possible?].
Oral long-term treatment with various antiarrhythmic drugs (aprindine, mexiletine, disopyramide, amiodarone) was assessed in 82 patients with recurrent tachycardias demonstrated in the ECG using programmed ventricular stimulation. It was shown that sudden cardiac death and recurrence of tachycardia were clearly reduced in the group of patients (n = 29) in whom drug treatment prevented ventricular tachycardia following electric stimulation. Amiodarone was demonstrated to be the most effective substance in this respect, notwithstanding some side effects.


Robustness of topologically protected surface states in layering of Bi2Te3 thin films.
Bulk Bi2Te3 is known to be a topological insulator. We investigate surface states of Bi2Te3(111) thin films of one to six quintuple layers using density-functional theory including spin-orbit coupling. We construct a method to identify topologically protected surface states of thin film topological insulators. Applying this method to Bi2Te3 thin films, we find that the topological nature of the surface states remains robust with the film thickness and that the films of three or more quintuple layers have topologically nontrivial surface states, which agrees with experiments.


[Recognizing and preventing disturbances in eruption].
Disturbances in eruption and related problems are quite common in permanent dentition but rare in deciduous dentition. For the timely recognition of disturbances in eruption, knowledge of the normal development of dentition is essential. Disturbances in eruption comprise disturbances in which eruption does not occur at all, in which it is delayed or incomplete, or in which the normal direction of eruption is influenced. If identified early enough, many undesirable dental conditions can be avoided or their seriousness can be limited. A possible impacting of permanent cuspids, for example, can be avoided by extracting the deciduous cuspids at the right moment; in cases of a large overjet or the threat of a cover-bite, lip interference can be prevented.


The Boltzmann distributions of molecular structures predict likely changes through random mutations.
New folded molecular structures can only evolve after arising through mutations. This aspect is modeled using genotype-phenotype maps, which connect sequence changes through mutations to changes in molecular structures. Previous work has shown that the likelihood of appearing through mutations can differ by orders of magnitude from structure to structure and that this can affect the outcomes of evolutionary processes. Thus, we focus on the phenotypic mutation probabilities φqp, i.e., the likelihood that a random mutation changes structure p into structure q. For both RNA secondary structures and the HP protein model, we show that a simple biophysical principle can explain and predict how this likelihood depends on the new structure q: φqp is high if sequences that fold into p as the minimum-free-energy structure are likely to have q as an alternative structure with high Boltzmann frequency. This generalizes the existing concept of plastogenetic congruence from individual sequences to the entire neutral spaces of structures. Our result helps us understand why some structural changes are more likely than others, may be useful for estimating these likelihoods via sampling and makes a connection to alternative structures with high Boltzmann frequency, which could be relevant in evolutionary processes.


Long-term treatment of chronic hepatitis C with ursodeoxycholic acid: influence of HCV genotypes and severity of liver disease.
Current therapy for chronic hepatitis C virus (HCV) infection is based on the administration of interferon alpha (IFN) alone or in combination with other anti-viral agents. However, such therapy is effective in only a minority of selected patients. Long-term ursodeoxycholic acid (UDCA) treatment has been reported to improve liver function and structure especially in cholestatic disorders. We investigated the effect of long-term UDCA treatment on liver function in respect to the severity of chronic liver disease and HCV genotypes. Forty-five patients with non-cholestatic laparoscopy-biopsy proven HCV-associated chronic hepatitis (n=16) or cirrhosis (n=29) who had not responded to, or were unsuitable for IFN, were randomly assigned to receive UDCA (600 mg/day; n=23) or no therapy (n=22) for 12 months. At entry, all patients were evaluated by means of conventional and quantitative liver function tests (LFTs), including galactose elimination capacity and antipyrine clearance, HCV antibodies, HCV-RNA and HCV genotypes. LFTs were measured at 6 and at 12 months, whereas HCV-RNA was determined again after treatment. Baseline characteristics were comparable in the two study groups. Long-term UDCA therapy was well tolerated. Based on the analysis of variance, there was a significant decrease in serum transaminase, LDH and GGT levels in UDCA treated patients. By contrast, the activities of these enzymes increased in untreated patients, with AST levels reaching statistical significance only. Statistical analysis also showed that the improvement in biochemical markers was more pronounced in UDCA treated patients with liver cirrhosis than in those with chronic hepatitis but was similar in patients with HCV genotype 1b and non-1b. However, HCV-RNA was positive in all patients after treatment. Quantitative LFTs remained, on average, stable over the 12 months of the trial in all groups. Long-term UDCA treatment is well tolerated in patients with HCV-associated chronic liver disease. The effect appears to be greater in cirrhotics than in patients with chronic hepatitis but is independent of HCV genotypes. Thus, long-term UDCA treatment, despite the absence of an anti-viral effect, seems beneficial in reducing disease activity in patients with chronic hepatitis or cirrhosis who are unsuitable for IFN therapy.


[Ofujis papuloerythroderma. Presentation of 3 cases and review of its concept and etiology].
Ofuji's papuloerythroderma is not a specific clinical entity, but a concequence of numerous inflammatory dermatoses and neoplasms. Some authors advocate that it is possible to find this erupcion in elderly patients with different types of erythroderma of known or unknown origin. It is necessary to recognize this condition since these patients can develop a lymphoma in the future. In this article three atopic patients are described with clinical lesions of papuloerythroderma respecting the cutaneous folds, with eosinophilia, increase of the IgE levels and histological characteristics of atopic eczema. We think that atopic dermatitis should be considered in the etiologic study of patients with papuloerythroderma.


Operator Perception of a Single-Use Flexible Bronchoscope: Comparison With Current Standard Bronchoscopes.
Single-use flexible bronchoscopes have gained popularity in recent years for various advantages over the traditional reusable bronchoscope. There are several commercially available disposable bronchoscopes; however, all have limitations compared to reusable bronchoscopes. The Vathin H-SteriScope is a single-use flexible bronchoscope that may have overcome some of these limitations. We designed a survey to evaluate the performance of this new single-use bronchoscope on a bronchoscopy model with operators who are familiar with current single-use and reusable bronchoscopes. The operators were asked to rank overall assessment, scope quality, handling, maneuverability, tool interaction, and image quality of the H-SteriScope on a scale of 0-100. These operators were then asked to rank their current single-use and reusable bronchoscopes with the same scale. The results were evaluated to determine the operator perception of the H-SteriScope. The H-SteriScope and current reusable bronchoscopes were perceived to have significant differences compared with currently available single-use bronchoscopes in overall assessment of the scope, scope quality, handling, maneuverability, tool interaction, and image quality (P < .001). The H-SteriScope was perceived to have similar maneuverability as the reusable bronchoscope (P = .86). There were no differences among the H-SteriScope (P = .88), the current single-use bronchoscope (P = .84), and the current reusable bronchoscope (P = .89) between the training and nontraining interventional pulmonology subgroups. In terms of operator perception, the H-SteriScope appears to have similar maneuverability as the reusable bronchoscope. Both the H-SteriScope and the reusable bronchoscopes performed better in all measured sectors than the current single-use bronchoscope. Additional studies are required to evaluate the practicality, safety, and cost efficiency of the H-SteriScope in clinical practice.


Attempts to increase inosinic acid in broiler meat by using feed additives.
To explore regulation of inosinic acid content in chicken meat as a result of feed additives, 576 one-day-old male Arbor Acres broilers were randomly allotted into 8 dietary treatments including control, purine nucleotide (P), betaine (B), soybean isoflavone (S), purine nucleotide + betaine (PB), purine nucleotide + soybean isoflavone (PS), betaine +soybean isoflavone (BS), and purine nucleotide + betaine + soybean isoflavone (PBS) by a 2 × 2 × 2 factorial arrangement. At d 42 of age, broilers were slaughtered, and growth performance, carcass characteristics, inosinic acid content, and activities of enzyme closely related to inosinic acid metabolism of broilers were measured. The results revealed that these feed additives did not affect ADG and ADFI of the broilers (P > 0.05). However, supplementing purine nucleotides lowered feed/gain of broilers in PS and PBS groups (P < 0.05). There was a significant interaction on feed/gain of broilers between purine nucleotides and soybean isoflavone (P < 0.05). The abdominal fat percentages in groups B, S, BS, and PBS were lower than the control group, respectively (P < 0.05). The thigh muscle percentages of groups P and B were higher than that of group PB (P < 0.05). There were certain interactions on the percentage of thigh muscle (P = 0.05) and abdominal fat (P < 0.05) between P, B, and S groups. Compared with the control group, inosinic acid content in broiler breast meat was improved by using feed additives (P < 0.05). Supplementing purine nucleotides, betaine, soybean isoflavone, and their combinations increased alkaline phosphatase activity in breast meat of broilers (P < 0.05). Purine nucleotides improved the activity of adenosine deaminase, but decreased the activity of 5'-nucleotidase. Soybean isoflavone lowered the activity of alkaline phosphatase. There were no significant interactions on activities of creatine kinase, adenosine deaminase, alkaline phosphatase, and 5'-nucleotidase between these additives (P > 0.05). The umami rating of broiler breast meat increased in conjunction with supplementing these additives. In conclusion, supplementing standard feed with the additives investigated in this study could improve inosinic acid content in chicken meat by increasing synthase activity or inhibiting degradation enzyme activity without inferior growth performance and carcass quality.


Multiple states in river and lake ecosystems.
Nonlinear models of ecosystem dynamics that incorporate positive feedbacks and multiple, internally reinforced states have considerable explanatory power. However, linear models may be adequate, particularly if ecosystem behaviour is primarily controlled by external processes. In lake ecosystems, internal (mainly biotic) processes are thought to have major impacts on system behaviour, whereas in rivers, external (mainly physical) factors have traditionally been emphasized. We consider the hypothesis that models that exhibit multiple states are useful for understanding the behaviour of lake ecosystems, but not as useful for understanding stream ecosystems. Some of the best-known examples of multiple states come from lake ecosystems. We review some of these examples, and we also describe examples of multiple states in rivers. We conclude that the hypothesis is an oversimplification; the importance of physical forcing in rivers does not eliminate the possibility of internal feedbacks that create multiple states, although in rivers these feedbacks are likely to include physical as well as biotic processes. Nonlinear behaviour in aquatic ecosystems may be more common than current theory indicates.


G-protein complex mutants are hypersensitive to abscisic acid regulation of germination and postgermination development.
Abscisic acid (ABA) plays regulatory roles in a host of physiological processes throughout plant growth and development. Seed germination, early seedling development, stomatal guard cell functions, and acclimation to adverse environmental conditions are key processes regulated by ABA. Recent evidence suggests that signaling processes in both seeds and guard cells involve heterotrimeric G proteins. To assess new roles for the Arabidopsis (Arabidopsis thaliana) Galpha subunit (GPA1), the Gbeta subunit (AGB1), and the candidate G-protein-coupled receptor (GCR1) in ABA signaling during germination and early seedling development, we utilized knockout mutants lacking one or more of these components. Our data show that GPA1, AGB1, and GCR1 each negatively regulates ABA signaling in seed germination and early seedling development. Plants lacking AGB1 have greater ABA hypersensitivity than plants lacking GPA1, suggesting that AGB1 is the predominant regulator of ABA signaling and that GPA1 affects the efficacy of AGB1 execution. GCR1 acts upstream of GPA1 and AGB1 for ABA signaling pathways during germination and early seedling development: gcr1 gpa1 double mutants exhibit a gpa1 phenotype and agb1 gcr1 and agb1 gcr1 gpa1 mutants exhibit an agb1 phenotype. Contrary to the scenario in guard cells, where GCR1 and GPA1 have opposite effects on ABA signaling during stomatal opening, GCR1 acts in concert with GPA1 and AGB1 in ABA signaling during germination and early seedling development. Thus, cell- and tissue-specific functional interaction in response to a given signal such as ABA may determine the distinct pathways regulated by the individual members of the G-protein complex.


External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life.
The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.


Emerging understanding of the ΔI=1/2 rule from lattice QCD.
There has been much speculation as to the origin of the ΔI=1/2 rule (ReA0/ReA2≃22.5). We find that the two dominant contributions to the ΔI=3/2, K→ππ correlation functions have opposite signs, leading to a significant cancelation. This partial cancelation occurs in our computation of ReA2 with physical quark masses and kinematics (where we reproduce the experimental value of A2) and also for heavier pions at threshold. For ReA0, although we do not have results at physical kinematics, we do have results for pions at zero momentum with mπ≃420 MeV [ReA0/ReA2=9.1(2.1)] and mπ≃330 MeV [ReA0/ReA2=12.0(1.7)]. The contributions which partially cancel in ReA2 are also the largest ones in ReA0, but now they have the same sign and so enhance this amplitude. The emerging explanation of the ΔI=1/2 rule is a combination of the perturbative running to scales of O(2 GeV), a relative suppression of ReA2 through the cancelation of the two dominant contributions, and the corresponding enhancement of ReA0. QCD and electroweak penguin operators make only very small contributions at such scales.


[Antigenic polysaccharides of bacteria of the genus Shigella. The structure of the polysaccharide chain of Shigella boydii type 14].
A specific acidic polysaccharide has been isolated from the Shigella boydii type 14 antigenic lipopolysaccharide after mild hydrolysis followed by chromatography on Sephadex G-50. The polysaccharide consists of the D-glucuronic acid, 2-acetamido-2-deoxy-D-glucose and D-galactose residues in the ratio 1:1:3. From the results of methylation analysis and partial acid hydrolysis, the structure of the repeating unit of the specific polysaccharide was deduced as follows: (-6DGalp alpha 1-4DGlcAp beta 1-6DGalp beta 1-4DGalp beta 1-4DGlcNAcp beta 1-)n. The 13C NMR spectra of native and carboxyl-reduced polysaccharides, as well as of oligosaccharides produced by partial acid hydrolysis fully confirmed the proposed structure. The approach was suggested to determine the type of substitution of uronic acid moieties in polysaccharide chain by use of chromato-mass-spectrometry of acetylated methyl esters of partially methylated aldonic acids. Serological characteristics of Sh. boydii LPS type 14 and its modified derivatives are discussed.


Pharmacy in Latvia during the first Soviet occupation (1940-1941).
The first period of the independent state of Latvia lasted from 1918 to 1940. During this period, pharmacy in Latvia had reached a high level of development. The study covers the period after the loss of independence, when the beginning of World War II marked a major crisis in the development of pharmacy in Latvia. The aim of the study was to compile and systematize information available in published and unpublished sources on the impact of the Soviet occupation (1940-1941) on pharmacy in Latvia, which has not been studied before. The main idea of the study was to find evidence that the Soviet occupation decreased the development capacity of Latvian pharmaceutical industry and narrowed its development opportunities. At the same time, the study reflects part of the general political, ideological and economic environment in Latvia over that period. The study is retrospective and descriptive. Materials from Latvian State Historical Archives and the National Archives of Latvia, and publications from the 20th century press of Latvia were used in the study. In one year, the Soviet system attempted to aggressively transform Latvian pharmaceutical industry to match the USSR standards. This meant the destruction of the capitalist system and the free market, as well as the introduction of centralised management. The radical changes were poorly organised and unsuitable candidates were appointed to positions of responsibility. There is evidence that pharmacy in Latvia experienced complete chaos during that period: private enterprises were nationalised, the number of pharmacy professionals decreased, and medical products from abroad were not supplied to the Latvian market. The Latvian population was rescued from total lack of medications by the last major medication purchase from Germany and the Netherlands shortly before the occupation. All the USSR actions in the pharmaceutical industry were coercive. With the occupation of Nazi Germany in the summer of 1941, the Soviet functionaries left the industry. However, in 1945, during the second occupation, the previous procedures were renewed and their results strengthened. It leads to the conclusion that the Soviet political system had an adverse effect on the development of pharmacy in Latvia.


Paraneoplastic Arthritis in a Patient with Non-Hodgkin's Lymphoma.
Paraneoplastic syndromes are a group of disorders associated with benign or malignant tumors but not related to mass effect or invasion directly. Paraneoplastic syndromes may affect any organic system of the human body, such as endocrine, neurologic, dermatologic, hematologic, rheumatologic. Paraneoplastic rheumatic syndromes are not quite common, about 7-10% of paraneoplastic syndromes, and may mimic rheumatic diseases. We present an interesting case of paraneoplastic arthritis in a woman with non-Hodgkin's lymphoma.


A multidisciplinary approach to giant cell tumors of tendon sheath and synovium--a critical appraisal of literature and treatment proposal.
Giant cell tumors deriving from synovium are classified into a localized (GCT of tendon sheath; GCT-TS) and diffuse form (diffuse-type GCT, Dt-GCT). We propose a multidisciplinary management based upon a systematic review and authors' opinion. Open excision for GCT-TS and open synovectomy (plus excision) for Dt-GCT is advised to reduce the relatively high recurrence risk. External beam radiotherapy should be considered in severe cases, as Dt-GCT commonly extends extra-articular.


Crossing microfluidic streamlines to lyse, label and wash cells.
We present a versatile method for continuous-flow, on-chip biological processing of cells, large bio-particles, and functional beads. Using an asymmetric post array in pressure-driven microfluidic flow, we can move particles of interest across multiple, independent chemical streams, enabling sequential chemical operations. With this method, we demonstrate on-chip cell treatments such as labeling and washing, and bacterial lysis and chromosomal extraction. The washing capabilities of this method are particularly valuable because they allow many analytical or treatment procedures to be cascaded on a single device while still effectively isolating their reagents from cross-contamination.


K-ras as a target for cancer therapy.
The central role K-, H- and N-Ras play in regulating diverse cellular pathways important for cell growth, differentiation and survival is well established. Dysregulation of Ras proteins by activating mutations, overexpression or upstream activation is common in human tumors. Of the Ras proteins, K-ras is the most frequently mutated and is therefore an attractive target for cancer therapy. The complexity of K-ras signaling presents many opportunities for therapeutic targeting. A number of different approaches aimed at abrogating K-ras activity have been explored in clinical trials. Several of the therapeutic agents tested have demonstrated clinical activity, supporting ongoing development of K-ras targeted therapies. However, many of the agents currently being evaluated have multiple targets and their antitumor effects may not be due to K-Ras inhibition. To date, no selective, specific inhibitor of K-ras is available for routine clinical use. In this review, we will summarize the structure and function of K-ras with attention to its role in tumorigenesis and discuss the successes and failures of the various strategies designed to therapeutically target this important oncogene.


Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis.
This prospective randomized, double-blind, placebo-controlled, clinical trial was performed to evaluate the effectiveness of estrogens plus low-dose alendronate on bone metabolism. A total of 150 surgically postmenopausal women with osteoporosis were randomized in three groups: group A, micronized E2 (2 mg/d) plus standard-dose alendronate (10 mg/d); group B, micronized E2 plus low-dose alendronate (5 mg/d); and group C, micronized E2 plus placebo (one tablet per day). In all women, bone mineral density (BMD) and serum bone metabolism markers were assessed at admission and every 6 months for 2 yr. After 2 yr, BMD significantly increased compared with baseline in all groups. The percentage BMD change was significantly higher in groups A and B than in group C. The differences in BMD detected between groups A and B were not statistically significant. Since the 6-month follow-up and throughout the study, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were significantly reduced in all groups. Serum bone alkaline phosphatase levels significantly decreased in groups A and B, without difference between them, in comparison with group C. In conclusion, in surgically postmenopausal osteoporotic women treated with estrogen replacement, the addition of alendronate at a low dose of 5 mg daily induces a gain of bone mass not significantly different in comparison with that obtained using a standard dose of 10 mg daily.


An experimental study on the use of a carbon fibre prosthesis for the repair of the cranial cruciate ligament in the dog.
The severed cranial cruciate ligament of Beagles was replaced with a carbon fibre tow. Post-operatively the animals were evaluated clinically and radiographically. The animals were sacrificed and specimens collected for histology. There was marked infiltration of the implant by granulation tissue which matured into longitudinally orientated collagen fibres to form a new ligament. A foreign body reaction which occurred at about 12 weeks subsided after a few more weeks. Fracture of the implant was present in a high percentage of knees. The advantages and disadvantages are discussed and technical errors identified.


The conscientious objection: debate on emergency contraception.
The authors discuss the emergency contraception (EC) topic, assessing scientific and ethical aspects. The almost totality of the studies carried out tends to report on the use of drugs as an emergency measure to prevent pregnancy. However, it is not yet completely excluded that emergency contraceptives can induce medical abortion. The debate on side effects of EC continues to be a highly emotional and controversial issue both for advocates who believe they will lower considerably the number of unintended pregnancies and abortions, and for opponents who believe that using emergency contraception amounts to an abortion. This latter hypothesis highlights the conflicting aspect of the conscientious objection to abortion of physicians and pharmacists. This research work is aimed at investigating the emergency contraception issue, paying particular attention to the medico-legal and regulatory aspects of this subject. Particularly, the authors focus on the conscientious objection in order to assess, if any, legal protection for physicians and pharmacists who claim a right to conscientious objection. Inappropriate use of EC could be resolved through a registry of user. This registry, of course, would not have the intention of persecution, but would only serve to detect possible cases of subjugation, exploitation and harassment.


A cell cycle kinase with tandem sensory PAS domains integrates cell fate cues.
All cells must integrate sensory information to coordinate developmental events in space and time. The bacterium Caulobacter crescentus uses two-component phospho-signalling to regulate spatially distinct cell cycle events through the master regulator CtrA. Here, we report that CckA, the histidine kinase upstream of CtrA, employs a tandem-PAS domain sensor to integrate two distinct spatiotemporal signals. Using CckA reconstituted on liposomes, we show that one PAS domain modulates kinase activity in a CckA density-dependent manner, mimicking the stimulation of CckA kinase activity that occurs on its transition from diffuse to densely packed at the cell poles. The second PAS domain interacts with the asymmetrically partitioned second messenger cyclic-di-GMP, inhibiting kinase activity while stimulating phosphatase activity, consistent with the selective inactivation of CtrA in the incipient stalked cell compartment. The integration of these spatially and temporally regulated signalling events within a single signalling receptor enables robust orchestration of cell-type-specific gene regulation.


A logic gate-based fluorogenic probe for Hg(2+) detection and its applications in cellular imaging.
A new colorimetric and fluorogenic probe (RN3) based on rhodamine-B has been successfully designed and synthesized. It displays a selective response to Hg(2+) in the aqueous buffer solution over the other competing metals. Upon addition of Hg(2+), the solution of RN3 exhibits a 'naked eye' observable color change from colorless to red and an intensive fluorescence with about 105-fold enhancement. The changes in the color and fluorescence are ascribed to the ring-opening of spirolactam in rhodamine fluorophore, which is induced by a binding of the constructed receptor to Hg(2+) with the association and dissociation constants of 0.22 × 10(5) M(-1) and 25.2 μM, respectively. The Job's plot experiment determines a 1:1 binding stoichiometry between RN3 and Hg(2+). The resultant "turn-on" fluorescence in buffer solution, allows the application of a method to determine Hg(2+) levels in the range of 4.0-15.0 μM, with the limit of detection (LOD) calculated at 60.7 nM (3σ/slope). In addition, the fluorescence 'turn-off' and color 'fading-out' happen to the mixture of RN3-Hg(2+) by further addition of I(-) or S(2-). The reversible switching cycles of fluorescence intensity upon alternate additions of Hg(2+) and S(2-) demonstrate that RN3 can perform as an INHIBIT logic gate. Furthermore, the potential of RN3 as a fluorescent probe has been demonstrated for cellular imaging.


[Diagnostic and therapeutic measures in acute catastrophic bleeding esophageal varices].
Principles of management of bleeding esophageal varices are 1. fluid therapy of bleeding shock, 2. prevention of hepatic coma, 3. emergency endoscopy, 4. balloon tubes (Senkstaken-Blakemore, Linton-Nachlas), and 5. with some restriction, selective infusion of vasopressin into the a. mesenterica superior. If these procedures fail, sclerosing of esophageal varices stops bleeding in more than 90% of the cases. Bleeding from varices of the gastric fundus may be stopped by gastro-esophageal disconnection (Pettinari-Hassab). Both procedures have with 15% and 25% respectively, the lowest mortality. Patients for surgical shunt are carefully selected within the interval after bleeding. Shunts are the distal splenal-renal and the mesenteric-caval anastomosis with dacron prothesis (H-shunt). The shunt is the favorable therapy for prehepatic block in patients older than 14 to 16 years. The endoscopic sclerosing of esophageal varices and the gastro-esophageal disconnection are chosen in younger patients or when shunt procedures are not possible. The posthepatic block is treated successfully by conservative means. In most cases, surgical therapy is contraindicated because of poor prognosis. When conservative measures fail, in few cases emergency endoscopic sclerosing of esophageal varices or latero-lateral porto-caval anastomosis can be tried.


Establishment, characterization, and long-term maintenance of cultures of human fetal hepatocytes.
Cultured human hepatocytes have broad research and clinical applications; however, the difficulties in culturing rodent and human hepatocytes are well known. These problems include the rapid loss of the hepatocytic phenotype in primary culture and the limited replicating capacity of the cultured cells. We describe the establishment of serum-free primary cultures of human fetal hepatocytes (HFHs) that retain hepatocytic morphology and gene expression patterns for several months and maintain sufficient proliferative activity to permit subculturing for at least 2 passages. Initially, HFH cultures contained 2 main cell types that morphologically resembled large and small hepatocytes. The fetal hepatocytes expressed alpha-fetoprotein (AFP), cytokeratin (CK) 19, albumin, and other hepatic proteins. Treatment of the cultures with oncostatin M (OSM) increased cell size and enhanced cell differentiation and formation of bile canaliculi, probably through an effect on hepatocyte nuclear factor (HNF) 4alpha. Approximately 1 month after plating, multiple clusters of very small cells became apparent in the cultures. These cells had very few organelles and are referred to as blast-like cells. Flow cytometric analysis of these cells showed that they express oval cell/stem cell markers such as CD90 (Thy-1), CD34, and OV-6 but do not stain with antibodies to beta(2)-microglobulin. HFH cultures maintained for 9 to 12 months produced grossly visible organoids containing ductular structures that stained for CK18, CK19, and AFP. In conclusion, HFH cultures, which might contain a population of hepatic stem cells, constitute an excellent tool for a variety of studies with human hepatocytes, including the mechanisms of viral infection.


Depressed erythropoietic activity of Nigerian pregnant women.
Reticulocytes production index was determined in 63 pregnant women and in 96 patients. The results show that 86% of the pregnant women, who were registering their pregnancy for the first time, were anaemic. There was significant reticulocytopenia in all the anaemic pregnant women and in the patients. Erythropoiesis was found to be depressed in all subjects patients by two to seven times those expected in normal responsive bone marrows. There was no correlation of the bone marrow impairment with parity of the pregnancy. The bone marrow impairment was more pronounced during the 16th week of gestation and less so in older pregnancies. Malnutrition and infection (especially malaria) are suggested as the aetiological factors of the bone marrow depression of erythropoiesis.


Mosquito bite-caused eosinophilic dermatitis in cats.
Eight cats had lesions on the nasal bridge, ears, and footpads, with histologic and hematologic features of a recently described seasonal form of eosinophilic granuloma complex. Four cats were examined in detail, and it was established that 2 of the 4 reacted to mosquito extract on intradermal skin testing read at 20 minutes. Neither of the 2 cats tested had deposits of immunoglobulins in lesional or perilesional skin. Lesions on all 4 cats resolved when kept at home behind insect screening, but flared up if the screening was removed. Mosquitoes that were observed to be biting and causing lesions were collected and identified. Other species of laboratory-reared mosquitoes were allowed to bite nonlesional skin of 1 affected cat, causing pruritus, erythematous crusting, and ulcerative lesions at the bite site, which was characterized histologically as eosinophilic dermatitis.


Reducing indwelling urinary catheter use in the emergency department: a successful quality-improvement initiative.
This quality-improvement project aimed to evaluate the effectiveness of implementing multidisciplinary education and deploying utilization tools aimed at reducing the inappropriate insertion of indwelling urinary catheters (IUCs) in the emergency department. Literature supports the use of decision support tools and education as proven techniques to reduce IUC use. Few studies have implemented a multidisciplinary approach involving the use of focus groups to understand the thought processes behind deciding to place an IUC. Focus groups were used to understand the current practice for inserting an IUC in the emergency department. These data were then used to create a nursing-based IUC decision support tool and educational presentation regarding appropriate uses for IUCs. Live, in-person education sessions were given to emergency nurses, emergency medical technicians, physicians, and residents; in addition, electronic education was assigned to all emergency nurses and technicians. Seventy-eight percent of ED staff received some form of education regarding appropriate IUC insertion criteria. Physicians and residents also received an in-person presentation on the topic. A survey was sent to all emergency nurses and emergency medical technicians to assess actual practice changes. In addition, an IUC utilization and appropriateness audit was completed before and immediately after the interventions. The project resulted in a 25% decrease in the proportion of patients admitted to inpatient status with IUCs placed in the emergency department and a 9% decrease in the inappropriate use of IUCs. Staff surveys after education showed that staff members were more likely to document the reason for placing an IUC and to use alternatives to IUCs. The potential risks associated with IUCs often go overlooked by direct-care staff members. Educating staff and creating new standards and utilization tools have often been used to decrease the initial insertion of IUCs and to improve recognition of appropriate removal of IUCs. Using direct feedback from staff to develop the interventions led to a reduction in IUC insertions in the emergency department in the short-term, but long-term changes were not seen. The project results suggest that incorporating staff into the decision making and implementation will lead to long-term acquisition of knowledge and longer-term results. Ongoing regularly scheduled education refreshers need to be assessed for their potential to affect long-term change.


DNA sequence of the Serratia marcescens lipoprotein gene.
The Serratia marcescens gene for the outer membrane lipoprotein (lpp) was cloned in lambda phage vector Charon 14. The recombinant phage was very unstable, and the lpp gene with a 300-base-pair deletion at the transcription termination site was further cloned in pBR322. The DNA sequence of 834 base pairs encompassing the lpp gene was determined and compared with that of the Escherichia coli lpp gene. The sequence comparisons exhibit several unique features. (i) The promoter region is highly conserved (84% homology) and has an extremely high A+T content (78%) as in E. coli (80%). (ii) The 5' nontranslated region of the lipoprotein mRNA is also highly conserved (95% homology). (iii) In the DNA sequence corresponding to the signal peptide of this secretory protein, there are three drastic changes, including addition of one base pair and deletion of four base pairs in S. marcescens as compared to E. coli. The resultant alterations in the amino acid sequence, however, do not change the basic properties of the signal peptide, which are assumed to be essential for its function in the secretory mechanism. (iv) The DNA sequence from the amino terminus to the 51st residue of the mature lipoprotein is highly conserved (95% homology) and there is no amino acid substitution. (v) The DNA sequence corresponding to the seven amino acid residues at the carboxyl terminus has only 42% homology, resulting in four amino acid substitutions. (vi) Within the section of 40 base pairs beginning with the termination codon (UAA) and ending immediately before the oligo(T) transcription termination site in the E. coli lpp gene, there is about 60% homology. However, after this section, there is no obvious homology between the two sequences, probably because of a deletion of 300 base pairs at this region. (vii) Seven stable stem-and-loop structures could be formed in the mRNA region. (viii) Alterations in the third position of codons used in the lpp gene suggest that the gene has evolved somewhat differently from other genes in S. marcescens.


Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies.
Pulmonary arterial hypertension is a rare and devastating disease characterized by an abnormal chronic increase in pulmonary arterial pressure above 20 mmHg at rest, with a poor prognosis if not treated. Currently, there is not a single fully effective therapy, even though a dozen of drugs have been developed in the last decades. Pulmonary arterial hypertension is a multifactorial disease, meaning that several molecular mechanisms are implicated in its pathology. The main molecular pathways regulating the pulmonary vasomotor tone-endothelin, nitric oxide, and prostacyclin-are the most biologically and therapeutically explored to date. However, drugs targeting these pathways have already found their limitations. In the last years, translational research and clinical trials have made a strong effort in suggesting and testing novel therapeutic strategies for this disease. These approaches involve targeting the main molecular pathways with novel drugs, drug repurposing for novel targets, and also using combinatorial therapies. In this review, we summarize current strategies and drugs targeting the endothelin, nitric oxide, and prostacyclin pathways, as well as, the emerging new drugs proposed to cope with vascular remodelling, metabolic switch, perivascular inflammation, epigenetic modifications, estrogen deregulation, serotonin, and other neurohumoral mechanisms characteristic of this disease. Nowadays, pulmonary arterial hypertension remains an incurable disease; however, the incoming new knowledge makes us believe that new promising therapies are coming to the clinical arena soon.


Genetic characterization of human immunodeficiency virus type 1 in elite controllers: lack of gross genetic defects or common amino acid changes.
Despite reports of viral genetic defects in persons who control human immunodeficiency virus type 1 (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers of subjects, primarily focused on subjects expressing HLA-B57, or have examined single viral genes, and they have focused on cellular proviral DNA rather than plasma viral RNA sequences. Here, we attempted viral sequencing from 95 HIV-1 elite controllers (EC) who maintained plasma viral loads of <50 RNA copies/ml in the absence of therapy, the majority of whom did not express HLA-B57. HIV-1 gene fragments were obtained from 94% (89/95) of the EC, and plasma viral sequences were obtained from 78% (61/78), the latter indicating the presence of replicating virus in the majority of EC. Of 63 persons for whom nef was sequenced, only three cases of nef deletions were identified, and gross genetic defects were rarely observed in other HIV-1 coding genes. In a codon-by-codon comparison between EC and persons with progressive infection, correcting for HLA bias and coevolving secondary mutations, a significant difference was observed at only three codons in Gag, all three of which represented the historic population consensus amino acid at the time of infection. These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms.


Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women.
1. A randomized controlled trial of the effect of oral hormone replacement therapy plus calcium compared with calcium alone on balance, muscle performance and falls was conducted over 48 weeks in 116 post-menopausal women (aged 45-70 years), all of whom had suffered a distal radial fracture during the previous 3 months. Treatment was with Prempak C or Premarin 0.625 mg in the test group with 1 g calcium daily (Sandocal) in both groups. Measurements were made of balance, assessed as sway, leg extensor power and self-paced walking speed, at 12-week intervals over 24 weeks. Hand grip strength was measured every 12 weeks for 48 weeks, and falls in the preceding 12 weeks were recorded at each visit. 2. There was no relation between initial levels of oestradiol and any other variable assessed, except body mass. Levels of follicle-stimulating hormone in the test group were in the premenopausal range. There was no significant change attributable to hormone replacement therapy at any time point in any of the outcome variables. The only significant difference was an increase of 4.2% (95% confidence interval 0.7-7.6%) in leg extensor power in the control group (calcium alone) compared with the group treated with hormone replacement therapy. 3. Of the total group, 37% fell again during the year, with three patients suffering a further fracture. Frequent fallers swayed significantly more often than the others, but there was no evidence that their muscle strength was poorer or that the group treated with hormone replacement therapy fell less frequently. 4. Hormone replacement therapy did not increase muscle performance, improve balance or reduce falls over a year in middle-aged women.


Introduction to hyphenated techniques and their applications in pharmacy.
The hyphenated technique is developed from the coupling of a separation technique and an on-line spectroscopic detection technology. The remarkable improvements in hyphenated analytical methods over the last two decades have significantly broadened their applications in the analysis of biomaterials, especially natural products. In this article, recent advances in the applications of various hyphenated techniques, e.g., GC-MS, LC-MS, LC-FTIR, LC-NMR, CE-MS, etc. in the context of pre-isolation analyses of crude extracts or fraction from various natural sources, isolation and on-line detection of natural products, chemotaxonomic studies, chemical fingerprinting, quality control of herbal products, dereplication of natural products, and metabolomic studies are discussed with appropriate examples.


Asthma/allergic airways disease: does postnatal exposure to environmental toxicants promote airway pathobiology?
The recent, dramatic increase in the incidence of childhood asthma suggests a role for environmental contaminants in the promotion of interactions between allergens and the respiratory system of young children. To establish whether exposure to an environmental stressor, ozone (O3), and an allergen, house dust mite (HDMA), during early childhood promotes remodeling of the epithelial-mesenchymal trophic unit (EMTU) of the tracheobronchial airway wall by altering postnatal development, infant rhesus monkeys were exposed to cyclic episodes of filtered air (FA), HDMA, O3, or HDMA plus O3. The following alterations in the EMTU were found after exposure to HDMA, O3, or HDMA plus O3: (1) reduced airway number; (2) hyperplasia of bronchial epithelium; (3) increased mucous cells; (4) shifts in distal airway smooth muscle bundle orientation and abundance to favor hyperreactivity; (5) interrupted postnatal basement membrane zone differentiation; (6) modified epithelial nerve fiber distribution; and (7) reorganization of the airway vascular and immune system. cyclic challenge of infants to toxic stress during postnatal lung development modifies the EMTU. This exacerbates the allergen response to favor development of intermittent airway obstruction associated with wheeze. And, exposure of infants during early postnatal lung development initiates compromises in airway growth and development that persist or worsen as growth continues, even with cessation of exposure.


Appraisal of sinus node artery disease.
The relationship of depressed sinus node function to coronary artery disease (CAD) was evaluated. The sinus node artery (SNA) was easily identified in all of 80 unselected normal coronary arteriograms. Angiographic disease of, or significant obstruction proximal to, the SNA was seen in 21% of 80 unselected CAD patients. Heart rate and sinoatrial recovery times (SART) were obtained in 50 consecutive unmedicated patients prior to arteriography. There was no difference between the SART of 23 CAD patients free of SNA involvement (1092 msec +/- 55 sem) and 18 normals (1070 +/- 40 msec). Nine patients with SNA involvement had shorter SART (941 +/- 52 MSEC) than normals (P less than 0.05) or other CAD patients (NS). Similar results were obtained for heart rate. No patient with SNA involvement had a prolonged SART or sick sinus syndrom (SSS). six of the 50 patients studied were symptomatic with SSS. Five of these SSS patients had CAD but none had angiographic evidence of SNA involvement. Obstructions involving the SNA were common in CAD but were not associated with altered heart rate or SART. Patients with SSS exhibited no angiographic evidence of SNA involvement. Therefore, it is unlikely that SSS is related to CAD of the SNA.


microRNA Sequencing of CD34+ Sorted Adipose Stem Cells Undergoing Endotheliogenesis.
While several microRNAs (miRNAs) that regulate the endotheliogenesis and further promote angiogenesis have been identified in various cancers, the identification of miRNAs that can drive the differentiation of adipose derived stromal/stem cells (ASCs) into the endothelial lineage has been largely unexplored. In this study, CD34+ ASCs sorted using magnetic bead separation were induced to differentiate along the endothelial pathway. miRNA sequencing of ASCs at day 3, 9, and 14 of endothelial differentiation was performed on Ion Proton sequencing system. The data obtained by this high-throughput method were aligned to the human genome HG38, and the differentially expressed miRNAs during endothelial differentiation at various time points (day 3, 9, and 14) were identified. The gene targets of the identified miRNAs were obtained through miRWalk database. The network-pathway analysis of miRNAs and their targets was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatic tools to determine the potential candidate miRNAs that promote endothelial differentiation. Based on these analyses, six upregulated miRNAs (miR-181a-5p, miR-330-5p, miR-335-3p, miR-15b-5p, miR-99a-5p, and miR-199a-5p) and six downregulated miRNAs (miR-145-5p, miR-155-5p, miR-193a-3p, miR-125a-5p, miR-221-5p, and miR-222-3p) were chosen for further studies. In vitro evaluation of these miRNAs to induce endothelial differentiation when transfected into CD34+ sorted ASCs was studied using Von Willebrand Factor (VWF) staining and quantitative real time-polymerase chain reaction (qRT-PCR). Our results suggest that miRNAs: 335-5p, 330-5p, 181a-5p and anti-miRNAs: 125a-5p, 145-5p can likely induce endothelial differentiation in CD34+ sorted ASCs. Further studies are clearly required to elucidate the specific mechanisms on how miRNAs or anti-miRNAs identified through bioinformatics approach can induce the endotheliogenesis in ASCs.


Clinical utility of breast magnetic resonance imaging in patients presenting with primary breast cancer.
Since magnetic resonance imaging (MRI) of the breast has been shown to be sensitive in identifying the extent of the primary tumor and other foci of cancer, we examined its clinical utility in the surgical management of breast cancer patients. From January 2004 to April 2007, 117 patients with newly diagnosed breast cancer underwent bilateral MRI prior to definitive surgical management. Additional lesions were found in 27 patients (23.1%) in the ipsilateral breast and 19 patients (16.2%) in the contralateral breast. Twelve patients (10.3%) had more than one new lesion identified. Six patients (5.1%) had a larger area of tumor than detected by mammography or ultrasound. Additional biopsies were performed in 27 patients (23.1%). Additional foci of cancer were identified in 17 patients (14.5%): 12 (10.2%) in the ipsilateral breast and 5 (4.3%) in the contralateral breast. This information changed the clinical management in 23 cases (19.7%). Further studies are needed to confirm the benefits of MRI relative to its costs and to further identify the appropriate patients to undergo this imaging procedure.


Sleep architecture as correlate and predictor of symptoms and impairment in inter-episode bipolar disorder: taking on the challenge of medication effects.
This study was designed to clarify the association between inter-episode bipolar disorder (BD) and sleep architecture. Participants completed a baseline symptom and sleep assessment and, 3 months later, an assessment of symptoms and impairment. The effects of psychiatric medications on sleep architecture were also considered. Participants included 22 adults with BD I or II (inter-episode) and 22 non-psychiatric controls. The sleep assessment was conducted at the Sleep and Psychological Disorders Laboratory at the University of California, Berkeley. Follow-up assessments 3 months later were conducted over the phone. Results indicate that, at the sleep assessment, BD participants exhibited greater rapid eye movement sleep (REM) density than control participants with no other group differences in sleep architecture. Sleep architecture was not correlated with concurrent mood symptoms in either group. In the BD group, duration of the first REM period and slow-wave sleep (SWS) amount were positively correlated with manic symptoms and impairment at 3 months, while REM density was positively correlated with depressive symptoms and impairment at 3 months. The amount of Stage 2 sleep was negatively correlated with manic symptoms and impairment at 3 months. In contrast, for the control group, REM density was negatively correlated with impairment at 3 months. SWS and Stage 2 sleep were not correlated with symptoms or impairment. Study findings suggest that inter-episode REM sleep, SWS and Stage 2 sleep are correlated with future manic and depressive symptoms and impairment in BD. This is consistent with the proposition that sleep architecture may be a mechanism of illness maintenance in BD.


Difficulties in diagnosis of SARS-CoV-2 myocarditis in an adolescent.
We present an adolescent with cardiogenic shock due to ventricular tachycardia 2 weeks after SARS-CoV-2 infection. Acute myocarditis or myocardial dysfunction is associated with SARS-CoV-2 infection, but diagnosis may be difficult, even including endomyocardial biopsy. A 15-year-old healthy adolescent was admitted to our hospital 2 weeks after SARS-CoV-2 infection with cardiogenic shock due to ventricular tachycardia. After cardioversion, antiarrhythmic treatment, ventilation, and inotropic support, the severely reduced myocardial function recovered completely within 2 weeks. Cardiac magnetic resonance imaging and cardiac catheterisation including right ventricular endomyocardial biopsy revealed an increased number of CD68+ macrophages in the myocardium, but nested (RT-) polymerase chain reaction (PCR) investigations revealed no viral or bacterial DNA/RNA. SARS-CoV-2 infection may be associated with myocarditis leading to life-threatening arrhythmia and severe myocardial systolic and diastolic dysfunction, which may be short lasting and completely recover. Although former SARS-Cov-2 infection might suggest SARS-CoV-2-associated myocarditis, definite histological diagnosis including nested PCR investigations remains difficult.


Structural requirements for ligand binding by a probable plant vacuolar sorting receptor.
How sorting receptors recognize amino acid determinants on polypeptide ligands and respond to pH changes for ligand binding or release is unknown. The plant vacuolar sorting receptor BP-80 binds polypeptide ligands with a central Asn-Pro-Ile-Arg (NPIR) motif. tBP-80, a soluble form of the receptor lacking transmembrane and cytoplasmic sequences, binds the peptide SSSFADSNPIRPVTDRAASTYC as a monomer with a specificity indistinguishable from that of BP-80. tBP-80 contains an N-terminal region homologous to ReMembR-H2 (RMR) protein lumenal domains, a unique central region, and three C-terminal epidermal growth factor (EGF) repeats. By protease digestion of purified secreted tBP-80, and from ligand binding studies with a secreted protein lacking the EGF repeats, we defined three protease-resistant structural domains: an N-terminal/RMR homology domain connected to a central domain, which together determine the NPIR-specific ligand binding site, and a C-terminal EGF repeat domain that alters the conformation of the other two domains to enhance ligand binding. A fragment representing the central domain plus the C-terminal domain could bind ligand but was not specific for NPIR. These results indicate that two tBP-80 binding sites recognize two separate ligand determinants: a non-NPIR site defined by the central domain-EGF repeat domain structure and an NPIR-specific site contributed by the interaction of the N-terminal/RMR homology domain and the central domain.


Relationship Between Neonatal Brain Injury and Objective Measures of Head Trauma: A Case-Control Study.
Neonatal brain injury is a common and devastating diagnosis conferring lifelong challenges for children and families. The role of mechanical forces applied to the head, often referred to as "birth trauma," are often considered although evidence for this association is lacking. The objective of this study was to investigate the association between common types of neonatal brain injury and scalp swelling using a novel method to quantify scalp swelling as an unbiased proxy for mechanical forces applied to the head. Case-control study using population-based, prospectively collected tertiary care center databases and healthy controls from the Human Connectome Development Project. Included were infants born 32-42 weeks gestational age and MRI in the first 9 days. Outcomes categories included healthy neonates, hypoxic ischemic encephalopathy (HIE) with or without brain injury, or stroke (ischemic or hemorrhagic). Volume of scalp swelling was objectively quantified by a novel imaging method blinded to brain injury. Variables included mode of delivery and use of instrumentation. Statistical tests included Kruskal-Wallis test, chi square, and multivariable and multinomial logistic regression. There were 309 infants included (55% male): 72 healthy controls, 77 HIE without brain injury on MRI, 78 HIE with brain injury, and 82 with stroke (60 ischemic, 22 hemorrhagic). Scalp swelling was present in 126 (40.8%, 95% confidence interval [CI] 35.2%-46.5%) with no difference in proportions between outcome groups. Compared to healthy controls, median volume was higher in those with HIE without brain injury (17.5 mL, 95% CI 6.8-28.2), HIE with brain injury (12.1 mL, 95% CI 5.5-18.6), but not ischemic stroke (4.7 mL, 95% CI -1.2-10.6) nor hemorrhagic stroke (8.3 mL, 95% CI -2.2-18.8). Scalp swelling was associated with instrumented delivery (OR 2.1, 95% CI 1.0-4.1), but not associated with increased odds of brain injury in those with HIE (OR 1.5, 95% CI 0.76-3.30). Scalp swelling measures were highly reliable (ICC = 0.97). "Birth trauma" quantified by scalp swelling volume was more common in infants with difficult deliveries, but not associated with greater odds of brain injury due to hypoxia or stroke. These results may help parents and practitioners to dissociate the appearance of trauma with the risk of brain injury.


Distribution of zinedin in the rat brain.
Members of the striatin family are scaffolding proteins involved in numerous signaling pathways principally in neurons. Zinedin is the only member of this protein family for which the brain distribution has not been determined so far. Here, we have validated a specific antibody against zinedin and used this tool to study the localization of zinedin at cellular and sub-cellular levels in the rat brain. Zinedin is primarily expressed in neurons of the hippocampus, cerebral cortex, olfactory bulb and caudate putamen nucleus. Like other members of the striatin family, zinedin displays a polarized distribution in the somato-dendritic compartment of neurons and is enriched in dendritic spines. The rostral expression of zinedin as well as its compartmented distribution in dendritic spines may have important implications not only for zinedin function but also in the physiology of dendritic spines of a particular subset of neurons.


Drug therapy adherence and health outcomes in the presence of physician and patient unobserved heterogeneity.
Understanding the role that drug adherence has on health outcomes in everyday clinical practice is central for the policy maker. This is particularly true when patients suffer from asymptomatic chronic conditions (e.g., hypertension, hypercholesterolaemia, and diabetes). By exploiting a unique longitudinal dataset at patient and physician level in Italy, we show that patients and physicians unobserved characteristics play an important role in determining health status, at least as important as drug adherence. Most importantly, we find that both adherence and prescribed treatment regimen effects are highly heterogeneous across physicians, highlighting their crucial role in shaping patients' health status.


Kinesin-1 acts with netrin and DCC to maintain sensory neuron position in Caenorhabditis elegans.
The organization of neurons and the maintenance of that arrangement are critical to brain function. Failure of these processes in humans can lead to severe birth defects, mental retardation, and epilepsy. Several kinesins have been shown to play important roles in cell migration in vertebrate systems, but few upstream and downstream pathway members have been identified. Here, we utilize the genetic model organism Caenorhabditis elegans to elucidate the pathway by which the C. elegans Kinesin-1 Heavy Chain (KHC)/KIF5 ortholog UNC-116 functions to maintain neuronal cell body position in the PHB sensory neurons. We find that UNC-116/KHC acts in part with the cell and axon migration molecules UNC-6/Netrin and UNC-40/DCC in this process, but in parallel to SAX-3/Robo. We have also identified several potential adaptor, cargo, and regulatory proteins that may provide insight into the mechanism of UNC-116/KHC's function in this process. These include the cargo receptor UNC-33/CRMP2, the cargo adaptor protein UNC-76/FEZ and its regulator UNC-51/ULK, the cargo molecule UNC-69/SCOCO, and the actin regulators UNC-44/Ankyrin and UNC-34/Enabled. These genes also act in cell migration and axon outgrowth; however, many proteins that function in these processes do not affect PHB position. Our findings suggest an active posterior cell migration mediated by UNC-116/KHC occurs throughout development to maintain proper PHB cell body position and define a new pathway that mediates maintenance of neuronal cell body position.


[Which truth for patients and their family].
Must the truth always be told to a cancer patient and/or his relatives? Taking a personal experience as the basis for discussion, the author examines this question in the context of Western cultural norms where death is taboo. The legal obligations to inform patients and the representation of cancer are discussed. Two key situations are considered: the delivery of a diagnosis of cancer and the announcement of a bad prognosis. What does it really mean "to tell the truth"? A best strategy for giving information to relatives is developed. The author's conclusion is that it seems more important to establish a "true" relationship with the cancer patient and his relatives than telling or not telling the whole truth.


Exploring stakeholders' experiences of comprehensive geriatric assessment in the community and out-patient settings: a qualitative evidence synthesis.
Comprehensive Geriatric Assessment (CGA) is a multidimensional interdisciplinary process that addresses an older adult's biopsychosocial capabilities to create an integrated and co-ordinated plan of care. While quantitative evidence that demonstrates the positive impacts of CGA on clinical and process outcomes has been synthesised, to date qualitative research reporting how older adults and service providers experience CGA has not been synthesised. This study aimed to systematically review and synthesise qualitative studies reporting community-dwelling older adults', caregivers' and healthcare professionals' (HCP) experiences of CGA in the primary care and out-patient (OPD) setting. We systematically searched five electronic databases including MEDLINE, CINAHL, PsycINFO, PsycARTICLES and Social Sciences Full Text targeting qualitative or mixed methods studies that reported qualitative findings on older adults', caregivers' and HCPs' experiences of CGA in primary care or out-patient settings. There were no language or date restrictions applied to the search. The protocol was registered with the PROSPERO database (Registration: CRD42021283167). The methodological quality of the included studies was appraised using the Critical Appraisal Skills Programme checklist for qualitative research. Results were synthesised according to Noblit and Hare's seven-step approach to meta-ethnography, which involves an iterative and inductive process of data synthesis. Fourteen studies were included where CGA was completed in the home, general practice, out-patient setting in acute hospitals and in hybrid models across the community and hospital-based OPD settings. Synthesis generated four key themes: (1) CGA is experienced as a holistic process, (2) The home environment enhances CGA, (3) CGA in the community is enabled by a collaborative approach to care, and (4) Divergent experiences of the meaningful involvement of older adults, caregivers and family in the CGA process. Findings demonstrate that CGA in a home-based or OPD setting allows for a holistic and integrated approach to care for community-dwelling older adults while increasing patient satisfaction and accessibility of healthcare. Healthcare professionals in the community should ensure meaningful involvement of older adults and their families or caregivers in the CGA process. Further robustly designed and well reported trials of different models of community-based CGA informed by the findings of this synthesis are warranted.


Mixed-Penetrant Sorption in Ultrathin Films of Polymer of Intrinsic Microporosity PIM-1.
Mixed-penetrant sorption into ultrathin films of a superglassy polymer of intrinsic microporosity (PIM-1) was studied for the first time by using interference-enhanced in situ spectroscopic ellipsometry. PIM-1 swelling and the concurrent changes in its refractive index were determined in ultrathin (12-14 nm) films exposed to pure and mixed penetrants. The penetrants included water, n-hexane, and ethanol and were chosen on the basis of their significantly different penetrant-penetrant and penetrant-polymer affinities. This allowed studying microporous polymer responses at diverse ternary compositions and revealed effects such as competition for the sorption sites (for water/n-hexane or ethanol/n-hexane) or enhancement in sorption of typically weakly sorbing water in the presence of more highly sorbing ethanol. The results reveal details of the mutual sorption effects which often complicate comprehension of glassy polymers' behavior in applications such as high-performance membranes, adsorbents, or catalysts. Mixed-penetrant effects are typically very challenging to study directly, and their understanding is necessary owing to a broadly recognized inadequacy of simple extrapolations from measurements in a pure component environment.


Exploring the genetic diversity within traditional Philippine pigmented Rice.
The wild ancestors of domesticated rice had red seed, white rice being the result of a mutation in the rice domestication gene Rc. Many pigmented rice landraces are still grown by ethnic communities for their nutritional and cultural value. This study assesses the genetic diversity in a collection of pigmented rice accessions from the Philippines. We undertook an analysis of the genetic and colour variation in a collection of 696 pigmented rice accessions held at PhilRice in the Philippines. The collection was reduced to 589 genotypes after removal of accessions with limited passport data or with low SNP marker call rates. Removal of duplicate genotypes resulted in a final, core collection of 307 accessions, representing all administrative districts of the Philippines, and composed predominately of japonica and indica sub-species. No genetic structure was observed in the core collection based on geographic origin. A pairwise comparison of accessions by region indicating that both local and long-distance exchange of rice accessions had occurred. The majority of the genetic variation was within regions (82.38%), rather than between regions (10.23%), with the remaining variation being within rice accession variance (7.39%). The most genetically diverse rice accessions originated from the Cordillera Administrative Region (CAR) in the far north of the Philippines, and in the regions of Davao and Caraga in the southeast. A comparison with pigmented rice accessions from the neighbouring countries Taiwan, Laos, China and India revealed a close relationship between accessions from Taiwan, supporting the hypothesis of southward diffusion of Austronesians from Taiwan to the Philippine. The 14-bp deletion within the gene Rc, known to result in loss of red pigmentation, was found in 30 accessions that still had coloured pericarps. Multi-spectral phenotyping was used to measure seed geometric and colour-appearance traits in 197 accessions from the core collection. The purple and variable purple rice accessions had the lowest values for the seed colour parameters - lightness (L*), intensity, saturation, a* (green - red; redness) and b* (blue - yellow; yellowness). These pigmented rice accessions represent a diverse genetic resource of value for further study and nutritional improvement of commercial rice varieties.


Evidence Gaps in the Use of Spinal Cord Stimulation for Treating Chronic Spine Conditions.
A review of literature. The aim of this study was to define and explore the current evidence gaps in the use of spinal cord stimulation (SCS) for treating chronic spine conditions. Although over the last 40 years SCS therapy has undergone significant technological advancements, evidence gaps still exist. A literature review was conducted to define current evidence gaps for the use of SCS. Areas of focus included 1) treatment of cervical spine conditions, 2) treatment of lumbar spine conditions, 3) technological advancement and device selection, 4) appropriate patient selection, 5) the ability to curb pharmacological treatment, and 6) methods to prolong efficacy over time. New SCS strategies using advanced waveforms are explored. The efficacy, safety, and cost-effectiveness of traditional SCS for chronic pain conditions are well-established. Evidence gaps do exist. Recently, advancement in waveforms and programming parameters have allowed for paresthesia-reduced/free stimulation that in specific clinical areas may improve clinical outcomes. New waveforms such as 10-kHz high-frequency have resulted in an improvement in back coverage. To date, clinical efficacy data are more prevalent for the treatment of painful conditions originating from the lumbar spine in comparison to the cervical spine. Evidence gaps still exist that require appropriate study designs with long-term follow-up to better define and improve the use of this therapy for the treatment of chronic spine pain in both the cervical and lumbar regions. N/A.


Comparison of Postoperative Outcomes Between Primary MIS TLIF and MIS TLIF With Revision Decompression.
Retrospective cohort. To compare postoperative improvements in surgical and patient-reported outcomes (PROs) between patients undergoing minimally invasive laminectomy and minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) as a primary procedure to patients undergoing MIS laminectomy and TLIF as a revision to primary lumbar decompression (LD). MIS TLIF and LD have demonstrated to be effective surgical options for lumbar degenerative disease. However, some patients undergoing LD experience recurrent symptoms and eventually require a revision decompression with fusion. A prospectively maintained surgical database of patients who underwent a primary or revision one-level MIS TLIF for degenerative spinal pathology between 2014 and 2016 was reviewed. Consecutive patients undergoing primary MIS TLIF and revision lumbar discectomy and/or laminectomy were matched in a one-to-one fashion to primary MIS TLIF patients who had not undergone a previous LD by age and preoperative diagnosis. Differences in patient demographic, comorbidity, and perioperative characteristics between procedure groups were assessed using Pearson chi-squared analysis and Student t test for categorical and continuous variables, respectively. Improvements in PROs from preoperative values were compared between primary and revision cohorts using Student t tests. Pearson chi-squared analysis was used to compare rates of minimum clinically important difference achievement between procedure groups. Statistical significant was set at P < 0.05. A total of 52 patients were included in this analysis. Twenty-six underwent primary MIS laminectomy and TLIF and 26 underwent MIS TLIF with a revision decompression. No differences in baseline or perioperative variables were observed. Revision and primary MIS TLIF patients experienced similar improvements in PROs at all postoperative time points. The results of the present study demonstrate patients undergoing primary MIS TLIF with LD as a revision to a primary decompression experienced similar postoperative improvements in PROs as compared to primary MIS TLIF patients. This indicates a primary decompression does not compromise clinical outcomes in patients undergoing MIS TLIF. As such, patients should not be precluded from undergoing MIS TLIF based on the history of a previous LD. 3.


Corneal and scleral dellen after an uneventful pterygium surgery and a febrile episode.
We describe a patient with corneal and scleral dellen, which occurred after an uneventful pterygium excision without adjunctive therapy and a subsequent febrile episode. A 43-year-old woman presented with a history of recurrent irritation in her right eye and a diagnosis of pterygium. The pterygium was excised under local anesthesia with the bare scleral technique and without the use of antimetabolites. No complications occurred until 14 days after surgery when corneal and sclera dellen appeared; this was 2 days after a concomitant febrile episode (39°C). Tobramycin and dexamethasone eye drops given after surgery were withdrawn and topical lubricants and antibiotic ointment, in combination with oral L-amino acids, were administered along with eye patching. One week later, the corneal dellen had completely healed and, 4 weeks later, the thinned sclera appeared regularly thick and white in color. Three months after surgery, a small recurrent pterygium was diagnosed, which remained stable without signs of inflammation for additional 18 months. Corneal and scleral dellen might be a late complication of uneventful pterygium surgery without antimetabolites and a subsequent febrile episode.


Management of advanced primary urethral carcinomas.
Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defıning the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity.


Denoising Adversarial Autoencoders.
Unsupervised learning is of growing interest because it unlocks the potential held in vast amounts of unlabeled data to learn useful representations for inference. Autoencoders, a form of generative model, may be trained by learning to reconstruct unlabeled input data from a latent representation space. More robust representations may be produced by an autoencoder if it learns to recover clean input samples from corrupted ones. Representations may be further improved by introducing regularization during training to shape the distribution of the encoded data in the latent space. We suggest denoising adversarial autoencoders (AAEs), which combine denoising and regularization, shaping the distribution of latent space using adversarial training. We introduce a novel analysis that shows how denoising may be incorporated into the training and sampling of AAEs. Experiments are performed to assess the contributions that denoising makes to the learning of representations for classification and sample synthesis. Our results suggest that autoencoders trained using a denoising criterion achieve higher classification performance and can synthesize samples that are more consistent with the input data than those trained without a corruption process.


Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.
Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.


[Pain in the hospital: from prevalence to quality standards].
Pain diminishes the quality of life of patients and a high prevalence of pain calls into question the quality of health care being delivered. The present study analyzes the prevalence of pain in one hospital, by departments and by therapeutic approach used. This cross-sectional study was carried out in a representative sample of 309 patients admitted to a tertiary care hospital. Information was gathered by patient interviews and by reviewing hospital records for personal characteristics, clinical situation, pain characteristics and analgesic treatment. The prevalence of pain was 54.7% overall. The prevalence of pain eligible for treatment (intensity >2 on a visual analog scale) was 43.5%. The prevalence of pain that was moderate to intense (>3) was 34.7%. No analgesia was prescribed for 18.7% of the patients eligible, and analgesia was effective for 47.3%. Analgesia was provided on demand (63.2%) in most clinic protocols, usually with nonsteroidal antiinflammatory drugs, acetaminophen, opioids and special techniques, administered in combination to half the patients. The prevalence and intensity of pain and the prescription protocols varied from one hospital department to another. Analgesic treatment was adequate for 67.1% of the patients. The results suggest that the prevalence of pain in the hospital is high and that it is possible to improve quality of clinical approach, in agreement with studies that have been appearing since the 1980s. The persistence of the problem of pain in health care centers requires action on all levels of the health care system.


Macromolecular Targets of Antiparasitic Germacranolide Sesquiterpenoids: An In Silico Investigation.
The parasitic protozoal infections leishmaniasis, human African trypanosomiasis, and Chagas disease are neglected tropical diseases that pose serious health risks for much of the world's population. Current treatment options suffer from limitations, but plantderived natural products may provide economically advantageous therapeutic alternatives. Several germacranolide sesquiterpenoids have shown promising antiparasitic activities, but the mechanisms of activity have not been clearly established. The objective is to use in silico screening of known antiparasitic germacranolides against recognized protozoal protein targets in order to provide insight into the molecular mechanisms of activity of these natural products. Conformational analyses of the germacranolides were carried out using density functional theory, followed by molecular docking. A total of 88 Leishmania protein structures, 86 T. brucei protein structures, and 50 T. cruzi protein structures were screened against 27 antiparasitic germacranolides. The in-silico screening has revealed which of the protein targets of Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are preferred by the sesquiterpenoid ligands.


The DNA damage response signaling cascade regulates proliferation of the phytopathogenic fungus Ustilago maydis in planta.
In the phytopathogenic fungus Ustilago maydis, the dikaryotic state dominates the period of growth occurring during the infectious phase. Dikaryons are cells in which two nuclei, one from each parent cell, share a single cytoplasm for a period of time without undergoing nuclear fusion. In fungal cells, maintenance of the dikaryotic state requires an intricate cell division process that often involves the formation of a structure known as the clamp connection as well as the sorting of one of the nuclei to this structure to ensure that each daughter dikaryon inherits a balance of each parental genome. Here, we describe an atypical role of the DNA damage checkpoint kinases Chk1 and Atr1 during pathogenic growth of U. maydis. We found that Chk1 and Atr1 collaborate to control cell cycle arrest during the induction of the virulence program in U. maydis and that Chk1 and Atr1 work together to control the dikaryon formation. These findings uncover a link between a widely conserved signaling cascade and the virulence program in a phytopathogen. We propose a model in which adjustment of the cell cycle by the Atr1-Chk1 axis controls fidelity in dikaryon formation. Therefore, Chk1 and Atr1 emerge as critical cell type regulators in addition to their roles in the DNA damage response.


[Marital violence, a social and public health problem: a study in a police station in the state of Rio de Janeiro].
This article presents data of an investigation for drawing the profile of men and women involved in domestic violence taken from reports made at a police station in a small city in the state of Rio de Janeiro between 1997 and 2001. Data were crossed with the speeches of the couples at the police station. The article highlights the importance of this issue for public health, confirmed both in the feminist literature and in health studies. The results show that cultural determinants have an important influence on the construction of the roles of males and females, legitimating the power of the man over the woman and turning men violent when they cannot control the situation. More than half of the reports of women (53%) was due to corporal injuries, the rest were threats and attempted murder (39%), and psychological abuse (8%) through insults and defamation. The article presents information about the profile, professional status, color and race of aggressors and victims. It is concluded that, despite the feminist movement and other achievements, domestic violence continues reproducing and investments are necessary for understanding, reporting and overcoming the problem and changing behavior patterns.


Interactive research and the construction of knowledge in conflict-affected settings.
This paper contributes to ongoing debates about the possibilities/impossibilities and particular challenges related to conducting field research in conflict settings by addressing a particular topic of concern: collaboration between researchers, organisations, respondents, and other actors present in the field. Whereas collaboration with local actors has been common for reasons of access and security, there seems to be a lack of recognition of the manner in which collaboration in the field shapes the generation of knowledge on conflict and post-conflict settings. The objectives of this paper are twofold: (i) to highlight the potential contribution of research collaborations in conflict environments beyond pragmatic considerations of access and security; and (ii) to argue for more explicit attention to how such forms of collaboration influence the construction of knowledge and for more rigour in tracing the implications of such cooperation. The paper seeks to contribute to continuous learning on the possibilities/impossibilities of working with interactive research under conditions of conflict and insecurity.