Zebrafish Mutant Lines Reveal the Interplay between nr3c1 and nr3c2 in the GC-Dependent Regulation of Gene Transcription.
Glucocorticoids mainly exert their biological functions through their cognate receptor, encoded by the nr3c1 gene. Here, we analysed the glucocorticoids mechanism of action taking advantage of the availability of different zebrafish mutant lines for their receptor. The differences in gene expression patterns between the zebrafish gr knock-out and the grs357 mutant line, in which a point mutation prevents binding of the receptor to the hormone-responsive elements, reveal an intricate network of GC-dependent transcription. Particularly, we show that Stat3 transcriptional activity mainly relies on glucocorticoid receptor GR tethering activity: several Stat3 target genes are induced upon glucocorticoid GC exposure both in wild type and in grs357/s357 larvae, but not in gr knock-out zebrafish. To understand the interplay between GC, their receptor, and the mineralocorticoid receptor, which is evolutionarily and structurally related to the GR, we generated an mr knock-out line and observed that several GC-target genes also need a functional mineralocorticoid receptor MR to be correctly transcribed. All in all, zebrafish mutants and transgenic models allow in vivo analysis of GR transcriptional activities and interactions with other transcription factors such as MR and Stat3 in an in-depth and rapid way.


Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrine-induced glucose oxidation.
Glucose is an important fuel for rat brown adipose tissue in vivo and its utilization is highly sensitive to insulin. In this study, the different glucose metabolic pathways and their regulation by insulin and norepinephrine were examined in isolated rat brown adipocytes, using [6-14C]glucose as a tracer. Glucose utilization was stimulated for insulin concentrations in the range of 40-1000 microU/ml. Furthermore, the addition of adenosine deaminase (200 mU/ml) or adenosine (10 microM) did not alter insulin sensitivity of glucose metabolism. The major effect of insulin (1 mU/ml) was a respective 7-fold and 5-fold stimulation of lipogenesis and lactate synthesis, whereas glucose oxidation remained very low. The 5-fold stimulation of total glucose metabolism by 1 mU/ml of insulin was accompanied by an 8-fold increase in glucose transport. In the presence of norepinephrine (8 microM), total glucose metabolism was increased 2-fold. This was linked to a 7-fold increase of glucose oxidation, whereas lipogenesis was greatly inhibited (by 72%). In addition, norepinephrine alone did not modify glucose transport. The addition of insulin to adipocytes incubated with norepinephrine, induced a potentiation of glucose oxidation, while lipogenesis remained very low. In conclusion, in the presence of insulin and norepinephrine glucose is a oxidative substrate for brown adipose tissue. However the quantitative importance of glucose as oxidative fuel remains to be determined.


Ear pruritus: a new otologic finding related to temporomandibular disorder.
This prospective clinical study evaluated the correlation among temporomandibular disorder (TMD), otologic manifestations, and parafunctional habits in a sample of 100 patients with TMD. The subjects were evaluated by clinical examination, use of a simplified anamnestic questionnaire for TMD diagnosis, and the investigation of otologic manifestations and parafunctional habits of the stomatognathic system. The prevalence of TMD and correlations with otologic manifestations and parafunctional habits were calculated. Patients ranged in age from 13 to 70 years, and 79.0% of the patients were between the ages of 30 and 59 years. Women represented 88.0% of the sample. Otologic manifestations were found in 92.0% of patients with TMD. Sex showed a significant correlation with severity of TMD (P = 0.024). A significant correlation was observed between female patients and both otalgia (P = 0.036) and ear pruritus (P < 0.001). Otalgia showed a significant association with the symptoms of TMD (P = 0.003). Significant correlations between severe TMD and otalgia (P < 0.001), tinnitus (P = 0.010), ear pruritus (P < 0.001), and aural fullness (P = 0.014) were also observed. Ear pruritus, otalgia, and aural fullness are the most common otologic manifestations in patients with TMD, showing a significant correlation with the female sex, severity of TMD, and frequency of TMD symptoms.


Brain metastases from non-central nervous system tumors: evaluation with PET.
Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) was performed in 19 patients with brain metastases from non-central nervous system (CNS) neoplasms and one patient with a primary CNS lymphoma. Various histopathologic types were represented by the primary neoplasms in the patients with metastases. Only 21 of the 31 lesions (68%) were detected with FDG PET as discrete, metabolically active foci (relative to surrounding structures). Six of the nondetected lesions may have been nondiscernible owing to their small size and/or isointensity relative to closely apposed normal gray matter. However, four lesions of at least 1.2 cm in diameter showed frankly decreased FDG accumulation relative to normal brain. These findings suggest that studies of FDG accumulation by a variety of non-CNS neoplasms and their CNS metastases are in order and that extrapolation of the successes of FDG PET in imaging of primary glial tumors to imaging of brain metastases should proceed with caution.


Atypical antipsychotics: experience and use in the elderly.
The use of antipsychotics is common in the elderly Typical antipsychotics are not without risk, especially in tardive dyskinesia, which, when balanced against relatively low efficacy, make their use debatable. Atypical antipsychotics have much less in the way of side-effects and are much less likely to induce tardive dyskinesia. However, there is much less in the published literature about the efficacy of these drugs in the elderly and how best to use them in primary psychosis, Parkinson's disease and the behavioural and psychological symptoms of dementia. This review attempts to summarise the current literature and make some tentative recommendations for each of the commonest atypicals, based on the current evidence.


Current characteristics of animal rabies cases in Thailand and relevant risk factors identified by a spatial modeling approach.
The situation of human rabies in Thailand has gradually declined over the past four decades. However, the number of animal rabies cases has slightly increased in the last ten years. This study thus aimed to describe the characteristics of animal rabies between 2017 and 2018 in Thailand in which the prevalence was fairly high and to quantify the association between monthly rabies occurrences and explainable variables using the generalized additive models (GAMs) to predict the spatial risk areas for rabies spread. Our results indicate that the majority of animals affected by rabies in Thailand are dogs. Most of the affected dogs were owned, free or semi-free roaming, and unvaccinated. Clusters of rabies were highly distributed in the northeast, followed by the central and the south of the country. Temporally, the number of cases gradually increased after June and reached a peak in January. Based on our spatial models, human and cattle population density as well as the spatio-temporal history of rabies occurrences, and the distances from the cases to the secondary roads and country borders are identified as the risk factors. Our predictive maps are applicable for strengthening the surveillance system in high-risk areas. Nevertheless, the identified risk factors should be rigorously considered and integrated into the strategic plans for the prevention and control of animal rabies in Thailand.


Structural, quantitative and functional comparison of amyloid P component in sera from patients with systemic lupus erythematosus and healthy donors.
Serum amyloid P component (SAP) is a serum protein that has a function as opsonin and is known to bind nuclear material with high affinity. Quantitative and/or qualitative deficiencies in SAP may possibly lead to the impairment of normal homoeostatic mechanisms of tissue turnover. Thus, SAP knockout mice display systemic lupus erythematosus (SLE)-like manifestations such as nephritis and circulating antinuclear antibodies. In the present study, we investigated whether there are changes in the structure, function or serum levels of SAP in serum from SLE patients as compared with those from healthy donors. We found that SAP in SLE sera has the same molecular mass as that of in the sera of normal individuals, when analysed by online immunoaffinity reversed phase mass spectrometry. Also, the serum levels of SAP did not differ significantly between the two groups. Finally, as an estimate of function, SAP from SLE patients appeared to have the same affinity for heparin and nucleosomes as SAP from normal individuals, when analysed by crossed affinity immunoelectrophoresis and enzyme-linked immunosorbent capture assay (ELISA). In conclusion, the data do not support alterations in the levels, structure or function of SAP circulating in SLE patients.


[Patient satisfaction in diabetes mellitus--measures and results].
The focus of this article is the satisfaction and health-related quality of life felt by patients with diabetes mellitus. Taking the LIVE-DE study as an example, it is demonstrated how various regimens of insulin treatment affect patient satisfaction. The standardized Insulin Treatment Experience Questionnaire (ITEQ) was produced for this purpose. It has 28 defined questions and answers. The 28 items describe in eight categories the experiences and problems which diabetic patients have had. It was found that there were significant differences between the insulin glargine and the NPH insulin-based regimens regarding quality of life and satisfaction with the treatment, a difference that ranged from small to moderate in favour of insulin glargine.


Plastic surgery research in the UK.
There is no single source of information on plastic surgery research in the UK. We sought to compile such information from a survey of trainees and consultants, and present an overview of the research activity, the number and designation of those engaged in research, sources of funds, principal areas of investigation and the perceived future for research.


Immunogenicity - implications for rheumatoid arthritis treatment.
Biologic agents used to treat rheumatoid arthritis are in- trinsically immunogenic, as they represent complex proteins which are manufactured outside of the recipient of the drug. This is true for chimeric antibodies, humanized antibod- ies, and for fusion proteins. The emergence of antibodies against biologic agents (AAB) will influence both short and long-term efficacy of these agents and may also play a role in adverse events such as infusion reactions. For patients who fail an initial biologic agent or for those who initially respond but lose efficacy, knowledge of whether an AAB is present will allow the clinician to more effectively choose the best agent to which the patient can be switched. The pres- ence of rising ANA titers or antibodies to double stranded DNA may be a good marker for the emergence of AABs. Concurrent use of non-biologic DMARDs at appropriate doses is critical to prevent the evolution of AABs and to ensure long-term efficacy of the biologic agent.


Two- and three-dimensional transesophageal echocardiographic diagnosis of intramyocardial dissecting hematoma after myocardial infarction.
The echocardiographic findings of an intramyocardial dissecting hematoma that formed after an extensive acute myocardial infarction of the anterior wall of a 42-year- old man are described. Serial transesophageal studies were used to construct 3-dimensional images that clarified the participation of various myocardial layers that surrounded the dissecting hematoma. The patient was successfully treated with intra-aortic balloon counterpulsation and subsequently coronary artery bypass grafting. Intramyocardial dissecting hematoma is a rare complication of acute infarction; differential diagnosis must be made with pseudoaneurysm by establishing integrity of epicardium and with intracavitary thrombosis by identifying the endomyocardial layer surrounding the neoformation and associated wall movement.


Trichomonas vaginalis transcription-mediated amplification-based analyte-specific reagent and alternative target testing of primary clinical vaginal saline suspensions.
Following wet mount analysis, 255 vaginal saline suspensions were aliquoted to lysis medium for transcription-mediated amplification (TMA)-based Trichomonas vaginalis analyte-specific reagent testing (ASR) (Gen-Probe, San Diego, CA). Specimens with visible T. vaginalis were then refrigerated, with additional aliquoting at later intervals. Twenty-four wet mount-positive specimens (9.4%) yielded a median luminescent value (x1000, relative light unit [RLU]) of 4736. In contrast, RLU ranged from 1 to 21 following ASR of 204 wet mount-negative specimens. Twenty-seven wet mount-negative specimens (10.5%) were positive by ASR and subsequently positive via T. vaginalis alternative target TMA (Gen-Probe). Discrepancies were additionally resolved by demonstration of T. vaginalis nucleic acid from a separate endocervical collection. T. vaginalis nucleic acid was detectable following prolonged storage, following minimal incubation in lysis medium, and from low-volume aliquots of sparsely populated specimens. T. vaginalis ASR adequately detects T. vaginalis from vaginal saline suspension aliquots, providing a simple specimen alternative for a highly sensitive laboratory diagnosis of trichomoniasis.


The determination of absolute intensity of 234mPa's 1001 keV gamma emission using Monte Carlo simulation.
The 1001 keV gamma line of (234m)Pa became important in gamma spectrometric measurements of samples with (238)U content with the advent of development of HpGe detectors of great dimension and high efficiency. In this study the emission probability of the 1001 keV (Y(gamma)) peak of (234m)Pa, was determined by gamma-ray spectrometric measurements performed on glass with Uranium content using Monte Carlo simulation code for efficiency calibration. This method of calculation was not applied for the values quoted in literature so far, at least to our knowledge. The measurements gave an average of 0.836 +/- 0.022%, a value that is in very good agreement to some of the recent results previously presented.


[Pathophysiology and genetics of obesity].
Obesity has become the most prevalent nutritional disorder in post-industrialised societies and it is associated with the development of severe and costly complications such as type 2 diabetes mellitus and coronary heart disease or cancer. A large proportion of the risk of obesity is determined by the genetic susceptibility of an individual, but environmental factors conducive for the disorder play an important role in its phenotypic expression. Several candidate genes emerged from studies in animal models of obesity, but human pathophysiology is likely to be more complex. Thus, most cases of human obesity probably result from subtle interactions of susceptibility genes with environmental factors favouring deposition of excess calories as fat. The recent surge of obesity may relate to past evolutionary pressure which favoured selection of mechanisms defending body-weight against caloric restriction rather than against caloric excess. Rapidly developing new techniques in quantitative genetics and growing information from functional genomics will help to understand the interaction of environmental factors with signalling networks that regulate energy metabolism. The role of previously unknown pathways in the aetiology of obesity will be uncovered. The typing of numerous genetic variants will become possible and allow individual risk assessment for obesity and/or its associated disorders. Thus, rational and individually tailored therapies may be developed to combat obesity and its associated disorders.


An integrated model to study varietal diversity in traditional agroecosystems.
Agricultural diversity is one of the bases of traditional agroecosystems, having great environmental and cultural importance. The current loss of agricultural diversity is causing serious concern, mainly because of its essential role in supporting global and local food security. Stopping this loss requires a better understanding of how diversity is managed locally and what mechanisms sustain agricultural diversity. Here we propose a generalist agent-based model that couples biological, cultural, and social dynamics to obtain varietal diversity as an emergent phenomenon at the community level. With a mechanistic approach, we explore how four of the model dynamics can shape systems diversity. To validate the model, we performed a bibliographic review on Manihot esculenta and Zea mays case studies. The model yielded compatible results for manioc and maize varietal richness at both community and household levels.


Remote Michelson interferometric phase sensor based on dual-core fiber transmission and linear phase demodulation.
We present a remote Michelson interferometric phase sensor based on dual-core fiber transmission and linear phase demodulation. The former allows for synchronous transmission of both sensing signal and reference lights, enabling efficient suppression for the environmental disturbances along the transmission link and for the incoherent phase noise between the two lights. The latter is conducted by two optical phase-locked loops, one of which consists of a fiber stretcher that is used to eliminate the residual phase noises, thus stabilizing the operation point while the other relies on a phase modulator that is used to track the remote phase changes, thus achieving a highly linearized phase demodulation. A remote phase sensing over a 20 km fiber link with less than 3% nonlinear phase error over 3π range has been readily realized, corresponding to more than 10 times extension in a linear phase demodulation range. The proposed system shows great potential in the field of remote phase sensing for a variety of physical quantities.


Recommendations on the Use of Injectable Poly-L-Lactic Acid for Skin Laxity in Off-Face Areas
Injectable poly-L-lactic acid (PLLA) is a biodegradable synthetic polymer that stimulates collagen production, leading to gradual volume restoration. The treatment of sagging skin in body areas is still a big challenge, as there are few aesthetic procedures aiming to improve it. This article provides recommendations on the use of PLLA in the treatment of skin laxity in off-face areas, as the neck, décolletage, arms, abdomen, buttocks, and thighs, including the patient selection, product preparation, and injection techniques. The use of PLLA is a promising method for the treatment of skin laxity in corporal areas, improving body contour and appearance. Further investigation is needed to better understand the efficacy and durability of PLLA in non-facial indications and to provide the best evidence for optimal patient outcomes. J Drugs Dermatol. 2019;18(9):929-935.


Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty acyl-CoAs.
Them2 (thioesterase superfamily member 2) is a 140-amino-acid protein of unknown biological function that comprises a single hotdog fold thioesterase domain. On the basis of its putative association with mitochondria, accentuated expression in oxidative tissues and interaction with StarD2 (also known as phosphatidylcholine-transfer protein, PC-TP), a regulator of fatty acid metabolism, we explored whether Them2 functions as a physiologically relevant fatty acyl-CoA thioesterase. In solution, Them2 formed a stable homotetramer, which denatured in a single transition at 59.3 degrees C. Them2 exhibited thioesterase activity for medium- and long-chain acyl-CoAs, with Km values that decreased exponentially as a function of increasing acyl chain length. Steady-state kinetic parameters for Them2 were characteristic of long-chain mammalian acyl-CoA thioesterases, with minimal values of Km and maximal values of kcat/Km observed for myristoyl-CoA and palmitoyl-CoA. For these acyl-CoAs, substrate inhibition was observed when concentrations approached their critical micellar concentrations. The acyl-CoA thioesterase activity of Them2 was optimized at physiological temperature, ionic strength and pH. For both myristoyl-CoA and palmitoyl-CoA, the addition of StarD2 increased the kcat of Them2. Enzymatic activity was decreased by the addition of phosphatidic acid/phosphatidylcholine small unilamellar vesicles. Them2 expression, which was most pronounced in mouse heart, was associated with mitochondria and was induced by activation of PPARalpha (peroxisome-proliferator-activated receptor alpha). We conclude that, under biological conditions, Them2 probably functions as a homotetrameric long-chain acyl-CoA thioesterase. Accordingly, Them2 has been designated as the 13th member of the mammalian acyl-CoA thioesterase family, Acot13.


Preoperative computed tomography-guided localization for lung nodules: localization needle versus coil.
To compare the clinical efficacy of computed tomography (CT)-guided localization needle and coil insertion as approaches to preoperative lung nodule (LN) localization. Between January 2018 and December 2019, 52 patients awaiting video-assisted thoracoscopic surgery (VATS) resection underwent CT-guided coil insertion to facilitate LN localization. Additionally, 41 patients underwent CT-guided localization needle insertion between January and June 2021. In total, 62 and 54 LNs were localized in 52 and 41 patients in the coil and localization needle groups, respectively, with respective technical localization success rates of 96.8% and 100% (p = .498). The localization needle group exhibited a significantly shorter duration of localization relative to the coil group (p < .001), whereas comparable rates of pneumothorax (p = .918) and hemorrhage (p = .712) were evident in these groups. VATS-guided LN resection procedures achieved 100% technical success rates in both groups, and there were no significant differences between groups with respect to the type of resection (p = .113) or the mean duration of VATS (p = .778). Coil- and localization needle-based approaches can be successfully used for LN localization prior to VATS resection, with localization needle insertion being associated with a shorter duration of localization.


Intrinsic dynamics and topography of sensory input systems.
The brain is continuously bombarded by external stimuli, which are processed in different input systems. The intrinsic features of these sensory input systems remain yet unclear. Investigating topography and dynamics of input systems is the goal of our study in order to better understand the intrinsic features that shape their neural processing. Using a functional magnetic resonance imaging dataset, we measured neural topography and dynamics of the input systems during rest and task states. Neural dynamics were probed by scale-free activity, measured with the power-law exponent (PLE), as well as by order/disorder as measured with sample entropy (SampEn). Our main findings during both rest and task states are: 1) differences in neural dynamics (PLE, SampEn) between regions within each of the three sensory input systems 2) differences in topography and dynamics among the three input systems; 3) PLE and SampEn correlate and, as demonstrated in simulation, show non-linear relationship in the critical range of PLE; 4) scale-free activity during rest mediates the transition of SampEn from rest to task as probed in a mediation model. We conclude that the sensory input systems are characterized by their intrinsic topographic and dynamic organization which, through scale-free activity, modulates their input processing.


Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study.
Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.


Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons.
Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of mammalian brains. Among these neuron-enriched nRTKs, two Src family kinase members (Src and Fyn) are particularly abundant at synaptic sites and have been most extensively studied for their roles in the regulation of synaptic activity and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs interacts with a number of local substrates, including glutamate receptors (both ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins, presynaptic proteins, and synapse-enriched enzymes. By phosphorylating specific tyrosine residues in the intracellular domains of these synaptic proteins either constitutively or in an activity-dependent manner, nRTKs regulate these substrates in trafficking, surface expression, and function. Given the high sensitivity of nRTKs to changing synaptic input, nRTKs are considered to act as a critical regulator in the determination of the strength and efficacy of synaptic transmission.


Angiographic embolization for hemorrhage following pelvic fracture: Is it "time" for a paradigm shift?
Major pelvic disruption with hemorrhage has a high rate of lethality. Angiographic embolization remains the mainstay of treatment. Delays to angiography have been shown to worsen outcomes in part because time spent awaiting mobilization of resources needed to perform angiography allows ongoing hemorrhage. Alternative techniques like pelvic preperitoneal packing and aortic balloon occlusion now exist. We hypothesized that time to angiographic embolization at our Level 1 trauma center would be longer than 90 minutes. A retrospective review was performed of patients with pelvic fracture who underwent pelvic angiography at our trauma center over a 10-year period. The trauma registry was queried for age, sex, injury severity score, hemodynamic instability (HI) on presentation, and transfusion requirements within 24 hours. Charts were reviewed for time to angiography, embolization, and mortality. A total of 4712 patients were admitted with pelvic fractures during the study period, 344 (7.3%) underwent pelvic angiography. Median injury severity score was 29. Median 24-hour transfusion requirements were five units of red blood cells and six units of fresh frozen plasma. One hundred fifty-one patients (43.9%) presented with HI and 104 (30%) received massive transfusion (MT). Median time to angiography was 286 minutes (interquartile range, 210-378). Times were significantly shorter when stratified for HI (HI, 264 vs stable 309 minutes; p = 0.003), and MT (MT, 230 vs non-MT, 317 minutes; p < 0.001), but still took nearly 4 hours. Overall mortality was 18%. Hemorrhage (35.5%) and sepsis/multiple-organ failure (43.5%) accounted for most deaths. Pelvic fracture hemorrhage remains a management challenge. In this series, the median time to embolization was more than 5 hours. Nearly 80% of deaths could be attributed to early uncontrolled hemorrhage and linked to delays in hemostasis. Earlier intervention by Acute Care Surgeons with techniques like preperitoneal packing, aortic balloon occlusion, and use of hybrid operative suites may improve outcomes. Therapeutic study, level V.


[The new aspects of treatment of severe sepsis and septic shock].
The mortality rate of infection-induced organ dysfunction or hypoperfusion abnormalities due to severe sepsis and septic shock remains unacceptably high. The adequacy and speed of treatment administered in the first hours after syndrome develops influence outcome. Initial resuscitation, appropriate antimicrobial treatment, selection of optimal control methods, properties of fluid therapy, use of vasopressors and inotropic therapy, proper corticosteroid administration, value of the use of recombinant human activated protein C, and glucose control are the most important points newly evaluated for severe and septic shock management.


Evaluation of posttraumatic vasospasm, hyperaemia, and autoregulation by transcranial colour-coded duplex sonography.
Serial transcranial colour-coded duplex sonography (TCCS) was performed on 24 adult patients with severe head injury (GCS 8 or less). Flow velocities were obtained from the middle cerebral artery (MCA) and extracranial internal carotid artery (EICA). An autoregulation study was done using the transient hyperaemic response test, evidence of vasospasm (V-MCA greater than 100 cm/s and Lindegaard ratio more than 3) was found in nine patients (37%). Two of these developed non-contusion-related infarction and two others contusion-related infarction. This was significant (p < 0.05). Vasospasm started around day 2, reaching maximum around day 4 and persisting until the second week. Vasospasm was significantly associated with a poor outcome (p < 0.05). There was no correlation between the extent of SAH as seen on CT and vasospasm. Evidence of hyperaemia were observed in two patients (8%) and impaired autoregulation in seven patients (29%). Impaired autoregulation was significantly associated with development of hyperaemia (p < 0.05). TCCS studies permit a non-invasive evaluation of cerebral haemodynamics that will help in the management of head injured patients.


Stereoselective synthesis of pamamycin-607.
A macrodiolide antibiotic pamamycin-607 was synthesized by joining two hydroxy acid components. Three cis-2, 5-disubstituted tetrahydrofuran rings in the molecule were stereoselectively prepared by radical cyclization reactions of beta-alkoxyvinyl ketone intermediates and a beta-alkoxymethacrylate substrate. The key step of the synthesis is characterized by the predominant threo product formation in the radical cyclization reaction of a beta-alkoxymethacrylate intermediate.


Community prevention and alcohol retail access.
This paper describes the design, rationale and implementation of the Alcohol Access Component within the Community Trials Project of the Prevention Research Center. The Alcohol Access Component was to reduce the concentration or density of alcohol outlets in each experimental community by a combination of local zoning and land-use planning approaches which was an effect to occur over several years. During the time of this trial, local regulations of alcohol outlets and public sites for drinking were changed in all three experimental communities. The amount of such alcohol policy change exceeded the goals for this component.


Lane distortions in gel electrophoresis patterns.
Distortions effects were studied as a function of gel environment, apparatus design and buffer type. Outward lanes distortions pronounced in low conductivity buffers for both continuous buffer systems and stacking gels, were field strength dependent. In discontinuous buffer systems, the moving boundary of the Laemmli buffer system deformed depending on the environment. In the Michov buffer system, the high conductivity resolving gel surrounded by a low conductivity electrode buffer, displayed straight pathways until a field strength of 15 V/cm, permitting to obtain information about lanes distortions depending on the acrylamide matrix structure. A decreased ammonium persulfate concentration, e.g. to 0.03%, induced phase segregation in gels at low temperature during the run: a critical endpoint near 11 degrees C for a gel in the Michov buffer system under conditions of electrophoresis was supposed. Gel collapse resulted in inward deviations in the lanes of the pattern and also faint bands in the zones where the gel was retracted. Besides this effect of catalyst concentration, the inwardly distorted pattern depended on temperature, field strength, solvent and hydrolysis due to gel aging. Amendments for overcoming lane distortions are suggested.


Clinical Characteristics, Treatments, and Outcomes of Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA): Results from a Multicenter National Registry.
Diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) requires both clinical evidence of acute myocardial infarction (AMI) and demonstration of non-obstructive coronary arteries using angiography. We compared the clinical features, treatments, and three-year outcomes in patients with MINOCA and myocardial infarction with obstructive coronary artery disease (MI-CAD). We retrospectively analyzed data for 205,606 hospitalized patients with AMI. MINOCA was indicated as a working diagnosis in 6063 patients (2.94% of all AMI patients). For the control group we included 160,886 patients with MI-CAD. We evaluated the baseline characteristics, medication management options, outcomes, and readmission causes at 36 months follow-up. Patients in the MINOCA group were younger. Females constituted a greater proportion of patients in the MINOCA group when compared to MI-CAD patients. STEMI during admission was diagnosed less frequently in the MINOCA group when compared to the MI-CAD group. All-cause mortality at 12 months was higher in the MINOCA group (10.94% vs. 9.54%, p < 0.001). At 36 months, there was no difference in the all-cause mortality rates (MINOCA 16.18% vs. MI-CAD 14.93%, p = 0.081). All-cause readmission rates were lower in the MINOCA group when compared to the MI-CAD group at both 12 months (45.19% vs. 54.33%, p < 0.001) and 36 months follow-up (56.42% vs. 66.66%, p < 0.001). This is the first description of the clinical features, treatments, and three-year outcomes in a large population of Polish patients. The main finding of this study was a relatively low rate of MINOCA, with high rates of adverse events both at 12 and 36 months follow-up.


Marine zooplankton studies in Brazil: a brief evaluation and perspectives.
Marine zooplankton research in Brazil has been primarily descriptive, with most studies focusing on community structure analysis and related issues. The composition and spatial distribution of several taxonomic groups are currently well known, although less-abundant and small-sized taxa as well as initial stages of almost all species have received little attention. Some numerically important taxa such as heterotrophic protists, ctenophores, acoel turbellarians and ostracods remain virtually unstudied. Large sectors of the continental shelf have not been sampled in detail, particularly those areas influenced by the North Brazil Current (5 degrees N-15 degrees S). Zooplankton abundance and biomass in offshore waters have seldom been quantified, and information on the distribution and vertical migration of meso- and bathypelagic species are lacking. Additional faunistic assessments must target those less-studied taxa and geographical locations. However, priority in ecological studies should be given to process-oriented investigations aimed at understanding the mechanisms controlling zooplankton distribution, trophic interactions within pelagic food webs and production cycles in relation to the physical environment. An effort should be made to incorporate state-of-the-art sampling technology and analytical methods into future research projects.


Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?
Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg x kg(-1) x day(-1) or 0.5 mg x kg(-1) x day(-1) cortisol. In both studies, aldosterone was infused at 3 microg x kg(-1) x day(-1). In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg x kg(-1) x day(-1), and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg x kg(-1) x day(-1). In adrenalectomized ewes chronically replaced to 0.35 mg x kg(-1) x day(-1) cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg x kg(-1) x day(-1) cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg x kg(-1) x day(-1) were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.


Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test-retest reliability.
Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test-retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 ± 16.3 years (range 18-80) at the time of video recording. Inter-rater agreement was assessed with five raters and test-retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test-retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test-retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.


Enzymatic rate assay of creatinine in serum and urine.
A two-step method for assaying creatinine in serum and urine samples, suitable with automated analyzers, is reported. Reagent 1, for the first step, contains a blanking system [creatine amidinohydrolase (CRTase), urease, glutamate dehydrogenase, NADPH, and 2-oxoglutarate] and a NADPH-regenerating system [Mg(2+)-dependent isocitrate dehydrogenase (ICD), MgCl2, and excess isocitrate]. Reagent 2, for the second step, contains the metal-chelating reagent trans-1,2-cyclohexanediamine-N,N,N',N'-tetraacetic acid (CyDTA) and a trigger system [creatinine amidohydrolase (CRNase)]. When a specimen is mixed with reagent 1, all the creatine, urea, and NH3 present are removed by the blanking and NADPH systems. On adding reagent 2, CyDTA inactivates ICD to inhibit the NADPH system. Simultaneously, the creatinine (1 mol) in the specimen is hydrolyzed into creatine by CRNase, and then releases NADP+ (2 mol) through the blanking system. Our optimized method can determine creatinine linearly up to 500 mg/L, with within-day CVs < 1.2% and day-to-day CVs < 2.7%.


The effect of kangaroo care on pain in premature infants during invasive procedures.
A total of 50 premature infants (25 in KC group, 25 in control group) were included in this comparative, randomized, controlled study. Gestational and postnatal ages of the infants were between 26-36 weeks and 0-28 days, respectively. Infants with congenital abnormalities or sepsis and those who needed mechanical ventilation or surgical intervention were not included in the study. None of the infants received narcotic analgesics. Behavioral and physiologic responses to pain were recorded and Premature Infant Pain Profile (PIPP) was used to evaluate the severity of pain. Collected data was evaluated using SPSS for Windows 11.5 program. Premature Infant Pain Profile scores were significantly lower at each measurement during or soon after the invasive procedure in infants in the KC group compared to controls. In conclusion, KC starting 30 minutes before and continuing 10 minutes after an invasive procedure was found to be effective in decreasing pain during and after the invasive procedure in premature infants.


Health Risks of Flood Disasters.
Floods are the most common natural disaster occurring worldwide, with their impact expected to grow in the future due to the effects of climate change and population shift. Floodwaters pose immediate dangers to human health, but also long-term effects resulting from displacement and worsened living conditions. This review examines the health impact of flood disasters, including skin and soft-tissue infections, gastroenteritis, and zoonotic infections such as leptospirosis, and the impact on noncommunicable diseases and health infrastructure. Further work in the development of cost-efficient preparedness strategies may mitigate the morbidity and mortality associated with such natural disasters.


Ethyl Ferulate Suppresses Esophageal Squamous Cell Carcinoma Tumor Growth Through Inhibiting the mTOR Signaling Pathway.
Ethyl ferulate is a phenylpropanoid compound isolated from the medicinal herb Ferula. Although ethyl ferulate has anti-inflammatory, antioxidant, and neuroprotective activities with potential use in the nutraceutical and pharmaceutical industry, its anticancer effects and underlying molecular mechanisms against esophageal squamous cell carcinoma (ESCC) have not been investigated. This study investigates the anticancer activity and molecular mechanism of ethyl ferulate in ESCC. MTT, focus formation, soft agar, and cell cycle analysis were used to determine the effect of ethyl ferulate on cell proliferation and cell cycle. Potential candidate proteins were screened and verified via Western blotting, in vitro kinase assay, and in vitro pull-down assay. Mammalian target of rapamycin (mTOR) knockdown cell lines were established by lentiviral infection with shmTOR. The effect of ethyl ferulate on tumor growth was assessed using ESCC patient-derived xenograft models. Ethyl ferulate significantly inhibited cell growth and induced G1 phase cell cycle arrest in ESCC cells. Ethyl ferulate reduced the activity of mTOR in vitro. The inhibition of ESCC cell growth by ethyl ferulate is dependent on mTOR expression. In addition, ethyl ferulate strongly reduced ESCC patient-derived xenograft tumor growth in an in vivo mouse model. Ethyl ferulate is an mTOR inhibitor that can suppress ESCC progression and may be a novel candidate compound for esophageal cancer chemoprevention.


Hemodynamic effects of endothelin-1 in the newborn piglet: influence on pulmonary and systemic vascular resistance.
The aim of this study was to investigate the influence of endothelin-1 (ET-1) on the pulmonary and systemic circulations in newborn piglets. Twelve piglets (mean age of 6.8 days, range of 1-12 days) were anesthetized with chloralose-urethane and ventilated at FiO2 = 1.0. Animals were instrumented to measure cardiac output (CO), pulmonary artery pressure (PAP), aortic pressure (AoP), left atrial pressure (LAP), and right atrial pressure (RAP). Six piglets received a control saline injection into the pulmonary artery (PA), and six piglets received one injection of ET-1 (500 ng/kg) into the PA while PAP, AoP, LAP, RAP, CO, and heart rate (HR) were measured simultaneously at 20-s intervals with pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) calculated by computer. Administration of ET-1 into the PA led to (a) a transient decrease in mean PAP (delta max of -4 +/- 2 mm Hg, p less than 0.001); (b) a biphasic response (an initial decline followed by a substantial increase) in PVR (delta max of -760 +/- 460 dyn cm/s5, p less than 0.01, and delta max of +1,490 +/- 1,360 dyn cm/s5, p less than 0.05) and in AoP (delta max of -12 +/- 7 mm Hg, p less than 0.005, and delta max of +11 +/- 6 mm Hg, p less than 0.005); (c) an increase in SVR (delta max of +5,930 +/- 2,330 dyn cm/s5, p less than 0.05); and (d) an initial increase in CO (delta max of +0.06 +/- 0.03 L/min, p less than 0.05) followed by a decrease (delta max of -0.09 +/- 0.05 L/min, p less than 0.05). These responses have not been observed in adult species and may indicate a developmental difference in the response of the pulmonary circulation to ET-1 administration.


Impact of lactoferrin on bone regenerative processes and its possible implementation in oral surgery - a systematic review of novel studies with metanalysis and metaregression.
Lactoferrin is an iron - binding glycoprotein with anti-inflammatory and anabolic properties found in many internal fluids. It is worth looking at novel studies, because of their methodology and observations that may once be applicable in modern implantology. The aim of the study is to answer the question if lactoferrin is a promising factor for bone regenerative process in oral surgery. An electronic search was conducted on 14th October 2019 on the PubMed, Scopus and Web of Science databases. The keywords used in the search strategy were: lactoferrin AND bone regeneration AND oral surgery. The qualitative evaluation was conducted using the Jadad and Newcastle-Ottawa Quality Assessment Form. Then a metanalysis of a new bone growth and percentage of the resorbed graft were performed with the metaregression of lactoferrin dose to its outcome effects on bone regeneration. The search strategy identified potential articles: 133 from PubMed, 2 from Scopus, 4 from Web of science. After removal of duplicates, 136 articles were analyzed. Subsequently, 131 papers were excluded because they did not meet the inclusion criteria. The remaining 5 papers were included in the qualitative synthesis. The use of lactoferrin clearly increases the growth of a newly formed bone (2.58, CI:[0.79, 4.37]), as well as shortens the time of the graft resorption (- 1.70, Cl:[3.43, 0.03]) and replaces it with a species-specific bone. Heterogeneity is significant at p < 0.001 level. Metaregression indicates that one unit increase in the log (Treatment dose), i.e. a 2.78 times increase of the Treatment dose, results in an increase of the Effect size by 0.682. The use of lactoferrin both systemically and locally promotes anabolic processes (new bone formation). There is a relationship between the increase in administered dose of lactoferrin and the intensity of new bone formation. However, it is not only necessary to continue experimental research, but also to extend it to the clinical studies on patients, due to the limitations of different animal model research and different methodology, to introduce lactoferrin as a standard procedure for the treatment of bone defects, because it is a promising product.


Fuzzy Modelling for Human Dynamics Based on Online Social Networks.
Human mobility mining has attracted a lot of attention in the research community due to its multiple implications in the provisioning of innovative services for large metropolises. In this scope, Online Social Networks (OSN) have arisen as a promising source of location data to come up with new mobility models. However, the human nature of this data makes it rather noisy and inaccurate. In order to deal with such limitations, the present work introduces a framework for human mobility mining based on fuzzy logic. Firstly, a fuzzy clustering algorithm extracts the most active OSN areas at different time periods. Next, such clusters are the building blocks to compose mobility patterns. Furthermore, a location prediction service based on a fuzzy rule classifier has been developed on top of the framework. Finally, both the framework and the predictor has been tested with a Twitter and Flickr dataset in two large cities.


Conscientious objection and the referral requirement as morally permissible moral mistakes.
Some contributions to the current literature on conscience objection in healthcare posit the notion that the requirement to refer patients to a non-objecting provider is a morally questionable undertaking in need of explanation. The issue is that providing a referral renders those who conscientiously object to being involved in a particular intervention complicit in its provision. This essay seeks to engage with such claims and argues that referrals can be construed in terms of what Harman calls morally permissible moral mistakes. I go on to suggest that one might frame the (in)actions of those who exercise the right of non-participation generated by the claim to conscientiously object in similar terms; they can also be considered morally permissible moral mistakes. Finally, and given that the arguments already advanced involve simultaneously looking at the same issue from competing ethical perspectives, I offer some brief remarks that support viewing conscientious objection as an ethicopolitical device.


Suppressive impact of metronomic chemotherapy using UFT and/or cyclophosphamide on mediators of breast cancer dissemination and invasion.
Metronomic chemotherapy using the 5-FU prodrug uracil-tegafur (UFT) and cyclophosphamide (CTX) was previously shown to only modestly delay primary tumor growth, but nevertheless markedly suppressed the development of micro-metastasis in an orthotopic breast cancer xenograft model, using the metastatic variant of the MDA-MB-231 cell line, 231/LM2-4. Furthermore, a remarkable prolongation of survival, with no toxicity, was observed in a model of postsurgical advanced metastatic disease. A question that has remained unanswered is the seemingly selective anti-metastatic mechanisms of action responsible for this treatment. We assessed the in vivo effect of metronomic UFT, CTX or their combination, on vascular density, collagen deposition and c-Met (cell mediators or modulators of tumor cell invasion or dissemination) via histochemistry/immunohistochemistry of primary tumor sections. We also assessed the effect of continuous exposure to low and non-toxic doses of active drug metabolites 5-fluorouracil (5-FU), 4-hydroperoxycyclophosphamide (4-HC) or their combination, on 231/LM2-4 cell invasiveness in vitro. In the in vivo studies, a significant reduction in vascular density and p-Met[Y1003] levels was associated with UFT+CTX treatment. All treatments reduced intratumoral collagen deposition. In the in vitro studies, a significant reduction of collagen IV invasion by all treatments was observed. The 3D structures formed by 231/LM2-4 on Matrigel showed a predominantly Mass phenotype under treated conditions and Stellate phenotype in untreated cultures. Taken together, the results suggest the low-dose metronomic chemotherapy regimens tested can suppress several mediators of tumor invasiveness highlighting a new perspective for the anti-metastatic efficacy of metronomic chemotherapy.


The Association of Low Blood Glucose and Low Serum Cortisol Levels in Severely Ill Children Admitted to Tertiary Referral Hospitals in Malawi: A Case-Control Study.
Low blood glucose concentrations < 5 mmol/L in severely ill children presenting to hospitals in low-income countries are associated with mortality. Adrenal insufficiency with low cortisol levels may contribute to low blood glucose concentrations. Understanding the association between low cortisol and low blood glucose may assist in improving guidelines for management of severely ill children. The study aimed to determine the association between low serum cortisol and low blood glucose in severely ill children. A matched case-control study of children aged 1 month to 15 years was conducted at two tertiary hospitals in Malawi. Cases were children with blood glucose < 5 mmol/L. Two age-matched controls with blood glucose of ≥ 5-15 mmol/L were enrolled per case. Low cortisol was defined as serum cortisol of < 25 µg/dL (690 nmol/L) and adrenal insufficiency as serum cortisol of < 10 µg/dL (276 nmol/L). A total of 54 cases and 108 controls were enrolled with, median age of 2.8 years (interquartile range [IQR]: 1.7-4.4). The median cortisol level was 58.7 µg/dL (IQR: 42.3-61.8) in cases and 40.9 µg/dL (IQR: 33.7-51.2) in controls (P = 0.911). The proportion of low cortisol was 4/54 (7.4%) in cases and 9/108 (8.3%) in controls. Logistic regression shows no association between low cortisol and low blood glucose (adjusted odds ratio: 0.33; 95% confidence interval, 0.04-3.02). Results suggest that there is no association between low cortisol and low blood glucose among severely ill children presenting to hospitals in Malawi. The reason for low blood glucose needs further investigation.


[Heme-iron in the human body].
Iron is essential for all living organism, although in excess amount it is dangerous via catalyzing the formation of reactive oxygen species. Absorption of iron is strictly controlled resulting in a fine balance of iron-loss and iron-uptake. In countries where the ingestion of heme-iron is significant by meal, great part of iron content in the body originates from heme. Heme derived from food is absorbed by a receptor-mediated manner by enterocytes of small intestine then it is degraded in a reaction catalyzed by heme oxygenase. Iron released from the porphyrin ring leaves enterocytes as transferrin associated iron. Prosthetic group of several proteins contains heme, therefore, it is synthesized by all cells. One of the most significant heme proteins is hemoglobin which transports oxygen in the erythrocytes. Hemoglobin released from erythrocyte during intravascular hemolysis binds to haptoglobin and is taken up by cells of the monocyte-macrophage lineage. Oxidation of hemoglobin (ferro) to methemoglobin (ferri) is inhibited by the structure of hemoglobin although it is not hindered. Superoxide anion is also formed in the reaction that initiates further free radical reactions. In contrast to ferrohemoglobin, methemoglobin readily releases heme, therefore, oxidation of hemoglobin drives the formation of free heme in plasma. Heme binds to a plasma protein, hemopexin, and is internalized by cells of monocyte-macrophage lineage in a receptor-mediated manner, then degraded in reaction catalysed by heme oxygenase. Heme is also taken up by plasma lipoproteins and endothelial cells leading to oxidation of LDL and subsequent endothelial cell damage. The purpose of this work was to summarize the processes related to heme.


Increased sensitivity to normal adherent suppressor cells in untreated advanced Hodgkin's disease.
Mononuclear leukocytes isolated from the peripheral blood of 10 untreated patients with advanced stages of Hodgkin's disease and 26 normal volunteers were stimulated with allogeneic cells from normal donors in a one-way mixed lymphocyte culture. When the patients' cells were stimulated by an increased number of normal cells, the baseline mixed lymphocyte culture was suppressed 77.1% +/- 4.1%. In contrast, when the normal responder cells were cultured with increased numbers of normal stimulator cells, mean suppression was only 46.6% +/- 4.4% (p less than 0.001), The removal of phagocytic cells from the high concentration of normal stimulators totally abolished the suppression observed with the patients' cells, resulting in a mean increase in stimulation of 84% above that found in the baseline culture. The suppression could also be reversed by depletion of adherent cells from stimulator leukocytes. When adherent and nonadherent stimulator cells were recombined, significant suppression of proliferation was again observed. The increased suppression was not caused by the presence of autologous plasma in patients' cultures, since similar results were obtained utilizing AB serum. The addition of indomethacin to the cultures only partially reversed the suppression observed with the patients' cells. These studies demonstrates that mononuclear leukocytes from the peripheral blood of untreated patients with advanced stages of Hodgkin's disease have increased sensitivity to a normal adherent suppressor cell system.


The Key Comorbidities in Patients with Rheumatoid Arthritis: A Narrative Review.
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.


Flap Monitoring Using Transcutaneous Oxygen or Carbon Dioxide Measurements.
Free tissue transfer is a cornerstone of complex reconstruction. In many cases, it represents the last option available for a patient and their reconstruction. At high-volume centers, the risk of free flap failure is low but its occurrence can be devastating. Currently, the mainstay for flap monitoring is the clinical examination. Though reliable when performed by experienced clinicians, the flap exam is largely subjective, is performed discontinuously, and often results in significant time delay between detection of flap compromise and intervention. Among emerging flap monitoring technologies, the most promising appear to be those that rely on noninvasive transcutaneous oxygen and carbon dioxide measurements, which provide information regarding flap perfusion. In this article, we review and summarize the literature on various techniques but primarily emphasizing those technologies that rely on transcutaneous gas measurements. We also define characteristics for the ideal flap monitoring tool and discuss critical barriers, predominantly cost, preventing more widespread utilization of adjunct monitoring technologies, and their implications.


Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip.
An effective method is presented for the on-chip analysis of chiral interactions with a successful depression of nonspecific adsorption. The alumina gel-derived protein network on poly(methyl methacrylate) (PMMA) microchannel was explored to form a protein-stationary phase and then used to carry out electrophoresis for fast enantioseparation coupled with electrochemical detection. On the basis of the chemical modification of a synthesized copolymer containing silane-functionalized scaffold, alumina sol-gel could react readily with the silane groups and form steady microstructure on the chip surface achieving the encapsulation of functional biomolecules. Compared with the native PMMA microchannels, the modified surfaces exhibited much better wettability, more stable and enhanced electroosmotic mobility, and less nonspecific adsorption. The water contact angle and EOF of alumina-gel-derived PMMA substrate were 22 degrees and 4.3 x 10(-4) cm(2) V(-1) s(-1), compared to those of 73 degrees and 1.9 x 10(-4) cm(2) V(-1) s(-1) from the untreated one, respectively. Bovine serum albumin, acting as a target protein, could be stably and homogeneously immobilized in the modified PMMA microchannel to fabricate a protein-stationary phase. Under a mild condition, D- and L-tryptophan were efficiently separated with a resolution of 1.57. The as-prepared microchip can perform chiral separations within short time, indicating that the general protocol has the potential to provide a platform for high throughput screening of enantiomer candidates such as those biochemical drugs with protein targets and the research of receptor interactions.


Mass spectrometric studies of trimethylsilylpantothenic acid and related substances.
The characteristic fragment of trimethylsilylated pantothenic acid (TMS-PA) at m/z 291 upon electron ionization was shown to originate from the molecular ion by a McLafferty rearrangement instead of by ejection of 1,1,3,3-tetramethyl-1,3-disilacyclobutane. The verification consisted of labelling experiments and high-resolution mass spectrometry of the fragment and studies on its isotopic distribution. The remaining fragmentation pathways of TMS-PA were clarified by B/E-linked scans and collision-induced dissociation.


Comparison of tomosynthesis plus digital mammography and digital mammography alone for breast cancer screening.
To compare screening recall rates and cancer detection rates of tomosynthesis plus conventional digital mammography to those of conventional digital mammography alone. All patients presenting for screening mammography between October 1, 2011, and September 30, 2012, at four clinical sites were reviewed in this HIPAA-compliant retrospective study, for which the institutional review board granted approval and waived the requirement for informed consent. Patients at sites with digital tomosynthesis were offered screening with digital mammography plus tomosynthesis. Patients at sites without tomosynthesis underwent conventional digital mammography. Recall rates were calculated and stratified according to breast density and patient age. Cancer detection rates were calculated and stratified according to the presence of a risk factor for breast cancer. The Fisher exact test was used to compare the two groups. Multivariate logistic regression was used to assess the effect of screening method, breast density, patient age, and cancer risk on the odds of recall from screening. A total of 13 158 patients presented for screening mammography; 6100 received tomosynthesis. The overall recall rate was 8.4% for patients in the tomosynthesis group and 12.0% for those in the conventional mammography group (P < .01). The addition of tomosynthesis reduced recall rates for all breast density and patient age groups, with significant differences (P < .05) found for scattered fibroglandular, heterogeneously dense, and extremely dense breasts and for patients younger than 40 years, those aged 40-49 years, those aged 50-59 years, and those aged 60-69 years. These findings persisted when multivariate logistic regression was used to control for differences in age, breast density, and elevated risk of breast cancer. The cancer detection rate was 5.7 per 1000 in patients receiving tomosynthesis versus 5.2 per 1000 in patients receiving conventional mammography alone (P = .70). Patients undergoing tomosynthesis plus digital mammography had significantly lower screening recall rates. The greatest reductions were for those younger than 50 years and those with dense breasts. A nonsignificant 9.5% increase in cancer detection was observed in the tomosynthesis group.


Syphilis Testing among Men Who Have Had Rectal Gonorrhea and Chlamydia Tests, United States.
The Centers for Disease Control and Prevention (CDC) recommends syphilis screening at least annually for sexually active men who have sex with men (MSM). The objective of this study is to assess the frequency of MSM testing for syphilis and how syphilis test results compared with results of rectal gonorrhea and chlamydia tests. In collaboration with a large US commercial laboratory, we identified men aged 15-60 years who had rectal chlamydia or gonorrhea tests during 09/01/2013-09/30/2015 as presumed MSM. We classified MSM as having current or past syphilis if during the study period they had (1) either a reactive qualitative non-treponemal test or at least a 1:1 quantitative non-treponemal test, and (2) they had a reactive treponemal test. Of 52,771 MSM, 14.3% had no syphilis testing, 4.8% had only treponemal testing (37.8% were reactive), 63.2% had only non-treponemal testing (2.0% were reactive), and 17.7% had both non-treponemal and treponemal testing (86.6% had current or past syphilis). Of those MSM who had reactive qualitative non-treponemal tests, at least 90% had no quantitative non-treponemal tests. Current or past syphilis was more common among MSM with positive rectal gonorrhea or chlamydia tests (24.1%) than MSM with negative rectal gonorrhea and chlamydia tests (13.0%, p < 0.005). Of MSM with any syphilis testing during 09/01/2013-09/30/2014, 64.8% also had annual repeat testing. Syphilis testing in general and repeat syphilis testing were frequent but suboptimal among MSM. It is important to continually monitor syphilis for MSM, especially for those MSM who had rectal chlamydia or gonorrhea infection.


EVAR in Patients With Abdominal Aortic Aneurysm and Horseshoe Kidney: A Systematic Review.
A systematic review of all patients that have been reported in the literature with abdominal aortic aneurysm (AAA) concomitant with horseshoe kidney (HSK) treated electively by endovascular aneurysm repair (EVAR) is presented. A new grouping system for describing HSK vasculature is implemented. We searched for published manuscripts using the Medical Subject Headings terms "abdominal aortic aneurysm," "AAA," "EVAR," "endovascular aneurysm repair," and "horseshoe kidney" in PubMed, Google Scholar, Scopus, and National Center for Biotechnology Information databases. Inclusion criteria include all published material of patients with AAA with HSK treated electively by an endovascular approach. We excluded patients who were treated by a hybrid or open repair or patients with ruptured AAA. Statistical analysis was carried out using SPSS Statistics version 25 (IBM Corp, Armonk, New York) software. A total of 50 patients from 30 studies were included for analysis. Males made up 88% (n=44) of the population. The median age for this cohort was 70 years (range: 47-86 years). Median aneurysmal diameter was 6.0 cm (range: 4.0-10.3 cm). The median operative time for endovascular repair was 84 minutes (range: 40-332 minutes). The most common graft used was Zenith, used in 40% (n=20) of the cases, followed by Endurant in 14% (n=7). The overall complication rate was 14% (n=7). The median follow-up was 19 months (range: 1-108 months). While comorbidities did not appear to impact outcomes significantly, median operative times for smokers were higher than those in nonsmokers, 84 versus 118 minutes, respectively (p=0.048). Univariate linear regression modeling of aneurysmal size with age, operative time, and length of stay revealed a significant coefficient association between aneurysmal size and operative times. After adjusting for comorbidities and aneurysmal size, prior history of chronic kidney disease significantly increased odds for renal infarction. This review presents the most complete data set possible of patients with concomitant HSK and AAA treated by an endovascular approach. Furthermore, the A + B + C classification for grouping the HSK vasculature is implemented. This systematic review suggests EVAR to be an excellent option with low complication rates for the treatment of AAA in patients with HSK.


[Sodium butyrate inhibits HMGB1 expression and release and attenuates concanavalin A-induced acute liver injury in mice].
The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.


Environmental Causation of Turtle Scute Anomalies in ovo and in silico.
The turtle shell is often described as an evolutionary novelty that facilitated the radiation of the clade Testudines. The scutes, or keratinous plates, of the turtle shell are hypothesized to be patterned by reaction-diffusion dynamics, and this property of their development provides explanatory power to mechanisms of anomalous variation. A mathematical model of scute development predicts that anomalous variation in the phylogenetically stable pattern of scutes is achieved by environmental influence on the developmental program. We test this prediction with data on patterns of scute variation from natural nests and controlled incubation of sea turtle eggs in Florida and Western Australia. We find that high temperatures are sufficient to produce anomalous patterns in turtle scutes, and that this correlation is even stronger when conditions are dry. Furthermore, we find that the patterns of variation are not random; greater anomalous variation is found in the midline vertebral scutes and during a critical period of turtle development.


Chemesthesis and the chemical senses as components of a "chemofensor complex".
An important function of the chemical senses is to warn against dangerous biological and chemical agents in the environment. The discovery in recent years of "taste" receptor cells outside the oral cavity that appear to have protective functions has raised new questions about the nature and scope of the chemical senses in general and of chemesthesis in particular. The present paper briefly reviews these findings within the context of what is currently known about the body's chemically sensitive protective mechanisms, including nonsensory processes that help to expel or neutralize threatening agents once they have been encountered. It is proposed that this array of defense mechanisms constitutes a "chemofensor complex" in which chemesthesis is the most ubiquitous, functionally diverse, and interactive chemosensory component.


Safety and efficacy of indocyanine green near-infrared fluorescent imaging-guided lymph nodes dissection during radical gastrectomy for gastric cancer: A systematic review and meta-analysis.
Indocyanine green (ICG) fluorescence imaging has been a new surgical navigation technique for gastric cancer. However, its clinical value should still be evaluated further. In this meta-analysis, we investigated the safety and efficacy of ICG near-infrared fluorescent imaging-guided lymph nodes (LNs) dissection during radical gastrectomy. Studies comparing ICG fluorescence imaging with standard care in patients with gastric cancer were systematically searched from PubMed, Embase, Web of Science, and Cochrane Library through August 2021. The current meta-analysis was performed according to the preferred reporting items for systematic review and meta-analysis guidelines. A pooled analysis was performed for the available data regarding the number of LNs dissection, the number of metastatic LNs dissection, other operative outcomes, and postoperative complications. R software version 4.2.0 and Stata 16.0 software were used for the present meta-analysis. This analysis included 12 studies with a total of 1365 gastric cancer patients (569 in the ICG group and 796 in the non-ICG group). The number of retrieved LNs in the ICG group was significantly higher (weighted mean difference [WMD]=7.67, 95% confidence intervals [CI]: 4.73 to 10.62, P<0.05) compared to the non-ICG group with moderate heterogeneity (P<0.001, I2 = 70%). The number of metastatic LNs, operative time, and postoperative complications were all comparable and without significant heterogeneity. Additionally, ICG near-infrared fluorescent imaging was associated with reduced intraoperative blood loss (WMD=-10.28, 95% CI: -15.22 to -5.35, P<0.05) with low heterogeneity (P=0.07, I2 = 43%). ICG near-infrared fluorescent imaging-guided lymphadenectomy was considered to be safe and effective in gastrectomy. ICG was used to increase the number of LNs harvested while reducing intraoperative blood loss without increasing operative time or postoperative complications. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021291863.


Thalidomide for the treatment of acquired immunodeficiency syndrome-associated refractory oral ulcers.
A case of severe, oral, not otherwise specified ulcers in a human immunodeficiency virus-infected patient is described. The lesions did not respond to acyclovir, prednisone, pentoxifylline, or foscarnet sodium therapy. Dramatic clinical improvement and progressive ulcer healing were observed after starting oral thalidomide therapy. Clinicians should be aware of the usefulness of thalidomide for the treatment of acquired immunodeficiency syndrome-associated not otherwise specified ulcerations.


[Disseminated cryptococcosis during ibrutinib treatment for chronic lymphocytic leukemia].
We report a case of invasive fungal infection (IFI) that ensued during ibrutinib treatment. A 79-year-old female was diagnosed with chronic lymphocytic leukemia seven years prior. She had undergone chemotherapy at the ages of 72 and 75. Subsequently, she was placed on ibrutinib treatment at the age of 79. On the 119th day after the ibrutinib treatment initiation, she was admitted to our hospital with the complaints of frequent urination and hematuria, and three days later, she died of disseminated cryptococcosis.IFIs should be considered in the event of infections that develop early after the ibrutinib treatment initiation.


Terribacillus aidingensis sp. nov., a moderately halophilic bacterium.
Three Gram-positive, moderately halophilic bacteria, designated YI7-61(T), IA7 and DB2, were isolated from sediments of Aiding salt lake in the Xinjiang region of China. Cells of the strains were rod-shaped, motile by means of peritrichous flagella and produced ellipsoidal spores. Colonies were pale yellow in colour. The strains grew optimally at 30-37 °C, pH 6-7 and 3-7 % (w/v) NaCl. The diamino acid in the murein was meso-diaminopimelic acid and the major quinone system was MK-7. The major cellular fatty acids were anteiso-C(15 : 0) and anteiso-C(17 : 0). The DNA G+C content was 44.6-45.0 mol%. 16S rRNA gene sequence analysis revealed that strains YI7-61(T), IA7 and DB2 were closely related to members of the genus Terribacillus and showed 96.8-97.6, 96.4-97.2 and 95.4-95.5 % 16S rRNA gene sequence similarity with Terribacillus halophilus 002-051(T), Terribacillus saccharophilus RB589 and Terribacillus goriensis CL-GR16(T), respectively. DNA-DNA relatedness among the isolates was 88-92 % and strain YI7-61(T) shared 24, 18 and 18 % DNA-DNA relatedness with T. halophilus JCM 21760(T), T. saccharophilus JCM 21759(T) and T. goriensis DSM 18252(T), respectively. On the basis of phenotypic and phylogenetic distinctiveness, the three isolates should be placed in the genus Terribacillus as representatives of a novel species, for which the name Terribacillus aidingensis sp. nov. is proposed. The type strain is YI7-61(T) (=CGMCC 1.8913(T) =NBRC 105790(T)).


One-pot syntheses of pseudopteroxazoles from pseudopterosins: a rapid route to non-natural congeners with improved antimicrobial activity.
Rapid one-pot methodologies to prepare pseudopteroxazole (1) and novel congeners from abundant natural pseudopterosins have been devised. This is highlighted here with the first synthesis of the marine natural product homopseudopteroxazole (2) utilizing a novel, silver(I)-mediated catechol to benzoxazole transformation. Pseudopteroxazoles and isopseudopteroxazoles exhibit potent activity against a range of important Gram-positive pathogens including Mycobacterium spp. and vancomycin-resistant Enterococcus faecium. Several non-natural pseudopteroxazoles exhibited strong activity against methicillin-resistant Staphylococcus aureus, thereby displaying a broader spectrum of antibiotic activity compared to pseudopteroxazole.


Zinc increases ciliary beat frequency in a calcium-dependent manner.
Dynamic regulation of respiratory ciliary beat frequency (CBF) is regulated by fluxes in intracellular calcium (Ca(2+)). P2X receptors (P2XR) are extracellular ATP-gated, Ca(2+)-permeable, nonselective cation channels. Zinc increases intracellular Ca(2+) in a sodium (Na(+))-free environment through activation of P2XR channels. We hypothesize that topical zinc increases CBF in a Ca(2+)-dependent fashion as a result of this mechanism. The apical surface of mouse sinonasal air-liquid interface cultures were bathed in zinc in a Na(+)-free solution with or without Ca(2+). High-speed digital video imaging captured and analyzed CBF at a sampling rate of 100 frames/s. CBF significantly increased fourfold over baseline from 5.99 +/- 3.16 Hz to 22.4 +/- 4.33 Hz in the presence of zinc chloride (50 micromoles) and calcium chloride (3 mM). This effect is abolished in the presence of extracellular Na(+) and was pH dependent. Zinc stimulates CBF in the presence of Ca(2+) likely through activation of P2X receptors. Thus, zinc represents a promising agent for stimulation of mucociliary clearance.


Nudging in Animal Disease Control and Surveillance: A Qualitative Approach to Identify Strategies Used to Improve Compliance With Animal Health Policies.
Professionals from seven European countries were interviewed to identify strategies used in the surveillance and control of animal infections to influence behaviors such as program enrollment, adoption of biosecurity measures, and engagement in surveillance. To find strategies that were well-designed from a theoretical perspective, three frameworks from nudge theory were applied to the strategies: the Nuffield ladder to determine the strength of the interventions, EAST to identify attributes of the strategies, and MINDSPACE to identify the psychological mechanisms involved. We found that almost two thirds (91/120) of the strategies were designed in a manner likely to trigger multiple psychological mechanisms, which is in line with the existing recommendations for successful effect, i.e., achieving a desired behavior. This was despite that the design of the strategies was based on professionals' empirical understanding of the requirements to achieve anticipated outcomes rather than the systematic use of methods from the behavioral sciences and psychology. The most commonly used strategy was provision of information, and the least used mechanism was making a desired behavior easy to perform. The findings in this study, with all the examples of strategies used, can serve as inspiration for others. The theoretical frameworks may also be beneficial to apply as a complement in future design of new strategies. This study did not include evaluation of how efficient different strategies have been, which would be an interesting area for future studies.


Quick method for mean frontal QRS axis determination.
ECGs are the recording of the electrical activity of the heart. The direction of it's current in the frontal plane can be determined by analyzing the QRS direction and magnitude in limb leads. Several methods for determination of the QRS frontal axis have been proposed, however most of them require memorization of the exact location of the leads in the frontal plane with pen and paper calculations. a new method of estimating the frontal mean QRS axis in the standard 12 lead ECG is proposed. This method consists of assigning pre-determined values to each frontal lead in ECGs, which have a positive or isoelectric QRS complexes in lead, I. The mnemonic "+/- 90, -30, +30, -60, +60, and 0" is obtained by plotting only the value of the axis which is perpendicular to the each lead on the left side of the hexaxial system. The right-sided perpendiculars are not considered since lead I indicates a left sided axis. The most isoelectric lead will have only one value plotted and that will be the mean QRS axis in the frontal plane. By finding the most equiphasic lead(s) and matching the corresponding pre-determined value we can estimate the frontal mean QRS axis in most of the cases. Interpolation between two leads is allowed if no single isoelectric lead is identified. We reviewed the standard 12 lead electrocardiograms of 155 patients who underwent open-heart coronary revascularization procedures at the VA Caribbean Health Center from 2003 to 2006. Frontal mean QRS axis was determined by the proposed new methodology and the results were compared to the QRS axis determined by the GE Marquette 5000 electrocardiographer utilized in all the reviewed ECG's. Simple regression analysis was used to determine the proposed methods predictive accuracy. We obtained a high coefficient of determination R2= 0.9505, p<0.001. The derived linear equation was obtained as follow: y = 1.0007 + 0.9580x (Where independent x= QRS axis estimated by the new method, dependent y = QRS axis estimated by ECG machine). The proposed new method is simple and is able to estimate accurately the ECG frontal axis as compared with the GE Marquette 5000 electrocardiographer in most of the cases.


Wheel-like Magnetic-Driven Microswarm with a Band-Aid Imitation for Patching Up Microscale Intestinal Perforation.
Microscale intestinal perforation can cause considerable mortality and is very difficult to treat using conventional methods owing to the numerous challenges associated with microscale operations, which require the development of new body-friendly and effective treatment methods. Swarming micro- and nanomotors have shown great potential in biomedical applications in complex and hard-to-reach environments. Herein, we present a wheel-like magnetic-driven microswarm (WLM) with a band-aid imitation to patch microscale intestinal perforations by pasting on the perforation point in mucus-filled environments. A method called "packing under rolling" was applied to make the formed microswarms denser and rounder. Microswarms with variable aspect ratios can be fabricated by tuning the frequency and strength of the external magnetic field. Actuation and navigation in a confined complex environment, locomotion on three-dimensional surfaces, and multiple switchable motion modes have been realized by combining AC and DC magnetic fields. Moreover, we demonstrated WLM controllable navigation, movement, and microscale perforation patching in the chicken intestines ex vivo. The proposed strategy will contribute to the treatment of microscale intestinal perforation and may be applicable to novel, precise topical medication and microsurgery.


Comparison of demographic and defect characteristics among different developmental stages of congenital limb reduction defects.
This study investigates how the timing of the development of limb reduction defects (LRDs) is associated with selected demographic, medical variables and defect characteristics. The LRD cases (n = 281) were ascertained from the Congenital Malformations Registry of New York State among 1983-1987 births. Cases were classified according to five stages of gestation based on when their earliest LRD developed. A control group consisted of a systematic random sample (n = 327) of non-malformed livebirths. Demographic and LRD characteristics were abstracted from birth certificates and medical charts. Among LRDs, the defects that occurred in the earlier stages of gestation were found to be more complex problems, compared with those developing in the later stages. Middle or late stage LRDs tended to occur more often with syndactyly than early stage LRDs, and had significantly higher frequencies of non-white infants compared with controls. In addition, some perinatal complications, pre-term delivery and low birthweight were positively associated with any LRD. Our findings suggest that the timing of a disturbance in limb development is important in terms of LRD characteristics. Demographics did not vary consistently with the stage of LRD development. Further studies testing this classification technique are suggested.


Influenza pneumonia.
Influenza A and B viruses exhibit frequent minor antigenic drift and type A viruses undergo a major antigenic shift every one to four decades, thus assuring that at least a portion of the population is always susceptible. Children and young adults have the highest incidence of influenza infection each winter, but the highest incidences of severe or complicated influenza illness leading to hospitalization or death are in infants, elderly persons (especially those in nursing homes), and persons of all ages with underlying heart or lung disease. Influenza viruses infect respiratory epithelial cells and can themselves cause diffuse pulmonary infiltrates and severe hypoxia, but concomitant or secondary bacterial pneumonia is a much more frequent complication of influenza. Although pneumococci predominate in these secondary pneumonias, the relative incidence of Staphylococcus aureus pneumonia also increases during influenza epidemics; empiric antibiotic therapy in this setting should be directed against both of these organisms. A variety of other bacteria can cause postinfluenzal pneumonia, especially in patients with alcoholism or chronic obstructive pulmonary disease, and broad antimicrobial coverage including gram-negative bacteria is justified in such patients when diagnostic studies provide no guidance. Early amantadine therapy of influenza-like illness during an influenza A epidemic will reduce the duration of symptoms and possibly reduce complications. Successful therapy of influenza virus pneumonia with ribavirin aerosol has been reported but not yet officially approved. Annual vaccination of persons at greatest risk for severe or complicated influenzal disease will reduce the morbidity and mortality due to this infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Transport of drugs in the kidney by the human organic cation transporter, OCT2 and its genetic variants.
The human organic cation transporter 2 (OCT2, SLC22A2) is a multispecific transporter of organic cations, including many clinically used drugs. OCT2 is primarily responsible for the uptake of organic cations across the basolateral membrane of renal tubular epithelial cells and is considered a major transporter in the active secretion of organic cations in the kidney. Uptake of organic cations by OCT2 is driven by the inside-negative membrane potential and is pH-sensitive. Regulation of OCT2 at the transcriptional level by steroid hormones and at the protein level by various protein kinases has been described. Several human genetic variants in the coding region of OCT2 have been identified and functionally characterized, including both polymorphic and rare variants. A variety of structurally diverse compounds have been shown to interact with OCT2, including endogenous compounds, drugs, and dietary supplements.


Polio health economics: assessing the benefits and costs of polio, non-polio, and integrated activities of the Global Polio Eradication Initiative.
Background: Investments made by countries and donors to support polio eradication and the Global Polio Eradication Initiative (GPEI) over the past 35 years provided financial support for significant health interventions beyond the prevention of polio. Prior economic analyses that sought to quantify the economic benefits of some interventions encountered insufficient data and evidence associated with non-polio-specific activities. The 2022-2026 GPEI Strategic Plan explicitly identified integration and gender equity as funded mandates that must move forward in parallel with polio eradication, but these goals remain vaguely defined from a health economic perspective. Methods: To ensure unambiguous and full accounting for all financial investments in the GPEI, polio eradication, and other desirable objectives, we identify the health economic analysis methods and inputs needed to ensure transparent financial accountability and cost-effective use of funds. Results: Sufficient inputs and methods exist to characterize the health and economic benefits of polio-specific activities, but we identified the need for additional information and method development for some non-polio-specific and cost-sharing activities. Donors who seek to support non-polio-specific objectives as part of the GPEI may want to provide dedicated support financing for which it may be difficult to apply typical health economic criteria and to expect net health and/or net economic benefits. Conclusions: Given the mixture of funding sources provided to the GPEI, which includes support by governments and private donors, we recommend that the GPEI separately account for financial needs that represent necessities for polio eradication from those used for other stated objectives. An added layer of specificity that identifies all funds according to each activity, the accountable party and/or parties, and the associated measurable health or other outcome(s), will enable improved health economic analyses and reporting to donors who seek to track returns on their investments.


Infection control 101.
Healthcare professionals in dialysis must provide safe, quality care, including the use of basic infection control practices when caring for immunocompromised patients on dialysis. These practices are not new, and for most, are integrated into the routine provision of dialysis care. The challenge within the existing time constraints is to make sure routine practices do not lapse into shortcuts around infection control practices. This article reviews basic infection control as a reminder of its importance in the daily provision of health care.


Phospholipases Involved in Activation of the Neutrophil NADPH Oxidase
Stimulation of neutrophils with a variety of stimuli can result in the activation of phospholipases A2, C, or D with the resultant hydrolysis of plasma membrane phospholipids and the formation of important second messenger molecules. In the neutrophil, the activities of these phospholipases have been implicated in the processes of both stimulating and maintaining oxidase activation. In this review, some of the methods currently used to measure the products of phospholipase activation in the neutrophil are described, along with the possible role of their products in reactive oxidant production by the neutrophil NADPH oxidase.


The high prevalence of pathologic calcium crystals in pre-operative knees.
Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals are important in the pathogenesis of osteoarthritis (OA) but are under recognized even in end stage disease. We determined the prevalence of these calcium crystals in synovial fluid (SF) of persons undergoing total knee arthroplasty for degenerative arthritis. SF samples were obtained from 53 knee joints undergoing total arthroplasty for a pre-operative diagnosis of OA. SF were analyzed via compensated light microscopy for CPPD crystals and a semiquantitative radiometric assay for BCP crystals. Fifty pre-operative radiographs were analyzed and graded according to the scale of Kellgren and Lawrence. Patients had an average age of 70 years at the time of surgery. CPPD and/or BCP crystals were identified in 60% of SF. Overall radiographic scores correlated with mean concentrations of BCP crystals. Higher mean radiographic scores correlated with the presence of calcium-containing crystals of either type in SF Radiographic chondrocalcinosis was identified in only 31% of those with SF CPPD. Pathologic calcium crystals were present in a majority of SF at the time of total knee arthroplasty. Intraoperative SF analysis could conveniently identify pathologic calcium crystals providing information that may be relevant to the future care of the patient's replaced joint and that of other joints. This information could also potentially aid in predicting the likelihood of the need for contralateral total knee arthroplasty.


Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure.
An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6-12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.


Effect of residual ascorbate on determination of nitrite in commercial cured meat products.
Residual ascorbate in cured meat slurries results in different amounts of pigment being produced from different Griess reagent combinations. The phenomenon was used to study residual ascorbate in commercial cured meat products which had a variety of textures, acidities, moisture and meat content, fat, homogeneity, initial nitrite, and processing conditions. Diluting and heating the samples according to the AOAC procedure did not completely eliminate the ascorbate interference, but making the sample alkaline did. Determining nitrite separately in supernate and precipitate from the first dilution showed the effect of heating to be the elimination of interferences and solubilization or extraction of nitrite from the precipitate.