Delayed administration of antibiotics and atypical presentation in community-acquired pneumonia.
The time to the first antibiotic dose (TFAD) has been adopted as a measure of quality of care in patients with community-acquired pneumonia (CAP) based on two retrospective studies of large Medicare databases. The mechanism by which a difference of a few hours in receiving antibiotics can be deleterious is difficult to understand given the historical data regarding how long it takes for antibiotics to influence outcome. We investigated the factors that predict a prolonged TFAD and their association with mortality. Prospective cohort study. A large tertiary hospital. Immunocompetent adults admitted to the hospital with CAP. A total of 451 patients with CAP were studied. A TFAD of > 4 h was associated with increased mortality (p = 0.017). Altered mental state (p = 0.001), absence of fever (p = 0.02), absence of hypoxia (p = 0.025), and increasing age (p = 0.038) were significant predictors of a TFAD of > 4 h. After adjusting for these factors, the association between TFAD and mortality was not statistically significant (p = 0.131). Similar findings were observed in patients who were > or = 65 years. A delay in administering antibiotics in patients with CAP is more common in patients who present with an altered mental state or minimal signs of sepsis. TFAD is likely to be a marker of comorbidities driving both an atypical presentation and mortality rather than directly contributing to outcome. Using TFAD as an indicator of quality of care in patients with CAP without significant additional clinical information is potentially misleading as the relationships among TFAD, comorbidities, and outcome are complex.


[Chagasic cardiomyopathy in Mexico].
Chronic Chagas disease, has been reported in Mexico, but changes in left ventricular function are not well known. We describe 25 patients with chronic trypanosomiasis with congestive cardiomyopathy. All of them lived in zones where the parasitosis is endemic and showed EKG abnormalities compatible with cardiomyopathy: A-V block in 8, RBBB in 9, LBBB in 7, RBBB + LAHB in 4, arrhythmias and ST-S abnormalities in 9 patients. All patients have at least one positive serological test for T Cruzi: indirect haemagglutination in 9, counterimmunoelectrophoresis in 9, complement fixation in 14 and passive agglutination of Latex sensitized beads in 4. The parasite was found by xenodiagnosis in 4 out of 5 cases. All cases had a normal coronary arteriography. The left ventriculography showed hypokinesia or akinesia of the apical, anterolateral and diaphragmatic segments in 8 patients and apical dyskinesia in 2. The ejection fraction varied from 22.3% to 51.6% with a mean of 39%. Chagas disease is a health problem in Mexico and the patients who are hospitalized present severe cardiac involvement.


Selection of method is crucial for the diagnosis of porcine circovirus type 2 associated reproductive failures.
During a 2-month period a newly repopulated Danish pig herd experienced an increase in numbers of stillborn and mummies, caused by porcine circovirus type 2 (PCV2) associated reproductive failure. Based on recordings of data over time, the progression of the clinical outbreak was studied and the diagnostic value of different techniques was evaluated. Foetal hearts (38 cases and 13 controls) were examined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) for the detection of PCV2; and total immunoglobulin G (IgG) was measured in pleura cavity fluid. PCV2 IHC was positive in 14/38 of the case foetuses, which were delivered during a 9 days period early in the outbreak. On the basis of the results obtained by IHC and PCR, the foetuses were divided into 3 categories: PCV2 negative; moderately positive (10(4) to 10(7) copies per 500 ng DNA); and massively positive for PCV2 (>10(7) copies per 500 ng DNA). All control- and IHC positive foetuses were included in the negative and massively positive groups, respectively. Ten case foetuses had elevated IgG levels, which did not correlate with the IHC or PCR results. Based on the clustering of the IHC positive foetuses, it is suggested that IHC only is suited for diagnosing acute stages of reproductive failure, whereas quantitative PCR can be used as a sensitive diagnostic method within a wider time span. It seems that IgG measurements are unpredictable as indication of intrauterine infection with PCV2.


Distribution of the fittest individuals and the rate of Muller's ratchet in a model with overlapping generations.
Muller's ratchet is a paradigmatic model for the accumulation of deleterious mutations in a population of finite size. A click of the ratchet occurs when all individuals with the least number of deleterious mutations are lost irreversibly due to a stochastic fluctuation. In spite of the simplicity of the model, a quantitative understanding of the process remains an open challenge. In contrast to previous works, we here study a Moran model of the ratchet with overlapping generations. Employing an approximation which describes the fittest individuals as one class and the rest as a second class, we obtain closed analytical expressions of the ratchet rate in the rare clicking regime. As a click in this regime is caused by a rare, large fluctuation from a metastable state, we do not resort to a diffusion approximation but apply an approximation scheme which is especially well suited to describe extinction events from metastable states. This method also allows for a derivation of expressions for the quasi-stationary distribution of the fittest class. Additionally, we confirm numerically that the formulation with overlapping generations leads to the same results as the diffusion approximation and the corresponding Wright-Fisher model with non-overlapping generations.


[Smoking in the workplace: role of occupational physicians].
In many industrialized countries smokers have been observed in high prevalence among workers with poor educational status, who are usually exposed to major occupational risks. The smoking habit and passive smoking may by themselves, or through interactions with other occupational risk factors, cause the onset of serious diseases. Therefore health reasons and the legal obligation to observe the smoking ban in the workplace make it essential to prevent and combat smoking in the workplace and to promote smoking cessation in workers who smoke. This initiative should benefit not only workers' health and well-being but also company finances. The Occupational Physician should engage in diverse activities ranging from encouraging young people not to start smoking to providing programmes to encourage workers who smoke to abandon the habit. For example, he or she should i) inform managers, supervisors and workers about the high risks linked to smoking, passive smoking and obligations established by law ii) collect information about the smoking habit among workers and supply workers with the so-called minimal clinical intervention during routine health surveillance appointments and iii) collaborate with specific health promotion programmes in the workplace.


Energy dissipation in multichromophoric single dendrimers.
Single-molecule spectroscopy of well-chosen dendritic multichromophoric systems allows investigation of fundamental photophysical processes such as energy or electron transfer in much greater detail than the respective ensemble measurements. In dendrimers with multiple chromophores, energy hopping and transfer to the chromophore with the energetically lowest S(1) state was observed. If more than one chromophore is in an excited state in one molecule, annihilation, either singlet-triplet or singlet-singlet, can occur. In the latter case, a higher singlet state is populated opening new deactivation pathways. In the presence of an electron donor, reversible electron transfer could be observed, and the rate constants of forward and backward electron transfer were established. The value of these rate constants fluctuates time-correlated with the rotational motion of the dendrimer arms and the mobility of the embedding matrix.


Effect of differing immunization policies on circulating measles antibody levels in US and Canadian children.
To examine the effect of differing age-at-immunization policies on measles antibody levels in US children immunized at the age of 15 months compared with Canadian children immunized at the age of 12 months. Healthy, volunteer US and Canadian children aged 6 to 11 years who had been immunized with a single dose of the measles vaccine were enrolled from 1991 to 1993. Measles antibody was measured with a whole-virus, measles-specific IgG enzyme-linked immunoassay. Age, race, sex, country of residence, general health status, age at time of measles immunization, and time from immunization to sampling were recorded. Of the 1052 children enrolled in the study, US children (n=719) had a significantly higher measles seroprevalence (87%) compared with Canadian children (n=333) (76%; P<.001). After adjustment for time from immunization and age at immunization, the differences in seropositive rates were no longer significant (odds ratio [OR], 1.53; 95% confidence interval, 0.87-2.69; P=.15). We found a significant dose-response relationship between age at the time of immunization and the odds of being seropositive after immunization, with ORs varying from 1 with immunization at 13 months or younger to 2.30 with immunization at 16 months of age (P=.01). The current US policy of immunizing with the first dose of measles at the age of 12 months may be less effective than a policy of immunizing at 12 to 15 months of age. These findings may be highly significant as we move toward an era in which measles exposure may be rare and policies are developed to eradicate measles.


Developmental changes in face processing skills.
Expertise in processing differences among faces in the spacing among facial features (second-order relations) is slower to develop than expertise in processing the shape of individual features or the shape of the external contour. To determine the impact of the slow development of sensitivity to second-order relations on various face-processing skills, we developed five computerized tasks that require matching faces on the basis of identity (with changed facial expression or head orientation), facial expression, gaze direction, and sound being spoken. In Experiment 1, we evaluated the influence of second-order relations on performance on each task by presenting them to adults (N=48) who viewed the faces either upright or inverted. Previous studies have shown that inversion has a larger effect on tasks that require processing the spacing among features than it does on tasks that can be solved by processing the shape of individual features. Adults showed an inversion effect for only one task: matching facial identity when there was a change in head orientation. In Experiment 2, we administered the same tasks to children aged 6, 8, and 10 years (N=72). Compared to adults, 6-year-olds made more errors on every task and 8-year-olds made more errors on three of the five tasks: matching direction of gaze and the two facial identity tasks. Ten-year-olds made more errors than adults on only one task: matching facial identity when there was a change in head orientation (e.g., from frontal to tilted up). Together, the results indicate that the slow development of sensitivity to second-order relations causes children to be especially poor at recognizing the identity of a face when it is seen in a new orientation.


Limbic system plasticity after electroacupuncture intervention in knee osteoarthritis rats.
Knee osteoarthritis (KOA) is characterized by debilitating pain. Electroacupuncture (EA), a traditional Chinese medical therapy, has shown promise in KOA pain management. This study investigated the therapeutic potential of EA in KOA and its impact on limbic system neural plasticity. Sixteen rats were randomly assigned into two groups: EA group and sham-EA group. EA or sham-EA interventions were administered at acupoints ST32 (Futu) and ST36 (Zusanli) for three weeks. Post-intervention resting-state fMRI was scanned, assessing parameters including Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and nodal characterizations of network within limbic system. The results showed that EA was strategically directed towards the limbic system, resulting in discernible alterations in neural activity, FC, and network characteristics. Our findings demonstrate that EA had a significant impact on the limbic system neural plasticity in rats with KOA, presenting a novel nonpharmacological approach for KOA treatment.


Excited state dynamics and time-resolved photoelectron spectroscopy of para-xylylene.
We investigated the excited-state dynamics of para-xylylene using a combination of field-induced surface hopping (FISH) simulations and time-resolved ionisation experiments. Our simulations predict an ultrafast decay of the initially excited bright state (S2/S3) to the S1 state on a sub-100 fs time scale, followed by return to the ground state within ∼1 ps. This is accompanied by a transient change of the biradical character of the molecule, as monitored by calculating natural orbital occupation numbers. Specifically, the initially low biradicality is increased by electronic excitation as well as by vibrational activation. Experimentally, para-xylylene was generated by pyrolysis from [2,2]paracyclophane and excited with 266 nm radiation into the S2/S3 bright state. The subsequent dynamics were followed using ionisation as the probe step, with both mass spectra and photoelectron spectra recorded as a function of pump-probe delay. The observed decay of photoelectron and photoion intensities closely matches the theoretical predictions and is consistent with the sequential mechanism found in the simulations. This mechanism exhibits characteristic signatures in both time-resolved mass and photoelectron spectra, in particular in the appearance of fragment ions that are exclusively generated from the S1 state. This allows for a separation of the S2 and S1 dynamics in the photoelectron and mass spectra. An excellent agreement between the observed and the simulated ion signal is observed.


Calcium Signaling Is Dispensable for Receptor Regulation of Endothelial Barrier Function.
Endothelial barrier function is tightly regulated by plasma membrane receptors and is crucial for tissue fluid homeostasis; its dysfunction causes disease, including sepsis and inflammation. The ubiquitous activation of Ca2+ signaling upon phospholipase C-coupled receptor ligation leads quite naturally to the assumption that Ca2+ signaling is required for receptor-regulated endothelial barrier function. This widespread hypothesis draws analogy from smooth muscle and proposes the requirement of G protein-coupled receptor (GPCR)-generated Ca2+ signaling in activating the endothelial contractile apparatus and generating interendothelial gaps. Notwithstanding endothelia being non-excitable in nature, the hypothesis of Ca2+-induced endothelial contraction has been invoked to explain actions of GPCR agonists that either disrupt or stabilize endothelial barrier function. Here, we challenge this correlative hypothesis by showing a lack of causal link between GPCR-generated Ca2+ signaling and changes in human microvascular endothelial barrier function. We used three endogenous GPCR agonists: thrombin and histamine, which disrupt endothelial barrier function, and sphingosine-1-phosphate, which stabilizes barrier function. The qualitatively different effects of these three agonists on endothelial barrier function occur independently of Ca2+ entry through the ubiquitous store-operated Ca2+ entry channel Orai1, global Ca2+ entry across the plasma membrane, and Ca2+ release from internal stores. However, disruption of endothelial barrier function by thrombin and histamine requires the Ca2+ sensor stromal interacting molecule-1 (STIM1), whereas sphingosine-1-phosphate-mediated enhancement of endothelial barrier function occurs independently of STIM1. We conclude that although STIM1 is required for GPCR-mediated disruption of barrier function, a causal link between GPCR-induced cytoplasmic Ca2+ increases and acute changes in barrier function is missing. Thus, the cytosolic Ca2+-induced endothelial contraction is a cum hoc fallacy that should be abandoned.


[Nursing activities in self-care and rehabilitation of patients who suffered stroke].
There can be serious damage to motor, sensatory, and perceptive capabilities when the brain suffers vascular alterations. With this in mind, the objective of this study is to report and share Nursing care to the individual who has suffered a cerebral vascular accident, emphasizing Orem-based rehabilitation and self-care. This study is a report of a practical care experiment, carried out in May and July of 2006 involving 15 individuals and their families in a rehabilitation center in southern Brazil. Integral Nursing care occurs with stimulation to sensatory, motor, postural control, movement amplitude, and marching practice activities when accompanied by health care education actions. These abilities grant nurses performance capacities, in turn proportioning reductions in damage and incapacities.


Objectively measured physical activity in a diverse sample of older urban UK adults.
There are many health and social benefits of physical activity (PA) for older adults, but little is known about their activity patterns. The purpose of this study was to objectively assess the PA patterns of older adults and the lifestyle and demographic factors associated with PA. Participants (N = 230, aged 78.1 yr) recruited from medical practices (between 2007 and 2008) completed journey logs and wore accelerometers for 7 d. Mean daily steps, counts per minute (CPM), minutes of sedentary, light, or moderate-to-vigorous PA (MVPA), and frequency of journeys were analyzed (in 2009). Younger participants (age = 70-74.9 yr) were significantly (P < 0.001) more active (5660.8 steps per day) than older participants aged 80+ yr (3409.6 steps per day). Men performed significantly (P = 0.035) more minutes MVPA than women (23.1 vs 13.8 min MVPA per day). Normal weight participants were significantly (P < 0.05) more active (5368.9 steps per day) than overweight (4532.7 steps per day) and obese (3251.4 steps per day) groups. Those performing many journeys (>11.6 journeys per week) were significantly (P < 0.001) more active (5838.2 steps per day) than those performing few (<7 journeys per week) (3094.2 steps per day). PA was significantly (P < 0.001) greater in mornings (259.3 CPM) than afternoons (181.8 CPM) and evenings (102.5 CPM). Sundays were significantly (P < 0.001) less active (3331.7 steps per day) than Saturdays (4193.1 steps per day) and weekdays (4623.5 steps per day). Light activity was significantly (P = 0.005) higher in spring (3.4 h·d(-1)) than that in winter (2.7 h·d(-1)). Older adults' PA patterns differ by age, gender, and weight status. Daily journeys are associated with more activity for all groups. Variability in volume of activity is high for all age groups. Temporal patterns of PA indicate that journeys out of the house for shopping and personal business are important in their contribution to PA levels.


Knee awareness and functionality after simultaneous bilateral vs unilateral total knee arthroplasty.
To investigate knee awareness and functional outcomes in patients treated with simultaneous bilateral vs unilateral total knee arthroplasty (TKA). Through a database search, we identified 210 patients who had undergone unilateral TKA (UTKA) and 65 patients who had undergone simultaneous bilateral TKA (SBTKA) at our institution between 2010 and 2012. All TKAs were cemented and cruciate retaining. The mean follow-up period was 3.2 (2 to 4) years. All the patients had symptomatic and debilitating unilateral or bilateral osteoarthritis for which all conservative and non-surgical treatments were failed, thus preoperatively the patients had poor functionality. All patients were asked to complete Forgotten Joint Score (FJS) and Oxford Knee Score (OKS) questionnaires. The patients were matched according to age, gender, year of surgery, Kellgren-Lawrence score and pre- and postoperative overall knee alignment. The FJS and OKS questionnaire results of the two groups were then compared. A mixed-effects model was used to analyze differences between SBTKA and UTKA. OKS: The mean difference in the OKS between the patients who had undergone SBTKA and those who had undergone UTKA was 1.5, which was not statistically significant (CI = -0.9:4.0, P-value = 0.228). The mean OKS of the SBTKA patients was 37.6 (SD = 9.0), and the mean OKS of the UTKA patients was 36.1 (SD = 9.9). FJS: The mean difference in the FJS between the patients who had undergone SBTKA and those who had undergone UTKA was 2.3, which was not statistically significant (CI = -6.2:10.8, P-value = 0.593). The mean FJS of the SBTKA patients was 59.9 (SD = 27.5), and the mean FJS of the UTKA patients was 57.5 (SD = 28.8). SBTKA and UTKA patients exhibited similar joint functionality and knee awareness. Our results support the use of SBTKA in selected patients suffering from clinically symptomatic bilateral osteoarthritis.


Simultaneous homographic and comparametric alignment of multiple exposure-adjusted pictures of the same scene.
An approach is presented that can simultaneously align multiple exposure-adjusted pictures of the same scene both in their spatial coordinates as well as in their pixel values. The approach is featureless and produces an image mosaic at a common spatial and exposure reference and also addresses the misalignment problem common to methods that compose mosaics from only pair-wise registered image pairs. The objective function considered minimizes the sum of the collective variance over pixels of a global coordinate grid on which to create the final image. The models employed relate images spatially by homographic transformations and tonally by comparametric functions. The importance of performing joint spatial and tonal registration on exposure-adjusted images is emphasized by providing two examples in which spatial-only registration fails. A discussion describing the performance between pair-wise and simultaneous registration under both spatial-only and joint registration procedures is provided.


Validity and Reliability of a Portable Isometric Mid-Thigh Clean Pull.
James, LP, Roberts, LA, Haff, GG, Kelly, VG, and Beckman, EM. Validity and reliability of a portable isometric mid-thigh clean pull. J Strength Cond Res 31(5): 1378-1386, 2017-This study investigated the test-retest reliability and criterion validity of force-time curve variables collected through a portable isometric mid-thigh clean pull (IMTP) device equipped with a single-axial load cell. Fifteen males with ≥6 months of resistance training experience attended two testing sessions. In each session, participants performed an IMTP in 2 separate conditions in a randomized counterbalanced manner. The criterion condition consisted of a closed-chain IMTP configured with a force plate (IMTPf), whereas the experimental test was undertaken using a portable IMTP with data acquired through a single-axial load cell (IMTPl). A very high reliability (coefficient of variation [CV] = 3.10, 90% confidence interval [CI]: 2.4-4.6%; intraclass correlation coefficient [ICC] = 0.96, 90% CI: 0.90-0.98) and acceptable validity (CV = 9.2, 90% CI: 7-14%; ICC = 0.88, 90% CI: 0.71-0.95) were found in the experimental condition for the measure of peak force. However, significant differences were present between the IMTPf and IMTPl (p < 0.0001). Alternate force-time curve variables did not reach acceptable levels of validity or reliability in the experimental condition. The IMTPl is a valid and highly reliable method for assessing peak force. This provides evidence supporting the use of an IMTPl as a cost-effective and portable alternative for those who wish to assess maximal force production in a similar fashion to a traditional IMTP. However, practitioners should be aware that these are slightly different tests.


The Ciliopathy Gene ahi1 Is Required for Zebrafish Cone Photoreceptor Outer Segment Morphogenesis and Survival.
Joubert syndrome (JBTS) is an autosomal recessive ciliopathy with considerable phenotypic variability. In addition to central nervous system abnormalities, a subset of JBTS patients exhibit retinal dystrophy and/or kidney disease. Mutations in the AHI1 gene are causative for approximately 10% of all JBTS cases. The purpose of this study was to generate ahi1 mutant alleles in zebrafish and to characterize the retinal phenotypes. Zebrafish ahi1 mutants were generated using transcription activator-like effector nucleases (TALENs). Expression analysis was performed by whole-mount in situ hybridization. Anatomic and molecular characterization of photoreceptors was investigated by histology, electron microscopy, and immunohistochemistry. The optokinetic response (OKR) behavior assay was used to assess visual function. Kidney cilia were evaluated by whole-mount immunostaining. The ahi1lri46 mutation in zebrafish resulted in shorter cone outer segments but did not affect visual behavior at 5 days after fertilization (dpf). No defects in rod morphology or rhodopsin localization were observed at 5 dpf. By 5 months of age, cone degeneration and rhodopsin mislocalization in rod photoreceptors was observed. The connecting cilium formed normally and Cc2d2a and Cep290 localized properly. Distal pronephric duct cilia were absent in mutant fish; however, only 9% of ahi1 mutants had kidney cysts by 5 dpf, suggesting that the pronephros remained largely functional. The results indicate that Ahi1 is required for photoreceptor disc morphogenesis and outer segment maintenance in zebrafish.


A method to culture chicken enterocytes and their characterization.
Enterocytes function as both absorptive and protective components of intestine that come in close contact with a variety of enteric factors, such as dietary, microbial, and parasites, that have potential to affect the organismal health. Understanding how enterocytes interact with this complex array of factors may help improve gut health particularly in the context of poultry production where it is also linked to food safety issues. The enterocyte in vitro culture can help screen different factors and their interactions with microbiome, and potentially be utilized in the development of interventions strategies for pathogens such as antibiotic alternatives. We developed a method to culture primary chicken enterocytes and conducted their characterization using cytochemical and proteomic methods, and investigated their potential to respond to different chemical stimuli. Using selected micronutrients, microbial toxins, and metabolic modulators, we assessed their effects on the viability and morphological changes in enterocytes. We found that whereas some nutritional factors (calcitriol, retinoic acid) produced different morphological changes, toxins such as aflatoxin B1 and deoxynivalenol produced enterocyte degeneration and death, and the bacterial lipopolysaccharide had very little effect compared on the basis of their mass. Both cyclic AMP and phorbol myristate acetate exhibited some cachectic effects on enterocytes with the later showing more severe changes. Thyroxin induced distinct morphological changes making the cells more cuboidal and Na-butyrate produced no significant change in morphology. The cytochemical and proteomic characterization suggest that these enterocytes largely belong to epithelial cell categories which may be amenable to analysis of biochemical paths and mechanisms of action of different factors that affect these cells. Based on these results we conclude that chicken enterocyte culture can be a useful in vitro model to study intestinal physiology.


Primary thyroid lymphoma: multi-slice computed tomography findings.
The objective of this study was to investigate the MSCT characteristics of PTL in order to enhance the awareness of this uncommon entity among both clinicians and radiologists. The clinicopathological data and MSCT images of 27 patients with PTL were retrospectively reviewed. The MSCT appearances were classified into three types: type 1, solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, enlarged thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. The patients were enrolled in the study with a mean age of 68 years (range, 51-86years) and compression symptoms or enlarged cervical lymph nodes at diagnosis. Hashimoto's thyroiditis was in 20 patients. All patients had non-Hodgkin lymphoma of B-cell in origin, including 22 cases of diffuse large B-cell lymphoma (DLBCL) and 5 of low-grade B-cell lymphoma of mucosa- associated lymphoid tissue (MALT). For MSCT appearance, type 1 pattern was observed in 2 patients, type 2 in 8, and seventeen type 3 in 17. The lesions occurred in more than one lobe with a mean maximal transverse diameter of 6.9 cm and an ill-defined margin. Most tumors showed a homogeneous attenuation equal to that of surrounding muscles before contrast and obvious enhancement after contrast. Cervical lymph node involvement and invasion of the trahea and (or) esophagus were mainly observed in patients with DLBCL. PTL should be clinically considered in elder patients presenting with a history of Hashimoto's thyroiditis and cervical lymphadenopathy. The MSCT characteristics of PTL includes a mass diffusely affecting more than one thyroid lobe, isointense to muscle and obvious enhancement before and after contrast. DLBCL, the most common histological subtype of PTL, is associated with a higher invasive tendency.


Assessing patient management plans of doctors and medical students: an illness script perspective.
Illness script theory offers explanations for expert-novice differences in clinical reasoning. However, it has mainly focused on diagnostic (Dx) performance, while patient management (Mx) has been largely ignored. The aim of the present study was to show the role of Mx knowledge in illness script development and how it relates to diagnostic knowledge in the course of development toward expertise. The participants were 10 fourth-year and 10 sixth-year medical students, and 10 experienced physicians (ie, internists). Participants were asked to study 4 written clinical cases and provide management plans. Based on propositional analysis the management plans were examined for accuracy and elaborateness as well as the number of Mx and Dx items. Providing accurate Mx plans that concurrently pay attention to Dx and Mx was a characteristic of doctors' performance. The Mx plans of sixth-year students were as accurate as fourth-year students, but the format and the size of sixth-year students' plans was more similar to those of doctors. While sixth-year students generated plans with an Mx focus, the plans of fourth-year students were characterized by a Dx focus. The experienced physicians' accurate management plans are characterized by a high number of the Mx and Dx items. For sixth-year students the management plans are still incomplete, which leads to generic as well as inaccurate Mx orders. For fourth-year students, the Mx focus is lacking, and hence they seem to treat an Mx task as if it were a Dx task.


Discontinuous gas-exchange cycles in Scarabaeus dung beetles (Coleoptera: Scarabaeidae): mass-scaling and temperature dependence.
Although discontinuous gas exchange cycles (DGC) are known from many insects, the effects of body size and temperature on DGC have not been widely examined. Here, these effects are investigated in five Scarabaeus dung beetle species from mesic and xeric habitats. The investigation tests two hypotheses: that previous estimates of the scaling exponents for the DGC and its characteristics are more broadly applicable to insects, and that, in response to temperature, both DGC frequency and the quantity of CO2 emitted during the open (O) phase (O-phase emission volume) are modulated. Like previous workers, we find that V&d2;co2 scaled as mass0.968 and that O-phase emission volume scaled as mass0.833. However, temperature-associated increases in .Vco2 (Q10's of 2.19-2.65) were modulated mostly by increases in DGC frequency since O-phase volumes remained constant across temperature. Flutter (F)-phase and O-phase durations were closely coupled to DGC duration, although the relationship between closed (C)-phase duration and DGC duration was less pronounced. We show that ventilation phase coefficients, previously considered a measure of the proportional duration of each phase of the DGC, calculated from the slopes of these relationships are a measure of change in phase duration with change in DGC duration and not a measure of the way in which total DGC duration is apportioned among phases. We suggest that proportions be used to estimate the contribution of each of the phases to the total duration of the DGC.


Prognostic indices of inflammatory markers, cognitive function and fatigue for survival in patients with localised colorectal cancer.
Inflammation promotes the development of malignancy, while a variety of systemic markers of inflammation predict for worse cancer outcomes including recurrence and survival. Here, we evaluate the prognostic impact of cytokine concentrations, full blood count (FBC) differential ratios, cognitive function and fatigue on survival in patients with localised colorectal cancer (CRC). Data are from a prospective longitudinal study comparing cognitive function and fatigue in patients with CRC who did (n=173) and did not (n=116) receive adjuvant/neoadjuvant chemotherapy. Baseline blood results (prior to any chemotherapy) included cytokines and FBC from which neutrophil lymphocyte ratio, lymphocyte monocyte ratio, platelet lymphocyte ratio and platelet monocyte ratio were derived. Fatigue was measured with the Functional Assessment of Cancer Therapy-Fatigue subscale and cognitive function by a neuropsychological test battery. Kaplan-Meier methods were used to estimate disease-free survival (DFS) and overall survival (OS). Univariable and multivariable Cox regression analyses were performed to evaluate factors potentially prognostic of outcomes. At a median follow-up of 91.2 months, 227 subjects (79%) are still alive, and 212 (73%) have no evidence of a recurrence. Five-year OS and DFS are 86% (95% CI 81% to 90%) and 77% (95% CI 71% to 82%), respectively. None of the cytokines (interleukin (IL-6), IL-1 and tumour necrosis factor) or differential ratios of blood components, fatigue or cognitive function was statistically related to DFS or OS. Patient educational status (P=0.018), stage of disease (P=0.032), alanine transaminase (P=0.003), lactate dehydrogenase (P=0.008) and carcinoembryonic antigen (P=0.002) were significant as prognostic covariates of OS in univariable analyses, with similar results for DFS. None of the a priori selected markers of inflammation, fatigue or cognitive function was associated with OS or DFS in this cohort of patients. NCT00188331, Post-results.


Conjugated polyelectrolytes: conformation-sensitive optical probes for detection of amyloid fibril formation.
The in vivo deposition of amyloid fibrils is a hallmark of many devastating diseases known as the amyloidoses. Amyloid formation in vitro may also complicate production of proteins in the biotechnology industry. Simple, sensitive, and versatile tools that detect the fibrillar conformation of amyloidogenic proteins are thus of great importance. We have developed a negatively charged conjugated polyelectrolyte that displays different characteristic optical changes, detected visually or by absorption and emission, depending on whether the protein with which it forms a complex is in its native state or amyloid fibril conformation. This simple, rapid, and novel methodology was applied here to two amyloidogenic proteins, insulin and lysozyme, and its validity for detection of their fibrillar conformation was verified by currently used methods such as circular dichroism, transmission electron microscopy, and Congo red absorption.


Gonadal hormone-dependent and -independent regulation of immune function by photoperiod in Siberian hamsters.
Siberian hamsters (Phodopus sungorus) exhibit changes in reproductive and immune function in response to seasonal variations in day length. Exposure to short days induces gonadal regression and inhibits testosterone secretion. In parallel, short days enhance immune function: increasing leukocyte numbers and attenuating cytokine and behavioral responses to infection. We examined whether photoperiodic changes in leukocyte phenotypes and sickness behaviors are dependent on concurrent photoperiodic changes in gonadal function. Male hamsters were gonadectomized or sham-gonadectomized and either exposed to short days (9 h light/day; SD) or kept in their natal long-day (15 h light/day; LD) photoperiod for 10-13 wk. Blood samples were obtained for leukocyte enumeration, and hamsters were challenged with bacterial LPS, which induced behavioral (anorexia, reductions in nest building) and somatic (weight loss) sickness responses. Among gonad-intact hamsters, exposure to SD increased total and CD62L+ lymphocytes and CD3+ T lymphocytes in blood and significantly attenuated LPS-induced sickness responses. Independent of photoperiod, castration alone increased total and CD62L+ lymphocyte and CD3+ T lymphocyte numbers and attenuated somatic and anorexic sickness responses. Among castrated hamsters, SD exposure increased lymphocyte numbers and suppressed sickness behaviors. In castrated hamsters, the magnitude of most immunological effects of SD were diminished relative to those evident in gonad-intact hamsters. The SD phenotype in several measures of immunity can be instated via elimination of gonadal hormones alone; however, photoperiodic effects on immune function persist even in castrated hamsters. Thus, photoperiod affects the immune system and neural-immune interactions underlying sickness behaviors via gonadal hormone-dependent and -independent mechanisms.


Bioresponsive hydrogels.
Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors, and regenerative medicine. Their ability to respond to specific biologically derived stimuli creates a design challenge in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range, limit of detection, and the potential for feedback control. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide sensing, transduction, and actuation of the hydrogel. Future advancements in bioresponsive hydrogels will out of necessity contain control loops similar to synthetic metabolic pathways. The use of these materials will continue to expand as they become coupled and integrated with new technologies.


Effect of anatomical variability on electric field characteristics of electroconvulsive therapy and magnetic seizure therapy: a parametric modeling study.
Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are conventionally applied with a fixed stimulus current amplitude, which may result in differences in the neural stimulation strength and focality across patients due to interindividual anatomical variability. The objective of this study is to quantify the effect of head anatomical variability associated with age, sex, and individual differences on the induced electric field characteristics in ECT and MST. Six stimulation modalities were modeled including bilateral and right unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular, cap, and double-cone coils. The electric field was computed using the finite element method in a parameterized spherical head model representing the variability in the general population. Head tissue layer thicknesses and conductivities were varied to examine the impact of interindividual anatomical differences on the stimulation strength, depth, and focality. Skull conductivity most strongly affects the ECT electric field, whereas the MST electric field is independent of tissue conductivity variation in this model but is markedly affected by differences in head diameter. Focal ECT electrode configurations such as FEAST is more sensitive to anatomical variability than that of less focal paradigms such as BL ECT. In MST, anatomical variability has stronger influence on the electric field of the cap and circular coils compared to the double-cone coil, possibly due to the more superficial field of the former. The variability of the ECT and MST electric fields due to anatomical differences should be considered in the interpretation of existing studies and in efforts to improve dosing approaches for better control of stimulation strength and focality across patients, such as individualization of the current amplitude. The conventional approach to individualizing dosage by titrating the number of pulses cannot compensate for differences in the spatial extent of stimulation that result from anatomical variability.


Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood.
Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (N = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.


Final results from 18 years of the International Lamotrigine Pregnancy Registry.
To monitor for a signal for major teratogenicity following in utero lamotrigine exposure. Health care providers reported lamotrigine exposure during pregnancy, and subsequent outcomes, on a voluntary basis. Prospective reporting early in pregnancy was encouraged. Major congenital malformations (MCMs) were classified according to the Centers for Disease Control and Prevention (CDC) criteria and were reviewed by a pediatrician on the Registry's Scientific Advisory Committee. The proportion of infants with MCMs was calculated by trimester and therapy type and descriptively compared to population-based reference estimates. Over an 18-year period, 35 infants with MCMs were observed among 1,558 first-trimester monotherapy exposures: 2.2%(95% confidence interval [CI] 1.6%-3.1%). This was similar to estimates from general population-based cohorts. The observed proportion of infants with MCMs among 150 lamotrigine/valproate polytherapy exposures was 10.7% (95% CI 6.4%-17.0%) and was 2.8% (95% CI 1.5%-5.0%) among 430 infants exposed to lamotrigine polytherapy without valproate. No consistent pattern of malformation type, or malformation frequency by dose, was observed. The Registry did not detect an appreciable increase in MCM frequency following first-trimester lamotrigine monotherapy exposure. With over 1,500 first-trimester monotherapy exposures, the Registry was powered to detect major teratogenicity. The proportion of infants with MCMs following lamotrigine/valproate polytherapy exposure was high, but similar to that previously reported with valproate monotherapy. The Registry failed to observe an increased MCM frequency with increasing lamotrigine dose. Monitoring of specific malformations among lamotrigine-exposed pregnancies will continue through case-control surveillance in the European Congenital Anomalies and Twins Registers network.


Streptococcal Adhesin P (SadP) contributes to Streptococcus suis adhesion to the human intestinal epithelium.
Streptococcus suis is a zoonotic pathogen, causing meningitis and septicemia. We previously demonstrated that the gastrointestinal tract (GIT) is an entry site for zoonotic S. suis infection. Here we studied the contribution of Streptococcal adhesin Protein (SadP) to host-pathogen interaction at GIT level. SadP expression in presence of Intestinal Epithelial Cells (IEC) was compared with expression of other virulence factors by measuring transcript levels using quantitative Real Time PCR (qRT-PCR). SadP variants were identified by phylogenetic analysis of complete DNA sequences. The interaction of SadP knockout and complementation mutants with IEC was tested in vitro. Expression of sadP was significantly increased in presence of IEC. Sequence analysis of 116 invasive strains revealed five SadP sequence variants, correlating with genotype. SadP1, present in zoonotic isolates of clonal complex 1, contributed to binding to both human and porcine IEC and translocation across human IEC. Antibodies against the globotriaosylceramide Gb3/CD77 receptor significantly inhibited adhesion to human IEC. SadP is involved in the host-pathogen interaction in the GIT. Differences between SadP variants may determine different affinities to the Gb3/CD77 host-receptor, contributing to variation in adhesion capacity to host IEC and thus to S. suis zoonotic potential.


The EFSA health claims 'learning experience'.
The European Food Safety Authority (EFSA) has recently highlighted the need to provide scientific requirements for health claims and to find new regulatory issues for healthy food products. For this reason, EFSA asked its Dietetic Products, Nutrition and Allergies (NDA) panel to draft additional guidelines on scientific assessment of these claims. A new approach for a strict substantiation of health issues in selected fields: the Regulation (EC) No. 1924/2006 established in fact that health claims applications should only be authorized after a high level of scientific validation conducted by EFSA using appropriate measures in this evaluation. The legislation should not only protect consumers but also define specific research areas with appropriate outcome measures to assess the quality, relevance and adequacy of studies conducted for scientific validation of health claims. The new system was not only a necessary support for consumers to make the correct choice of products, but rather a way for EFSA to demonstrate transparency of this new approach. This was the field of the pharmaceutical industry, this new regulation is, therefore, also for EFSA, an expensive learning process.


circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations.
circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.


Intravenous Steroids With Antibiotics on Admission for Children With Orbital Cellulitis.
To compare the outcomes of children with orbital cellulitis treated with intravenous (IV) dexamethasone and antibiotics on admission to patients treated with antibiotics alone. Prospective comparative interventional study. Forty-three children admitted to a tertiary institution with orbital cellulitis were enrolled. On admission, all patients were started on broad spectrum IV antibiotics and parents were offered IV dexamethasone (0.3 mg/kg/d every 6 hours for 3 days). Patients whose parents refused steroid treatment served as the control group. Twenty-eight (65%) patients received IV steroids and antibiotics on admission while 15 (35%) received IV antibiotics alone. Children who received IV steroids had significantly shorter hospital stays than those who did not receive steroids (3.8 ± 0.2 days vs. 6.7 ± 0.3 days; p < 0.001). This was true both for children who underwent surgery (5/28 with steroids, 3/15 without; 5.0 ± 0.7 days vs. 7.3 ± 1.2 days; p = 0.011) and for those who did not require surgical intervention (23/28 with steroids, 12/15 without; 3.6 ± 0.6 and 6.5 ± 1.0 days; p < 0.001). Side effects of steroid treatment were mild and did not require termination of therapy. During follow up, all study patients had returned to their baseline health without any cases of decreased vision or disease recurrence. The results of the current study give additional evidence to the relative safety and efficacy of systemic steroid use concurrently with IV antibiotics in children with orbital cellulitis. This is the first study to recommend IV steroids on hospital admission and a standardized dosing regimen. Children who received steroids had a shorter hospital stay than those who did not.


Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity.
Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types - a lineage-specific sensory effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for cnidarian hair cell development are unknown. Here, we show that the class IV POU homeodomain transcription factor (POU-IV) - an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria - controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes - including the transmembrane receptor-encoding gene polycystin 1 - specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.


Application of metagenomic next-generation sequencing (mNGS) in diagnosing pneumonia of adults.
Accurate identification of pathogens that cause pulmonary infections is essential for effective treatment and hastening recovery in adults diagnosed with pneumonia. At present, despite metagenomic next-generation sequencing (mNGS) technology has been widely used in clinical practice for pathogen identification, the clinical significance and necessity of detecting pathogen in bronchoalveolar lavage fluid (BALF) for pneumonia-stricken adults remain ambiguous. In this study, 80 patients suffering from pulmonary infection were enrolled, who were admitted to the Affiliated Changzhou Second People's Hospital of Nanjing Medical University between January 2020 and September 2022. The diagnostic performances of mNGS and conventional methods (CM) were systematically analyzed based on BALF samples, and we further investigated the influence of mNGS and CM in diagnosis modification and treatment. We found a significantly higher positive rate for the mNGS method in contrast to CM. Bacteria were the most common pathogens, and Streptococcus pneumoniae was the most commonly identified pathogen. Candida albicans and Epstein-Barr virus were the most frequently identified fungus and virus. Atypical pathogens such as Mycobacterium tuberculosis, virus Nontuberculous mycobacteria, and Chlamydia psittaci were also identified. A total of 77 patients were identified with mixed infections by mNGS. As the disease progressed and recurrent antibiotic treatment persisted, significant dynamic changes in the clinical manifestation from the BALF samples could be found by mNGS. This study underscores the efficacy of mNGS in detecting pathogens in BALF samples from patients suffering pulmonary infections. Compared with the CM, mNGS significantly enhanced the positive diagnosis ratio, particularly in diagnosing Mycobacterium tuberculosis, atypical pathogens, and viral or fungal infections.


Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis.
Progress in understanding the abnormal regulation of hematopoiesis in chronic myelogenous leukemia (CML) would be facilitated if neoplastic cells, at all stages of the disease, could be studied in an animal model. In this report, we show that irradiated severe combined immunodeficient (SCID) mice can be transplanted with both normal (Philadelphia chromosome [Ph]-negative) and neoplastic (Ph+) cells from CML patients with either chronic or blast phase disease. Mice transplanted with peripheral blood (PB) or bone marrow (BM) cells from 9 of 12 chronic phase CML patients were well engrafted with human cells including multilineage colony-forming progenitors and CD34+ cells for at least 90 days posttransplantation. Repeated posttransplant injections of cytokines did not enhance the number of engrafted human cells. Interestingly, approximately 70% of the human progenitors found in the engrafted SCID BM were Ph-, suggesting that the growth of primitive normal cells is favored in this in vivo transplant model. A similar number of normal cells were found in mice transplanted with either PB or BM cells, suggesting that elevated numbers of primitive normal cells are present in CML PB. When cells from patients with CML in either myeloid or lymphoid blast crisis were transplanted into SCID mice, the BM of these mice was more rapidly repopulated and to a higher level than that observed with transplants of chronic phase cells. Moreover, all human colony-forming progenitors present in the BM of mice transplanted with blast crisis cells were Ph+, and the majority of cells showed the same morphological features of the blast crisis cells originally transplanted. These experiments provide a starting point for the creation of an animal model of CML and establish the feasibility of using this model for the future characterization of transplantable CML stem cells during disease progression.


Ultrasound evaluation of piglet diaphragm function before and after fatigue.
Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.


Molecular characterization and ocular hypotensive properties of the prostanoid EP2 receptor.
The cloning of the genes that encode for prostaglandin (PG) receptors has resolved much of the complexity and controversy in this area by confirming the classification proposed by Coleman, et al. Two issues that remained unresolved were (1) the inability of the EP2 agonist butaprost to interact with the cloned putative EP2 receptor and (2) molecular biological confirmation of a fourth PGE2-sensitive receptor, which was pharmacologically designated EP4. In order to provide clarification, we attempted to clone further PGE2-sensitive receptors. By using a cDNA probe that encodes for the human EP3A receptor, a cDNA clone that encoded for a novel PGE2-sensitive receptor was obtained by screening a human placenta library. This cDNA clone was transfected into COS-7 cells for pharmacological studies. The cDNA clone obtained from human placenta had only about 30% amino acid identity with cDNAs for other PG receptors, including those that encode for the previously proposed murine and human EP2 receptors. Radioligand binding studies on the novel EP receptor expressed in COS-7 cells revealed that selective EP2 agonists such as butaprost, AH 13205, AY 23626 and 19(R)-OH PGE2 all competed with 3H-PGE2 for its binding sites, whereas selective agonists for other PG receptor subtypes had minimal or no effect. This receptor was coupled to adenylate cyclase and EP2 agonists caused dose-related increases in cAMP. It appears that the cDNA described herein encodes for the pharmacologically defined EP2 receptor. Ocular studies revealed that AH 13205 decreased intraocular pressure in normal and ocular hypertensive monkeys by a mechanism that does not appear to involve inhibition of aqueous humor secretion.


Utilization of current pyrolysis technology to convert biomass and manure waste into biochar for soil remediation: A review.
Traditional disposal of animal manures and lignocellulosic biomass is restricted by its inefficiency and sluggishness. To advance the carbon management and greenhouse gas mitigation, this review scrutinizes the effect of pyrolysis in promoting the sustainable biomass and manure disposal as well as stimulating the biochar industry development. This review has examined the advancement of pyrolysis of animal manure (AM) and lignocellulosic biomass (LB) in terms of efficiency, cost-effectiveness, and operability. In particular, the applicability of pyrolysis biochar in enhancing the crops yields via soil remediation is highlighted. Through pyrolysis, the heavy metals of animal manures are fixated in the biochar, thereby both soil contamination via leaching and heavy metal uptake by crops are minimized. Pyrolysis biochar is potentially use in soil remediation for agronomic and environmental co-benefits. Fast pyrolysis assures high bio-oil yield and revenue with better return on investment whereas slow pyrolysis has low revenue despite its minimum investment cost because of relatively low selling price of biochar. For future commercialization, both continuous reactors and catalysis can be integrated to pyrolysis to ameliorate the efficiency and economic value of pyrolysis biochar.


Racial Disparities in the Clinical Presentation and Prognosis of Patients with Mycosis Fungoides.
Racial and gender disparities in mycosis fungoides (MF) are understudied. The objective of this study was to test the hypothesis that worse prognosis in blacks with MF is mediated by higher disease stage at diagnosis and by earlier disease onset in black females. We conducted retrospective chart review of 337 patients with clinically-suspected MF seen at Johns Hopkins between 2003 and 2018, requiring biopsy-proven disease for study inclusion. Patient demographics, initial stage/percent body surface area (BSA) involvement, pathology type, flow cytometry results, and treatment regimens were recorded. Of 303 patients with confirmed MF, 166 (55%) were white, 107 (35%) black, 10 (3.3%) Middle Eastern, 6 (2.0%) Asian, and 14 (4.6%) Hispanic/other. Blacks were 3 times as likely (95% CI: 1.2, 8.0) to have Stage 2 disease to have Stage 2 disease at diagnosis as compared to whites as whites. In females, blacks were younger at diagnosis (p = 0.003) and at death (p = 0.008) compared to whites. In males, blacks had 4 times the odds of late-stage disease (p = 0.017) and presented with 19% greater BSA involvement on average compared to whites (p < 0.001). Compared to their white counterparts in this cohort, black males were diagnosed with MF at a higher stage with greater skin involvement while black females were diagnosed and died earlier. Earlier recognition of MF in skin of color and closer follow-up of black females with early-onset, aggressive disease may help to mitigate disparities in outcomes.


Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2.
A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (V(A)/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to V(A)/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from V(A)/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (V(A)/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with V(A)/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%), and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high V(A)/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO(2) dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventilation, we conclude that it is well suited to the investigation of pulmonary gas exchange in man.


Final safety assessment of Coal Tar as used in cosmetics.
Coal Tar is a semisolid by-product obtained in the destructive distillation of bituminous coal, which functions in cosmetic products as a cosmetic biocide and denaturant--antidandruff agent is also listed as a function, but this is considered an over-the-counter (OTC) drug use. Coal Tar is a nearly black, viscous liquid, heavier than water, with a naphthalene-like odor and a sharp burning taste, produced in cooking ovens as a by-product in the manufacture of coke. Crude Coal Tar is composed of 48% hydrocarbons, 42% carbon, and 10% water. In 2002, Coal Tar was reported to the Food and Drug Administration (FDA) to be used in four formulations, all of which appear to be OTC drug products. Coal Tar is monographed by the FDA as Category I (safe and effective) OTC drug ingredient for use in the treatment of dandruff, seborrhoea, and psoriasis. Coal Tar is absorbed through the skin of animals and humans and is systemically distributed. In short-term studies, mice fed a diet containing Coal Tar found it unpalatable, but no adverse effects were reported other than weight loss; rats injected with Coal Tar experienced malaise in one study and decreased water intake and increased liver weights in another; rabbits injected with Coal Tar residue experienced eating avoidance, respiratory difficulty, sneezing, and weight loss. In a subchronic neurotoxicity study using mice, a mixture of phenols, cresols, and xylenols at concentrations approximately equal to those expected in Coal Tar extracts produced regionally selective effects, with a rank order of corpus striatum > cerebellum > cerebral cortex. Coal Tar applied to the backs of guinea pigs increases epidermal thickness. Painting female rabbits with tar decreases the absolute and relative weights of the ovaries and decreased the number of interstitial cells in the ovary. Four therapeutic Coal Tar preparations used in the treatment of psoriasis were mutagenic in the Ames assay. Urine and blood from patients treated with Coal Tar were genotoxic in bacterial assays. Coal Tar was genotoxic in a mammalian genotoxicity assay and induced DNA adducts in various tissue types. Chronic exposure of mice to Coal Tar significantly decreased survival and liver neoplasms were seen in a significant dose-related trend; in other studies using mice lung tumors and perianal skin cancers were found. Coal Tar was comedogenic in three small clinical studies. Folliculitis is associated with the prolonged use of some tars. Several published reports describe cases of contact sensitivity to Coal Tar. Polycyclic aromatic hydrocarbons, which make up Coal Tar, are photosensitizers and cause phototoxicity by an oxygen-dependent mechanism. A retrospective study of the reproductive toxicity of Coal Tar in humans compared exposed women to controls and found little difference in spontaneous abortion and congenital disorders. Cancer epidemiology studies of patients who have received Coal Tar therapy of one form or other have failed to link treatment with an increase in the risk of cancer. Although the Cosmetic Ingredient Review (CIR) Expert Panel believes that Coal Tar use as an antidandruff ingredient in OTC drug preparations is adequately addressed by the FDA regulations, the Panel also believes that the appropriate concentration of use of Coal Tar in cosmetic formulations should be that level that does not have a biological effect in the user. Additional data needed to make a safety assessment include product types in which Coal Tar is used (other than as an OTC drug ingredient), use concentrations, and the maximum concentration that does not induce a biological effect in users.


High-performance liquid chromatography of type-III heptocarboxylic porphyrinogen isomers.
A reversed-phase h.p.l.c. system is described for the separation of the four type-III heptacarboxylic porphyrinogen isomers. The effects of buffer concentration, pH and type and proportion of organic modifier in the mobile phase on retention and resolution of isomers were studied. Optimum separation on an ODS-Hypersil column was by elution with a ternary mobile phase of acetonitrile, methanol and 1 M-ammonium acetate, pH 5.16 (7:3:90, by vol.). Isomer identification was based on a comparison of their retention times with those of authentic standards, and was further confirmed by h.p.l.c. analysis of the characteristic mixture of three pentacarboxylic porphyrins formed after partial decarboxylation of individual isomers in 0.3 M-HCl at 160 degrees C.


[Qualitative assessment of a noncarcinogenic risk to human health].
The existing methodic approaches to analyzing a noncarcinogenic risk fail to fully solve the tasks set within the basic lines of the activities of the Russian Agency for Consumer Surveillance since there are limited capacities of the quantitative assessment of a noncarcinogenic risk to human health. An algorithm is proposed for basing the indicators assessing a noncarcinogenic risk to human health, which assumes to determine exposure or an exposure marker for a cohort to be examined, to define a response to human health exposure, to construct mathematical "exposure (an exposure marker)-response" models, to determine the ineffective levels exposure for each type of a response, to make the piecewise-linear approximation of a model, and to calculate a slope factor for each linearized interval of an exposure-response model. Application of the proposed methodic approaches makes it possible, provided that the estimation of the cost of risk units, to assess the economic loss risk associated with the pollution of environmental objects, including a preventable risk, and to calculate the indicators of the effectiveness and efficiency of the activities of the bodies and organizations of the Russian Agency for Consumer Surveillance in reducing the risk to the population's health.


Relationship between quality of life, self-efficacy and social support in patients with multiple sclerosis.
Multiple sclerosis (MS) causes patients' perceptions of self-efficacy and social support to decline. Patients with MS have to change day-to-day activities and encounter various physical and psychosocial problems while adapting to the new lifestyle. The research aimed to define the quality of life, self-efficacy and social support in patients with MS and to determine the relationship between quality of life, perception of self-efficacy and perceived social support. It is descriptive and correlational research. Data were collected using surveys. The sample consisted of 116 patients with MS. Patients who applied at the neurology in-patient and outpatient clinics between March 2021 and September 2021 were assessed for inclusion criteria. Written and verbal consent was obtained. The patients read and answered the questionnaires. Their quality of life was assessed using the Functional Assessment of Multiple Sclerosis Scale (FAMS). Self-efficacy perception was measured using the General Self-Efficacy Scale (GSE), and social support was assessed using the Multidimensional Scale of Perceived Social Support (MSPSS). The study found that the other concerns, symptoms, thinking and fatigue were most negatively affected the quality of life subscales. Perception of self-efficacy was found to be moderate, while social support was high. Analyses revealed a positive correlation between MSPSS scores, FAMS scores and GSE scores (p<0.05). Health professionals need to provide education and counselling to manage MS-related symptoms, use therapeutic communication techniques to improve self-efficacy, give positive reinforcement and cooperate with families to increase social support.


Ras Suppressor-1 (RSU-1) in Cancer Cell Metastasis: Friend or Foe?
Metastasis to distant organs and not the primary tumor itself is usually the cause of death for cancer patients. Hence, studying the key molecules and molecular pathways involved in metastasis are essential. Metastasis is a complex process in which cancer cells detach from the original tumor, migrate, and invade through surrounding tissues and metastasize to other sites of the body through the circulation. The cell-extracellular matrix (ECM) adhesion proteins play a fundamental role in this process as cancer cells need to weaken their adhesions to dissociate from the ECM as well as the neighboring cells within the tumor and finally form new adhesions and invade surrounding tissues. Ras suppressor-1 (RSU-1) was originally identified as a suppressor of Ras-dependent oncogenic transformation and found to be localized to cell-ECM adhesions where it binds to PINCH-1, a focal adhesion involved in cell survival. Although RSU-1 was connected to cancer early on, little is known about its expression in various cancer types or its role in metastasis. In this article, we review the recent literature regarding the expression of RSU-1 in various cancer types and its potential role in metastasis, discussing interesting findings and issues that still need to be addressed.


Clinical-demographic and laboratory profile of the mother-child binomial with syphilis in a tertiary-level hospital in Mexico.
Congenital syphilis remains a major public health problem, and its incidence is increasing worldwide. Retrospective, observational and descriptive study of cases with CS and their mothers at a tertiary-level hospital in Mexico from 2017 to 2022. Medical records of patients with CS and a structured collection of epidemiological, clinical, and laboratory data were analyzed and classified in the CDC scenarios as confirmed, probable, less probable, or unlikely. 180 cases were diagnosed with a compatible definition of congenital syphilis, and we identified 43 (21.21%) confirmed proven. Among those proven cases, 15.6% had a hematological, 13.3% skin, 12.2% liver, 6.7% pulmonary, 6.6% neurological, 5.8% eye, 5.6% bone, and 0.6% hearing involvement. According to the clinical stages of maternal syphilis, 119 (66.1%) were in the late latent phase, 49 (27.2%) in the early latent phase, 7 (3.9%) in the secondary stage, and 5 (2.8%) in the primary stage. Mothers with tertiary syphilis were not detected. Regardless of negative antenatal screening, healthcare workers should consider the diagnosis of congenital syphilis. Infants are still undiagnosed at birth and only a tiny percentage exhibit symptoms. The wide range of clinical manifestations of this preventable infection can be misdiagnosed for various other diseases, causing diagnostic delays that can have serious consequences.


Typology of parent-child ties within families: Associations with psychological well-being.
Middle-aged adults often have relationships with multiple family members (e.g., children and parents). The constellation of parent-child relationships within families may have implications for individuals' psychological well-being. This study created typologies of parent-child ties by combining multiple dimensions of relationships and examined the extent to which middle-aged adults showed variability across typologies of parent-child ties within multigenerational families. Using 2,252 parent-child ties across three generations from 633 middle-aged adults, this study identified typologies of parent-child ties based on 5 indicators (i.e., contact, downward and upward support, and positive and negative relationship qualities), and examined the associations of specific typologies of parent-child ties as well as within-family variability in typologies with middle-aged adults' psychological well-being. This study found 7 types of parent-child ties as distinct combinations of contact, support exchanges, and relationship quality. Within-family variability in these types was associated with more depressive symptoms, and having types characterized by conflicted ties was associated with more depressive symptoms and lower life satisfaction. Middle-aged adults seem to be happiest when they are able to maintain homogeneous, harmonious patterns of relationships with their parents and grown children. Findings were discussed with regard to factors that also may predict greater variability in family relationship patterns. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Molecular Docking and Dynamics Simulations Studies of a Dataset of NLRP3 Inflammasome Inhibitors.
The organism's defense against aggressive agents is performed by the innate immune system, via activation of pattern-recognition receptors (PRRs). Initially, these agents are recognized by the immune system, resulting in the inflammatory response that activates the pathogen elimination and tissue repair. Inflammasomes are macromolecules related to the host's response to endo or exogenous aggressive agents. Thus, inflammation mediated by inflammasomes plays an important role in the pathogenesis of diseases, such as neurodegenerative disorders, autoimmune diseases, and type 2 diabetes, justifying their attractiveness as drug targets. One of the most important tasks remains in the ATPase nucleotide-binding oligomerization domain nucleotide-binding domain leucine-rich repeat-containing receptors protein 3 (NLRP3), in which the blocking of its oligomerization is related to the functional inhibition of inflammasomes. Here, we performed molecular docking and dynamics simulations for NP3-146, an analog of MCC950, and to obtain information about the complex stability and main interactions with amino acid residues from NLRP3. Using the crystalized structure recently deposited in the protein data bank (7alv), molecular docking in GOLD software and Molecular dynamics simulations in GROMACS software were performed, to generate the RMSD, RMSF, Rg, SASA, and H-bond plots. The results of RMSD, RMSF, Rg, SASA, and H-bond plots of both complexes confirmed the stability at the active site. Besides, the analyses of the most stable conformation showed that the main interactions are performed with Ala227, Ala228, Pro352, Ile411, Phe575, and Arg578 residues. This report confirmed the stability of NP3-146, similar to the know inhibitor MCC950, and provides various information useful to design NLRP3 inhibitors.


Soft tissue sarcomas in dermatology.
Dermatofibrosarcoma protuberans, atypical fibroxanthoma, and cutaneous leiomyosarcoma are uncommon soft tissue sarcomas that tend to have a high recurrence rate when removed with standard excisional surgery, and in some cases have been reported to metastasize. These tumors have been reported in the surgical, medical, and pathology literature. The diagnosis and treatment of these tumors is still evolving. Wide excision and surgical techniques involving meticulous surgical margin control appear to be the most efficacious treatment for these problematic tumors. The surgical, medical, and pathology literature was extensively reviewed to collate the observations of multiple investigators, and to summarize their findings. Literature from medical journals of multiple subspecialties as well as textbooks were reviewed with particular emphasis on diagnosis, histologic features including immunohistochemistry, and useful surgical techniques that facilitate the removal of these difficult tumors. Dermatofibrosarcoma protuberans is a soft tissue neoplasm of intermediate malignancy that shows a high recurrence rate when treated with standard excision. Wide surgical excision using a 3-cm margin greatly reduces the risk of recurrence, but is not practical in some cases. Evidence is continuing to accumulate that Mohs micrographic surgery may be the treatment of choice for this tumor. Atypical fibroxanthoma is best thought of as a superficial form of malignant fibrous histiocytoma. It is histologically indistinguishable from certain forms of malignant fibrous histiocytoma and differs primarily in its size and superficial location. These tumors are best removed surgically. For most smaller tumors a 1-cm margin, which is carried down to the subcutaneous tissue, provides adequate treatment. In cases where tissue conservation is important, Mohs micrographic surgery has been shown to be very effective. Cutaneous leiomyosarcoma is a rare superficial soft tissue sarcoma that has a high incidence of recurrence after excision and can metastasize. Because of the small number of patients treated, treatment recommendations are still evolving. Currently, wide local excision is recommended with a 3-5 cm margin and removal of the underlying subcutaneous tissue. Mohs micrographic surgery has been used in a small number of cases with good success. Dermatofibrosarcoma protuberans, atypical fibroxanthoma, and cutaneous leiomyosarcoma are soft tissue sarcomas that have a high rate of recurrence when treated with standard surgical techniques and may occasionally metastasize. When removing these tumors it is very important to take adequate margins. Mohs micrographic surgery is proving to be very useful in treating these difficult neoplasms.


Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.
Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.


Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation.
Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX. We report the construction and initial characterization of a mouse model expressing the A140V MeCP2 mutation. These initial descriptive studies in male hemizygous mice have revealed brain abnormalities seen in both RTT and mental retardation. The abnormalities found include increases in cell packing density in the brain and a significant reduction in the complexity of neuronal dendritic branching. In contrast to some MeCP2 mutation mouse models, the A140V mouse has an apparently normal lifespan and normal weight gain patterns with no obvious seizures, tremors, breathing difficulties or kyphosis. We have identified various neurological abnormalities in this mouse model of Rett syndrome/X-linked mental retardation which may help to elucidate the manner in which MECP2 mutations cause neuronal changes resulting in mental retardation without the confounding effects of seizures, chronic hypoventilation, or other Rett syndrome associated symptoms.


Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides.
Amphiphilicity is the most critical parameter in the self-assembly of surfactant-like peptides (SLPs), regulating the way by which hydrophobic attraction holds peptides together. Its effects go beyond supramolecular assembly and may also trigger different cell responses of bioactive peptide-based nanostructures. Herein, we investigate the self-assembly and cellular effects of nanostructures based on isomeric SLPs composed by arginine (R) and phenylalanine (F). Two amphipathic designs were studied: a diblock construct F4R4 and its bolaamphiphile analog R2F4R2. A strong sequence-dependent polymorphism emerges with appearance of globules and vesicle-like assemblies, or flat nanotapes and cylindrical micelles. The diblock construct possesses good cell penetrating capabilities and effectiveness to kill SK-MEL-28 melanoma tumor cells, in contrast to reduced intracellular uptake and low cytotoxicity exhibited by the bolaamphiphilic form. Our findings demonstrate that amphipathic design is a relevant variable for self-assembling SLPs to modulate different cellular responses and may assist in optimizing the production of nanostructures based on arginine-enriched sequences in cell penetrating and antimicrobial peptides.


Family instability and child maladjustment trajectories during elementary school.
This study examines the relation between family instability and child maladjustment over a 6-year period in 369 children from four communities. Measures were collected annually from kindergarten through fifth grade. In associative growth curve models, family instability trajectories predicted children's externalizing and internalizing behavior trajectories during this time period. High levels of family instability also incrementally predicted the likelihood of meeting criteria for a DSM IV diagnosis during elementary school, above and beyond prediction from earlier measures of maladjustment. However, the timing of family instability had a different effect on externalizing versus internalizing disorders. In general, stronger relations were found between family instability and externalizing behaviors relative to internalizing behaviors, although children with comorbid disorders experienced the highest levels of family instability.


Lumbar Spinal Stenosis Severity by CT or MRI Does Not Predict Response to Epidural Corticosteroid versus Lidocaine Injections.
Epidural steroid injections may offer little-to-no short-term benefit in the overall population of patients with symptomatic spinal stenosis compared with lidocaine alone. We investigated whether imaging could identify subgroups of patients who might benefit most. A secondary analysis of the Lumbar Epidural Steroid Injections for Spinal Stenosis prospective, double-blind trial was performed, and patients were randomized to receive an epidural injection of lidocaine with or without corticosteroids. Patients (n = 350) were evaluated for qualitative and quantitative MR imaging or CT measures of lumbar spinal stenosis. The primary clinical end points were the Roland-Morris Disability Questionnaire and the leg pain numeric rating scale at 3 weeks following injection. ANCOVA was used to assess the significance of interaction terms between imaging measures of spinal stenosis and injectate type on clinical improvement. There was no difference in the improvement of disability or leg pain scores at 3 weeks between patients injected with epidural lidocaine alone compared with corticosteroid and lidocaine when accounting for the primary imaging measures of qualitative spinal stenosis assessment (interaction coefficients for disability score, -0.1; 95% CI, -1.3 to 1.2; P = .90; and for the leg pain score, 0.1; 95% CI, -0.6 to 0.8; P = .81) or the quantitative minimum thecal sac cross-sectional area (interaction coefficients for disability score, 0.01; 95% CI, -0.01 to 0.03; P = .40; and for the leg pain score, 0.01; 95% CI, -0.01 to 0.03; P = .33). Imaging measures of spinal stenosis are not associated with differential clinical responses following epidural corticosteroid injection.


Comparison of hemodynamic response and postoperative pain score between general anaesthesia with intravenous analgesia versus general anesthesia with caudal analgesia in pediatric patients undergoing open-heart surgery.
Regional anesthesia may attenuate adverse physiological stress responses associated with cardiothoracic surgery. In this study, hemodynamic stress response at the different time of surgical stimuli was compared between patients receiving general anesthesia (GA) along with caudal epidural analgesia with GA with intravenous analgesia in pediatric population undergoing open-heart surgery. This study aims to compare the hemodynamic response at the different time of surgical stimuli and postoperative pain score, in pediatric patients undergoing open-heart procedures. We designed a prospective randomized controlled trial to study hemodynamic effects between Group I and Group II. Fifty patients were randomly allocated equally into Group I (GA + caudal epidural) and Group II (GA + intravenous analgesia) by sealed envelope technique. After obtaining approval from Institutional Ethical Committee, this prospective study was conducted in 50 American Society of Anesthesiologist Classes II and III pediatric patients aged between 1 and 12 years posted for cardiac surgery in our institution. ANOVA, two-way ANOVA, and Student's test. The heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure variations were compared between Groups I and II at different time intervals. The variations were found to be significantly higher at the time of skin incision and 2 min after skin incision in Group II as compared to Group I. Pain score was compared between the groups and was found to be significantly lower with Group I (2.5 ± 1.2) as compared to Group II (4.6 ± 1.7), P = (0.004). Caudal analgesia with GA (Group I) was found to have better hemodynamic control and significantly better postoperative pain relief in the first 24 h after awakening.


Blood and marrow transplantation compensation: perspective in payer and provider relations.
The high cost per patient of hematopoietic cell transplantation (HCT) causes this therapy to be the focus of much controversy, given the competing societal demands to provide all possible therapy to preserve life while simultaneously limiting global health care expenditures. Treatment and eligibility decisions for HCT often are heavily scrutinized by both governmental and private payers and not simply determined by physicians, facility providers, and the patient. In an effort to control costs, payers have administrative infrastructure to review resource utilization by these patients. Additionally payers have developed payment methodologies, usually in the form of a case rate payment structure, that place facilities and physician providers of HCT at financial risk for adverse patient financial outcomes in an effort to promote optimal utilization and selection of patients for HCT. As providers enter into such financial risk arrangements with payers, the providers need to understand the true cost of care and be able to identify predictable and unpredictable outlier risks for the financial consequences of medical complications. HCT providers try to protect themselves from excessive financial risk by having different payment rates for different types of transplant, eg, autologous versus HLA or genotypically matched related versus HLA mismatched transplants. Because at certain times in the HCT process risk is more unpredictable, HCT providers require different payment system strategies for the different time periods of care such as evaluation, pre-transplant disease management, harvesting, and cell processing, as well as short- and long-term follow-up. Involvement by clinicians is essential for this process to be done well, especially given the rapid changes technological innovation brings to HCT. Constant dialogue and interaction between providers and payers on these difficult financial issues with HCT is essential to preserve patient access to this potentially lifesaving therapy.


Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China.
A woman with coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.


QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study.
Increased QTc dispersion has been associated with an increased risk for ventricular arrhythmias and cardiac death in selected patient populations. We examined the association between computerized QTc-dispersion measurements and mortality in a prospective analysis of the population-based Rotterdam Study among men and women aged > or = 55 years. QTc dispersion was computed with the use of the Modular ECG Analysis System as the difference between the maximum and minimum QTc intervals in 12 and 8 leads (ie, the 6 precordial leads, the shortest extremity lead, and the median of the 5 other extremity leads). After exclusion of those without a digitally stored ECG, the population consisted of 2358 men and 3454 women. During the 3 to 6.5 years (mean, 4 years) of follow-up, 568 subjects (9.8%) died. The degree of QTc dispersion was categorized into tertiles. Data were analyzed using the Cox proportional hazards model, with adjustment for age. For QTc dispersion in 8 leads, those in the highest tertile relative to the lowest tertile had a twofold risk for cardiac death (hazard ratio, 2.5; 95% confidence interval [CI], 1.6 to 4.0) and sudden cardiac death (hazard ratio, 1.9; 95% CI, 1.0 to 3.7) and a 40% increased risk for total mortality (hazard ratio, 1.4; 95% CI, 1.2 to 1.8). Additional adjustment for potential confounders, including history of myocardial infarction, hypertension, and overall QTc, did not materially change the risk estimates. Hazard ratios for QTc dispersion in 12 leads were comparable to those found for QTc dispersion in 8 leads. QTc dispersion is an important predictor of cardiac mortality in older men and women.


Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.
Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.