Assessing patient-reported outcomes and preferences for same-day discharge after percutaneous coronary intervention: results from a pilot randomized, controlled trial.
Same-day discharge after percutaneous coronary intervention (PCI) may be safe for some patients. Few data are available on patient-reported outcomes and preferences for same-day discharge after PCI. Between March 2008 and March 2010, a total of 298 patients undergoing elective PCI via femoral access at 2 medical centers (Mount Sinai Hospital, New York, NY, and Baylor Medical Center, Dallas, TX) were randomized to same-day (n=150) or next-day (n=148) discharge. The primary outcome was high patient coping during the 7 days after discharge defined as scores <20 on the validated postdischarge coping difficulty scale. Safety outcomes, clopidogrel adherence, and patient preferences were secondary outcomes. Before discharge, patients randomized to same-day and next-day discharge were similar with respect to sociodemographic and clinical characteristics. High-coping ability, assessed 7 days after PCI, was present for 79% of patients randomized to same-day discharge and for 77% of patients randomized to next-day discharge. The difference in high coping ability, 2 (95% confidence interval, -7 to 11), did not cross the noninferiority threshold of -12% (P<0.001 that same-day discharge is not noninferior to next-day discharge). At 30 days after PCI, clopidogrel adherence, physician and emergency room visits, and hospitalization were similar in the 2 randomization groups. In addition, 80% and 68% of those randomized to same-day and next-day discharge, respectively, stated they would prefer same-day discharge if they were to have another PCI procedure. Same-day discharge after PCI was associated with patient-reported and clinical outcomes similar to those of next-day discharge and was preferred by most patients.


Preparation of the cervix: hydrophilic and prostaglandin dilators.
The use of laminaria has made possible safe uterine evacuation in the second-trimester and has been identified as a protective factor in the prevention of uterine perforation in first-trimester abortion. Two additional approaches to cervical dilation are now available - synthetic hydrophilic dilators and prostaglandin analogues. Neither has been in use long enough to undergo thorough evaluation, but it seems possible that they may confer similar advantages while avoiding the discomfort and inconvenience associated with laminaria. New approaches to the use of laminaria have increased their value as cervical dilators. They may be left in the cervix for 6-48 hours. Multiple sets may be employed to achieve adequate cervical dilation for late second-trimester uterine evacuation. When fetal membranes are intact, prolonged use or multiple insertions of laminaria do not appear to increase rates of post-abortion infection. Lamicel and Dilapan are new synthetic dilators which affect the cervix much more rapidly than laminaria. The former does not apply radial force to the walls of the cervical canal, but the latter does. Significant dilation may be achieved in a few hours. Prostaglandins can also alter the cervix in only a few hours. Meteneprost appears to do so with minimal gastrointestinal side-effects and with a low risk of bleeding or abortion.


The potential for regeneration of articular cartilage in defects created by chondral shaving and subchondral abrasion. An experimental investigation in rabbits.
Animal models for chondral shaving and subchondral abrasion were created to resolve the controversy about the nature of the repair tissue after these procedures and to determine the effect of continuous passive motion on the quality of the repair tissue. Chondral shaving was performed on the patella in forty adolescent rabbits, and subchondral abrasion was performed on the patella in another forty rabbits. In both procedures, a three-millimeter-diameter defect was created. After the operation, twenty animals from each group were allowed intermittent active motion; the remainder were treated by continuous passive motion for two weeks, followed by intermittent active motion. Half of the animals from each group were killed at four weeks and the other half, at twelve weeks. There was no evidence of repair tissue in the defects at either four or twelve weeks after chondral shaving, regardless of the postoperative treatment. The remaining underlying cartilage, however, had degenerated. After abrasion of subchondral bone, the defects in animals that were treated with only intermittent active motion healed at twelve weeks, although the quality of the repair tissue varied. All ten of the animals that were treated with continuous passive motion, however, had mature, hyaline-like cartilage as the predominant repair tissue at twelve weeks, compared with six of the ten animals that were treated with intermittent active motion (p less than 0.05). We concluded that, in this model, partial-thickness defects created by chondral shaving do not heal; rather, the remaining underlying cartilage degenerates. Full-thickness defects created by subchondral abrasion can heal by regeneration of hyaline-like cartilage. Such healing is enhanced by continuous passive motion for two weeks postoperatively.


Role of crotonyl coenzyme A reductase in determining the ratio of polyketides monensin A and monensin B produced by Streptomyces cinnamonensis.
The ccr gene, encoding crotonyl coenzyme A (CoA) reductase (CCR), was cloned from Streptomyces cinnamonensis C730.1 and shown to encode a protein with 90% amino acid sequence identity to the CCRs of Streptomyces collinus and Streptomyces coelicolor. A ccr-disrupted mutant, S. cinnamonensis L1, was constructed by inserting the hyg resistance gene into a unique BglII site within the ccr coding region. By use of the ermE* promoter, the S. collinus ccr gene was expressed from plasmids in S. cinnamonensis C730. 1/pHL18 and L1/pHL18. CCR activity in mutant L1 was shown to decrease by more than 90% in both yeast extract-malt extract (YEME) medium and a complex fermentation medium, compared to that in wild-type C730.1. Compared to C730.1, mutants C730.1/pHL18 and L1/pHL18 exhibited a huge increase in CCR activity (14- and 13-fold, respectively) in YEME medium and a moderate increase (3.7- and 2. 7-fold, respectively) in the complex fermentation medium. In the complex fermentation medium, S. cinnamonensis L1 produced monensins A and B in a ratio of 12:88, dramatically lower than the 50:50 ratio observed for both C730.1 and C730.1/pHL18. Plasmid (pHL18)-based expression of the S. collinus ccr gene in mutant L1 increased the monensin A/monensin B ratio to 42:58. Labeling experiments with [1, 2-(13)C(2)]acetate demonstrated the same levels of intact incorporation of this material into the butyrate-derived portion of monensin A in both C730.1 and mutant C730.1/pLH18 but a markedly decreased level of such incorporation in mutant L1. The addition of crotonic acid at 15 mM led to significant increases in the monensin A/monensin B ratio in C730.1 and C730.1/pHL18 but had no effect in S. cinnamonensis L1. These results demonstrate that CCR plays a significant role in providing butyryl-CoA for monensin A biosynthesis and is present in wild-type S. cinnamonensis C730.1 at a level sufficient that the availability of the appropriate substrate (crotonyl-CoA) is limiting.


Feasibility of near-infrared spectroscopy to detect and to quantify adulterants in cow milk.
Cow milk adulteration involves the dilution of milk with a less-expensive component, such as water or whey. Near-infrared spectroscopy (NIRS) was employed to detect the adulterations of milk, non-destructively. Two adulteration types of cow milk with water and whey were prepared, respectively. NIR spectra of milk adulterations and natural milk samples in the region of 1100 - 2500 nm were collected. The classification of milk adulterations and natural milk were conducted by using discriminant partial least squares (DPLS) and soft independent modelling of class analogy (SIMCA) methods. PLS calibration models for the determination of water and whey contents in milk adulteration were also developed, individually. Comparisons of the classification methods, wavelength regions and data pretreatments were investigated, and are reported in this study. This study showed that NIR spectroscopy can be used to detect water or whey adulterants and their contents in milk samples.


Dental microwear profilometry of African non-cercopithecoid catarrhines of the Early Miocene.
The Early Miocene of Kenya has yielded the remains of many important stem catarrhine species that provide a glimpse of the East African primate radiation at a time of major faunal turnover. These taxa have been subject to innumerable studies, yet there is still no consensus on their dietary niches. Here we report results of an analysis of dental microwear textures of non-cercopithecoid catarrhines from the Early Miocene of Kenya. Scanning confocal profilometry of all available molar specimens with undamaged occlusal surfaces revealed 82 individuals with unobscured antemortem microwear, representing Dendropithecus, Micropithecus, Limnopithecus, Proconsul, and Rangwapithecus. Scale-sensitive fractal analysis was used to generate microwear texture attributes for each individual, and the fossil taxa were compared with each other using conservative non-parametric statistical tests. This study revealed no discernible variation in microwear texture among the fossil taxa, which is consistent with results from a previous feature-based microwear study using smaller samples. Our results suggest that, despite their morphological differences, these taxa likely often consumed foods with similar abrasive and fracture properties. However, statistical analyses of microwear texture data indicate differences between the Miocene fossil sample and several extant anthropoid primate genera. This suggests that the African non-cercopithecoid catarrhines included in our study, despite variations in tooth form, had generalist diets that were not yet specialized to the degree of many modern taxa.


Summary of two questionnaires designed to understand the research climate for Bioimage Analysts in the UK between 2016-2019.
Background: Bioimage analysis is an emerging field within the global research community. It is an interdisciplinary discipline which requires knowledge of biology, image analysis and biophysics. This report represents the analysis and discussion of two questionnaires run by the Image Analysis Focused Interest Group of the Royal Microscopical Society (IAFIG-RMS). The goal of this document, which represents the analysis and interpretation of these questionnaires, is to highlight the current research climate for Bioimage Analysts in the UK and discusses some of the problems and possibilities for this emerging discipline. Methods: Two questionnaires (2016 and 2019) were developed and sent to researchers in the UK using mailing lists and forums specific for microscopy and image analysis. The participants were asked a range of questions spanning different aspects of their work and funding. Respondents were collected and analysed using Jupyter notebooks. Results: The analysis of the responses from these questionnaires highlighted many interesting issues and aspects of this community. It is clear that a major issue for the community is the nature of the funding and the long-term career possibilities available. Furthermore, the issue of independence is discussed with clear evidence that researchers would like to pursue their own research with the option of dedicated time to support the research of others. Conclusions: It is our hope that this study will help catalyse funding opportunities which help support this emerging discipline and help it establish a unique identity for itself within the research community in the UK and beyond.


SeqFeatR for the Discovery of Feature-Sequence Associations.
Specific selection pressures often lead to specifically mutated genomes. The open source software SeqFeatR has been developed to identify associations between mutation patterns in biological sequences and specific selection pressures ("features"). For instance, SeqFeatR has been used to discover in viral protein sequences new T cell epitopes for hosts of given HLA types. SeqFeatR supports frequentist and Bayesian methods for the discovery of statistical sequence-feature associations. Moreover, it offers novel ways to visualize results of the statistical analyses and to relate them to further properties. In this article we demonstrate various functions of SeqFeatR with real data. The most frequently used set of functions is also provided by a web server. SeqFeatR is implemented as R package and freely available from the R archive CRAN (http://cran.r-project.org/web/packages/SeqFeatR/index.html). The package includes a tutorial vignette. The software is distributed under the GNU General Public License (version 3 or later). The web server URL is https://seqfeatr.zmb.uni-due.de.


Shallow genomics, phylogenetics, and evolution in the family Drosophilidae.
The effects of the genomic revolution are beginning to be felt in all disciplines of the biological sciences. Evolutionary biology in general, and phylogenetic systematics in particular, are being revolutionized by these advances. The advent of rapid nucleotide sequencing techniques have provided phylogenetic biologists with the tools required to quickly and efficiently generate large amounts of character information. We use family Drosophilidae as a model system to study phylogenetics and genome evolution by combining high throughput sequencing methods from the field genomics and standard phylogenetic methodology. This paper presents preliminary results from this work. Separate data partitions, based on either gene function or linkage group, are compared to a combined analysis of all the data to assess support on phylogenetic trees.


Coronary revascularization in Japan. Part 4: coronary artery bypass surgery during 1997.
The Japanese Coronary Intervention Study (JCIS) has revealed that 17,667 coronary artery bypass grafting (CABG) procedures were performed at 477 facilities during 1997, and this report describes the demographic and clinical characteristics, treatment strategies, and the in-hospital and the long-term outcomes in patients treated with CABG in Japan. A total of 1,862 CABG cases, which corresponded to approximately 10% of the overall CABGs, were selected at random. The mean age was 65 years, and 76% of cases were males. The most prevalent clinical diagnosis was stable angina (54%), followed by myocardial infarction (MI) excluding acute myocardial infarction (AMI) (48%), unstable angina (25%), and AMI (5%). A large proportion of cases had multivessel coronary artery disease: 3-vessel disease (56%) and left main trunk disease (29%). The CABG procedures were emergency in 16%, and 93% of anastomotic sites were patent. In-hospital mortality and MI occurred in 5.1% and 3.5% of cases, respectively. The in-hospital mortality rate for emergency CABG was 12.0%, whereas that for elective CABG was 3.8%. The overall mortality rate during the follow-up period of 2.3 years was 10%. During the follow-up period, MI and angina occurred in 2% and 8% of cases, respectively. Percutaneous coronary intervention (PCI) was performed for 8%, and repeat CABG for 0.8%. In Japan, CABG was performed in patients with multivessel coronary artery disease with extensive risk factors. Angiographically determined success was achieved in 93% and the need for subsequent revascularization was relatively low.


[Changes in the lungs in patients with lymphogranulomatosis, Stages I-II, following combination therapy].
Early and late pulmonary changes in 140 patients with Hodgkin's disease, Stages I-II, following combined treatment (polychemo- and radiotherapy) are analysed. Radiation pulmonitis and local paramediastinal fibrosis occur less frequently and they are less noticeable in combined therapy as compared to similar changes developing after radiation therapy only. It can be due to the fact that a course of polychemotherapy at its first stage results in a considerable decrease of the mediastinal lymph nodes (up to their complete regression) thus making it possible to shape irradiation fields of smaller sizes and to decrease the volume of pulmonary tissue to be irradiated.


Analogue femurs for laboratory investigations of prosthesis stress distributions and fixation failures.
A polymeric analogue femur in combination with a brittle-coating stress-analysis technique was used to compare the relative femoral surface-strain distributions for various hip prostheses. The influence of prosthesis design factors, such as the geometry and material, the effect of a collar, and surface texturing, were readily ascertained and in agreement with previous investigations using other techniques. The fixation failures observed with this laboratory test model were similar to those of published clinical findings.


Endovascular recanalization of complete subacute to chronic atherosclerotic occlusions of intracranial arteries.
Symptomatic subacute/chronic large artery intracranial occlusive disease represents a common medical dilemma. We now report a multicenter experience of endovascular recanalization of intracranial atherosclerotic occlusions refractory to medical therapy. Retrospective multicenter case series of consecutive endovascularly treated patients presenting with symptomatic (transient ischemic attack (TIA) or stroke) subacute (>48 h) or chronic complete occlusion of an intracranial artery of presumed atherosclerotic etiology. All of the patients were considered to be in the high risk category with symptomatic intracranial occlusions and progression or recurrence of their symptoms despite the best medical therapies. 24 patients (median age 63 years; mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score 10; 66% men) presenting with recurrent TIAs (n=1) or strokes (n=23) were treated in two academic centers from April 2005 to June 2012. Median time from symptoms/documented occlusion to treatment was 5 days. Periprocedural complications included one symptomatic intracranial hemorrhage, one reperfusion syndrome, three asymptomatic dissections, and one asymptomatic perforation. There were no periprocedural strokes. Immediate postprocedural improvement (NIHSS decrease ≥4 at hospital discharge) occurred in 43% (10/23) of patients. There were no recurrent TIAs or strokes in the 22 patients with clinical follow-up at 90 days. At 90 days, there were two deaths (unrelated to the procedure) and 9/22 patients with an available modified Rankin Scale (mRS) score achieved a good outcome (mRS score of 0-2). Endovascular recanalization can be performed with an acceptable safety profile in selected patients with symptomatic complete subacute to chronic intracranial atherosclerotic occlusion. Additional studies are warranted to investigate whether this treatment compares favorably with best medical management.


Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.
Pouchitis may occur following ileal pouch-anal anastomosis for chronic ulcerative colitis in approximately 30% of patients. The primary objective was to determine the efficacy of medical therapies for pouchitis (including antibiotic, probiotic, and other agents) as substantiated by data from randomized controlled trials (RCTs). A search for RCTs from 1966 to October 2009 was performed using the MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus databases. Randomized controlled treatment or prevention trials of adult patients who underwent ileal pouch-anal anastomosis for ulcerative colitis who subsequently developed pouchitis or were at risk for pouchitis were considered for inclusion. Extracted data were converted to 2X2 tables and then synthesized in to a summary statistic using the Peto odds ratio (OR) and [95% confidence intervals], or weighted mean difference (WMD), using RevMan-5 for Mac OS 10.6. Eleven RCTs fulfilled the inclusion criteria and were included in the review. The efficacy of 10 different pharmacologic agents was assessed. For the treatment of acute pouchitis (4 RCTS, 5 agents), ciprofloxacin was more effective at inducing remission than metronidazole. Neither rifaximin nor lactobacillus GG were more effective than placebo, while budesonide enemas and metronidazole were similarly effective, for inducing remission of acute pouchitis. For the treatment and maintenance of remission of chronic pouchitis (4 RCTs, 4 agents), glutamine suppositories were not more effective than butyrate suppositories, and bismuth carbomer foam enemas were not more effective than placebo, while VSL#3 was more effective than placebo in maintaining remission of chronic pouchitis in patients with chronic pouchitis who achieved remission with antibiotics. For the prevention of pouchitis (3 RCTs, 2 agents), in one study VSL#3 was more effective than placebo while in another study VSL#3 was not more effective than no treatment. Allopurinol was not more effective than placebo, while inulin was more effective than placebo but the results were not clinically significant. For acute pouchitis, ciprofloxacin was more effective than metronidazole, while budesonide enemas and metronidazole were similarly effective. For chronic pouchitis, VSL#3 was more effective than placebo. For the prevention of pouchitis, VSL#3 was more effective than placebo. Larger RCTs are needed to determine the optimal agent(s) for the treatment and prevention of pouchitis.


Abnormal vasoreaction to arousal stimuli--an early sign of diabetic sympathetic neuropathy demonstrated by laser Doppler flowmetry.
Early diagnosis of diabetic autonomic neuropathy contributes to the prevention of serious complications and improves the prognosis of patients with diabetes. Common tests of peripheral autonomic function are the quantitative sudomotor axon reflex test or the sympathetic skin response (SSR). Quantitative sudomotor axon reflex test is quantifiable but technically demanding. Sympathetic skin response cannot be quantified easily. To study whether measurement of skin vasomotion is suited to assess early sympathetic peripheral neuropathy, we monitored skin blood flow at the index finger pulp using laser Doppler flowmetry before and after electrical stimulation. We assured that the stimulus was sufficient to elicit an efferent sympathetic response by monitoring palmar SSR ipsilateral to the flow measurement. In 21 diabetic patients with at least stage one polyneuropathy and 21 age-matched controls, SSR was recorded from one palm and sole following electrical stimulation at the contralateral wrist. Sympathetic skin response was present at the palms in all patients and controls and absent at the sole of two patients only. Eight patients (38.9%) had abnormal SSR, with absent plantar responses in two patients, prolonged plantar latencies in six patients, and prolonged volar SSR latencies in two patients. Skin blood flow responses were more often abnormal (46.1%) than SSR (P < 0.05), responses were delayed in two patients and absent in another 8 patients. Skin blood flow retest reliability was high with a repeatability coefficient of 10.64% in controls and 12.34 % in patients. Skin blood flow monitoring after sympathetic stimulation provides a reproducible parameter of sympathetic vasomotor control and complements the diagnostic value of SSR testing.


Low Serologic Prevalences Suggest Sporadic Infections of Hepatitis E Virus in Chamois (Rupicapra rupicapra) and Red Deer (Cervus elaphus) in the Italian Alps.
Hepatitis E virus (HEV) is a worldwide public health concern, with an increase in human autochthonous cases in Europe. Although domestic pigs and wild boar (Sus scrofa) are the main reservoirs of HEV, the constant expansion of wild ruminants increases the potential for HEV transmission. We investigated HEV infection in chamois (Rupicapra rupicapra) and red deer (Cervus elaphus) in the Italian Alps using an enzyme-linked immunosorbent assay (ELISA). We detected HEV antibodies from 2013 to 2015 in both host species, with seroprevalences of 1.2% and 0.8% in chamois and red deer, respectively. All serum samples that were positive to HEV antibodies by ELISA were negative when tested by real-time reverse-transcriptase PCR to detect HEV RNA. The observed low seroprevalence of HEV suggested a sporadic circulation of HEV in the alpine environment, and it was consistent with the low seroprevalence observed in wild boar in the Alps. Our observations supported the role of chamois and red deer as spillover hosts of HEV infections in the Italian Alps.


Coitus and orgasm at term: effect on spontaneous labour and pregnancy outcome.
Coitus and orgasm in late pregnancy are believed to facilitate the onset of labour. We aim to evaluate the relationship at term of reported coitus and orgasm with spontaneous labour. Women at term scheduled for non-urgent labour induction were asked to keep a coitus and orgasm diary. These women were recruited for a randomised trial on the effect of coitus to promote spontaneous labour. For this analysis, the women were categorised into coitally-active and abstinent groups according to their coital diary. Spontaneous labour prior to the date of scheduled labour induction was the primary outcome. Labour, delivery and neonatal outcome were also evaluated. Multivariable logistic regression analysis was used to control for significant variables. On univariate analysis, the inverse association of coitus with spontaneous labour was borderline (odds ratio [OR] 0.6; 95 percent confidence interval [CI] 0.3-1.0; p-value is 0.052). Orgasm was not associated with spontaneous labour (p-value is 0.33). After adjustment, coitus (adjusted OR 0.4; 95 percent CI 0.2-0.8; p-value is 0.009) displayed a significant inverse association with spontaneous labour. Coitus and orgasm were not associated with any other adverse pregnancy outcome. Women who reported coitus were less likely to go into spontaneous labour prior to their scheduled labour induction. Reported coitus and orgasm were not associated with adverse pregnancy outcome.


Decoding aging-dependent regenerative decline across tissues at single-cell resolution.
Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1+ macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.


Metabolic mapping of a cardiac reflex mediated by sympathetic ganglia in dogs.
The hypothesis tested was that some cardiac reflexes can be mediated by the neural mechanisms in thoracic sympathetic ganglia in addition to those existing in the spinal cord or brain stem. In mongrel dogs anesthetized with pentobarbital sodium the left stellate (SG) and middle cervical (MCG) ganglion were decentralized, and the left thoracic vagosympathetic trunk was cut cranial to the MCG and caudal to the MCG but above the heart. The left thoracic vagosympathetic trunk below the MCG was then stimulated afferently. A single bolus of 2-[14C]deoxyglucose was injected intravenously and the stimuli repeated periodically toward the decentralized ganglia for 45 min. The heart and ganglia were then removed, frozen, and sectioned for autoradiography. Significant increases in glucose utilization were found in both the SG and MCG compared with ganglia from nonstimulated control animals. Significant increases in the glucose utilization of the endocardial third of the left ventricle were also observed in the reflexly stimulated hearts. Neural mechanisms in the acutely decentralized SG and MCG could modify cardiac glucose utilization within specific areas of the heart. In addition, such ganglionic mechanisms may be concentrated within the caudal half of the SG. These data suggest that many neurons in the thoracic autonomic ganglia may be involved in local cardiac reflexes.


Immunological Implications of Physical Inactivity among Older Adults during the COVID-19 Pandemic.
Social distancing has been adopted worldwide to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Social isolation is likely to lead to a decline in physical activity, which could result in immune system dysfunction, thereby increasing infection susceptibility and exacerbating the pathophysiology of conditions that are common among older adults, including cardiovascular disease, cancer, and inflammatory disorders. Older adults and people living with these comorbidities are at a greater risk for complications during coronavirus disease 2019 (COVID-19). In this review, we discuss the negative impact of physical inactivity on immune function and showcase evidence that regular physical activity may be an effective strategy to counter some of the deleterious effects of social isolation. Furthermore, we briefly highlight key research questions in exercise immunology, with a focus on older adults in the context of COVID-19. Although it is worth emphasizing that there is no direct evidence that physical activity can prevent or treat -COVID-19, promoting an active lifestyle is a key intervention to counteract the effects of social isolation, especially in older adults and other at-risk individuals, such as those living with chronic diseases associated with ageing and lifestyle.


Lipase Treatment of Dietary Krill Oil, but Not Fish Oil, Enables Enrichment of Brain Eicosapentaenoic Acid and Docosahexaenoic Acid.
Currently available omega-3 fatty acid supplements do not enrich the docosahexaenoic acid (DHA) of the adult brain because they are absorbed as triacylglycerol, whereas the transporter at the blood brain barrier requires lysophosphatidylcholine (LPC)-DHA. The hypothesis that treatment of krill oil (KO), which contains DHA/eicosapentaenoic acid (EPA) at the SN2 position of phosphatidylcholine, with SN1-specific lipase will generate LPC-DHA/EPA and which can be absorbed intact and transported into the brain, is tested. KO and fish oil (FO) are treated with Mucor meihei lipase, incorporated into AIN 93G diet, and fed to 2-month-old mice for 30 days. Fatty acid composition is analyzed by gas chromatography/mass spectroscopy. Brain derived neurotrophic factor (BDNF) is measured by ELISA. Lipase-treated (LT) KO increases brain DHA and EPA, respectively, 5-and 70-fold better than untreated (UT) KO. FO, whether lipase-treated or not, has no effect on brain DHA/EPA. LTKO is also more efficient in enriching liver DHA/EPA, but less efficient than UTKO and FO in enriching adipose tissue and heart. Brain BDNF is significantly increased by LTKO, but only marginally by other preparations. Pretreatment of dietary KO with lipase enables it to efficiently increase brain DHA/EPA because of the generation of LPC-DHA/EPA.


[Experiences with the Janetta operation in patients with trigeminal neuralgia].
From a small group of 20 patients treated by us those 13 patients were selected for whom the permanent therapy results could be assessed with a certain reliability. This procedure made the value of a precise establishment of the case history with respect to the possibility of a trigeminal root alteration evident. Only in one operation there was no relation between trigeminal root and vessels, but there was a concomitant arachnoiditis. In 12 cases the immediate effect of the operation was excellent to good, and although the permanent effect reduced these figures after one year, it was still higher than that obtained by other methods. The absence of an additional damage of the nerve and/or the surrounding brain should be pointed out. Thus the Janetta method became the operation technique of first choice provided there are the general physical pre-requisites to an exposure of the cerebellopontile angle.


Maternal and fetal outcomes of acute pancreatitis in pregnancy: a population-based study.
Acute pancreatitis during pregnancy can have negative effects on both the mother and the fetus. The primary aim of this study is to evaluate the trends, maternal and fetal outcomes, and associated comorbidities of acute pancreatitis during pregnancy using data from the USA National Inpatient Sample (NIS) database. This study is a retrospective analysis of hospital discharge records from the NIS database from 2009 to 2019. Delivery patients with acute pancreatitis faced a higher risk of maternal mortality (AOR 91.02, 95% CI 28.47-291.06), postpartum hemorrhage (AOR 1.59, 95% CI 1.02-2.49), and hypertensive complications (defined as preeclampsia, eclampsia, or HELLP syndrome) (AOR 3.42, 95% CI 2.56-4.56) compared to those without acute pancreatitis. Moreover, we saw an increased incidence of preterm labor (AOR 3.94, 95% CI 3.02-5.12) and fetal death (AOR 3.12, 95% CI 1.76-5.53). Rates of fetal restriction and large fetal size were comparable. Additionally, the acute pancreatitis group showed higher rates of acute kidney injury (4.2% vs. 0.06%; AOR, 31.02, 95% CI 12.50-76.98), severe sepsis (0.8% vs. 0.01%; AOR, 34.49, 95% CI 7.67-155.14), and respiratory failure (2.4% vs. 0.06%; AOR, 20.77, 95% CI (8.55-50.41). There were no significant differences in maternal and perinatal outcomes in biliary pancreatitis after the intervention compared to conservative treatment. Acute pancreatitis during pregnancy can have negative effects on both the mother and fetus. Treatment for biliary pancreatitis does not affect maternal and fetal outcomes. An interdisciplinary approach is essential to ensure optimal outcomes for mothers and their offspring in these cases.


What Do We (Not) Know About Global Views of Human Gene Editing? Insights and Blind Spots in the CRISPR Era.
As research on human applications of CRISPR advances, researchers, advisory bodies, and other stakeholder organizations continue calling for global public discourses and engagement to shape the development of human gene editing (HGE). Research that captures public views and tests ways for engaging across viewpoints is vital for facilitating these discourses. Unfortunately, such research lags behind advances in HGE research and applications. Here, we provide the first review of nationally representative public-opinion surveys focused on HGE to discuss limitations and remaining gaps, illustrating how these gaps hinder interpretation of existing studies. Rigorous research with proper methods for capturing representative public opinion of HGE is limited, especially in countries outside of the United States and on a global scale. The result is severely restricted understanding of even the surface level of public views concerning HGE. We identify broad areas where we need more and better research capturing public views, and describe how future surveys can help collect insights necessary for discourse and decision making on HGE.


A study of childhood non-Hodgkin's lymphoma.
The pathologic and clinical features of 31 cases of childhood non-Hodgkin's lymphoma (NHL) were reviewed retrospectively using Rappaport's classification and a modification of the Ann Arbor staging system. Twenty-nine (93.5%) of the patients had diffuse and 2 (6.5%) had nodular lymphoma. Diffuse histiocytic lymphoma accounted for 10 cases (32.3%), diffuse undifferentiated for 9 (29%), and diffuse lymphocytic, poorly differentiated for 5 (16.1%). Five cases (16.1%) were unclassifiable. No cases of well-differenitated lymphocytic or mixed cell lymphoma were found. A modified classification was attempted, which included also large basophilic cell (LBC), convoluted T-lymphocytic (CTL), and Burkitt's lymphomas. These pathologic subgroups accounted for 35.4%, 16.1%, and 6.5% of the cases, respectively. The patients were almost equally divided between clinically localized and generalized stages, and their survival was stage-dependent. The overall survival was 32.3%; the 3-year survival was 50% for Stages I and II, compared to 7.7% for Stages III and IV. The gastrointestinal tract was the most common site of origin. In 22% of the cases, the disease originated in extra-lymphatic tissues. Central nervous syste, involvement occurred in 10 of 31 children (32%), and a leukemic picture developed in 6 of 31 (19%). The Ctl lymphomas were confined to the mediastinum, whereas the LBC lymphomas arose mostly in Waldeyer's ring and Peyer's patches. We conclude that the extent of the disease as determined by clinical staging had prognostic significance in childhood NHL. The prognostic value of the histological classification could not be clearly established from our data.


Variability in Minimally Invasive Surgery for Sagittal Craniosynostosis.
Minimally invasive approaches to the surgical correction of sagittal craniosynostosis are gaining favor as an alternative to open cranial vault remodeling. In this systematic review, the reviewers evaluate the variability in described surgical techniques for minimally invasive correction of sagittal craniosynostosis. Articles were selected based on predetermined inclusion and exclusion criteria from an online literature search through PubMed, EMBASE, and the Cochrane library. Extracted data included the incisions, method of dissection, osteotomies performed, and type of force therapy utilized.A total of 28 articles from 15 author groups were included in the final analysis. Of the 28 articles, 17 distinct techniques were identified. Significant variation existed in both the technique and the terminology used to describe it. Access to the cranium varied between a standard bicoronal incision (n = 2), a "lazy S" incision (n = 2), and multiple short incisions along the fused sagittal suture (n = 13). Additional variations were found in the size and design of the osteotomy, the usage (and duration, if applicable) of force therapy, and the age of the patient at the time of surgical intervention.This systematic review demonstrates that minimally invasive approaches to sagittal craniosynostosis vary widely in technique with respect to the incisions, osteotomies, and force therapy used. Additionally, the terminology employed in describing minimally invasive approaches is inconsistent across centers. This discrepancy between technique and terminology presents challenges for reporting and interpreting the increasing body of literature on this subject. We recommend standard terminology be used for future publications on minimally invasive techniques.


Can killers be saviors?
Autoimmunity and cancer have a multifarious epidemiology. Often, it is because of an impaired genome, culminating in functional aberrations in the human system. Systemic lupus erythematosus (SLE) is a heterogeneous complex disease which ensues due to the failure of the immune system to distinguish between self and non-self antigens, thus producing autoantibodies against DNA, RNA and proteins. Cancer, the other side of the same coin, results from an excessive proliferation of cells that evade immune regulation as a result of incompetent defense by T-cells, B-cells and macrophages. Recent findings have indicated that lupus autoantibodies could be used as an effective weapon to kill cancerous cells. This is an attempt to take an account of malicious 'lupus autoantibodies' and their role in neutralizing cancerous cells which may help in enhancing the survival rate of cancer patients, hence, killers can be saviors.


Adaptation or exaptation? An experimental test of hypotheses on the origin of salinity tolerance in Bufo calamita.
The natterjack toad (Bufo calamita) shows variation in embryonic and larval salinity tolerance across populations in southern Spain. However, its aquatic/terrestrial biphasic life cycle, together with remarkable differences in salinity tolerance between Spanish and UK freshwater populations suggest an alternative hypothesis to local adaptation. Drought resistance during the terrestrial phase and salinity tolerance during the aquatic phase are both related to osmotic stress tolerance, and if there were an association between them, one could have evolved as an exaptation from the other. To test such an association, we reared B. calamita juveniles from three populations known to differ genetically in their salinity tolerance, under either dry or humid conditions. Drought decreased growth rate, enhanced burying behaviour, and decreased foraging activity and efficiency. No significant population x treatment interaction was found for any variable, i.e. populations were equally affected by drought. These results do not support the hypothesis of a genetic association between salinity and drought tolerance.


Development of a rapid qualitative assay for determining elevated antibody levels to periodontopathic organisms.
To allow more widespread use of systemic antibody analysis in clinical settings, a rapid test for determining elevated antibody to periodontitis-associated bacteria was developed. The technique utilizes dot-immunoblotting (DIB) on nitrocellulose paper with whole formalinized Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. An ELISA was used to compare IgG antibody levels to these organisms in venous serum and peripheral capillary blood from 44 subjects. Correlation between serum and capillary levels ranged from r = 0.760 to 0.900 (P less than 0.00001). Capillary blood antibody levels averaged 55% of those detected in serum. The assay was developed using a variety of antigen and reagent concentrations and multiple chromogenic enzyme-substrate systems. Subsequently, 34 periodontally diseased and 10 periodontally healthy subjects were analyzed for serum IgG antibodies using a quantitative ELISA. The qualitative DIB was performed using capillary blood obtained by digi-puncture and results were compared in a blind fashion to the ELISA data. Relative to its ability to detect elevated antibody levels to these 3 organisms, the DIB had an overall sensitivity of 93% and a specificity of 87% (P less than 0.000001). Using peripheral capillary blood and the DIB, detection of elevated systemic antibody levels can be performed in approximately 2 hours. The DIB may be a useful aid in assessing the host response to putative periodontopathic microorganisms.


Socioeconomic factors that affect artisanal fishers' readiness to exit a declining fishery.
The emerging world crisis created by declining fish stocks poses a challenge to resource users and managers. The problem is particularly acute in poor nations, such as those in East Africa, where fishing is an important subsistence activity but high fishing intensity and use of destructive gear have resulted in declining catches. In this context developing effective management strategies requires an understanding of how fishers may respond to declines in catch. We examined the readiness of 141 Kenyan fishers to stop fishing under hypothetical scenarios of declines in catch and how socioeconomic conditions influenced their decisions. As expected, the proportion of fishers that would exit the fishery increased with magnitude of decline in catch. Fishers were more likely to say they would stop fishing if they were from households that had a higher material style of life and a greater number of occupations. Variables such as capital investment in the fishery and the proportion of catch sold had weak, nonsignificant relationships. Our finding that fishers from poorer households would be less likely to exit a severely declining fishery is consistent with the literature on poverty traps, which suggests the poor are unable to mobilize the necessary resources to overcome either shocks or chronic low-income situations and consequently may remain in poverty. This finding supports the proposition that wealth generation and employment opportunities directed at the poorest fishers may help reduce fishing effort on overexploited fisheries, but successful interventions such as these will require an understanding of the socioeconomic context in which fishers operate.


Seasonal, spatial, and interspecific variation in quercetin in Apocynum venetum and Poacynum hendersonii, Chinese traditional herbal teas.
Quercetin is of particular importance as it has been found to have functions of suppressing tumors, reducing blood pressure, and scavenging free radicals. It is one of the major flavonoids in Apocynum venetum and Poacynum hendersonii, whose leaves have long been used as traditional herbal teas in China and Japan. Both species are also cultivated as fiber plants because of their outstanding quality of phloem fiber in stems. To obtain high output of both quercetin and fiber, it is necessary to optimize harvesting time for their leaves. Thus, understanding the developmental patterns of quercetin in leaves and fiber in stems is crucial to achieving this goal. In the present study, temporal and interspecific variations in quercetin in the leaves between A. venetum and P. hendersonii and spatial variation among P. hendersonii populations were studied by HPLC during the period from April to October in 1999. The results show that the content of quercetin in both species reached its highest level in summer and its lowest in autumn. The quercetin content in the leaves of P. hendersonii was generally higher than that of A. venetum no matter when their leaves were harvested. There was significant difference in quercetin content among three geographical populations of P. hendersonii, which might be the result of climatic difference-cooler climate might favor accumulation of quercetin in the leaves of P. hendersonii. Furthermore, the developmental patterns of total phenolics in the leaves of the two species were the same as that of the quercetin, that is, summer is an optimal harvesting season for both quercetin and other phenolics. The results obtained here suggest that P. herdersonii is a better material for herbal tea or pharmaceutical purposes, and that the best harvest time of its leaves should be summer.


The renewable chemicals industry.
The possibilities for establishing a renewable chemicals industry featuring renewable resources as the dominant feedstock rather than fossil resources are discussed in this Concept. Such use of biomass can potentially be interesting from both an economical and ecological perspective. Simple and educational tools are introduced to allow initial estimates of which chemical processes could be viable. Specifically, fossil and renewables value chains are used to indicate where renewable feedstocks can be optimally valorized. Additionally, C factors are introduced that specify the amount of CO2 produced per kilogram of desired product to illustrate in which processes the use of renewable resources lead to the most substantial reduction of CO2 emissions. The steps towards a renewable chemicals industry will most likely involve intimate integration of biocatalytic and conventional catalytic processes to arrive at cost-competitive and environmentally friendly processes.


Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice.
Heterozygous hTau mice were used for the study of tau seeding. These mice express the six human tau isoforms, with a high predominance of 3Rtau over 4Rtau. The following groups were assessed: (i) non-inoculated mice aged 9 months (n = 4); (ii) Alzheimer's Disease (AD)-inoculated mice (n = 4); (iii) Globular Glial Tauopathy (GGT)-inoculated mice (n = 4); (iv) Pick's disease (PiD)-inoculated mice (n = 4); (v) control-inoculated mice (n = 4); and (vi) inoculated with vehicle alone (n = 2). AD-inoculated mice showed AT8-immunoreactive neuronal pre-tangles, granular aggregates, and dots in the CA1 region of the hippocampus, dentate gyrus (DG), and hilus, and threads and dots in the ipsilateral corpus callosum. GGT-inoculated mice showed unique or multiple AT8-immunoreactive globular deposits in neurons, occasionally extended to the proximal dendrites. PiD-inoculated mice showed a few loose pre-tangles in the CA1 region, DG, and cerebral cortex near the injection site. Coiled bodies were formed in the corpus callosum in AD-inoculated mice, but GGT-inoculated mice lacked globular glial inclusions. Tau deposits in inoculated mice co-localized active kinases p38-P and SAPK/JNK-P, thus suggesting active phosphorylation of the host tau. Tau deposits were absent in hTau mice inoculated with control homogenates and vehicle alone. Deposits in AD-inoculated hTau mice contained 3Rtau and 4Rtau; those in GGT-inoculated mice were mainly stained with anti-4Rtau antibodies, but a small number of deposits contained 3Rtau. Deposits in PiD-inoculated mice were stained with anti-3Rtau antibodies, but rare neuronal, thread-like, and dot-like deposits showed 4Rtau immunoreactivity. These findings show that tau strains produce different patterns of active neuronal seeding, which also depend on the host tau. Unexpected 3Rtau and 4Rtau deposits after inoculation of homogenates from 4R and 3R tauopathies, respectively, suggests the regulation of exon 10 splicing of the host tau during the process of seeding, thus modulating the plasticity of the cytoskeleton.


Migration of neutrophils across monolayers of cultured microvascular endothelial cells. An in vitro model of leucocyte extravasation.
Monolayers of bovine microvascular endothelial cells (BMECs) grown on connective tissue derived from human amniotic membrane were used to examine the transendothelial migration of human neutrophils in vitro. Neutrophils placed above these cultures migrated in response to a chemotactic gradient generated by placing 10(-7) M-formyl-methionyl-leucyl-phenyl-alanine (fMLP) below the cultures. Under these conditions, an average of 29 +/- 12% of the total population of neutrophils migrated beneath the endothelium after 1 or 2 h of incubation. Neutrophil migration in the absence of fMLP or in the presence of equal concentrations of fMLP above and below the cultures was less than 8% of the response to a 10(-7) M-fMLP gradient. Migration was a rapid event. Neutrophils began adhering to the apical surface of the endothelium within 2 min following exposure to an fMLP gradient; Ca2+ was required for this initial adhesion. Within 10 min, the majority of neutrophils associated with the BMEC-amnion cultures had migrated beneath the endothelial monolayer. Ultrastructural studies revealed that the initial adhesion between migrating neutrophils and endothelium was characterized by close contact between the two types of cell in focal areas. This close association was maintained as the neutrophils traversed the clefts between endothelial cells. Following their migration across the endothelium, neutrophils often were observed lying between the endothelium and its basement membrane. With time, the neutrophils penetrated the basement membrane and moved into the underlying amniotic connective tissue. To test the role of neutrophil proteinases in breaching endothelial and subendothelial barriers, migration was allowed to proceed in the presence of a variety of proteinase inhibitors, including p-nitrophenyl p'-guanidinobenzoate, soybean trypsin inhibitor, 6-aminocaproic acid, alpha 1-proteinase inhibitor, leupeptin, antipain and methoxysuccinyl alanine-alanine-proline-valine chloromethyl ketone. None of these had a significant effect on the number of neutrophils that migrated or the depth to which they penetrated the amniotic tissue as compared with controls. In contrast, pepstatin and chymostatin reduced migration in response to fMLP to 7% and 52% of control values, respectively. However, these two inhibitors did not affect migration in response to another chemoattractant, leukotriene B4. Migration was neither enhanced nor inhibited by the following treatments: (1) removal of plasminogen from the calf serum used in the assay medium and addition of polyclonal antibody to plasminogen; (2) addition of monoclonal or polyclonal antibody to plasminogen activator.(ABSTRACT TRUNCATED AT 400 WORDS)


Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells from patients with multiple sclerosis.
Recent studies have investigated the potential of autologous bone marrow-derived mesenchymal stem cells (MSCs) as a therapy for multiple sclerosis. Whether MSCs from individuals with multiple sclerosis are functionally and/or phenotypically abnormal has received less attention. Through our Phase I clinical trial, SIAMMS, we were able to isolate and characterize MSCs from individuals with multiple sclerosis. The objective of the study was to demonstrate that MSCs from individuals with multiple sclerosis show no significant differences from MSCs derived from individuals without multiple sclerosis. MSCs were isolated from bone marrow aspirates from four SIAMMS participants. We were also able to isolate MSCs from bone marrow obtained during a total hip replacement operation on an individual with multiple sclerosis. Control MSCs were isolated from bone marrow acquired during total hip replacement operations on five individuals without MS. MSCs were characterized using standard criteria: plastic adherence, differentiation along adipogenic/osteogenic/chondrogenic lineages, and expression of specific cell surface antigens. We also determined their proliferation potential. MSCs from individuals with multiple sclerosis and individuals without multiple sclerosis were similar in proliferation, differentiation potential and cell surface antigen expression. This has relevance to scientific studies investigating the therapeutic potential of autologous MSCs which primarily utilize MSCs from individuals without multiple sclerosis, and relevance to clinical studies extrapolating from these scientific findings.


A Keyword-Enhanced Approach to Handle Class Imbalance in Clinical Text Classification.
Recent applications ofdeep learning have shown promising results for classifying unstructured text in the healthcare domain. However, the reliability of models in production settings has been hindered by imbalanced data sets in which a small subset of the classes dominate. In the absence of adequate training data, rare classes necessitate additional model constraints for robust performance. Here, we present a strategy for incorporating short sequences of text (i.e. keywords) into training to boost model accuracy on rare classes. In our approach, we assemble a set of keywords, including short phrases, associated with each class. The keywords are then used as additional data during each batch of model training, resulting in a training loss that has contributions from both raw data and keywords. We evaluate our approach on classification of cancer pathology reports, which shows a substantial increase in model performance for rare classes. Furthermore, we analyze the impact of keywords on model output probabilities for bigrams, providing a straightforward method to identify model difficulties for limited training data.


Some aspects of maternal behaviour in mammals.
Lactation is the one common factor in the behaviour patterns of maternal care in mammals. A series of behaviour patterns is elicited by the different stages of the developing young and these are related to the way of life of the animals concerned. Infants which are born naked, blind and helpless elicit retrieving and nest building and are cleaned and cared for by the female. Older animals or those born with fur, but with poor locomotion, are still carried and cleaned. When the young can move well other behaviour patterns which keep the young and mother together are important, so signals for communication and recognition of individuals develop. At the end of lactation various behaviour patterns bring about weaning. Sometimes this is the result of dispersal by the young, and sometimes the young are actively rejected or deliberately abandoned. Several examples of maternal behaviour are given in relation to the classes of mammals and some related problems are discussed.


[Effects of strength and endurance training on skeletal muscles in the elderly. New muscles for old!].
A well-known effect of increasing age is the gradual reduction of muscle function, and thus of performance in the activity of daily living. Recent research has shown that, even among the very elderly, exercise can improve not only strength and endurance, but also balance and mobility, thus reducing the risk of falls. The possibility of counteracting some of the age-related muscle changes has also been demonstrated. The article reviews current knowledge of strength and endurance training in the elderly, the importance of exercise to improve physical performance, and how lifelong exercise can counteract the effects associated with the ageing of the neuromuscular system.


Differential gene expression profiles of normal human parotid and submandibular glands.
Parotid and submandibular glands have different properties including characteristics of the secreted saliva and tumor incidences. The differences in properties of parotid and submandibular glands are not clear from a genetic viewpoint. To study differential gene expression profiles between normal human parotid and submandibular glands. Three pairs of normal parotid and submandibular glands were obtained. RNA was extracted from these samples. After reverse transcription, the cDNA was in vitro-transcribed to produce biotin-labeled cRNA. The purified biotin-labeled cRNA samples were hybridized to microarray chips. Among the 54 675 tested transcripts, 47 transcripts were upregulated at least twofold in the parotid gland compared with the submandibular gland, including tumor-associated genes (pleiotrophin, WNT5A, ABCC1) and transport-associated genes (SLCO1A2, SLC13A5, KCNJ15). Ninety-eight transcripts were upregulated at least twofold in the submandibular gland compared with the parotid gland, including the chloride channel CFTR and mucin-associated genes that belong to the starch and sucrose metabolism pathway (GalNAc-T4, GalNAc-T7 and GalNAc-T13). Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of nine differentially expressed genes confirmed the microarray results. This study revealed the different gene expression profiles of normal human parotid and submandibular glands, providing a genetic basis for their differing properties.


Meta-analysis of extremely low frequency electromagnetic fields and cancer risk: a pooled analysis of epidemiologic studies.
Studies have suggested that extremely low frequency electromagnetic fields (ELF-EMF) may affect physiological functions in animal models. However, epidemiologic studies investigating the association of ELF-EMF with the susceptibility to cancer yield contradictory results. In this comprehensive analysis, we conducted a search for case-control surveys regarding the associations of ELF-EMF and cancer susceptibility in electronic databases. A total of 42 studies involving 13,259 cases and 100,882 controls were retrieved. Overall, increased susceptibility to cancer was identified in the ELF-EMF exposed population (OR=1.08, 95% CI: 1.01, 1.15, P=0.02). In the stratified analyses, increased risk was found in North America (OR=1.10; 95% CI: 1.02, 1.20, P=0.02), especially the United States (OR=1.10; 95% CI: 1.01, 1.20, P=0.03). However, studies from Europe contradict these results. Moreover, a higher risk was found to be statistically significantly associated with the residential exposed population (OR=1.18; 95% CI: 1.02, 1.37, P=0.03). Furthermore, an increased cancer risk was found in interview-based surveys (OR=1.16; 95% CI: 1.00, 1.35, P=0.04). In device measurement-based studies, a slight increased risk was found only in premenopausal breast cancer (OR=1.23; 95% CI: 1.01, 1.49, P=0.04). Our meta-analysis suggests that ELF-EMFs are associated with cancer risk, mainly in the United States and in residential exposed populations. Methodological challenges might explain the differences among studies.


Simultaneous detection of phenacetin and paracetamol using ELISA and a gold nanoparticle-based immunochromatographic test strip.
We have developed a sensitive and rapid gold nanoparticle-based immunochromatographic strip (GNP-ICS) for the detection of phenacetin (PNCT) and paracetamol (PAP) using an anti-PNCT monoclonal antibody (mAb). The sensitive anti-PNCT mAb (2D6) had a half maximal inhibitory concentration (IC50) and limit of detection (LOD) of 3.51 and 0.21 ng mL-1, respectively. Additionally, its cross-reactivity with PAP was approximately 10.1%. The developed GNP-ICS assay based on GNP-labeled mAb was sensitive for the detection of PNCT with vLOD and cut-off values of 2.5 and 50 ng mL-1 respectively and a vLOD value of 25 ng mL-1 for PAP. Furthermore, the developed icELISA and GNP-ICS assays were applied to determine PNCT-spiked beverage samples without pretreatment, in addition to a kind of PAP-containing drug. The recoveries were validated using high performance liquid chromatography (HPLC). The results revealed that the developed GNP-ICS assay was reliable for the detection of PNCT in practical samples.


[The right to healthcare: integrity, diversity, and territoriality].
Examining some issues and challenges for ensuring the universal right to healthcare in Brazil, this paper explores the findings of a government project conducted in 2003 to broaden the approach to healthcare problems in Brazil, based on dialogs between government and society that supplement institutionalized approaches to social participation in healthcare management. Starting with an overview of the complex international backdrop against which government actions take place for implementing social rights, this paper highlights three issues among the problems listed that are rated as crucial for drawing up public policies: integrity and dignity as pillars for the organization and regulation of public interventions; recognition and respect for difference as a condition for achieving the right to healthcare; and territorialization of problems and policies for the production of responses to new realities. Finally, it lists some aspects that challenge Brazilian government and society in their efforts to guarantee the right to healthcare, affirming the timeliness of the steps taken by the government administration, moving steadily ahead towards effective universal access to this right through an appreciation of aspects related to human rights and citizenship.


Anthropogenic lead inputs to the western Pacific during the 20th century.
Unlike in the North Atlantic, no continuous record of anthropogenic lead (Pb) has been available in the western Pacific. We reconstructed historical changes in anthropogenic Pb on the basis of Pb isotope ratios recorded in annually-banded coral retrieved from Ogasawara Island, Japan. Whereas the predominant natural source of Pb to the surface of the western Pacific apparently is Chinese loess, anthropogenic Pb has affected the western Pacific at least since the late 19th century. From the late 19th to the early 20th century, Australian Pb used in Japan was an important source of anthropogenic Pb. During 1920-1940, Pb emitted from parts of the world other than Japan contributed somewhat to the western Pacific, and the amount of Pb imported from Australia declined. Alkyl Pb used in Japan became the main source from 1950 until the mid-1970s, when leaded gasoline began to be regulated in Japan. Since the mid-1980s, aerosols from China have been the predominant source of Pb in the western Pacific. During the 1990s, around 60% of Pb in the surface of the western Pacific was from Chinese aerosols. We also investigated the present spatial distribution and likely sources of Pb in the western Pacific by using coral samples. Enrichment in 208Pb, which is a characteristic of Pb from China, was found in all coral samples except that from Pohnpei, Micronesia, suggesting that at present anthropogenic Pb is transported to the western Pacific mainly from China via westerly winds.


Effects of Ocean Acidification on Molting, Oxidative Stress, and Gut Microbiota in Juvenile Horseshoe Crab Tachypleus tridentatus.
Anthropogenic elevation of atmospheric carbon dioxide (CO2) drives global-scale ocean acidification (OA), which has aroused widespread concern for marine ecosystem health. The tri-spine horseshoe crab (HSC) Tachypleus tridentatus has been facing the threat of population depletion for decades, and the effects of OA on the physiology and microbiology of its early life stage are unclear. In this study, the 1st instar HSC larvae were exposed to acidified seawater (pH 7.3, pH 8.1 as control) for 28 days to determine the effects of OA on their growth, molting, oxidative stress, and gut microbiota. Results showed that there were no significant differences in growth index and molting rate between OA group and control group, but the chitinase activity, β-NAGase activity, and ecdysone content in OA group were significantly lower than those of the control group. Compared to the control group, reactive oxygen species (ROS) and malondialdehyde (MDA) contents in OA group were significantly increased at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), and alkaline phosphatase (AKP) activities increased first and then decreased, glutathione peroxidase (GPX) decreased first and then increased, and GST activity changed little during the experiment. According to the result of 16S rRNA sequencing of gut microbiota, microbial-mediated functions predicted by PICRUSt showed that "Hematopoietic cell lineage," "Endocytosis," "Staphylococcus aureus infection," and "Shigellosis" pathways significantly increased in OA group. The above results indicate that OA had no significant effect on growth index and molting rate but interfered with the activity of chitinolytic enzymes and ecdysone expression of juvenile horseshoe crabs, and caused oxidative stress. In addition, OA had adverse effects on the immune defense function and intestinal health. The present study reveals the potential threat of OA to T. tridentatus population and lays a foundation for the further study of the physiological adaptation mechanism of juvenile horseshoe crabs to environmental change.


Efficacy and safety of suprascapular nerve block combined with axillary nerve block for arthroscopic shoulder surgery: A systematic review and meta-analysis of randomized controlled trials.
A variety of peripheral nerve block methods are used in the clinic to enhance the effect of postoperative analgesia. In recent years, an increasing number of surgeons have considered the efficacy and safety of suprascapular nerve block (SSNB) combined with axillary nerve block (ANB) for controlling perioperative pain in shoulder arthroscopy. The purpose of this study was to compare the efficacy and safety of SSNB + ANB and interscalene block (ISB) versus SSNB alone for shoulder arthroscopic surgery. Systematic review; Level of evidence, 1. The protocol for this meta-analysis is registered with PROSPERO (CRD42021254008). PubMed, Cochrane Library, Embase and CNKI were searched for RCTs from inception to April 30, 2021. A meta-analysis was performed with Review Manager 5.3 to calculate the RR or WMD of related outcome indicators. Nine RCTs involving 543 cases from 5 countries were included. Compared with SSNB alone, SSNB + ANB was more effective at pain relief at 6, 12, 24, 36 and 48 h postoperatively. In terms of patient satisfaction score, scores for SSNB + ANB at 12 (WMD = 2.01, 95% CI = 0.25 to 3.78) and 24 (WMD = 1.68, 95% CI = 0.11 to 3.24) hours after the operation were higher than those of SSNB alone, but there was no significant difference at 36 and 48 h postsurgery. There was no significant difference in pain score between SSNB + ANB and ISB at 6 and 12 h after surgery or in patient satisfaction at 24 h (WMD = 0.13, 95% CI = -0.36 to 0.63) postsurgery between SSNB + ANB and ISB. In terms of safety, compared with ISB, SSNB + ANB reduced the incidence of dyspnea (RR = 0.25, 95% CI = 0.09 to 0.68). Compared with SSNB alone, SSNB + ANB has better advantages regarding pain relief and patient satisfaction within 24 h after surgery. Compared with ISB, SSNB + ANB shows no difference in postoperative pain relief or patient satisfaction, but SSNB + ANB can reduce the incidence of dyspnea more than ISB.


Chemo/tomotherapy stereotactic body radiation therapy (chemo/SBRT) for the salvage treatment of esophageal carcinoma following trimodality therapy: a case report.
Esophageal cancer (EC) patients presenting a local recurrence following trimodality therapy (chemoradiaton and surgery) have limited palliative treatment options when the three major modalities of therapy have been exhausted. In addition, some patients experience a local recurrence or develop a metachronous cancer in a previously irradiated site, without evidence of systemic disease. For these patients there is a potential for cure, although the risk of further distant recurrences remains high. We report of a successful concomitant chemo/SBRT treatment in a case of locally advanced metachronous squamous cervical EC, which was diagnosed in a patient previously treated with trimodality therapy for a squamous tonsillar carcinoma. Chemo/SBRT seems to be a reasonable salvage option for patients without distant metastases who have exhausted standard therapies. Our experience also suggests that a concomitant chemo/SBRT treatment appears to be either feasible or effective and chemo/SBRT can be considered also in selected patients affected by EC with squamous histology and with neoplastic infiltration of the trachea.


Exploring the perspectives of underrepresented voices: Perceptions and experiences of uterine cancer for black African, Caribbean, black British, and mixed-black women in the UK to develop strategies for early symptom presentation.
The uterine cancer (UC) mortality rate in the UK is significantly higher for women who belong to a Black ethnic group compared to those from other ethnic groups. This study aimed to understand the views and experiences of UC amongst Black ethnic minority women in the UK, with a focus on awareness and presentation of red-flag symptoms. Women of Black African, Caribbean, Black British and Mixed-Black ethnicity were purposefully recruited to participate in focus groups and individual semi-structured interviews. Twenty women from different regions in England participated in the study. Reflexive thematic analysis of the data led to the identification of three main themes: 1) Healthcare inequities; 2) Support and sense making with other Black women; and 3) Knowledge dissemination, mobilisation, and empowerment. Perceptions of inequitable healthcare provision and distrust influenced how participants, and their peer networks, approached seeking assistance from healthcare professionals. Concerns were also raised about culturally insensitive information resources, including issues of language, literacy, and representation, all of which served as potential barriers for women within Black ethnic minority groups. The deficiency of targeted knowledge mobilisation and specific UC information aimed at Black ethnicity women living in the UK, reportedly contributes to the dissemination of misconceptions and an atmosphere of apprehension around a UC diagnosis. The insights from this study highlight the significance of designing culturally sensitive strategies to promote informed decision-making and empower the dissemination of accurate health knowledge amongst Black women.


Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes.
Acetaminophen is a widely used analgesic antipyretic agent. When used at low doses, it is a safe drug, but at higher doses it can cause acute hepatic necrosis in humans and experimental animals. The key mechanism in the hepatotoxicity is cytochrome P450 (CYP)-catalysed formation of the reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI) that is capable of binding to cellular macromolecules and in that way an LC/MS liquid chromatography/mass spectrometry (LC/MS) method was developed to measure NAPQI formation by trapping it to reduced glutathione. This method was used to determine the bioactivation of acetaminophen at two concentrations: 50 microM therapeutic and 1 mM toxic by using nine human recombinant CYP enzymes: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4; and with different microsomes from experimental animals. At the toxic concentration the formation of NAPQI-glutathione was highest with CYP3A4 followed by CYP2E1, CYP1A2, and CYP2D6. At the therapeutic concentration, CYP3A4 had also the highest bioactivation capacity. In a comparison of the enzyme kinetics, CYP3A4 was the most efficient CYP with the lowest K(m) value 130 microM (95% confidence interval = 63-210 microM). Dexamethasone-induced rat liver microsomes had the most effective bioactivation capacity at therapeutic and toxic acetaminophen concentrations. This study suggests that CYP3A4 is the major CYP enzyme form catalysing acetaminophen oxidation to NAPQI in human liver.


Micronutrients: A Double-Edged Sword in Microbe-Induced Gastric Carcinogenesis.
Epidemiologic studies throughout the world have uniformly demonstrated significant relationships between the intake of dietary micronutrients and gastric cancer risk. An exciting concept that has recently gained considerable traction is that micronutrients modulate gene expression within Helicobacter pylori, the strongest identified risk factor for gastric carcinogenesis. We present evidence here that essential micronutrients have a direct effect on H. pylori virulence, which subsequently affects interactions at the host-pathogen interface, thereby facilitating the development of premalignant and malignant lesions in the stomach. Further, these fundamental concepts provide a framework for understanding mechanisms driving the development of other malignancies that arise from foci of gastrointestinal inflammation.


Life-threatening cat-scratch disease in an immunocompromised host.
We describe a renal allograft recipient with cat-scratch disease in whom refractory hypotension, severe metabolic acidosis, pulmonary infiltrates, and encephalopathy developed. The patient first presented with a history of cat bites and scratches, fever, headache, and arthralgias. Four weeks later, the clinical presentation of septic shock suddenly developed in the patient. Cat-scratch disease was documented clinically and by finding delicate pleomorphic bacilli in Warthin-Starry silver stains of biopsy specimens taken from the primary inoculation site and regional lymph node. The administration of intravenous sulfamethoxazole and trimethoprim, erythromycin lactobionate, and tobramycin sulfate therapy correlated with recovery. Although cat-scratch disease is usually a benign, self-limited illness, this article illustrates its systemic nature, its potential for devastating complications in the immunocompromised host, and its possible response to vigorous antibiotic therapy.


[HEMODYNAMIC CHILDREN WITH ISOLATED ANOMALOUS CHORDS OF THE LEFT VENTRICLE DEPENDING ON LOCATION AND QUANTITY].
A total of 156 children group (children born to parents exposed to the Chernobyl disaster), in which, according to Doppler echocardiography, revealed isolated abnormal chords of the left ventricle (AHLV). Analysis of morphometric parameters and central hemodynamics conducted according to the localization AHLV. Found that concomitant localization AHLV at the threshold of the number of the most influencing change morphoinetric indicators and central hemodynamics. Condition of systemic circulation indicates a decline in their adaptive capacity of the cardiovascular system due to changes in the dynamics and power of the heartbeat. The decrease in stroke volume, stroke and cardiac index suggests hypokinetic type of organization of central hemodynamics, which can be considered an early sign of stress features of the heart and blood vessels. In this subgroup of children revealed significant changes in transmitral flow, indicating the initiation they have diastolic dysfunc tion. When the number of prethreshold AHLV most pronounced changes were found in the middle of their localization. Almost a third of children in this subgroup with individual assessment also revealed signs of initiation of diastolic dysfunction.


Simulations of the roles of multiple cyclic nucleotide phosphodiesterases.
1. Simulations were performed using a model for cellular cyclic AMP metabolism involving a hormone-activated adenylate cyclase and two cyclic nucleotide phosphodiesterases with different Michaelis constants. 2. The response curves of cyclic AMP concentration as a function of hormone concentration were affected by regulating the phosphodiesterases. The maximum velocity of the high-affinity phosphodiesterase (V1) was important in determining the position of the response curve; when v1 was less than the maximal activity of adenylate cyclase (Vc), sigmoid response curves were readily produced. The maximum attainable concentration of cyclic AMP was determined primarily by V1 when Vc less than V1, and primarily by the activity of the low-affinity enzyme when Vc greater than V1 (V2 much greater than Vc in all cases). 3. The glucagon-stimulated adenylate cyclase and insulin-stimulated phosphodiesterase of the rat liver plasma membrane were simulated using experimentally determined values for the enzyme-kinetic parameters, and a considerable potential for regulation of the system by insulin was demonstrated. 4. Other possible functions for the regulation of phosphodiesterases are considered, in particular the value of increasing the speed of response to decreases in hormone concentration.


Enzymic capacities of purine de Novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues.
The enzymic capacities of the de novo and the salvage pathways for purine nucleotide synthesis were compared in rat in normal, differentiating, and regenerating liver, and in three hepatomas of widely different growth rates. The activities of the key de novo and salvage enzymes were also determined in mouse lung and Lewis lung carcinoma, in human kidney and liver, and in renal cell carcinoma and hepatocellular carcinomas. A precise and reproducible assay was worked out for measuring the activities of adenine phosphoribosyltransferase (EC 126.96.36.199) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 184.108.40.206) in crude liver and hepatoma systems. Kinetic studies on the salvage enzymes were carried out in the crude 100,000 X g supernatant fluid from normal liver and rapidly growing hepatoma 3924A. In both tissue extracts, Michaelis-Menten kinetics was observed for adenine phosphoribosyltransferase and HGPRT. The reciprocal plots for 5-phosphoribosyl-1-pyrophosphate (PRPP) of liver and hepatoma enzymes gave apparent KmS of 2 microM for adenine phosphoribosyltransferase and 4 microM for HGPRT, showing two orders of magnitude higher affinities for PRPP than that of the rate-limiting enzyme of de novo purine synthesis, amidophosphoribosyltransferase (EC 126.96.36.199) (Km = 400 to 900 microM). The apparent Km values for adenine of liver and hepatoma adenine phosphoribosyltransferase were 0.6 to 0.9 microM, respectively. For both liver and hepatoma HGPRT, the reciprocal plots for hypoxanthine and guanine yielded the same Km of 3 microM. The specific activities of purine phosphoribosyltransferases were markedly higher than that of amidophosphoribosyltransferase in rat thymus, spleen, testis, bone marrow, colon, liver, kidney cortex, lung, heart, brain, and skeletal muscle, but were lower in the small intestine. In hepatomas and regenerating and differentiating liver, the activities of the salvage enzymes were 2.1- to 32-fold higher than that of amidophosphoribosyltransferase. The purine phosphoribosyltransferase activities were also higher than that of amidophosphoribosyltransferase in Lewis lung carcinoma (8.2- to 32-fold), human renal cell carcinoma (3.5- to 22-fold), and hepatocellular carcinoma (3.4- to 30-fold). The high activities and the high affinity to PRPP of the purine phosphoribosyltransferases might explain the lack of linkage of the behavior of these enzymic activities with proliferation in normal, regenerating, differentiating, or neoplastic tissues. In contrast, the specific activity of the amidophosphoribosyltransferase, which is lower than that of the salvage enzymes, is linked with transformation as it is increased in all examined tumors.4


Intravenous immunoglobulins in multiple sclerosis.
The spectrum of diseases being treated with intravenous immunoglobulins (IVIg) appears to be ever broadening, including use in neurologic diseases. After a period of anectodal reports and smaller uncontrolled series, recently there have been several randomized, prospective, double-blind, placebo-controlled studies employing IVIg in patients with relapsing remitting (RR) multiple sclerosis (MS). Reduction in relapse rate and some evidence of decreased MRI activity has been reported, but to date no effect on disability or MRI lesion burden has been noted. Because of differences in methodologic design and patient populations, as well as the relatively small number of patients in some of these studies, a rigorous direct comparison of efficacy with the type I interferons and glatiramer acetate is not possible. Given these data and the high cost of IVIg, routine use of this mode of therapy cannot be recommended, certainly not as a first-line treatment. Larger studies would clearly be helpful. At present there is no evidence to support the use of IVIg in secondary progressive (SP) or primary progressive (PP) MS.


Stabilization of a linear nanomechanical oscillator to its thermodynamic limit.
The rapid development of micro- and nanomechanical oscillators in the past decade has led to the emergence of novel devices and sensors that are opening new frontiers in both applied and fundamental science. The potential of these devices is however affected by their increased sensitivity to external perturbations. Here we report a non-perturbative optomechanical stabilization technique and apply the method to stabilize a linear nanomechanical beam at its thermodynamic limit at room temperature. The reported ability to stabilize a nanomechanical oscillator to the thermodynamic limit can be extended to a variety of systems and increases the sensitivity range of nanomechanical sensors in both fundamental and applied studies.


Haemodynamic consequences of changing potassium concentrations in haemodialysis fluids.
A rapid decrease of serum potassium concentrations during haemodialysis produces a significant increase in blood pressure parameters at the end of the session, even if effects on intra-dialysis pressure are not seen. Paradoxically, in animal models potassium is a vasodilator and decreases myocardial contractility. The purpose of this trial is to study the precise haemodynamic consequences induced by acute changes in potassium concentration during haemodialysis. In 24 patients, 288 dialysis sessions, using a randomised single blind crossover design, we compared six dialysate sequences with different potassium profiles. The dialysis sessions were divided into 3 tertiles, casually modulating potassium concentration in the dialysate between the value normally used K and the two cut-off points K+1 and K-1 mmol/l. Haemodynamics were evaluated in a non-invasive manner using a finger beat-to-beat monitor. Comparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p < 0.05, < 0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p < 0.01, < 0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm-5, p < 0.05, < 0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p < 0.01 for comparison K-1 vs. K and K-1 vs. K+1). A rapid decrease in the concentration of serum potassium during the initial stage of the dialysis-obtained by reducing the concentration of potassium in the dialysate-translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate. NCT01224314.


[Continent urinary diversion and pregnancy].
We report on our experience with 7 pregnancies in 6 women who previously underwent reconstruction of the urinary tract with a continent urinary diversion using an ileo caecal segment (Mainz-Pouch I), ureterosigmoidostomy or bladder augmentation. Urinary tract infection and upper tract dilatation were the only complications during pregnancy which required bilateral nephrostomies in one case. All other sequelae were handled conservatively. The continence mechanisms were not compromised during pregnancy or delivery. Deliveries were vaginal in two cases and by Caesarean section in five. All seven newborn were healthy. Pregnancy is not contraindicated after any type of urinary diversion including continent reservoirs. Close urological and gynaecological observation of these women throughout pregnancy is mandatory. The mode of delivery is in the majority of cases guided by obstetric indications. If Caesarean section is necessary, the obstetrician should be familiar with the intraabdominal situation.


Opposite fate of endocytosed CCR7 and its ligands: recycling versus degradation.
The chemokine receptor CCR7 and its ligands CCL19 and CCL21 play a crucial role for the homing of lymphocytes and dendritic cells to secondary lymphoid tissues. Nevertheless, how CCR7 senses the gradient of chemokines and how migration is terminated are poorly understood. In this study, we demonstrate that CCR7(-GFP) is endocytosed into early endosomes containing transferrin receptor upon CCL19 binding, but less upon CCL21 triggering. Internalization of CCR7 was independent of lipid rafts but relied on dynamin and Eps15 and was inhibited by hypertonic sucrose, suggesting clathrin-dependent endocytosis. After chemokine removal, internalized CCR7 recycled back to the plasma membrane and was able to mediate migration again. In contrast, internalized CCL19 was sorted to lysosomes for degradation, showing opposite fate for endocytosed CCR7 and its ligand.


Bivalent Peptide- and Chelator-Containing Bioconjugates as Toolbox Components for Personalized Nanomedicine.
While personalized therapy bears an enormous potential in cancer therapy, the development of flexible, tailorable delivery systems remains challenging. Here, we present a "tool-kit" of various avidin-based bioconjugates (BCs) for the preparation of personalized delivery systems. Corresponding BCs were synthesized using the self-assembly of avidin with various biotinylated ligands, such as one cationic glycodendrimer for dendriplex adsorption and two functional ligands for imaging (glycodendrimers with DOTA or NOTA units) or targeting (biotinylated PEG decorated with ligands). Substituting antibodies for targeting small molecules were coupled to biotin-PEG compounds for addressing the folate receptor (FR), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA). After successful characterization and proof of good storage and redispersion properties of BCs, cytotoxicity assays and first in vivo imaging studies with 99mTc-complexing bioconjugates provide evidence that these BCs and their avidin analogues can be used as tool-kit components in theranostic systems for personalized medicine.


[Miliary tuberculosis - report of a case].
This is a case report of generalized miliary tuberculous infection in a 80-year old white male without the acquired immunodeficiency syndrome, whose death was caused by progressive hematogenous seeding similar to those cases of preantibiotic era. The importance of autopsy studies to uncover silent or protean infections specially in cases of cryptic or chronic hematogenous miliary tuberculosis, is emphasized.


[Undifferentiated osteoclastic-type giant cell carcinoma].
Initially described 40 years ago (Rosai), the undifferentiated osteoclastic-type giant cell carcinoma (IOGCC) is a variant of ductal adenocarcinoma and accounts for less than 1% of exocrine pancreatic tumors. Its extreme rarity, with consequent existence of few reports and clinical experience, leads to the arousal of doubts with regard to its histogenesis, types of approach and therapeutical attitudes. It is important to note that in Portugal no similar case is registered in medical literature. A 61 year old patient admitted to the Internal Medicine Ward 3 at Coimbra University Hospital presents with a voluminous intra-abdominal mass in the left hypochondrium and microcytic anemia. During the investigation, a pancreatic neoplasm was identified, and the patient was submitted to surgical resection, the anatomo-pathological study of the tumor having revealed IOGCC. The particularities of the case, current available therapeutical options and its evolution are discussed, as well as a revision of the existing literature.


Use of haemostatic parameters as a diagnostic and prognostic index in persistent jaundice: a Zaria experience.
Haemostatic parameters (PT,KCCT and platelet counts) were measures in conjunction with other biochemical tests in 80 consecutive jaundiced patients here in Zaria. The investigations were performed on admission and within 72 hours after parenteral vitamin K therapy. The prothrombin time and kaolin cephalin clotting time remained prolonged after the administration of vitamin K in cases of liver cirrhosis. Prothrombin times in obstructive jaundice returned to normal after the administration of vitamin K. The prothrombin time, therefore, differentiates between the jaundice of liver cirrhosis from obstructive jaundice.


hymA (hypha-like metulae), a new developmental mutant of Aspergillus nidulans.
Asexual fruiting body development in Aspergillus nidulans requires a precise spatial and temporal coordinated expression of many genes. Insertional mutagenesis was used to isolate and characterize a new mutant of A. nidulans in which hyphal growth was slightly reduced and conidiophore development was specifically blocked at the metula stage. In contrast to the uninucleate metulae of the wild-type, in the mutant these structures were elongated, multinucleate and septate. Further differentiation and production of phialides by a budding-like process was not observed. The mutant metulae thus resembled hyphae rather than metulae and the gene was therefore named hypha-like metulae (hymA). The hymA gene was mapped to linkage group VI. The integrated vector was rescued with border sequences from the integration site. The border sequences were used to isolate a cosmid from a wild-type library which was subcloned to a 5 kb fragment able to complement the mutation in trans. This fragment encoded a 1.8 kb transcript expressed in hyphae and throughout development. It is proposed that hymA is involved in budding processes, and is required for the formation of metulae and for their further differentiation.


Dietary Isoflavone Intake and Breast Cancer Prognosis: A Prospective Analysis and Meta-Analysis.
We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60-2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67-0.98) for recurrence and 0.85 (0.76-0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation.


The impact of the lung EDRN-CVC on Phase 1, 2, & 3 biomarker validation studies.
The Early Detection Research Network's (EDRN) purpose is to discover, develop and validate biomarkers and imaging methods to detect early-stage cancers or at-risk individuals. The EDRN is composed of sites that fall into four categories: Biomarker Developmental Laboratories (BDL), Biomarker Reference Laboratories (BRL), Clinical Validation Centers (CVC) and Data Management and Coordinating Centers. Each component has a crucial role to play within the mission of the EDRN. The primary role of the CVCs is to support biomarker developers through validation trials on promising biomarkers discovered by both EDRN and non-EDRN investigators. The second round of funding for the EDRN Lung CVC at Vanderbilt University Medical Center (VUMC) was funded in October 2016 and we intended to accomplish the three missions of the CVCs: To conduct innovative research on the validation of candidate biomarkers for early cancer detection and risk assessment of lung cancer in an observational study; to compare biomarker performance; and to serve as a resource center for collaborative research within the Network and partner with established EDRN BDLs and BRLs, new laboratories and industry partners. This report outlines the impact of the VUMC EDRN Lung CVC and describes the role in promoting and validating biological and imaging biomarkers.


The Haitian refugee: concerns for health care providers.
This paper reports an exploratory study of the situation of Haitian refugees in the U.S., based on extensive interviews and conversations with health care providers around the state of Florida. The study raises issues that are applicable to other disadvantaged subcultures, and illustrates the need for further, more rigorous fact-finding and attention by health care providers. Suggestions for social workers working in cross-cultural settings are also discussed.


Mapping remodeling reversals with the aid of the scanning electron microscope.
The histologic research on craniofacial remodeling is briefly summarized. A new methodologic approach using the scanning electron microscope (SEM) and high-resolution replicas of craniofacial bone is evaluated. Two maxillae were chosen for illustrative purposes. The specimens were replicated and prepared for routine SEM examination. In addition, a grid was applied to the replicas so that the bone growth activity states could be mapped on a coordinate system. The topographic ("T") principle is introduced as a precedent for discriminating remodeling bone growth activity states with the SEM. These activity states in vivo specify characteristic microscopic surface topographies. The three distinctive surfaces are resorptive, depository, and resting, which are mapped on a coordinate system. Results obtained are similar to those of histologic studies. The primary advantage of the SEM/replica technique is that it does not damage the specimen. This feature will facilitate more extensive investigations of craniofacial remodeling. The time and financial investments for the SEM/replica technique are significantly less than the histologic technique in the investigation of similar material. The SEM/replica technique, however, cannot be used to study nonexternal surfaces and evidence of remodeling contained within the bone cortex.


Design, synthesis, and structure-activity correlations of novel dibenzo[b,d]furan, dibenzo[b,d]thiophene, and N-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of Mycobacterium tuberculosis.
A molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. In this study, 1,2,3-triazole-based Mycobacterium tuberculosis inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo[b,d]furan, and dibenzo[b,d]thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. Structure-activity correlations and in vitro activity against M. tuberculosis strain H37Rv of new analogues revealed the order: dibenzo[b,d]thiophene > dibenzo[b,d]furan > 9-methyl-9H-carbazole series. Two of the most potent M. tuberculosis inhibitors 13h and 13q with MIC = 0.78 μg/mL (∼1.9 μM) displayed a low cytotoxicity and high selectivity index (50-255) against four different human cancer cell lines. These results together provided the potential importance of molecular hybridization and the development of triazole clubbed dibenzo[b,d]thiophene-based lead candidates to treat mycobacterial infections.