Incidence and risk factors of subclinical umbilical catheter-related thrombosis in neonates.
This study aimed to determine the risk factors for subclinical umbilical catheter-related thrombosis (UCRT) and its association with clinical morbidities. In infants without any symptoms associated with umbilical catheterization, the presence of thrombosis was monitored using abdominal ultrasonography within 1 week after umbilical catheter removal. The association between UCRT and the clinical variables was analyzed by comparing the groups with and without UCRT. UCRT occurred in 26 (19.0%) of 137 infants. The relative incidence rate of thrombosis was 12.3% at the umbilical artery and 21.7% at the umbilical vein. However, the type of umbilical vessels with a catheter was not associated with thrombosis (P = 0.095). Subclinical UCRT was associated with high serum calcium concentration in the multivariate analysis (95% confidence interval, 1.26-15.32; P = 0.020). UCRT was resolved within 3 weeks in 13 infants (50.0%), although the thrombosis persisted for up to 2 months in 2 infants (7.7%). We found no significant association between the subclinical UCRT and the neonatal morbidities in preterm infants. Though a rare cause of thrombosis, hypercalcemia should be considered in the assessment of infants with subclinical UCRT, and calcium levels should be routinely checked in infants with umbilical catheters.


The therapeutic effects of Lagopsis supina (Steph. ex Willd.) Ikonn.-Gal. fractions in trauma-induced blood stasis model rats.
Lagopsis supina (Steph. ex Willd.) Ikonn.-Gal. has been a traditional Chinese medicine (TCM) for the treatment of blood stasis, inflammation, and diuresis. Moreover, Huo Xue Li Shui theory was an important TCM theory that used to treat many ailments. Nevertheless, the scientific connotation of this theory has not been clearly elucidated so far. The aim of this study was to explore the scientific connotation of Huo Xue Li Shui with promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuretic effects in trauma-induced blood stasis model (TBSM) rats, taking microporous adsorption resin with water (LSB) and 30% ethanol (LSC) elution fractions from L. supina as a classical demonstration. 48 rats were randomly assigned into six groups (n = 8/group): the control group, the model group, and model groups treatment with LSB or LSC. The biochemical parameters and protein expression were measured using kit method and Western blot assay, respectively. Both LSB and LSC were effective in elevating body weight, food consumption, and water intake in model rats. In PBCRBS efficacy evaluation, LSB and LSC remarkably improved histopathological tissues. On the other hand, LSB and LSC prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, thromboxane B2, thromboxane B2/6-keto-prostaglandin F1α, urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1(PAI-1), PAI-1/tissue-type plasminogen activator (t-PA), and PAI-1/u-PA, while significantly enhanced the contents of antithrombin III, 6-keto-prostaglandin F1α, and t-PA. In parallel, LSB and LSC obviously down-regulated the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8, and remarkably up-regulated the level of IL-10. In determining diuretic activities, LSB and LSC prominently elevated urinary excretion volume and the level of atriopeptin, and remarkably reduced the levels of angiotensin II, anti-diuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3. In addition, LSB and LSC clearly suppressed protein expressions of AQP1, AQP2, and AQP3. Finally, LSB and LSC did not caused urinary pH, Na+, and Cl- electrolytes and had minor effects on K+ and Ca2+ concentrations. LSB and LSC exhibited prominent PBCRBS, anti-inflammatory, and diuretic effects in TBSM rats, thereby supported the traditional folk use of L. supina. This study successfully provided an experimental basis for the scientific connotation of Huo Xue Li Shui.


Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure.
Although home parenteral nutrition (PN) can save the lives of patients with massive bowel loss that results in short-bowel syndrome and intestinal failure, quality of life is impaired by PN and its complications. We examined the 12-month tolerability and efficacy of teduglutide to reduce PN dependency. Patients who received teduglutide (0.05 or 0.10 mg/kg/d) for 24 weeks in a randomized controlled trial were eligible for a 28-week double-blind extension study; 52 patients were given 52 weeks of the same doses of teduglutide. We investigated the safety, tolerability, and clinical efficacy (defined as a clinically meaningful ≥20% reduction in weekly PN volume from baseline) at week 52. The most common adverse events reported included headache (35%), nausea (31%), and abdominal pain (25%); 7 patients withdrew because of adverse events (gastrointestinal disorders in 4). Both groups had progressive reduction in PN. At week 52, 68% of the 0.05-mg/kg/d and 52% of the 0.10-mg/kg/d dose group had a ≥20% reduction in PN, with a reduction of 1 or more days of PN dependency in 68% and 37%, respectively. Four patients achieved complete independence from PN. For patients with short-bowel syndrome intestinal failure, the efficacy of teduglutide was maintained over 52 weeks and the safety profile was sufficient for it to be considered for long-term use. Further studies are needed to determine whether these effects will translate into improved quality of life and reduced PN complications. ClinicalTrials.gov number, NCT00172185.


[Hygienic aspects of healthy life style development in students].
Medical students have shown a high prevalence of major behavioral factors of health risk, such as inadequate physical activity, changes in the routine, nutrition quality, study-and-rest regimens, as well as smoking and frequent alcohol use. Proposals to educate the students on the importance of living a healthy lifestyle are given.


Rectal prolapse: which surgical option is appropriate?
Numerous surgical procedures have been suggested to treat rectal prolapse. In elderly and high-risk patients, perineal approaches such as Delorme's procedure and perineal rectosigmoidectomy (Altemeier's procedure) have been preferred, although the incidence of recurrence and the rate of persistent incontinence seem to be high when compared with transabdominal procedures. Functional results of transabdominal procedures, including mesh or suture rectopexy and resection-rectopexy, are thought to be associated with low recurrence rates and improved continence. Transabdominal procedures, however, usually imply rectal mobilization and fixation, colonic resection, or both, and some concern is voiced that morbidity, in terms of infection or leakage, and mortality could be increased. If we focus on surgical outcome, our own experience of laparoscopic resection-rectopexy for rectal prolapse shows that the laparoscopic approach is safe and effective, and functional results with respect to recurrence are favorable. However, the controversy "which operation is appropriate?" cannot be answered definitely, as a clear definition of rectal prolapse, the extent of a standardized diagnostic assessment, and the type of surgical procedure have not been identified in published series. Randomized trials are needed to improve the evidence with which the optimal surgical treatment of rectal prolapse can be defined.


The prevalence of potential alcohol-drug interactions in older adults.
The aim of this study was to assess the possibility of clinically significant drug-alcohol interactions among home-dwelling older adults aged ≥ 65 years. This study was a cross-sectional assessment of a stratified random sample of 2100 elderly people (≥ 65 years) in Espoo, Finland. The response rate was 71.6% from the community-dwelling sample. The drugs were coded according to their Anatomical Therapeutic Chemical (ATC) classification index (ATC DDD 2012). Significant alcohol interactive (AI) drugs were examined according to the Swedish, Finnish, INteraction X-referencing (SFINX) interaction database, as well as concomitant use of central nervous system drugs, hypoglycaemics, and warfarin with alcohol. "At-risk alcohol users" were defined consuming > 7 drinks/week, or ≥ 5 drinks on a typical drinking day, or using ≥ 3 drinks several times/week, "moderate users" as consuming at least one drink/month, but less than 7 drinks/week, and "minimal/non-users" less than one drink/month. Of the total sample (n = 1395), 1142 respondents responded as using at least one drug. Of the drug users, 715 (62.6%) persons used alcohol. The mean number of medications was 4.2 (SD 2.5) among "at-risk users", 4.0 (SD 2.6) among "moderate users", and 5.4 (SD 3.4) among "minimal/non-users" (p < 0.001). The concomitant use of AI drugs was widespread. Among the "at-risk users", "moderate users", and "minimal/nonusers" 42.2%, 34.9%, and 52.7%, respectively, were on AI drugs (p < 0.001). One in 10 of "at-risk users" used warfarin, hypnotics/sedatives, or metformin. Use of AI drugs is common among older adults, and this increases the potential risks related to the use of alcohol.


Comparison among different measurement systems for fibrinogen using fresh samples and frozen samples.
Many laboratories in China have several types of coagulation analyzers. Differences in fibrinogen results among different systems may cause inappropriate medical decisions. Our aim was to set the comparability evaluation criteria and evaluate comparability of different fibrinogen measurement systems using fresh and frozen samples. Biological variation (BV) publications on fibrinogen were reviewed. Total error based on reliable BV data and external quality assessment (EQA) criteria were combined to set allowable limit. The compliance rate of samples for the limit should achieve at least 80% if the results obtained from different systems were comparable. Fifty-seven samples before and after freeze-thaw were measured by three measurement systems and the percentage of compliant samples was calculated. The allowable limit was 11.3%. The compliance rates of fresh samples were 78.2-84.2%, and the rates of frozen samples were 54.5-93.0%. The comparability results were different using two kinds of samples. It is feasible to set allowable limits of comparability based on BV and state of the art; and fresh samples are recommended for evaluating systems comparability. The results of comparability are related to samples' concentrations distribution, which should range over the concentration ranges in routine laboratory tests.


Abnormalities of granule cell dendritic structure are a prominent feature of the intrahippocampal kainic acid model of epilepsy despite reduced postinjury neurogenesis.
Aberrant plastic changes among adult-generated hippocampal dentate granule cells are hypothesized to contribute to the development of temporal lobe epilepsy. Changes include formation of basal dendrites projecting into the dentate hilus. Innervation of these processes by granule cell mossy fiber axons leads to the creation of recurrent excitatory circuits within the dentate. The destabilizing effect of these recurrent circuits may contribute to hyperexcitability and seizures. Although basal dendrites have been identified in status epilepticus models of epilepsy associated with increased neurogenesis, we do not know whether similar changes are present in the intrahippocampal kainic acid model of epilepsy, which is associated with reduced neurogenesis. In the present study, we used Thy1-YFP-expressing transgenic mice to determine whether hippocampal dentate granule cells develop hilar-projecting basal dendrites in the intrahippocampal kainic acid model. Brain sections were examined 2 weeks after treatment. Tissue was also examined using ZnT-3 immunostaining for granule cell mossy fiber terminals to assess recurrent connectivity. Adult neurogenesis was assessed using the proliferative marker Ki-67 and the immature granule cell marker calretinin. Significant numbers of cells with basal dendrites were found in this model, but their structure was distinct from basal dendrites seen in other epilepsy models, often ending in complex tufts of short branches and spines. Even more unusual, a subset of cells with basal dendrites had an inverted appearance; they completely lacked apical dendrites. Spines on basal dendrites were found to be apposed to ZnT-3 immunoreactive puncta, suggestive of recurrent mossy fiber input. Finally, YFP-expressing abnormal granule cells did not colocalize Ki-67 or calretinin, indicating that these cells were more than a few weeks old, but were found almost exclusively in proximity to the neurogenic subgranular zone, where the youngest granule cells are located. Recent studies have demonstrated in other models of epilepsy that dentate pathology develops following the aberrant integration of immature, adult-generated granule cells. Given these findings, one might predict that the intrahippocampal kainic acid model of epilepsy, which is associated with a dramatic reduction in adult neurogenesis, would not exhibit these changes. Herein we demonstrate that hilar basal dendrites are a common feature of this model, with the abnormal cells likely resulting from the disruption of juvenile granule cell born in the weeks before the insult. These studies demonstrate that postinjury neurogenesis is not required for the accumulation of large numbers of abnormal granule cells.


Prognostic role of the advanced lung cancer inflammation index in cancer patients: a meta-analysis.
Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg's test, Egger's test, and the funnel plot were applied to assess the significance of publication bias. In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5-37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41-1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all). These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer patients.


Reproduction and production performance of improved chickens, their production constraints, and opportunities under Ethiopian conditions.
Chickens have important roles in human food security and social and cultural values throughout the world. The current review focused on improved chickens' reproduction and production performance, their production constraints, and opportunities under Ethiopian conditions. The review covered nine performance traits, thirteen commercial breeds, and eight crossbreds between commercial breeds, and local chicken. The genotypes affected the age of the first egg, eggs per hen per year, and average egg weight. The three exotic breeds with short ages at first egg were Lohmann Brown, Novo Brown, and Potchefstroom Koekoek at 137, 140, and 142 days, respectively. The three genotypes with the highest egg production were Sasso T44, Bovans Brown, and Isa Browns laying 229, 235, and 276 eggs per hen per year. The three with the highest egg weight were Isa Browns, Bovans Brown, and Sasso T44 with their eggs weighing 58.8, 60.3, and 65.6 g each, respectively. Crossbreeding indigenous chicken with exotic breeds improved the age at first egg-lay, eggs per hen per year, and egg weigh. Crossbreeding indigenous chicken with exotic breeds shortened the age at first egg-lay. Crossbred of indigenous chicken with Fayoumi, Rhode Island Red, and White Leghorn reduced age at first egg-lay to 196.0, 198.3 and 224.3 days, respectively. Crossbreeding Dominant Red Barred with indigenous chicken reduced the age at first egg-lay from 137.3 to 130.7 days. Among the crossbred chicken, crossing between local chicken and Fayoumi, White Leghorn, and Yarkon laid the most eggs per hen per year being 119, 120, and 129 eggs, respectively. The crossbreed between Dominant Red Barred, and Horro ecotype aged 41-44 weeks laid eggs weighing 56.3 g. The management practices affected age at first egg with the smallholder production system tending to delay it and reduced the eggs per hen per year and average egg weight. The age at first egg-lay for Bovans Brown breed ranged from 165.6 to 196.2 days under this system. Potchefstroom Koekoek chicken breed reared under this system laid 130.5 to 187.0 eggs per hen per year. When additional feed was provided, Bovans Brown chicken breed increased their egg production from 133.5 to 235.9 eggs per hen per year. The average egg weight was 43.0, 52.1, and 52.5 g for Fayoumi, White Leghorn, and Rhode Island Red chicken, repectivelly, under this system in northern Ethiopia. Most chicken breeds were reared under inadequate management practices resulting in suboptimal performance. Crossbreeding exotic and indigenous chicken breeds and intensifying the management will improve performance. The existence of suitable market demand for chicken products, readily available commercial feeds, and government and private investor involvement are emerging opportunities for enhanced chicken performance in Ethiopia.


Chylothorax and chylopericardial tamponade following Blalock-Taussig anastomosis.
A case of chylothorax following a right-sided Blalock-Taussig shunt is presented. Chylopericardial tamponade eventually developed, because the mediastinal leakage of chyle was sealed off from the pleural cavity and diverted into the pericardium. Chylopericardium is a rare cause of an enlarged cardiac silhouette on a postoperative chest roentgenogram, but the importance of differentiating it from congestive heart failure is illustrated. When chylopericardial tamponade occurs, treatment consists of (1) aspiration for immediate relief and, if there is recurrence, (2) surgical evacuation of the pericardium with tube drainage or pericardiectomy and (3) ligation of the source of chylous drainage.


An innovative technique for colorectal specimen retrieval: a new era of "natural orifice specimen extraction" (N.O.S.E).
The common incisions for transabdominal specimen retrieval after laparoscopic colorectal surgery are lower quadrant, midline, or transverse suprapubic incision. This study was designed to evaluate a novel method of specimen extraction after totally laparoscopic proctocolectomies. We retrospectively studied seven women patients from 2004 to 2007. The indication for surgery was familial polyposis coexisting with adenocarcinoma of the upper rectum. A totally laparoscopic proctocolectomy with ileal pouch-anal anastomosis was successfully performed for all cases. The entire specimen was extracted via a transvaginal route. The mean age of the patients was 49.5 years, and mean body mass index was 25.3 kg/m(2). The mean operating time was 222.5 minutes, and average blood loss was 172 ml. The average hospital stay was 25.5 days. Postoperative complications included ileus (n = 1), pouchitis (n = 1), and deep vein thrombosis (n = 1). The vaginal wound had healed completely by the first follow-up. There was no mortality. Our technique of transvaginal retrieval effectively prevents wound-related complications by completely eliminating minilaparotomies for specimen retrieval. It could be called "Natural Orifice Specimen Extraction," or N.O.S.E. We stress the need for innovations in specimen extraction, for which importance is not given by surgeons.


Implementation and outcomes of group medical appointments in an outpatient specialty care clinic.
To describe the outcomes of a nurse practitioner (NP)-facilitated group medical appointment (GMA) intervention for chronic obstructive pulmonary disease (COPD) clients in a pulmonary practice in the Midwest. Medical records from a convenience sample of six established pulmonary patients in a Midwest specialty clinic who received care in a group format were retrospectively audited. Outcome measures included examination of changes in the utilization of healthcare services, exercise tolerance, and use of nonpharmacological and pharmacological interventions pre- and postparticipation in the GMA program. NP-facilitated GMAs are feasible and can help improve health outcomes. Results showed a significant increase in exercise tolerance measured by 6-min walk distance. Anecdotally, patient and provider response to the GMA was very positive. The GMA format is an innovative solution for the management of chronic disease patients that is comprehensive, time efficient, reimbursable, and well suited to NP practice. GMAs can be implemented in most practice settings.


Rapid memory encoding in a recurrent network model with behavioral time scale synaptic plasticity.
Episodic memories are formed after a single exposure to novel stimuli. The plasticity mechanisms underlying such fast learning still remain largely unknown. Recently, it was shown that cells in area CA1 of the hippocampus of mice could form or shift their place fields after a single traversal of a virtual linear track. In-vivo intracellular recordings in CA1 cells revealed that previously silent inputs from CA3 could be switched on when they occurred within a few seconds of a dendritic plateau potential (PP) in the post-synaptic cell, a phenomenon dubbed Behavioral Time-scale Plasticity (BTSP). A recently developed computational framework for BTSP in which the dynamics of synaptic traces related to the pre-synaptic activity and post-synaptic PP are explicitly modelled, can account for experimental findings. Here we show that this model of plasticity can be further simplified to a 1D map which describes changes to the synaptic weights after a single trial. We use a temporally symmetric version of this map to study the storage of a large number of spatial memories in a recurrent network, such as CA3. Specifically, the simplicity of the map allows us to calculate the correlation of the synaptic weight matrix with any given past environment analytically. We show that the calculated memory trace can be used to predict the emergence and stability of bump attractors in a high dimensional neural network model endowed with BTSP.


Extending relapse prevention models to couples.
A model is proposed which extends Marlatt's Relapse Prevention model to couples. The model includes macroscopic and microscopic levels of analysis. At the macroscopic level, it is proposed that the probability of client coping responses is affected by the quality of the client's social support network, the quality of primary intimate relationships, the density of reinforcement for abstinence, and the expectation of loss of reinforcement for drinking. At the microscopic level, it is proposed that spouses may engage in a variety of coping responses that may either facilitate client coping and help maintain changes in drinking, or which are nonfacilitative and increase the likelihood of relapse. Clinical implications of the model are discussed.


Development and evaluation of mucoadhesive bigel containing tenofovir and maraviroc for HIV prophylaxis.
Sexual transmission of HIV is the most common means of acquiring the disease. Topical microbicides have been investigated to prevent transmission. This study will use a specific entry inhibitor, maraviroc, and a nucleotide reverse transcriptase inhibitor (NRTI), tenofovir, a dual combination which will provide a synergist effect that can enhance the efficacy of HIV microbicides via a mucoadhesive dual compartment bigel. Bigel formulation via hydrogel organogel linkages were developed and evaluated for their physicochemical characteristics, safety, and anti-HIV efficacy. In vitro diffusion studies were performed with Franz diffusion cells having effective diffusion surface area of 1.76cm2 and receiver chamber volume of 15mL. The bigel formulations showed a viscosity ranging from 14179 to 14560 cPs and had a good spreadability and acidic pH in the range of 4.0 ± 0.34 to 5.2 ± 0.18. The bigel formulations showed good anti-HIV activity at a concentration of 0.1 μg/mL. The in vitro release study of maraviroc from the bigel formulations showed a release rate ranging from 2.675 to 3.838 μg/cm2/min½ while the release rate for tenofovir ranged from 3.475 to 3.825 μg/cm2/min½. The bigel formulations were non-toxic to the human vagina as there was < 1 log10 change in Lactobacilli crispatus viability. This study successfully developed a dual compartment bigel containing maraviroc and tenofovir. BG C was found to be stable and safe towards vaginal and rectal epithelium, and it actively prevented HIV transmission. This bigel has the potential for long-term pre-exposure prophylaxis prevention of HIV transmission.


Simultaneous determination of rifampicin and isoniazid by continuous-flow chemiluminescence with artificial neural network calibration.
In this paper a continuous-flow chemiluminescence (CL) system with artificial neural network calibration is proposed for simultaneous determination of rifampicin and isoniazid. This method is based on the different kinetic spectra of the analytes in their CL reaction with alkaline N-bromosuccinimide as oxidant. The CL intensity was measured and recorded every second from 1 to 300 s. The data obtained were processed chemometrically by use of an artificial neural network. The experimental calibration set was 20 sample solutions. The relative standard errors of prediction for both analytes were approximately 5%. The proposed method was successfully applied to the simultaneous determination of rifampicin and isoniazid in a combined pharmaceutical formulation.


Distorted zinc coordination polyhedra in bis-(1-eth-oxy-2-{[(2-meth-oxy-eth-yl)imino]-meth-yl}propan-1-olato)zinc, a possible CVD precursor for zinc oxide thin films.
A new metal-organic precursor for the chemical vapor deposition of zinc oxide thin films, [Zn(C9H16NO3)2], has been synthesized and characterized by 1H and 13C NMR spectroscopy, single-crystal X-ray diffraction and thermogravimetric analysis. The asymmetric unit of the title compound consists of two mol-ecules (Z' = 2), with different zinc coordination polyhedra. In one mol-ecule, the metal atom is in a distorted trigonal-bipyramidal ZnN2O3 environment (τ5 = 0.192) with a long bond to an ether O donor atom [Zn-O = 2.727 (6) Å]. In the other, the Zn atom is in a distorted ZnN2O4 octa-hedral environment with long bonds to the ether O donors of both ligands [Zn-O = 2.514 (4) and 2.661 (4) Å; O-Zn-O = 82.46 (14)°]. The crystal structure features weak C-H⋯·O inter-actions.


Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation.
The comparative effects of intravenous aspirin, the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) and F(ab')2 fragments of monoclonal antibody 7E3 against platelet glycoprotein IIb/IIIa (7E3-F[ab']2) on thrombolysis, reocclusion and bleeding associated with 0.45 mg/kg body weight bolus injections of recombinant tissue-type plasminogen activator (rt-PA) were studied in a canine coronary artery thrombosis model. Coronary patency was monitored for 2 h both by flow probe and by coronary angiography. Four groups were studied: Group I = pretreated with 17 mg/kg intravenous aspirin (n = 6), Group II = pretreated with 200 micrograms/kg per min intravenous Argatroban for 60 min (n = 5), Group III = pretreated with aspirin and Argatroban (n = 5) and Group IV = pretreated with 0.8 mg/kg intravenous 7E3-F(ab')2 (n = 5). In Group I, reflow occurred in four of six dogs, but did not persist; reflow was induced in Group II in four of five dogs, persisting in one; in Group III, reflow occurred in all five dogs, persisting in four; in Group IV reflow was achieved in four of five dogs, persisting in two. The frequency of persistent reflow in Group III was significantly higher than in the combined Groups I and II (p = 0.012), whereas the time to reflow was significantly shorter in the groups receiving Argatroban than in the aspirin group (median 25 versus 55 min, p = 0.04). There were no significant differences between Groups III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)


Current Understandings of Molecular Biology of Echinococcus multilocularis, a Pathogen for Alveolar Echinococcosis in Humans- a Narrative Review Article.
Echinococcus multilocularis is a tiny tapeworm, responsible for 0.3~0.5 million alveolar echinococcosis in humans. We searched relevant papers published between 1981 and 2013 based on the database sources such as PubMed and Google scholar, and collected and integrated the data for analysis. The parasite is able to use host-originated molecules to modulate its development and has complex signalling pathways than expected previously. E. multilocularis utilizes many types of alternative splicing approaches to generate transcript isoforms. Recently, the genome of E. multilocularis has been deciphered. These data will give us a profound understanding of biology of E. multilocularis, which will promote the use as a model to study helminths.


Root bark of Discaria americana attenuates pain: A pharmacological evidence of interaction with opioidergic system and TRP/ASIC channels.
Discaria americana (Rhamnaceae) root bark infusion have been used in traditional medicine as antipyretic, tonic, ameliorative of stomach and skin diseases and diabetes. This study was designed to investigate whether the methanolic extract of the root bark of Discaria americana (MEDa) exhibits antinociceptive effects in mice. Furthermore, it was investigated the involvement of the opioidergic system in MEDa mechanism of action as well the interactions with TRP/ASIC channels in its effect. The antinociceptive effect of intra-gastric gavage (i.g.) of MEDa (0.3-300 mg/kg) was evaluated in mice subjected to acute chemical (acetic-acid, formalin, glutamate, capsaicin, cinnamaldehyde, and acidified saline) or thermal (hot plate) tests of pain. The involvement of opioid system was evaluated in the formalin test. A nonspecific effect of MEDa was observed by measuring locomotor activity and exploratory behavior in open field test. MEDa significantly reduced the number of writhing induced by acetic acid and inhibited the nociception in the two phases of formalin. These effects were inhibited by pretreatment with naloxone. The nociception induced by hot plate and intraplantar injection of glutamate, capsaicin, cinnamaldehyde and acidified saline were significantly inhibited by MEDa. Only the dose of 300 mg/kg altered the locomotor activity. Our results demonstrated, for the first time, that the methanolic extract of the root bark of Discaria americana presents antinociceptive effect in chemical and thermal stimuli and its analgesic properties can be due activation of the opioidergic system. These results support the use of Discaria americana in traditional medicine and demonstrate that this plant presents a therapeutic potential for the development of phytomedicines with antinociceptive profile.


Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.
To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction.


Multivalent ions are necessary for poly[d(AC).d(GT)] to assume the Z form: a CD study.
In previous work, it was shown that poly[d(AC).d(GT)] could be forced into the Z form by strong dehydrating conditions, provided EDTA was not present. Presumably multivalent impurities were also necessary for the transition. In order to gain control over the B to Z transition for this DNA, we carefully removed all divalent contaminants from the sample and asked the obvious question: What ions are necessary for the transition under dehydrating conditions? We systemically investigated the effect of various multivalent ions. The common contaminants Ca2+, Mg2+, and Fe3+ will not cause the transition, but Co2+ and Ni2+ facilitate the transition, undoubtedly because of their well-known propensity to bind to purine N7. Since the transition also depends on the synergistic dehydrating action of sodium perchlorate and ethanol, we include CD spectra for the independent variations of these two factors. In addition, vacuum-uv CD spectra for the A form and various B forms of poly[d(AC).d(GT)] are presented for the first time.


Magnetic Resonance Imaging: Principles and Techniques: Lessons for Clinicians.
The development of magnetic resonance imaging (MRI) for use in medical investigation has provided a huge forward leap in the field of diagnosis, particularly with avoidance of exposure to potentially dangerous ionizing radiation. With decreasing costs and better availability, the use of MRI is becoming ever more pervasive throughout clinical practice. Understanding the principles underlying this imaging modality and its multiple applications can be used to appreciate the benefits and limitations of its use, further informing clinical decision-making. In this article, the principles of MRI are reviewed, with further discussion of specific clinical applications such as parallel, diffusion-weighted, and magnetization transfer imaging. MR spectroscopy is also considered, with an overview of key metabolites and how they may be interpreted. Finally, a brief view on how the use of MRI will change over the coming years is presented.


Long-term results of tissue development and cell differentiation on Dacron prostheses seeded with microvascular cells in dogs.
The purpose of this study was to investigate in vivo the long-term development, differentiation, and proliferation of the subendothelial tissue on Dacron prostheses seeded with microvascular cells (MVC). Autologous MVC from omental adipose tissue were seeded on 4 mm Dacron prostheses and the prostheses interposed in the carotid arteries of mongrel dogs for 5, 13, and 26 weeks. Light and electron microscopic evaluation of patent seeded prostheses demonstrated an almost complete monolayer of endothelial cells and well-organized subendothelial tissue, whereas patent control prostheses were mainly covered by red and white thrombi, which were partially replaced by organized tissue with increased implantation time. The measurements of the thickness of the luminal cell layer in seeded and control grafts showed no statistically significant increase between 5 and 26 weeks of implantation. The subendothelial tissue of seeded prostheses demonstrated a time-dependent maturation of highly synthesizing myofibroblasts embedded in a collagen matrix to cells with features of smooth muscle cells located in a collagen-elastin matrix. In control grafts examined after 26 weeks the spontaneous endothelialization was accompanied by a delayed or incomplete maturation of subendothelial tissue. Our study indicates that MVC seeded onto Dacron prostheses are able to generate a vascular wall that does not continue to proliferate after prolonged implantation and that increasingly resembles the wall of a normal artery in cell differentiation and intercellular matrix.


Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta-analysis of 24 cohort studies.
The incidence and mortality of colorectal cancer (CRC) were quantified in persons with and without diabetes mellitus (DM). Medline and Embase were searched for articles published before July 2010. Cohort studies that evaluated incidence and mortality of DM and CRC were included. The initial search identified 1887 titles, of which 24 articles met the inclusion criteria. We defined the relative risk (RR) as the metric of choice; 95% confidence intervals (CIs) were calculated with a random-effects model. There was an increase in the RR of developing CRC in persons with DM compared with those without DM (RR 1.28; 95% CI 1.19-1.39), without heterogeneity between studies (P(heterogeneity) = 0.13). The association between duration of DM and CRC incidence was stronger in the 11-15-year group (RR 1.51; 95% CI 1.12-2.03) than in the <10-year group (RR 1.05; 95% CI 0.90-1.22) and the >15-year group (RR 1.25; 95% CI 0.80-1.94), and there was significant heterogeneity among subgroups (P(heterogeneity) = 0.01). In studies reporting standardized incidence ratios (SIRs), there was an increased incidence of CRC with DM (RR 1.27; 95% CI 1.14-1.42; P(heterogeneity) = 0.09), and the association was stronger among men (RR 1.47; 95% CI 1.15-1.86) than women (RR 1.08; 95% CI 1.00-1.17); there was significant heterogeneity among gender (P(heterogeneity) = 0.01). This meta-analysis suggests that individuals with DM have a significant increase in risk of developing CRC.


Fusion of isolated plant protoplasts.
A first step towards somatic hybridization in plants has been achieved. Protoplasts have been isolated and seen to fuse.


Oral and Dental Examination Findings in Beech Martens (Martes foina).
Detailed clinical and radiographical descriptions of oral/dental pathology in the beech marten (Martes foina) are lacking. In the present study, skulls of M. foina from a museum collection (n = 109) were examined macroscopically according to predefined criteria and full-mouth dental radiographs were obtained. Occlusion was diagnosed as 'scissor bite' in 22.5% of evaluated skulls, 77% of evaluated skulls showed 'level bite' of incisors and 9.2% of evaluated skulls had 'open bites'. In three skulls, class III malocclusion was diagnosed. Linguoversion of the mandibular second incisor teeth was noted in all skulls. Of the maximum possible number of teeth (i.e. full set of teeth in each skull), 90.4% were available for examination, 6.4% were missing artifactually, 2.0% were absent presumably congenitally and in 1.2 % the absence was presumably acquired. In three skulls supernumerary teeth were noted, all being incisor teeth. In four skulls, unerupted maxillary canine teeth were noted and in one skull odontodysplasia of the maxillary canine teeth was diagnosed. All other teeth were considered normal in morphology. The number of roots per tooth varied in the mandibular second premolar, maxillary first molar and mandibular second molar teeth. The most common dental pathology was attrition/abrasion with 72 skulls (66%) and 857 teeth (24.1% of evaluated teeth) affected, followed by periodontal disease affecting 52 (47.7%) of skulls and 773 teeth (18.9% of evaluated teeth). Dental fractures were present in 49 (45%) skulls and 148 teeth (3.8% of evaluated teeth). Radiographically evident periapical lesions were detected in 11 (10.1%) skulls and 18 teeth (0.5% of evaluated teeth). Other rare abnormal findings included tooth resorption, enamel hypoplasia/hypocalcification, fenestrations at palatal root of maxillary first molar tooth and different bony changes.


Ensemble structure description of Lys63-linked diubiquitin.
The data described herein are related to the article entitled "Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition" [1], and to the coordinates for the ensemble structure of Lys63-linked diubiquitin (PDB code 2N2K). A Lys63-linked diubiquitin exists in three conformational states with different orientations for the two subunits, each responsible for binding to a target protein and encoding a specific cell signal. An atomic entry in the ensemble structure file consists multiple lines, representing alternative locations of the atom and recapitulating the dynamics of the protein. Experimental details about obtaining strictly intramolecular paramagnetic restraints and determining the relative occupancies of the conformational states are presented. The experimental design and procedures in this Data article can be useful for characterizing the structure and dynamics of other multi-domain proteins.


Procedural sedation and analgesia with propofol (PSA) for gynecologic surgery: A systematic review of the literature.
To identify which gynecologic procedures are eligible to be performed under PSA with propofol and to describe safety and effectiveness of these procedures in this setting. A systematic review of the literature was conducted in Pubmed (MEDLINE), Embase and The Cochrane Library from inception until September 21st 2022. Cohort studies and randomized controlled trials were included when they reported on clinical outcomes of gynecologic procedures under procedural sedation and analgesia in which propofol was used as an anesthetic. Studies were excluded when sedation without propofol was used, when they only mentioned the use of procedural sedation and analgesia but did not describe any clinical outcome parameters or when < 10 patients were included. The primary outcome parameter was completeness of procedure. Secondary outcome parameters were type of gynecologic procedure, intraoperative complication rate, patient satisfaction, postoperative pain, duration of hospital admission, patient's discomfort and ease of procedure as judged by the surgeon. The Cochrane risk of bias tool and the ROBINS-I tool were used for bias assessment. A narrative synthesis of the findings from the included studies was provided. Numbers and percentages were presented, as well as means with standard deviations and medians with interquartile range where applicable. Eight studies were included. A total of 914 patients underwent gynecologic surgical procedures with procedural sedation and analgesia with propofol. Gynecological procedures varied from hysteroscopic procedures, vaginal prolapse surgery and laparoscopic procedures. The percentage of complete procedures was 89.8%-100%. Complications occurred in 0-6.5% of patients. Other outcomes were measured in various ways, but overall patient satisfaction was high and postoperative pain was low. The use of PSA with propofol is promising for a wide range of gynecologic procedures, including hysteroscopic procedures, vaginal prolapse surgery and laparoscopic procedures. The use of PSA with propofol seems to be effective and safe and leads to high degree of patient satisfaction. More research is needed in order to determine for which types of procedures PSA can be used.


High serum concentrations of dimeric inhibins A and B in normal newborn girls.
To establish the serum pattern of dimeric inhibins in normal girls during the newborn period and to examine its relationship with the postnatal gonadotropic surge. Retrospective study. SETTING; Division of endocrinology of a children's hospital. Thirty-one girls 4 to 65 days of age. Serum levels of FSH, LH, and inhibin A and B. High serum concentrations of both dimeric inhibins were detected during the first weeks of life. Concentrations tended to decrease through the second month of age. Inhibin A and B concentrations positively correlated with age only during the first 2 weeks of life (r =.57, P<.05 and r =.70, P<.01, respectively). Inhibin A and B were positively and significantly correlated with LH (r =.57, P<.05 and r =.52, P<.05, respectively) and with each other (r =.68, P<.0001). No correlation was found between dimeric inhibins and FSH. The high inhibin concentrations observed in newborn girls, which indicate advanced follicular development and granulosa cell differentiation, may be useful markers for congenital gonadal disorders.


Rhodamine B derivatives-modified upconversion nanoparticles as a fluorescent turn-off-on sensor for the highly sensitive detection of Cu2+ and pyrophosphate.
Rhodamine B derivatives (RBP)-modified UCNPs (UCNPs@mSiO2-RBP) were developed as a fluorescent turn-off-on sensor based on FRET and IFE to detect Cu2+ and pyrophosphate (PPi) with a wide linear response range (0-10 μM for Cu2+ and 5-35 μM for PPi, much wider than that reported previously) and high sensibility (117 nM for Cu2+ and 70 nM for PPi). The MTT experiments and the bioimaging experiments show its promising prospect in tissue imaging.


Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap).
Meta-analyses were conducted to characterize patterns of mutation incidence in non small-cell lung cancer (NSCLC). Nine genes with the most complete published mutation coincidence data were evaluated. One meta-analysis generated a 'mutMap' to visually represent mutation coincidence by ethnicity (Western/Asian) and histology (adenocarcinoma [ADC] or squamous cell carcinoma). Another meta-analysis evaluated incidence of individual mutations. Extended analyses explored incidence of EGFR and KRAS mutations by ethnicity, histology, and smoking status. Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. The mutMap highlighted mutation coincidences occurring in ≥5% of patients, including TP53 with KRAS or EGFR mutations in patients with ADC, and TP53 with LKB1 mutation in Western patients. TP53 was the most frequently mutated gene overall. Frequencies of TP53, EGFR, KRAS, LKB1, PTEN, and BRAF mutations were influenced by histology and/or ethnicity. Although EGFR mutations were most frequent in patients with ADC and never/light smokers from Asia, and KRAS mutations were most frequent in patients with ADC and ever/heavy smokers from Western countries, both were detected outside these subgroups. Potential molecular pathology segments of NSCLC were identified. Further studies of mutations in NSCLC are warranted to facilitate more specific diagnoses and guide treatment.


Importance of the hour of sampling in the lymphoblastic transformation assay of sheep peripheral blood lymphocytes.
This paper describes the effect of the nycthemeral cycle on the lymphocyte response of sheep to different mitogens (PHA, Con A and PWM). A considerable decline in the lymphocyte response was evident in the afternoon and early in the morning in all 6 animals tested. Three peak responses were identified during a 24 hour study period, at 14.00 h, 24.00 h and 08.00 h. The results presented here suggest that this variation in lymphocyte response is a meaningful difference in the response ability of individual lymphocytes. Factors affecting the number of leukocytes and the proportion of different types of lymphocytes in peripheral blood might be the essential causes of variation. To obtain an accurate indication of an individual's immunocompetence, it is important to make a preliminary determination of the optimal hour for sampling. If this is not possible, all the samples must be taken at the same hour on each test day, in order to make significant comparisons.


BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial.
BMS-927711 is a potent, selective, competitive human calcitonin gene-related peptide (CGRP) receptor antagonist that has shown in vivo efficacy without vasoconstrictor effect. The objective of the current study was to determine an effective and tolerable dose range of BMS-927711 for the acute treatment of migraine. In this randomized, double-blind, placebo controlled, dose-ranging study, 885 patients were randomized using an adaptive design to one of the following dose groups: BMS-927711 (10, 25, 75, 150, 300, or 600 mg); sumatriptan 100 mg (active comparator); and placebo. Patients were treated for a single migraine attack. The primary endpoint was pain freedom at two hours post-dose. Of patients who took the study drug, 799 had one post-randomization efficacy evaluation. Significantly more patients in the BMS-927711 75 mg (31.4%, P = 0.002), 150 mg (32.9%, P < 0.001), and 300 mg (29.7%, P = 0.002) groups and the sumatriptan group (35%, P < 0.001) had pain freedom at two hours post-dose versus placebo (15.3%). For the secondary endpoint of sustained pain freedom from two to 24 hours post-dose, BMS-927711 doses (25-600 mg) were also statistically significant compared with placebo. No deaths or treatment-related serious adverse events (AEs) were reported, and no patients discontinued because of AEs. BMS-927711 is superior to placebo at several different doses (75 mg, 150 mg, and 300 mg) and has an excellent tolerability profile.


Temperature and land use influence tree swallow individual health.
Aerial insectivorous bird populations have declined precipitously in both North America and Europe. We assessed the effects of insect prey availability, climate and shifts in water quality associated with urbanization on haematocrit, haemoglobin concentration and heterophil-lymphocyte (H/L) ratios among ~13-day-old tree swallow (Tachycineta bicolor) nestlings in the Columbus, Ohio area. Higher mean temperature and increased frequency of extreme heat days during the early breeding period (May-June) were linked to reduced nestling physiological condition as evidenced by lower concentrations of haemoglobin and haematocrit, potentially due to increased heat stress, shifts in insect prey availability or altered parental provisioning efforts. Urbanization and the size and density of emergent aquatic insects were associated with elevated physiological stress, whereas higher mean temperatures and terrestrial insect size were related to lower stress as measured by H/L ratios. Overall, these findings highlight the complex environmental conditions driving nestling health, which may be indicative of post-fledging survival and, consequently, population growth. Our results underscore the need for conservation approaches that adequately address the interrelated effects of changes in climate, land use and food resources on aerial insectivorous birds.


Changing dynamics of psychoneuroimmunology during the COVID-19 pandemic.
The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and a cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.


Similar behaviour of lecithin:cholesterol acyltransferase and pseudocholinesterase in liver disease and hyperlipoproteinemia.
Using exogenous substrate for its assay, lecithin:cholesterol acyltransferase (LCAT) was found to be decreased in liver disease and higher than normal in endogenous hypertriglyceridemia. LCAT activity was positively correlated with serum cholesterol and triglyceride. However in the six patients with excessive hypertriglyceridemia (type V), LCAT activity was lower than in type IV hyperlipoproteinemia. LCAT activity was not changed significantly in type II-a hyperlipoproteinemia. A striking parallel was noted between plasma LCAT and serum pseudocholinesterase activity. It suggested that both these liver secretion enzymes might be induced by an accelerated turnover of serum lipids and lipoproteins. Pathogenical implications of these findings are briefly discussed.


Desipramine subsensitizes nicotinic mechanism involved in regulating core temperature.
Desipramine HCl, 10 mg/kg i.p. twice daily, produced subsensitivity to the hypothermic effects of nicotine, 1 mg/kg, after 1 and 2 weeks of treatment in male Sprague-Dawley rats, Phenelzine sulfate, fluoxetine HCl, and bright artificial light produced the same effect. The capacity of three chemically distinct classes of anti-depressants and bright artificial light (a treatment for seasonal depression) to produce this result suggests that effects on nicotinic mechanisms may be involved in the mechanism of action of these treatments.


Biphasic extrathoracic cuirass ventilation for resuscitation.
The MRTX portable lightweight respirator (MRTX) provides noninvasive respiratory support using biphasic extrathoracic ventilation via a cuirass fitted around the patient's chest. MRTX was applied with or without full protective gear, on adult volunteers simulating nerve agent (NA) victims by nonmedical caregivers. Assessment was made based on scores for correct positioning of the cuirass, quality of seal, and rapidness. For the unprotected and protected personnel, the respective median (+/-95% confidence interval) scores for correct positioning of the cuirass were 2 (1.4-1.9) and 1 (1.2-1.8) (n = 15 per group, P = NS); quality of seal scores were 2 (1.5-2.0) and 2 (1.3-1.8) ( P = NS); and mean (+/-SD) time required for instituting mechanical ventilation was 90.5 +/- 10.9 and 100.3 +/- 7.9 seconds ( P < .05). The respirator was activated at first attempt 11 times in the group of 15 without protective gear and 8 times in the group of 15 with protective gear ( P = NS). Biphasic cuirass ventilation is an easily learned and rapidly applied method suitable for use by nonmedical personnel, even when wearing cumbersome protective gear.


Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.
MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study.


[Sternocostoclavicular hyperostosis: a space-occupying lesion of the superior thoracic aperture].
Sternocostoclavicular hyperostosis is a rare disease characterized by soft-tissue ossifications and hyperostosis of the clavicles, anterior segments of the upper ribs and sternum. These changes may imitate other disorders and thus may be misinterpreted. We present the radiologic appearances of this entity and discuss the diagnostic value of computerized tomography, magnetic resonance imaging and scintigraphy.


Data, data, burning deep, in the forests of the net.
Continuous and imaginative technological developments are leading to a massive accumulation of various types of data in all areas of biological research. As a result, the central importance of databases is increasing. Databases related to biology must not only be structured using controlled vocabularies, but also be fully integrated into the whole biological domain. To achieve this goal, they must be systematically grounded in biological evolution and exploit the available tools of evolutionary systematics to contribute to our understanding of life processes.


Traits that define the different alcohol intensive consume type during the practice of "botellon".
There is a phenomenon contributing to the current pattern of alcohol consumption among youngsters in Spain known as "botellon". From research financed by the National Plan on Drugs (2004-2007), data of 6009 youngsters (14-25 years old) were collected from three Spanish cities. Only individuals who engage in intensive consumption of alcohol (n = 2807) have been included. The purpose of this work has been to identify the different types of consumers at risk through a cluster analysis and to establish a profile for each particular group. Four groups were differentiated by age, gender, alcohol consumption and years of consumption. It was observed that adolescent students and university students of the same sex consume similar quantities of alcohol, and justify their consumption alluding to personal factors, whereas university students refer to issues related to control of leisure. The consumption by males is the highest, and they are the most likely to seek drunkenness. They associate to a lesser degree their consumption with the possibility of developing an addictive process. In general, all youngsters consider that their consumption will have no negative consequences. These results indicate the need to come up with different alternatives, addressing the particularities of each group.


DNAzyme based dual signal amplification strategy for ultrasensitive myocardial ischemia related MiRNA detection.
Abnormal expression of microRNAs (miRNAs) is closely associated with a diverse of important biological processes, such as metastasis, myocardial ischemia and progression. Development of a facile and enzyme-free method for sensitive miRNA detection remains a huge challenge. Herein, we proposed a cross-catalytic circuit for trace miRNA detection by facilely integrating hairpin catalytic reaction (HCR) and DNAzyme biocatalyst through an ingenious feedback loop. The DNAzyme functional part was originally grafted in the designed hairpin structure probes, which would be released from hairpin structure probe and induce subsequent signal amplification after the recognition of target miRNA and the formation of double-strand DNA products. Through the dual signal amplification, the method exhibited a favorable detection sensitivity with a low of detection of 56 fM. These two indispensable catalytic reactions play vital roles in executing high-performance signal amplification, as demonstrated experimentally and theoretically.


Torsion of giant occipital encephalocoele in a 2-day-old infant: emergent surgery and outcome.
Torsion of a giant occipital encephalocele leading to necrosis is an extremely rare complication found in neonates with only two such cases reported in literature previously. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocele showing progressive necrosis during the first day of his life. A new-born baby, delivered vaginally, with no antenatal imaging was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the first day of his life, the sac started becoming ulcerated accompanied with a rapid colour change in the skin, gradually turning darker and then black. The pedicle of the encephalocele was twisted with progressive necrosis of the encephalocele. MRI showed a giant encephalocele with single vein draining into the torcula and dysplastic occipital lobe herniating into the defect. The neonate was taken up for urgent excision and repair of the encephalocele. The encephalocele was excised 'in-total' with 'figure-of-8' repair of the meninges. One year after the operation, she appears to be well-developed without any neurological problems. Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocele may be another predisposing factor. In view of the risk of meningitis and rupture, immediate surgery with repair with minimal blood loss is indicated.


A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.
DNA demethylation plays a critical role in transcriptional regulation in differentiated somatic cells. However, there is no experimental evidence that CpG methylation in a small region of a genome restricts gene expression. Here, we show that the anti-CD3repsilon/CD28 antibody stimulation of human CD4+ T cells induces IL2 expression following epigenetic changes, including active demethylation of a specific CpG site, recruitment of Oct-1, and changes in histone modifications. When the stimulatory signal is withdrawn, Oct-1 remains on the enhancer region as a stable marker of the stimulation, causing the second induction to be faster and stronger. Our observations indicate that Oct-1-binding followed by CpG demethylation are key events in the epigenetic regulation of IL2 expression and may act as a memory of the regulatory event.


Nutrition education with or without oral nutrition supplements has contrasting effects on nutrition status in older adults: A randomized controlled study.
Oral nutrition supplements (ONSs) play an important role in the management of malnutrition. This aim of study was to examine whether a comprehensive intervention, combining ONSs, family-centered health education, and nutrition and medical consultations, could improve the nutrition and health status of malnourished older adults living in community dwellings. A randomized controlled trial was conducted from October 2017 to May 2018 in Shanghai. All participants were screened using the Mini Nutritional Assessment-Short Form (MNA-SF). Participants with MNA-SF scores ≤11 and age ≥65 were selected. Participants with potential nutrition risk were randomized into two groups: intervention group (n = 101) were prescribed ONSs (400 kcal/day) and family-centered nutrition education (once every 2 weeks) and control group (n = 100) received only family-centered nutrition education. Anthropometric measurements, including weight and height, and nutrition and functional scales, including MNA-SF, grip strength, and activities of daily living scores, were collected at the beginning of the study and 12 weeks later. Of the 201 study participants, 182 completed the study (mean age, 75.48 ± 7.47 years). After 12 weeks, nutrient intake improvements in the intervention group (+370.6 ± 432.6 kcal/day, +17.6 ± 24.1 g/day) exceeded that of the control group (-67.5 ± 378.2 kcal/day, -0.9 ± 16.7 g/day). In addition, improvements in weight, body mass index, and handgrip strength were significantly higher in the intervention vs control group (P < .05). Comprehensive nutrition interventions improved nutrition status in malnourished older people living in community dwellings. Use of ONSs may be a good strategy to improve nutrition status and strength in community-dwelling older adults.


Measures of frequency and effect in clinical research.
The assessment of risk and effect size of a specific endpoint associated to the presence/absence of a certain exposure is a hallmark in clinical and epidemiological research. In fact, before recommending any treatment, it is mandatory to investigate the magnitude of the benefits and harms between the exposure under investigation (e.g. a given treatment) and a specific disease or event. To do this, clinicians and statisticians use absolute (risk differences, number needed to treat, likelihood to be helped or harmed) and relative (risk ratio, incidence rate ratio, hazard ratio and odds ratio) measures of effect. Herein, using a series of clinical examples, we aim to present a step by step methodologic approach of measures of effect in the area of nephrology and urology.


The Comparison between Cemented and Uncemented Hemiarthroplasty in Patients with Femoral Neck Fractures: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Hemiarthroplasty is the standard treatment for patients with femoral neck fractures (FNFs). Controversy exists over the use of bone cement in hip fractures treated with hemiarthroplasty. We performed an updated systematic review and meta-analysis to compare cemented and uncemented hemiarthroplasty in patients with femoral neck fractures. A literature review was conducted using Cochrane Library, ScienceDirect, PubMed, Embase, Medline, Web of Science, CNKI, VIP, Wang Fang, and Sino Med databases. Studies comparing cemented with uncemented hemiarthroplasty for FNFs in elderly patients up to June 2022 were included. Data were extracted, meta-analyzed, and pooled as risk ratios (RRs) and weighted mean differences (WMDs) with a 95% confidence interval (95% CI). Twenty-four RCTs involving 3471 patients (1749 cement; 1722 uncemented) were analyzed. Patients with cemented intervention had better outcomes regarding hip function, pain, and complications. Significant differences were found in terms of HHS at 6 weeks (WMD 12.5; 95% CI 6.0-17.0; P < 0.001), 3 months (WMD 3.3; 95% CI 1.6-5.0; P < 0.001), 4 months (WMD 7.3; 95% CI 3.4-11.2; P < 0.001), and 6 months (WMD 4.6; 95% CI 3.3-5.8; P < 0.001) postoperatively. Patients with cemented hemiarthroplasty had lower rates of pain (RR 0.59; 95% CI 0.39-0.9; P = 0.013), prosthetic fracture (RR 0.24; 95% CI 0.16-0.38; P < 0.001), subsidence/loosening (RR 0.29; 95% CI 0.11-0.78; P = 0.014), revisions (RR 0.59; 95% CI 0.40-0.89; P = 0.012), and pressure ulcers (RR 0.43; 95% CI 0.23-0.82; P = 0.01) at the expense of longer surgery time (WMD 7.87; 95% CI 5.71-10.02; P < 0.001). This meta-analysis demonstrated that patients with cemented hemiarthroplasty had better results in hip function and pain relief and lower complication rates at the expense of prolonged surgery time. Cemented hemiarthroplasty is recommended based on our findings.


A Prodromal Brain-Clinical Pattern of Cognition in Synucleinopathies.
Isolated (or idiopathic) rapid eye movement sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Biomarkers are lacking to predict conversion to a dementia or a motor-first phenotype. Here, we aimed at identifying a brain-clinical signature that predicts dementia in iRBD. A brain-clinical signature was identified in 48 patients with polysomnography-confirmed iRBD using partial least squares between brain deformation and 27 clinical variables. The resulting variable was applied to 78 patients with iRBD followed longitudinally to predict conversion to a synucleinopathy, specifically DLB. The deformation scores from patients with iRBD were compared with 207 patients with PD, DLB, or prodromal DLB to assess if scores were higher in DLB compared to PD. One latent variable explained 31% of the brain-clinical covariance in iRBD, combining cortical and subcortical deformation and subarachnoid/ventricular expansion to cognitive and motor variables. The deformation score of this signature predicted conversion to a synucleinopathy in iRBD (p = 0.036, odds ratio [OR] = 2.249; 95% confidence interval [CI] = 1.053-4.803), specifically to DLB (OR = 4.754; 95% CI = 1.283-17.618, p = 0.020) and not PD (p = 0.286). Patients with iRBD who developed dementia had scores similar to clinical and prodromal patients with DLB but higher scores compared with patients with PD. The deformation score also predicted cognitive performance over 1, 2, and 4 years in patients with PD. We identified a brain-clinical signature that predicts conversion in iRBD to more severe/dementing forms of synucleinopathy. This pattern may serve as a new biomarker to optimize patient care, target risk reduction strategies, and administer neuroprotective trials. ANN NEUROL 2021;89:341-357.


Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study.
Leukocyte telomere length (LTL) is ostensibly a bio-indicator of human aging. Here we report that African Americans have longer LTL than whites. We studied cross-sectionally 2453 individuals from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study (age = 30-93 years) and the Bogalusa Heart Study (age = 19-37 years), comprising 1742 whites and 711 African Americans. We measured LTL by Southern blots of the terminal restriction fragments length. In 234 participants, telomere repeats were also measured by quantitative polymerase chain reaction (qPCR). Adjusted for age and body mass index (BMI), the respective leukocyte telomere lengths (mean +/- SEM) were considerably longer in African Americans than in whites both in the Family Heart Study (7.004 +/- 0.033 kb vs. 6.735 +/- 0.024 kb, p < 0.0001) and the Bogalusa Heart Study (7.923 +/- 0.063 kb vs. 7.296 +/- 0.039 kb, p < 0.0001). We confirmed the racial effect on LTL by qPCR (3.038 +/- 0.565 T/S units for African Americans vs. 2.714 +/- 0.487 T/S units for whites, p < 0.001). Cross-sectionally, sex- and BMI-adjusted LTL became shorter with age (range 19-93 years) at a steeper slope in African Americans than in whites (0.029 kb year(-1) vs. 0.020 kb year(-1), respectively, p = 0.0001). We suggest that racial difference in LTL arises from a host of interacting biological factors, including replication rates of hematopoietic stem cells.


Synthesis and biological evaluation of marine natural product, Cryptoechinuline D derivatives as novel antiangiogenic agents.
Tumor angiogenesis is an important biological process involved in the proliferation and migration of endothelial cells, regulated by Ang/Tie-2 signaling pathways, which is essential for tumor growth and metastasis. Therefore, blocking Ang/Tie-2 signaling pathways is a promising anti-angiogenic strategy for tumor treatment. 2,5-Diketopiperazines (DKPs) are a kind of bioactive compounds derived from marine fungi and they present a wide spectrum of pharmacological properties, particularly in the field of cancer treatment. Herein, a DKP marine natural product, Cryptoechinuline D (Cry D) was applied to structural modification and twelve derivatives were synthesized. Among which, compound 5 showed significant inhibitory activity against HUVECs with an IC50 value of 12.6 μmol/L, which weakened the proliferation, migration and invasion of HUVECs by inhibiting the Ang2/Tie-2 signaling pathway. The results of these evaluations indicated that compound 5 might be a promising anti-angiogeneic agent and worth further optimization and development for cancer therapy.


Progressive psychiatry: a research agenda.
It is possible to create a new research agenda based on an alternative perspective of human behavior and mind. After describing the theoretical tenets of this alternative perspective, illustrations of a new research agenda are presented. Such a research agenda would: (1) create new points of departure; (2) examine social relations underlying all variables; (3) more fully explore "unexplained variance;" (4) focus on the adaptive interaction of individuals within their world. Such research aims towards enhancing human uniqueness, action, and spirit.


Axillary fossaa microbial dysbiosis and its relationship with axillary osmidrosis patients.
Skin is one of the largest human bacterial reservoirs, especially the human axilla. The microbiota of the human axilla plays an important role in the creation of axillary smell. To explore the structure and composition of the axillary fossa microbiota between bromhidrosis patients and normal people, skin samples were collected from the armpits of 40 individuals, including 20 patients (10 males (aM), 10 females (aF), osmidrosis), and 20 healthy individuals (10 males (NM), 10 females (NF), control). High-throughput sequencing of the 16S rRNA gene was carried out on a Hiseq2500 platform with the V3+V4 regions. According to the bacterial Shannon diversity index and Simpson, we found that aF was significantly higher than the control but aM had no obvious distinction. Actinobacteria, Firmicutes, Proteobacteria and Deinococcus-Thermus were the dominant phyla in the four groups. Actinobacteria was distinctly higher in aM, while Firmicutes was significantly lower in aM. Furthermore, the aF displayed inverse results with aM. Corynebacterium-1 and Staphylococcus were the dominant genera in the four groups. Interestingly, Staphylococcus was the most abundant in aF, and Corynebacterium-1 was the dominant genus in aM and Corynebacterium-kroppenstedtii was significantly different in aM. Moreover, functional capacity analysis showed that genes associated with amino acid metabolism and lipid metabolism were higher in aM than in other groups, while pyruvate metabolism (carbohydrate metabolism) was obviously high in aF. There were clearly distinct of axillary microbiota undergoes changes between bromhidrosis patients and controls. Staphylococcus and Corynebacterium-1 in aF and aM, respectively, were detected with distinctly elevated proportions, which might be strongly related to human axilla odor.


Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.
The AAA+ ATPase valosin containing protein (VCP) is essential for cell and organ homeostasis, especially in cells of the nervous system. As part of a large network, VCP collaborates with many cofactors to ensure proteostasis under normal, stress, and disease conditions. A large number of mutations have revealed the importance of VCP for human health. In particular, VCP facilitates the dismantling of protein aggregates and the removal of dysfunctional organelles. These are critical events to prevent malfunction of the brain and other parts of the nervous system. In line with this idea, VCP mutants are linked to the onset and progression of neurodegeneration and other diseases. The intricate molecular mechanisms that connect VCP mutations to distinct brain pathologies continue to be uncovered. Emerging evidence supports the model that VCP controls cellular functions on multiple levels and in a cell type specific fashion. Accordingly, VCP mutants derail cellular homeostasis through several mechanisms that can instigate disease. Our review focuses on the association between VCP malfunction and neurodegeneration. We discuss the latest insights in the field, emphasize open questions, and speculate on the potential of VCP as a drug target for some of the most devastating forms of neurodegeneration.


Changes in lung volume and work of breathing: A comparison of two variable-flow nasal continuous positive airway pressure devices in very low birth weight infants.
Variable flow nasal continuous positive airway pressure (VF-NCPAP) recruits lung volume more effectively and reduces work of breathing (WOB) compared to constant-flow NCPAP (CF-NCPAP) in very low birth weight (VLBW) infants. Because different VF-NCPAP devices have somewhat different flow patterns, whether different VF-NCPAP devices function similarly is unknown. We compared two VF-NCPAP devices: the Infant Flow trade mark (EME, Ltd.) and the Arabella(R) (Hamilton Medical) to assess whether lung volume recruitment and WOB were similar in VLBW infants requiring NCPAP. Eighteen infants <1,500 g were studied on both NCPAP devices applied in random order. All infants required NCPAP for mild respiratory distress. Calibrated DC-coupled respiratory inductance plethysmography (RIP) was used to assess lung volume changes. NCPAP was first increased to 8 cmH(2)O to allow comparable recruitment in all infants, and then was slowly decreased to 6, 4, and 0 cmH(2)O, with data collection at each level. Mean birth weight (+/-SD) was 1,107 +/- 218 g, gestational age was 27.9 +/- 2.0 weeks, weight at study was 1,092 +/- 222 g, and age at study was 4.6 +/- 4.3 days. There were no differences in lung volume recruitment overall or at any NCPAP level (P = 0.943). No differences were found in either inspiratory WOB (P = 0.468) or in resistive WOB (P = 0.610) between devices. Compliance, tidal volume, respiratory rate, and minute ventilation were also similar. Despite differences in flow characteristics between the two VF-NCPAP devices we studied, lung volume recruitment and WOB were similar.


Thalamic reticular nucleus in Caiman crocodilus: Relationship with the dorsal thalamus.
The thalamic reticular nucleus was investigated in one group of crocodilians, Caiman crocodilus. This neuronal aggregate is composed of two parts: a compact portion and a diffuse region made up of scattered cells within the forebrain bundles. In Caiman, both the lateral and medial forebrain bundles project to the telencephalon and the thalamic reticular nucleus is associated with each fiber tract. In the lateral forebrain bundle, the compact area is termed the nucleus of the dorsal peduncle (dorsal peduncular nucleus) while the diffuse part is called the perireticular area. In the medial forebrain bundle, the interstitial nucleus comprises one part of the compact area while another region without a specific neuronal label is also present. Similar to the perireticular cells of the lateral forebrain bundle, scattered cells are also present in the medial forebrain bundle. Morphological features of the thalamic reticular nucleus are revealed with stains for the following: fibers; cells; succinic acid dehydrogenase; and acetylcholinesterase. Regardless of which dorsal thalamic nucleus was injected, a localized region of the thalamic reticular nucleus contained retrogradely labeled cells and anterogradely labeled axons and terminals. This grouping was termed clusters and was felt to represent the densest interconnection between the dorsal thalamus and the reticular nucleus. Using clusters as an index of interconnections, the reticular nucleus was divided into sectors, each of which was associated with a specific dorsal thalamic nucleus. An organization similar to that found in Caiman is present in other sauropsids as well as in mammals. These data suggest that a thalamic reticular nucleus is present in all amniotes and has morphological properties similar to those described in this analysis. Lastly, a hypothesis is presented to explain how the external shape of the reticular nucleus in Caiman might be transformed into the homologous area in a representative bird and mammal.


Asymmetry between Activators and Deactivators in Functional Protein Networks.
Are "turn-on" and "turn-off" functions in protein-protein interaction networks exact opposites of each other? To answer this question, we implement a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. We study the roles of activators and deactivators, two core components of oscillatory protein interaction networks, and find a striking asymmetry in the roles of activating and deactivating proteins, where activating proteins tend to be synergistic and deactivating proteins tend to be competitive.


LSm proteins form heptameric rings that bind to RNA via repeating motifs.
Members of the LSm family of proteins share the Sm fold--a closed barrel comprising five anti-parallel beta strands with an alpha helix stacked on the top. The fold forms a subunit of hexameric or heptameric rings of approximately 7nm in diameter. Interactions between neighboring subunits center on an anti-parallel interaction of the fourth and fifth beta strands. In the lumen of the ring, the subunits have the same spacing as nucleotides in RNA, enabling the rings to bind to single-stranded RNA via a repeating motif. Eubacteria and archaea build homohexamers and homoheptamers, respectively, whereas eukaryotes use >18 LSm paralogs to build at least six different heteroheptameric rings. The four different rings in the nucleus that permanently bind small nuclear RNAs and function in pre-mRNA maturation are called Sm rings. The two different rings that transiently bind to RNAs and, thereby, assist in the degradation of mRNA in the cytoplasm and the maturation of a wide spectrum of RNAs in the nucleus are called LSm rings.


Wheat variety carrying 2NvS chromosomal segment provides yield advantage through lowering terminal heat-induced oxidative stress.
A 2NvS chromosomal segment carrying bread wheat variety, BARI Gom 33 ('BG33'), showed tolerance to terminal heat stress and higher yield over a heat-tolerant non-2NvS BARI Gom 26 ('BG26') and a heat-susceptible Pavon 76 ('Pavon'). This study aimed to ascertain the potential of the 2NvS 'BG33' in terminal heat-induced oxidative stress tolerance compared to non-2NvS 'BG26' and heat-susceptible 'Pavon' under two heat regimes at the reproductive stages viz. control (optimum sowing time) and heat stress (late sowing). We found that both 'BG26' and 'BG33' showed significantly higher tolerance to oxidative stress by limiting the generation of reactive oxygen species (ROS), methylglyoxal under heat stress. During terminal heat stress, both 'BG33' and 'BG26' exhibited greater cellular homeostasis than heat-susceptible 'Pavon', which was maintained by the increased accumulation of osmolytes, nonenzymatic antioxidants, and enzymes associated with ROS scavenging, ascorbate-glutathione cycle, and glyoxalase system. Lesser cellular damage in 'BG26' and 'BG33' was eventually imitated in a smaller reduction in grain yield (15 and 12%, respectively) than in 'Pavon', which had a 33% reduction owing to heat stress. Collectively, our findings revealed that the chromosomal segment 2NvS provides yield advantage to 'BG33' under terminal heat stress by lowering oxidative damage. As 2NvS translocation contains multiple nucleotide-binding domain leucine-rich repeat containing, cytochrome P450, and other gene families associated with plant stress tolerance, further studies are warranted to dissect the underlying molecular mechanisms associated with higher heat stress tolerance of 2NvS carrying 'BG33'.


Management of Early-Stage Cervical Cancer: A Literature Review.
Cervical cancer (CC) remains a public health issue worldwide despite preventive measures. Surgical treatment in the early-stage CC has evolved during the last decades. Our aim was to review the advances in the literature and summarize the ongoing studies on this topic. To this end, we conducted a literature review through PubMed focusing on English-language articles on the surgical management of early-stage CC. The emergent topics considered here are the FIGO 2018 staging system update, conservative management with less radical procedures for selected patients, lymph node staging, fertility preservation, preferred surgical approach, management of tumors up to 2 cm, and prognosis. In terms of updating FIGO, we highlight the inclusion of lymph node status on staging and the possibility of imaging. Regarding the preferred surgical approach, we emphasize the LACC trial impact worldwide in favor of open surgery; however, we discuss the controversial application of this for tumors < 2 cm. In summary, all topics show a tendency to provide patients with tailored treatment that avoids morbidity while maintaining oncologic safety, which is already possible in high-income countries. We believe that efforts should focus on making this a reality for low-income countries as well.


Screening of immune cell activators from Astragali Radix using a comprehensive two-dimensional NK-92MI cell membrane chromatography/C18 column/time-of-flight mass spectrometry system.
Astragali Radix (AR) is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer (NK) cells. However, owing to the complexity of its composition, the specific active ingredients in AR that act on NK cells are not clear yet. Cell membrane chromatography (CMC) is mainly used to screen the active ingredients in a complex system of herbal medicines. In this study, a new comprehensive two-dimensional (2D) NK-92MI CMC/C18 column/time-of-flight mass spectrometry (TOFMS) system was established to screen for potential NK cell activators. To obtain a higher column efficiency, 3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column. In total, nine components in AR were screened from this system, which could be washed out from the NK-92MI/CMC column after 10 min, and they showed good affinity for NK-92MI/CMC column. Two representative active compounds of AR, isoastragaloside I and astragaloside IV, promoted the killing effect of NK cells on K562 cells in a dose-dependent manner. It can thus suggest that isoastragaloside I and astragaloside IV are the main immunomodulatory components of AR. This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.


Hydroxychloroquine sulfate: A novel treatment for lipin-1 deficiency?
Lipin-1 deficiency is a life-threatening disease that causes severe rhabdomyolysis (RM) and chronic symptoms associated with oxidative stress. In the absence of treatment, Hydroxychloroquine sulfate (HCQ) was administered to patients off label use on a compassionate basis in order to improve their physical conditions. Eleven patients with LPIN1 mutations were treated with HCQ. Clinical and biological efficacy and tolerance were assessed, including pain and quality of life, physical capacities, cardiopulmonary parameters, creatine kinase levels and plasma proinflammatory cytokines. To explore a dose-dependent effect of HCQ, primary myoblasts from 4 patients were incubated with various HCQ concentrations in growth medium (GM) or during starvation (EBSS medium) to investigate autophagy and oxidative stress. Under HCQ treatment, patient physical capacities improved. Abnormal cardiac function and peripheral muscle adaptation to exercise were normalized. However, two patients who had the highest mean blood HCQ concentrations experienced RM. We hypothesized that HCQ exerts deleterious effects at high concentrations by blocking autophagy, and beneficial effects on oxidative stress at low concentrations. We confirmed in primary myoblasts from 4 patients that high in vitro HCQ concentration (10 µM) but not low concentration (1 µM and 0.1 µM) induced autophagy blockage by modifying endolysosomal pH. Low HCQ concentration (1 µM) prevented reactive oxygen species (ROS) and oxidized DNA accumulation in myoblasts during starvation. HCQ improves the condition of patients with lipin-1 deficiency, but at low concentrations. In vitro, 1 µM HCQ decreases oxidative stress in myoblasts whereas higher concentrations have a deleterious effect by blocking autophagy.


The connections from botzinger expiratory neurons to upper cervical inspiratory neurons in the cat.
These experiments examined possible inhibitory inputs to upper cervical inspiratory neurons from the expiratory neurons of the Botzinger complex. Eighty-one Botzinger neurons were tested with antidromic mapping for a projection to the C1 segment of the spinal cord; 44/81 (54%) were found to project, 27/79 (34%) contralaterally, 17/68 (25%) ipsilaterally, and 1/66 (2%) both contralaterally and ipsilaterally. Antidromic mapping in contralateral C1 demonstrated the presence of a collateral in 3/15 (20%) of the Botzinger neurons tested, while 3/9 (33%) had collateral arborizations in ipsilateral C1. The collaterals mapped were not localized to the region of the upper cervical inspiratory neurons. Microstimulation in C3 (12-17 microA, 0.2-ms duration) at locations which produced short-latency (2.7-3.5 ms) inhibition of phrenic nerve discharge resulted in the short latency (3.0 ms) inhibition of 1/27 (3.7%) upper cervical inspiratory neurons as demonstrated by cross-correlation. It was concluded that while some upper cervical inspiratory neurons may be inhibited during expiration by the Botzinger expiratory neurons, this connection is not a strong one.


Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury.
Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury.


Does mutarotation influence lactose digestion? Experimental investigations and a mathematical model.
The nutrient lactose acts as a potential dietary fibre. Depending on the composition of diet, lactose can partially escape from digestion and absorption in the small intestine and is utilised by the colonic microflora. The suggested mechanism, i.e. different rates of enzymatic hydrolysis of the lactose anomers and an influence of food ingredients on lactose mutarotation, seems to be supported by experimental results. The Michaelis constant of the mucosal beta-galactosidase of rats is 14 mmol/l with alpha-lactose and 50 mmol/l with beta-lactose as substrates. During intestinal perfusion of human infants, alpha-lactose is digested at a significantly higher rate than beta-lactose. The mutarotation of lactose is influenced by general acid-base catalysis. Milk formulae containing a high concentration of weak-acid anions, e.g. cow milk which is rich in phosphate and citrate, accelerate mutarotation, but milk formulae with a low content of these anions do not. With these experimental results a mathematical model has been set up simulating lactose digestion in the small intestine of human infants and of rats. The data show that certain dietary components may influence the ratio between lactose anomers, but, surprisingly, they do not influence the amount of digested lactose.


Anti-angiogenic therapy: rationale, challenges and clinical studies.
Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.


The Danish model for the quick and safe implementation of infliximab and etanercept biosimilars.
A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept). We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation. The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds. We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars.


An enclosed system for continuous postoperative mediastinal aspiration.
Blockage of mediastinal drainage tubes in the postoperative cardiac surgical patient can result in tamponade, and the small child, with a necessarily small drainage tube, is particularly susceptible to instability arising from accumulating blood in the mediastinum. A system for continuous evacuation of blood in drainage tubes is described that decreases the likelihood of blocked tubes and resultant tamponade.


[Effectiveness of broncholytics and positive end expiratory pressure in bronchial asthma].
To improve treatment with bronchodilators, the study was made of 60 bronchial asthma patients' external respiration upon berotek administration and Positive end expiration pressure (PEEP). More distinct bronchodilatation was achieved with combination of the two modalities in aggravated asthma. IPPV, as allowing minimal drug administration, is recommended for use in rehabilitation.


Alpha-fetoprotein assay in patients treated with low-dose oral contraceptives.
AFP has proven to be a useful marker for liver neoplasms. The authors assayed AFP plasma levels in patients taking low-dose estro- progestinics . Patients were divided into three groups on the basis of their living habits. No difference was found in any group between AFP levels before and after treatment. However, in the group of smokers using oral contraceptives AFP levels were significantly higher.