Abdominal muscle function and incisional hernia: a systematic review.
Although ventral incisional hernia (VIH) repair in patients is often evaluated in terms of hernia recurrence rate and health-related quality of life, there is no clear consensus regarding optimal operative treatment based on these parameters. It was proposed that health-related quality of life depends largely on abdominal muscle function (AMF), and the present review thus evaluates to what extent AMF is influenced by VIH and surgical repair. The PubMed and EMBASE databases were searched for articles following a systematic strategy for inclusion. A total of seven studies described AMF in relation to VIH. Five studies examined AMF using objective isokinetic dynamometers to determine muscle strength, and two studies examined AMF by clinical examination-based muscle tests. Both equipment-related and functional muscle tests exist for use in patients with VIH, but very few studies have evaluated AMF in VIH. There are no randomized controlled studies to describe the impact of VIH repair on AMF, and no optimal surgical treatment in relation to AMF after VIH repair can be advocated for at this time.


Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
Neuronal damage mediated by the TRAIL-system might be involved in the pathogenesis of neuroinflammatory diseases of the central nervous system. Here we used an investigator-independent approach to quantify TRAIL-mediated death of total CNS cells and neurons in a living human brain slice culture system, a model which is much closer to the in vivo situation than dissociated cell culture. We observed dose-dependent TRAIL-mediated death of both total human CNS cells and neurons, which was prevented by flupirtine-maleate, a centrally acting analgesic drug with proposed neuroprotective properties. Our data suggest flupirtine-maleate as an orally available neuroprotective approach in the course of neuroinflammation.


Thrombophilic gene polymorphisms are risk factors for unexplained infertility.
Earlier studies have shown inherited thrombophilia to be a risk factor for recurrent implantation failure, raising the question of whether this risk is related to the underlying cause of unexplained infertility or to the mechanisms involved in the implantation process. When nine thrombophilic gene polymorphisms were compared among 92 women with the diagnosis of unexplained infertility and 60 fertile control women, women with a history of unexplained infertility displayed a higher prevalence of MTHFR C677T polymorphisms than control women.


Habitat Imaging of Tumors Enables High Confidence Sub-Regional Assessment of Response to Therapy.
Imaging biomarkers are used in therapy development to identify and quantify therapeutic response. In oncology, use of MRI, PET and other imaging methods can be complicated by spatially complex and heterogeneous tumor micro-environments, non-Gaussian data and small sample sizes. Linear Poisson Modelling (LPM) enables analysis of complex data that is quantitative and can operate in small data domains. We performed experiments in 5 mouse models to evaluate the ability of LPM to identify responding tumor habitats across a range of radiation and targeted drug therapies. We tested if LPM could identify differential biological response rates. We calculated the theoretical sample size constraints for applying LPM to new data. We then performed a co-clinical trial using small data to test if LPM could detect multiple therapeutics with both improved power and reduced animal numbers compared to conventional t-test approaches. Our data showed that LPM greatly increased the amount of information extracted from diffusion-weighted imaging, compared to cohort t-tests. LPM distinguished biological response rates between Calu6 tumors treated with 3 different therapies and between Calu6 tumors and 4 other xenograft models treated with radiotherapy. A simulated co-clinical trial using real data detected high precision per-tumor treatment effects in as few as 3 mice per cohort, with p-values as low as 1 in 10,000. These findings provide a route to simultaneously improve the information derived from preclinical imaging while reducing and refining the use of animals in cancer research.


Circadian motor activity of non-dominant hand reaches acrophase later than dominant hand.
Motor activity during the first half of nocturnal sleep is lateralized to the non-dominant hand. What remains is to determine which account could explain this phenomenon: the more pronounced homeostatic deactivation of the dominant hemisphere or the circadian asymmetry in the hemispheric activation. To better understand the nature of these motor asymmetries, we performed an ecological study assessing the circadian motor activity in 34 evening, 52 intermediate, and 27 morning types. We observed a significant circadian phase delay of the 24-h motor activity pattern of the left hand in comparison to the right hand, regardless of chronotype. Moreover, we replicated higher motor activity in the left hand in comparison to the right hand in late evening that reached statistical significance only in evening and intermediate types. Analysing motor activity around bedtime and wake-up time, we observed a reverse pattern between circadian typologies: evening types showed higher activity in the left hand in comparison to the right hand before bedtime, while morning types showed significantly higher motor activity in the right hand in comparison to the left after wake-up time. Results support the hypothesis of a different circadian phase relationship between the two hemispheres.


Chemotherapy-related cognitive dysfunction: current animal studies and future directions.
Cognitive impairment is a potential long-term side effect of adjuvant chemotherapy that can have a major impact on the quality of life of cancer survivors. There is a growing number of preclinical studies addressing this issue, thereby extending our knowledge of the mechanisms underlying chemotherapy-induced neurotoxicity. In this review, we will summarize the recent advances and important findings presented in these studies. Emerging challenges, such as the development of neuroprotective strategies, and the role of the blood-brain barrier on cognitive impairment will be described and future directions in this field of investigation will be outlined.


Large-scale identification of secretome glycoproteins recognized by Wisteria floribunda agglutinin: A glycoproteomic approach to biomarker discovery.
One of the promising approaches to the development of cancer diagnostic systems is quantification of a specific protein carrying cancerous glycans. Potential utility of Wisteria floribunda agglutinin (WFA) for such assays has been suggested for several cancer types. To develop such diagnostic systems, identification of WFA-recognized glycoproteins is essential. Here, we successfully identified 504 WFA-recognized glycoproteins from the secretome of HEK293T cells. Most of the identified proteins were likely soluble or single-pass transmembrane proteins, which may serve as specific proteins for the diagnosis using biological fluids. Our method may help to discover marker glycoproteins for various cancers generating WFA-recognized glycans.


Prevalence and factors associated with chronic school absenteeism among 207,107 in-school adolescents: Findings from cross-sectional studies in 71 low-middle and high-income countries.
Despite the negative impact of chronic school absenteeism on the psychological and physical health of adolescents, data on the burden of adolescent chronic school absenteeism (ACSA) and interventions and programs to address it are lacking. We estimated the global, regional and national level prevalence of ACSA and its correlation with violence and unintentional injury, psychosocial, protective, lifestyle, and food security-related factors among in-school adolescents across low and middle-income, and high-income countries (LMICs-HICs). This study aimed to estimate the prevalence of chronic school absenteeism (CSA) as well as to determine its associated factors among in-school adolescents across 71 low-middle and high-income countries. We used data from the most recent Global School-based Student Health Survey of 207,107 in-school adolescents aged 11-17 years in 71 LMICs-HICs countries across six WHO regions. We estimated the weighted prevalence of ACSA from national, regional and global perspectives. Multiple binary logistic regression analyses were used to estimate the adjusted effect of independent factors on ACSA. The overall population-weighted prevalence of CSA was 11·43% (95% confidence interval, CI: 11·29-11·57). Higher likelihood of CSA was associated with severe food insecurity, peer victimisation, loneliness, high level of anxiety, physically attack, physical fighting, serious injury, poor peer support, not having close friends, lack of parental support, being obese, and high levels of sedentary behaviours. Lower likelihood of CSA was associated with being female (odds ratio, OR = 0·76, 95% CI: 0·74-0·78). Our findings indicate that a combination of different socio-economic factors, peer conflict and injury factors, factors exacerbate CSA among adolescents. Interventions should be designed to focus on these risk factors and should consider the diverse cultural and socioeconomic contexts.


Secretin alleviates biliary and liver injury during late-stage primary biliary cholangitis via restoration of secretory processes.
Primary biliary cholangitis (PBC) is characterised by ductopenia, ductular reaction, impairment of anion exchanger 2 (AE2) and the 'bicarbonate umbrella'. Ductulo-canalicular junction (DCJ) derangement is hypothesised to promote PBC progression. The secretin (Sct)/secretin receptor (SR) axis regulates cystic fibrosis transmembrane receptor (CFTR) and AE2, thus promoting choleresis. We evaluated the role of Sct/SR signalling on biliary secretory processes and subsequent injury in a late-stage PBC mouse model and human samples. At 32 weeks of age, female and male wild-type and dominant-negative transforming growth factor beta receptor II (late-stage PBC model) mice were treated with Sct for 1 or 8 weeks. Bulk RNA-sequencing was performed in isolated cholangiocytes from mouse models. Biliary Sct/SR/CFTR/AE2 expression and bile bicarbonate levels were reduced in late-stage PBC mouse models and human samples. Sct treatment decreased bile duct loss, ductular reaction, inflammation, and fibrosis in late-stage PBC models. Sct reduced hepatic bile acid levels, modified bile acid composition, and restored the DCJ and 'bicarbonate umbrella'. RNA-sequencing identified that Sct promoted mature epithelial marker expression, specifically anterior grade protein 2 (Agr2). Late-stage PBC models and human samples exhibited reduced biliary mucin 1 levels, which were enhanced by Sct treatment. Loss of Sct/SR signalling in late-stage PBC results in a faulty 'bicarbonate umbrella' and reduced Agr2-mediated mucin production. Sct restores cholangiocyte secretory processes and DCJ formation through enhanced mature cholangiocyte phenotypes and bile duct growth. Sct treatment may be beneficial for individuals with late-stage PBC. Secretin (Sct) regulates biliary proliferation and bicarbonate secretion in cholangiocytes via its receptor, SR, and in mouse models and human samples of late-stage primary biliary cholangitis (PBC), the Sct/SR axis is blunted along with loss of the protective 'bicarbonate umbrella'. We found that both short- and long-term Sct treatment ameliorated ductular reaction, immune cell influx, and liver fibrosis in late-stage PBC mouse models. Importantly, Sct treatment promoted bicarbonate and mucin secretion and hepatic bile acid efflux, thus reducing cholestatic and toxic bile acid-associated injury in late-stage PBC mouse models. Our work perpetuates the hypothesis that PBC pathogenesis hinges on secretory defects, and restoration of secretory processes that promote the 'bicarbonate umbrella' may be important for amelioration of PBC-associated damage.


Young student's motivations to choose an undergraduate midwifery program.
Within the context of an ageing health workforce it is important to gain a greater understanding of the motivations of young people (aged less than 21 years) to choose a career in midwifery. To explore the reasons why young students decided to study midwifery and enrol in one Australian Bachelor of Midwifery program. A descriptive exploratory qualitative design was used. Eleven midwifery students aged less than 21 years on enrollment participated in a semi-structured tape-recorded interview. The transcribed interviews were analysed using thematic analysis. Direct and indirect exposure to positive constructions of childbirth as well as the midwives role fuelled young student's fascination with midwifery and drove their desire to enrol. While some young students entered midwifery studies as a result of their 'love of babies' others took a more pragmatic 'wait and see' approach about their career choice. Many young students however clearly distinguished midwifery from nursing demonstrating an intention to be a midwife rather than a nurse. This decision often took place within the context of opposition from within their family, school and social networks where the public discourse continued to reinforce nursing as the preferred pathway to midwifery. Creating opportunities for young people to be exposed to positive constructions of childbirth as well as midwifery role models may increase the number of young students entering midwifery. There is also a need for information to be provided to school careers officers to assist them to understand the distinction between midwifery and nursing.


High-resolution spectroscopy with a femtosecond laser frequency comb.
The output of a mode-locked femtosecond laser is used for precision single-photon spectroscopy of 133Cs in an atomic beam. By changing the laser's repetition rate, the cesium D1 (6s 2S(1/2)-->6p 2P(1/2)) and D2 (6s 2S(1/2)-->6p 2P(3/2)) transitions are detected and the optical frequencies are measured with accuracy similar to that obtained with a cw laser. Control of the femtosecond laser repetition rate by use of the atomic fluorescence is also implemented, thus realizing a simple cesium optical clock.


Hyaluronic acid in elastic cartilage.
Bovine ear cartilage contains more hyaluronic acid than do hyaline cartilages of the same animal. Most of it is in the elastin-rich residue not extractable by 4 M guanidinium chloride where it is associated with chondroitin sulphate in low relative concentration and of lower molecular weight than in non-elastic cartilage residue.


Postoperative Emergency Department Visits After Urinary Stone Surgery: Variation Based on Surgical Modality.
Introduction: Urinary stone disease is responsible for more than 1 million emergency department (ED) visits annually. There is increasing regulatory and cost pressure to reduce unplanned episodes of care, particularly after elective surgery. However, the frequency of ED visits in the early postoperative period after different modalities of stone surgery is not well characterized. We aimed at describing rates of postoperative ED visits after percutaneous nephrolithotomy (PCNL), ureteroscopy (URS), and extracorporeal shockwave lithotripsy (SWL). Methods: The Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) state databases for Florida (2010-2012), Iowa (2010-2012), California (2010-2011), and New York (2006-2012) were used to identify patients undergoing PCNL, URS, or SWL. The HCUP State Emergency Department Database was used to identify postoperative ED visits in the first 30 days after surgery. Rates of postoperative ED visits were compared across surgery types with chi-square and multivariate logistic regression. Results: A total of 321,899 patients undergoing stone surgery during the study period were identified, including 151,006 (46.9%) URS, 128,040 (39.8%) SWL, and 42,853 (13.3%) PCNL. PCNL had the highest rate of 30-day postop ED visits (13.2%), followed by URS (10.6%) and SWL (7.5%; p < 0.0001). On multivariate logistic regression adjusting for baseline clinical and sociodemographic characteristics, both PCNL (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.56-1.69) and URS (OR 1.33, 95% CI 1.30-1.37) were independently associated with increased risk of postop ED visit when compared with SWL. Conclusion: Among kidney stone surgeries, PCNL has the highest rate of 30-day postoperative ED visits, whereas SWL has the lowest. Postoperative ED visits are an important outcome for both patients and surgeons, and observed differences across surgical modalities should be incorporated into the preoperative shared decision-making process.


Tackling molecular targets beyond PD-1/PD-L1: Novel approaches to boost patients' response to cancer immunotherapy.
In the new era of immunotherapy, which has changed the clinical oncology practice guidelines, there is a pressing need for finding novel approaches to tune up the clinical outcomes of immunotherapy and extend its benefits to a wider cohort of cancer patients. Several non-classical molecular immune targets beyond PD-1/PD-L1 signaling were shown to be engaged as feedback resistance circuits to shut down the antitumor immune response mediated by the classical immune checkpoint inhibitors. Those include T-cell inducible co-stimulator (ICOS), CD40, CD47, V-domain Ig suppressor of T-cell activation (VISTA), cyclin-dependent kinase (CDK)12, enhancer of Zeste homolog 2 (EZH2), toll-like receptors (TLRs) and OX-40 (CD134). Herein we critically discussed the latest studies concerned with understanding the mechanisms involved in the negative clinical response to classical immunotherapies and strategies to optimize the efficacy of cancer immunotherapy through novel combinatorial approaches.


Mucin-fused myeloid-derived growth factor (MYDGF164) exhibits a prolonged serum half-life and alleviates fibrosis in chronic kidney disease.
Although no effective therapy is available to stop or reverse CKD progression targeting its key feature, the loss of peritubular capillaries (PTCs) leading to interstitial fibrosis, myeloid-derived growth factor (MYDGF) with tissue-repairing activities enlightens its therapeutic potential for CKD. However, the extremely short circulatory lifetime (15 min) restricts its application. We selected a tandem repeated (TR) region of human CD164 as a carrier to fuse with MYDGF and then investigated for biophysical and pharmacokinetic changes. The MYDGF164 bioactivities were validated in HUVECs and then assessed in HK-2 cells. We also investigated its efficacy in unilateral ureteral obstruction (UUO)-treated mice and in adenine-induced CKD rats. MYDGF164 was modified with sialoglycans, improving its resistance to serum proteases and increasing its hydrodynamic radius. The half-life of MYDGF164 was significantly prolonged but retained its original cell proliferation, anti-apoptosis, and tubulogenesis activities. It selectively stimulated the proliferation in endothelial and epithelial cells through phosphorylating MAPK1/3. MYDGF164 alleviated capillary rarefaction, hypoxia, renal fibrosis, and tubular atrophy in UUO mice and in adenine-induced CKD rats. MYDGF164 restored renal function, with normalized creatinine and urea levels in adenine-induced CKD rats. Histopathology and immunohistochemistry revealed that MYDGF164 protection was related to its cell-proliferative, anti-apoptosis, and angiogenesis activities. This study is the first successful example of using a tandem repeated region of hCD164 as a cargo protein for the pharmacokinetic improvement of therapeutic proteins. Our findings highlight the potential of MYDGF164 in alleviating renal fibrosis in CKD.


Prognostic factors and classification in multiple myeloma.
Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series.


Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity.
In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor.


Usefulness of preoperative three-dimensional volumetric analysis of carotid body tumors.
The Shamblin classification is the commonest method to predict complications and outcomes during carotid body tumor (CBT) resection. The aim of this study is to describe the utility of the three-dimensional volumetric reconstruction (3DVR) analysis of the CBT and its relationship with postoperative outcomes. Preoperative computed tomography angiography (CTA) was obtained to perform 3DVR of the CBT. Imaging data were analyzed and correlated with surgical outcomes: estimated blood loss (EBL), surgical time (ST), and hospital length of stay (HLOS). The Pearson test was used to determine the correlation between volume and postoperative outcomes. Fifty-seven patients were studied, 13 had Shamblin type I tumors with a mean 3DVR of 7.69 cm3 (standard deviation [SD 8.27]), 21 were type II with a mean 3DVR of 15.57 cm3 (SD 8.40), and 23 were type III with a mean 3DVR of 30.58 cm3 (SD 20.16). EBL mean was 559 milliliters (mL) (standard error [SE] 80.44), the mean ST of resection was 202 min (SD 67), and the mean HLOS was 5.8 days (SD 3.23). The Pearson test showed a correlation of r = 0.69 (p < 0.0001) between 3DVR and EBL, a r = 0.4 (p = 0.05) was obtained between 3DVR and ST, and finally, a r = 0.3 (p = 0.05) between 3DVR and HLOS was obtained. The preoperative 3DVR determination of CBTs allows to analyze possible predictors of surgical outcomes. We found a positive correlation between the 3DVR volume and EBL. Further research is necessary to validate this method in the evaluation of these rare neoplasms.


Improvement of esophagojejunostomy technique after total gastrectomy with overlap method: reduce the difficulty of surgery and shorten operation time.
Gastric cancer (GC) is one of the most malignant human cancers. Totally laparoscopic total gastrectomy (TLTG) is a difficult operation, especially esophagojejunostomy. Our team has adopted the method of suspending and pulling the esophagus with the visceral retractor and two needles of barbed wire interlocking to suture the common opening, which reduces the difficulty of the operation. From January to December 2020, 20 patients underwent TLTG with the overlap method by improved esophagojejunostomy technique and 20 patients with the traditional overlap method after TLTG were used as the control group. The surgery was performed using a five-trocar system. After lymphadenectomy, the esophagus was separated at least 2 cm from the upper edge of the tumor. Improved esophagojejunostomy technique was completed by the following steps: (1) cutting end of the esophagus suspension; (2) jejuno-jejunostomy; (3) esophagojejunostomy; (4) close the esophagojejunum common incision opening. The results showed that the operative time, and anastomosis time of the modified group were shorter than those of the traditional group, There were no postoperative complications such as anastomotic leakage, anastomotic stenosis, duodenal stump fistula and Roux stasis syndrome in the both group. There was no statistically significant difference in postoperative complications between the two groups. Taken together, our modified esophagojejunostomy technique after total gastrectomy is feasible and safe. This procedure is an efficient method to shorten the operation time and reduce the difficulty of surgery in esophagojejunostomy of laparoscopic total gastrectomy.


In vivo 31P magnetic resonance spectroscopy for evaluation of testicular function in cryptorchid rats.
To assess in vivo metabolism of rat testicles in experimental cryptorchidism, we used 31P magnetic resonance (MR) spectroscopy and compared testicular MR spectroscopic parameters with flow cytometric DNA analysis. In vivo 31P MR spectroscopy and flow cytometric DNA analysis of rat testis were performed before and during 14 days of experimental cryptorchidism. The testicular phosphomonoester (PM)/ATP ratio showed a transient increase when multinuclear giant cells appeared in the seminiferous tubules. However, the ratio returned to the preoperative level when these cells disappeared. The phosphodiester (PD)/ATP ratio gradually decreased and the inorganic phosphate (Pi)/ATP ratio slowly increased. DNA flow cytometry showed a decrease in the percentage of haploid cells and an increase in the percentage of diploid cells from 7 days after cryptorchidism. The percentage of tetraploid cells did not change before and during cryptorchidism. This study indicates that in vivo 31P MR spectroscopy in combination with flow cytometric DNA analysis provides useful biochemical and histological information for evaluation of testicular function.


Locating the lateral antebrachial cutaneous nerve.
Dissections of 20 antebrachial specimens were done to define the location of the proximal lateral antebrachial cutaneous nerve, which is the distal sensory extension of the musculocutaneous nerve. Our findings varied from those noted in most anatomic and surgical texts in that the nerve emerges from the lateral aspect of the biceps tendon at the level of the interepicondylar line. At the point defined, the distribution of the nerve in ten volunteers was successfully anesthetized with 1.5 ml of 1% lidocaine. The accurate anatomic localization of this nerve should be of interest to surgeons and anesthesiologists in supplementing failed axillary blockade, in diagnosing and treating the musculocutaneous impingement syndrome, in harvesting the proximal nerve for diagnostic tests or donor graft purposes, and in differentiating the sensory distribution of this nerve from that of the radial nerve.


Method for screening influenza neutralizing antibodies in crude human plasma and its derivatives using SPR.
We applied Surface Plasmon Resonance (SPR) technology to develop a method for potency screening and quantification of anti-influenza antibodies in minimally processed human plasma samples and intravenous immunoglobulin (IGIV) products. We found that specific antibodies in human plasma or IGIV capable of inhibiting binding of influenza hemagglutinin to receptor-analogous glycans do so in concentration-dependent manner. We ranked the inhibitory activity of plasma samples from multiple donors and found a good correlation (r = 0.87) of SPR assay measurements and conventional hemagglutination inhibition (HAI) assay results. This method was also applied to screen for specific anti-influenza antibodies in IGIV lots manufactured pre- and post-2009 H1N1 pandemic. The SPR method was also applied to study binding inhibition of the intact A/California/04/2009 H1N1 and B/Victoria/504/2000 influenza viruses to α2,6 or α2,3-linked synthetic glycans. In contrast to recombinant H1 hemagglutinin, which was found to interact primarily with α2,6-linked terminal sialic acids, intact H1N1 or influenza B virus recognized both types of receptor analogs with different observed dissociation rates and the inhibitory activity of plasma antibodies was dependent on the type of sialic acid link. The SPR method can provide a high-throughput, time-saving and semi-automated alternative to conventional assays such as HAI or microneutralization in situations where screening of large numbers of plasma donations to identify high titer units is needed to product highly potent immunoglobulins.


Note on the dispersion of generations among cells in senescing diploid fibroblast populations.
The cells in a cultured diploid fibroblast population have heterogeneous intermitotic times--even cells derived from the same mitosis may divide at different ages. This heterogeneity of inter-mitotic times results in asynchronous population growth and a dispersion of generations among members of the cell population. Because the appearance of non-dividing cells in middle-age populations has been attributed to the presence of lineages with more generations than average, we estimated the magnitude of the dispersion of cell generations as functions of the population doubling level and of the coefficient of variation of inter-mitotic times. For some data, such as that of Macieira-Coelho and Azzarone (Exp. Cell Res., 141 (1982) 325, the rate at which such non-proliferating lineages appear could be explained by a reasonable coefficient of variation of inter-mitotic times (25%). Most other data, however, would be fit only if the coefficient of variation of inter-mitotic times were 50% or greater, a variability that exceeds what has been observed in microcinematography experiments.


Brain abscess.
Brain abscess is a serious and life-threatening disease among children despite advances in diagnosis and management. Changes in the epidemiology of predisposing conditions for brain abscess are associated with changes in the patient population and causative organisms. Though still a potentially fatal infection, there have been recent improvements in diagnosis, treatment, and outcome. Although mortality appears to be decreasing, a significant percentage of children continue to have residual neurological deficits, including epilepsy, permanent motor or sensory dysfunction, visual field defects, and personality change. Some children also require placement of a ventriculoperitoneal shunt. The most common origin of microbial infection in children remains direct or indirect cranial infection arising from the middle ear, paranasal sinuses, or teeth. No prospective clinical trials have compared the various surgical and medical treatment strategies available to guide the management of cerebral abscesses in children. Most surgical and medical treatment guidelines are based on populations consisting primarily of adult patients. The use of corticosteroids for treatment of brain abscess is controversial. Anticonvulsants are recommended in children who have developed seizures potentially to prevent further episodes. Duration of anticonvulsant therapy should be individualized and guided by electroencephalographic (EEG) study in the follow-up phase of disease.


Lipoprotein(a) in patients initiating antiretroviral therapy.
The interaction between lipoprotein(a), an emerging cardiovascular risk factor, and antiretrovirals (ARVs) has been less well studied than the interaction between either cholesterol or triglycerides and these drugs. In this study we assessed the effect of initiating antiretroviral therapy (ART) on lipoprotein(a) levels. Fasting samples from 95 patients initiating ART with nucleoside/nucleotide reverse transcriptase inhibitors plus nonnucleoside reverse transcriptase inhibitors or protease inhibitors were obtained. Lipids and lipoproteins were determined until week 48. As in the general population, the study population showed a highly skewed lipoprotein(a) distribution (median 9.9 mg/dL, range 0.1-110 mg/dL). The study population was divided into individuals with lipoprotein(a) >or=30 mg/dL at baseline (n=28) and those with <30 mg/dL (n=67). Almost exclusively, patients with high lipoprotein(a) at baseline (median 51.6 mg/dL) showed a profound increase of median 26.7 mg/dL (week 24). This effect was not associated with specific ARVs and was independent of changes in other lipids. The low-lipoprotein(a) group (baseline median 7 mg/dL) showed a small increase of median 2.6 mg/dL (week 24). Marked increases in lipoprotein(a) after initiation of ART were mainly restricted to patients with high baseline levels. This may have clinical implications as patients with high lipoprotein(a) are at higher risk for myocardial infarction and stroke.


Stepwise in vitro screening of MMV pathogen box compounds against Plasmodium falciparum to identify potent antimalarial candidates.
Development of resistance to deployed antimalarial drugs is inevitable and needs prompt and continuous discovery of novel candidate drugs. Therefore, the antimalarial activity of 125 compounds from the Medicine for Malaria Ventures (MMV) pathogen box was determined. Combining standard IC50 and normalised growth rate inhibition (GR50) analyses, we found 16 and 22 compounds had higher potencies than CQ respectively. Seven compounds with relatively high potencies (low GR50 and IC50) against P. falciparum 3D7 were further analysed. Three of these were tested on 10 natural P. falciparum isolates from The Gambia using our newly developed parasite survival rate assay (PSRA). According to the IC50, GR50 and PSRA analyses, compound MMV667494 was most potent and highly cytotoxic to parasites. MMV010576 was slow acting but more potent than dihydroartemisinin (DHA) 72 h after exposure. MMV634140 was potent against the laboratory-adapted 3D7 isolate, but 4 out of 10 natural Gambian isolates survived and replicated slowly despite 72 h of exposure to the compound, suggesting potential drug tolerance and risk of resistance development. These results emphasise the usefulness of in vitro testing as a starting point for drug discovery. Improved approaches to data analyses and the use of natural isolates will facilitate the prioritisation of compounds for further clinical development.


A Phase I Study of Clofarabine With Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee).
Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi-drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m(2)/d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post-transplant ALL relapse. Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose-limiting toxicity (DLT) appeared at dose level 3 (32 mg/m(2)), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m(2)), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m(2). There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. Clofarabine MTD was 32 mg/m(2)/d in this combination which appeared feasible and effective in this population.


Shape variability of the central sulcus in the developing brain: A longitudinal descriptive and predictive study in preterm infants.
Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in infants can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development? In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI - once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA -, in order to quantify the sulcus's shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcus's variability at both ages and to assess hemispheric and age-group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcus's shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain.


Deep underground gamma spectrometric measurement of 26Al in meteorite samples.
26Al is routinely measured in meteorite samples by accelerator mass spectrometry (AMS). PTB participates in an international intercomparison between laboratories using AMS and gamma-ray spectrometry to improve the quality of such measurements. We performed gamma spectrometric measurements at the underground laboratory UDO using the GESPECOR software to calculate corrections for efficiency transfer, self-attenuation and coincidence summing. Four meteorite samples were measured for more than 30 days each but nevertheless, the uncertainty budgets are dominated by the uncertainties of the count rates.


Polycyclic aromatic hydrocarbons (PAHs) in water and sediment from a river basin: sediment-water partitioning, source identification and environmental health risk assessment.
The information on concentration levels, partitioning and sources of pollutants in aquatic environment is quite necessary for pollution treatment and quality criteria. In this work, sixteen priority polycyclic aromatic hydrocarbons (PAHs) recommended by U.S. Environmental Protection Agency in the water and sediment of Yinma River Basin were firstly investigated. Among 16 individual PAHs, naphthalene was the highest average concentration in water samples as well as in sediment samples, 67.2 ng/L and 825.06 ng/g, respectively, whereas benzo(g,h,i)perylene was undetected in water samples nor in sediment samples. For three PAH compositional patterns, concentrations of light (2-3 ring) PAHs were dominant in water and sediment, accounting for 71.69 and 86.98 % respectively. The PAH partitioning in the sediment-water system was studied, results showed that PAH partitioning was in an unsteady state and tended to accumulate in the sediment. The possible sources of PAHs in water and sediment were both identified as a mixed source of petroleum and combustion. The benzo(a)pyrene equivalents (EBaP) values for PAHs in the water and sediment in some sites were relatively higher, suggesting the existence of environmental health risk.


Assessing neurological prognosis in post-cardiac arrest patients from short vs plain text EEG reports: A survey among intensive care clinicians.
Electroencephalography (EEG) patterns are predictive of neurological prognosis in comatose survivors from cardiac arrest but intensive care clinicians are dependent of neurophysiologist reports to identify specific patterns. We hypothesized that the proportion of correct assessment of neurological prognosis would be higher from short statements confirming specific EEG patterns compared with descriptive plain text reports. Volunteering intensive care clinicians at two university hospitals were asked to assess the neurological prognosis of a fictional patient with high neuron specific enolase. They were presented with 17 authentic plain text reports and three short statements, confirming whether a "highly malignant", "malignant" or "benign" EEG pattern was present. Primary outcome was the proportion of clinicians who correctly identified poor neurological prognosis from reports consistent with highly malignant EEG patterns. Secondary outcomes were how the prognosis was assessed from reports consistent with malignant and benign patterns. Out of 57 participants, poor prognosis was correctly identified by 61% from plain text reports and by 93% from the short statement "highly malignant" EEG patterns. Unaffected prognosis was correctly identified by 28% from plain text reports and by 40% from the short statement "malignant" patterns. Good prognosis was correctly identified by 64% from plain text reports and by 93% from the short statement "benign" pattern. Standardized short statement, "highly malignant EEG pattern present", as compared to plain text EEG descriptions in neurophysiologist reports, is associated with more accurate identification of poor neurological prognosis in comatose survivors of cardiac arrest.


Distamycin A and its analogs as agents for blocking of endo R. EcoRI activity.
Distamycin A (Dst) and its analogs protect the lambda phage DNA from cleavage with endoR. EcoRI and show selective affinity for different recognition sites of endoR. EcoRI on this DNA producing enlarged DNA fragments of various composition and length. The affinity of the antibiotic for DNA is influenced by the number of pyrrol carboxamide units in Dst molecule and does not strongly depend on the substitution of the N-methyl group by the N-propyl one. Since in the complex with DNA the antibiotics of the Dst type are localized in its minor groove a conclusion can be made that the minor groove of DNA is needed for the interaction of the restriction endonuclease with DNA.


Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review.
Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.


Exploring the relation between plastic ingestion in species and its presence in seafloor bottoms.
In order to have a wider understanding of the impacts of plastics on marine ecosystems, studies should approach different environmental compartments, such as seafloor and biota, at the same time. The aim of this research is to study the relation between microplastic ingestion in species and the amount of seafloor plastics caught in the same bottom trawls hauls of the western Mediterranean Sea to describe a potential overlap between these two indicators of plastic pollution. According to results, 15% of the sampled individuals ingested microplastics with a mean value of 0.30 ± 0.40 microplastics/individuals. Regarding seafloor plastics, these were present in 58% of the hauls with a mean value of 1.31 ± 0.09 kg/km2. The highest overlap between ingestion of microplastic in species and seafloor plastics was observed in the bay of Palma, the most urbanized area, but also in areas close to Marine Protected Areas (MPAs).


Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol.
Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 μM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was usually not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system.


The relationship between pain management and psychospiritual distress in patients with advanced cancer following admission to a palliative care unit.
Although many cross-sectional studies have demonstrated the association between cancer pain and psychospiritual distress, the time-dependent relationship has not been fully explored. For that reason, this study aims to investigate the time-dependent relationship between psychospiritual distress and cancer pain management in advanced cancer patients. This is a prospective observational study. Two hundred thirty-seven advanced cancer patients were recruited from a palliative care unit in Taiwan. Demographic and clinical data were retrieved at admission. Pain and psychospiritual distress (i.e.: anxiety, depression, anger, level of family and social support, fear of death) were assessed upon admission and one week later, by using a "Symptom Reporting Form". Patients were divided into two groups according to the pain status one week post-admission (improved versus not improved groups). One hundred sixty-three (68.8 %) patients were assigned to the improved group, and 74 (31.2 %) patients were assigned to the not improved group. There were no differences in the psychospiritual variables between groups upon admission. In overall patients, all psychospiritual variables improved one week post-admission, but the improvement of depression and family/social support in the not improved group was not significant. Consistent with this, for depression scores, there was a statistically significant pain group x time interaction effect detected, meaning that the pain group effect on depression scores was dependent on time. We demonstrated a time-dependent relationship between depression and pain management in advanced cancer patients. Our results suggest that poor pain management may be associated with intractable depression. The inclusion of interventions that effectively improve psychospiritual distress may contribute to pain management strategies for advanced cancer patients.


FMNL2 suppresses cell migration and invasion of breast cancer: a reduction of cytoplasmic p27 via RhoA/LIMK/Cofilin pathway.
Formin-like protein 2 (FMNL2) belongs to a highly conserved family of cytoskeletal remodeling proteins that have been reported to be implicated in various actin-dependent physiological and cancer-associated processes. In this study, we mainly investigated the effects of FMNL2 on breast cancer cell migration and invasion, and the underlying mechanisms involved. We found that FMNL2 reduced cell migration and invasion of breast cancer in vitro and in vivo. Further, FMNL2 disrupted actin cytoskeleton rearrangement and hampered the RhoA/LIMK/Cofilin pathway in breast cancer cells. Critically, both Rho inhibitor ZOL and LIMK inhibitor BMS3 significantly abrogated these migration-promoting effects in FMNL2-silencing MDA-MB-231 and BT549 cells. RhoA/LIMK/Cofilin pathway was involved in FMNL2 silencing-induced actin cytoskeleton rearrangement in MDA-MB-231 and BT549 cells. More importantly, cytoplasmic p27 promoted FMNL2-mediated cell migration and invasion through RhoA/LIMK/Cofilin pathway in MCF7 and MDA-MB-231 cells. In addition, the expression and prognosis of FMNL2 were associated with ER in breast cancer. Furthermore, ERα overexpression reduced the protein levels of FMNL2 in breast cancer cells, which were reversed by MG132. In conclusion, FMNL2 suppressed cell migration and invasion of breast cancer by inhibiting RhoA/LIMK/Cofilin pathway through a reduction of cytoplasmic p27. This finding implies that the interference of FMNL2-mediated RhoA/LIMK/Cofilin pathway involving the cytoplasmic p27 may be a promising strategy for ameliorating breast cancer metastasis and prognosis.


Effect of extraction method on structure and antioxidant activity of Hohenbuehelia serotina polysaccharides.
The impacts of four extraction methods (hot water, enzyme assistance, ultrasonic assistance and ultrasonic-enzyme assistance) on the extraction yields, preliminary structure and antioxidant activities of the Hohenbuehelia serotina polysaccharides (HW-HSP, EA-HSP, UA-HSP and UEA-HSP) were systematically investigated. The yield of the polysaccharides (20.70±0.17%) obtained by ultrasonic-enzyme assistance was higher than the polysaccharides by other methods'. Four kinds of polysaccharides possessed the different preliminary structural characteristics including molecular weight distributions, monosaccharide compositions, crystallization and spiral structures, while different surface morphology. Through the measurements of antioxidant activities in vitro, UEA-HSP exhibited the most significant scavenging capacities on non-physiological ABTS free radicals and physiological hydroxyl radicals. These data showed that ultrasonic-enzyme assistance was more beneficial to enhance the extraction yields of the polysaccharides, and obtain higher bioactive polysaccharides. The results also suggested that H. serotina polysaccharides possessed potential healthcare application in food field due to their antioxidant activities.


Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)?
Diabetic patients are postulated to be in a perpetual state of oxidative stress and inflammation at sites where chronic complications occur. The accumulation of AGEs derived from both endogenous and exogenous sources (such as the diet) have been implicated in the development and progression of diabetic complications, particularly nephropathy. There has been some interest in investigating the potential for reducing the AGE burden in chronic disease, through the action of AGE "clearance" receptors, such as the advanced glycation end-product receptor 1 (AGE-R1). Reducing the burden of AGEs has been linked to attenuation of inflammation, slower progression of diabetic complications (in particular vascular and renal complications) and has been shown to extend lifespan. To date, however, there have been no direct investigations into whether AGE-R1 has any role in modulating normal kidney function, or specifically during the development and progression of diabetes. This mini-review will focus on the recent advances in knowledge around the mechanistic function of AGE-R1 and the implications of this for the pathogenesis of diabetic kidney disease.


Self-injurious behavior produced in rats by daily caffeine and continuous amphetamine.
Self-biting (SB) is an unusual behavioral effect of high doses of certain amphetamine-like drugs in rats. This bizarre behavior has received little attention, perhaps because the high doses of drug required and the dramatic disturbance of the animals' behavioral repertoire have raised the possibility that SB is a high dose phenomenon. However, we have found that continuous administration of very low amounts of amphetamine reliably produces SB in rats, and that this behavioral change can be very selective. We compared SB produced by continuous amphetamine to SB produced by daily caffeine; the latter has been proposed as an animal model for self-injurious behavior (SIB) in the Lesch-Nyhan syndrome. Subcutaneous silicone pellets containing amphetamine base were implanted for 4.5 days; caffeine was administered daily for 10 days. The amphetamine pellets produced the highest rate of SB (75% vs 40%) with the least toxic effects (no deaths vs three deaths). Neither drug produced stereotypy. The dopamine antagonist haloperidol was only marginally effective in controlling SB produced by daily caffeine but the dopamine antagonist pimozide (which has a longer duration of action) prevented SB by amphetamine pellet rats. Continuous release amphetamine pellets may provide an alternative to the caffeine model of SIB in humans, particularly for the Lesch-Nyhan syndrome.


Variability within individuals of plasma ionic magnesium concentrations.
With the invention of the ion-selective electrode (ISE), ionic magnesium (iMg) is a common blood assay. This could be advantageous, as iMg is the biologically active form of Mg. There is some evidence that iMg has considerable within subject variability. Individual ranges averaged.08 mmol/L (range.05 to.14). Coefficients of variation (CV) ranged from 3% to 7% (mean 4%) while analytical variation was determined to be 2.3%. Biological variability thus accounts for almost half of the variability, which is clinically significant, as 9 of the 13 subjects recorded at least one value below a reference range of.46 -.60 mmol/L. A significant within-day variation (p <.001) was noted, with differences between 7:00 and 10:00 as well as 10:00 and 22:00. Between day variations were not significant (p =.56). A plausible explanation of this data is that iMg has a circadian rhythm. Thus, cautious interpretation of single iMg values is warranted until future research determines the nature of iMg variability.


Systematic Review and Meta-analysis of the Outcomes of Drug-Eluting Stent Versus Drug-Coated Balloon Angioplasty for Lower Extremity Peripheral Artery Diseases.
Recent evidence raised the concern that paclitaxel-containing therapy was associated with an increased risk of mortality in patients with peripheral artery diseases (PADs). However, it is unclear whether drug-eluting stent (DES) versus drug-coated balloon (DCB) have a different effect on mortality of PAD patients. Our study aimed to systematically review current literature comparing clinical outcomes of patients treated with DES versus DCB for PAD. MEDLINE and Embase were searched for eligible studies from January 2000 to December 31, 2020. Randomized controlled trials (RCTs) or cohort studies that reported outcomes of DES versus DCB were included in our study. The primary outcome was 12-month all-cause mortality. A random-effect model was used to pool the odds ratios (ORs) and related 95% confidence intervals (CIs). Our review included 7 studies, involving 2 RCTs and 5 cohort studies. A total of 4,237 patients with DES and 9,234 patients with DCB were analyzed. All included cohort studies were of high quality with Newcastle-Ottawa scores from 7 to 8. No significant difference in 12-month all-cause mortality was found between DES and DCB without significant heterogeneity (OR 1.02, 95% CI 0.91-1.14, I2 = 0%). As for primary patency, no significant difference between treatments was observed (OR 1.27, 95% CI 0.75-2.15, I2 = 55%). Similar results were observed for freedom from target lesion revascularization (OR 0.94, 95% CI 0.64-1.40, I2 = 0%). This systematic review and meta-analysis suggest that no significant difference in 12-month all-cause mortality was found between DES and DCB. Primary patency and freedom from target lesion revascularization of lower extremity PAD were also comparable between the 2 groups.


Morphometric analysis of liver macrophages in patients with colorectal liver metastasis.
Kupffer cells, residential liver macrophages, have binding sites for carcinoembryonic antigen (CEA), but their role in metastatic liver tumor progression has not been well addressed clinically. Liver macrophages were analyzed morphometrically and their relationship with CEA and tumor microvessel density (MVD) was examined in 71 patients who underwent macroscopic curative hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin-embedded sections, MVD was evaluated by CD34-positive cell counts, liver macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The area of liver macrophages in peritumoral regions (43.0 +/- 11.6 microm2) was significantly larger than that in non-tumor regions (25.2 +/- 24.2 microm2) (P < 0.0001). The liver macrophage density in peritumoral regions was 154 +/- 49 per field, and was significantly higher than in non-tumor regions (74 +/- 24 per field) (P < 0.001). The density and the area of liver macrophages had no correlation with serum CEA levels and the degree of tumor CEA expression. A weak positive correlation was observed between MVD and liver macrophage density (P = 0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate regression analysis showed that MVD greater than 50 (P = 0.0233, hazard ratio = 2.463), and the area of liver macrophages larger than 40.9 microm2 (P = 0.0485, hazard ratio = 2.127), were significant independent prognostic factors. The present morphometric analysis suggests that the liver macrophages are accumulated and activated in peritumoral regions in patients with colorectal liver metastasis and this accumulation and activation of liver macrophages, with which soluble or membrane-bound CEA might not be associated, are related with patients' poor prognosis.


Profile of Dengue Fever in Hospitalized Children in Saurashtra, Gujarat, 2013-2017.
To study the five year trend of epidemiological and demographic characteristics of dengue infections from year 2013 to 2017 among children upto 15 years. This study presents data from review of microbiology department records of samples for dengue testing with information supplied by clinicians on the investigation request form. Patients were tested for NS1 Ag, IgM Ab or both. Out of 4216 samples, 1072 (25.4%) were positive for dengue. Positivity ranged from 44.2% in year 2013, 25.8% in 2015 to 16.2% in year 2017. Most cases reported were among male (57.9%), from urban areas (77.9%) and Rajkot district (75.7%). Reporting of dengue cases increased from July to November with peak during October every year. Serum samples for dengue serology were more commonly positive in July-September months during the study period, and in male children, and those from urban areas.


PDGF signaling inhibits mitophagy in glioblastoma stem cells through N6-methyladenosine.
Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. Here, we demonstrate that platelet-derived growth factor (PDGF) signaling induces N6-methyladenosine (m6A) accumulation in glioblastoma (GBM) stem cells (GSCs) to regulate mitophagy. PDGF ligands stimulate early growth response 1 (EGR1) transcription to induce methyltransferase-like 3 (METTL3) to promote GSC proliferation and self-renewal. Targeting the PDGF-METTL3 axis inhibits mitophagy by regulating m6A modification of optineurin (OPTN). Forced OPTN expression phenocopies PDGF inhibition, and OPTN levels portend longer survival of GBM patients; these results suggest a tumor-suppressive role for OPTN. Pharmacologic targeting of METTL3 augments anti-tumor efficacy of PDGF receptor (PDGFR) and mitophagy inhibitors in vitro and in vivo. Collectively, we define PDGF signaling as an upstream regulator of oncogenic m6A regulation, driving tumor metabolism to promote cancer stem cell maintenance, highlighting PDGF-METTL3-OPTN signaling as a GBM therapeutic target.


Effects of geriatric evaluation and management on adverse drug reactions and suboptimal prescribing in the frail elderly.
To determine if inpatient or outpatient geriatric evaluation and management, as compared with usual care, reduces adverse drug reactions and suboptimal prescribing in frail elderly patients. The study employed a randomized 2 x 2 factorial controlled design. Subjects were patients in 11 Veterans Affairs (VA) hospitals who were > or =65 years old and met criteria for frailty (n = 834). Inpatient geriatric unit and outpatient geriatric clinic teams evaluated and managed patients according to published guidelines and VA standards. Patients were followed for 12 months. Blinded physician-pharmacist pairs rated adverse drug reactions for causality (using Naranjo's algorithm) and seriousness. Suboptimal prescribing measures included unnecessary and inappropriate drug use (Medication Appropriateness Index), inappropriate drug use (Beers criteria), and underuse. For serious adverse drug reactions, there were no inpatient geriatric unit effects during the inpatient or outpatient follow-up periods. Outpatient geriatric clinic care resulted in a 35% reduction in the risk of a serious adverse drug reaction compared with usual care (adjusted relative risk = 0.65; 95% confidence interval: 0.45 to 0.93). Inpatient geriatric unit care reduced unnecessary and inappropriate drug use and underuse significantly during the inpatient period (P <0.05). Outpatient geriatric clinic care reduced the number of conditions with omitted drugs significantly during the outpatient period (P <0.05). Compared with usual care, outpatient geriatric evaluation and management reduces serious adverse drug reactions, and inpatient and outpatient geriatric evaluation and management reduces suboptimal prescribing, in frail elderly patients.


Histopathological observations of a polylactic acid-based device intended for guided bone/tissue regeneration.
Barrier devices have been shown to support alveolar bone and periodontal regeneration, a procedure also known as guided bone/tissue regeneration (GBR/GTR). Popular demand and clinical convenience have raised an interest in bioresorbable barrier devices. Tissue reactions to such bioresorbable devices are, however, generally not well explored. The objective of this study was to evaluate short- and long-term tissue reactions following implantation of a bioresorbable polylactic acid (PLA)-based barrier device using a rat model. Twenty-one young adult male Sprague-Dawley rats were used. The animals were divided into three groups including 15 animals receiving the PLA device and animals serving as sham surgery (five) or nonoperated (one) controls. Using aseptic techniques, the PLA device was surgically implanted in direct contact with the calvarial bone. Animals receiving the PLA device were sacrificed at 3, 5, 7, and 12 months postsurgery to provide longitudinal histopathological observations of tissue and biomaterials reactions. Control animals were sacrificed at 3 months. Animals were maintained without adverse events. Sham surgery and nonoperated control animals showed no signs of new bone formation or resorption, or signs of inflammatory reactions in adjoining soft tissues. In contrast, extensive amounts of residual biomaterial with evidence of foreign body reactions and bone resorption were observed in animals receiving the PLA device over 12 months. The results suggest that the PLA device may induce bone resorbing foreign body reactions. Importantly, the PLA device does not resorb within a 12-month healing interval. These biomaterials properties may influence new bone formation and maintenance when applying the device for GBR/GTR.


Determination of Ni2+ using an equilibrium ion exchange technique: Important chemical factors and applicability to environmental samples.
In natural waters, the determination of free metal concentrations is a key parameter for studying bioavailability. Unfortunately, few analytical tools are available for determining Ni speciation at the low concentrations found in natural waters. In this paper, an ion exchange technique (IET) that employs a Dowex resin is evaluated for its applicability to measure [Ni(2+)] in freshwaters. The presence of major cations (e.g. Na, Ca and Mg) reduced both the times that were required for equilibration and the partition coefficient to the resin (lambdaNi). IET measurements of [Ni(2+)] in the presence of known ligands (citrate, diglycolate, sulfoxine, oxine and diethyldithiocarbamate) were verified by thermodynamic speciation models (MINEQL(+) and VisualMINTEQ). Results indicated that the presence of hydrophobic complexes (e.g. Ni(DDC)(2)(0)) lead to an overestimation of the Ni(2+) fraction. On the other hand, [Ni(2+)] measurements that were made in the presence of amphiphilic complexes formed with humic substances (standard aquatic humic acid (SRHA) and standard aquatic fulvic acid (SRFA)) were well correlated to free ion concentrations that were calculated using a NICA-DONNAN model. An analytical method is also presented here to reduce the complexity of the calibration (due to the presence of many other cations) for the use of Dowex equilibrium ion exchange technique in natural waters.


Mononuclear five-coordinate molybdenum(IV) and -(V) monosulfide complexes coordinated with dithiolene ligands: reversible redox of Mo(V)/Mo(IV) and irreversible dimerization of [MoVS]- cores to a dinuclear [MoV2(mu-S)2]2- Core.
A mononuclear five-coordinate molybdenum(IV) monosulfide complex, (Et4N)2[MoS(L)2] (L = cyclohexene-1,2-dithiolate) (1), was obtained and characterized by IR, UV-vis spectroscopic methods, and X-ray crystallography. 1 was oxidized by an equivalent ferrocenium cation to give the corresponding mononuclear molybdenum(V) complex, (Et4N)[MoS(L)2] (2), which was stable for a few minutes under a lower concentration than 0.3 mM and then further dimerized to (Et4N)2[Mo(L)2]2(mu-S)2 (3).


The effect of berotec (Th 1165a) on spontaneous and induced uterine activity in the pregnant baboon.
Berotec (Th 1165a), a specific beta-adrenergic agent, has been found to be a more potent agent than metaproterenol in the inhibition of uterine activity in animals and human beings. The effect of berotec on spontaneous (postinduced) and induced uterine activity in the pregnant baboon near term was investigated. Berotec administered intravenously in a dose of 5 mug per minute consistently and significantly reduced spontaneous uterine activity as well as uterine activity by either oxytocin or prostaglandin F2-alpha. The frequency of contractions was consistently reduced whereas the effect on the amplitude of contractions was less marked. There was no reduction of the baseline muscle tonus. Berotec infusion produced a marked increase in the maternal heart rate, averaging 40 beats per minute. Berotec appears to be a potent inhibitor of spontaneous, oxytocin-induced, and prostaglandin-induced uterine activity in the pregnant baboon, but it has considerable cardiovascular side effects.


Associations of OSA and Nocturnal Hypoxemia with Strength and Body Composition in Community Dwelling Middle Aged and Older Men.
Reduced hand grip strength (HGS) is associated with poorer health in chronic conditions, yet there has been little research examining the association with hand grip strength and obstructive sleep apnea (OSA). Further, these studies have not examined, nor adjusted, for muscle mass. The aim of this study was to determine associations between OSA indices, HGS, muscle mass, and fat mass. A total of 613 participants (age range 41-88, BMI 28.6 ± 4.3) from the population-based Men Androgen Inflammation Lifestyle Environment and Stress Study underwent in-home overnight polysomnography, assessment of dominant and non-dominant HGS, and dual x-ray absorptiometry to determine whole body muscle mass and fat mass. Linear models determined cross-sectional associations of polysomnographic-derived OSA indices with hand grip strength, muscle mass, and fat mass, whilst adjusting for lifestyle information (income, smoking status, diet, self-reported physical activity), blood sample derived testosterone and systemic inflammation (C-reactive protein), cardiometabolic health (cardiovascular disease, hypertension, type 2 diabetes), and depression. In adjusted models, reduced dominant HGS was associated with lower oxygen nadir (unstandardised β [B] = 0.19, 95% confidence interval [CI] 0.08 to 0.29), greater time spent below 90% oxygen saturation (B = -0.08, 95% CI -0.14 to -0.02), and increased apnea duration (B = -0.3, 95% CI -0.23 to -0.02). By contrast, there were no associations between HGS and both AHI and REM AHI. Fat mass was consistently associated with worsening OSA indices, whereas muscle mass demonstrated no associations with any OSA index. Our findings suggest impairments in HGS may be related to fat infiltration of muscle, hypoxemia-induced reductions in peripheral neural innervation, or even endothelial dysfunction, which is a common outcome of hypoxemia. Longitudinal data are needed to further examine these hypotheses and establish if reduced grip strength in patients with OSA is associated with long-term adverse health outcomes.


The dilemma of Crohn's disease: long-term follow-up of Crohn's disease of the small intestine.
Seventy-four patients having primary Crohn's disease of the small intestine have had follow-up studies for at least 10 years after initial resection, and the results of treatment are presented. The commonest indication for operative treatment was obstruction, followed by fistula formation, intractability, abscess formation, and free perforation. Disease recurred in 69 per cent of patients in this series, and 55 per cent of this group required fruther operative treatment. It is necessary to have a lengthy follow-up period if we are to appreciate fully the serious nature of the recurrence problems of Crohn's disease of the small intestine.


Peptide formation in the prebiotic era: thermal condensation of glycine in fluctuating clay environments.
As geologically relevant models of prebiotic environments, systems consisting of clay, water, and amino acids were subjected to cyclic variations in temperature and water content. Fluctuations of both variables produced longer oligopeptides in higher yields than were produced by temperature fluctuations alone. The results suggest that fluctuating environments provided a favorable geological setting in which the rate and extent of chemical evolution would have been determined by the number and frequency of cycles.


Rapid and green synthesis of cadmium telluride quantum dots with low toxicity based on a plant-mediated approach after microwave and ultrasonic assisted extraction: Synthesis, characterization, biological potentials and comparison study.
In this work, a quick, facile and efficient approach was presented for green synthesis of cadmium telluride quantum dots (CdTe QDs) based on an aqueous extract of the Ficus johannis plant. Two extraction methods involving microwave assisted extraction (MWAE; 90 and 270 w; 15 min) and ultrasonic assisted extraction (USAE; 15 min; 45 °C) were performed as eco-friendly, effective, green and fast techniques for the extract preparation of the fruit's plant. The as-prepared plant extracts were used as natural stabilizing precursors in the synthesis of CdTe QDs. The synthesized QDs were characterized using various techniques. The average particle size of the QDs from the X-ray diffraction patterns was calculated to be 1.2 nm. UV-Vis absorption and fluorescence spectroscopic studies show a wide absorption band from 400 to 425 nm and a maximum emission peak around 470 nm, which confirmed the successful synthesis of CdTe QDs via the applied synthetic method. After synthesis and characterization of the samples, the antimicrobial properties, genotoxicity, toxicity and antifungal activities of the as-prepared CdTe QDs were investigated. In addition, antioxidant properties of the samples (QDs and extracts), were evaluated by different antioxidant assays. The results indicate the significant antimicrobial activity of the extract and CdTe QDs samples, with negligible toxicity and genotoxicity impacts.


Efficacy of subcutaneous and topical local anaesthesia for pain relief after resection of malignant breast tumours.
Infiltration and topical application of local anaesthetics close to the surgical wound may be used to prevent postoperative pain. We evaluated the efficacy of these treatments after breast surgery for cancer. Double-blind randomised trial with two treatment groups and one control group. University hospital, Sweden. Patients were allocated to treatment with bupivacaine infiltration (n = 29), topical application of lignocaine/prilocaine (n = 31), or no local treatment (n = 30). Difference and time related patterns in pain scores measured on a visual analogue scale (VAS), and morphine consumption. RESULTS. None of the local anaesthetics significantly reduced the VAS score or morphine consumption. However, fewer patients in the anaesthetic groups had high VAS scores than controls, the 75 centile for the mean score after operation being 2.7, 2.0 and 2.1 for the controls, infiltration, and topical anaesthetic groups, respectively. The controls had higher scores from 6 hours postoperatively onwards. The corresponding median morphine consumption was 24.5, 18.5, and 16.2 mg. CONCLUSIONS. Local anaesthesia slightly reduced the overall pain scores and the morphine consumption, but was of potential clinical value only in the patients who had the highest pain scores.


Synthesis and characterization of cellulose nanocrystal-Fe composite nanoparticles and their digestion behavior in simulated gastric fluid.
Cellulose nanocrystals (CNC) exhibit great potential as a food emulsifier or functional material template. Herein, CNC-Fe nanoparticles were successfully prepared via an in situ chemical reduction approach. Zeta potential measurements, low-field nuclear magnetic resonance spectroscopy, and atomic force microscopy showed that Fe(III) ions were adsorbed onto CNC when FeCl3 was added to a CNC dispersion. Micromorphological analysis revealed small (diameter = 10.0 ± 2.4 nm) spherical nanoparticles synthesized on the surface of aggregated CNC after the reduction of the Fe(III) ions. Fourier transform infrared spectroscopy revealed an intense peak at 779 cm-1 in the CNC-Fe nanoparticles, which was attributed to FeO stretching vibrations. X-ray photoelectron spectroscopy indicated that the valence state of Fe in CNC-Fe nanoparticles was predominantly ferrous. The synthesized CNC-Fe nanoparticles demonstrated excellent colloidal stability in a dispersion for 21 d and complete, rapid, and spontaneous dissolution in vitro simulated gastric fluid. Our results highlight the potential use of CNC as a template for loading Fe into nanoparticles for Fe fortification in food.


Gastrointestinal transit after proctocolectomy with ileal pouch-anal anastomosis or ileostomy.
Proctocolectomy with ileal pouch-anal anastomosis increases the frequency of stooling, perhaps due in part to the loss of an ileocecal or colonic braking effect on gastrointestinal transit. To assess whether colectomy with ileal pouch-anal anastomosis (IPAA) or with ileostomy accelerates gastrointestinal transit, we studied 16 IPAA patients (mean +/- SEM stool frequency, 8 +/- 1 stools/day), 5 patients after colectomy and Brooke ileostomy, and 8 healthy, unoperated controls (1 +/- 1 stools/day). Gastric emptying of liquids and small bowel transit of chyme were measured concurrently with a dual isotope technique. Gastric emptying was similar among all groups. In contrast, postprandial small bowel transit of the head of a duodenal marker was slowed, not accelerated, in IPAA patients (178 +/- 26 min) compared to Brooke subjects (80 +/- 32 min, P less than 0.05) and controls (75 +/- 15 min, P less than 0.01). Maximal filling of both the ileal pouch (341 +/- 19 min) and the ileostomy bag (348 +/- 12 min) occurred later than filling of the colon in controls (243 +/- 32 min, P less than 0.01). Overall stool frequency did not correlate with small bowel transit in the ileoanal patients, but the two ileoanal subjects with greatest stool frequency (11 and 18 stools/day) had the earliest arrival of marker at the pouch. In conclusion, removal of the colon markedly slowed small bowel transit in most patients, although it did not alter gastric emptying of liquids. Creation of an ileal pouch and ileoanal anastomosis further slowed transit of the head of the meal.(ABSTRACT TRUNCATED AT 250 WORDS)


Isotretinoin and oral contraceptive use in female acne patients varies by physician specialty: analysis of data from the National Ambulatory Medical Care Survey.
To determine whether oral contraceptives (OCPs) are underutilized in the treatment of acne in women of reproductive age, how use of OCPs compares with use of isotretinoin and whether adequate use and documentation of OCPs is occurring with isotretinoin. The National Ambulatory Medical Care Survey (NAMCS) was analyzed over the years 1993-2008 for isotretinoin and OCP use in females aged 12-55 with acne. Isotretinoin was prescribed more often than OCPs at both first visits (4.7% vs. 3.3%) and overall visits (13% vs. 2.6%) for acne. Documentation of OCP or other contraceptive use occurred only 4.1% of the time overall in patients treated with isotretinoin. Specialties varied in both OCP use for acne and contraceptive use with isotretinoin, with ob/gyn specialists most likely to prescribe OCPs and isotretinoin and to report contraceptive use in patients using isotretinoin, and dermatologists least likely to prescribe OCPs. The findings of the current study indicate that OCPs may be underutilized in women with acne. Underreporting of contraceptive use with isotretinoin and variations between specialties in OCP and isotretinoin use indicate a potential for education about the viability of OCPs in acne treatment and the importance of reporting contraceptive use with isotretinoin.


Spontaneous improvement of levator palpebrae superioris function after traumatic transection.
Direct traumatic injury to the levator palpebrae superioris aponeurosis typically results in upper eyelid ptosis. The mechanisms can involve mechanical or neurogenic etiologies. Prompt surgical exploration and repair are required for restoration of normal function. In cases where prompt surgical intervention is not performed or the levator palpebrae superioris aponeurosis cannot be repaired, the restorative options are limited. The options are further restricted by concurrent ipsilateral frontalis paresis. This report details a spontaneous return of levator function nine months after complete traumatic transection of the levator palpebrae superioris aponeurosis complicated by concurrent ipsilateral frontalis paresis.


Recovery from hypopnea in preterm lambs: effects of breathing air or oxygen.
The aim of this study was to determine if resuscitation from hypopnea when breathing oxygen resulted in a slower recovery than that seen when breathing room air. Hyperoxia, in preterm human neonates and lambs, decreases minute ventilation (Vl), but no study has shown this effect during recovery from apnea or hypopnea, a common clinical setting. Thus, recovery from hypopnea was studied in eight unanesthesized preterm lambs, breathing spontaneously via an endotracheal tube placed into a tracheostomy. Hypopnea, defined here as a decrease in Vl from baseline greater than 50%, was induced by instillation of distilled water onto the larynx. After a baseline 30 sec when Vl, heart rate, and arterial blood gas were measured, a standard hypopnea stimulus was given over 30 sec. The lambs then breathed air or oxygen during a 2-min recovery period, which started with 15 sec of artificial ventilation. The degree of recovery at 2 min was less in the oxygen (O2) breathing group: Vl (ml/kg/min) = 381 +/- 27 in air and 270 +/- 18 in O2, P less than 0.01; pH = 7.38 +/- 0.005 in air and 7.34 +/- 0.008 in O2, P less than 0.01; arterial carbon dioxide tension (PaCO2, mmHg) = 45.0 +/- 1.3 in air and 49 +/- 1.3 in O2, P less than 0.01; base excess = 2.1 +/- 0.6 in air and 1.1 +/- 0.5 oxygen, P less than 0.01. By 2 min a return to baseline values of Vl, pH, and PaCO2 was noted only in the air breathing group, where the arterial oxygen tension also returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)


Resolution of model Holliday junctions by yeast endonuclease is dependent upon homologous DNA sequences.
Holliday junctions, in which two double-stranded DNA molecules are linked by single-stranded crossovers, are thought to be central intermediates in genetic recombination. We report here the in vitro specificity of a yeast endonuclease for structures analogous to Holliday junctions. Plasmids that extrude inverted repeat sequences into cruciform junctions are cleaved by the introduction of nicks into strands of like polarity, approximately 4-8 nucleotides from the base of the junction. In all cases, cleavage occurs within homologous sequences, and with precise symmetry across the junction. In contrast, a junction containing four arms of unrelated sequence is cleaved asymmetrically. The dependence upon homology for symmetrical cleavage is not found with T4 endonuclease VII, which cleaves branched structures in vitro. Holliday junction resolution appears to occur in a concerted manner by the introduction of nicks into two homologous DNA helices held in alignment.


Final Analysis of a Phase 2 Trial of Once Weekly Hypofractionated Whole Breast Irradiation for Early-Stage Breast Cancer.
We hypothesize that 5-fraction once weekly hypofractionated (WH) whole breast irradiation (WBI) would be safe and effective after breast-conserving surgery for medically underserved patients with breast cancer. We report the protocol-specified primary endpoint of in-breast tumor recurrence (IBTR) at 5 years. After provided informed consent, patients were treated with WH-WBI after breast-conserving surgery were followed prospectively on an institutional review board-approved protocol. Women included in this study had stage 0-II breast cancer treated with negative surgical margins and met prespecified criteria for being underserved. WH-WBI was 28.5 or 30 Gy delivered to the whole breast with no elective coverage of lymph nodes. The primary endpoint was IBTR at 5 years. Secondary endpoints were distant disease-free survival, recurrence-free survival, overall survival, adverse events, and cosmesis. One hundred fifty-eight patients received WH-WBI on protocol from 2010 to 2015. Median follow-up was 5.5 years (range, 0.2-10.0 years). Stage distribution was 22% ductal carcinoma in situ, 68% invasive pN0, and 10% invasive pN1. Twenty-eight percent of patients had grade 3 tumors, 10% were estrogen receptor negative, and 24% required adjuvant chemotherapy. There were 6 IBTR events. The 5-, 7-, and 10-year risks of IBTR for all patients were 2.7% (95% confidence interval [CI], 0.89-6.34), 4.7% (95% CI, 1.4-11.0) and 7.2% (95% CI, 2.4-15.8), respectively. The 5-, 7-, and 10-year rates of distant disease-free survival were 96.4%, 96.4%, and 86.4%; the recurrence-free survival rates were 95.8%, 93.6%, and 80.7%; and the overall survival rates were 96.7%, 88.6%, and 76.7%, respectively. Improvement in IBTR-free time was seen in ductal carcinoma in situ, lobular histology, low-grade tumors, T1 stage, Her2-negative tumors, and receipt of a radiation boost to the lumpectomy bed. Postoperative WH-WBI has favorable disease-specific outcomes that are comparable to those seen with conventional and moderately hypofractionated radiation techniques. WH-WBI could improve access to care for underserved patients with stage 0-II breast cancer.


MOF-5(Zn)-Fe2O4 nanocomposite based magnetic solid-phase microextraction followed by HPLC-UV for efficient enrichment of colchicine in root of colchicium extracts and plasma samples.
In present work, facile method is developed for determination of colchicine in human plasma sample, autumn and spring root of colchicium extracts by ultrasound assisted dispersive magnetic solid phase microextraction followed by HPLC-UV method (UAD-MSPME-HPLC-UV). Magnetic (Fe2O4-nanoparticles) metal organic framework-5, (MOF-5(Zn)-Fe2O4NPs) was synthesized by dispersing MOF-5 and Fe(NO3)3.9H2O in ethylene glycol (as capping agent) and NaOH (pH adjustment agent) by hydrothermal method. The prepared sorbent was characterized via XRD and SEM analysis and applied as magnetic solid phase in UAD-MSPME-HPLC-UV method. In this method, colchicine molecules were sorbed on MOF-5(Zn)-Fe2O4NPs sorbent by various mechanisms like ion exchange, hydrogen bonding and electrostatic, ᴨ-ᴨ, hard-hard and dipole-ion interaction followed by exposing sonication waves as incremental mass transfer agent and then the sorbent was separated from the sample matrix by an external magnetic fields. Subsequently, accumulated colchicine were eluted by small volume of desorption organic solvent. Influence of operational variables such as MOF-5(Zn)-Fe2O4NPs mass, volume of extracting solvent and sonication time on response property (recovery) were studied and optimized by central composite design (CCD) combined with desirability function (DF) approach. Under optimum condition, the method has wide linear calibration rang (0.5-1700ngmL-1) with reasonable detection limit (0.13ngmL-1) and R2=0.9971. Finally, the UAD-MSPME-HPLC-UV method was successfully applied for determination of colchicine autumn and spring root of colchicium extracts and plasma samples.


Heterologous expression of a novel linoleic acid isomerase BBI, and effect of fusion tags on its performance.
Functional proteins with the ability to isomerise free linoleic acid (LA) to conjugated linoleic acid (CLA) are termed linoleic acid isomerases (LAI). BBI is a novel LAI from Bifidobacterium breve with unique advantages in the production of a single CLA isomer; however, its complex membrane-bound form hampers over-expression of the protein in its natural host. To overcome this challenge, heterologous expression of BBI in Pichia pastoris was studied. Further, to investigate the influence of His-tags on the heterologous expression of BBI, three P. pastoris recombinant strains carrying either a C-terminal His-tag, an N-terminal His-tag, or none were constructed. The expression of recombinant proteins was analysed by dot and western blotting, and the enzyme activity was determined by GC-MS. The results show that the three P. pastoris recombinant strains successfully expressed the recombinant protein and had LAI activity. Compared with those BBIs without a His-tag or carrying a His-tag on the C-terminus, the BBI carrying an N-terminal His-tag had reduced expression and enzyme activity and that was also explained by the protein modelling analysis. Moreover, this study highlights the advantages of using P. pastoris for BBI expression to achieve efficient production of c9, t11-CLA monomers; the highest conversion rate of the substrate LA was over 80%, resulting in the production of 0.81 mg of c9, t11-CLA per mg of crude enzyme.


Hans Loeschcke, Robert Mitchell and the medullary CO2 chemoreceptors: a brief historical review.
In the late 1950s, stimulated by reports from Leusen in Belgium and Winterstein in Germany on ventilatory responses to spinal fluid acid, Hans Loeschcke from Göttingen, and Robert Mitchell of the University of California in San Francisco were independently seeking the site of respiratory chemosensitivity to CO2 which they presumed to be mediated by cerebro-spinal fluid hydrogen ions. In 1960 Loeschcke came to San Francisco to join Mitchell for 3 months of intensive hunting for the site of action. This essay describes the events surrounding the localization of ventral medullary superficial (VMS) chemosensitivity to topical acidification, and some of their subsequent and largely independent work on the location, nature and function of this structure. The discovery led to a vast literature on all aspects of the regulation of respiration.


Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha.
The high-cholesterol/high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. Liver X receptors (LXRs) are oxysterol sensors that are required for normal cholesterol and triglyceride homeostasis, yet synthetic LXR agonists produce undesirable hypertriglyceridemia. Here we report a previously unrecognized role for hepatic LXRalpha in the links between diet, serum lipids, and atherosclerosis. A modest increase in hepatic LXRalpha worsened serum lipid profiles in LDL-receptor null mice fed normal chow but had the opposite effect on lipids and afforded strong protection against atherosclerosis on a Western diet. The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. Thus, the interplay between diet and hepatic LXRalpha is a critical determinant of serum lipid profiles and cardiovascular risk, and selective modulation of LXR target genes in liver can ameliorate hyperlipidemia and cardiovascular disease.


Lower urinary tract injury: is urology consultation necessary?
There is a paucity of data regarding urology involvement in the management of lower urinary tract injuries (LUTI). We seek to analyze the incidence and epidemiology of LUTI with special attention to trends in urology consultation. A retrospective review was conducted of patients presenting to our Level I trauma center with LUTI from 2002 to 2016. Demographics, mechanism of injury, associated injuries, injury severity score (ISS), American Association for the Surgery of Trauma (AAST) injury scales, and clinical hospital course were analyzed. A total of 140 patients (0.47% of all trauma patients) were identified with LUTI, with 72.1% of these presenting with blunt trauma. Bladder injuries were more common than urethral injuries (79% vs. 14%) with 6% of patients having both. In-hospital mortality was 9.2% (13/140). Among patients with LUTI, 115 patients (82%) received urology consultation. There was no significant difference in sex, age, or LOS (hospital and ICU) between the groups. The consult group had a lower mean ISS (21.7 vs 27.9, p = 0.034), but a higher mean AAST bladder injury scale (2.57 vs 2.00, p = 0.016), than the non-consult group. There was a statistically significant difference in the diagnosis methods between the two groups (χ2 test of independence, p = 0.002). Urology service is important in the management of LUTI with high AAST injury scale. While further study is needed to look at degree of urology service involvement in the management of LUTI, we recommend a consultation for severe LUTI or when the management of injuries is out of the comfort zone of the trauma surgeons. Whether consultation is obtained or not, there is room for improvement in appropriate work up of lower urinary tract injury.


Prolog-based system for nursing staff scheduling implemented on a personal computer.
An approach to the problem of nursing staff scheduling in a hospital is presented. For scheduling nurses, a variety of requirements with varied levels of significance has to be taken into account simultaneously. Because of the nature of the problem, where it is difficult to define what is the optimal solution in a strict sense, we aimed at automating scheduling by following the manual method in a faithful manner. A system for nurse scheduling has been implemented on a personal computer using Prolog. It determines favorable shift assignments on a day-to-day basis, referring to the information accumulated in the data base. In Prolog, various requirements can be expressed with relative ease, and the process of the manual method can be incorporated into the system in a natural way. The computer simulation has been conducted to test the system performance, and the obtained results demonstrated the validity of the approach.


Impact of permethrin-impregnated mosquito nets compared with DDT house-spraying against malaria transmission by Anopheles farauti and An.punctulatus in the Solomon Islands.
In villages of northern Guadalcanal in the Solomon Islands, where the predominant malaria vector is An.farauti No. 1 and An.puctulatus is also involved, malaria transmission rates were compared for three zones: (1) non-intervention: 438 people in seventeen villages; (2) residual DDT house-spraying two cycles per year: 644 people in thirty villages; (3) bednets impregnated with permethrin 0.5 g/m2 twice per year, used by 580 people in sixteen villages. Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously. Malariological blood smear surveys of children aged 1-9 years in August 1986 to January 1987 showed a mean baseline malaria parasite rate of 38% (32/84). By February 1988, 18 months after introduction of impregnated bednets, the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets (21% of 29), intermediate in the untreated zone (29% of 34) and highest in the DDT zone (46% of 53), but these differences were not statistically significant. P. vivax infection rates were 9-14%. Using ELISA tests for malaria circumsporozoite antigen in the vectors, overall positivity rates were 0.7% of 49,902 An.farauti and 2.54% of 118 An.punctulatus, comprising 228 P.falciparum and 124 P.vivax infections. In the study zones, vector positivity rates were 0.93% of 31,615 An.farauti in the untreated zone; 0.32% of 16,883 An.farauti in the DDT zone; 0.07% of 1404 An.farauti and 2.54% of 118 An.puctulatus in the impregnated bednet zone. here was no significant correlation between malaria parasite rates in the vectors and the children.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic control and development expression of malate dehydrogenase in Apis mellifera.
Starch gel electrophoresis of extracts of Apis mellifera indicates that genetic variability exists for the enzyme cytoplasmic malate dehydrogenase (E.C. 220.127.116.11). Analysis of individuals throughout development indicates that the isozyme patterns are identical for larvae and adults and suggests a dimeric structure for the molecule. The isozyme pattern observed in pupae is more complex than that of larvae and adults may be due to an additional pupal-specific MDH gene being expressed or to an epigenetic modification of the isozymes. Forty-three colonies with artificially inseminated queens were used to study the Mendelian pattern of inheritance. The data revealed that the MDH isozymes are encoded by three alleles, Mdh-1A, Mdh-1B, and Mdh-1C. The frequency of the Mdh-1 alleles is different in two analyzed subspecies, A. m. adansonii (African bees) and A. m. ligustica (Italian bees), with Mdh-1A and Mdh-1B in the African bees being 0-768 and 0.202, respectively. For the Italian bees, these frequencies are 0.136 and 0:154, respectively.