Pregnancy, Contraception, and Menopause in Advanced Chronic Kidney Disease and Kidney Transplant.

Abstract: Reproductive health is an essential part of the care of women with kidney disease. However, the self-reported patient experience of reproductive issues has been underexplored.  We identified a cohort of women ages 18 to 44 at the time of kidney transplant from 1996 to 2014 at our 3-site program (n = 816). We sent each woman a survey on her reproductive lifespan, characterizing features from menarche to menopause.  We received survey responses from 190 patients (27%). One third of respondents reported amenorrhea before transplant, and 61.5% of these women reported resumption of menses post-transplant. The average age of menopause was 45.5 years, earlier than the general population (51.3 years). There were 204 pregnancies pretransplant and 52 pregnancies post-transplant. Pregnancies post-transplant were more likely to be complicated by preeclampsia, preterm delivery, and small for gestational age babies than pregnancies that occurred >5 years before transplant. Pregnancies <5 years before transplant were similar to post-transplant pregnancies with respect to complications. Forty-two percent of women were advised to avoid pregnancy after transplant, most often by a nephrology provider.  In our cohort of kidney transplant recipients, women report increased pregnancy-related complications post-transplant and in the 5 years before transplant, compared with pregnancies that occurred greater than 5 years before transplant. They were often counseled to avoid pregnancy altogether. Women reported a younger age of menopause relative to the general population. This should be considered when counseling patients with chronic kidney disease regarding optimal pregnancy timing.

pregnancy
contraception
menopause
chronic kidney disease
kidney transplant


Prosthetic joint infections due to Mycobacterium tuberculosis: A retrospective study.

Abstract:
OBJECTIVE
Tuberculous prosthetic joint infection (PJI) is uncommon and often diagnosed late. The objective here is to describe the management of tuberculous PJI at an osteoarticular infection referral center.

METHODS
A single-center retrospective study of patients managed between 1987 and 2016 was performed.

RESULTS
We identified 9 patients with a median age of 80 years. The hip was involved in all 9 patients. A known history of tuberculosis was noted in 2 patients and tuberculosis was present at other sites in 4 patients (lung, n = 3; urinary tract and scrotum, n = 1; and spine, n = 1). The diagnosis was established by routine intra-operative microbiological sampling, during (n = 4) or at a distance from (n = 5) hip arthroplasty. In the 8 patients with available follow-up data, mean antibiotic therapy duration was 16 months (range, 12-18 months). None of the 4 patients in whom the infection was diagnosed during arthroplasty required surgical revision because of the infection. Of the other 5 patients, 3 were managed by exchange arthroplasty and 1 by excision of the hip without subsequent prosthesis implantation; the remaining patient did not undergo revision surgery. The infection was eradicated in all 9 patients, after 15 months to 10 years.

CONCLUSION
Tuberculous PJI is uncommon. The prognosis is good with prolonged antibiotic therapy, although the optimal duration remains unclear. The surgical strategy should be discussed on a case-by-case basis. The prosthesis can be retained if the tuberculous infection is an unexpected finding during arthroplasty.

Meyssonnier|Vanina|V| Zeller|Valérie|V| Malbos|Stéphanie|S| Heym|Beate|B| Lhotellier|Luc|L| Desplaces|Nicole|N| Marmor|Simon|S| Ziza|Jean-Marc|JM|

Mycobacterium tuberculosis
Periprosthetic joint infection


Contrast-associated transient cortical blindness: three cases with MRI and electrophysiology findings.

Abstract: Transient cortical blindness (TCB) is a rare but striking complication following contrast agent injection. TCB might be secondary to a direct toxicity of the contrast agent, leading to an osmotic disruption of the blood-brain barrier (BBB), with a preferential involvement of the posterior circulation and occipital cortex. We report a series of three patients with contrast medium-associated TCB (intra-arterial injection of non-ionic contrast agent during diagnostic cerebral angiography for two of them and coronary angioplasty for the other one). In two patients, the magnetic resonance imaging (MRI) was unremarkable; in the other patient, typical MRI findings were observed, with FLAIR hyperintensities in the right occipital cortex and decreased apparent diffusions coefficient (ADC). Interestingly, this patient also presented posterior rhythmic epileptiform activities on electroencephalogram during the first 36 h. Visual evoked potentials (VEPs) showed normal retinal potential, but a massive destructuration of the later potentials of the cortical origin. To our knowledge, this is the first time that VEPs acquired during TCB are reported. We discuss these findings with respect to the pathophysiology of TCB.

Baguma|Marius|M| Younan|Nadia|N| London|Frédéric|F| Ossemann|Michel|M| Vandermeeren|Yves|Y|

Cortical blindness
Electrophysiology
Contrast agent
Angiography


Forecasting the effect of social distancing on COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires.

Abstract: Forecasting the extent of the domestic health risk of epidemics by mathematical modeling is a useful tool for evaluating the feasibility of policies for controlling outbreaks. The objective of this study was to develop a time-dependent dynamic simulation model to forecast the COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires, and to assess the effect of social distancing on epidemic spread. The model used was the "Susceptible-Exposed-Infectious-Recovered" framework which incorporated appropriate compartments relevant to interventions such as quarantine, isolation and treatment. In a low-intervention scenario including only 2-week isolation for international travelers and their contacts, the model estimated a maximum peak of nearly 90 000 symptomatic cases for early May. For an intervention scenario with mandatory quarantine during a 5-month period, the curve of cases flattened and receded as the proportion of quarantined individuals increased. The maximum peak was expected to appear between May 8 and Jul 8 depending on the quarantine strategy, and the average number of infectious symptomatic cases were 46 840, 30 494, 23 164, 16 179, and 13 196 when 10%, 20%, 30%, 40%, and 50% of the population remained in a 5-month-term continuous quarantine, respectively. Only mandatory quarantine was able to delay the maximum peak of infection and significantly reduce the total number of infected individuals and deaths at a 150-day term. The interruption of the quarantine before 120 days of its beginning could generate an even more serious outbreak 30 days later, and surpass the scarce medical resources available for the intensive care of critically-ill patients.

Borracci|Raul A|RA|
Giglio|Norberto D|ND|

outbreak
epidemic
mathematical model
Argentina
coronavirus


Decreased Shoulder and Elbow Joint Loads During the Changeup Compared With the Fastball and Curveball in NCAA Division I Collegiate Softball Pitchers.

Abstract:
Background
Baseball leagues have implemented pitch count and pitch type restrictions based on biomechanical concepts associated with pitch type. Softball has not yet adopted these practices, although softball pitchers continue to pitch at a high volume and learn multiple pitches at a young age.

Purpose
To examine shoulder and elbow kinetics between the fastball, curveball, and changeup, as well as to provide descriptive upper extremity pain data in National Collegiate Athletic Association (NCAA) softball pitchers.

Study Design
Descriptive laboratory study.

Methods
Study participants consisted of 27 female NCAA Division I softball pitchers (age, 20.2 ± 1.9 years; height, 175.7 ± 5.7 cm; weight, 83.6 ± 12.7 kg). The participants pitched 3 balls of each pitch type, and kinetic data were recorded. A one-way within-participants repeated-measures multivariate analysis of variance was used to determine significant differences in kinetics and pitch speed between pitch types.

Results
Results revealed a statistically significant main effect for pitch type (Wilks λ = .087; F = 36.523; P < .001). Post hoc testing showed that the changeup produced less anterior elbow force compared with the fastball (P < .001) and the curveball (P = .012). In addition, the changeup produced less shoulder distraction force compared with the fastball (P < .001) and the curveball (P = .001). Additionally, there was a significant difference in pitch speed between all 3 pitch types (P = .006). The curveball revealed no statistically significant kinetic differences compared with the fastball.

Conclusion
The fastball and curveball placed similar stress on the upper extremity in collegiate softball pitchers. However, in comparison with the changeup, the fastball and curveball placed increased stress on the upper extremity. More research is needed to fully explain the differences seen between pitch type and injury risk.

Clinical Relevance
Sports medicine professionals, coaches, and athletes should use the current study results to note these differences in shoulder distraction and elbow anterior forces between softball pitch types. The study results can be used as a reference and basis for future research investigating kinetic differences across varying pitch types.

Oliver|Gretchen D|GD|
Downs Talmage|Jessica L|JL|
Friesen|Kenzie B|KB|
Saper|Michael G|MG|
Dugas|Jeffrey R|JR|

pitch types
kinetics
windmill softball pitching


Proteo-lipobeads to encapsulate cytochrome c oxidase from Paracoccus denitrificans.

Abstract: Proteo-lipobeads (PLBs) are investigated as cell-free model systems to encapsulate membrane proteins such as ion channels and transporters. PLBs are based on nickel nitrile tri-acetic acid (Ni-NTA)-functionalized agarose beads, onto which membrane proteins (MP) are bound via histidine(his)-tag. Composite beads thus obtained (subsequently called proteobeads) are dialyzed in the presence of lipid micelles to form PLBs. As an example we employed cytochrome c oxidase from P. denitrificans with a his-tag fused to the C-terminus of subunitI. In this orientation the P side of CcO faces the outside of the PLB and hence protons are released to the outer aqueous phase, when electron transfer is initiated by light excitation of Ru complexes. Proton release kinetics was probed by fluorescence microscopy using the pH-sensitive sensor molecule fluorescein DHPE inserted into the lipid layer. In order to monitor the generation of membrane potentials we performed a FLIPR assay on the CcO embedded in PLBs using the FRET pair CC2-DMPE/DiSBAC2(3). The combined results show that PLBs can be used as a model system designed to quantify the kinetic parameters of membrane proteins. In addition, the FLIPR assay demonstrates the feasibility of PLBs for high throughput screening applications.

Geiss|Andreas F|AF|
Bliem|Christina|C|
Frank|Pinar|P|
Reiner-Rozman|Ciril|C|
Kewney|Justin|J|
Boersch|Michael|M|
Naumann|Renate L C|RLC|

Fluorescence imaging plate reader assay (FLIPR)

Protein-tethered bilayer lipid membrane (ptBLM)


Design and synthesis of a tetrahydroisoquinoline-based hydroxamate derivative (ZYJ-34v), an oral active histone deacetylase inhibitor with potent antitumor activity.

Abstract: In our previous study, we developed a novel series of tetrahydroisoquinoline-based hydroxamic acid derivatives as histone deacetylase inhibitors (Bioorg Med Chem, 2010, 18, 1761-1772; J Med Chem, 2011, 54, 2823-2838), among which, compound ZYJ-34c (1) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency (J Med Chem, 2011, 54, 5532-5539.). Herein, further modification in 1 afforded another oral active analog ZYJ-34v (2) with simplified structure and lower molecular weight. Biological evaluation of compound 2 showed efficacious inhibition against histone deacetylase 1, 2, 3, and 6, which was confirmed by Western blot analysis results. Most importantly, compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved histone deacetylase inhibitor SAHA.

Zhang|Yingjie|Y|
Liu|Chunxi|C|
Chou|C James|CJ|
Wang|Xuejian|X|
Jia|Yuping|Y|
Xu|Wenfang|W|

oral active
histone deacetylases
inhibitor
antitumor
tetrahydroisoquinoline
valproic acid


Risk factors for acute kidney injury after pediatric cardiac surgery: a meta-analysis.

Abstract:
BACKGROUND
Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality in both adults and children.

OBJECTIVES
This study aimed to identify clinical risk factors for AKI following cardiac surgery in the pediatric population.

DATA SOURCES
PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for studies published by August 2020.

STUDY ELIGIBILITY CRITERIA
Studies were included if (1) the population consisted of pediatric patients (< 18 years old), (2) patients underwent cardiac surgery, (3) risk factors were compared between patients who developed AKI and those who did not, and (4) studies were prospective or retrospective observational studies or randomized controlled trials.

PARTICIPANTS AND INTERVENTIONS
Children undergoing pediatric cardiac surgery.

STUDY APPRAISAL AND SYNTHESIS METHODS
Random-effects meta-analysis was performed, comparing potential risk factors between pediatric patients who developed CS-AKI and those who did not.

RESULTS
Sixty-one publications including a total of 19,680 participants (AKI: 7257 participants; no AKI: 12,423 participants) were included from studies published between 2008 and 2020. The pooled estimated incidence of AKI was 34.3% (95% confidence interval 30.0-38.8%, I2 = 96.8%). Binary risk factors that were significantly and consistently associated with AKI were the presence of pulmonary hypertension, cyanotic heart disease, univentricular heart, risk adjustment for congenital heart surgery 1 (RACHS-1) score ≥ 3, vasopressor use, cardiopulmonary bypass use, reoperation, and sepsis. Significant continuous risk factors included younger age, lower body weight, lower preoperative creatinine, higher preoperative estimated glomerular filtration rate (eGFR), higher RACHS-1 score, longer surgery time, longer cardiopulmonary bypass time, longer aortic cross-clamp time, and higher red blood cell transfusion volume.

LIMITATIONS
Results are limited by heterogeneity and potential residual confounding.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Our meta-analysis identified clinical risk factors that are associated with AKI in children undergoing cardiac surgery. This might help clinicians anticipate and manage more carefully this population and implement standardized preventive strategies.

SYSTEMATIC REVIEW REGISTRATION NUMBER
CRD42021262699. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk factors
Acute kidney injury
Pediatric
Cardiac surgery
Meta-analysis


Widespread methanotrophic primary production in lowland chalk rivers.

Abstract: Methane is oversaturated relative to the atmosphere in many rivers, yet its cycling and fate is poorly understood. While photosynthesis is the dominant source of autotrophic carbon to rivers, chemosynthesis and particularly methane oxidation could provide alternative sources of primary production where the riverbed is heavily shaded or at depth beneath the sediment surface. Here, we highlight geographically widespread methanotrophic carbon fixation within the gravel riverbeds of over 30 chalk rivers. In 15 of these, the potential for methane oxidation (methanotrophy) was also compared with photosynthesis. In addition, we performed detailed concurrent measurements of photosynthesis and methanotrophy in one large chalk river over a complete annual cycle, where we found methanotrophy to be active to at least 15 cm into the riverbed and to be strongly substrate limited. The seasonal trend in methanotrophic activity reflected that of the riverine methane concentrations, and thus the highest rates were measured in mid-summer. At the sediment surface, photosynthesis was limited by light for most of the year with heavy shading induced by dense beds of aquatic macrophytes. Across 15 rivers, in late summer, we conservatively calculated that net methanotrophy was equivalent to between 1% and 46% of benthic net photosynthetic production within the gravel riverbed, with a median value of 4%. Hence, riverbed chemosynthesis, coupled to the oxidation of methane, is widespread and significant in English chalk rivers.

rivers
photosynthesis
carbon
chemosynthesis
methane oxidation


Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis: evidence for metformin-based "starvation" strategies in BRCA1 carriers.

Abstract: We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human breast epithelial cells in which the knock-in of 185delAG mutation in a single BRCA1 allele leads to genomic instability. Mutant BRCA1 one-hit epithelial cells displayed constitutively enhanced activation of biosynthetic nodes within mitochondria. This metabolic rewiring involved the increased incorporation of glutamine- and glucose-dependent carbon into tricarboxylic acid (TCA) cycle metabolite pools to ultimately generate elevated levels of acetyl-CoA and malonyl-CoA, the major building blocks for lipid biosynthesis. The significant increase of branched-chain amino acids (BCAAs) including the anabolic trigger leucine, which can not only promote protein translation via mTOR but also feed into the TCA cycle via succinyl-CoA, further underscored the anabolic reprogramming of BRCA1 haploinsufficient cells. The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling. Metformin-induced restriction of mitochondrial biosynthetic capacity was sufficient to impair the tumor-initiating capacity of BRCA1 one-hit cells in mammosphere assays. Metabolic rewiring of the breast epithelium towards increased anabolism might constitute an unanticipated and inherited form of metabolic reprogramming linked to increased risk of oncogenesis in women bearing pathogenic germline BRCA1 mutations. The ability of metformin to constrain the production of mitochondrial-dependent biosynthetic intermediates might open a new avenue for "starvation" chemopreventive strategies in BRCA1 carriers.

Cuyàs|Elisabet|E|
Fernández-Arroyo|Salvador|S|
Alarcón|Tomás|T|
Lupu|Ruth|R|
Joven|Jorge|J|
Menendez|Javier A|JA|

BRCA1
bioenergetics
breast cancer susceptibility
glutamine
hereditary breast cancer


Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice.

Abstract: Application of cytostatics in cancer patients' chemotherapy results in a number of side effects, including the inhibition of various parts of hematopoiesis. Two sulfated polysaccharides, fucoidan from the seaweed Chordaria flagelliformis (PS-Fuc) and fucosylated chondroitin sulfate from the sea cucumber Massinium magnum (PS-FCS), were studied as stimulators of hematopoiesis after cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF) was applied as a reference. Both tested polysaccharides PS-Fuc and PS-FCS have a similar activity to r G-CSF, causing pronounced neutropoiesis stimulation in animals with myelosuppression induced by cyclophosphamide (CPh). Moreover, these compounds are also capable to enhance thrombopoiesis and erythropoiesis. It should be noted that PS-FCS demonstrated a greater activity than r G-CSF. The results indicate the perspective of further studies of PS-Fuc and PS-FCS, since these compounds can be considered as potentially promising stimulators of hematopoiesis. Such drugs are in demand for the accompanying treatment of cancer patients who suffer from hematological toxicity during chemo and/or radiation therapy.

Anisimova|Natalia|N| Ustyuzhanina|Nadezhda|N| Bilan|Maria|M| Donenko|Fedor|F| Usov|Anatolii|A| Kiselevskiy|Mikhail|M| Nifantiev|Nikolay|N|

fucoidan
fucosylated chondroitin sulfate
hematopoiesis
cyclophosphamide
immunosuppression
granulocyte colony-stimulating factor


Validation of an MRI-based method to assess patellofemoral joint contact areas in loaded knee flexion in vivo.

Abstract:
PURPOSE
To develop and validate short axial and sagittal MRI scans (<1min) to assess in vivo patellofemoral contact areas in loaded knee flexion.

MATERIALS AND METHODS
Contact area was assessed in four cadaver knee specimens from axial and sagittal scans using two contact area extraction techniques (delineation and intersection) and three calculation techniques (slice thickness multiplication, linear interpolation, and spline interpolation). Error was expressed as the mean absolute and percentage difference from a dye staining-based reference standard. Intrareader and intrasubject repeatability, expressed as the mean standard deviation, was determined.

RESULTS
Contact area assessments from the sagittal MRI scans using the delineation and slice thickness multiplication technique had the smallest error (47.7 ± 38.1 mm(2) or 10.7%). The intrareader repeatability from assessments using the sagittal scans was smaller than those using the axial scans when the delineation method was used (<9.4 ± 4.3 mm(2) and <15.4 ± 14.1 mm(2) , respectively). The intrasubject repeatability of the assessment from the sagittal scan was less than 39.9 ± 23.0 mm(2) .

CONCLUSION
This protocol yields assessments of contact area in less than 1 minute that have errors similar to those made using scans many times longer and can be used in series with kinematic scans to carry out simultaneous assessments in vivo to study patellofemoral joint disease.

McWalter|Emily J|EJ|
O'Kane|Colm M|CM|
Fitzpatrick|David P|DP|
Wilson|David R|DR|

validation
patellofemoral
contact area
knee
kinematics
magnetic resonance imaging
patella


Repair of extensive apical root resorption associated with apical periodontitis: radiographic and histologic observations after 25 years.

Abstract:
INTRODUCTION
Root resorption is a frequent finding in teeth with apical periodontitis. In cases of severe apical periodontitis, root resorption may involve not only cementum but also dentin. Resorbed tooth structures can only be repaired with cementum because stem cells in the periradicular tissues are not capable of differentiating into odontoblasts. This article reports the repair of extensive apical root resorption associated with apical periodontitis 25 years after treatment.

METHODS
A 51-year-old man presented with pulp necrosis and symptomatic apical periodontitis in tooth #7. The periapical radiograph showed a large radiolucent periradicular lesion and severe root resorption. Nonsurgical root canal therapy was performed. Twenty-five years after treatment, a crown fracture developed, and the tooth could not be restored. The periapical radiograph revealed complete healing of the previous apical periodontitis lesion and restoration of the resorbed root structure. The tooth was removed and examined histologically.

RESULTS
The apical canal was almost completely filled with a cementumlike tissue with some strands of entrapped vital uninflamed connective tissue. Areas of cementum and dentin resorption in the apical third were repaired by a combination of cellular and acellular cementum to which periodontal ligament fibers were attached.

CONCLUSIONS
Root resorption caused by apical periodontitis can be restored almost to its normal structure after adequate nonsurgical root canal treatment that succeeded in controlling infection. The mechanisms behind this process are not clear but probably involve signaling pathways regulating root development, cell-cell and cell-matrix interaction, and morphogens.

Ricucci|Domenico|D|
Siqueira|José F|JF|
Loghin|Simona|S|
Lin|Louis M|LM|

D003739:Dental Cementum
D003786:Dental Pulp Cavity
D003790:Dental Pulp Necrosis
D003804:Dentin
D005500:Follow-Up Studies
D006801:Humans
D007180:Incisor
D008297:Male
D008875:Middle Aged
D010485:Periapical Periodontitis
D010513:Periodontal Ligament
D016300:Radiography, Bitewing
D012390:Root Canal Therapy
D012391:Root Resorption
D019227:Tooth Apex
D019228:Tooth Crown
D014082:Tooth Fractures

apical root resorption
Apical periodontitis
cementum repair
wound healing


Hydrothermal carbonization of sewage sludge: Effect of feed-water pH on hydrochar's physicochemical properties, organic component and thermal behavior.

Abstract: In this study, hydrothermal carbonization (HTC) of sewage sludge(SS) was carried out at a temperature of 270℃ and a resulting pressure of 7-9 MPa with 2 h. The effect of feed water pH values in the range of 2-12 on hydrochar characteristics, organic component and thermal behavior was evaluated. The result shows that with the pH value increasing, ash content shows a trend of decline, and organic components in the hydrochar become significantly simpler than SS. hydrochar is more beneficial to produce a fatty substance during an acidic environment and alkaline environments favor the formation of N-containing organic compounds and ketone organics, especially in strongly alkaline environments. Compared to the SS, hydrochar burning interval shortened 100℃ and the combustion of hydrochar is more durable. Considering the organic composition and combustion performance of hydrochar, it is found that the hydrochar prepared under 270-5 condition has the best effect.

Liu|Xiangmin|X| Zhai|Yunbo|Y| Li|Shanhong|S| Wang|Bei|B| Wang|Tengfei|T| Liu|Yali|Y| Qiu|Zhenzi|Z| Li|Caiting|C|

Sewage sludge
pH
Hydrochar
Organic component
Thermal behavior


Peripheral blood CD34+ cells as a novel and noninvasive early marker of first trimester miscarriage: results from a case-control analysis.

Abstract:
PURPOSE
To evaluate the levels of peripheral blood CD34+ cells in women who subsequently had a spontaneous miscarriage (SM).

MATERIALS AND METHODS
We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th-11th weeks of pregnancy, we evaluated PAPP-A, free β-hCG, T (suppressor and helper), NK, B, CD34+ cells.

RESULTS
In peripheral blood of women who had SM, PAPP-A and CD34+ cells were significantly lower (p < 0.001) compared to control group.

CONCLUSIONS
CD34+ cell low level in peripheral blood is associated with increased risk of SM.

peripheral blood
CD34
first trimester
miscarriage
Hematopoietic stem cells


Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer.

Abstract:
BACKGROUND
Tumor-infiltrating lymphocyte (TIL) count in breast cancer carries prognostic information and represents a potential predictive marker for emerging immunotherapies. However, the distribution of the lymphocyte subpopulations is not well defined. The goals of this study were to examine intratumor heterogeneity in TIL subpopulation counts in different fields of view (FOV) within each section, in different sections from the same biopsy, and between biopsies from different regions of the same cancer using quantitative immunofluorescence (QIF).

METHODS
We used multiplexed QIF to quantify cytokeratin-positive epithelial cells, and CD3-positive, CD8-positive and CD20-positive lymphocytes in tissue sections from multiple biopsies obtained from different areas of 31 surgically resected primary breast carcinomas (93 samples total). Log2-transformed QIF scores or concordance and variance component analyses with linear mixed-effects models were used. Cohen's kappa index [k] of high versus low scores, defined as above and below the median, was used to measure sample similarity between areas.

RESULTS
We found a strong positive correlation between CD3 and CD8 levels across all patients (Pearson correlation coefficient [CC] = 0.827). CD3 and CD8 showed a weaker but significant association with CD20 (CC = 0.446 and 0.363, respectively). For each marker, the variation between different FOVs in the same section was higher than the variation between sections or between biopsies of the same cancer. The intraclass correlation coefficients (ICC) were 0.411 for CD3, 0.324 for CD8, and 0.252 for CD20. In component analysis, 66-69 % of the variance was attributable to differences between FOVs in the same section and 30-33 % was due to differences between biopsies from different areas of the same cancer. Section to section differences were negligible. Concordance for low versus high marker status assignment in single biopsies compared to all three biopsies combined yielded k = 0.705 for CD3, k = 0.655 for CD8, and k = 0.603 for CD20.

CONCLUSIONS
T and B lymphocytes show more heterogeneity across the dimensions of a single section than between different sections or regions of a given breast tumor. This observation suggests that the average lymphocyte score from a single biopsy of a tumor is reasonably representative of the whole cancer.

Mani|Nikita L|NL|
Schalper|Kurt A|KA|
Hatzis|Christos|C|
Saglam|Ozlen|O|
Tavassoli|Fattaneh|F|
Butler|Meghan|M|
Chagpar|Anees B|AB|
Pusztai|Lajos|L|
Rimm|David L|DL|

Breast cancer
Immunofluorescence
B cells
Stroma
T cells
Tumor microenvironment


An energetics perspective on geroscience: mitochondrial protonmotive force and aging.

Abstract: Mitochondria are organelles that provide energy to cells through ATP production. Mitochondrial dysfunction has long been postulated to mediate cellular declines that drive biological aging. Many well-characterized hallmarks of aging may involve underlying energetic defects that stem from loss of mitochondrial function with age. Why and how mitochondrial function declines with age is an open question and one that has been difficult to answer. Mitochondria are powered by an electrochemical gradient across the inner mitochondrial membrane known as the protonmotive force (PMF). This gradient decreases with age in several experimental models. However, it is unclear if a diminished PMF is a cause or a consequence of aging. Herein, we briefly review and define mitochondrial function, we summarize how PMF changes with age in several models, and we highlight recent studies that implicate PMF in aging biology. We also identify barriers that must be addressed for the field to progress. Emerging technology permits more precise in vivo study of mitochondria that will allow better understanding of cause and effect in metabolic models of aging. Once cause and effect can be discerned more precisely, energetics approaches to combat aging may be developed to prevent or reverse functional decline.

Metabolism
AMPK
Autophagy
Membrane potential
mTOR


Efficacy of Primaquine in Preventing Short- and Long-Latency Plasmodium vivax Relapses in Nepal.

Abstract:
BACKGROUND
Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously.

METHODS
Patients with P. vivax malaria were randomized to receive chloroquine (CQ; 25 mg base/kg given over 3 days) alone or together with primaquine (PQ; 0.25 mg base/kg/day for 14 days) and followed intensively for 1 month, then at 1- to 2-month intervals for 1 year. Parasite isolates were genotyped.

RESULTS
One hundred and one (49%) patients received CQ and 105 (51%) received CQ + PQ. In the CQ + PQ arm, there were 3 (4.1%) recurrences in the 73 patients who completed 1 year of follow-up compared with 22 of 78 (28.2%) in the CQ-only arm (risk ratio, 0.146 [95% confidence interval, .046-.467]; P < .0001). Microsatellite genotyping showed relatively high P. vivax genetic diversity (mean heterozygosity, 0.843 [range 0.570-0.989] with low multiplicity of infection (mean, 1.05) reflecting a low transmission preelimination setting. Of the 12 genetically homologous relapses, 5 (42%) occurred in a cluster after 9 months, indicating long latency.

CONCLUSIONS
Although there may be emerging CQ resistance, the combination of CQ and the standard-dose 14-day PQ regimen is highly efficacious in providing radical cure of short- and long-latency P. vivax malaria in Nepal.

Rijal|Komal Raj|KR|
Adhikari|Bipin|B|
Ghimire|Prakash|P|
Banjara|Megha Raj|MR|
Das Thakur|Garib|G|
Hanboonkunupakarn|Borimas|B|
Imwong|Mallika|M|
Chotivanich|Kesinee|K|
Day|Nicholas P J|NPJ|
White|Nicholas J|NJ|
Pukrittayakamee|Sasithon|S|

primaquine
Plasmodium vivax
relapse
Nepal
chloroquine


Parenting and Child Development: A Relational Health Perspective.

Abstract: A child's development is embedded within a complex system of relationships. Among the many relationships that influence children's growth and development, perhaps the most influential is the one that exists between parent and child. Recognition of the critical importance of early parent-child relationship quality for children's socioemotional, cognitive, neurobiological, and health outcomes has contributed to a shift in efforts to identify relational determinants of child outcomes. Recent efforts to extend models of relational health to the field of child development highlight the role that parent, child, and contextual factors play in supporting the development and maintenance of healthy parent-child relationships. This review presents a parent-child relational health perspective on development, with an emphasis on socioemotional outcomes in early childhood, along with brief attention to obesity and eating behavior as a relationally informed health outcome. Also emphasized here is the parent-health care provider relationship as a context for supporting healthy outcomes within families as well as screening and intervention efforts to support optimal relational health within families, with the goal of improving mental and physical health within our communities.

Frosch|Cynthia A|CA|
Schoppe-Sullivan|Sarah J|SJ|
O'Banion|D David|DD|

parenting
child development
relational health
parent-child relationships
health outcomes


The magnitude of placebo analgesia effects depends on how they are conceptualized.

Abstract:
OBJECTIVE
Placebo effects are usually calculated as the difference between placebo treatments and no treatments. Recently, placebo-like effects have been investigated using open and hidden administrations of active treatments. The aim of the study was to directly compare the two types of placebo effects and examine how they are influenced by personality traits.

METHODS
In a within-subject, randomized, blinded, balanced placebo trial design study with 48 healthy volunteers, we compared placebo and placebo-like effects and tested if expectancy, absorption and suggestibility correlated with these effects. Subjects completed the Tellegen Absorption Scale and the Sensory Suggestibility Scale, and pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections of hypertonic saline with lidocaine or matching placebo in randomized order: open treatment, hidden treatment, placebo and control. The placebo effect was defined as the difference in pain between the placebo and the control condition and the placebo-like effect as the difference in pain between the open and hidden condition.

RESULTS
Placebo effects were significant both in the traditional paradigm: mean placebo effect AUC 1626 mm(2) (95% CI 958-2293) and the open-hidden paradigm: mean placebo-like effect AUC 801 mm(2) (95% CI 134-1469), but there was a significant difference between the magnitude of the two effects (p=0.049). Absorption and suggestibility did not predict the placebo or the placebo-like effect. Estimated expected pain relief correlated with placebo effects but not placebo-like effects.

CONCLUSION
The magnitude of placebo effects differs depending on how they are conceptualized and calculated.

Lund|Karen|K|
Petersen|Gitte L|GL|
Erlandsen|Mogens|M|
De Pascalis|Vilfredo|V|
Vase|Lene|L|
Jensen|Troels S|TS|
Finnerup|Nanna B|NB|

Placebo effect
Expectation
Absorption
Suggestibility
Pain


Host switching of human lice to new world monkeys in South America.

Abstract: The coevolution between a host and its obligate parasite is exemplified in the sucking lice that infest primates. In the context of close lice-host partnerships and cospeciation, Pediculus mjobergi, the louse of New World primates, has long been puzzling because its morphology resembles that of human lice. To investigate the possibility that P. mjobergi was transmitted to monkeys from the first humans who set foot on the American continent thousands of years ago, we obtained and compared P. mjobergi lice collected from howler monkeys from Argentina to human lice gathered from a remote and isolated village in Amazonia that has escaped globalization. Morphological examinations were first conducted and verified the similarity between the monkey and human lice. The molecular characterization of several nuclear and mitochondrial genetic markers in the two types of lice revealed that one of the P. mjobergi specimens had a unique haplotype that clustered with the haplotypes of Amazonian head lice that are prevalent in tropical regions in the Americas, a natural habitat of New World monkeys. Because this phylogenetic group forms a separate branch within the clade of lice from humans that were of American origin, this finding indicates that human lice have transferred to New World monkeys.

Drali|Rezak|R|
Abi-Rached|Laurent|L|
Boutellis|Amina|A|
Djossou|Félix|F|
Barker|Stephen C|SC|
Raoult|Didier|D|

Cospeciation
Pediculus mjobergi
Amazonian head louse
Host-switching


FoxO3 regulates hepatic triglyceride metabolism via modulation of the expression of sterol regulatory-element binding protein 1c.

Abstract:
BACKGROUND
Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism.

METHODS
Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid.

RESULTS
FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter.

CONCLUSIONS
FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation.

Wang|Liu|L| Zhu|Xiaopeng|X| Sun|Xiaoyang|X| Yang|Xinyu|X| Chang|Xinxia|X| Xia|Mingfeng|M| Lu|Yan|Y| Xia|Pu|P| Yan|Hongmei|H| Bian|Hua|H| Gao|Xin|X|

D065626:Non-alcoholic Fatty Liver Disease

D060888:Real-Time Polymerase Chain Reaction

D051780:Sterol Regulatory Element Binding Protein 1

Sterol regulatory element-binding protein1c


Myosin motor isoforms direct specification of actomyosin function by tropomyosins.

Abstract: Myosins and tropomyosins represent two cytoskeletal proteins that often work together with actin filaments in contractile and motile cellular processes. While the specialized role of tropomyosin in striated muscle myosin-II regulation is well characterized, its role in nonmuscle myosin regulation is poorly understood. We previously showed that fission yeast tropomyosin (Cdc8p) positively regulates myosin-II (Myo2p) and myosin-V (Myo52p) motors. To understand the broader implications of this regulation we examined the role of two mammalian tropomyosins (Tpm3.1cy/Tm5NM1 and Tpm4.2cy/Tm4) recently implicated in cancer cell proliferation and metastasis. Like Cdc8p, the Tpm3.1cy and Tpm4.2cy isoforms significantly enhance Myo2p and Myo52p motor activity, converting nonprocessive Myo52p molecules into processive motors that can walk along actin tracks as single molecules. In contrast to the positive regulation of Myo2p and Myo52p, Cdc8p and the mammalian tropomyosins potently inhibited skeletal muscle myosin-II, while having negligible effects on the highly processive mammalian myosin-Va. In support of a conserved role for certain tropomyosins in regulating nonmuscle actomyosin structures, Tpm3.1cy supported normal contractile ring function in fission yeast. Our work reveals that actomyosin regulation by tropomyosin is dependent on the myosin isoform, highlighting a general role for specific isoforms of tropomyosin in sorting myosin motor outputs.

Clayton|Joseph E|JE|
Pollard|Luther W|LW|
Murray|George G|GG|
Lord|Matthew|M|

actin
regulation
myosin isoforms
motor sorting
tropomyosin isoforms


Efficacy of CPET Combined with Systematic Education of Cardiac Rehabilitation After PCI: A Real-World Evaluation in ACS Patients.

Abstract:
INTRODUCTION
There are scarce real-world data on the long-term efficacy and safety of cardiopulmonary exercise testing (CPET) combined with the systematic education of cardiac rehabilitation (CR) approach for patients post-coronary stenting, which is, therefore, the subject of this study.

METHODS
Data collected between 1 April 2015 and 20 May 2017 from 11,345 patients in the rehabilitation center database at our hospital were retrospectively analyzed. Five hundred thirty-six patients with incomplete information, or unable to cooperate with telephone follow-up, were excluded; 4001 patients received the combined CR approach; and 6808 patients received only routine post-procedure education (controls). Of these, 2805 CR participants (CR group) were matched 1:1 to controls (control group) using propensity scores. The main outcome was quality of life in Seattle Angina Questionnaire (SAQ) scores. SAQ was measured in hospital and at follow-up; meanwhile, volume/type of habitual exercise, major adverse cardiovascular event (MACE), and its components of target vessel revascularization, myocardial infarction, and cardiac death were recorded and analyzed.

RESULTS
At median 583 (range 184-963) day follow-up, compared with controls, the CR group showed fewer patients not engaging in physical exercise (22 vs. 956, p < 0.05); more cumulative exercise time (h/week) (8.22 ± 6.17 h vs. 3.00 ± 1.65 h, p < 0.05); higher SAQ scores (physical limitation, 69.59 ± 10.96 vs. 57.49 ± 7.19; anginal stability, 80.50 ± 18.21 vs. 58.82 ± 11.95; anginal frequency, 78.58 ± 11.07 vs. 67.14 ± 22.41; treatment satisfaction, 82.33 ± 13.21 vs. 56.84 ± 21.61; quality of life, 68.69 ± 18.33 vs. 60.26 ± 17.13, all p < 0.01), but a similar MACE rate (log-rank p = 0.621).

CONCLUSION
Compared with only routine post-procedure education, CR combining at least one-time CPET with a systematic cardiac education program before discharge improved engagement in physical activity and quality of life for patients after percutaneous coronary intervention (PCI) without increasing clinical adverse events.

Zhang|Quan-Yu|QY| Hu|Qiang|Q| Li|Yi|Y| Sun|Yi|Y| He|Jing-Fei|JF| Qiu|Miao-Han|MH| Zhang|Jian|J| Liang|Yan-Chun|YC| Han|Ya-Ling|YL|

Cardiac rehabilitation
Quality of life
Percutaneous coronary intervention
Cardiopulmonary function exercise test
Coronary artery disease


Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer.

Abstract: The identification of cancer-associated long non-coding RNAs (lncRNAs) and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The lncRNA-LET, a newly identified lncRNA, was demonstrated to be down-regulated in hepatocellular cancer. However, little is known about its role in gallbladder cancer. In the present study, an obvious down-regulation of lncRNA-LET was observed in gallbladder cancer compared to their adjacent normal tissues. Meanwhile, patients with low expression of lncRNA-LET have significantly poorer prognosis than those with high expression. We confirmed that hypoxia decreased lncRNA-LET levels in gallbladder cancer cells. Moreover, lncRNA-LET overexpression was further validated to inhibit the invasion of gallbladder cancer cells under hypoxic or normoxic conditions in vitro. We demonstrated that lncRNA-LET overexpression conferred a proliferative advantage to tumor cells under hypoxic conditions. The ectopic expression of lncRNA-LET led to the promotion of cell cycle arrest at G0/G1 phase and to the induction of apoptosis under hypoxic conditions. Ectopic expression of LncRNA-LET also suppressed gallbladder tumor growth in vivo. Our findings indicate that lncRNA-LET may represent a prognostic marker and a potential therapeutic target for gallbladder cancer.

Ma|Ming-zhe|MZ| Kong|Xiang|X| Weng|Ming-zhe|MZ| Zhang|Ming-di|MD| Qin|Yi-yu|YY| Gong|Wei|W| Zhang|Wen-jie|WJ| Quan|Zhi-wei|ZW|

D015972:Gene Expression Regulation, Neoplastic

gallbladder cancer
long non-coding RNA
lncRNA-LET
prognosis
hypoxia


Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with outcome of patients treated with BRAF inhibitors.

Abstract:
PURPOSE
The aim of this study is to verify if baseline hematological markers, in patients with advanced melanoma receiving BRAF inhibitor (BRAFi)-based therapies, are independently associated with progression free survival (PFS) and overall survival (OS).

METHODS
We retrospectively analyzed 90 patients with metastatic melanoma harboring BRAF V600 mutation, who received treatment with either BRAFi alone or combined with a MEK inhibitor (MEKi) at the recommended dosages. Study population included 28 women and 62 men. Median age was 53 years. Seventy-three (82%) patients presented with M1c disease, 49 (56%) had elevated LDH and 54 (60%) had three or more metastatic sites.

RESULTS
The median PFS was 9.1 and 3.5 months, respectively, for patients with baseline NLR < 5 and NLR ≥ 5, while median OS was 17.2 and 5.5 months, respectively, for patients with NLR < 5 and NLR ≥ 5. Multivariate analysis confirmed that baseline NLR < 5 was significantly associated with half risk of relapse (HR = 0.49; 95% CI = 0.28-0.85; p = 0.01) and half risk of death (HR = 0.46; 95% CI = 0.23-0.76; p = 0.004), independent of age, sex, stage, LDH > 2xULN, previous treatments, concomitant use of steroids and type of therapy. In patients with LDH ≥ ULN, NLR < 5 remained significantly and independently associated with improved PFS (HR = 0.28; 95% CI = 0.13-0.62; p = 0.002,) and OS (HR = 0.23; 95% CI = 0.10-0.55; p = 0.001).

CONCLUSIONS
These biomarkers are easily reproducible, affordable and costless and NLR could help to identify patients who have the best benefit from BRAF inhibitors.

NLR
Metastatic melanoma
Targeted therapy


Osteopathic structure/function models renovation for a person-centered approach: a narrative review and integrative hypothesis.

Abstract:
OBJECTIVES
The construct of the osteopathic structure-function models is reported as a cornerstone of clinical reasoning and treatment processes. Nevertheless, there are no shared procedures described for their use in clinical practice. The present narrative review aims to analyze a more comprehensive perspective on the phenomenon.

METHODS
A structured narrative review was conducted. A database search was conducted using Pubmed, ScienceDirect, and Google Scholar. Peer-reviewed papers without specifying limits on dates and design were included.

RESULTS
Twenty-five findings were reported and grouped into two main themes: 1) Debate on models and theoretical frameworks for osteopathic care; 2) Clinical reasoning and decision-making process in the osteopathic field.

CONCLUSIONS
An integrated osteopathic care approach based on the structure/function models represents a starting point to establish a shared osteopathic diagnostic and clinical reasoning and an evidence-informed practice promoting health in an interdisciplinary person-centered care process. The present review highlights the limited amount of literature on using osteopathic conceptual models in decision-making and treatment strategies. A research plan is required to develop a common framework for an evidence-based osteopathic practice that promotes well-being in an interdisciplinary person-centered care process.

clinical reasoning
osteopathic care
allostatic load
decision making process
integrative medicine
interprofessional care
interprofessional education


Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity.

Abstract: The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity in vitro and in vivo. After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability in vitro. Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells in vitro and was further evaluated in a CT 26 allograft mouse model in vivo. GM07 was identified as Odoribacter splanchnicus through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of O. splanchnicus (OsCFS) induced anti-proliferative activity via apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.

Oh|Byeong Seob|BS|
Choi|Won Jung|WJ|
Kim|Ji-Sun|JS|
Ryu|Seoung Woo|SW|
Yu|Seung Yeob|SY|
Lee|Jung-Sook|JS|
Park|Seung-Hwan|SH|
Kang|Se Won|SW|
Lee|Jiyoung|J|
Jung|Won Yong|WY|
Kim|Young-Min|YM|
Jeong|Jae-Ho|JH|
Lee|Ju Huck|JH|

cell-free supernatant
Odoribacter splanchnicus
gut microbiota
colorectal cancer
apoptosis
murine model


Dietary medium-chain 1-monoglycerides modulates the community and function of cecal microbiota of broilers.

Abstract:
BACKGROUND
Medium-chain monoglycerides (MGs) are a group of 1-monoglycerides of medium-chain fatty acids with strong antibacterial activity, which may influence the gut microbiota in the diet of broilers. The present study evaluated the effects of mixed MGs on the community and function of gut microbiota in broilers. A total of 528 newly hatched male yellow feathered broiler chicks were weighed and randomly assigned into four groups, including a basal diet (CON), a basal diet containing 300 mg kg-1 MG (MG300), 450 mg kg-1 MG (MG450), or 600 mg kg-1 MG (MG600).

RESULTS
The cecal acetic acid, propionic acid, butyric acid, isobutyric acid, isovaleric acid and total short-chain fatty acid of broilers in the MG-containing groups were notably increased compared with the CON group. Dietary MG selectively increased the relative abundance of Bifidobacteriaceae, Bacteroides and an unclassified genus of Lachnospiraceae family, but decreased the proportion of an unclassified genus of Barnesiellaceae and a norank genus of Flavobacteriaceae family in the cecum of broilers. Functional prediction revealed that MG supplementation enriched the microbial gene abundance of amino acid metabolism and carbohydrate metabolism, while depleted the gene abundance of fat metabolism and energy metabolism. Moreover, the modulation of gut microbiota by MG supplementation was closely correlated with the alteration of muscle amino acids.

CONCLUSION
Dietary MGs altered the gut microbiota community structure and metabolites, and modulated the gene abundance of microbial metabolism pathways in the cecum of broilers, which may further influence the growth performance, nutrient utilization and meat quality of the host. © 2021 Society of Chemical Industry.

monoglycerides
gut microbiota
functional prediction
feed additive
poultry


Development of a smart-fit system for CPAP interface selection.

Abstract: Continuous Positive Airway Pressure (CPAP) therapy is commonly prescribed for longstanding, acute cases of Obstructive Sleep Apnea (OSA) during which patients must wear a tight-fitting breathing mask overnight for the duration of the treatment. Because this condition frequently leads to the permanent use of CPAP masks, interface selection is a crucial factor influencing the treatment quality and effectiveness. Masks/interface selection is normally performed on a trial an error basis with clinicians informing their selection based on OSA-related factors with basic fitting feedback from patients. However, it is not uncommon for patients to abandon the treatment or request additional consultations due to ill-fitting CPAP mask with the main sources of discomfort being perceived air leakage and mask/strap overtightening leading to skin damage. This work introduces a novel system (Smart-Fit), for CPAP interface selection using advanced digital technologies, such as Reverse Engineering and Computational Modeling (Finite Element Analysis) which are paired to evaluate and determine the best fitting interface for each clinical case. The model simplifies the number of 3D facial landmarks to 12 and established that a 2 mm scan resolution is enough for accurate scans. The Von Mises stress map in ANSYS serves as an indicator of potential high-pressure areas, triggering the need for a chance of mask size. Current results indicate the Smart Fit System can enable a "best fit CPAP interface" to be selected considering individual's physical characteristics and existing CPAP interface configurations. The development of the Smart Fit System is an evolution compared to traditional CPAP interface selection approach, which optimizes the CPAP interface selection process.

D045422:Continuous Positive Airway Pressure

CPAP interface selection
reverse engineering
finite element analysis
human factors


Post-fire summer rainfall differentially affects reseeder and resprouter population recovery in fire-prone shrublands of South Africa.

Abstract: Summer rainfall can have strong effects on post-fire mediterranean-type shrubland recovery patterns, with potentially long-lasting implications on communities. Our three-year field rainfall manipulation experiment tested post-fire survival and physiological responses of reseeders and resprouters to contrasting summer rainfall patterns in Fynbos and Renosterveld shrublands in South Africa. Climate projections are uncertain for this region but indicate that increased convective summer rainfall events could occur. We irrigated treatment plots during the hottest summer months (i.e. Jan, Feb, March) to contrast the naturally dry summer conditions. This allowed for assessments of the potential limiting effects of summer drought on post-fire vegetation recovery and the responsiveness of vegetation to moisture inputs during this time. Natural summer droughts led to leaf dehydration, reduced photosynthesis and reduced photosynthetic capacity. This had a particularly severe effect on reseeders during the first summer after fire leading to high mortality rates. Summer irrigations strongly reduced levels of reseeder stress and mortality. Resprouters in both vegetation types were physiologically less sensitive to rainfall patterns and showed little drought-related mortality. Comparisons of final population sizes with emergence and survival patterns showed that summer rainfall during the first summer after fire had the potential to strongly alter reseeder population sizes. The physiological sensitivity of plants to summer rainfall patterns was higher in shrubland communities occurring on fine-textured, moderately fertile soils (e.g. Renosterveld). Shrublands occurring on sandy, nutrient-poor soils (e.g. Fynbos) were remarkably insensitive to summer drought after the first summer with lower irrigation responses. Our study demonstrated the potential for variation in post-fire summer rainfall to strongly affect reseeder and resprouter population recovery patterns.

van Blerk|J J|JJ|
West|A G|AG|
Altwegg|R|R|
Hoffman|M T|MT|

Shrubland
Rainfall manipulation
Fire
Climate-change
Demography
Post-fire regeneration


A Viral Ecogenomics Framework To Uncover the Secrets of Nature's "Microbe Whisperers".

Abstract: Microbes drive critical ecosystem functions and affect global nutrient cycling along with human health and disease. They do so under strong constraints exerted by viruses, which shape microbial communities' structure and shift host cell metabolism during infection. While the majority of viruses and their associated impacts remain poorly characterized, a number of mechanisms by which viruses alter microbial cells and ecosystems have already been revealed. Here I outline how a comprehensive host-resolved mapping of viral sequence space will enable a thorough characterization of virus-encoded mechanisms for microbial manipulation. With soon-to-be millions of virus genomes obtained from metagenomes, one of the major challenges resides in the development of methods for high-throughput and high-resolution virus-host pairing, before multi-omics approaches can be leveraged to fully decipher virus-host dynamics in nature. Beyond novel fundamental biological knowledge, these studies will likely provide new molecular tools enabling a precise engineering of microbial cells and communities.


Comparison of abo antibody levels in apheresis platelets suspended in platelet additive solution and plasma.

Abstract:
BACKGROUND
Transfusion of platelets (PLTs) with high ABO antibody titres can pose a risk of hemolysis if the unit crosses the ABO type. The PLTs stored in the platelet additive solution (PAS) remove asubstantial fraction of plasma and replace it with an isotonicbuffered solution.We aimed to assess the difference in anti-A/B antibody levels in Groups O, A and B apheresis platelets (APs) suspended in plasma and PAS.

METHODOLOGY
Apheresis donors are categorized into two groups, Plasma (Group I) and PAS (Group II), each blood group (A, B and O) had 20 samples. The anti-A/B(IgM)antibody levels were recorded from the AP donor (Group II) and from the AP units for both groups. The reduction in the anti-A/B(IgM) antibody levels in the APs suspended in the PAS for each blood group was determined.

RESULTS
The median anti-A titres in blood Groups B (p = 0.009) and O (p = 0.005) was significantly lower in Group II. However, the difference in anti-B levels was not significant in the blood groups A (p = 0.057) and O (p = 0.205). The median level of reduction in IgM antibody titres across donor samples and the PAS-stored platelets was two-fold. The regression showed a level of reduction in antibody titres which can be explained by baseline donor antibody titres in blood groups A and B compared to blood group O.

CONCLUSION
The medianABO antibody titres were lower in APs suspended in PAS than in plasma. Addition of the PAS significantly lowered the IgM antibody titres by twofold, compared to plasma.

Kc|Gayathiri|G|
Murugesan|Mohandoss|M|
Nayanar|Sangeetha K|SK|
Malodan|Riyas|R|
Padmanaban|Maya|M|

Apheresis
Platelets
Plasma
Titre
ABO blood group


Reducing late-onset neonatal sepsis in very low birthweight neonates with central lines in a low-and-middle-income country setting.

Abstract:
BACKGROUND
Late-onset neonatal sepsis (LONS) is a significant contributor to morbidity and mortality in very low birthweight (VLBW) neonates with indwelling central lines. Compliance to central line care bundles is suboptimal in low-and-middle-income country settings. Point of care quality improvement (POCQI) method may be used to improve the compliance gap. We used the POCQI method to achieve an improvement in compliance to central line care bundles with an aim to reduce LONS in a subset of VLBW neonates.

METHODS
A pre and post-intervention study consisting of three phases was conducted in a tertiary care neonatal intensive care unit. A root-cause analysis was undertaken to find the causes of LONS in VLBW babies with central lines. Multiple change ideas were identified and tested using sequential Plan-Do-Study-Act (PDSA) cycles to address the issue of reduced compliance to the central line care bundles. The change ideas tested in PDSA cycles which were successful were adopted. Compliance to the insertion and maintenance bundles was measured as process indicators. LONS, central line associated bloodstream infections and all-cause mortality rates were measured as outcome indicators.

RESULTS
A total of 10 PDSA cycles testing multiple change ideas (staff education, audio-visual aids, supply issues) were undertaken during the study duration. Bundles were not being used in the study setting prior to the initiation of the study. Insertion bundle compliance was above 90% and maintenance bundle compliance increased from 23.3% to 42.2% during the intervention and sustenance phases, respectively. A 43.3% statistically significant reduction in LONS rates was achieved at the end of the study. No effect on mortality was seen.

CONCLUSION
POCQI method can be used to improve compliance to central line care bundles which can lead to a reduction of LONS in VLBW neonates with central lines in situ.

Batthula|Vinay|V|
Somnath|Sanjana H|SH|
Datta|Vikram|V|0000-0002-1047-6884

D002405:Catheterization, Central Venous
D006801:Humans
D007223:Infant
D007231:Infant, Newborn
D019102:Infant, Very Low Birth Weight
D007363:Intensive Care Units, Neonatal
D000071074:Neonatal Sepsis
D064872:Patient Care Bundles

quality improvement
checklists
infection control
nosocomial infections


Enzymatic hydrolysis in an aqueous organic two-phase system using centrifugal partition chromatography.

Abstract: Multi-phase reaction systems, mostly aqueous organic systems, are used in enzyme catalysis to convert hydrophobic substrates which are almost insoluble in aqueous media. In this study, a Centrifugal Partition Chromatograph is used as a compact device for enzymatic multi-phase reaction that combines efficient substrate supply to the aqueous phase and separation of both phases in one apparatus. A process design procedure to systematically select the aqueous and organic phase to achieve stable and efficient reaction rates and operation conditions in Centrifugal Partition Chromatography for efficient mixing and separation of the phases is presented. The procedure is applied to the hydrolysis of 4-nitrophenyl palmitate with a lipase derived from Candida rugosa. It was found that the hydrolysis rate of 4-nitrophenyl palmitate was two times higher in Centrifugal Partition Chromatography than in comparable stirred tank reactor experiments.

Krause|J|J| Oeldorf|T|T| Schembecker|G|G| Merz|J|J|

Centrifugal Partition Chromatography
Multi-phase reaction system
Biocatalysis
Countercurrent chromatography
Lipase Candida rugosa


Attention modulates topology and dynamics of auditory sensory gating.

Abstract: This work challenges the widely accepted model of sensory gating as a preattention inhibitory process by investigating whether attention directed at the second tone (S2) within a paired-click paradigm could affect gating at the cortical level. We utilized magnetoencephalography, magnetic resonance imaging and spatio-temporal source localization to compare the cortical dynamics underlying gating responses across two conditions (passive and attention) in 19 healthy subjects. Source localization results reaffirmed the existence of a fast processing pathway between the prefrontal cortex (PFC) and bilateral superior temporal gyri (STG) that underlies the auditory gating process. STG source dynamics comprised two gating sub-components, Mb1 and Mb2, both of which showed significant gating suppression (>51%). The attention directed to the S2 tone changed the gating network topology by switching the prefrontal generator from a dorsolateral location, which was active in the passive condition (18/19), to a medial location, active in the attention condition (19/19). Enhanced responses to the attended stimulus caused a significant reduction in gating suppression in both STG gating components (>50%). Our results demonstrate that attention not only modulates sensory gating dynamics, but also exerts topological rerouting of information processing within the PFC. The present data, suggesting that the cortical levels of early sensory processing are subject to top-down influences, change the current view of gating as a purely automatic bottom-up process.

attention
auditory sensory gating
paired-click paradigm
magnetoencephalography
gating network
auditory gating generators
dorsolateral prefrontal cortex
gating stream
medial prefrontal cortex
neuroimaging
sensory pathways


The Effects of the Global Economic Recession and a Reduced Alcohol Tax on Hospitalizations Due to Alcohol-Attributed Diseases in Taiwan.

Abstract: This study is to assess the effects of the 2008 economic crisis and a 2009 alcohol tax reduction on alcohol-related morbidity for men of different socioeconomic statuses in Taiwan. Admissions data for the period from 2007 to 2012 for men aged 24-59 years in 2007 was retrieved from the National Health Insurance Research Database. With stratification over three income levels, an interrupted time-series analysis examining the effects of the crisis and taxation reduction on incidence rates of hospitalization for alcohol-attributed diseases (AADs) was employed. The low income group showed a significant (p < 0.05) change in the rate of AAD-related hospitalizations in July 2008; specifically, an abrupt 7.11% increase that was then sustained for several months thereafter. In contrast, while the middle income group exhibited a significant 22.9% decline in the rate of AAD-related hospitalizations over the course of the crisis, that downward trend was gradual. The reduction of the alcohol tax resulted in increased rates of AADs among both the low and high income groups. The economic recession and the reduction of the alcohol tax resulted in an increased rate of AAD among low income men.

economic recession
alcohol-attributed disease
morbidity
time-series
ARIMA


Comprehensive Characterization of the Perioperative Morbidity of Cytoreductive Nephrectomy.

Abstract:
BACKGROUND
Although cytoreductive nephrectomy (CN) has been associated with perioperative morbidity, data are lacking regarding the risk of prolonged length of stay (pLOS) and delay to receipt of systemic therapy (ST).

OBJECTIVE
To evaluate the association of clinicopathologic features with postoperative complications, pLOS, and time to receipt of ST.

DESIGN, SETTING, AND PARTICIPANTS
We evaluated 294 patients with M1 renal cell carcinoma treated between 1990 and 2009.

INTERVENTIONS
CN.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Logistic and Cox regressions were used to evaluate associations of clinicopathologic features with 30-d postoperative complications, pLOS (LOS ≥75th percentile), and time to receipt of ST.

RESULTS AND LIMITATIONS
Fifteen (5%) patients experienced at least one Clavien grade ≥3 early complication. Among patients for whom postsurgical ST was recommended, 61% did not receive ST within 60 d, but the delay was surgery-related in only 11%. In multivariable models limited to preoperative features, liver metastases were associated with complications (odds ratio [OR] 3.73, p=0.004) and pLOS (OR 2.46, p=0.03), while a laparoscopic approach was associated with earlier administration of ST (hazard ratio [HR] 5.05, p<0.001). In multivariable models incorporating operative features, intraoperative transfusion was associated with complications (OR 1.14, p<0.001) and pLOS (OR 1.22, p<0.001), while pN1 disease was associated with pLOS (OR 2.12, p=0.049) and delay to ST (HR 0.38, p=0.004). Limitations include the retrospective design and surgical selection bias.

CONCLUSIONS
Overall, 61% of CN patients did not receive timely ST, but only 5% of patients experienced Clavien grade ≥3 complications and the delay to ST was surgery-related in 11%. Liver metastases, intraoperative transfusion, and pN1 disease were independently associated with perioperative morbidity.

PATIENT SUMMARY
We evaluated the morbidity of cytoreductive nephrectomy and identified predictors of unfavorable perioperative outcomes. Although 61% of patients did not receive timely systemic therapy, the rates of complications and surgery-related delay to systemic therapy were low.

Gershman|Boris|B|
Moreira|Daniel M|DM|
Boorjian|Stephen A|SA|
Lohse|Christine M|CM|
Cheville|John C|JC|
Costello|Brian A|BA|
Leibovich|Bradley C|BC|
Thompson|R Houston|RH|

Cytoreductive nephrectomy
Systemic therapy
Complications
Renal cell carcinoma
Prolonged hospitalization


Effects of strain on the electronic, optical, and ferroelectric transition properties of HfO2:ab initiosimulation study.

Abstract: The amazing ferroelectricity observed in Hafnium oxide (HfO2) thin films is due to the existence of non-centrosymmetric orthorhombicPca21phase. In this study, the structural, electronic, optical, and polarization switching properties of the orthorhombicPca21phase with various strains are investigated by employing density functional theory (DFT) calculations based on the DFT. Out-of-plane and in-plane strains are taken into consideration. The results indicate that the band-gap values of orthorhombic HfO2increase at first and then decrease from compressive strain to tensile strain due to the variation of the valence band maximum and the conduction band minimum. Moreover, orthorhombic HfO2transforms into a direct bandgap material when compressive strain along thezdirection is larger than or equal to 5%. A red-shift occurs under both tensile and compressive strains in the absorption edge compared with instinct HfO2in the absorption spectra. The absorption intensity of the strained HfO2is enhanced with the energy below 5.5 eV. The energy barriers of path A and path B of the polarization switching mediated by non-polar tetragonal phase are 116.8 and 91.2 meV per formula unit (meV/f.u.), respectively. In polarization switching without mediated by non-polar phase, the energy barriers decrease with the increasing of out-of-plane compressive strain along thexdirection and tensile strain along theydirection compared with strain free structures.

strains
hafnium oxide
polarization switching
density functional theory
minimum energy pathways


DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Non-syndromic Cleft Lip and Palate.

Abstract: Non-syndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect. The etiology of NSCLP is complex with multiple genes and environmental factors playing causal roles. Although studies have identified numerous genetic markers associated with NSCLP, the role of epigenetic variation remains relatively unexplored. Because of their identical DNA sequences, monozygotic (MZ) twins discordant for NSCLP are an ideal model for examining the potential contribution of DNA methylation to non-syndromic orofacial clefting. In this study, we compared the patterns of whole genome DNA methylation in six MZ twin pairs discordant for NSCLP. Differentially methylated positions (DMPs) and regions (DMRs) were identified in NSCLP candidate genes, including differential methylation in MAFB and ZEB2 in two independent MZ twin pairs. In addition to DNA methylation differences in NSCLP candidate genes, we found common differential methylation in genes belonging to the Hippo signaling pathway, implicating this mechanosensory pathway in the etiology of NSCLP. The results of this novel approach using MZ twins discordant for NSCLP suggests that differential methylation is one mechanism contributing to NSCLP, meriting future studies on the role of DNA methylation in familial and sporadic NSCLP.

Young|Juan I|JI|
Slifer|Susan|S|
Hecht|Jacqueline T|JT|
Blanton|Susan H|SH|

non-syndromic cleft lip and cleft palate


Fungal Gastroduodenitis.

Abstract:
Candida infection of the gastrointestinal (GI) tract is rare in the immunocompetent individual. In immunocompromised patients, it frequently involves the oesophagus, but extra-oesophageal involvement is uncommon. We report a case of primary and isolated gastroduodenal candidiasis. Upper GI endoscopy with biopsy of gastric mucosa was crucial for making the diagnosis. The patient showed transient improvement after therapy with fluconazole.

LEARNING POINTS
Gastroduodenal candidiasis is rarely documented in the literature.Old age is an independent risk factor for fungal infection of the gastrointestinal tract.In this case, fungal gastroduodenitis was associated with gastroparesis.

Branco|Sara Castelo|SC|
Ferreira|Ana Teresa|AT|
Saraiva|Sofia|S|
Silva|Mário Jorge|MJ|
Garcia|Teresa|T|

Gastroduodenitis
Fungal infection
Candida spp


Investigating Two-Photon-Induced Fluorescence in Rhodamine-6G in Presence of Cetyl-Trimethyl-Ammonium-Bromide.

Abstract: We investigate the effect of cetyl-trimethyl-ammonium-bromides (CTAB) concentration on the fluorescence of Rhodamine-6G in water. This spectroscopic study of Rhodamine-6G in presence of CTAB was performed using two-photon-induced-fluorescence at 780 nm wavelength using high repetition rate femtosecond laser pulses. We report an increment of ∼10 % in the fluorescence in accordance with ∼12 % enhancement in the absorption intensity of the dye molecule around the critical micellar concentration. We discuss the possible mechanism for the enhancement in the two-photon fluorescence intensity and the importance of critical micellar concentration.

Maurya|Sandeep Kumar|SK|
Yadav|Dheerendra|D|
Goswami|Debabrata|D|

Cetyltrimethylammonium bromides (CTAB)
Critical micelle concentration (CMC)
Rhodamine 6G
Two photon induced fluorescence (TPIF)


Complementary and Alternative Medicine Use at a Comprehensive Cancer Center.

Abstract:
BACKGROUND
Complementary and alternative medicine (CAM) use is common among cancer patients, but the majority of CAM studies do not specify the time periods in relation to cancer diagnoses. We sought to define CAM use by cancer patients and investigate factors that might influence changes in CAM use in relation to cancer diagnoses.

METHODS
We conducted a cross-sectional survey of adults diagnosed with breast, prostate, lung, or colorectal cancer between 2010 and 2012 at the Lineberger Comprehensive Cancer Center. Questionnaires were sent to 1794 patients. Phone calls were made to nonrespondents. Log binomial/Poisson regressions were used to investigate the association between cancer-related changes in CAM use and conversations about CAM use with oncology providers.

RESULTS
We received 603 (33.6 %) completed questionnaires. The mean age (SD) was 64 (11) years; 62% were female; 79% were white; and 98% were non-Hispanic. Respondents reported the following cancer types: breast (47%), prostate (27%), colorectal (14%), lung (11%). Eighty-nine percent reported lifetime CAM use. Eighty-five percent reported CAM use during or after initial cancer treatment, with category-specific use as follows: mind-body medicine 39%, dietary supplements 73%, body-based therapies 30%, and energy medicine 49%. During treatment CAM use decreased for all categories except energy medicine. After treatment CAM use returned to pretreatment levels for most CAMs except chiropractic. Initiation of CAM use after cancer diagnosis was positively associated with a patient having a conversation about CAM use with their oncology provider, mainly driven by patient-initiated conversations.

CONCLUSIONS
Consistent with previous studies, CAM use was common among our study population. Conversations about CAM use with oncology providers appeared to influence cessation of mind-body medicine use after cancer diagnosis.

D000529:Complementary Therapies
D003430:Cross-Sectional Studies
D019587:Dietary Supplements
D005260:Female
D015438:Health Behavior
D006801:Humans
D008297:Male
D008875:Middle Aged
D026441:Mind-Body Therapies
D009369:Neoplasms
D016522:Oncology Service, Hospital
D011795:Surveys and Questionnaires

complementary and alternative medicine
cancer survivorship
patient behavior
patient-provider communication
treatment phase


Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation.

Abstract: Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV.

Maximova|Natalia|N| Antonio|Pizzol|P| Marilena|Granzotto|G| Rovere|Francesca|F| Tamaro|Paolo|P|

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

VZV
valganciclovir
lymphocyte depletion
HSCT


Kinetics of the TL phenomenon in LiF:Mg irradiated to different dose of gamma radiation of 60Co using two different programs of deconvolution.

Abstract: In this work, the results on determination of kinetic parameters using the method of deconvolution of glow curves obtained from the LiF doped with Mg(2+) ions, after having been irradiated to 5, 10 and 25 Gy of (60)Co gamma radiation, corresponding to the range of TL-vs-dose response linearity, are presented. The deconvolution is performed using two functions obtained by the method of asymptotic series and by the method based on the approximation of continued fractions. The glow curve of the studied material shows a dosimetric glow peak at 518 K and three peaks of very low intensity at 383, 423 and 463 K, all of a general-order kinetics. Kinetic parameters obtained with both methods showed that the values of kinetics, b, the energy of the traps, E, and the factor of frequency, s, do not differ significantly. However, the figure of merit, FOM, and the second derivative criteria indicate that the accuracy of the calculations with the second method improves considerably.

González|P R|PR|
Gutiérrez-Tapia|C|C|
Flores-Llamas|H|H|

TL phenomenon
Determination of kinetic parameters
Deconvolution of glow curves


Ludwig Guttmann's Academic Relationship with Postwar Germany.

Abstract: Sir Ludwig Guttmann's pioneering work in the treatment of spinal injury not only improved the care for patients with paraplegia up to now but revolutionized basic principles of neurorehabilitation. A wide selection of publications honors the personal and academic life of this singular German neurologist and neurosurgeon of Jewish descent. When the Nazis came into power, Guttmann was dismissed from his hospital workplace, humiliated, and later forced to leave Germany. Surprisingly, after the Second World War, the psychiatrist Friedrich Panse, who had been a member of the Nazi party, initiated Guttmann's academic rehabilitation up to his nomination as emeritus professor of Cologne University in 1964. The present article recounts the difficult academic restitution and poses the question why Guttmann sought to re-establish connections to Germany, a country that had expelled him so harshly some decades before.

D064846:Sports for Persons with Disabilities

Ludwig Guttmann
Postwar Germany
Friedrich Panse
Academic rehabilitation
Emeritus professor
Cologne University


Prevalence of microplastic contamination in the digestive tract of fishes from mangrove ecosystem in Cispata, Colombian Caribbean.

Abstract: Plastics in Colombian marine-coastal ecosystems are being fragmented by various environmental factors, generating microplastics (size < 5 mm), an emerging pollutant that is ingested by marine organisms, representing a threat to ecosystems and potentially also to humans. This study aims to evaluate the incidence of microplastic ingestion by fishes from mangrove ecosystems in Cispata, Colombian Caribbean. The digestive tract content of 302 specimens of 22 fish species were analyzed using the KOH digestion method (500 g/5 L), stereoscopic visual identification and infrared spectroscopy. A total of 69 microplastics were found in the digestive tract of 7% of the analyzed fishes. 55% of the ingested microplastics were filaments, 23% fragments, 19% films, and 3% foam. The results of this study raised concerns about microplastic contamination in the marine environments, a threat to the fishery resource and to public health, which requires actions to prevent and reduce its negative effects.

Garcés-Ordóñez|Ostin|O|
Mejía-Esquivia|Kevin Alexander|KA|
Sierra-Labastidas|Tatiana|T|
Patiño|Albert|A|
Blandón|Lina Marcela|LM|
Espinosa Díaz|Luisa F|LF|

Mangrove ecosystem
Fishery resource
Marine litter
Microplastic pollution


GRAPPA Trainees Symposium 2015: A Report from the GRAPPA 2015 Annual Meeting.

Abstract: At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, rheumatology and dermatology trainees engaged in psoriasis or psoriatic arthritis research presented their work to meeting attendees in a trainees symposium. This report briefly reviews 6 oral presentations and 20 posters presented at the meeting.

Milliken|Michael|M|
Generali|Elena|E|
Marin|Josefina|J|
Ritchlin|Christopher T|CT|

GRAPPA
TRAINEE
PSORIASIS
PSORIATIC ARTHRITIS
DERMATOLOGIST
RHEUMATOLOGIST


Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis.

Abstract:
BACKGROUND
Despite the clinical recommendation of exercise and diet for people with knee osteoarthritis (OA), there are no systematic reviews synthesising the effectiveness of combining physical activity and dietary restriction interventions on the musculoskeletal function of overweight and obese older adults with knee OA.

OBJECTIVE
To evaluate the effectiveness of combined physical activity and dietary restriction programmes on body weight, body mass index (BMI) and the musculoskeletal function of overweight and obese older adults with knee OA.

INFORMATION SOURCES
A detailed search strategy was applied to key electronic databases (Ovid, Embase, Web of Science andCumulative Index to Nursing and Allied Health Literature (CINAHL)) for randomised controlled trials (RCTs) published in English prior to 15 January 2017.

PARTICIPANTS
Participants with BMI ≥25 kg/m2, aged ≥55 years of age and with radiographic evidence of knee OA.

INTERVENTIONS
Physical activity plus dietary restriction programmes with usual care or exercise as the comparators.

OUTCOME MEASURES
Primary outcome measures were body weight, BMI or musculoskeletal function. Secondary outcome measures were pain and quality of life.

RESULTS
One pilot and two definitive trials with n=794 participants were included. Two articles reporting additional data and outcome measures for one of the RCTs were identified. All included RCTs had an unclear risk of bias. Meta-analysis was only possible to evaluate mobility (6 min walk test) at 6 months and the pooled random effect 15.05 (95% CI -11.77 to 41.87) across two trials with n=155 participants did not support the combined intervention programme. Narrative synthesis showed clear differences in favour of a reduced body weight and an increased 6 min walk in the intervention group compared with control groups.

CONCLUSION
The quality of evidence of benefit of combining exercise and dietary interventions in older overweight/obese adults with knee OA is unclear.

TRAIL REGISTRATION NUMBER
CRD42015019088 and ISRCTN, ISRCTN12906938.

Alrushud|Asma S|AS|
Rushton|Alison B|AB|
Kanavaki|Archontissa M|AM|
Greig|Carolyn A|CA|

obesity
Exercise
diet
randomised controlled trials
elderly


Hereditary antithrombin III deficiency and neuraxial anaesthesia.

Abstract: Antithrombin III (ATIII) deficiency offers unique challenges to the anaesthetist in the perioperative setting due to the inherent thrombophilia, the anticoagulant therapies instituted and replacement of the deficient intrinsic natural anticoagulant. A particular challenge is the use of intrathecal anaesthesia, which requires a safe level of coagulation at the time of subarachnoid puncture. We describe the use of intrathecal anaesthesia on two occasions in a patient with ATIII deficiency who received human-derived ATIII concentrate as part of a perioperative anticoagulant regimen. The patient sustained no thrombotic or bleeding events. Our experience suggests that ATIII deficiency does not preclude the use of regional anaesthetic techniques so long as there is timely referral to a multidisciplinary perioperative service for anticoagulant management and that ATIII concentrate is used to ensure safe levels of ATIII throughout the perioperative period.

D000775:Anesthesia, Spinal
D020152:Antithrombin III Deficiency
D006801:Humans
D008297:Male
D008875:Middle Aged
D019990:Perioperative Care

antithrombin III
blood coagulation
thrombosis


MASQC: Next Generation Sequencing Assists Third Generation Sequencing for Quality Control in N6-Methyladenine DNA Identification.

Abstract: DNA N6-methyladenine (6mA) modification has been discovered as the most prevalent DNA modification in prokaryotes and eukaryotes, involving gene expression, DNA replication and repair, and host-pathogen interactions. Single-molecule real-time sequencing (SMRT-seq) can detect 6mA events in prokaryotic and eukaryotic genomes at the single-nucleotide level. However, there are no strict and economical quality control methods for high false-positive 6mA events in eukaryotic genomes. Therefore, by analyzing the distribution of 6mA in eukaryotic and prokaryotes, we proposed a method named MASQC (MeDIP-seq assists SMRT-seq for quality control in 6mA identification), which can identify 6mA events without doing the whole genome amplification (WGA) sequencing. The proposed MASQC method was assessed on two eukaryotic genomes and six bacterial genomes, our results demonstrate that MASQC performs well in quality control of false positive 6mA identification for both eukaryotic and prokaryotic genomes.

Yang|Siqian|S| Wang|Yaoxin|Y| Chen|Ying|Y| Dai|Qi|Q|

DNA N6-methyladenine
prokaryotes
eukaryotes
SMRT-seq
MeDIP-seq


The complete chloroplast genome and phylogenetic analysis of Cuminum cyminum.

Abstract: Cuminum cyminum (Apiaceae) is an economically important plant, whose fruits are usually used as flavoring, and also have pharmacological activities such as antioxidant, antibacterial, hypolipidemic, and so on. In this study, we assembled and annotated complete chloroplast (cp) genome sequence of C. cyminum. The results showed that the complete cp genome of C. cyminum was 157,839 bp in length, consisting of a large single-copy (LSC) region of 83,927bp, a small single-copy (SSC) region of 17,598bp, and two inverted repeat regions (IRa and IRb) of 28,157bp. In total, 131 genes were annotated, comprising of 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis indicated that C. cyminum belongs to the tribe Scandiceae, and showed close relationship with Daucus carota.

complete chloroplast genome
Cuminum cyminum
phylogeny


Specialist antenatal clinics for women at high risk of preterm birth: a systematic review of qualitative and quantitative research.

Abstract:
BACKGROUND
Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Women with previous prenatal loss are at higher risk of preterm birth. A specialist antenatal clinic is considered as one approach to improve maternity and pregnancy outcomes.

METHODS
A systematic review of quantitative, qualitative and mixed method studies conducted on women at high risk of preterm birth (PTB). The review primary outcomes were to report on the specialist antenatal clinics effect in preventing or reducing preterm birth, perinatal mortality and morbidity and women's perceptions and experiences of a specialist clinic whether compared or not compared with standard antenatal care. Other secondary maternal, infant and economic outcomes were also determined. A comprehensive search strategy was carried out in English within electronic databases as far back as 1980. The reviewers selected studies, assessed the quality, and extracted data independently. Results were summarized and tabulated.

RESULTS
Eleven studies fully met the review inclusion criteria, ten were quantitative design studies and only one was a qualitative design study. No mixed method design study was included in the review. All were published after 1989, seven were conducted in the USA and four in the UK. Results from five good to low quality randomised controlled trials (RCTs), all conducted before 1990, did not illustrate the efficacy of the clinic in reducing preterm birth. Whereas results from more recent low quality cohort studies showed some positive neonatal outcomes. Themes from one good quality qualitative study reflected on the emotional and psychological need to reduce anxiety and stress of women referred to such a clinic. Women expressed their negative emotional responses at being labelled as high risk and positive responses to being assessed and treated in the clinic. Women also reported that their partners were struggling to cope emotionally.

CONCLUSIONS
Findings from this review were mixed. Evidence from cohort studies indicated a specialist clinic may be a means of predicting or preventing preterm birth. Testing this in a randomised controlled trial is desirable, though may be hard to achieve due to the growing focus of such clinics on managing women at high risk of preterm birth. Ongoing research has to recognize women's experiences and perceptions of such a clinic. Further clarification of the optimal referral route and a clear and standardized management and cost economic evaluation plan are also required. Fathers support and experience of PTB clinics should also be included in further research.

D005260:Female
D014943:Global Health
D006801:Humans
D007231:Infant, Newborn
D054238:Perinatal Mortality
D011247:Pregnancy
D011256:Pregnancy Outcome
D047928:Premature Birth
D011295:Prenatal Care
D036301:Qualitative Research

Preterm birth
Systematic review
High risk pregnancy
Preterm birth clinic


Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against Yersinia pestis Infection in a Bubonic Plague Model.

Abstract: Plague is a zoonotic disease that is caused by Yersinia pestis. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by Y. pestis, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antigen was made to assess binding sites, avidities, and affinities. Anti-V mAbs were screened for their efficacy in a murine model of plague. Antigen-binding sites of protective V mAbs were determined with a linear peptide library, V-antigen fragment, competitive binding, and surface plasmon resonance. The avidities to the V-antigen was determined by ELISA, and affinities of the mAbs to the V-antigen were determined by surface plasmon resonance. The most protective mAb 7.3 bound to a unique conformational site on the V-antigen, while a less protective mAb bound to a different conformational site located on the same V-antigen fragment as mAb 7.3. The avidity of mAb 7.3 for the V-antigen was neither the strongest overall nor did it have the highest affinity for the V-antigen. The binding site of the most protective mAb was critical in its ability to protect against a lethal plague challenge.

Amemiya|Kei|K|
Dankmeyer|Jennifer L|JL|
Keasey|Sarah L|SL|
Trevino|Sylvia R|SR|
Wormald|Michael M|MM|
Halasohoris|Stephanie A|SA|
Ribot|Wilson J|WJ|
Fetterer|David P|DP|
Cote|Christopher K|CK|
Worsham|Patricia L|PL|
Adamovicz|Jeffrey J|JJ|
Ulrich|Robert G|RG|

binding sites
monoclonal antibodies
avidities
affinities
passive protection
Yersinia pestis
plague


Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease.

Abstract: Ca2+ homeostasis is essential for multiple neuronal functions and thus, Ca2+ dyshomeostasis can lead to widespread impairment of cellular and synaptic signaling, subsequently contributing to dementia and Alzheimer's disease (AD). While numerous studies implicate Ca2+ mishandling in AD, the cellular basis for loss of cognitive function remains under investigation. The process of synaptic degradation and degeneration in AD is slow, and constitutes a series of maladaptive processes each contributing to a further destabilization of the Ca2+ homeostatic machinery. Ca2+ homeostasis involves precise maintenance of cytosolic Ca2+ levels, despite extracellular influx via multiple synaptic Ca2+ channels, and intracellular release via organelles such as the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) and IP3R, lysosomes via transient receptor potential mucolipin channel (TRPML) and two pore channel (TPC), and mitochondria via the permeability transition pore (PTP). Furthermore, functioning of these organelles relies upon regulated inter-organelle Ca2+ handling, with aberrant signaling resulting in synaptic dysfunction, protein mishandling, oxidative stress and defective bioenergetics, among other consequences consistent with AD. With few effective treatments currently available to mitigate AD, the past few years have seen a significant increase in the study of synaptic and cellular mechanisms as drivers of AD, including Ca2+ dyshomeostasis. Here, we detail some key findings and discuss implications for future AD treatments.

D019837:Ryanodine Receptor Calcium Release Channel

synaptic
lysosome
mitochondria
autophagy
calcium
glutamate
nicotinic receptors


Attendance in Recreational Groups for Persons With Dementia: The Impact of Stimulus and Environmental Factors.

Abstract:
OBJECTIVES
Participation in group activities can benefit persons with dementia, alleviating boredom, improving affect, maintaining function, and decreasing problematic behaviors.

METHODS
We describe patterns of attendance of residents with dementia at nursing home activity groups and investigate stimulus and environmental factors that may affect attendance.

RESULTS
Residents participated in 60.8% of the activities, with reasons for nonattendance including refusal (9.7%), not being on the unit (7.8%), being asleep (6.8%), and being involved in activities of daily living and other activities (8.3%). On average, 3.5 other residents not recruited for the study chose to participate in each group session. Group attendance was significantly related to group topic.

IMPLICATION
The need for activities was evident by the attendance of both invited and other residents. Understanding the factors that affect attendance is the first step toward developing procedures to maximize participation in activities in order to decrease loneliness and boredom in this population.

group activities
boredom
nursing homes
social engagement


High Capacitive Storage Performance of Sulfur and Nitrogen Codoped Mesoporous Graphene.

Abstract: Mesoporous graphene is synthesized based on the chemical vapor deposition methodology by using heavy MgO flakes as substrates in a fluidized-bed reactor. Subsequently, sulfur and nitrogen coincorporation into graphene frameworks is realized by the reaction between carbon atoms and thiourea molecules. The as-obtained sulfur and nitrogen codoped mesoporous graphene (SNMG) exhibits remarkable capacitive energy-storage behavior, as a result of well-developed pore channels, in terms of that in a symmetric supercapacitor and lithium-ion hybrid capacitor (LIHC). The ultrahigh durability of the SNMG/SNMG symmetric supercapacitor is demonstrated by long-term cycling, for which no capacitance decay is found after 20 000 cycles. A LIHC constructed from commercial Li4 Ti5 O12 (LTO) as the anode and SNMG as the cathode is capable of delivering much enhanced lithium-storage ability and better rate capability than that of activated carbon (AC)/LTO LIHC. Moreover, SNMG/LTO LIHC exhibits maximum energy and power densities of 86.2 Wh kg-1 and 7443 W kg-1 and maintains 87 % capacitance retention after 2000 cycles.

graphene
supercapacitors
doping
electrochemistry
mesoporous materials