Relationship between perceived organizational justice and moral distress in intensive care unit nurses.

Abstract:
BACKGROUND:
The nature of the nursing profession pays more attention to ethics of healthcare than its therapeutic dimension. One of the prevalent moral issues in this profession is moral distress. Moral distress appears more in intensive care units due to the widespread need for moral decision-making regarding treatment and care in emergency situations. In this connection, organizational justice is of high importance and, as a significant motivational tool, leaves important impacts upon attitude and behavior of personnel.

AIM/OBJECTIVE:
This study aimed at investigation of the relationship between perceived organizational justice and moral distress in intensive care unit nurses.

RESEARCH DESIGN:
This is a descriptive-correlational research which examined the relationship between perceived organizational justice and moral distress in intensive care unit nurses.

PARTICIPANTS AND RESEARCH CONTEXT:
A total of 284 intensive care unit nurses were selected via census sampling. The data were collected through questionnaires and then were analyzed via SPSS-20 using Pearson and Spearman correlation tests.

ETHICAL CONSIDERATIONS:
This study was approved by the Committee of Ethics in Medical Research. Completion of informed consent form, guarantee of the confidentiality of information, explanation on purposes of the research, and voluntary participation in the study were moral considerations observed in this study.

FINDINGS:
There was a statistically significant negative correlation between the total perceived organizational justice and the total moral distress (p = 0.024, r = -0.137) and also between "procedural and interactional justice and errors" and "not respecting the ethics principles." Meanwhile, no relationship was found by the findings between distributive justice and dimensions of moral distress.

CONCLUSION:
According to the results of the study, there was a reverse significant relationship between moral distress and perceived organizational justice; therefore, the head nurses are expected to contribute to reduce moral distress and to increase perceived organizational justice in nurses.

Haghighinezhad|Ghazaleh|G| Atashzadeh-Shoorideh|Foroozan|F| Ashktorab|Tahereh|T| Mohtashami|Jamileh|J| Barkhordari-Sharifabad|Maasoumeh|M|

perceived organizational justice
moral distress
intensive care unit nurses
interactional justice
Distributive justice
procedural justice


Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats.

Abstract: Three experiments were done to better assess the gastrointestinal (GI) site(s) of action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI) were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric artery (CMA, supplying small and all of the large intestine except the rectum), femoral artery (FA, control) or portal vein (PV, control). Second, infusion of 0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R) antagonist exendin-4(3-39) via the same routes. Third, the regional distribution of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1 reduced first MS relative to saline, with the CMA route more effective than the others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more effective than the CA route. CMA exendin-4 (3-39) infusion reduced the effect of CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the small and part of the large intestine, plays the leading role.

Williams|Kasey E|KE|
Washington|Martha C|MC|
Johnson-Rouse|Tanisha|T|
Johnson|Ruth E|RE|
Freeman|Corren|C|
Reed|Chris|C|
Heath|John|J|
Sayegh|Ayman I|AI|

Intermeal interval
GLP-1
Satiety ratio
Celiac artery
Portal vein


Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.

Abstract:
OBJECTIVE
To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism.

METHODS
ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1β, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1β, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB.

RESULTS
Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation.

CONCLUSIONS
Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.

Junyuan|Zheng|Z| Hui|Xu|X| Chunlan|Huang|H| Junjie|Fan|F| Qixiang|Mei|M| Yingying|Lu|L| Lihong|Lou|L| Xingpeng|Wang|W| Yue|Zeng|Z|

D053594:Myeloid Differentiation Factor 88

D048051:p38 Mitogen-Activated Protein Kinases

Quercetin
Acute necrotizing pancreatitis
Ileum
Endoplasmic reticulum stress
TLR4/MyD88/p38 MAPK pathway


Microbiological and molecular epidemiological analyses of community-associated methicillin-resistant Staphylococcus aureus at a tertiary care hospital in Japan.

Abstract: Molecular characterization of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is generally conducted referred to staphylococcal cassette chromosome mec (SCCmec) type IV or V. CA-MRSA is now a cause of concern since such strains have been isolated not only from individuals in a community but also from patients in healthcare settings. The aim of this study was to analyze microbiological and molecular epidemiological features of CA-MRSA strains at a Japanese tertiary care hospital using PCR based-open reading frame typing (POT). This technique allows for molecular classification into CA-MRSA (POT-CA) and hospital-associated (HA-) MRSA (POT-HA) with clonal discrimination. Clinical MRSA isolates obtained from consecutive patients between October 1, 2012 and September 30, 2013 at the hospital were analyzed in combination with the clinical definition for CA-MRSA by the Centers for Disease Control and Prevention and POT. Of 219 isolates (76 clonal groups), 64 (29.3%) were clinical-HA/POT-CA isolates (22 clonal groups). Some clones of them accumulated in this hospital and might be involved in nosocomial transmission. Virulent factors of the isolates were analyzed, and only one (1.6%) Panton-Valentine leukocidin gene positive isolate but no arginine catabolic mobile element genes positive isolate were found in clinical-HA/POT-CA. Additionally, clinical-HA/POT-CA isolates showed higher antimicrobial susceptibility than clinical-HA/POT-HA, especially to minocycline, doxycycline, and amikacin. The most frequent genotype of molecular CA-MRSA was multi-locus sequence type 5-SCCmecIV, previously not detected in Japan. Although CA-MRSA at this hospital showed low virulence and higher antimicrobial susceptibility, the risk of nosocomial infection from them should be recognized, requiring stricter infection control measures.

Inomata|Shinya|S| Yano|Hisakazu|H| Tokuda|Koichi|K| Kanamori|Hajime|H| Endo|Shiro|S| Ishizawa|Chiyuki|C| Ogawa|Miho|M| Ichimura|Sadahiro|S| Shimojima|Masahiro|M| Kakuta|Risako|R| Ozawa|Daiki|D| Aoyagi|Tetsuji|T| Gu|Yoshiaki|Y| Hatta|Masumitsu|M| Oshima|Kengo|K| Nakashima|Kazutoshi|K| Kaku|Mitsuo|M|

PCR based-open reading frame (ORF) typing (POT)


Effect of the volatile anesthetic agent isoflurane on lateral diffusion of cell membrane proteins.

Abstract: The volatile anesthetic isoflurane (ISO) has previously been shown to increase the fluidity of artificial lipid membranes, but very few studies have used biological cell membranes. Therefore, to investigate whether ISO affects the mobility of membrane proteins, fluorescence-labeled transferrin receptor (TfR) and glycosylphosphatidylinositol (GPI)-anchored protein were expressed in human embryonic kidney 293T cells and neural cells and lateral diffusion was examined using fluorescence recovery after photobleaching. Lateral diffusion of the TfR increased with ISO treatment. On the other hand, there was no effect on GPI-anchored protein. We also used GC/MS to confirm that there was no change in the concentration of ISO due to vaporization during measurement. These results suggest that ISO affects the mobility of transmembrane protein molecules in living cells.

Ono|Junichiro|J| Fushimi|Satoko|S| Suzuki|Shingo|S| Ameno|Kiyoshi|K| Kinoshita|Hiroshi|H| Shirakami|Gotaro|G| Kabayama|Kazuya|K|

volatile anesthetic agent
live cell imaging
membrane fluidity


NADPH oxidase mediates TNF-α-evoked in vitro brain barrier dysfunction: roles of apoptosis and time.

Abstract: The pro-inflammatory cytokine TNF-α severely perturbs the integrity of the blood-brain barrier (BBB). This study explored the specific roles of NADPH oxidase and associated downstream effectors by using human brain microvascular endothelial cells (HBMECs) and human astrocytes (HAs), the key components of BBB, alone or in co-cultures to mimic human BBB. Exposure to TNF-α (6h) impaired BBB integrity as evidenced by marked decreases in transendothelial electrical resistance and concurrent increases in paracellular flux which appeared to subside with time (24h). Increased barrier dysfunction concurred with increases in endothelial NADPH oxidase activity, O2(-) production, actin stress fibre formation, MMP-2/9 activities and concomitant decreases in antioxidant (CuZn-SOD and catalase) and tight junction (claudin-5 and occludin) protein expressions. Conversely, TNF-α did not affect astrocytic MMP activities and antioxidant enzyme expressions. Unlike BBB damage, rates of HBMEC and HA apoptosis increased by time. Suppression of NADPH oxidase by apocynin or diphenyleneiodonium prevented TNF-α-evoked morphological changes and apoptosis, attenuated endothelial MMP activity and helped retain usual tight junction protein expression and barrier function. In conclusion, HBMECs constitute the main source of oxidative stress and basement-membrane degrading endopeptidases in inflammatory conditions associated with excessive release of TNF-α where targeting NADPH oxidase may prove extremely beneficial in maintaining proper barrier activity through prevention of cytoskeletal and tight junction reorganisations.

D000098:Acetophenones
D017209:Apoptosis
D001253:Astrocytes
D002374:Catalase
D018920:Coculture Techniques
D045304:Cytochromes c
D017097:Electric Impedance
D042783:Endothelial Cells
D004791:Enzyme Inhibitors
D005786:Gene Expression Regulation
D006801:Humans
D066298:In Vitro Techniques
D020778:Matrix Metalloproteinase 2
D020780:Matrix Metalloproteinase 9
D019255:NADPH Oxidases
D009861:Onium Compounds
D010100:Oxygen
D017382:Reactive Oxygen Species
D013482:Superoxide Dismutase
D013997:Time Factors
D014409:Tumor Necrosis Factor-alpha

NADPH oxidase
TNF-α
MMP
Blood–brain barrier
Cytoskeleton


Pancreas-sparing duodenectomy with regional lymph node dissection for early-stage ampullary carcinoma: A case control study using propensity scoring methods.

Abstract:
AIM
To investigate the outcomes of pancreas-sparing duodenectomy (PSD) with regional lymph node dissection vs pancreaticoduodenectomy (PD).

METHODS
Between August 2001 and June 2014, 228 patients with early-stage ampullary carcinoma (Amp Ca) underwent surgical treatment (PD, n = 159; PSD with regional lymph node dissection, n = 69). The patients were divided into two groups: the PD group and the PSD group. Propensity scoring methods were used to select patients with similar disease statuses. A total of 138 matched cases, with 69 patients in each group, were included in the final analysis.

RESULTS
The median operative time was shorter among the patients in the PSD group (435 min) compared with those in the PD group (481 min, P = 0.048). The median blood loss in the PSD group was significantly less than that in the PD group. The median length of hospital stay was shorter for patients in the PSD group vs the PD group. The incidence of pancreatic fistula was higher among patients in the PD group vs the PSD group. The 1-, 3-, and 5-year overall survival and disease-free survival rates for patients in the PSD group were 83%, 70%, 44% and 73%, 61%, 39%, respectively, and these values were not different than compared with those in the PD group (P = 0.625).

CONCLUSION
PSD with regional lymph node dissection presents an acceptable morbidity in addition to its advantages over PD. PSD may be a safe and feasible alternative to PD in the treatment of early-stage Amp Ca.

Liu|Bin|B| Li|Jing|J| Zhang|Yong-Jiu|YJ| Yan|Lu-Nan|LN| You|Sheng-Yi|SY| Lau|Wan-Yee|WY| Sun|Hao-Ran|HR| Yan|Shi-Yan|SY| Wang|Zhi-Qiang|ZQ|

D013505:Digestive System Surgical Procedures

Ampullary carcinoma
Propensity scoring methods
Surgical treatments
Early stage
Prognosis


Biomarkers versus traditional risk factors to predict cardiovascular events in very old adults: cross-validated prospective cohort study.

Abstract:
OBJECTIVES
To test new cardiovascular (CV) risk models in very old adults with and without a history of CV disease (CVD), based on traditional risk factors and biomarkers.

DESIGN
Cross-validated prospective cohort study. The models were tested in the BELFRAIL Study and externally validated in the Leiden 85-plus Study.

SETTING
General practice, Belgium and The Netherlands.

PARTICIPANTS
The BELFRAIL cohort consisted of 266 patients aged 80 years or older without a history of CVD and 260 with a history of CVD. The Leiden 85-plus Study consisted of 264 patients aged 85 years without a history of CVD and 282 with a history of CVD.

OUTCOME MEASURES
The model with traditional risk factors and biomarkers, as well as the model using only biomarkers, was compared with the model with only traditional risk factors to predict 3-year CV morbidity and mortality. A competing-risk analysis was performed, and the continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI) and net benefit were used to compare the predictive value of the different models.

RESULTS
Traditional risk factors poorly predicted CV mortality and morbidity. In participants without a history of CVD, adding N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) improved the prediction (NRI 0.56 (95% CI 0.16 to 0.99) and relative IDI 4.01 (95% CI 2.19 to 6.28)). In participants with a history of CVD, the NRI with the addition of NT-pro-BNP and high-sensitivity C reactive protein was 0.38 (95% CI 0.09 to 0.70), and the relative IDI was 0.53 (95% CI 0.23 to 0.90). Moreover, in participants without a history of CVD, NT-pro-BNP performed well as a stand-alone predictor (NRI 0.32 (95% CI -0.12 to 0.74) and relative IDI 3.44 (95% CI 1.56 to 6.09)).

CONCLUSIONS
This study tested new risk models to predict CV morbidity and mortality in very old adults. Especially, NT-pro-BNP showed a strong added predictive value. This opens perspectives for clinicians who are in need of an easily applicable strategy for CV risk prediction in very old adults.

Vaes|Bert|B|0000-0001-5244-1930
Indestege|Paulien|P|
Serneels|Tinne|T|
Hegendörfer|Eralda|E|
van Peet|Petra G|PG|
Poortvliet|Rosalinde K E|RKE|
Wallemacq|Pierre|P|
Gussekloo|Jacobijn|J|
Degryse|Jan|J|

cardiac epidemiology
epidemiology
geriatric medicine


Investigating Relationships Between Drinking Venues, Drinking Companions, and Corporal Punishment of Children.

Abstract: Limited evidence suggests that how much a parent drinks in a particular venue, such as a bar, restaurant, or a friend's home, is associated with use of corporal punishment. However, these relationships could differ depending on their drinking companions (e.g., spouse or friends). In this study, weighted zero-inflated Poisson models were used to examine whether the relationships between venue-specific drinking frequency, heavier drinking, and corporal punishment are moderated by drinking companions in a mixed-mode sample of parents ( n = 1,599). The relationships between drinking frequency, heavier drinking, and corporal punishment varied by drinking companions, with some combinations being protective and others conferring risk. While most alcohol screening tools focus on individual alcohol use, more nuanced assessment examining where and with whom parents are drinking could be helpful in understanding risk of physical discipline.

Price Wolf|Jennifer|J|
Dellor|Elinam D|ED|

drinking venues
drinking companions
corporal punishment
alcohol


Glycosides from Buddleja officinalis with their protective effects on photoreceptor cells in light-damaged mouse retinas.

Abstract: A new phenylethanoid, hebitol IV (1), along with fifteen known glycosides (2-16), were isolated from water extract of the flower buds of Buddleja officinalis. Their structures were elucidated on the basis of 1 D-NMR, 2 D-NMR and MS data. Molecular docking showed the potential activities of the natural products against VEGFR-2. Bioassay results revealed that the compounds 10 and 14 exhibited strong inhibitory activity against VEGFR-2 with IC50 values of 0.51 and 0.32 μM, respectively. Moreover, the potential retinal protective effects of 10 and 14 were then investigated in the mouse model featuring bright light-induced retinal degeneration. The results demonstrated remarkable photoreceptor protective activities of 10 and 14 in vivo.

glycosides
Buddleja officinalis
photoreceptor protective activity
Loganiaceae
VEGFR-2 inhibitory activity


Origin and diversification of ECERIFERUM1 (CER1) and ECERIFERUM3 (CER3) genes in land plants and phylogenetic evidence that the ancestral CER1/3 gene resulted from the fusion of pre-existing domains.

Abstract: ECERIFERUM1 (CER1) and ECERIFERUM3 (CER3) are key genes in synthesis of alkanes, a major component of cuticular waxes in land plants. The genes share extensive similarity, including the N-terminal (ERG3/FAH) and C-terminal (WAX2) domains. This study, traces the origin, evolutionary history, phylogenetic relationships and variation in copy number of the two genes within and beyond the Viridiplantae (green plants). Protein homologs of both CER1 and CER3 were identified across most Embryophyta (land plants), a single homolog (CER1/3) in charophytes and prasinophytes, and none in the other green, red or brown algae. Ancestral state reconstructions in 100 sequenced Archaeplastida using presence/absence of CER1/3 family genes revealed that the CER1/3 gene probably originated in the common ancestor of Viridiplantae. Phylogenetic analysis of CER1 and CER3 protein sequences from 146 plant species strongly suggests that the two genes originated by duplication of CER1/3 in the ancestral embryophyte. The evolution of CER1 and CER3 genes involved differential divergence of the two domains. Outside Embryophyta, CER1/3 similar sequences identified in diatoms and a cryptophyte, were the closest relatives of the CER1/3 family proteins. Proteins harbouring WAX2-wxAR (WAX2 associated region) similar regions were identified in proteins of bacteria, Archaea, cryptophytes, dinoflagellates and Stramenopiles. The independent existence of both ERG3/FAH and WAX2-wxAR domains in diverse lineages strongly points to the origin of CER1/3 gene in green plants by the fusion of pre-existing domains.

D018506:Gene Expression Regulation, Plant

Alkanes
Cuticular waxes
Evolution
CER1/CER3 gene
Gene fusion
WAX2 domain


The Macroalgal Holobiont in a Changing Sea.

Abstract: When studying the effects of climate change on eukaryotic organisms we often oversee a major ecological process: the interaction with microbes. Eukaryotic hosts and microbes form functional units, termed holobionts, where microbes play crucial roles in host functioning. Environmental stress may disturb these complex mutualistic relations. Macroalgae form the foundation of coastal ecosystems worldwide and provide important ecosystem services - services they could likely not provide without their microbial associates. Still, today we do not know how environmental stress will affect the macroalgal holobiont in an increasingly changing ocean. In this review, we provide a conceptual framework that contributes to understanding the different levels at which the holobiont and environment interact, and we suggest a manipulative experimental approach as a guideline for future research.

van der Loos|Luna M|LM|
Eriksson|Britas Klemens|BK|
Falcão Salles|Joana|J|

holobiont
climate change
macroalgae
microbiome
microbiota


Resurrection of antibiotics that methicillin-resistant Staphylococcus aureus resists by silver-doped bioactive glass-ceramic microparticles.

Abstract: This work describes a novel strategy to combat methicillin-resistant Staphylococcus aureus (MRSA) via the reactivation of inert antibiotics. This strategy exploits a multifunctional system consisting of bioactive glass-ceramic microparticles with antibacterial properties combined with various antibiotics to kill MRSA. Specifically, sol-gel derived silver-doped bioactive glass-ceramic microparticles (Ag-BG) combined with antibiotics that MRSA resists such as oxacillin or fosfomycin, significantly decreased the viability of MRSA. Ag-BG also potentiated the activity of vancomycin on static bacteria, which are typically resistant to this antibiotic. Notably, the synergistic activity is restricted to cell-envelope acting antibiotics as Ag-BG supplementation did not increase the efficacy of gentamicin. Bacteria viability assays and electron microscopy images demonstrate that Ag-BG synergizes to restore antibacterial activity to antibiotics that MRSA resists. The low cytotoxicity previously studied against oral bacteria, together with the known regenerative properties presented in previous studies, and the unique antibacterial properties observed in this work when they are combined with antibiotics, make this multifunctional system a promising approach for healing infected tissue. STATEMENT OF SIGNIFICANCE: This study addresses a very significant issue in the field of antibiotic resistance presenting an innovative way to clear MRSA, by utilizing bioactive glass-ceramic microparticles in combination with antibiotics. Multifunctional glass-ceramic microparticles doped with silver ions (Ag-BG) have been previously observed to exhibit bioactive and antibacterial properties. In this study Ag-BG microparticles were observed to synergize with antibiotics restoring their sensitivity against MRSA. This research work presents a novel approach to resurrect ineffective antibiotics and render them effective against MRSA. Cytotoxicity to eukaryotic cells is not anticipated, as it has been previously observed that these microparticles can trigger hard and soft dental tissue regeneration, when they are utilized in certain concentrations. This study opens a new avenue in the treatment of multidrug resistance bacteria.

Pajares-Chamorro|Natalia|N|
Shook|John|J|
Hammer|Neal D|ND|
Chatzistavrou|Xanthippi|X|

Silver-doped bioactive glass–ceramic microparticles


Sexual and Gender Minority Health Research at the National Institutes of Health.

Abstract: Sexual and gender minority (SGM) populations experience many diseases and conditions at higher prevalence rates than their non-SGM counterparts. In 2009, the National Institutes of Health (NIH) commissioned an Institute of Medicine (IOM) report to better understand the health of SGM populations. Following the release of the report, NIH, including the National Cancer Institute (NCI), initiated new activities, and continued and expanded its existing efforts to advance the health of SGM individuals. Such efforts include various forms of outreach to solicit feedback, support of extramural researchers, analysis of the research portfolio to identify areas of opportunity, and the development of the NIH Strategic Plan for SGM Health Research.

sexual and gender minority
National Institutes of Health (NIH)
strategic plan
biomedical research


A Phase-Locked Loop Epilepsy Network Emulator.

Abstract: Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control.

Watson|P D|PD|
Horecka|K M|KM|
Cohen|N J|NJ|
Ratnam|R|R|

electrocorticography
approximate entropy
epilepsy emulation
neural network
phase locked loop


Drug-induced fatal arrhythmias: Acquired long QT and Brugada syndromes.

Abstract: Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc. Among these, long QT and Brugada syndromes are the most extensively studied, and drugs cause a phenocopy of these two diseases. To date, more than 10 different genes have been reported to be responsible for each syndrome. More recently, it was recognized that long QT syndrome can be latent, even in the presence of an unequivocally pathogenic mutation (silent mutation carrier). Co-existence of other pathological conditions in these silent mutation carriers may trigger a malignant form of ventricular arrhythmia, the so called torsade de pointes (TdP) that is most commonly brought about by drugs. In analogy to the drug-induced long QT syndrome, Brugada type 1 ECG can also be induced or unmasked by a wide variety of drugs and pathological conditions; so physicians may encounter patients with a latent form of Brugada syndrome. Of particular note, Brugada syndrome is frequently associated with atrial fibrillation whose therapeutic agents such as Vaughan Williams class IC drugs can unmask the dormant and asymptomatic Brugada syndrome. This review describes two types of drug-induced arrhythmias: the long QT and Brugada syndromes.

Turker|Isik|I| Ai|Tomohiko|T| Itoh|Hideki|H| Horie|Minoru|M|

Brugada syndrome
Ion channelopathy
Long QT syndrome
Silent mutation carrier
Drug-induced arrhythmias
Genetic variants


Effectiveness of mouth self-examination for screening of oral premalignant/malignant diseases in tribal population of Dehradun district.

Abstract:
Background
Mouth self-examination (MSE) is shown as a speedy, economical, and effortless method of oral cancer detection. As previous studies were conducted in population with high literacy, the current survey was performed to explore the usefulness of MSE for finding the oral cancerous precancerous lesions in indigenous low literate population of Dehradun district.

Materials and Methods
It is a cross-sectional survey which was done on the Buksa tribal communities in Dehradun district, India. Out of seven tehsils in the district, two were randomly selected, from which two villages were selected. Individuals belonging to Buksa tribe above the age of 18 years were gathered in commonplace. A total of 539 people who gave their consent were enrolled for study. Using a questionnaire, information regarding sociodemographic details, history of risk factors, and practice of MSE was obtained by interview method, followed by recording oral findings by a single expert. Later, performance of MSE was taught to the participants and they were asked to record the same. Descriptive analysis and Chi-square test were applied wherever applicable and significance level was kept at below 0.05.

Results
It was observed that out of 539 participants, 220 (40.8%) practiced MSE and 319 (59.2%) have never practiced MSE. Further analysis showed that a total of 39% males and 42.7% females had MSE habits and this difference was not statistically significant (P > 0.05). In totality, the prevalence of oral lesions identified by health worker was 213 (39.5%), whereas MSE showed only prevalence rate of 69 (12.8%). MSE had low sensitivity (24.6%), whereas high specificity (87.4%) for all the lesions and most sensitive in detecting ulcers (72.7%), and highest specificity in identifying red lesions (99.2%).

Conclusion
Even though the sensitivity of MSE for detecting oral premalignant/malignant lesions was low, specificity was very high. Frequent efforts to educate and encourage public on MSE may enhance efficacy and compliance.

Shah|Amit|A|
Bhushan|Bharat|B|
Akhtar|Saifullah|S|
Singh|Pankaj Kumar|PK|
Garg|Madhur|M|
Gupta|Mayank|M|

self-examination
oral cancer
Indigenous population


Association between one-time prostate-specific antigen (PSA) test with free/total PSA ratio and prostate cancer mortality: A 30-year prospective cohort study.

Abstract:
OBJECTIVES
To explore if there is a long-term association between baseline prostate-specific antigen (PSA), including free/total PSA ratio and long-term (30-year) risk for prostate cancer death.

SUBJECTS AND METHODS
In all, 1782 men were screened for prostate cancer through PSA analysis. Some years later, frozen plasma samples were used to calculate the ratio of free to total PSA (f/t PSA). At 30-year follow-up, baseline PSA and f/t PSA were compared with recent data extracts from the Swedish Cause of Death Registry and Swedish Cancer Registry. PSA values and f/t PSA values were treated as continuous variables in a multivariable analysis and also stratified according to their distribution and useful clinical thresholds.

RESULTS
Risk of death from prostate cancer after 30 years of follow-up was significantly increased with a higher baseline PSA level, with the hazard ratio being 1.04 (95% confidence interval 1.03-1.09) per increase of one unit of PSA. Adding f/t PSA increased the model's ability to discriminate (concordance index 0.84-0.88). Men with PSA levels <1.0 ng/mL had a very low long-term risk of prostate cancer death (1.2% risk). An f/t PSA ≥ 0.25 extended the low-risk range to PSA < 2.0 ng/mL (1.5% risk).

CONCLUSION
Prostate-specific antigen testing can be carried out less frequently or can be discontinued in men aged 55-70 years if their PSA levels are <2.0 ng/mL and the f/t PSA is ≥0.25.

D000368:Aged
D015331:Cohort Studies
D055088:Early Detection of Cancer
D006801:Humans
D008297:Male
D008875:Middle Aged
D011446:Prospective Studies
D017430:Prostate-Specific Antigen
D011471:Prostatic Neoplasms
D018570:Risk Assessment
D013997:Time Factors

prostate-specific antigen
prostate cancer
mortality
screening
#PCSM
#ProstateCancer
#uroonc
prognosis


A novel Siglec-F+ neutrophil subset in the mouse nasal mucosa exhibits an activated phenotype and is increased in an allergic rhinitis model.

Abstract: Neutrophils are important phagocytic cells for host defense against pathogens. They are rapidly recruited to the site of infection, release antimicrobial peptides and cytokines, and engulf and kill microbes. Neutrophils also accumulate in allergic inflammatory sites. Here we characterized neutrophil accumulation in the nasal mucosa using a mouse model of allergic rhinitis, in which mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and then challenged by intranasal administration of OVA or PBS. In the nasal mucosa of both PBS- and OVA-challenged mice, we found a cell subset expressing the eosinophil marker Siglec-F in the Ly-6G+ neutrophil population. Morphological analysis of the sorted Ly-6G+Siglec-F+ cells revealed that they were devoid of eosinophilic granules in the cytosol and were apparently neutrophils, but compared to conventional Ly-6G+Siglec-F- neutrophils, they had a more lobulated, "botryoid" nucleus. Siglec-F+ neutrophils were barely found in the nasopharynx-associated lymphoid tissue, cervical lymph nodes, the spleen, or blood. Both Siglec-F+ neutrophils and conventional neutrophils showed increased numbers in the nasal mucosa of OVA-challenged mice. Compared to conventional Siglec-F- neutrophils, Siglec-F+ neutrophils exhibited an activated phenotype and enhanced effector functions. Taken together, our findings identify Siglec-F+ neutrophils as a novel neutrophil subset with an activated phenotype that resides specifically in the nasal mucosa.

Matsui|Makoto|M| Nagakubo|Daisuke|D| Satooka|Hiroki|H| Hirata|Takako|T|

D063265:Sialic Acid Binding Immunoglobulin-like Lectins

Neutrophil subset
Nasal mucosa
Allergic rhinitis
Siglec-F
Inflammation


Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice?

Abstract: There is a new generation of antiobesity drugs in development or just arriving on the scene. First, setmelanotide has been approved for three of the ultrarare genetic conditions that cause obesity-pro-opiomelanocortin deficiency, proprotein convertase subtilisin and kexin type 1 (an important enzyme in the melanocortin pathway) and leptin receptor deficiency. Setmelanotide marks the first in a personalized medicine approach to obesity. Second, semaglutide 2.4 mg once weekly has been submitted to regulators in the United States and the European Union for approval for patients with obesity (body mass index [BMI] ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) and at least one weight related comorbidity. This drug has been studied in five phase 3 clinical trials, four discussed herein: semaglutide produces roughly twice as much weight loss as we have seen in older antiobesity medications. Semaglutide is already in use for treatment of diabetes and, as a glucagon-like peptide 1 (GLP-1) receptor analog, is part of a class of drugs used widely in diabetes. Tirzepatide, a glucose-insulin peptide and GLP-1 dual agonist is in phase 3 study for obesity management, and bimagrumab is a new agent in phase 2 with a unique mechanism of action; they are generating much interest. The purpose of this narrative review is lay the groundwork for a discussion of the clinical impact of these new medications on the clinical practice of obesity. Further, these developments shall be used to launch a speculation of what is likely to be their impact on the future of obesity pharmacotherapy.

Setmelanotide
Semaglutide
Tirzepatide
Bimagrumab
Anti-obesity agents
Anti-obesity drugs
Weight loss agents


Clinical significance of reduced expression of lncRNA TUG1 in the peripheral blood of systemic lupus erythematosus patients.

Abstract:
OBJECTIVE
To investigate the expression and clinical significance of long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) in the peripheral blood of systemic lupus erythematosus (SLE) patients.

METHODS
With the peripheral blood mononuclear cells (PBMCs: T-cells, B-cells and monocytes) collected from SLE patients and healthy controls, TUG1 expression was determined to identify the correlation with the clinicopathological features of SLE patients. Thereby, the diagnostic value of TUG1 expression in diagnosis of SLE was evaluated by receiver operating characteristic (ROC) curve analysis.

RESULTS
As compared to healthy controls, SLE patients manifested a lower expression of TUG1 in PBMCs, which was further decreased in SLE patients with lupus nephritis (P < .05). The lowest level of TUG1 was found in monocytes, rather than T-cells or B-cells (P < .05). Negative correlations were identified between TUG1 levels and SLE Disease Activity Index score (r = -.904, P < .001), erythrocyte sedimentation rate (r = -.779, P < .001), disease duration (r = -.503, P < .001) and 24-hour urinary protein (r = -.807, P < .001). Complement C3 levels were positively associated with TUG1 expression (r = .817, P < .001). In addition, the area under the ROC curve of diagnostic efficiency for SLE based on TUG1 was 0.982, and 0.930 for SLE with lupus nephritis.

CONCLUSIONS
The levels of lncRNA TUG1 was markedly lower in the SLE patients, which was more obvious in SLE patients with lupus nephritis, and thus, it could be a promising clinical diagnostic tool for SLE patients or SLE patients with lupus nephritis.

lncRNA
TUG1
systemic lupus erythematosus
monocytes
lupus nephritis


Intelligence in young adulthood and alcohol use disorders in a prospective cohort study of Danish men: the role of psychiatric disorders and parental psychiatric history.

Abstract:
OBJECTIVES
The aims were to estimate the association between intelligence measured in young adulthood and risk of alcohol use disorders (AUD) in men and to investigate the potential modification of this association by psychiatric disorders, parental AUD and parental psychiatric disorders.

DESIGN
Prospective cohort study based on a linkage of intelligence test scores from draft board examinations and register data on AUD diagnoses during 36 years of follow-up.

SETTING
Denmark.

PARTICIPANTS
3287 Danish men from the Copenhagen Perinatal Cohort (born 1959-1961) who appeared before the draft board at a mean age of 18.7 years.

PRIMARY OUTCOME MEASURE
First registration with AUD during follow-up was the primary outcome. Information on AUD was based on diagnoses retrieved from national hospital and outpatient treatment registers, defined according to the International Classification of Diseases.

RESULTS
361 (11.0%) men were registered with AUD during follow-up. Low intelligence scores were associated with increased odds of AUD adjusting for parental AUD, parental psychiatric disorders, maternal smoking during pregnancy, birth weight, maternal age at birth, parity and childhood socioeconomic position (OR per SD decrease in intelligence=1.69, 95% CI 1.49 to 1.92). Separate analyses indicated significant interaction (p<0.001) between intelligence and psychiatric disorders. The adjusted OR per SD decrease in intelligence score was 2.04 (95% CI 1.67 to 2.49) in men without other psychiatric disorders whereas the OR was 1.21 (95% CI 1.01 to 1.46) in men with other psychiatric disorders. No interaction was found between intelligence and parental AUD or between intelligence and parental psychiatric disorders.

CONCLUSIONS
The association between intelligence in young adulthood and AUD is modified by other psychiatric disorders as low intelligence is primarily a risk factor for men without other psychiatric disorders. Future studies should take other psychiatric disorders into account when investigating associations between intelligence and AUD.

Intelligence
Alcohol Use Disorders
Cohort Study
Psychiatric Disorders
Early Life


Professional support during the postpartum period: primiparous mothers' views on professional services and their expectations, and barriers to utilizing professional help.

Abstract:
BACKGROUND
Primiparous mothers who lack of experience and knowledge of child caring, are usually overwhelmed by multifarious stressors and challenges. Although professional support is needed for primiparas, there is a gap between the necessary high-quality services and the currently provided poor services. This study aimed to explore Chinese primiparous mothers' views on professional services, identify barriers to utilizing professional support, and further understand mothers' expectations of and preferences for the delivery of professional services.

METHOD
A descriptive phenomenological study design was utilized in this study, and semi-structured interviews were conducted with 28 primiparous mothers who had given birth in the first year period before the interview and were selected from two community health centres in Xi'an city, Shaanxi Province, Northwest China. Each conversational interview lasted between 20 and 86 min. Colaizzi's seven-step phenomenological approach was used to analyse the data.

RESULTS
Three major themes were identified: (a) dissatisfaction with current professional services for postpartum mothers, (b) likelihood of health care professional help-seeking behaviour, (c) highlighting the demands for new health care services. The related seven sub-themes included being disappointed with current hospital services; distrusting services provided by community health centres, private institutes and commercial online platforms; preferring not seeking help from professionals as their first choice; hesitating to express their inner discourse to professionals; following confinement requirement and family burden prevents mothers from seeking professional help; experiencing urgent needs for new baby-care-related services; and determining the importance of mothers' needs. The necessity of professional support in the first month after childbirth was strongly emphasized by the participants. Online professional guidance and support were perceived as the best way to receive services in this study.

CONCLUSION
The results of this descriptive phenomenological study suggested that the current maternal and child health care services were insufficient and could not meet primiparous mothers' need. The results also indicated that identifying barriers and providing services focused on mothers' needs may be an effective strategy to enhance primiparous mothers' well-being, and further suggested that feasibility, convenience, and the cultural adaptability of health care services should be considered during the delivery of postpartum interventions.

Nan|Yiping|Y| Zhang|Jingjun|J| Nisar|Anum|A| Huo|Lanting|L| Yang|Lei|L| Yin|Juan|J| Wang|Duolao|D| Rahman|Atif|A| Gao|Yan|Y| Li|Xiaomei|X|

Professional support
Primiparous mothers
Needs
Maternal and child services
Utilizing support


Paraneoplastic neuromyelitis optica spectrum disorder: A case report and review of the literature.

Abstract: Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating, autoimmune diseases affecting the central nervous system. Typically, recurrent optic neuritis and longitudinal extensive transverse myelitis dominates the clinical picture. In most cases NMOSD are associated with autoantibodies targeting the water channel aquaporin-4 (AQP-4). NMOSD usually present in young adults. Clinical findings suggestive of NMOSD in elderly patients should raise the suspicion of a paraneoplastic etiology. To our knowledge, we report the first case of a 66 year-old female patient with paraneoplastic NMOSD that is associated with squamous cell lung carcinoma. Anti-AQP-4 was present in both the serum and cerebrospinal fluid of the patient. However, immunhistological staining of the malignant tissue did not show presence of AQP-4 on the surface of tumour cells.

Annus|Ádám|Á|
Bencsik|Krisztina|K|
Obál|Izabella|I|
Kincses|Zsigmond Tamás|ZT|
Tiszlavicz|László|L|
Höftberger|Romana|R|
Vécsei|László|L|

Paraneoplastic
Neuromyelitis optica
Aquaporin-4


Phase I study of taselisib in Japanese patients with advanced solid tumors or hormone receptor-positive advanced breast cancer.

Abstract: Taselisib is a potent and selective phosphatidylinositide 3-kinase (PI3K) inhibitor. The present article reports the first study of taselisib administration in Japanese patients. The aim of this 2-stage, phase I, multicenter, open-label, dose-escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)-positive locally advanced or recurrent breast cancer (stage 2). In stage 1, oral taselisib tablets 2, 4, and 6 mg/d were given in 28-day cycles. In stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/d) with i.m. fulvestrant 500 mg. Nine and 6 patients were enrolled in stage 1 and stage 2, respectively. Taselisib was well tolerated. No dose-limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment-related adverse events in stage 1 and stage 2, respectively, were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), and stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after dosage; its half-life was 12.9-32.0 hours in stage 1 and 16.1-26.5 hours in stage 2. Two patients achieved partial response (PR), 5 patients had stable disease (SD) and 2 patients had progressive disease (PD) in stage 1, and 1 patient had PR and 3 patients had SD in stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA-mutated solid tumors or HR-positive advanced breast cancer.

taselisib
Japanese
breast cancer
PI 3-kinase
protein kinase inhibitor


Tattoo pigment agglomerates measured in skin biopsies by computerised light microscopy: Study of 161 patients with adverse reactions in black and red tattoos.

Abstract:
BACKGROUND
Black tattoo reactions are suggested to be foreign body reactions manifested as papulo-nodular inflammation that is associated with active sarcoidosis.

AIM
To study the morphology of black and red pigment agglomerates in skin biopsies from tattoo reactions, referenced to clinical diagnoses.

METHOD
Agglomerate count, area, width, height, circumference and circularity were measured in 161 patients by light microscopy (Olympus BX51™); 161 unstained skin biopsies from 64 black tattoo reactions and 97 reactions in red tattoos with allergy. Images (Jenoptic Gryphax RGB camera) were taken through a 40× objective using immersion oil. Computerised analysis of agglomerates was performed using ImageJ software. Student t test, chi-square test, Fisher Exact test, ANOVA and Bonferroni tests were applied.

RESULTS
Comparison of black and red pigment agglomerates showed no overall differences in count, area, width, height or circumference. However, in black tattoo reactions, the count of agglomerates was higher in patients with sarcoidosis (P = .009) vs no sarcoidosis. Black agglomerates were more circular shaped as compared to red, P = .023. In red tattoo reactions, agglomerates in patients with allergic cross-reactivity were slightly more circular (P = .036) vs patients with milder allergy. The count of red agglomerates was lower in patients clinically typed excessive hyperkeratosis (P = .041) compared with other clinical types of allergy.

CONCLUSION
Patients with reactions in black tattoos associated with sarcoidosis have increased count of pigment agglomerates vs those without associated sarcoidosis indicating that black pigment agglomeration is one among a number of factors triggering sarcoid tattoo complication. Circular shape of agglomerates may code for bioactivity.

tattoo pigment agglomerate reaction sarcoidosis sarcoid


Frequency-Independent Terahertz Anomalous Hall Effect in DyCo5 , Co32 Fe68 , and Gd27 Fe73 Thin Films from DC to 40 THz.

Abstract: The anomalous Hall effect (AHE) is a fundamental spintronic charge-to-charge-current conversion phenomenon and closely related to spin-to-charge-current conversion by the spin Hall effect. Future high-speed spintronic devices will crucially rely on such conversion phenomena at terahertz (THz) frequencies. Here, it is revealed that the AHE remains operative from DC up to 40 THz with a flat frequency response in thin films of three technologically relevant magnetic materials: DyCo5 , Co32 Fe68 , and Gd27 Fe73 . The frequency-dependent conductivity-tensor elements σxx and σyx  are measured, and good agreement with DC measurements is found. The experimental findings are fully consistent with ab initio calculations of σyx for CoFe and highlight the role of the large Drude scattering rate (≈100 THz) of metal thin films, which smears out any sharp spectral features of the THz AHE. Finally, it is found that the intrinsic contribution to the THz AHE dominates over the extrinsic mechanisms for the Co32 Fe68 sample. The results imply that the AHE and related effects such as the spin Hall effect are highly promising ingredients of future THz spintronic devices reliably operating from DC to 40 THz and beyond.

terahertz ellipsometry
terahertz spintronics
terahertz time-domain spectroscopy


Transcription analysis on response of porcine alveolar macrophages to co-infection of the highly pathogenic porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae.

Abstract: Porcine respiratory disease complex (PRDC) is of great concern economically, for swine producers worldwide. Co-infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhp) are considered the major causative agents of PRDC, and responsible for mass mortality in pigs. Nevertheless, the molecular mechanisms underlying the host factors involved in pathogenesis and persistent infection have not been clearly established because of a lack of information regarding host responses following co-infection. In the current study, high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages (PAM) to co-infection with highly pathogenic PRRSV (HP-PRRSV) and Mhp. A total of 2152 and 1760 genes were identified as being differentially expressed between the control group and PRRSV+Mhp co-infected group at 6 and 15 h post infection, respectively. The DE genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, defense response, signal transduction. The pathway analysis demonstrated that the most significant pathways were associated with chemokine signaling pathway, cytokine, TLR, RLR and NLR signaling pathways and Jak-STAT signaling pathway. STRING analysis demonstrated that IL-1β is an integral gene in co-infections with PRRSV and Mhp. The present study is the first to document the response of PAMs to co-infection with HP-PRRSV and Mhp. The observed gene expression profile could help with the screening of potential host agents for reducing the prevalence of co-infections, and to further develop our understanding of the molecular pathogenesis associated with PRRSV and Mhp co-infection in pigs.

Li|Bin|B| Du|Luping|L| Xu|Xiangwei|X| Sun|Bing|B| Yu|Zhengyu|Z| Feng|Zhixin|Z| Liu|Maojun|M| Wei|Yanna|Y| Wang|Haiyan|H| Shao|Guoqing|G| He|Kongwang|K|

D019318:Porcine Reproductive and Respiratory Syndrome

D019316:Porcine respiratory and reproductive syndrome virus

Co-infection
Mycoplasma hyopneumoniae
PRRSV
Microarray analysis


Intravenous Laser Therapy in Patients With Acute Kidney Injury: A Randomized Clinical Trial.

Abstract: Introduction: Although intravascular laser irradiation of blood (ILIB) is deemed an innocuous and useful technique for laser therapy, particularly when systemic effects are required, no study, to our knowledge, has been conducted on the effectiveness and innocuousness of ILIB in treating acute kidney injury (AKI). Objective: This study aimed to assess the feasibility and outcomes of ILIB in the management of patients with AKI and comparing them with the Sham-laser group. Materials and Methods: Twenty-six patients with intra-renal AKI (24-95 years old) at Tajrish Hospitals were evaluated for enrollment eligibility in this clinical trial study. This study was conducted at the nephrology department of Shahid Beheshti University of Medical Science, Tehran, Iran, between 2018 and 2019. Based on the treatment method, the patients' assignment to two groups (ILIB or Sham-laser) was randomly done. Demographic characteristics, need for dialysis, hemoglobin and serum biochemistry changes, serum and urine neutrophil gelatinase-associated lipocalin (NGAL) changes, laser complications, and the hospitalization period were recorded. Results: In terms of the baseline characteristics and biochemistry serum level, no differences were seen between the two groups. All post-treatment parameters, except the hemoglobin value, significantly improved in both groups. Urine NGAL and serum NGAL show declines from the baseline in both groups; however, the reduction slope of these parameters occurred faster in the laser group in a statistically significant manner. Conclusion: A decline in NGAL levels in the laser group during the treatment may suggest that the ILIB can help patients with AKI recover better.


A Polymerization-Cutting Strategy: Self-Protection Synthesis of Thiol-Based Nanoporous Adsorbents for Efficient Mercury Removal.

Abstract: Highly toxic heavy metal ions such as mercury ions (Hg2+ ) are a great threat to human life and the environment. Developing new strategies and materials to remove the toxic heavy metal ions has attracted more and more attentions. Herein a facile self-protection synthesis of thiol-based nanoporous adsorbents for efficient mercury removal via a polymerization-cutting strategy is reported. The direct free-radical polymerization of divinyl disulfide derivative and subsequently cutting off the disulfide linkage, without post-synthesis or modification, can give rise to an exceptionally high density of thiol chelating sites. Moreover, the resultant thiol-based nanoporous adsorbents (NAs-SH) exhibit a high saturation uptake capacity (1240 mg g-1 ) and reused ability for mercury removal from water solution. The proposed polymerization-cutting strategy may provide an alternative and cost-effective method for the design and synthesis of various efficient nanoporous adsorbents at large scale in the future.

self-protection adsorbent mercury polymerization thiol


An ethnomedicinal survey of a Tashelhit-speaking community in the High Atlas, Morocco.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional knowledge about medicinal plants from a poorly studied region, the High Atlas in Morocco, is reported here for the first time; this permits consideration of efficacy and safety of current practises whilst highlighting species previously not known to have traditional medicinal use.

AIM OF THE STUDY
Our study aims to document local medicinal plant knowledge among Tashelhit speaking communities through ethnobotanical survey, identifying preferred species and new medicinal plant citations and illuminating the relationship between emic and etic ailment classifications.

MATERIALS AND METHODS
Ethnobotanical data were collected using standard methods and with prior informed consent obtained before all interactions, data were characterized using descriptive indices and medicinal plants and healing strategies relevant to local livelihoods were identified.

RESULTS
151 vernacular names corresponding to 159 botanical species were found to be used to treat 36 folk ailments grouped in 14 biomedical use categories. Thirty-five (22%) are new medicinal plant records in Morocco, and 26 described as used for the first time anywhere. Fidelity levels (FL) revealed low specificity in plant use, particularly for the most commonly reported plants. Most plants are used in mixtures. Plant use is driven by local concepts of disease, including "hot" and "cold" classification and beliefs in supernatural forces.

CONCLUSION
Local medicinal plant knowledge is rich in the High Atlas, where local populations still rely on medicinal plants for healthcare. We found experimental evidence of safe and effective use of medicinal plants in the High Atlas; but we highlight the use of eight poisonous species.

Teixidor-Toneu|Irene|I|
Martin|Gary J|GJ|
Ouhammou|Ahmed|A|
Puri|Rajindra K|RK|
Hawkins|Julie A|JA|

D007722:Health Knowledge, Attitudes, Practice

Ethnomedicine
Traditional knowledge
Medicinal plants
Berber
Informant Consensus Factor


Effect of oral Utrogestan in comparison with Cetrotide on preventing luteinizing hormone surge in IVF cycles: A randomized controlled trial.

Abstract:
Background
Oral progesterone is recommended as an alternative to gonadotropin-releasing hormone (GnRH) agonists and antagonists to prevent luteinizing hormone (LH) surge in assisted reproductive technology (ART) cycles. However, there are little data regarding its use.

Objective
We aimed to compare the effect of oral Utrogestan and Cetrotide (a GnRH antagonist) on preventing LH surge in ART cycles.

Materials and Methods
In this randomized clinical trial, 100 infertile women undergoing ART who received recombinant follicle-stimulating hormone (FSH) at 150-225 IU/day were randomly assigned to receive either Utrogestan 100 mg twice a day (case group) or GnRH antagonist protocol (control group) from cycle day 3 until the trigger day. Triggering was performed with 10,000 IU hCG) when there were at least three mature follicles. Viable embryos were cryopreserved for transfer in the next cycle for both groups. The number of oocytes retrieved and transferred embryos were compared between groups.

Results
The case group had significantly higher progesterone levels on triggering day, more follicles of  14 mm with higher maturity, and more oocytes retrieved with a higher rate of embryos transferred. A small increase in the pregnancy rate was observed in the case group, with no significant between-group differences. The most important result was the lack of premature LH surge in either group upon serum LH assessment on the triggering day.

Conclusion
Utrogestan is an alternative treatment that could reduce the LH surge rate and increase the ART outcomes including the number of oocytes retrieved and transferred embryos compared with GnRH agonists and antagonists.

Ghasemzadeh|Alieh|A|
Dopour Faliz|Masumeh|M|
Farzadi|Laya|L|
Navali|Nazli|N|
Bahramzadeh|Behzad|B|
Fadavi|Arash|A|
Hakimi|Parvin|P|
Tehrani-Ghadim|Sepideh|S|
Abdollahi Fard|Sedigheh|S|
Hamdi|Kobra|K|

Premature luteinization
Utrogestan.
In vitro fertilization


Coagulation biomarkers are independent predictors of increased oxygen requirements in COVID-19.

Abstract:
BACKGROUND
Hypercoagulability seems to contribute to SARS-CoV-2 pneumonia pathogenesis. However, age and metabolic syndrome are potential confounders when assessing the value of coagulation biomarkers' prediction of COVID-19 outcomes. We assessed whether coagulation biomarkers, including factor VIII (FVIII) and von Willebrand factor (VWF) levels, measured at time of admission, were predictive of COVID-19 adverse outcomes irrespective of age and major comorbidities associated with metabolic syndrome.

METHODS
Blood was sampled at admission in 243 adult COVID-19 patients for analysis of coagulation biomarkers including FVIII and VWF on platelet-poor plasma. The association between baseline C-reactive protein (CRP), activated partial thromboplastin time ratio, prothrombin time ratio, D-dimers, fibrinogen, FVIII, VWF antigen (VWF:Ag), and FVIII/VWF:Ag ratio levels and adverse outcomes (increased oxygen requirements, thrombosis, and death at day 30) was assessed by regression analysis after adjustment on age, sex, body mass index (BMI), diabetes, and hypertension.

RESULTS
In univariable regression analysis increased CRP (subdistribution hazard ratio [SHR], 1.68; 95% confidence interval [CI], 1.26-2.23), increased fibrinogen (SHR, 1.32; 95% CI, 1.04-1.68), and decreased FVIII/VWF:Ag ratio (SHR, 0.70; 95% CI, 0.52-0.96) levels at admission were significantly associated with the risk of increased oxygen requirement during follow-up. Leucocytes (SHR, 1.36; 95% CI, 1.04-1.76), platelets (SHR,1.71; 95% CI, 1.11-2.62), D-dimers (SHR, 2.48; 95% CI, 1.66-3.78), and FVIII (SHR, 1.78; 95% CI, 1.17-2.68) were associated with early onset of thrombosis after admission. After adjustment for age, sex, BMI, hypertension, and diabetes, these associations were not modified.

CONCLUSION
Coagulation biomarkers are early and independent predictors of increased oxygen requirement in COVID-19 patients.

Rauch|Antoine|A|0000-0002-1182-4131
Labreuche|Julien|J|
Lassalle|Fanny|F|0000-0003-0494-823X
Goutay|Julien|J|
Caplan|Morgan|M|
Charbonnier|Leslie|L|
Rohn|Aurelien|A|
Jeanpierre|Emmanuelle|E|
Dupont|Annabelle|A|
Duhamel|Alain|A|
Faure|Karine|K|
Lambert|Marc|M|
Kipnis|Eric|E|
Garrigue|Delphine|D|
Lenting|Peter J|PJ|0000-0002-7937-3429
Poissy|Julien|J|
Susen|Sophie|S|0000-0001-5953-163X

oxygen
factor VIII
von Willebrand factor
body mass index
SARS-CoV2


IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer.

Abstract: Women with triple-negative breast cancer (TNBC) are generally treated by chemotherapy but their responsiveness may be blunted by DNA double-strand break (DSB) repair. We previously reported that IGFBP-3 forms nuclear complexes with EGFR and DNA-dependent protein kinase (DNA-PKcs) to modulate DSB repair by non-homologous end-joining (NHEJ) in TNBC cells. To discover IGFBP-3 binding partners involved in chemoresistance through stimulation of DSB repair, we analyzed the IGFBP-3 interactome by LC-MS/MS and confirmed interactions by coimmunoprecipitation and proximity ligation assay. Functional effects were demonstrated by DNA end-joining in vitro and measurement of γH2AX foci. In response to 20 µM etoposide, the DNA/RNA-binding protein, non-POU domain-containing octamer-binding protein (NONO) and its dimerization partner splicing factor, proline/glutamine-rich (SFPQ) formed complexes with IGFBP-3, demonstrated in basal-like TNBC cell lines HCC1806 and MDA-MB-468. NONO binding to IGFBP-3 was also shown in a cell-free biochemical assay. IGFBP-3 complexes with NONO and SFPQ were blocked by inhibiting EGFR with gefitinib or DNA-PKcs with NU7026, and by the PARP inhibitors veliparib and olaparib, which also reduced DNA end-joining activity and delayed the resolution of the γH2AX signal (i.e. inhibited DNA DSB repair). Downregulation of the long noncoding RNA in NHEJ pathway 1 (LINP1) by siRNA also blocked IGFBP-3 interaction with NONO-SFPQ. These findings suggest a PARP-dependent role for NONO and SFPQ in IGFBP-3-dependent DSB repair and the involvement of LINP1 in the complex formation. We propose that targeting of the DNA repair function of IGFBP-3 may enhance chemosensitivity in basal-like TNBC, thus improving patient outcomes.

D015972:Gene Expression Regulation, Neoplastic

D018972:Insulin-Like Growth Factor Binding Protein 3

D064726:Triple Negative Breast Neoplasms

TNBC
PARP inhibitors
IGF binding protein
P54NRB
PSF
lncRNA


Dermatological Manifestations in Pediatric Inflammatory Bowel Disease.

Abstract:
Background and Objectives: Over the last years, inflammatory bowel disease (IBD) has been reported on a high incidence in pediatric populations and has been associated with numerous extraintestinal manifestations, making its management a real challenge for the pediatric gastroenterologist. Dermatological manifestations in IBD are either specific, related to the disease activity or treatment-associated, or non-specific. This literature review aims to identify and report the dermatological manifestations of IBD in children, the correlation between their appearance and the demographical characteristics, the relationship between these lesions and disease activity, and to highlight the impact of dermatological manifestations on an IBD treatment regime.

MATERIALS AND METHODS
A systemic literature review was performed, investigating articles and case reports on dermatological manifestations in children with IBD starting from 2005. A total of 159 potentially suitable articles were identified and after the exclusion process, 75 articles were selected.

RESULTS
The most common dermatological manifestations reported in pediatric IBD are erythema nodosum and pyoderma gangrenosum. More rare cases of metastatic Crohn's disease, epidermolysis bullosa acquisita, small-vessel vasculitis, necrotizing vasculitis, leukocytoclastic vasculitis, cutaneous polyarteritis nodosa, and Sweet's syndrome have been reported. Oral manifestations of IBD are divided into specific (tag-like lesions, mucogingivitis, lip swelling with vertical fissures, aphthous stomatitis, and pyostomatitis vegetans) and non-specific. IBD treatment may present with side effects involving the skin and mucosa. Anti-tumor necrosis factor agents have been linked to opportunistic skin infections, psoriasiform lesions, and a potentially increased risk for skin cancer. Cutaneous manifestations such as acrodermatitis enteropathica, purpuric lesions, and angular cheilitis may appear secondary to malnutrition and/or malabsorption.

CONCLUSIONS
The correct diagnosis of dermatological manifestations in pediatric IBD is of paramount importance because of their impact on disease activity, treatment options, and a patient's psychological status.

Diaconescu|Smaranda|S|
Strat|Silvia|S|
Balan|Gheorghe G|GG|
Anton|Carmen|C|
Stefanescu|Gabriela|G|
Ioniuc|Ileana|I|
Stanescu|Ana Maria Alexandra|AMA|

D018124:Receptors, Tumor Necrosis Factor

dermatological
pediatric
treatment
Crohn’s disease
ulcerative colitis


Anesthetic Management of Right Single-lung Ventilation in a Patient with Anomalous Left Superior Pulmonary Venous Return for Left Pulmonary Lobectomy.

Abstract: Partial anomalous pulmonary venous return (PAPVR) is a rare congenital anomaly in which one or more of the pulmonary veins are connected to the right atrium or to the systemic venous system. One lung ventilation (OLV) is required for a number of thoracic procedures. When switching to OLV, right-to-left shunt fraction increases, oxygenation is impaired, and hypoxemia may occur. Hypoxemia during OLV may affect the safety of the patient and is a challenge for the anesthesiologist and the surgeon. This case details the intraoperative anesthetic management of an elderly patient with a PAPVR who underwent single-lung ventilation for lung resection surgery.

Zhang|Yu|Y|
Escher|Allan R|AR|
Cohen|Jonathan B|JB|
Liu|Jinhong|J|

partial anomalous pulmonary venous return


Commuter exposure to particulate matter and particle-bound PAHs in three transportation modes in Beijing, China.

Abstract: Exposure to fine and ultrafine particles as well as particulate polycyclic aromatic hydrocarbons (PAHs) by commuters in three transportation modes (walking, subway and bus) were examined in December 2011 in Beijing, China. During the study period, real-time measured median PM2.5 mass concentration (PMC) for walking, riding buses and taking the subway were 26.7, 32.9 and 56.9 μg m(-3), respectively, and particle number concentrations (PNC) were 1.1 × 10(4), 1.0 × 10(4) and 2.2 × 10(4) cm(-3). Commuters were exposed to higher PNC in air-conditioned buses and aboveground-railway, but higher PMC in underground-subway compared to aboveground-railway. PNC in roadway modes (bus and walking) peaked at noon, but was lower during traffic rush hours, negatively correlated with PMC. Toxic potential of particulate-PAHs estimated based on benzo(a)pyrene toxic equivalents (BaP TEQs) showed that walking pedestrians were subjected to higher BaP TEQs than bus (2.7-fold) and subway (3.6-fold) commuters, though the highest PMC and PNC were observed in subway.

Yan|Caiqing|C| Zheng|Mei|M| Yang|Qiaoyun|Q| Zhang|Qunfang|Q| Qiu|Xinghua|X| Zhang|Yanjun|Y| Fu|Huaiyu|H| Li|Xiaoying|X| Zhu|Tong|T| Zhu|Yifang|Y|

Commuter exposure
Particulate matter
PAHs
Walking
Subway
Bus


The parkinsonism-associated protein FBXO7 cooperates with the BAG6 complex in proteasome function and controls the subcellular localization of the complex.

Abstract: The regulation of proteasome activity is essential to cellular homeostasis and defects have been implicated in various disorders including Parkinson disease. The F-box protein FBXO7 has been implicated in early-onset parkinsonism and has previously been shown to have a regulatory role in proteasome activity and assembly. Here, we report the association of the E3 ubiquitin ligase FBXO7-SCF (SKP1, cullin-1, F-box protein) with the BAG6 complex, consisting of the subunits BAG6, GET4 and UBL4A. We identify the subunit GET4 as a direct interactor of FBXO7 and we show that the subunits GET4 and UBL4A are required for proper proteasome activity. Our findings demonstrate reduced binding of FBXO7 variants to GET4 and that FBXO7 variants bring about reduced proteasome activity. In addition, we find that GET4 is a non-proteolytic substrate of FBXO7, that binding of GET4 to BAG6 is enhanced in the presence of active FBXO7-SCF and that the cytoplasmic localization of the BAG6 complex is dependent on the E3 ubiquitin ligase activity. Taken together, our study shows that the parkinsonism-associated FBXO7 cooperates with the BAG6 complex in proteasome function and determines the subcellular localization of this complex.

Wang|Quan|Q| Crnković|Vanessa|V| Preisinger|Christian|C| Stegmüller|Judith|J|0000-0003-4172-7778

proteasome
Parkinsons disease
E3 ubiquitin ligase
ubiquitination


Validation of octanoate breath test for measuring gastric emptying in rats.

Abstract:
BACKGROUND/AIMS
Lack of simple and repeatable tests hampers gastric emptying studies in rats. The aim of this study was to adapt the (14)C-octanoate solid gastric emptying breath test for application in rats, and to validate it against radioscintigraphic method.

METHODS
After ingestion of a meal containing 3 mCi (99m)Tc and 2 µCi (14)C-octanoate, 23 male Wistar rats were placed on a gamma camera in a airflow container. Scintigraphic images were taken at regular intervals. The amount of (14)CO2 in a regularly replaced hyamine hydroxide solution, capturing CO2 in the outflow air, was counted using liquid scintillation spectrometry. (99m)Tc gastric retention curves and (14)CO2-excretion curves were fitted to their respective data. Three rats underwent the same procedures after administration of atropine.

RESULTS
Overall Tr10% (time at which 10% of the original amount of (99m)Tc remained in the stomach) was 355 ± 64 minutes; Te90% (time at which 90% of total amount of (14)CO2 was excreted) was 325 ± 106 minutes. Their correlation coefficient was 0.71, R-square 0.50 and P < 0.005. Tr1/2 (50% of original amount of (99m)Tc remained) was 124 ± 28 minutes; Te1/2 (50% of total amount of (14)CO2 excreted) 114 ± 32 minutes. Their correlation coefficient was 0.83 with R-square of 0.69 and P < 0.00005. In 12 immobilized animals correlation was even better: correlation coefficient 0.84; R-square 0.71 and P < 0.001 (Tr10% was 388 ± 117 minutes; Te90% 532 ± 219 minutes; Tr1/2 of 165 ± 54 minutes; Te1/2 of 175 ± 67 minutes). Atropine significantly lengthened all emptying times: 904 ± 307 and 1461 ± 684 minutes for Tr10% and Te90%, respectively; and 432 ± 117 minutes for Tr1/2 and 473 ± 190 minutes for Te1/2.

CONCLUSIONS
We adapted and validated the (14)C-octanoate gastric emptying breath test for application in rats.

Demedts|Ingrid|I|
Vanormelingen|Christophe|C|
Van Billoen|Hubert|H|
Vanuytsel|Tim|T|
Farré|Ricard|R|
Masaoka|Tatsuhiro|T|
Verbruggen|Alfons|A|
Verbeke|Kristien|K|
Vanden Berghe|Pieter|P|
Tack|Jan|J|

Breath tests
Gastric emptying
Rats
14C-octanoate


Study On Potential Factors Of Patient Satisfaction: Based On Exploratory Factor Analysis.

Abstract:
Objective
To explore the potential common factors of patient satisfaction and the influencing factor of it.

Methods
A questionnaire survey was organized and 2626 valid answers were obtained. Through correlation analysis and exploratory factor analysis, the potential factors of patient satisfaction were extracted.

Results
Potential factors of patient satisfaction include "Medical service quality factor", "Medical expenditure factor", and "Medical convenience factor". Patients younger than 35 years old were more concerned about the medical expenditure, and patients aged from 36 to 50 years old were more concerned about medical service quality. Patients with high reimbursement ratio insurance payed more attention to medical quality, and patients with lower reimbursement ratio insurance were dissatisfied with medical expenses. Patients were dissatisfied with the expenditure of the high-level hospitals and the medical quality of low-level hospitals. Outpatient's satisfaction was lower than Inpatients in all aspects. Hierarchical diagnosis system was not established, and registration channels were highly centralized in the hospital.

Conclusion
Three potential factors can well explain patients' demands for the quality, price and convenience of medical services. According to social-demographic characteristics, people of different groups have different concerns. Medical reform departments should adjust policies according to the actual situation and promote the medical reform process.

patient satisfaction
hospitals
health care reform
public policy
urban


Off-pump coronary artery bypass prevents visceral organ damage.

Abstract:
OBJECTIVES
Visceral malperfusion after coronary artery bypass grafting (CABG) results in high morbidity and mortality. This study was designed to evaluate the effect of CABG performed by surgical techniques on visceral perfusion and function.

METHODS
Pigs (n = 28) were studied in four groups: I. Sham; II. Off-pump coronary artery bypass grafting (OPCAB): 1 h stabilizer with 40 min intracoronary shunt; III. Extracorporeal circulation (ECC): 1 h ECC with 40 min aortic cross-clamping and cardioplegic arrest; IV. Impella: 1 h left ventricular blood-pump support and stabilizer with 40 min intracoronary shunt. A left internal mammary to left anterior descending coronary artery bypass was performed in Groups II-IV. All animals were observed for a further 240 min. During the experiment haemodynamics, creatinine clearance, intestinal fatty acid binding protein (iFABP), pancreatic (lipase and amylase) and liver enzymes (α-glutathione s-transferase, glutamate-oxaloacetate transaminase (GOT), gamma-glutamyl transferase (GGT), glutamate dehydrogenase and glutamate-pyruvate transaminase (GPT)) were measured. Visceral perfusion (VP) was assessed in both kidneys, intestine, pancreas, liver and spleen with 15 µm fluorescent microspheres.

RESULTS
During OPCAB surgery, VP decreased slightly. Renal functional parameters, iFABP, pancreatic and liver enzymes remained unchanged. ECC and Impella led to significantly reduced renal, pancreatic and intestinal blood flow (P < 0.05). Creatinine clearance, pancreatic and liver (GPT, GGT) enzymes were significantly decreased only after ECC (P < 0.05). ECC and Impella resulted in a significantly increased iFABP level (P < 0.05). GOT was elevated significantly after surgery in Groups II, III and IV (P < 0.05).

CONCLUSIONS
CABG with ECC or Impella leads to impaired visceral blood flow and function. OPCAB minimizes these procedure associated alterations.

Bierbach|Benjamin|B| Bomberg|Hagen|H| Pritzer|Hartmut|H| Prabhu|Sudesh|S| Petzina|Rainer|R| Kempski|Oliver|O| Horstick|Georg|G| Cremer|Jochen|J| Hoffmann|Grischa|G|

D047549:Coronary Artery Bypass, Off-Pump

OPCAB
Renal function
Cardiopulmonary bypass
Intestinal ischaemia
Microaxial blood pump


Endogenous fibrinolysis-Relevance to clinical thrombosis risk assessment.

Abstract: The development of an obstructive luminal thrombus is pathological and considered a failure of endogenous fibrinolysis. The consequences may be fatal, or result in lasting downstream organ damage. Therefore, assessment of endogenous fibrinolytic status in an individual may identify those at risk of occlusive thrombus formation and provide prognostic information. Arterial thrombi are more platelet rich and more resistant to fibrinolysis than venous thrombi. Several recent studies using global tests of fibrinolysis in patients with acute coronary syndromes (ACS) have shown that despite dual antiplatelet therapy, patients with impaired fibrinolytic status have an increased risk of adverse cardiovascular events, compared with those with effective fibrinolytic function. Such data add significantly to the predictive value of established cardiovascular risk factors and conventional biomarkers. Most data reported have been obtained with the Global Thrombosis Test and the turbidimetric plasma clot lysis assay. A few small studies in patients with ischaemic stroke suggest a similar predictive role of fibrinolytic status assessment in these patients. Studies reporting an association between impaired fibrinolysis and future venous thrombotic events are limited, and in the form of case-control studies. Viscoelastic assays may have a role in the prediction of venous thromboembolic risk. Assays of fibrinolytic function should be used to obtain a more accurate risk of future thrombotic events, particularly in the setting of ACS. The availability of point-of-care tests helps facilitate this and should encourage future studies to assess personalised antithrombotic treatment combinations to optimise fibrinolytic status and reduce thrombosis risk.

thrombosis
fibrinolysis
acute coronary syndrome
clot lysis
stroke
venous thrombosis


Changing phenotype and disease behaviour of chronic pancreatitis in India: evidence for gene-environment interactions.

Abstract:
Background
The idiopathic variety of chronic pancreatitis (CP) in India particularly in Kerala state was earlier called 'tropical pancreatitis' with peculiar features: early age of onset, severe malnutrition, diabetes and poor prognosis. A change in disease phenotype and behaviour has been observed recently.

Objective
To review the changing profile of CP in India and examine its relationship with environmental influences and socio-economic development.

Methods
Relevant studies on CP in India were reviewed along with social and economic parameters in Kerala over the past 4 decades.

Results
There has been a definite change in the phenotype of CP in India with onset in mid twenties, better nutritional status, and a much better prognosis compared with the reports in 1970s. Genetic susceptibility due to genetic mutations particularly in SPINK1, CFTR, CTRC, and CLDN2/MORC4 genes is the most important factor and not malnutrition or dietary toxins for idiopathic CP suggesting the term 'tropical pancreatitis' is a misnomer. We observed a close relationship between socio-economic development and rising income in Kerala with late onset of disease, nutritional status, and better prognosis of CP.

Conclusion
Changing profile of CP in India and better understanding of risk factors provide evidence for gene-environmental interactions in its pathobiology.

phenotype
Chronic pancreatitis
tropical pancreatitis
SPINK1


When Project Commitment Leads to Learning from Failure: The Roles of Perceived Shame and Personal Control.

Abstract: Facing a remarkably changing world, researchers have gradually shifted emphasis from successful experiences to failures. In the current study, we build a model to explore the relationship between project commitment and learning from failure, and test how emotion (i.e., perceived shame after failure) and cognition (i.e., attribution for failure) affect this process. After randomly selecting 400 firms from the list of high-tech firms reported by the Beijing Municipal Science and Technology Commission, we use a two-wave investigation of the employees, and the final sample consists of 140 teams from 58 companies in the technology industry in mainland China. The results provide evidence for the positive role of personal control attribution in the relationship between project commitment and learning from failure. However, in contrast to previous studies, perceived shame, as the negative emotion after failed events, could bring desirable outcomes during this process. Based on the results, we further expand a model to explain the behavioral responses after failure, and the implications of our findings for research and practice are discussed. The failures and reverses which await men - and one after another sadden the brow of youth - add a dignity to the prospect of human life, which no Arcadian success would do. -Henry David Thoreau.

Wang|Wenzhou|W| Wang|Bin|B| Yang|Ke|K| Yang|Chong|C| Yuan|Wenlong|W| Song|Shanghao|S|

project commitment
learning from failure
shame
personal control
proactive behavior


Serum-derived hepatitis C virus 1a infection of human astrocyte cell line SVG.

Abstract: Neuroinvasion of hepatitis C virus (HCV) is evidenced by recent clinical studies. In this study, serum-derived HCV infection of astrocytes was analysed. Astrocytes were infected with HCV-positive serum, and viral replication was assessed on different days postinfection. RT-PCR was positive for HCV-negative strand on 5th and 7th day postinfection in the HCV-positive serum-infected astrocytes. Real-time RNA count in the cell culture supernatant was steadily increasing from day 3 to day 7. To reconfirm the viral replication, astrocytes were treated with an antiviral before the serum infection, and the antiviral treatment significantly reduced the viral RNA count. Further, the virus-infected cells stained positive for the presence of viral core protein. Electron microscopy revealed the presence of HCV-like particles in the astrocyte cell culture supernatant. In conclusion, serum-derived HCV replicates in human astrocyte cell line SVG.

Rajalakshmy|A R|AR|
Malathi|J|J|
Madhavan|H N|HN|

D060888:Real-Time Polymerase Chain Reaction

hepatitis C virus
astrocytes
viral replication
immunofluorescence
neuroinflammation
polymerase chain reaction


Current and future trends in men's health clinics.

Abstract: Men's health is a unique field that requires a multi-disciplinary approach to appropriately treat the full spectrum of men's health needs. Given that interest in men's health is relatively new, the definition of a men's health clinic continues to evolve. Originally conceived as testosterone replacement centers, men's health clinics are increasingly understood to encompass male endocrine, surgical, urologic, physical performance, and psychological issues. As interest in men's health continues to grow, it is important to focus on the field's future, including pharmacies, telemedicine, and the diffusion of healthcare.

Houman|Justin J|JJ|
Eleswarapu|Sriram V|SV|
Mills|Jesse N|JN|


Discriminatory power of scoring systems for outcome prediction in patients with extracorporeal membrane oxygenation following cardiovascular surgery†.

Abstract:
OBJECTIVES
Although extracorporeal membrane oxygenation (ECMO) represents a rapidly evolving treatment option in patients with refractory heart or lung failure, survival remains poor and appropriate risk stratification challenging because established risk prediction models have not been validated for this specific population.

METHODS
This observational single-centre registry included a total of 240 patients treated with venoarterial ECMO therapy following cardiovascular surgery and analysed the discriminatory power of the European System of Cardiac Operative Risk Evaluation (EuroSCORE) additive, the EuroSCORE II, the Sequential Organ Failure Assessment (SOFA) score, the Simplified Acute Physiology Score (SAPS) II, the SAPS III, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal failure (RIFLE) classification, the survival after venoarterial ECMO (SAVE) score, the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score and the Society of Thoracic Surgeons (STS) risk model for outcome prediction.

RESULTS
During a median follow-up time of 37 months (interquartile range 19-67), 65% of the patients died. Only the SAVE score and the SAPS II were significantly associated with the 30-day mortality rate with a hazard ratio (HR) of 1.06 [95% confidence interval (CI) 1.02-1.11; P = 0.002] for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P = 0.004) for the SAPS II with a modest discriminatory power displayed by a C-index of 0.61 and 0.57, respectively. Seven out of 10 scoring systems revealed significant association with long-term mortality, with the SAVE score and the SAPS II remaining the strongest predictors of long-term mortality with an HR of 1.06 (95% CI 1.03-1.09; P < 0.001, C-index 0.61) for the SAVE score and an HR of 1.02 (95% CI 1.01-1.03; P < 0.001, C-index 0.58) for the SAPS II.

CONCLUSIONS
Risk assessment based on established risk models in patients with ECMO remains difficult. Only the SAPS II and the SAVE score were exclusively found to be suitable for short- and long-term outcome prediction in this specific vulnerable patient population.

Schrutka|Lore|L|
Rohmann|Felix|F|
Binder|Christina|C|
Haberl|Thomas|T|
Dreyfuss|Ben|B|
Heinz|Gottfried|G|
Lang|Irene M|IM|
Felli|Alessia|A|
Steinlechner|Barbara|B|
Niessner|Alexander|A|
Laufer|Günther|G|
Goliasch|Georg|G|
Wiedemann|Dominik|D|
Distelmaier|Klaus|K|

Scoring systems
Outcome
Extracorporeal membrane oxygenation
Risk prediction
Cardiovascular surgery


Grade IV Liver Injury Following Mechanical Cardiopulmonary Resuscitation with Postoperative Three-dimensional Evaluation.

Abstract: A 48-year-old female presented to the emergency department with chest pain and collapsed at the front desk. She was reanimated with mechanical chest compression, and after coronary angiography, a left anterior descending/diagonal bifurcation mini-crush stenting was performed. Few hours after the procedure, the patient showed severe hypotension. Abdominal ultrasound and computed tomography (CT) scan evidenced a massive subcapsular liver hematoma (Grade IV, American association for the surgery of trauma (AAST) liver injury scale) of the right lobe with extrahepatic blushing. Transhepatic embolization was attempted but without benefit, so the patient underwent emergency laparotomy for damage control surgery with perihepatic packing. After hemodynamic stabilization, right hepatectomy was performed with a favorable outcome and full recovery. The patient CT scan was retrospectively processed to obtain a virtual model visualizable through a head-mounted display. The virtual reconstruction could improve the comprehension of the injury and the liver surgical anatomy for educational purpose, and it could represent a new tool for preoperative planning.

Aseni|Paolo|P| Vezzulli|Federico|F| Rizzetto|Francesco|F| Cassin|Simone|S| Rantas|Sofia|S| Cereda|Alberto|A| Chiara|Osvaldo|O| Vanzulli|Angelo|A| Vertemati|Maurizio|M|


Society for Maternal-Fetal Medicine (SMFM) Special Statement: Race in maternal-fetal medicine research: Dispelling myths and taking an accurate, anti-racist approach.

Abstract: Profound inequities in maternal and infant outcomes based on race exist, and the maternal-fetal medicine community has an important role in eliminating these disparities. Accurately employing race and ethnicity as social constructs within research that guides clinical practice is essential to achieving health equity. We must abandon commonly propagated myths that race is a surrogate for genetics or economic status and that data are exempt from potential bias. These myths can lead to harmful misconceptions that exacerbate racial disparities in maternal and infant health outcomes. Further, these myths obscure racism as the true underlying etiology of racial disparities. Understanding that race is a social construct and utilizing an anti-racist approach to research are essential in combatting racism and eliminating unacceptable disparities in maternal and infant health. This document provides specific suggestions to approach the research process with an anti-racist framework.

|||
Wheeler|Sarahn M|SM|
Bryant|Allison S|AS|
Bonney|Elizabeth A|EA|
Howell|Elizabeth A|EA|

health equity
racism
anti-racism
health disparity
health inequity
intersectionality


Differential Influence of Acupuncture Somatosensory and Cognitive/Affective Components on Functional Brain Connectivity and Pain Reduction During Low Back Pain State.

Abstract: The underlying mechanism of pain reduction by acupuncture is still unclear, because acupuncture treatment involves multidimensional factors. In this study, we investigated the differential influence of acupuncture components on brain functional connectivity and on pain reduction. We used a specific form of sham acupuncture (phantom acupuncture; PHNT), which only has a needling-credibility (a belief that they were treated with real acupuncture needles), while real acupuncture (REAL) has a somatosensory needling stimulation, as well as a needling-credibility. Forty-three patients with low back pain were randomized into the REAL group (n = 25) and the PHNT group (n = 18). They underwent two pain steady-state fMRI runs implemented by a low back extension (LBE) pain model (lifting the low back using air-cuff inflation) before and after REAL or PHNT stimulation. Subjective pain ratings, perceived throughout the LBE runs due to the posture, were reported (LBEpain). The regions of interest (ROI) were (1) the main nodes of the default mode network (DMN) - the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), (2) the main nodes of the salience network (SN) - the anterior/posterior insular cortices (a/pINS), and (3) the low back-specific region of sensorimotor network (SMN), S1back. Significant reductions in LBEpain were observed in both groups (REAL = -1.02 ± 1.53, PHNT = -1.26 ± 2.20). In REAL group, decreased LBEpain was positively correlated with decreased functional connectivity between the mPFC and pINS (r = 0.58, P < 0.05). Reduced LBEpain in PHNT was negatively correlated with increased PCC-aINS connectivity (r = -0.48, P < 0.05) and tended toward positive correlation with decreased S1back-pINS connectivity (r = 0.44, P = 0.07). Our findings might suggest different brain mechanisms of observed pain reduction; REAL seems to involve detachment of the self from the sensory aspect of pain, while PHNT does to shift attention to self and disengages physical pain processing hubs. This exploratory study proposes a sham methodology to dissociate the influence of different acupuncture components in acupuncture research. Further studies need to be followed with more elaborated hypothesis, study design, and analysis considering various cognitive/affective factors for better understanding of brain mechanisms of pain reduction regarding the different acupuncture aspects.

Lee|Jeungchan|J| Eun|Seulgi|S| Kim|Jieun|J| Lee|Jun-Hwan|JH| Park|Kyungmo|K|

functional connectivity
default mode network
salience network
sensorimotor network
needling credibility
somatosensory afference


Impact of Membrane Drug Transporters on Resistance to Small-Molecule Tyrosine Kinase Inhibitors.

Abstract: Small-molecule inhibitors of tyrosine kinases (TKIs) are the mainstay of treatment for many malignancies and represent novel treatment options for other diseases such as idiopathic pulmonary fibrosis. Twenty-five TKIs are currently FDA-approved and >130 are being evaluated in clinical trials. Increasing evidence suggests that drug exposure of TKIs may significantly contribute to drug resistance, independently from somatic variation of TKI target genes. Membrane transport proteins may limit the amount of TKI reaching the target cells. This review highlights current knowledge on the basic and clinical pharmacology of membrane transporters involved in TKI disposition and their contribution to drug efficacy and adverse drug effects. In addition to non-genetic and epigenetic factors, genetic variants, particularly rare ones, in transporter genes are promising novel factors to explain interindividual variability in the response to TKI therapy.

Neul|Claudia|C|
Schaeffeler|Elke|E|
Sparreboom|Alex|A|
Laufer|Stefan|S|
Schwab|Matthias|M|
Nies|Anne T|AT|

D000818:Animals
D004351:Drug Resistance
D044127:Epigenesis, Genetic
D014644:Genetic Variation
D006801:Humans
D054990:Idiopathic Pulmonary Fibrosis
D026901:Membrane Transport Proteins
D009369:Neoplasms
D047428:Protein Kinase Inhibitors
D011505:Protein-Tyrosine Kinases

tyrosine kinase inhibitors
clinical trials
drug resistance
interindividual variability
ABC transporters
SLC transporters
pharmacogenomics


Ethidium Binding to Salmonella enterica ser. Typhimurium Cells and Salmon Sperm DNA.

Abstract: Bacterial resistance to antibiotics due to increased efficiency of the efflux is a serious problem in clinics of infectious diseases. Knowledge of the factors affecting the activity of efflux pumps would help to find the solution. For this, fast and trustful methods for efflux analysis are needed. Here, we analyzed how the assay conditions affect the accumulation of efflux indicators ethidium (Et+) and tetraphenylphosphonium in Salmonella enterica ser. Typhimurium cells. An inhibitor phenylalanyl-arginyl-β-naphtylamide was applied to evaluate the input of RND family pumps into the total efflux. In parallel to spectrofluorimetric analysis, we used an electrochemical assessment of Et+ concentration. The results of our experiments indicated that Et+ fluorescence increases immediately after the penetration of this indicator into the cells. However, when cells bind a high amount of Et+, the intensity of the fluorescence reaches the saturation level and stops reacting to the accumulated amount of this indicator. For this reason, electrochemical measurements provide more trustful information about the efficiency of efflux when cells accumulate high amounts of Et+. Measurements of Et+ interaction with the purified DNA demonstrated that the affinity of this lipophilic cation to DNA depends on the medium composition. The capacity of DNA to bind Et+ considerably decreases in the presence of Mg2+, Polymyxin B or when DNA is incubated in high ionic strength media.

D024901:Drug Resistance, Multiple, Bacterial

ethidium
tetraphenylphosphonium
phenylalanyl-arginyl-β-naphtylamide
Polymyxin B
efflux inhibitor
multidrug resistance
outer membrane permeability


Should we use a vaginal pack to reduce blood loss at the time of prolapse surgery?

Abstract:
OBJECTIVE
Vaginal packs are commonly inserted after pelvic organ prolapse (POP) surgery to absorb excess blood loss and to reduce haematoma formation. Randomised trials have shown little benefit in terms of reduced haematoma formation. However, the amount of blood loss absorbed on the pack has not been studied. The use of packs has financial costs and is associated with catheterisation and may delay hospital discharge. If packs are not effective in reducing blood loss and haematoma formation there could be an argument that packs should not be used at all. This study was designed to identify how much blood is actually absorbed onto packs after POP surgery.

STUDY DESIGN
Consecutive patients undergoing elective vaginal surgery for POP were prospectively recruited by the lead author. Demographics were recorded. Vaginal packs inserted after POP surgery in 63 women were weighed before insertion and at the time of removal the day after surgery. Pain score were noted and the difference in the weight of packs recorded. Any complications were reported by the patients at the 6 week routine post operative visit and cross referenced with the clinical records.

RESULTS
There was a statistically significant increase in pack weight of 6.7g (p<0.01). Five percent of the patients had a bleed of more than 25g into the pack. Removal of the pack was associated with minor discomfort. Complications in the post operative period were low with 11% of patients seen in the first 6 weeks with bleeding or discharge.

CONCLUSION
The majority of women undergoing prolapse surgery have minimal bleeding onto a routinely introduced vaginal pack placed after POP surgery. Packs are probably not required for controlling post operative blood loss in the majority of patients.

Subramanya|Jyothi|J| Curtiss|Natasha|N| Balachandran|Aswini|A| Duckett|Jonathan|J|

Vaginal pack
Surgery
Pelvic organ prolapse
Bleeding


C1-C2 stabilization by Harms arthrodesis: indications, technique, complications and outcomes in a prospective 26-case series.

Abstract:
INTRODUCTION
C1-C2 arthrodesis is a surgical challenge due to the proximity of neurovascular structures (vertebral arteries and spinal cord) and the wide range of motion of the joint, hampering bone fusion. A variety of techniques have been successively recommended to reduce anatomic risk and improve results in terms of biomechanical stability and fusion rates. Recently, Harms described a new technique using polyaxial screws in the C1 lateral masses and C2 pedicles.

MATERIAL AND METHOD
The present study reports our experience in a consecutive series of 26 patients operated on by C1-C2 arthrodesis using the Goel and Harms technique, and details technical aspects step by step. Routine systematic immediate postoperative CT and 6-month CT controlled screw positioning and assessed fusion. Follow-up was at least 1 year, except in 2 cases (10 months).

RESULTS
Twenty-six patients with a mean age of 57 years were included. Indications comprised: C2 non-union (n=11), C1-C2 fracture and/or dislocation (n=11), inflammatory pathology (n=2) and tumoral pathology (n=2). The results showed the technique to be reliable (no neurovascular complications and 85% of screws with perfect positioning) and an excellent rate of fusion (100% at 6 months).

CONCLUSION
Anatomic and biomechanical considerations, combined with the present clinical and radiological outcomes, indicate that Goel and Harms fusion is to be considered the first-line attitude of choice for posterior C1-C2 arthrodesis.

LEVEL OF EVIDENCE
Level IV prospective study.

Bourdillon|P|P| Perrin|G|G| Lucas|F|F| Debarge|R|R| Barrey|C|C|

Harms
C1-C2 fusion
C1-C2 instability
C1-C2 screws
Cervical fusion
Cervical spine arthrodesis