The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway.
As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development-related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual-luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR-93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6 K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6 K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC.


Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance in osteosarcoma.
Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.


Variation in practice for preoperative antibiotic prophylaxis: a survey from an academic tertiary referral center in the United States.
Antibiotic surgical prophylaxis is a core strategy for prevention of surgical site infections (SSI). Despite best practice guidelines and known efficacy of antibiotic prophylaxis in decreasing SSI risk, there is often wide variation in its use. This study was designed to determine the individual perspectives of perioperative providers at an academic tertiary referral center regarding their knowledge of preoperative antibiotic choice, dosing, and timing. A prospective survey was conducted amongst surgical and anesthesia team members involved in preoperative antibiotic decision making. The survey addressed ten key principles relating to preoperative antibiotic use, including antibiotic choice, timing and rate of infusion, and dosing. The survey was distributed among orthopaedic surgeons, residents, and anesthesia providers at their respective monthly service line meetings between August 2017 to June 2019. The data was stored and analyzed in a Microsoft Excel worksheet. A total of 73 providers completed the survey. Twenty-two (30 %) of the providers agreed and 47 (64 %) disagreed that both vancomycin and cefazolin are equally effective for antibiotic prophylaxis. As for antibiotic choice in patients with penicillin allergies, 37 (51 %) agreed with vancomycin, 21 (29 %) agreed with clindamycin, and 15 (21 %) disagreed with both alternatives. When providers were surveyed regarding the appropriateness of standard versus weight adjusted dosing, 67 (92 %) agreed that vancomycin should be weight adjusted and 63 (86 %) agreed that cefazolin should be weight adjusted. There is no clear consensus amongst providers for which antibiotic to administer for antibiotic prophylaxis despite existing guidelines. Discrepancy also exists between orthopaedic surgery and anesthesia providers in regards to appropriate antibiotic choice for patients with reported penicillin allergies. Institutions should implement evidence-based protocols for preoperative antibiotic prophylaxis and continue to prospectively monitor compliance in order to identify any inconsistencies that could result in inappropriate antibiotic prophylaxis for patients.


Solid-state NMR concepts for the investigation of supported transition metal catalysts and nanoparticles.
In recent years, solid-state NMR spectroscopy has evolved into an important characterization tool for the study of solid catalysts and chemical processes on their surface. This interest is mainly triggered by the need of environmentally benign organic transformations ("green chemistry"), which has resulted in a large number of new catalytically active hybrid materials, which are organized on the meso- and nanoscale. Typical examples of these catalysts are supported homogeneous transition metal catalysts or transition metal nanoparticles (MNPs). Solid-state NMR spectroscopy is able to characterize both the structures of these materials and the chemical processes on the catalytic surface. This article presents recent trends both on the characterization of immobilized homogeneous transition metal catalysts and on the characterization of surface species on transition metal surfaces.


Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression.
Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8. DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2. The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification. Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.


The relationship between breast cancer molecular subtypes and mast cell populations in tumor microenvironment.
Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples. Positive cells were counted within the tumor bed and at the invasive margin. For all analyzed MC subpopulations, we observed statistically significant differences between individual molecular subtypes of breast cancer. The significantly higher numbers of intratumoral chymase- and tryptase-positive mast cells were observed in luminal A and luminal B tumors compared to triple-negative and HER2+ non-luminal lesions. A denser MC infiltration was associated with lower tumor grade, higher ER and PR expression, lower proliferation rate as well as the lack of HER2 overexpression. The results obtained in our study indicate a possible association of chymase- and tryptase-positive MCs with more favorable cancer immunophenotype and with beneficial prognostic indicators in breast cancer.


The Effects of Workplace-Based HIV Self-testing on Uptake of Testing and Linkage to HIV Care or Prevention by Men in Uganda (WISe-Men): Protocol for a Cluster Randomized Trial.
HIV testing uptake remains low among men in sub-Saharan Africa. HIV self-testing (HIVST) at the workplace is a novel approach to increase the availability of, and access to, testing among men. However, both access and linkage to posttest services remain a challenge. The aim of this protocol is to describe a cluster randomized trial (CRT)-Workplace-Based HIV Self-testing Among Men (WISe-Men)-to evaluate the effect of HIVST in workplace settings on the uptake of HIV testing services (HTS) and linkage to treatment and prevention services among men employed in private security services in Uganda. This is a two-arm CRT involving men employed in private security services in two Ugandan districts. The participants in the intervention clusters will undergo workplace-based HIVST using OraQuick test kits. Those in the control clusters will receive routine HTS at their work premises. In addition to HTS, participants in both the intervention and control arms will undergo other tests and assessments, which include blood pressure assessment, blood glucose and BMI measurement, and rapid diagnostic testing for syphilis. The primary outcome is the uptake of HIV testing. The secondary outcomes include HIV status reporting, linkage into HIV care and confirmatory testing following HIVST, initiation of antiretroviral therapy following a confirmatory HIV test, the uptake of voluntary medical male circumcision, consistent condom use, and the uptake of pre-exposure prophylaxis by the most at-risk populations. Participant enrollment commenced in February 2020, and the trial is still recruiting study participants. Follow-up for currently enrolled participants is ongoing. Data collection and analysis is expected to be completed in December 2021. The WISe-Men trial will provide information regarding whether self-testing at worksites increases the uptake of HIV testing as well as the linkage to care and prevention services at male-dominated workplaces in Uganda. Additionally, the findings will help us propose strategies for improving men's engagement in HTS and ways to improve linkage to further care following a reactive or nonreactive HIVST result. ClinicalTrials.gov NCT04164433; https://clinicaltrials.gov/ct2/show/NCT04164433. DERR1-10.2196/25099.


Effective rotational correlation times of proteins from NMR relaxation interference.
Knowledge of the effective rotational correlation times, tauc, for the modulation of anisotropic spin-spin interactions in macromolecules subject to Brownian motion in solution is of key interest for the practice of NMR spectroscopy in structural biology. The value of tauc enables an estimate of the NMR spin relaxation rates, and indicates possible aggregation of the macromolecular species. This paper reports a novel NMR pulse scheme, [15N,1H]-TRACT, which is based on transverse relaxation-optimized spectroscopy and permits to determine tauc for 15N-1H bonds without interference from dipole-dipole coupling of the amide proton with remote protons. [15N,1H]-TRACT is highly efficient since only a series of one-dimensional NMR spectra need to be recorded. Its use is suggested for a quick estimate of the rotational correlation time, to monitor sample quality and to determine optimal parameters for complex multidimensional NMR experiments. Practical applications are illustrated with the 110 kDa 7,8-dihydroneopterin aldolase from Staphylococcus aureus, the uniformly 15N-labeled Escherichia coli outer membrane protein X (OmpX) in 60 kDa mixed OmpX/DHPC micelles with approximately 90 molecules of unlabeled 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), and the 16 kDa pheromone-binding protein from Bombyx mori, which cover a wide range of correlation times.


Functional molecule-mediated assembled copper nanozymes for diabetic wound healing.
The complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy. Herein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs). Secondly, the Cu-DCA NZs have excellent multicatalytic activity, and photothermal response under 808 nm irradiation. In vitro and in vivo experiments showed that it not only could efficiently inhibit bacterial growth though photothermal therapy, but also could catalyze the conversion of intracellular hydrogen peroxide to oxygen which relieves wound hypoxia and improving inflammatory accumulation. More importantly, the slow release of copper ions could accelerate cellular proliferation, migration and angiogenesis, synergistically promote the healing of diabetic wound furtherly. The above results indicate that this multifunctional nanozymes Cu-DCA NZs may be a potential nanotherapeutic strategy for diabetic wound healing.


Healing modulation induced by freeze-dried platelet-rich plasma and micronized allogenic dermis in a diabetic wound model.
The incidence and prevalence of chronic and diabetic wounds are increasing and clinical treatments to tackle these epidemics are still insufficient. In this study, we tested the ability of freeze-dried platelet-rich plasma (PRP) and an allogenic micronized acellular dermal matrix alone and in combination to modulate diabetic wound healing. Therapeutic materials were applied to 1.0 cm(2) excisional wounds on genetically diabetic (db/db) mice. Wound-healing kinetics and new tissue formation were studied at 9 and 21 days posttreatment. Quantitative immunohistochemistry was used to study vascularity and cellular proliferation (days 9 and 21), and collagen deposition was evaluated 21 days postwounding. In vitro, micronized allogenic dermis, when combined with PRP, absorbed nearly 50% of original platelet-derived growth factor, transforming growth factor-beta, vascular endothelial growth factor, and epidermal growth factor from platelets and stimulated fibroblast proliferation. In vivo, micronized dermis increased the formation of vascularized wound tissue by day 9. Freeze-dried PRP alone or in combination with micronized dermis increased wound tissue revascularization and proliferation compared with spontaneous healing. The increase in cell proliferation persisted until day 21 only when freeze-dried PRP was used in combination with micronized dermis. These results indicate that micronized allogenic dermis may be used to provide a dermal matrix to stimulate tissue formation and the combination with PRP may confer additional beneficial growth factors to chronic or diabetic wounds.


Does catheter type effect pregnancy rate in intrauterine insemination cycles?
To determine if a soft insemination catheter increases pregnancy rates. Seven hundred forty-seven consecutive intrauterine insemination (IUI) cycles in 364 women in a reproductive endocrinology office between October 1998 and March 2000. Patients with even birth years were inseminated with the Tomcat catheter, and those with odd birth year with the Wallace IUI catheter. Clinical pregnancy rates were compared. The Wallace catheter group included 180 women for 372 cycles and an overall pregnancy rate of 16.4%. The Tomcat catheter group included 184 women for 375 cycles and an overall pregnancy rate of 18.1%. This difference is not statistically significant (P = 0.61). Potential confounders were accounted for. When comparing the softer Wallace catheter to the less pliable Tomcat catheter during IUI cycles, there was no significant difference in pregnancy rate when using a standard gentle technique that includes not touching the top of the fundus with the catheter.


Adherence to a femoral neck fracture treatment guideline.
In 2007 the Dutch Surgical Society published a clinical practice guideline for the treatment of hip fracture patients, based on the best available international evidence at that time. We investigated to what extent treatment of femoral neck fracture patients in the Netherlands corresponded with these guidelines, and determined differences in patient characteristics between the treatment groups. All femoral neck fracture patients treated in 14 hospitals between February 2008 and August 2009 were included. Patient characteristics, X-rays, and treatment data were collected retrospectively. From a total of 1,250 patients 59% had been treated with arthroplasty, 39% with internal fixation, and 2% with a non-operative treatment. While 74% of the treatment choices complied with the guideline, 12% did not. In 14% adherence could not be determined from the available data. Arthroplasty was preferred over internal fixation in elderly patients with severe comorbidity, pre-fracture osteoporosis and a displaced fracture, who were ambulatory with aids pre-fracture (odds ratio, OR 2.2-58.1). Sliding hip screws were preferred over cancellous screws in displaced fractures (OR 1.9). Overall guideline adherence was good. Most deviations concerned treatment of elderly patients with a displaced fracture and implant use in internal fixation. Additional data on these issues, preferably at a higher scientific level of evidence, is needed in order to improve the guideline and to reinforce a more uniform treatment of these patients.


Autophagy regulates odontoblast differentiation by suppressing NF-κB activation in an inflammatory environment.
Odontoblasts are derived from dental papilla mesenchymal cells and have an important role in defense against bacterial infection, whereas autophagy can recycle long-lived proteins and damaged organelles to sustain cellular homeostasis. Thus, this study explores the role of autophagy in odontoblast differentiation with lipopolysaccharide (LPS) stimulation in vitro and the colocalization of p-NF-κB and LC3 in caries teeth. The odontoblasts differentiation was enhanced through LPS stimulation, and this outcome was reflected in the increased number of mineralized nodules and alkaline phosphatase (ALP) activity. The expression levels of the autophagy markers LC3, Atg5, Beclin1 and TFE3 increased time dependently, as well along with the amount of autophagosomes and autophagy fluxes. This result suggests that autophagy was enhanced in odontoblasts cultured with mineralized-induced media containing LPS. To confirm the role of autophagy in differentiated odontoblasts with LPS stimulation, chloroquine (CQ) or rapamycin were used to either block or enhance autophagy. The number of mineralized nodules decreased when autophagy was inhibited, but this number increased with rapamycin treatment. Phosphorylated nuclear factor-κB (NF-κB) expression was negatively related to autophagy and could inhibit odontoblast differentiation. Furthermore, p-NF-κB and LC3 colocalization could be detected in cells stimulated with LPS. The nucleus translocation of p-NF-κB in odontoblasts was enhanced when autophagy was inhibited by Atg5 small interfering RNA. In addition, the colocalization of p-NF-κB and LC3 in odontoblasts and sub-odontoblastic layers was observed in caries teeth with reactionary dentin. Therefore, our findings provide a novel insight into the role of autophagy in regulating odontoblast differentiation by suppressing NF-κB activation in inflammatory environments.


(Membrane) Protein Production in Context.
Great progress has been made in elucidating the structural and mechanistic basis of (membrane) protein production. Here, we attempt to look ahead and indicate four directions in which our understanding of the protein production process can grow: (i) determine how the molecular mechanisms influence higher-level processes, such as the distribution of protein copy number over a population of cells or the cell growth rate; (ii) explore the functional landscape that the molecular mechanisms of protein production exist in, for instance by comparing membrane protein insertion mechanisms; (iii) uncover the life history of proteins - that is, what happens to them between their synthesis and degradation; and (iv) determine, and connect by calculation, the numbers that are associated with (membrane) protein production.


Design and synthesis of transparent and flexible nanofibrillated cellulose films to replace petroleum-based polymers.
Nanofibrillated cellulose films have garnered attention due to their interesting proprieties such as transparency and high mechanical strength. However, they are brittle, very hydrophilic, which is decreasing their potential applications. We have successfully achieved a simple and effective chemical modification based on polymer grafting and through plasticizer additions to increase the performance of the films as well as to improve the compatibility within conventional polymer. A preliminary study shows the possibility of using this film as an interlayer in safety glazing and/or bulletproof glass with polyvinyl butyral (PVB). The modified NFC films displays high optical transmittance (93 %), increases tensile stretch and is more hydrophobic (83°). A higher flexibility was also achieved, as the film was greatly stretched and bended without cracking or breaking. The NFC / PVB composite has three times more elongation at break, 13 % more specific energy absorbed with a half-tensile stress compared to an interlayer of PVB.


A review of high-dose intravenous immunoglobulin treatment for atopic dermatitis.
Atopic dermatitis generally responds to topical therapy; however, small numbers of patients have severe resistant disease despite second line therapies. High-dose intravenous immunoglobulin (HdIVIg) which is being used increasingly for dermatological indications has been suggested to be of benefit in a small number of uncontrolled trials and case reports. The mode of action is via a number of immunomodulatory mechanisms and it is not associated with the many side-effects of steroids and other immunosuppressive agents. There are now reports of 32 atopic dermatitis patients treated with HdIVIg, and this review aims to make a critical assessment of the current data. These have been obtained from a Medline search of the English literature from 1966 to 2001 for intravenous immunoglobulin and atopic dermatitis/eczema. Taken together an improvement was observed in 61% of atopic dermatitis patients treated with HdIVIg. Adults appeared less likely to respond (48%) than children (90%) and the duration of response was also more prolonged in children. Adjunctive therapy in adults was more effective than monotherapy (59% vs 0%), whereas monotherapy was effective in 90% of children. HdIVIg may offer a safe potential therapeutic avenue for resistant cases of atopic dermatitis, particularly in children, but should be further assessed using double-blind placebo-controlled trials.


Prevalence of dry eye syndrome among US women.
Dry eye syndrome (DES) is believed to be one of the most common ocular problems in the United States (US), particularly among older women. However, there are few studies describing the magnitude of the problem in women and how this may vary with demographic characteristics. Cross-sectional prevalence survey. we surveyed 39,876 US women participating in the Women's Health Study about a history of diagnosed DES and dry eye symptoms. we defined DES as the presence of clinically diagnosed DES or severe symptoms (both dryness and irritation constantly or often). We calculated the age-specific prevalence of DES and adjusted the overall prevalence to the age distribution of women in the US population. We used logistic regression to examine associations between DES and other demographic factors. The prevalence of DES increased with age, from 5.7% among women < 50 years old to 9.8% among women aged > or = 75 years old. The age-adjusted prevalence of DES was 7.8%, or 3.23 million women aged > or = 50 in the US. Compared with Whites, Hispanic (odds ratio [OR] = 1.81, confidence interval [CI] = 1.18-2.80) and Asian (OR = 1.77, CI = 1.17-2.69) women were more likely to report severe symptoms, but not clinically diagnosed DES. There were no significant differences by income (P([trend]) =.78), but more educated women were less likely to have DES (P([trend]) =.03). Women from the South had the highest prevalence of DES, though the magnitude of geographic differences was modest. Dry eye syndrome leading to a clinical diagnosis or severe symptoms is prevalent, affecting over 3.2 million American women middle-aged and older. Although the condition is more prevalent among older women, it also affects many women in their 40s and 50s. Further research is needed to better understand DES and its impact on public health and quality of life.


Novel surgical quality metrics in abdominal aortic aneurysm repair.
Existing surgical quality metrics have limited utility, are primarily used for high-mortality procedures, and often fail to account for differences in non-fatal outcomes. Our objective was to develop more comprehensive, novel surgical quality metrics, for patients undergoing abdominal aortic aneurysm (AAA) repair. Non-ruptured open and endovascular AAA repair (EVAR) from the Vascular Quality Initiative database were studied, 2016-2019. A win was defined as AAA repair without major complication (in-hospital) or mortality (in-hospital or within 30 days). Centers were divided into quality quartiles based on performance in two novel win-based metrics: (1) Wins Above Average (WAA) and (2) weighted Wins Above Average (wWAA). Patient-level and center-level analyses compared demographics and outcomes between "best" and "worst" quartiles, including wins, mortality, and failure to rescue (FTR) rates. Additional patient-level analyses were performed based on center stratification into volume quartiles. Correlation in surgical quality for open repair and EVAR was determined at centers performing both procedures. Overall, 3683 patients underwent open repair and 21,165 patients underwent EVAR. For open repair, crude rates of win, mortality, and FTR were 62.8%, 4.2%, and 10.3%, respectively. For EVAR, crude rates for win, mortality, and FTR were 94.4%, 1.1%, and 12.3%, respectively. When stratified by wWAA, patients undergoing open repair at "best" quartile centers had a higher win rate (72.0% vs 52.7%; risk ratio [RR], 1.37; 95% confidence interval [CI], 1.28-1.46) and lower mortality (3.1% vs 6.2%; RR, 0.50; 95% CI, 0.33-0.74) compared with "worst" quartile centers. Similarly, for EVAR, "best" quartile centers had a higher win rate (96.2% vs 92.1%; RR, 1.04; 95% CI, 1.03-1.05), lower mortality (0.4% vs 2.2%; RR, 0.19; 95% CI, 0.13-0.29), and a lower FTR rate (5.7% vs 17.9%; RR, 0.32; 95% CI, 0.18-0.56) compared with "worst" quartile centers. Stratification by volume showed that high-volume centers demonstrated improved wWAA for open repair (P = .04) but not for EVAR (P = .3) compared with low-volume centers. For centers that performed both open repair and EVAR, there was no correlation in quality as determined by wWAA (r = -0.056; P = .6). wWAA is a novel, risk-adjusted, complication-weighted surgical quality metric that also accounts for volume differences. wWAA successfully distinguishes high- and low-quality centers for both open AAA repair and EVAR. This methodology is potentially broadly applicable for measuring surgical quality.


Adaptation and validation of the chronic illness-related shame scale among patients with knee osteoarthritis in Singapore.
Osteoarthritis (OA) of the knee is one of the most common and disabling conditions worldwide. A neglected aspect of knee OA is its psychosocial impact, such as shame. However, assessment tools to measure shame among patients diagnosed with knee OA are lacking. In this study, the psychometric properties of the Chronic Illness-related Shame Scale (CISS) were evaluated among knee OA patients in Singapore. Adaptations were made to CISS for use among the knee OA population. An exploratory factor analysis (EFA) was performed to analyze the factor structure. Cronbach's Alpha and corrected item-total correlations were used to evaluate the internal consistency. Spearman correlation coefficient was used to test the correlation between CISS and Patient Health Questionnaire-4 (PHQ-4) to determine the validity of the instrument. The EFA yielded a one-factor structure, with an eigenvalue of 4.78 explaining 68.25% of variance. Cronbach Alpha was 0.92, which indicated good internal consistency. The Spearman correlation revealed a significant correlation between CISS and PHQ-4. The adapted CISS is a valid and reliable instrument to measure shame for knee OA patients. Both research and clinical settings can benefit from the use of the adapted CISS for assessing shame among knee OA patients.


Managing healthcare supply chain through artificial intelligence (AI): A study of critical success factors.
Healthcare is one of the most critical sectors due to its importance in handling public health. With the outbreak of various diseases, more recently during Covid-19, this sector has gained further attention. The pandemic has exposed vulnerabilities in the healthcare supply chain (HSC). Recent advancements like the adoption of various advanced technologies viz. AI and Industry 4.0 in the healthcare supply chain are turning out to be game-changers. This study focuses on identifying critical success factors (CSFs) for AI adoption in HSC in the emerging economy context. Rough SWARA is used for ranking CSFs of AI adoption in HSC. Results indicate that technological (TEC) factors are the most influential factor that impacts the adoption of AI in HSC in the context of emerging economies, followed by institutional or environmental (INT), human (HUM), and organizational (ORG) dimensions.


A case series of coinfection with SARS-CoV-2 and influenza virus in Louisiana.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the novel coronavirus initially detected in Wuhan, China, and is responsible for the worldwide pandemic coronavirus disease 2019 (Covid-19). Influenza is a common endemic respiratory virus that causes seasonal outbreaks of respiratory illness. There are currently few reports in the literature describing patients with coexisting infections. This case series of 4 patients identified at our single institution in Louisiana highlights the patient characteristics, laboratory findings, and outcomes in patients with both Covid-19 and influenza infection.


Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3.
The RNA-mediated pathogenesis model for the myotonic dystrophies DM1 and DM2 proposes that mutant transcripts from the affected genes sequester a family of double-stranded RNA-binding factors, the muscleblind proteins MBNL1, MBNL2 and MBNL3, in the nucleus. These proteins are homologues of the Drosophila muscleblind proteins that are required for the terminal differentiation of muscle and photoreceptor tissues, and thus nuclear sequestration of the human proteins might impair their normal function in muscle and eye development and maintenance. To examine this model further, we analyzed the expression pattern of the mouse Mbnl1, Mbnl2, and Mbnl3 genes during embryonic development and compared muscleblind gene expression to Dmpk since the RNA pathogenesis model for DM1 requires the coordinate synthesis of mutant Dmpk transcripts and muscleblind proteins. Our studies reveal a striking overlap between the expression of Dmpk and the muscleblind genes during development of the limbs, nervous system and various muscles, including the diaphragm and tongue.


[Migraine prophylaxis with calcium antagonists: a haemodynamic study using transcranial Doppler ultrasound].
Despite its widespread use, a good explanation for the mechanism of action of calcium antagonists (CA) in the prophylaxis of migraine has still not been proposed. To determine whether nicardipine and flunarizine therapy is capable of inducing changes in the brain haemodynamics of migraine sufferers that lend support to a vascular mechanism of action for these drugs, as evaluated by transcranial Doppler ultrasound (TCD). We present a prospective, descriptive study based on observation conducted in a Neurology outpatients department. Patients between the ages of 16 and 50 with migraine (following IHS criteria) who were being treated with nicardipine and flunarizine as a prophylactic measure and did not fulfil any of the exclusion criteria were selected consecutively. The TCD study was performed before and during treatment with CA (flunarizine or nicardipine), for a minimum of one month. The following haemodynamic variables were determined: mean speed, Gosling's pulsatility index and cerebrovascular reserve, determined by the breath holding index. Pre and post-prophylaxis variables were compared using the Wilcoxon signed rank test. Eight patients with migraine were included in the study and no significant differences in any of the three haemodynamic variables were observed between the values obtained prior to or during treatment. The absence of haemodynamic changes in TCD does not lend support to a vascular mechanism of action for CA in migraine.


Casticin and chrysosplenol D from Artemisia annua L. induce apoptosis by inhibiting topoisomerase IIα in human non-small-cell lung cancer cells.
Artemisia annua L. (A. annua) and its active components exhibit antitumour effects in many cancer cells. However, the biological processes and mechanisms involved are not well understood, especially for the treatment of non-small-cell lung cancer (NSCLC). This study aimed to comprehensively explore the biological processes of A. annua and its active components in NSCLC cells and to identify the mechanism by which these compounds induce apoptosis. Cell viability and flow cytometry assays were used to evaluate the cytotoxicity of A. annua active components casticin (CAS) and chrysosplenol D (CHD) in A. annua in NSCLC cells. After treatment with CAS and CHD, A549 cells were subjected to RNA sequencing (RNA-seq) analysis, differentially expressed genes (DEGs) were screened and subjected to functional enrichment analysis (KEGG and GO analysis) as well as protein interaction network analysis. The key targets associated with apoptosis induction in A549 cells were screened by Cytoscape, and the screened DEGs were validated by qRT-PCR. Immunoblotting, immunofluorescence, and molecular docking assays were used to determine whether CAS and/or CHD could induce apoptosis in NSCLC cells by inducing DNA damage through down-regulation of topoisomerase IIα (topo IIα) expression. The same experiments were verified again in the H1299 lung cancer cell line. CAS and CHD inhibited NSCLC cells proliferation in a time- and dose-dependent manner, and significantly induced apoptosis. A total of 115 co-upregulated DEGs and 277 co-downregulated DEGs were identified in A549 cells following treatment with CAS and CHD. Comprehensive and systematic data about biological processes and mechanisms were obtained. DNA damage pathways and topo IIα targets were screened to study the apoptosis effects of CAS and CHD on NSCLC cells. CAS and CHD may be able to induce DNA damage by binding to topo IIα-DNA and reducing topo IIα activity. This study suggested that CAS and CHD may reduce topo IIα activity by binding to topo IIα-DNA, affecting the replication of DNA, triggering DNA damage, and inducing apoptosis. It described a novel mechanism associated with topo IIα inhibition to reveal a novel role for CAS and CHD in A. annua as potential anticancer agents and/or adjuvants in NSCLC cells.


Cesarean section and the manipulation of exact delivery time.
Physicians are often alleged responsible for the manipulation of delivery timing. We investigate this issue in a setting that negates the influence of financial incentives on physician's behavior. Working on a sample of women admitted at the onset of labor in a big public hospital in Italy we estimate a model for the exact time of delivery as driven by individual Indication to Cesarean Section (ICS) and covariates. We find that ICS does not affect the day of delivery but leads to a circadian rhythm in the likelihood of delivery. The pattern is consistent with the postponement of high ICS deliveries in the late night\early morning shift. Our evidence hardly supports the manipulation of timing of births as driven by medical staff's "demand for leisure". Physicians seem to manipulate the exact timing of delivery to reduce exposure to risk factors extant during off-peak periods.


Meniscal bucket handle tears: a retrospective study of arthroscopy and the relation to MRI.
In this study, we aim to evaluate the arthroscopic findings of meniscal bucket handle tears and to correlate them with the proposed MR imaging signs of meniscal bucket handle tears suggested in the literature. Thirty-six patients who had a diagnosis of bucket handle tear in arthroscopy, in either medial or lateral meniscus, were included in our study (32 males and 4 females). Meniscal tears were evaluated in arthroscopy according to Dandy's classification. The MRIs were retrospectively analyzed regarding the following findings: absence of bow tie sign, presence of double posterior cruciate ligament (PCL) sign, double anterior horn sign, flipped meniscus sign, disproportional posterior horn sign, and fragment within the intercondylar region. Locked types I and II fragment of medial meniscus and half-length, whole-width and whole length-half-width fragment of lateral meniscus in arthroscopy were basically correlated with fragment within the intercondylar notch and absent bow tie signs in MRI. We did not find the double PCL sign in any of the patients with a lateral meniscal bucket handle tear. The most common signs in MR images of meniscal bucket handle tears were the fragment in the notch sign and the absent bow tie sign. They were observed with equal frequency of 88.8%. The presence of double PCL sign, double anterior horn sign, flipped meniscus sign, disproportional posterior horn sign were less common (41.66, 33, 25, and 27.7%, respectively). We conclude that the presence of at least two of the six MRI signs should be regarded as highly suggestive for bucket handle tears of menisci.


Intraluminal esophageal diverticulum.
An intraluminal esophageal diverticulum (IED) is an uncommon entity defined as a double-layered mucosal pouch lying within the lumen of the esophagus. Its characteristic radiological finding is an intraluminal barium collection surrounded by a radiolucent halo. True IED, which is different from a transient radiological artifact, has not been previously reported in the international literature. This article describes the first case of true IED. Differential diagnosis between a true lesion and a transient flow artifact on barium meal is discussed.


Suicide associated with COVID-19 infection: an immunological point of view.
Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. Patients infected with COVID-19 have high amounts of IL-1β, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.


Neurotypicals with higher autistic traits have delayed visual processing of an approaching life-sized avatar's gait: an event-related potentials study.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which is reportedly related to difficulties in the visual processing of human motion, such as biological motion and gestures. Moreover, neurotypical (here, we mention it as individuals without a diagnosis) adults with autistic traits are clumsier than those without autistic traits when passing by others. It is still unclear whether the clumsiness derived from atypical visual processing of another's approaching gait motion. We aim to address this question by investigating the association between autistic traits in neurotypical adults and the visual processing of an approaching life-sized avatar's gait. We clarified a typical visual motion processing and autistic traits in daily life in 26 neurotypical adults by analyzing the subthreshold autism trait questionnaire (SATQ) score, a 24-item self-report scale of ASD, and event-related potentials (ERPs) in response to walking motion of a passing avatar. Videos of walking life-sized virtual avatars approaching and retreating were presented as visual stimuli. The association between the participants' SATQ scores and the latencies and amplitudes of the ERPs was examined. ERP components (N170 and P200) components were identified at T5 and T6 electrodes. Participants reporting higher SATQ scores had longer latencies of P200 at T6 and lower amplitudes of P200 at T5 and T6 electrodes for the approaching avatar than those reporting lower SATQ scores. These findings indicate that adults with autistic traits have delayed and less sensitive visual processing of the approaching avatar. It suggests that while passing another person, these individuals have atypical visual processing of their approach. This study may contribute to elucidating autistic traits from the perspective of visual processing in an environment simulating daily life.


Stable interaction between alpha5beta1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1.
During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could cross-talk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that alpha5beta1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and alpha5beta1 interact constitutively; alpha5beta1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively alpha5beta1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and alpha5beta1 receptors that could cross-talk when Tie2/alpha5beta1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that alpha5beta1, but not alphavbeta3 activation, is essential to Ang-1-dependent angiogenesis in vivo.


Alcohol and Sexual Risk Behaviors Among Male Central Asian Labor Migrants and Non-migrants in Kazakhstan: Implications for HIV Prevention.
This paper examines the association between alcohol consumption and sexual risk behaviors (unprotected sex, multiple sex partners, sex under influence of drugs or alcohol and commercial sex) in a sample of Central Asian migrant and non-migrant laborers in the largest marketplace in Kazakhstan. We used data from The Silk Road Health Project, conducted from 2010 to 2013 with 1342 male migrant and non-migrant market workers. Participants were selected through respondent driven sampling at the Baraholka Market in Almaty, Kazakhstan. We used regression analyses adjusting for potential confounders to examine the relationship between alcohol consumption and sexual risk behavior. We found that hazardous drinking was associated with an increase in the odds of sex under the influence of drugs (aOR = 6.09, 95% CI 3.48, 10.65; p < .001) and purchasing commercial sex (aOR = 2.02, 95% CI 1.02, 4.02; p < .05). We identified potential targets for HIV interventions to reduce sexual risk behaviors among this key population.


Exploiting differences in caspase-2 and -3 S₂ subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors.
Several caspases have been implicated in the pathogenesis of Huntington's disease (HD); however, existing caspase inhibitors lack the selectivity required to investigate the specific involvement of individual caspases in the neuronal cell death associated with HD. In order to explore the potential role played by caspase-2, the potent but non-selective canonical Ac-VDVAD-CHO caspase-2 inhibitor 1 was rationally modified at the P(2) residue in an attempt to decrease its activity against caspase-3. With the aid of structural information on the caspase-2, and -3 active sites and molecular modeling, a 3-(S)-substituted-l-proline along with four additional scaffold variants were selected as P(2) elements for their predicted ability to clash sterically with a residue of the caspase-3 S(2) pocket. These elements were then incorporated by solid-phase synthesis into pentapeptide aldehydes 33a-v. Proline-based compound 33h bearing a bulky 3-(S)-substituent displayed advantageous characteristics in biochemical and cellular assays with 20- to 60-fold increased selectivity for caspase-2 and ∼200-fold decreased caspase-3 potency compared to the reference inhibitor 1. Further optimization of this prototype compound may lead to the discovery of valuable pharmacological tools for the study of caspase-2 mediated cell death, particularly as it relates to HD.


Multiple large splenic abscesses managed with computed tomography-guided percutaneous catheter drainage in children.
Splenic abscess is a rare finding in children. Splenectomy combined with broad-spectrum antibiotics has been the treatment of choice for multiple splenic abscesses. Herein, we report the case of a 14-year-old girl with multiple large splenic abscesses that were successfully managed after two image-guided percutaneous drainage procedures and administration of intravenous antibiotics. Initially, an abscess located at the periphery in the lower pole of the spleen was aspirated under ultrasound guidance. Finally, another abscess located near the hilum of the spleen was drained under computed tomography guidance. To the best of our knowledge, this is the first report of multiple large splenic abscesses treated with computed tomography-guided percutaneous drainage.


The role of rhynchophylline in alleviating early brain injury following subarachnoid hemorrhage in rats.
Rhynchophylline (Rhy) has been demonstrated protective effects on some neurological diseases. However, the roles of Rhy in the subarachnoid hemorrhage (SAH) are still to be cleared. In the present study, the effects of Rhy on attenuation of early brain injury (EBI) after SAH have been evaluated. The adult male Sprague-Dawley rats (280-300g) were used to establish the SAH models using endovascular perforation method. Rhy was administered by intraperitoneal injection immediately following SAH. Brain edema was assessed by magnetic resonance imaging (MRI) at 24h after SAH. Neurological deficits, brain water content, malondialdehyde (MDA) concentration, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) content in hippocampus were also evaluated. Immunofluorescence and western blot were used to explore the underlying protective mechanism of Rhy. The results showed that, following 10mg/kg Rhy treatment, the brain edema and neurological deficits, and blood-brain barrier (BBB) disruption were significantly attenuated at 24h after SAH. Additionally, in hippocampus, MDA concentration, MPO activity and ROS content were markedly decreased. Meanwhile, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase (NQO-1) were increased, while the expressions of p-p53, cleaved-caspase-3 and tumor necrosis factor-α (TNF-α) were significantly decreased. Our results indicated that Rhy could attenuate early brain injury by reducing inflammation and apoptosis in hippocampus after SAH.


[Morbidity of alcoholic employees. Examples from 2 public facilities in Switzerland].
Morbidity of of alcoholic employees. Results of a case/control study on 2 samples of civil servants. The data of this retrospective study were obtained mainly from files kept at the centralized medical service. The observation period was 10 years. The alcoholics (n = 64) lost in the average 19.3 or 16.1 days more per year through sickness absence and they spent considerably more days in hospitals than their control groups. Significant differences occurred also concerning frequences of medical diagnoses.


Invited article: Neurology education research.
There is a need to rigorously study the neurologic education of medical students, neurology residents, and neurologists to determine the effectiveness of our educational efforts. We review the status of neurologic education research as it pertains to the groups of interest. We identify opportunities and impediments for education research. The introduction of the Accreditation Council for Graduate Medical Education core competencies, the Accreditation Council of Continuing Medical Education requirement to link continuing medical education to improved physician behavior and patient care, and the American Board of Medical Specialties/American Board of Psychiatry and Neurology-mandated maintenance of certification program represent research opportunities. Challenges include numerous methodologic issues such as definition of the theoretical framework of the study, adequate sample size ascertainment, and securing research funding. State-of-the-art education research will require multidisciplinary research teams and innovative funding strategies. The central goal of all concerned should be defining educational efforts that improve patient outcomes.


Historical Perspective of Imaging Contrast Agents.
Contrast agents were introduced early in the history of medical imaging. Iodine-based intravascular agents became the radiographic compounds of choice and refinements of their chemical structures led to the highly tolerated low-osmolarity agents in use today. Gadolinium became the most popular compound for MR imaging; however, recognition of nephrogenic systemic fibrosis and in vivo dechelation intensified research on their safety profile. Ultrasonography contrast media evolved from manual injections of air through agitated saline solutions to microbubbles with different gases. Research has concentrated on bubble stabilization and development of small but sufficiently echogenic particles.


Influence of social rank on the development of long-term ethanol drinking trajectories in cynomolgus monkeys.
Chronic stress contribute to the development of alcohol use disorder (AUD). However, characterizing the role of chronic social stressors in the development of problematic drinking trajectories in humans is complicated by practical and ethical constraints. Group-housed nonhuman primates develop social dominance hierarchies that represent a continuum of social experiences from enrichment in higher-ranked (dominant) monkeys to chronic social stress in lower-ranked (subordinate) individuals. This framework provides a translationally relevant model of chronic social stress that can be used to characterize its effects on vulnerability to AUD. Twelve male cynomolgus monkeys living in three social groups with established social dominance hierarchies were provided access to ethanol and water for 22 h/day, 4-5 days/week, for 1 year. Ethanol-free periods (2- or 3-day "weekends" or longer periods up to 10 days) were spent in social groups to maintain the stability of the social hierarchies. Observational studies conducted 6 months into the year of drinking assessed signs of ethanol withdrawal. After 1 year, monkeys were individually housed 24 h/day, 7 days/week for four consecutive weeks to examine the effect of eliminating the "weekends" spent socially housed. Subordinate monkeys had significantly higher mean daily ethanol intakes than dominant monkeys across 1 year of open access. Subordinates also had higher intakes on the first day back drinking following ethanol-free periods of 9-10 days. Moreover, during the last 4 weeks of open access, intakes on the first drinking day after an ethanol-free weekend increased significantly in subordinate monkeys. This effect diminished when all monkeys were individually housed for 4 weeks, indicating that the increased intake in subordinates was driven by the social environment. These data demonstrate that social subordination, which is associated with chronic social stress, results in increased vulnerability to the development and maintenance of heavy drinking trajectories.


Strategies for successfully managing the anemia of chronic kidney disease in the long-term care setting.
To provide an overview of the challenges of and strategies for treating anemia associated with chronic kidney disease (CKD) in geriatric patients. Recent literature (1995-present) Papers that focused on geriatric patients and provided background on erythropoiesis and management of anemia that is associated with CKD disease were reviewed and included. Data included in the review are relevant to the risks and benefits of treatments for anemia that is associated with CKD. A review of the data allowed a relevant discussion of the current knowledge base of anemia that is associated with CKD in geriatric patients with a goal of enhancing the clinician's ability to effectively manage anemia in this population. The treatment of the anemia of CKD in the long-term care setting requires an understanding of the risks and limitations of the currently available therapies. Erythropoiesis-stimulating agents are often indicated in combination with iron supplementation. The activity and adverse effect profiles of the available agents are comparable. The decision to treat anemia in the long-term care setting should be based on a consideration of the risks and benefits of treatment.


Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.
The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.


The significance of alpha/beta interferons and gamma interferon produced in mice infected with Listeria monocytogenes.
Interferon (IFN)-alpha/beta was induced in the circulation of mice infected intravenously with Listeria monocytogenes 24 to 72 hr after infection, but was not induced by the administration of heat-killed Listeria, listerial cell wall fraction (LCWF), or listerial soluble fraction. Appearance of IFN-alpha/beta showed a pattern similar to that of the growth of bacteria in the spleen and the liver of mice. IFN-alpha/beta production was abrogated by pretreatment of mice with anti-asialo GM1 antibody, antithymocyte serum, or hydrocortisone, but not with cyclophosphamide or carrageenan. Such treatments which suppressed IFN-alpha/beta production did not influence bacterial growth in the organs of mice in the early stage of Listeria infection. Administration of IFN-alpha/beta exogenously also did not. After 5 days of infection when the specific resistance against reinfection with Listeria was established, IFN-gamma but not IFN-alpha/beta was induced in the circulation 3 to 6 hr after stimulation with LCWF or reinfection with Listeria. IFN-gamma production was abrogated completely by cyclophosphamide and antithymocyte serum, and partially by hydrocortisone and carrageenan, but not by anti-asialo GM1 antibody in Listeria-infected mice treated with these agents before induction of IFN-gamma by LCWF. Presumably, IFN-alpha/beta might be produced by asialo GM1-bearing cells but IFN-gamma might not. However, IFN-gamma production was suppressed in Listeria-infected mice, when IFN-alpha/beta production had been inhibited by treatment with anti-asialo GM1 antibody or when the IFN produced had been neutralized with anti-mouse IFN-alpha/beta antibody. Therefore, it is conceivable that IFN-alpha/beta might be essential for the generation or the expression of antigen-specific T cells involving IFN-gamma production and acquired resistance during Listeria infection. In fact, the bacterial growth in the organs of mice in the early stage of infection was normal in IFN-alpha/beta-depleted mice but it resulted in the delay of T-cell-dependent elimination of bacteria from the organs of mice in the late stage.


Effect of coconut oil on growth performance, carcass criteria, liver and kidney functions, antioxidants and immunity, and lipid profile of broilers.
The aim of this study is to evaluate the beneficial effects of coconut essential oil on growth performance, carcass criteria, antioxidant status, and immune response of broiler chicks. A total of 192 un-sexed 7-days broiler chicks were divided into six treatment sets with four copies of 8 chicks per set. The groups were as follows: (1) basal diet (without additive), (2) basal diet plus 0.5 ml coconut essential oil/kg, (3) basal diet plus 1 ml coconut essential oil/kg, (4) basal diet plus 1.5 ml coconut essential oil/kg, (5) basal diet plus 2 ml coconut essential oil/kg and (6) basal diet plus 2.5 ml coconut essential oil/kg. The results showed that the most prevalent compound in coconut oil is 6-Octadecenoic acid (oleic acid) representing 46.44% followed 2(3H)-Furanone, dihydro-5-pentyl- (CAS) (11.36%), Hexadecanoic acid (CAS) (4.71%), and vanillin (2.53%). Dietary 1 and 1.5 ml of coconut oil improved significantly the body weight and gain of broiler chickens. Dietary supplementation of 1 ml of coconut oil improved significantly liver function compared to control and other treatment groups. The supplementation with 1 ml coconut oil significantly reduced TG and VLDL compared to control and other treatment groups, while no significant differences in TC, HDL, and LDL due to dietary coconut oil. The present findings showed that dietary coconut oil with 1 and 1.5 ml/kg feed improved significantly antioxidants status through increased antioxidant enzymes like SOD and GSH while decreasing significantly MDA levels compared to control and other treatment groups. Therefore, it was concluded that the diets of broiler chickens could be fortified with coconut oil with 1 or 1.5 ml to improve the growth, feed utilization, and antioxidant status of broiler chickens.


Improving the antidepressant action and the bioavailability of sertraline by co-crystallization with coumarin 3-carboxylate. Structural determination.
To improve the antidepressant action of sertraline a new salt with coumarin-3-carboxylate anion (SerH-CCA) has been synthesized by two different methods and characterized by FTIR spectroscopy and structural determinations by X-ray diffraction methods. The new salt is stabilized by strong intermolecular H-bonds involving the protonated amine group of SerH and the deprotonated carboxylate group of CCA. These findings can be correlated with the interpretation of the infrared spectrum. The salt, sertraline (SerHCl) and the sodium salt of coumarin-3-carboxylate (NaCCA) were orally administered male Wistar rats (10 mg/kg, based on sertraline). Rats were evaluated in separate groups by means of the forced swimming (FST). SerH-CCA produced antidepressant effects in a magnitude that exceeded SerHCl individual effects. None of these treatments affected activity levels by the open field OFT tests. We have also determined that the ion pair also improve the binding to bovine serum albumin (BSA) of the drug but retain its antimicrobial activity. It is reasonable to conclude that the replacement of chloride anion by a large organic anion in sertraline strengthens the pharmacological action of the native drug, binding to BSA with higher activity and retaining the antimicrobial activity of the antidepressant compound.


Recent developments in research on water oxidation by photosystem II.
Photosynthetic water oxidation chemistry at the unique manganese-calcium complex of photosystem II (PSII) is of fundamental importance and serves as a paragon in the development of efficient synthetic catalysts. A recent crystal structure of PSII shows the atoms of the water-oxidizing complex; its Mn4CaO5 core resembles inorganic manganese-calcium oxides. Merging of crystallographic and spectroscopic information reverses radiation-induced modifications at the Mn-complex in silico and facilitates discussion of the O-O bond chemistry. Coordinated proton movements are promoted by a water network connecting the Mn4CaO5 core with the oxidant, a tyrosine radical and one possibly mobile chloride ion. A basic reaction-cycle model predicts an alternating proton and electron removal from the catalytic site, which facilitates energetically efficient water oxidation.


High-level secretory expression, purification and characterization of Ailuropoda melanoleuca growth hormone in Pichia pastoris.
Growth hormone is one of the most important hormones, which is involved in many reproductive processes of giant panda Ailuropoda melanoleuca. In this study, the mature peptide of A. melanoleuca growth hormone (AmGH) was successfully expressed and secreted in Pichia pastoris under the control of AOX1 promoter. The expression condition for AmGH in P. pastoris, such as the expression time, pH value and methanol concentration in the BMMY were optimized and the AmGH expression level is about 100 mg/L using GS115 recombinant under optimized condition (96 h of 1.5% methanol induction). The secreted nascent AmGH were purified using ammonium sulfate fractionation. The mature AmGH protein exhibited a molecular mass of approximately 22 kDa on SDS-PAGE. This study would provide a new opportunity for large-scale expression and purification of AmGH, which might facilitate studies on the biological activity of AmGH.


The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils.
The function of the kinase Btk in neutrophil activation is largely unexplored. Here we found that Btk-deficient neutrophils had more production of reactive oxygen species (ROS) after engagement of Toll-like receptors (TLRs) or receptors for tumor-necrosis factor (TNF), which was associated with more apoptosis and was reversed by transduction of recombinant Btk. Btk-deficient neutrophils in the resting state showed hyperphosphorylation and activation of phosphatidylinositol-3-OH kinase (PI(3)K) and protein tyrosine kinases (PTKs) and were in a 'primed' state with plasma membrane-associated GTPase Rac2. In the absence of Btk, the adaptor Mal was associated with PI(3)K and PTKs at the plasma membrane, whereas in control resting neutrophils, Btk interacted with and confined Mal in the cytoplasm. Our data identify Btk as a critical gatekeeper of neutrophil responses.


Waist circumference, BMI, and visceral adipose tissue in white women and women of African descent.
Although waist circumference (WC) is a marker of visceral adipose tissue (VAT), WC cut-points are based on BMI category. We compared WC-BMI and WC-VAT relationships in blacks and whites. Combining data from five studies, BMI and WC were measured in 1,409 premenopausal women (148 white South Africans, 607 African-Americans, 186 black South Africans, 445 West Africans, 23 black Africans living in United States). In three of five studies, participants had VAT measured by computerized tomography (n = 456). Compared to whites, blacks had higher BMI (29.6 ± 7.6 (mean ± s.d.) vs. 27.6 ± 6.6 kg/m², P = 0.001), similar WC (92 ± 16 vs. 90 ± 15 cm, P = 0.27) and lower VAT (64 ± 42 vs. 101 ± 59 cm², P < 0.001). The WC-BMI relationship did not differ by race (blacks: β (s.e.) WC = 0.42 (.01), whites: β (s.e.) WC = 0.40 (0.01), P = 0.73). The WC-VAT relationship was different in blacks and whites (blacks: β (s.e.) WC = 1.38 (0.11), whites: β (s.e.) WC = 3.18 (0.21), P < 0.001). Whites had a greater increase in VAT per unit increase in WC. WC-BMI and WC-VAT relationships did not differ among black populations. As WC-BMI relationship did not differ by race, the same BMI-based WC guidelines may be appropriate for black and white women. However, if WC is defined by VAT, race-specific WC thresholds are required.


Lysophosphatidylcholine plays critical role in allergic airway disease manifestation.
Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C(+)TCRβ(+) NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d-restricted LY49C(+)TCRβ(+) NKT cells.


Blunt injuries to the innominate artery.
Two patients with aneurysm secondary to blunt traumatic subadventitial rupture of the distal innominate artery (IA) are reported. IA rupture was identified because of a cervical bruit in one patient and detected during thoracic aortography in the other patient. The patients had associated cardiovascular lesions consisting of traumatic aneurysm of the subclavian artery and rupture of the aortic valve, respectively. Both lesions were surgically repaired by resection of the lacerated intima and direct closure of the adventitia. In the patient who underwent repair of the aortic valve with simultaneous cardiopulmonary bypass the IA was approached after cannulation of the right common carotid artery. In the other patient the IA was repaired without use of a shunt under close EEG monitoring. Injury to the IA is rare because the artery is short and relatively well protected by the bony cage. Other cardiovascular lesions may be associated with IA rupture and a routine search should be made.


Cadaver study on the location of suboccipital lymph nodes: Guidance for suboccipital node dissection.
The purpose of this study was to provide anatomic guidance for the extent (technique) of suboccipital node dissection. Five human cadaver necks (9 sides) were studied. Boundaries were the superior nuchal line and external occipital protuberance (cranial), the nuchal ligament (medial), an imaginary line through C7 (caudal), and the posterior wall of the auditory channel (anterior). The overlying skin and complete thickness of the cranial part of the trapezius muscle and fascia sheath was included (deep). An average number of 4 lymph nodes per suboccipital side were found. Diameters ranged from 1 to 6 mm. Twenty nodes (63%) were located in the subcutaneous tissue, 12 (37%) were found just underneath the superficial fascia of the trapezius muscle. Suboccipital nodes are small and mainly located in the subcutaneous layer, with a minority just underneath the superficial fascia of the trapezius muscle. This anatomic knowledge was used to refine the suboccipital dissection.


Mice lacking the MHC class II-associated invariant chain.
The invariant chain (li) has aroused much interest because of its close association with major histocompatibility complex (MHC) class II molecules. Various functions have been proposed for it; several of these have received experimental support, but most have not been definitively proven, owing largely to uncertainties inherent in the experimental systems employed. We have now generated a line of mice devoid of the invariant chain by introducing a drastic mutation into the li gene. Cells from mutant animals show aberrant transport of MHC class II molecules, resulting in reduced levels of class II complexes at the surface, and these do not have the typical compact conformation indicative of tight peptide binding. Consequently, mutant cells present protein antigens very poorly and mutant mice are deficient in producing and at negatively selecting CD4+ T cells.


Development and Validation of a UPLC-DAD Method for Quantitative Analysis of Coumarin, trans-Cinnamic Acid, trans-Cinnamaldehyde, and Eugenol in Encapsulated Cinnamon Flavoring Powder.
Cinnamon is a popular spice used in food products. Its flavor varies by its chemical profile. Cinnamon flavoring powder is a unique form of material with essential oil encapsulated in wall material, which improves the stability and homogeneity but also increases the difficulties for analysis. A specific and rapid method is needed to analyze the main components for its quality and safety. An analytical method for the quantification of cinnamon flavoring powder was developed and validated. The characteristic components for analysis were selected as coumarin, trans-cinnamic acid, trans-cinnamaldehyde, and eugenol. This quantitation method with ultra-performance liquid chromatography coupled with diode array detector analysis was achieved by material extraction followed by chromatographic separation on C18 columns eluted with a gradient acetonitrile-water mobile phase. The detected wavelength was determined as 280 nm. Linear regression of calibration curves for each component was validated (R2 > 0.9995). The specificity, LOD and LOQ, precision, accuracy, and ruggedness of the developed method were also evaluated. Such an approach is applicable for the simultaneous determination of these four characteristic constituents in cinnamon flavoring powder used in manufacturing and quality control of nutritional products. This study describes the selection of four components for analysis, the efficient extraction of them from cinnamon flavoring powder, and the rapid quantitation of these four characteristic components in these materials.


A smart and sustainable pathway for abatement of single and binary mixtures of dyes through magnetically retrievable Ca4Fe9O17 anchored on Biochar matrix.
In this work, the author developed Ca4Fe9O17/biochar (CFB) via a green method through a facile co-precipitation procedure involving egg shells as calcium precursor and investigating its performance in single as well as binary solution of methylene blue (MB) and rhodamine B (RhB). The CFB nanocomposite was characterized by XRD, SEM, TEM, XPS, Raman, FTIR, BET, and VSM. ESR studies show the presence of hydroxyl (·OH) and superoxide (O2·¯) radicals, which are primary radical species for pollutant degradation. The average crystalline size of CFB nanocomposites was found to be 32.992 nm using XRD, whereas TEM analysis indicates a particle diameter of 35-36 nm. The degradation efficacy of MB and RhB dyes was achieved at 99.2% and 98.6%, respectively, in a single solution, whereas 99.4% and 99.2%, respectively, in a binary solution within 36 min. Additionally, an iron cluster was formed during the degradation process of MB dye. The degradation of organic contaminants and generation of iron clusters from the degraded dye products were both expedited by the remarkable extension effect of the Ca4Fe9O17 in the CFB nanocomposites. The three processes were achieved using CFB nanocomposite: (1) the advanced oxidation process; (2) degradation of MB and RhB dye in single as well as binary solution with enhanced efficiency, (3) the production of the iron cluster from degraded products. Thus, these three steps constitute a smart and sustainable way that leads to an effective effluent water treatment system and the generation of iron clusters preventing secondary pollution.


Optimal cutoff value of carotid stump pressure for determining the need for a carotid shunt in carotid artery endarterectomy.
This study was conducted to identify the diagnostic value of carotid stump pressure for determining the need for a carotid artery shunt in patients undergoing carotid artery endarterectomy. Carotid stump pressure was prospectively measured in all carotid artery endarterectomies performed under local anesthesia between January 2020 and April 2022. The shunt was selectively used when neurological symptoms appeared after carotid cross-clamping. Carotid stump pressure was compared between patients who needed shunting and those who did not. Demographic and clinical characteristics, hematological and biochemical parameters, and carotid stump pressure of the patients with and without shunts were statistically compared. To determine the optimal cutoff value and diagnostic performance of carotid stump pressure for identifying the patients who need a shunt, receiver operating characteristic analysis was performed. Overall, 102 patients (61 men and 41 women) who underwent carotid artery endarterectomy under local anesthesia were included, with an age range of 51-88 years. A carotid artery shunt was used in 16 (8 men and 8 women) patients. The carotid stump pressure values of the patients with a shunt were lower than those without a shunt (median (min-max): 42 (20-55) vs 51 (20-104), p < 0.0006). In the receiver operating characteristic curve analysis performed to determine the need for a shunt, the optimal cutoff value of carotid stump pressure was ≤48 mmHg, sensitivity was 93.8%, and specificity was 61.6% (area under the curve: 0.773, p < 0.0001). Carotid stump pressure has sufficient diagnostic power to determine the need for a shunt, but it cannot be used alone in the clinical setting. Instead, it can be used in combination with other neurological monitoring methods.


Prevalence, associated factors and consequences of substance use among health and medical science students of Haramaya University, eastern Ethiopia, 2018: a cross-sectional study.
Substance use has a terrible impact on health, behavior and country's economy because the number of people particularly the youngsters being involved in this practice is increasing rapidly. However, the prevalence, determinants and consequence of substance use in the study area has been overlooked. A descriptive quantitative cross-sectional study was conducted among 254 health science students of Haramaya University. The respondents were selected randomly after double stratification based on their department and batch respectively. A pre-tested self-administrable anonymous questionnaire was used. The collected data were entered into epidata version 3.1 and exported to SPSS version 23. Descriptive statistical analysis was done to examine findings. Besides, chi-square (X2) test was considered to examine the nonparametric association of factors with ever substance use. Prevalence of ever substance use for at least one substance was found to be 114(45.4%). Ever khat chewers take the highest percentage [107(93.9%)] followed by ever smokers 45(39.5%) and ever drinkers 44(38.6%). Among these ever substance users, 80(70.2%) were found to be current substance users. Being a preparatory student (26.3%) and freshman at university (57.9%) were critical times to initiate substance use. Sex, monthly income, sexual risk behavior and family history of substance use were found to be significantly associated with being ever substance user as witnessed by their respective X2 values of 19.67, 72.28, 28.99 and 139.72 at P-value = 0.05 and degree of freedom (df = 1). From the overall ever substance users, 31.6% had undesirable health consequences. Among these consequences, anorexia [40 (35.1%)] accounted for the highest percentage followed by insomnia [29 (25.4%)], depression [25 (22%)], gastritis [25 (22%)], dental caries [23 (20.2%)] and increased sexual activity [12 (10.5%)]. Prevalence of ever substance use in the study area was relatively high. Therefore attention should be given to the major reasons for substance use mainly orientation of freshman students about better stress coping mechanisms and expansion of adequate recreational activities.


Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time.
It has been suggested that irritable bowel syndrome (IBS) and functional dyspepsia represent the same disease entity, the irritable gut. The aim of this study was to test the stability, consistency, and relevance of the current classification in the entire, unselected population of persons with gastrointestinal and/or abdominal symptoms, including those who had not consulted physicians. Sequential postal questionnaires were sent to 1290 representative persons (age range, 20-79 years) sampled from the population. Questions were asked about the prevalence of 24 gastrointestinal and/or abdominal symptoms and the site and type of abdominal pain, if any. The prevalence of dyspepsia was 14% (32% if predominant reflux symptoms and concomitant IBS symptoms were included), and the prevalence of IBS was 12.5%. The 3-month incidence rates of reflux, dyspepsia, and IBS among previously symptomless persons were 0.5, 8, and 2 per 1000, respectively. Of persons with IBS, 87% also fulfilled the dyspepsia criteria, and the overlap between dyspepsia subgroups was more than 50%. The use of stricter criteria did not eliminate this overlap. Over a 1-year period, approximately 50% changed their symptom profile. Principal component analysis did not show any natural clustering of the symptoms. The separation of functional gastrointestinal symptoms into dyspepsia, its subgroups, and IBS may be inappropriate.


Performance monitoring method based on balanced partial least square and Statistics Pattern Analysis.
For process monitoring, it's of significance to pay more attention to some performance indexes related to quality, economy or security. To this end, a novel performance monitoring method based on the prediction of the performance indexes is proposed in this paper to promote the efficiency of process monitoring. In this study, firstly, the process variables are classified into two categories according to the correlation with the performance indexes. Based on the two categories of variables, a balanced Partial Least Square algorithm is proposed by constructing an enhanced objective function to predict the performance indexes which cannot be measured online. Then, the prediction residual is modeled for monitoring via the Statistics Pattern Analysis to capture the variation in the performance indexes. Finally, two Simulink examples and a practical example are utilized for illustration and validation.


Deciphering MECP2-associated disorders: disrupted circuits and the hope for repair.
MECP2 is a critical gene for neural development, mutations or duplication of which led to severe neurodevelopmental disorders, such as Rett syndrome (RTT) and autism spectrum disorders (ASD). Extensive works during the past decade yield ample insights into the molecular and cellular functions of MeCP2 in neural development. Furthermore, genetic manipulations in Mecp2 mouse models strongly suggested that deficiency in synaptic plasticity and various behaviors of Mecp2 null or transgenic mice could be rescued in adulthood. Further studies elucidating neural circuits responsible for symptoms in MECP2-associated disorders in rodent and non-human primate models will shed light on the development of potential therapeutic interventions.


Mechanistic insight into the hydroxylation of alkanes by a nonheme iron(V)-oxo complex.
Hydroxylation of alkanes by a mononuclear nonheme iron(V)-oxo complex, [Fe(V)(O)(TAML)](-), is initiated by a rate-determining hydrogen atom (H-atom) abstraction, followed by an oxygen non-rebound process. Evidence for the H-atom abstraction-oxygen non-rebound mechanism is obtained experimentally and supported by DFT calculations.


Novel, rapid, low-cost screen-printed (bio)sensors for the direct analysis of boar taint compounds androstenone and skatole in porcine adipose tissue: Comparison with a high-resolution gas chromatographic method.
This is the first report on the fabrication, characterisation and application of an electrochemical (bio)sensor system for the simultaneous measurement of skatole and androstenone. A biosensor for androstenone was fabricated using a Meldola's Blue modified SPCE (MB-SPCE) by depositing NADH and the enzyme 3α-hydroxysteroid dehydrogenase onto the MB-SPCE surface; samples of adipose tissue were analysed using the biosensors in conjunction with chronoamperometry. Cyclic voltammetry was used to investigate the electrochemical behaviour of skatole at a screen-printed carbon electrode (SPCE vs. Ag/AgCl). An oxidation peak was observed around +0.55 V (vs. Ag/AgCl) and differential pulse voltammetry was applied for quantification of skatole in adipose tissue (in-situ). Quantitative analysis was achieved using calibration plots obtained from fortified meat samples. The concentrations obtained by the electrochemical and gas chromatographic (GC) methods demonstrated a good positive correlation. The (bio)sensor system completed both measurements within 60 s, as compared to several hours for GC, and at a considerably reduced cost and complexity. Consequently, the novel (bio)sensor system should have applications for analysis of carcasses on the abattoir processing line.


1,25-Dihydroxy-16-ene-23-yne-vitamin D3 and prostate cancer cell proliferation in vivo.
1,25-Dihydroxyvitamin D can inhibit the proliferation of prostate cancer cells, but its clinical use is limited by hypercalcemia. We examined the effects of a "noncalcemic" vitamin D analogue, 1,25-Dihydroxy-16-ene-23-yne-cholecalciferol (16-23-D3), on the proliferation of human prostate cancer cells in a mouse model. Twenty-four athymic nude mice were inoculated with human prostate carcinoma cells from the PC-3 cell line. Twelve mice (experimental group) received injections of 1.6 micrograms of 16-23-D3 on alternate days over a 22-day period. Twelve mice (control group) received sham injections. Tumor volumes, pathologic findings, and terminal serum calcium levels were compared between groups. The relative increase in tumor volume was significantly lower in the experimental than in the control group in the first interval following treatment (P < 0.01). Mean tumor volumes in the experimental group were approximately 15% smaller than in the control group. Serum calcium levels did not differ between groups. 16-23-D3 showed modest antiproliferative effects on prostate cancer cells in this model without evidence of drug-induced hypercalcemia. These findings support the concept that vitamin D analogues can inhibit the proliferation of human prostate cancer cells in vivo.


Biobased plastic: A plausible solution toward carbon neutrality in plastic industry?
Biobased plastic exhibits unique benefits for achieving carbon neutrality, a key step toward reducing atmospheric greenhouse gases, due to its stability, high carbon content, and origin of carbon by photosynthesis. Herein we evaluate the role and potential of biobased plastic as an alternative carbon reservoir which is completely artificial, since most plastic polymers are synthetic and massively produced after the 1950 s. Model simulation indicates that plastic, under usage, burial, and littering, forms a growing carbon reservoir, sinking 6.82 gigatons of carbon (GtC) in 2020. Plastic-formed carbon is estimated to stack up to 19.4-23.2 GtC in 2060 under various production scenarios. However, only 18-40% of carbon stored in plastic is biobased carbon, equivalent to approximately 31-48 gigatons of carbon dioxide. Without any low carbon energy upgrade, carbon neutrality is difficult to achieve even with 90% biobased plastic substitution and 50% recycling ratio. Because extra GHG emissions are generated as a result of increasingly using incineration as a post-treatment strategy in response to increasing waste generation, the annual net GHG emission continues to rebound after the bio-based plastic substitution and plastic recycling approach their upper limits. Additional strategies are therefore needed to achieve complete carbon neutrality.


Fluorine nuclear magnetic resonance spectra of rabbit carbonmonoxyhemoglobin.
Carbonmonoxyhemoglobin prepared from protein isolated from rabbits maintained on a diet supplemented with 4-fluorophenylalanine (Phe (4F)) has been studied by fluorine NMR spectroscopy. Substitution of Phe(4F) appears to take place randomly at the sixteen nonequivalent phenylalanine positions of the globins; examination of hybrid hemoglobins in which only one type of globin chain contained the fluorinated amino acid, as well as changes in the spectrum upon exposure to oxygen, aided in the assignment of fluorine resonances from the alpha- or beta-globin chains. The effects of modification of Cys-beta-93 with a spin label and variation of pH and sample temperature on the spectrum were also examined. These data in association with theoretical estimates of aromatic ring current and van der Waals effects on chemical shifts were used to support tentative assignments of several signals observed to specific amino acid residues. Evidence suggesting the presence of two conformational forms of the protein, possibly due to disorder of the heme groups, is described.


Using an age and fibrinogen levels adjusted D-dimer cutoff significantly improves the specificity of two equivalent D-dimer assays for excluding pulmonary embolism.
Our single-center prospective study compared two methods of D-dimer determination used in the exclusion of pulmonary embolism: bioMérieux method, VIDAS® D-Dimer Exclusion™ II, and Diagnostica Stago method, STA®-Liatest® D-Di Plus. For each of these two methods, we calculated optimized variable cutoffs based on fibrinogen and/or age to improve the specificity of the methods. 2530 patients admitted to the Emergency Department of the Brest University Hospital for suspected pulmonary embolism were included in this study. The comparison of the two methods was performed by calculating their different characteristics: sensitivity, specificity and negative predictive value for different cutoffs systems: fixed or age-adjusted according to Douma et al. An optimization of the variable cutoff according to age and fibrinogen was then performed. The two methods VIDAS and STAGO are approximately equivalent in terms of performance even if the STAGO method presents a better specificity (57.1 %) at the fixed cutoff of 0.5 μg/mL. The adoption of age-adjusted, fibrinogen-adjusted or doubly-adjusted (age and fibrinogen) cutoffs, significantly improves the specificity of the tests without affecting their excellent sensitivity. These specificities peak respectively at 75.8 % and 76 % for the VIDAS and STAGO tests when using a doubly-adjusted, age and fibrinogen, cutoff, i.e. a gain in specificity of approximately 10 % compared with the age-adjusted cutoff of Douma et al. and of approximately 20 % compared with the fixed cutoff of 0.5 μg/mL. Adopting an optimized variable cutoff based on fibrinogen and/or age significantly improves specificity of D-dimer methods for pulmonary embolism exclusion.


Accidental hypothermia and active rewarming: the metabolic and inflammatory changes observed above and below 32 degrees C.
In accidental hypothermia the underlying physiological mechanisms responsible for poor outcome during rewarming through 32 degrees C remain obscure, although possible associations include changes in acid-base balance, divalent cations, and inflammatory markers. This study investigated the metabolic and inflammatory changes that occur during the rewarming of hypothermic patients. Eight patients, four men and four women, age 45 to 85 years, admitted with core temperatures <35 degrees C were included in the study. Patients were rewarmed with dry warm blankets and fluid replaced by crystalloid at 40 degrees C. Bloods for pH, ionised calcium (Ca(2+)) and magnesium (Mg(2+)), parathyroid hormone (PTH), interleukin 1 (IL1), interleukin 6 (IL6), tissue necrosis factor alpha (TNFalpha), were collected at presentation, during rewarming, and at 24 hours. Four patients were admitted with mild (32 degrees -35 degrees C) and four with moderate (28 degrees -32 degrees C) hypothermia. Rewarming to 32 degrees C had no significant effect on the presenting acidosis (p=0.1740), although above 32 degrees C pH increased with temperature (p<0.0001). There was a negative correlation between pH and both Ca(2+) (p=0.0005) and Mg(2+) (p=0.0488) below 32 degrees C; above this temperature the relation was significant only for Ca(2+) (p=0.0494). PTH and Ca(2+) correlated positively (p=0.0041) and negatively (p=0.0039) below and above 32 degrees C respectively. There was no relation between IL1 or TNFalpha with Ca(2+) during rewarming, but IL6 and Ca(2+) correlated positively (p=0.0039) and negatively (p=0.0018) when presentation temperature was below and above 32 degrees C respectively. During rewarming pH remains unchanged until patient temperature approaches 32 degrees C. Ca(2+) and Mg(2+) decline is associated with the pH increase above 32 degrees C. Poor outcome is associated with presentation temperature (<32 degrees C), non-physiological correlation between IL6-PTH-Ca(2+), and age (>or=84 years).


Analytical and clinical performance evaluation of a new high-sensitivity cardiac troponin I assay.
To validate the analytical performance and diagnostic accuracy for non-ST-segment elevation myocardial infarction (NSTEMI) with a new high-sensitivity cardiac troponin I (hs-cTnI) assay on the automated light-initiated chemiluminescent assay (LiCA®) platform. Comprehensive analytical validations were performed, and the 99th percentile upper reference limit (URL) from apparently healthy individuals were established. We evaluated the diagnostic performance of the assay for NSTEMI. The limit of quantitation (LoQ) were 1.9 ng/L (20% CV) and 5.1 ng/L (10% CV). The sex-specific 99th percentile URLs were 17.6 ng/L (4.2% CV) for men (age 20-79y) and 14.2 ng/L (4.9% CV) for women (age 19-89y) in serum, 14.4 ng/L (4.9% CV) for men (age 19-88y) and 12.9 ng/L (5.2% CV) for women (age 19-87y) in plasma, respectively. Detection rates in healthy individuals were from 98.7 to 99.1%. The correlation coefficient and median bias between LiCA and Architect were 0.985 and 0.1% (-2.0-2.9%) in full analytical range of serum specimens. In lower range (<100 ng/L), LiCA had an overall positive bias 6.7% (-1.6-13.3%), R=0.949. At the specific medical decision levels (15.2, 26.2 and 64.0 ng/L), assay difference was estimated to be <10%. No significant differences on AUC, sensitivity and specificity, NPV and PPV were found between LiCA and Architect for the diagnosis of NSTEMI. LiCA hs-cTnI is a precise, highly sensitive and specific assay that meets the requirement of a 3rd generation (level 4) high-sensitivity method. The diagnostic accuracy of LiCA assay for NSTEMI is comparable to the established Architect hs-cTnI assay.


[Total small bowel volvulus complicating common incomplete mesentery, an exceptional complication in adults: about a case].
Total small bowel volvulus complicating common incomplete mesentery is an arrest of rotation of the primary intestinal loop at 180°. The root of the mesentery is very short and the whole small intestine is located on the superior mesenteric artery axis. Patients are at very high risk of small bowel volvulus and enteromesenteric infarction. Acute volvulus requires emergency surgery; imaging must not delay surgery. Surgery is based on the untwisting of the volvulus (counterclockwise) after the assessment of intestinal viability. The intestine placed in the complete common mesentery position: the cœcum is situated in the right iliac region. We report the case of a 60-year old patient admitted with total small bowel volvulus on an incomplete common mesentery who underwent emergency surgery with favorable postoperative outcome.


The Nordic back pain subpopulation program: the long-term outcome pattern in patients with low back pain treated by chiropractors in Sweden.
(1) To describe the low back pain (LBP) pattern at baseline; (2) to describe the long-term outcome pattern; (3) to investigate the presence of distinct subgroups in relation to outcome; (4) to establish whether short-term outcome is a predictor of long-term outcome. A 3- to 6- and 12- to 18-month, multicenter practice-based, prospective descriptive study was performed in private chiropractic practices in Sweden. Fifty-eight of 64 previously compliant chiropractors each recruited a maximum of 30 consecutive patients with LBP. Complete baseline clinical information was provided on 1054 patients, of which 93% were interviewed approximately 3 months later, and 57% responded to a questionnaire at approximately 12 months. Chiropractic treatment was decided by the treating chiropractor. Twelve descriptive subgroups were created based on (1) duration of LBP at baseline, (2) duration of LBP in the past year, and (3) LBP pattern in the past year. The predictive value was tested for outcome status at the fourth visit. Information on self-reported LBP status and improvement over the past months were collected. Patients were spread in a U-shaped fashion from benign to severe with the 2 extreme groups being most prevalent. About half the participants reported "no LBP in the past week" at 3 months and somewhat fewer at 12 months. Almost 75% claimed to be definitely better at 3 months, and approximately 50% at 12 months. Specific predictive subgroups can be identified, mainly in relation to the past-year history of LBP. Improvement at the fourth visit is a predictor of long-term outcome. Knowledge of specific subgroups may improve the quality of care and the selection of homogeneous study populations in clinical trials.