The federal and Ontario budgets of 2012: what's in it for health equity?
Health equity has started to receive significant attention among Canadian policy-makers, with acknowledgement at both the federal and provincial levels of the importance of reducing health inequities. However, a challenging budget environment has led to a number of budget cutbacks in areas that are likely to negatively influence social determinants of health, such as housing, education, and social assistance. This article analyzes both the federal and Ontario budgets of 2012 and their potential impacts on and implications for health equity. Even though health care services have largely remained untouched in both budgets, the article argues that existing health inequities will be further amplified through the implementation of cutbacks in sectors other than health, given the importance of social determinants of health (SDH) for health equity outcomes.


Quantitative analysis of earthy and musty odors in drinking water sources impacted by wastewater and algal derived contaminants.
The goal of this study was to develop a robust method capable of quantifying taste and odor compounds (i.e., geosmin and 2-methylisoborneol) at very low aqueous concentrations in the presence of wastewater and algal derived contaminants. A polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used to perform headspace-solid phase microextraction (HS-SPME) to extract and analyze taste and odor compounds from model, source water, and finished drinking water samples. Gas chromatography coupled with mass spectrometery (GC/MS) in full scan mode was used to analyze the compounds desorbed from the fiber in the GC inlet. The following parameters were optimized in order to enhance analyte recovery: extraction temperature, extraction time, desorption time, sonication temperature, sonication time and GC/MS configuration/temperature program. After optimization, the method provided a linear response from 1 to 300 ng L(-1) and yielded limit of detections (LODs) of 1 ng L(-1) for both 2-MIB and geosmin. In MS full scan mode, wastewater contaminants and other algal derived volatile organic compounds (ADVOCs) relevant to cyanobacterial bloom dynamics were detected and monitored in real source water samples. In the presence of known interferents with similar mass/charge fragments and elution times, the optimized method yielded low detection limits as well as exact molecular confirmation for taste and odor compounds in impacted source water samples. This method could be used as a tool to aid in the development of source water protection plans by identifying potential sources of anthropogenic and algal derived contamination in drinking water sources.


Adaption of microbial communities to the hostile environment in the Doce River after the collapse of two iron ore tailing dams.
In November 2015, two iron ore tailing dams collapsed in the city of Mariana, Brazil. The dams' collapse generated a wave of approximately 50 million m3 of a mixture of mining waste and water. It was a major environmental tragedy in Brazilian history, which damaged rivers, and cities 660 km away in the Doce River basin until it reached the ocean coast. Shortly after the incident, several reports informed that the concentration of metals in the water was above acceptable legal limits under Brazilian laws. Here the microbial communities in samples of water, mud, foam, and rhizosphere of Eichhornia from Doce River were analyzed for 16S and 18S rRNA-based amplicon sequencing, along with microbial isolation, chemical and mineralogical analyses. Samples were collected one month and thirteen months after the collapse. Prokaryotic communities from mud shifted drastically over time (33% Bray-Curtis similarity), while water samples were more similar (63% Bray-Curtis similarity) in the same period. After 12 months, mud samples remained with high levels of heavy metals and a reduction in the diversity of microeukaryotes was detected. Amoebozoans increased in mud samples, reaching 49% of microeukaryote abundance, with Discosea and Lobosa groups being the most abundant. The microbial communities' structure in mud samples changed adapting to the new environment condition. The characterization of microbial communities and metal-tolerant organisms from such impacted environments is essential for understanding the ecological consequences of massive anthropogenic impacts and strategies for the restoration of contaminated sites such as the Doce River.


Psychosocial factors impacting community-based pressure ulcer prevention: A systematic review.
Pressure ulcers are a major health concern. They have a significant impact on the healthcare system and individuals, reducing quality of life across several domains. In community settings, self-management behaviours are central to their prevention. However, adherence with pressure ulcer prevention guidelines remains low, with little evidence guiding the relationship between patients and healthcare professionals to establish a concordant partnership. To synthesise evidence on factors contributing to community-based pressure ulcer prevention using the Theoretical Domains Framework and the Capability, Opportunity, Motivation, Behaviour (COM-B) model of behaviour. Mixed methods systematic review and narrative synthesis. Systematic searches were conducted in the CINAHL, Cochrane, EMBASE, PsycINFO, PubMed, Scopus, and Web of Science databases on 14th December 2022. Studies were eligible if they contained data on the factors associated with adherence and concordance with pressure ulcer prevention guidelines in the community for patients, caregivers, and healthcare professionals. Methodological quality was assessed using the Hawker tool. Findings were synthesised using the Theoretical Domains Framework. The resulting themes were mapped onto the Capability, Opportunity, Motivation, Behaviour (COM-B) model. Thirty studies were included in the review, including quantitative, qualitative, and mixed methods research. The synthesis identified 12 of the 14 Theoretical Domains Framework domains, with knowledge, social influences, beliefs about consequences, and beliefs about capabilities the most prevalent. Although knowledge appears to be an important contributor to adherence with prevention guidelines, knowledge alone does not appear sufficient to achieve concordance. A concordant relationship was facilitated by healthcare professionals' knowledge, motivation to work alongside patients and their priorities, and interpersonal skills to build rapport and trust, whilst barriers included lack of healthcare professional skills to navigate sensitive issues, paternalistic views of patient compliance and organisational processes that impact building rapport. Several psychosocial factors may affect the ability to achieve concordance between individuals, caregivers and healthcare professionals with pressure ulcer prevention guidelines in the community. However, data regarding the efficacy of behaviour change interventions targeting these constructs is limited, with further research required to guide intervention development in this area.


The role of triple therapy and therapy sequence in treatment of BRAF-mutant metastatic melanoma. Response to overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study.
Novel therapies have achieved unprecedented benefit in survival of advanced melanoma patients. While immunotherapy (ICI) can be administered independent of mutational status, BRAF and MEK kinase inhibitors represent another effective treatment option for patients with BRAF mutant melanoma. Given the benefits these therapies demonstrate, the natural instinct was to combine. Three studies have investigated the benefit of combination of ICI using anti-PD-1 or anti-PD-L1 antibody and targeted therapy (TT) with BRAF and MEK inhibitors over TT and placebo. Among these studies, statistically significantly superior duration of response was observed, however overall and progression-free survival were only numerically superior, if at all. One triple combination was approved for BRAF mutant metastatic melanoma; however, the expected synergistic effect of triple therapy could not be universally confirmed and the observed benefits with triple seem to depend on statistical considerations rather than a biological reason. As patients with BRAF mutant melanoma have both ICI and TT as their first-line treatment options, the question whether the sequence matters was addressed. Two prospective trials compared first-line ICI, followed by TT at progression, or vice-versa, with additional "sandwich" approach (8 weeks of TT followed by ICI until progression, then TT again) in the Secombit study. The benefit of first-line ICI was demonstrated in both studies with Secombit study showing the "sandwich" approach to have similar effect. Current data advices for immunotherapy based regiments in patients with BRAF mutant melanoma or, possibly, sandwich approach. Whether triple therapy is superior to ICI monotherapy still needs to be addressed considering not only efficacy, but also safety.


Effects of nationwide lockdown during COVID-19 epidemic on lifestyle and other medical issues of patients with type 2 diabetes in north India.
During the current pandemic of COVID-19, India is under lockdown which could cause disruption in diet and lifestyle in patients with type 2 diabetes (T2DM). We aimed to study lifestyle changes and other common issues related to treatment in our previously seen and treated patients with T2DM. Patients (n, 150) who were regularly following up before lockdown were interviewed telephonically (after 45 days of start of lockdown) regarding lifestyle changes, stress and other diabetes-related questions. Carbohydrate consumption and frequency of snacking increased in 21% and 23% patients, respectively. Interestingly, 27% patients reported an increase in consumption of fruits. Exercise duration was reduced in 42% and weight gain occurred in 19% patients. Frequency of doing self-monitoring of blood glucose (SMBG) was decreased in 23% patients. 'Mental stress' of any kind was reported in 87% patients. Availability of medicines and insulin was uninterrupted in 91% patients. Knowledge about telemedicine was present in 69% and majority (92%) of these patients preferred video consultation. During 45 days of lockdown increase in carbohydrate intake, decrease in exercise, decreased SMBG and widespread mental stress in patients with T2DM was recorded, factors which may destabilize or exacerbate hyperglycemia and hypertension. Some positive changes (e.g. increased intake of fruits) were also observed.


Patient-specific reconstruction plates are the missing link in computer-assisted mandibular reconstruction: A showcase for technical description.
Preoperative planning of mandibular reconstruction has moved from mechanical simulation by dental model casts or stereolithographic models into an almost completely virtual environment. CAD/CAM applications allow a high level of accuracy by providing a custom template-assisted contouring approach for bone flaps. However, the clinical accuracy of CAD reconstruction is limited by the use of prebent reconstruction plates, an analogue step in an otherwise digital workstream. In this paper the integration of computerized, numerically-controlled (CNC) milled, patient-specific mandibular plates (PSMP) within the virtual workflow of computer-assisted mandibular free fibula flap reconstruction is illustrated in a clinical case. Intraoperatively, the bone segments as well as the plate arms showed a very good fit. Postoperative CT imaging demonstrated close approximation of the PSMP and fibular segments, and good alignment of native mandible and fibular segments and intersegmentally. Over a follow-up period of 12 months, there was an uneventful course of healing with good bony consolidation. The virtual design and automated fabrication of patient-specific mandibular reconstruction plates provide the missing link in the virtual workflow of computer-assisted mandibular free fibula flap reconstruction.


The aging human recipient of transfusion products.
In this review the different mechanisms of aging and frailty such as DNA defects due to impaired DNA repair, inflammatory processes, disturbances of oxidative phosphorylation are discussed together with mechanisms of cell repair. Components of blood plasma, such as the growth-differentiation protein GDF11, were shown to enhance neurogenesis and to improve the vasculature in the animal cortex and to rejuvenate muscle tissue. Advances in laboratory assays allow to identify plasma proteins that may affect tissue regeneration. This new knowledge from animal research might affect transfusion practice in geriatric patients in the future. Provided it can be translated and confirmed in human research, blood products might no longer be considered only as oxygen carriers or drugs to improve hemostasis. In the present time blood transfusion (RBCs, plasma or platelets) should be directed by differentiated guidelines considering not only cut-off values of hemoglobin, platelet count or coagulation but also old age-specific biologic variation, comorbidities and the clinical context e.g. of bleeding.


Real-Time Projections of SARS-CoV-2 B.1.1.7 Variant in a University Setting, Texas, USA.
We used the incidence of spike gene target failures identified during PCR testing to provide an early projection of the prevalence of severe acute respiratory syndrome coronavirus 2 variant B.1.1.7 in a university setting in Texas, USA, before sequencing results were available. Findings from a more recent evaluation validated those early projections.


"Menstrual" migraine: towards a definition.
"Menstrual" migraine, a term misused by both patients and doctors, lacks precise definition. This dissertation critically reviews papers on the subject and examines the problem from a clinical perspective. A definition is proposed that the term "menstrual" migraine should be restricted to attacks exclusively starting on or between day 1 +/- 2 days of the menstrual cycle; the woman should be free from attacks at all other times of the cycle. This definition, unlike many used previously, links to a specific mechanism; the timing is consistent with oestrogen withdrawal. If this is correct, "oestrogen withdrawal" migraine may be a better term. Future studies, necessary to support or refute these proposals, are suggested.


Comparison of culture methods for enumeration of microaerophilic bacteria in marine sediments.
Agar-mixed cultures in semi-solid media provide a range of oxygen concentrations which fulfill microaerophilic bacterial requirements. Such conditions are more suitable than those provided by liquid media since, in broth cultures, the oxygen concentration must be determined at a level which might later show a lack of or excess of sensitivity to microaerophilic bacteria, thereby giving an erroneous count. A high content of organic substrates appears to be disadvantageous. It can prevent enumeration of microaerophilic growing rings or even induce false results. Minielectrodes permit the control of the oxygen concentration in each growing ring so as to confirm the efficiency of the culture method used for a selective count of microaerophilic bacteria. Semi-solid seawater culture medium supplemented with calcium succinate at 0.5 gram per litre appears to be an adequate culture medium for counting microaerophilic bacteria in marine sediments.


Newborns not at raised risk if flu drugs taken in pregnancy.
There is no evidence to suggest an increased risk to newborns whose mothers take drugs to prevent or treat influenza during pregnancy, research suggests.


[Aids].
The number of cases with tuberculosis and human immunodeficiency virus infection is increasing in Japan. Tuberculosis is more likely to cause disease at an earlier stage of immunodeficiency, because M. tuberculosis is more virulent than other HIV-associated pathogens. Reactivation of latent infection has been traditionally considered the most important mechanism in the pathogenesis of active tuberculosis. However, recent exogenous infection may be higher among HIV-infected persons. The most striking clinical feature of tuberculosis in patients with HIV infection is the extremely high frequency of extrapulmonary involvement, usually with concomitant pulmonary tuberculosis. Among severely immunosuppressed patients with HIV infection, chest roentgenogram findings are hilar adenopathy, pleural effusions, and a miliary pattern. Antituberculosis therapy is effective in most patients with HIV infection.


Pulsed Doppler echocardiographic description of a circular flow pattern in spontaneous left ventricular contrast.
Pulsed Doppler echocardiography was performed in nine patients with spontaneous intracavitary dynamic echoes, revealing a circular flow pattern. All patients had a severely dilated left ventricle as a result of ischemic heart disease. The sample volume was placed in the apical four-chamber view near the lateral wall and near the interventricular septum, halfway between the mitral valve anulus and apex. A continuous (i.e., during both systole and diastole) positive signal was recorded near the lateral wall and a continuous negative signal at the interventricular septum. This indicates flow continuously toward the transducer along the lateral wall and away from the transducer along the interventricular septum. This is consistent with the circular flow pattern, as demonstrated by the spontaneous intracavitary dynamic echoes. In 22 normal volunteers a positive prominent shift was recorded during diastole near the lateral wall and either a negative (nine of 22) or no (13 of 22) shift at all during systole. Near the interventricular septum a negative systolic shift followed by a positive, early-diastolic shift was consistently recorded. In the large majority (18 of 22) negative waves were recorded during middle and late diastole. A continuous positive or negative Doppler signal was consistently absent in healthy subjects. The angle between the proximal part of the interventricular septum and the anterior mitral valve leaflet during maximal early diastolic opening in the patients was 74 +/- 4.8 degrees (mean +/- SD), which may give rise to a preferential eccentric inflow and the maintenance of the circular apical flow pattern.


Accuracy of metal 3D printed frameworks for removable partial dentures evaluated by digital superimposition.
To evaluate the accuracy of metal 3D printed frameworks (MEP group) for removable partial dentures (RPDs) by digital superimposition, in comparison to that of frameworks produced by the conventional (CON group) and resin printing/casting (RPC group) workflows. A partially edentulous maxillary dentiform was prepared with rest seats and guiding planes on the right canine, left first premolar, and left second molar. Thirty master casts were prepared via repeated impressions of the dentiform. Frameworks were fabricated by three different workflows (n = 10 for each group). The internal discrepancies of the frameworks were assessed at 12 points by digital scanning with an optical triangulation principle-based tabletop scanner and superimposition using a reference best-fit alignment method. First, the master cast was scanned alone. Subsequently, a thin silicone material was applied to the framework and fitted onto the master cast, after which the framework was removed. Finally, the master cast with the silicone material attached was rescanned. The data from the two scans were matched, with the reference being the area not occupied by the silicone. For the CON, MEP, and RPC groups, respectively, the mean overall internal discrepancies (279.72 µm, 241.02 µm, and 331.70 µm), and the mean internal discrepancies on palate areas (292.92 µm, 250.72 µm, and 355.84 µm) and rest seat areas (240.12 µm, 211.91 µm, and 259.26 µm) did not significantly differ among the three fabrication methods (p = 0.558, 0.542, and 0.774). The reference best-fit alignment of scan datasets is a useful approach to evaluate the internal discrepancy of frameworks. Metal 3D printing produces RPD frameworks that are comparable to conventional frameworks and meet clinical standards.


Axial four-dimensional computed tomographic images to analyze crosswise differences in protrusive condylar movement in patients who underwent mandibulectomy and free flap reconstruction.
Few studies evaluate condylar movement following mandibular reconstruction. The main objective of this study was to show that axial four-dimensional computed tomography (4DCT) could visualize bilateral protrusive condylar movement directly. We used axial 4DCT images to assess condylar protrusion in patients who underwent mandibular reconstruction. We enrolled seven healthy volunteers (median age 30 years, range 27-38 years) and seven patients (median age 65 years, range 52-80 years), who underwent mandibulectomy (segmental in five, hemi in one, marginal in one) and free flap reconstruction (using the fibula in six and the radial forearm in one). Six study subjects were instructed to masticate a cookie during the 4DCT scan (the seventh made chewing motions). The distance between the most anterior and posterior positions of the bilateral condyles on 4DCT (axial view) images was then measured and compared between controls and patients using the Mann-Whitney U-test. The crosswise difference in the distances of condylar protrusion was significantly greater in patients than in the controls. Axial 4DCT images can visualize a bilateral condylar protrusive path. Axial 4DCT images for patients who have undergone mandibulectomy and reconstruction may be useful for evaluation of functional movement of condyles.


Antibodies to food and environmental antigens in serum, respiratory tract and intestine of pigs.
Serum antibodies to food, bedding and dust were detected in pigs by precipitation and ELISA. There was an age-related decrease in the number of animals with precipitating antibodies and in the specific activity of IgG and IgM antibodies. Antibodies to food, bedding and dust were detected in respiratory and intestinal secretions, but there were differences in the distribution and isotype of antibodies to these three antigens.


Modulation of antibody synthesis by an anti-tumour alga.
An unicellular alga, Chlorella pyrenoidosa, which had been reported to protect C3H mice against sarcoma BP8, is shown, when injected in Freund's incomplete adjuvant, to modulate the antibody synthesis induced by immunization with a hapten-carrier complex. C. pyrenoidosa appeared to be able to initiate an antigenic competition between hapten and carrier determinants of the antigen molecule during antibody synthesis, and thus it could be speculated that C. pyrenoidosa modulates the immune response at the macrophage level.


Routine total bilateral adrenalectomy is not warranted in childhood familial pheochromocytoma.
The surgical management of familial childhood pheochromocytoma is based on data derived from clinical series that have focused primarily on the multiple endocrine neoplasia (MEN)-associated cases. Prophylactic bilateral total adrenalectomy has been advocated for this group due to a high incidence of bilateral adrenal involvement and the propensity for tumor recurrence after partial adrenal resections. We retrospectively reviewed our experience with a cohort of children with nonsyndromatic familial pheochromocytoma to see if their surgical management should parallel that advocated for patients with the MEN syndrome. From 1977 through 1991, 17 children from 9 families with a strong family history of pheochromocytoma were treated at the Children's Hospital of Pittsburgh. None of the patients or their families displayed an association with the MEN syndrome. There were 13 males and 4 females with a mean age of 10.1 years. Follow-up was obtained on all patients and averaged 6 years. All tumors were located within the abdominal cavity. Seven patients presented with unilateral adrenal tumors while four patients had synchronous bilateral tumors. Eight patients had tumors in extra-adrenal locations; 2 with concomitant adrenal tumors. Ten patients underwent total unilateral adrenalectomy with or without resection of extra-adrenal tumor(s). All patients with synchronous bilateral adrenal tumors underwent unilateral adrenalectomy in combination with a partial contralateral adrenal resection without a recurrence after an average of 7.3 years. Three patients developed metachronous adrenal tumors an average of 4.2 years after their initial surgery. All required complete removal of the affected adrenal, resulting in two patients with bilateral adrenalectomies.(ABSTRACT TRUNCATED AT 250 WORDS)


The diversity of antimicrobial resistance genes among staphylococci of animal origin.
Staphylococci of animal origin harbor a wide variety of resistance genes. So far, more than 40 different resistance genes have been identified in staphylococci from animals. This includes genes that confer resistance to virtually all classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents. The resistance mechanisms specified by the resistance genes fall into three major categories: (i) enzymatic inactivation, (ii) active efflux, or (iii) protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate the exchange of resistance genes with staphylococci of human origin but also with other Gram-positive bacteria.


Prediction of the rovibrational emission spectroscopy of B2Σ(+)-X2Σ(+) system in 12C17O+.
An analytical formula based on the Herzberg's conventional rovibrational energy levels for diatomic system is proposed by taking multiple differences of spectral lines to predict the R-branch high-lying rovibrational emission spectroscopy, where only 15 accurate known transition lines and rotational constants D(v'), D(v'') are needed. Using the formula, the R(11ee) and R(22ff) branches of (0, 2) and (0, 3) transition bands in the B(2)Σ(+)-X(2)Σ(+) system of (12)C(17)O(+) are studied. The results show that not only the relatively lower order rovibrational transition lines given by experiments are reproduced but also the higher and the absent spectral lines are correctly predicted for each band.


A monoclonal antibody to human transitional-cell carcinoma of the bladder cross-reacting with a differentiation antigen of neutrophilic lineage.
A monoclonal antibody (MAb) to human transitional-cell carcinoma of the bladder (TCCB) was obtained by immunization of a BALB/c mouse with formalin-fixed TCCB cells and subsequent fusion of the spleen cells with SP2-OAg14 myeloma line. GF 26.7.3 MAb was selected by indirect immunofluorescence (IIF) as reacting agent with target cells and negative with autologous lymphocytes and Epstein-Barr virus (EBV)-transformed lymphoblastoid cell-line. GF 26.7.3 reacts with a high percentage of bladder and colon carcinomas when examined by IIF and immunoperoxidase techniques and cross-reacts with a determinant expressed on neutrophilic cell lineage. The IIF analysis performed on bone marrow and peripheral blood (PB) from healthy subjects and leukemic patients and on leukemic cell lines showed that the expression of the structure detected by GF 26.7.3 is restricted to the neutrophilic cell lineage and first expressed at the promyelocytic level. Immunoprecipitation and SDS-polyacrylamide gel electrophoresis (PAGE) of 125 I-labelled membrane proteins from target cells were performed, but no bands were detected by autoradiography. In addition, pronase insensitivity and periodate sensitivity suggest the possible involvement of a carbohydrate determinant.


A prognostic model based on readily available clinical data enriched a pre-emptive pharmacogenetic testing program.
We describe the development, implementation, and evaluation of a model to pre-emptively select patients for genotyping based on medication exposure risk. Using deidentified electronic health records, we derived a prognostic model for the prescription of statins, warfarin, or clopidogrel. The model was implemented into a clinical decision support (CDS) tool to recommend pre-emptive genotyping for patients exceeding a prescription risk threshold. We evaluated the rule on an independent validation cohort and on an implementation cohort, representing the population in which the CDS tool was deployed. The model exhibited moderate discrimination with area under the receiver operator characteristic curves ranging from 0.68 to 0.75 at 1 and 2 years after index dates. Risk estimates tended to underestimate true risk. The cumulative incidences of medication prescriptions at 1 and 2 years were 0.35 and 0.48, respectively, among 1,673 patients flagged by the model. The cumulative incidences in the same number of randomly sampled subjects were 0.12 and 0.19, and in patients over 50 years with the highest body mass indices, they were 0.22 and 0.34. We demonstrate that prognostic algorithms can guide pre-emptive pharmacogenetic testing toward those likely to benefit from it.


Texture maintenance and degradation mechanism of ice-stored grass carp (Ctenopharyngodon idella): A scope of intramuscular connective tissue.
Although intramuscular connective tissue (IMCT) is low in fish, its impact on texture cannot be ignored due to its special location. Therefore, this study was aimed to investigate the contribution of IMCT degradation to fish softening and its mechanism induced by endogenous proteases. Results showed that IMCT honeycomb-like structure collapsed entirely on the 10th day of ice storage, along with a decrease of shear force by 36.5%. Meanwhile, IMCT and myofibrils (MF) degradation accelerated softening by 25.1% and 15.3% during 10 days of ice storage, respectively. Next, IMCT deterioration was indicated to be highly correlated with decorin degradation (0.956**), followed by elastin (0.928**) and collagen (0.904**). Ulteriorly, endogenous collagenase was shown to degrade IMCT crucial components, while endogenous cathepsins had little effect. In conclusion, this study confirmed that IMCT played an essential role in maintaining fish texture and was mainly degraded by endogenous collagenase.


Mechanical analysis of maxillofacial miniplates.
The effect of compression and tensile forces on different types of maxillofacial miniplates was measured, in both as supplied and after bending states. Tests showed all plates showed values of tensile force at failure in excess of that found in most clinical situations; twisting through 90 degrees about the long axis had little effect. In flatwise bending tests there was a wide scatter of values of bending stiffness and ultimate load, indicating that some plates may be stronger than necessary. Repeatedly bending the plates reduced their bending stiffness, particularly in the continuous holed plates, and increased their ultimate load to failure. Values of bending stiffness and ultimate load were much larger when bending in the edgewise direction, with large differences between manufacturers. The data generated in the current study may assist the surgeon in deciding which type of plate to select for a particular clinical situation.


p38α deficiency and oxidative stress cause cytokinesis failure in hepatocytes.
Cytokinesis is the last step in mitosis and it implies re-organization of the actin cytoskeleton. Its failure is one of the major mechanisms of polyploidy and binucleation in mammals. Our aims were 1) to assess the role of redox-sensitive p38α MAPK in cytokinesis by studying the liver of wild type mice or liver-specific p38α knock-out mice; 2) to assess the role of oxidative stress associated with hepatocyte isolation on cytokinesis. When p38α was down-regulated in hepatocytes, MK2 phosphorylation on threonine 334 was completely abrogated. Activation of MNK-1, required for abscission of the intercellular bridge, was diminished. Key proteins of the RhoA pathway (phospho-PRK2, nuclear phosphorylated cofilin, and cytosolic p27) were assessed confirming the impairment of this pathway. The absence of p38α in aging liver also led to a decrease in HSP27 phosphorylation, which is required for actin polymerization. Indeed, a severe impairment in the F-actin filamentous structure was found in the liver of old mice upon p38α deficiency. Consequently, long-term p38α MAPK down-regulation markedly affects the RhoA pathway and actin cytoskeleton dynamics inducing actin disassembly and cytokinesis failure upon aging. On the other hand, hepatocyte isolation caused marked glutathione depletion, increased generation of reactive oxygen species, and activated cell cycle entry. Addition of N-acetyl cysteine to isolation media prevented glutathione depletion, restrained the cell cycle entry, and abrogated defective cytokinesis and the formation of binucleated hepatocytes during isolation. Our results show that hepatocytes do enter into S phase but they do not complete cell division with age upon p38α deficiency or upon oxidative stress associated with isolation leading in both cases to cytokinesis failure and binucleation.


Needlescopic fundoplication.
Minimally invasive surgery continues to evolve, with an emphasis on developing new techniques and applying new technology to surgical procedures. The purpose of this study was to compare the short-term outcomes of needlescopic fundoplication with those of conventional laparoscopic fundoplication. Between January 1999 and June 2000, 38 needlescopic fundoplications were performed, and the short-term outcomes for these patients were compared with those for a contemporary matched cohort of patients who had undergone a conventional laparoscopic fundoplication. There was a nonsignificant trend toward decreased operative time (143.4 to 127 min; p = 0.13), blood loss (54.3 to 48 ml; p = 0.30), narcotic requirements (29.5 to 19.5 morphine equivalents; p = 0.32), and length of hospital stay (1.78 to 1.49 days; p = 0.10) in the needlescopic group. There were no significant differences in intraoperative complications (2.6% vs 2.6%; p = 1.0). Two needlescopic cases were converted to laparoscopic cases because of obesity. Postoperatively, there were no significant differences in rates of early dysphagia (7.9% vs 7.9%), bloating (13.2% vs 5.3%; p = 0.43), or other complications (5.3% vs 5.3%) between the groups. There was a significant reduction in mean operative time for needlescopic fundoplication after the first four cases (166 +/- 44 vs 120 +/- 32 min; p = 0.03). Needlescopic fundoplication poses no disadvantage, and it offers the added cosmetic benefit of smaller incisions.


Preliminary demonstration of benchtop NMR metabolic profiling of feline urine: chronic kidney disease as a case study.
The use of benchtop metabolic profiling technology based on nuclear magnetic resonance (NMR) was evaluated in a small cohort of cats with a view to applying this as a viable and rapid metabolic tool to support clinical decision making. Urinary metabolites were analysed from four subjects consisting of two healthy controls and two chronic kidney disease (CKD) IRIS stage 2 cases. The study identified 15 metabolites in cats with CKD that were different from the controls. Among them were acetate, creatinine, citrate, taurine, glycine, serine and threonine. Benchtop NMR technology is capable of distinguishing between chronic kidney disease case and control samples in a pilot feline cohort based on metabolic profile. We offer perspectives on the further development of this pilot work and the potential of the technology, when combined with sample databases and computational intelligence techniques to offer a clinical decision support tool not only for cases of renal disease but other metabolic conditions in the future.


Temporal profile of magnetic resonance imaging changes following forebrain ischemia in the gerbil.
Quantitative T2 magnetic resonance (MR) imaging was used to examine gerbil brains 1, 3, 10, and 30 days after 5 min forebrain ischemia. T2 was increased in the dorsal-lateral striatum 1 and 3 days post-ischemia, and in the hippocampus 3 days post-ischemia. T2 was normal 10 days post-ischemia, and decreased in the hippocampus and dorsal-lateral striatum 30 days post-ischemia. Neuronal counts in the dorsal-lateral striatum and CA1 hippocampal region were uniformly decreased 30 days post-ischemia. The increase in T2 shortly after ischemia is attributed to brain edema localized to regions where neuronal injury developed. The late decrease in T2 may be due to decreased water in gliotic tissue, or to ferritin-positive microglia, following forebrain ischemia. Tissue atrophy at later times gave enlarged ventricles on MR images.


Diabetic Retinopathy as a Risk Factor for Chronic Kidney Disease Progression: A Multicenter Case⁻Control Study in Taiwan.
It has rarely been studied whether the presence and severity of diabetic retinopathy (DR) could influence the renal disease progression among all chronic kidney disease (CKD) diabetic patients. This study investigates the characteristics of diabetic patients, with different stages of chronic kidney disease (CKD), according to the occurrence of diabetic retinopathy and determines the influence of retinopathy in the deterioration of renal function. We conduct a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of the CKD project (2008⁻2013) and the National Health Insurance Research Database (NHIRD) (2001⁻2013). A total of 4050 diabetic patients with CKD, 20⁻85 years of age, from 14 hospitals and the community are included in this study. As compared to CKD patients without DR, CKD patients with DR have a lower baseline estimated glomerular filtration rate (eGFR) (39.17 ± 30.36 mL/min per 1.73 m² vs. 54.38 ± 33.67 mL/min per 1.73 m² ); poorer glycemic control (higher glycated hemoglobin (HbA1c) 7.85 ± 4.97 vs. 7.29 ± 4.02, p < 0.01); higher proteinuria (urine protein-to-creatinine ratio (UPCR )1.94 ± 2.96 g/dL vs. 0.91 ± 2.11 g/dL, p < 0.01); more anemia (Hb 11.22 ± 2.43 g/dL vs. 12.39 ± 3.85 g/dL, p < 0.01), and more hypoalbuminemia (3.88 ± 0.95 g/dL vs. 4.16 ± 1.74 g/dL, p < 0.01). Later stage (stage 3b⁻5) CKD patients with DR had significantly higher CKD progression compared with patients without DR (OR (odds ratio) 1.66 (1.36⁻2.02)). Patients with proliferative DR had significantly higher CKD progression events compared to patients with non-proliferative DR (OR 2.18 (1.71⁻2.78)). The presence and severity of DR is a risk factor for CKD progression among our Taiwanese CKD patients with diabetes. Prevention and early detection of DR are important and DR should be routinely screened as early as possible among diabetic CKD patients.


Evaluation of robotically controlled advanced endoscopic instruments.
Advanced flexible endoscopes and instruments with multiple degrees of freedom enable physicians to perform challenging procedures such as the removal of large sections of mucosal tissue. However, these advanced endoscopes are difficult to control and require several physicians to cooperate. In this article, we present a robotic system that allows the physician to control an instrument in an intuitive way, using a haptic device. Performance with the robotic and conventional control methods were compared in a human subjects experiment. Subjects used both methods to tap a series of targets. They performed four trials while looking at the endoscopic monitor, and two trials while looking at the instrument directly. Subjects were significantly faster using the robotic method, 54 s vs 164 s. Their performance in the second trial was significantly improved with respect to the first trial. This study provides evidence that the robotic control method can be implemented to improve the performance of physicians using advanced flexible endoscopes.


Modification by some antagonists of the shape changes of venous endothelial cells in response to inflammatory agents in vitro.
Endothelial cells lining guinea pig inferior venae cavae change shape when exposed to histamine, bradykinin, A23187 or platelet-activating factor (PAF) in vitro. Pre-treatment of the endothelium with isoprenaline or quin 2 significantly reduced the shape changes produced in response to histamine, bradykinin and A23187, but not those to PAF. Since both isoprenaline and quin 2 may reduce the concentration of cytoplasmic Ca++, the former by raising cyclic AMP (cAMP) levels and the latter by acting as a Ca++ buffer, the results provide further evidence for the involvement of Ca++ in the responses of large vein endothelial cells to inflammatory agents in vitro. The effects of pre-treating the endothelium with the histamine receptor-blockers mepyramine (H1) or cimetidine (H2), or the bradykinin receptor-blockers des-arg9[leu8] bradykinin (B1) or des-arg[Hyp3, Thi5,8,D-Phe7] bradykinin (B2) suggest that the response to histamine is both H1 and H2 receptor-mediated, while the response to bradykinin is only B2 receptor-mediated.


Study of beta endorphin metabolism in inflamed tissue, serum and trypsin solution by liquid chromatography-tandem mass spectrometric analysis.
Beta endorphin (β-END) is recognised as one of the most significant endogenous neuropeptides, responsible for a wide range of biological activities in the body. However, within the body β-END is exposed to hydrolysis by a variety of enzymes. In this study, we investigated the metabolism and fragmentation pattern of β-END in rat inflamed tissue, in rat serum and in trypsin solution. β-END (1-31)-rat was incubated at 37 °C in each matrix for different incubation times. The resultant fragments were separated using a C4 column and detected by mass spectrometry using total ion current mode. Structural information for the fragments was elucidated using tandem mass spectrometry. Incubation of β-END (1-31)-rat in trypsin solution and in rat serum resulted in 8 and 13 fragments, respectively. Incubation in inflamed rat paw tissue resulted in 22 fragments at pH 7.4 and 26 fragments at pH 5.5. Some of these fragments were common to both pH values. The degradation of β-END (1-31)-rat in inflamed tissue at pH 5.5 was faster than that at pH 7.4. Secondary fragmentation of some larger primary fragments was also observed in this study.


Directed evolution of the fusion enzyme for improving astaxanthin biosynthesis in Saccharomyces cerevisiae.
The accumulation of the intermediate zeaxanthin and canthaxanthin in the astaxanthin biosynthesis pathway catalyzed by β-carotene hydroxylase (crtZ) and β-carotene ketolase (crtW) decreases the content of the astaxanthin. Here, we exploited directed evolution of the fusion of crtZ and crtW for improving astaxanthin biosynthesis in Saccharomyces cerevisiae. The results demonstrated that the fusion enzyme of crtZ-crtW with 2 X GGGGS peptides linker can effectively reduce the accumulation of intermediates and improves the content of astaxanthin. Compared with the control strain, the fusion enzyme of ketase and hydroxylase reduced zeaxanthin and canthaxanthin by 7 and 14 times and increased astaxanthin by 1.6 times, respectively. Moreover, 9 variant fusion mutants with improved astaxanthin production were generated through directed evolution. Combining these dominant mutants generated a variant, L95S + I206L, which increased the astaxanthin content of 3.8 times than the control strain. The AlphaFold2 assisted structural analysis indicated that these two mutations alter the interaction between the substrate and the enzymes pocket. Our research provided an efficient idea to reduce the accumulation of the intermediate products in complex biosynthesis pathway.


Short-type PB-cadherin promotes survival of gonocytes and activates JAK-STAT signalling.
Neonatal development of the rat testis involves a number of critical events including re-entry of gonocytes into the cell cycle and eventual loss of many of these cells and their progeny via apoptosis. Since surviving gonocytes give rise to subsequent generations of germ cells, regulation of their fate is critical for adult testicular function. Here, we have identified a role for short-type PB-cadherin (STPB-C) in promoting survival of gonocytes in neonatal rats and we have linked its expression to the JAK-STAT signaling pathway. These findings were obtained with varied approaches including use of transgenic rats overexpressing STPB-C which were studied with protein microarrays and other techniques, direct examination of germ cell apoptosis and survival in gonocyte-Sertoli cell co-cultures, and direct study of the JAK-STAT pathway in these models and in L cells transfected with STPB-C. These data provide new information on the regulation of gonocyte fate and exciting new evidence supporting a link between the JAK-STAT pathway and cadherin-based cell-cell interactions.


Update on the cardiometabolic syndrome.
An array of metabolic, hemodynamic, and renal abnormalities constitutes the cardiometabolic syndrome. A hallmark of this syndrome is visceral obesity and associated insulin resistance/hyperinsulinemia. The syndrome is also associated with essential hypertension, abnormalities in the circadian rhythm of blood pressure and heart rate, the diabetic dyslipidemic syndrome, hypercoagulability, hyperuricemia, increased cardiovascular inflammation, and microalbuminuria, all of which contribute to an increased risk of cardiovascular disease morbidity and mortality. This article reviews current knowledge about the interrelationship of the various factors that make up the cardiometabolic syndrome and its implications for individuals with and without diabetes mellitus.


Effect of endogenous beta-hydroxybutyrate on brain glucose metabolism in fetuses of diabetic rabbits, studied by (13)C magnetic resonance spectroscopy.
The aim of our research was to uncover perturbations in in-utero fetal cerebral metabolism resulting from hyperglycemia and hyperketonemia, which occur during maternal diabetes. Therefore, we examined the effects of glucose overload and hyperketonemia on glucose metabolism in the diabetic fetal brain; more specifically, the effect of diabetes on the glucose flux via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) and subsequent metabolism in the fetal cerebral tricarboxylic acid (TCA) cycle were examined, as well as the effect of diabetes on energy fuel utilization in the neurons and glia. Diabetes was induced in pregnant rabbits, and towards term, [U-(13)C(6)]glucose was infused into maternal circulation, and [(13)C]glucose metabolites were subsequently studied in fetal brain extracts by (13)C MRS isotopomer analysis. Significantly elevated maternal and fetal plasma glucose levels (three- and up to fivefold, respectively) and fetal brain glucose levels (up to eightfold) accompanied by an increase of beta-hydroxybutyrate (beta-HBA) levels (approximately 20-fold) were found in the hyperketonemic diabetic animals, whereas fetal cerebral lactate levels were decreased. Alterations in the (13)C labeling patterns, mainly of glutamine, led us to suggest that the entry of beta-HBA-derived acetyl-CoA inhibits formation and entry of labeled glucose-derived acetyl-CoA into the TCA cycle, mainly in glia. Accumulation of glucose and the decrease in lactate levels in the fetal brain are most likely the result of an inhibitory effect of beta-HBA on glycolysis. In addition, loss of (13)C enrichment of TCA cycle intermediates and products, glutamate and glutamine, in the hyperketonemic diabetic fetal brain may be attributed to the effect of beta-HBA fuel utilization by the fetal brain.


Study of performance and propagation characteristics of wire and planar structures around human body.
Continued miniaturization of electronic devices and technological advancements in wireless communications has made wearable body-centric telemedicine systems viable. Antennas play a crucial role in characterizing the efficiency and reliability of these systems. The performance characteristics such as the radiation pattern, gain, efficiency of the antennas get adversely affected due to the presence of lossy human body tissues. In this paper we investigate the above mentioned performance parameters and radio frequency transmission properties of wire and planar structures operating at ISM frequency band of 2.40-2.50 GHz in the proximity of human body.


Functions of p53 in pluripotent stem cells.
Pluripotent stem cells (PSCs) are capable of unlimited self-renewal in culture and differentiation into all functional cell types in the body, and thus hold great promise for regenerative medicine. To achieve their clinical potential, it is critical for PSCs to maintain genomic stability during the extended proliferation. The critical tumor suppressor p53 is required to maintain genomic stability of mammalian cells. In response to DNA damage or oncogenic stress, p53 plays multiple roles in maintaining genomic stability of somatic cells by inducing cell cycle arrest, apoptosis, and senescence to prevent the passage of genetic mutations to the daughter cells. p53 is also required to maintain the genomic stability of PSCs. However, in response to the genotoxic stresses, a primary role of p53 in PSCs is to induce the differentiation of PSCs and inhibit pluripotency, providing mechanisms to maintain the genomic stability of the self-renewing PSCs. In addition, the roles of p53 in cellular metabolism might also contribute to genomic stability of PSCs by limiting oxidative stress. In summary, the elucidation of the roles of p53 in PSCs will be a prerequisite for developing safe PSC-based cell therapy.


Predictability of short implants ( < 10 mm) as a treatment option for the rehabilitation of atrophic maxillae. A systematic review.
Short implants (< 10 mm) are one of the treatment options available in cases of limited vertical bone. Although such implants are now widely used, there is controversy regarding their clinical reliability. The purpose of this paper is to evaluate the predictability of short implants as an alternative to technically more complex treatments in patients with atrophic maxillae, based on a systematic review of the literature and the analysis of the implant survival rates, changes in peri-implant bone level, and associated complications. It is postulated that short implants offer clinical results similar to those of longer implants. A Medline-PubMed search was made covering the period between January 2004 and December 2014 (both included). Studies in English published in indexed journals, involving at least 20 implants and with a follow-up period of at least 12 months were considered. A manual search in four high impact journals was also conducted. A total of 37 studies meeting the inclusion criteria were included in this review. 9792 implants placed in over 5000 patients were analyzed. Based on the results of this review, short implants are seen to offer clinical results in terms of survival, bone loss and complications similar to those of longer implants.


Household transmission investigation: Design, reporting and critical appraisal.
Household transmission investigations (HHTIs) contribute timely epidemiologic knowledge in response to emerging pathogens. HHTIs conducted in the context of the COVID-19 pandemic in 2020-21 reported variable methodological approaches, producing epidemiological estimates that vary in meaning, precision and accuracy. Because specific tools to assist with the optimal design and critical appraisal of HHTIs are not available, the aggregation and pooling of inferences from HHTIs to inform policy and interventions may be challenging. In this manuscript, we discuss key aspects of the HHTI design, provide recommendations for the reporting of these studies and propose an appraisal tool that contributes to the optimal design and critical appraisal of HHTIs. The appraisal tool consists of 12 questions that explore 10 aspects of HHTIs and can be answered 'yes', 'no' or 'unclear'. We provide an example of the use of this tool in the context of a systematic review that aimed to quantify the household secondary attack rate from HHTIs. We seek to fill a gap in the epidemiologic literature and contribute to standardised HHTI approaches across settings to achieve richer and more informative datasets.


Simultaneous determination of quinapril and its active metabolite quinaprilat in human plasma using high-performance liquid chromatography with ultraviolet detection.
A high-performance liquid chromatography (HPLC) procedure for the simultaneous determination of quinapril and its active metabolite quinaprilat in human plasma samples is described. A one-step solid-phase extraction (SPE) with C18 cartridges was coupled with a reversed-phase HPLC system. The system requires two mobile phases composed of tetrabutyl ammonium hydrogensulfate (10 mM adjusted to pH 7)-acetonitrile (62:38, v/v) for quinapril, and (25:75, v/v) for quinaprilat elution through a C18 Symmetry column and detection at a wavelength of 215 nm. Calibration curves were linear over the ranges 20 to 1,000 ng/ml for quinaprilat and 10 to 500 for quinapril. The limits of quantification were 20 and 10 ng/ml for quinaprilat and quinapril, respectively. Extraction recoveries were higher than 90% for quinapril and 80% for quinaprilat. This method has been successfully applied to a bioequivalence study of quinapril in healthy subjects.


The influence of friends on smoking commencement and cessation in undergraduate nursing students: a survey.
Smoking is one of the leading causes of morbidity and mortality in most countries. Despite the fact that nurses have an important role in health promotion, and are in a good position to see and reflect on the detrimental effects of tobacco smoking, research has shown that the rate of smoking among nurses is similar to the rest of the population. The objective of this study was to examine the attitudes and experiences of undergraduate nursing students in relation to smoking commencement and cessation. It was part of a larger study that explored students smoking behaviours, knowledge and attitudes. A non-probability sample of 366 undergraduate nursing students from a large Australian school of nursing and midwifery took part in the study. The participants completed the Smoking and Health Promotion instrument. Ethics approval was obtained prior to the commencement of the study. Peers and friends were an important influence on the decision to commence smoking. The wish to comply with peer norms was especially prominent in mid-adolescence. Most smokers wanted to cease smoking, and many had tried unsuccessfully to stop on one or more occasions. They conceded that the pleasure they obtained from smoking and the effects of stress acted as barriers to stopping. The participants acknowledged the adverse health effects of smoking and some had already experienced these effects, but neither of these was enough to prompt them to cease. Undergraduate nursing curricula need to place greater emphasis on examining smoking related illnesses, as well as health promotion and role modelling in particular. Health promotion strategies that target peers are needed as an alternative to programmes that use fear or appeals to moral authority to prevent individuals from commencing smoking or encouraging cessation.


A novel anatomo-physiologic high-grade spondylolisthesis model to evaluate L5 nerve stretch injury after spondylolisthesis reduction.
L5 nerve palsy is a well-known complication following reduction of high-grade spondylolisthesis. While several mechanisms for its occurrence have been proposed, the hypothesis of L5 nerve root strain or displacement secondary to mechanical reduction remains poorly studied. The aim of this cadaveric study is to determine changes in morphologic parameters of the L5 nerve root during simulated intraoperative reduction of high-grade spondylolisthesis. A standard posterior approach to the lumbosacral junction was performed in eight fresh-frozen cadavers with lumbosacral or lumbopelvic screw fixation. Wide decompressions of the spinal canal and L5 nerve roots with complete facetectomies were accomplished with full exposure of the L5 nerve roots. A 100% translational slip was provoked by release of the iliolumbar ligaments and cutting the disc with the attached anterior longitudinal ligament. To evaluate the path of the L5 nerves during reduction maneuvers, metal bars were inserted bilaterally at the inferomedial aspects of the L5 pedicle at a distance of 10 mm from the midpoint of the L5 pedicle screws. There was no measurable change in length of the L5 nerve roots after 50% and 100% reduction of spondylolisthesis. Mechanical strain or displacement during reduction is an unlikely cause of L5 nerve root injury. Further anatomical or physiological studies are necessary to explore alternative mechanisms of L5 nerve palsy in the setting of high-grade spondylolisthesis correction, and surgeons should favor extensive surgical decompression of the L5 nerve roots when feasible.


Triester glycerothiophosphates of cholecalciferol (vitamin D3).
Tris(N,N-dimethyl)amide of phosphorous acid activated by addition of iodine at an optimal molar ratio of 1.05:0.05 was used as a phosphorylating reagent to synthesize cholecalciferyl-3-O-(1-2-isopropylidene-rac-glycero-3-O-)-thiophos phate and cholecalciferyl-3-O-(1,2-dipalmitoyl-rac-glycero-3-O-)thiophosphat e of methyl alcohol, 2-dimethylaminoethanol, 3-dimethylamino-1-propanol and 1,2-isopropylidene-rac-glycerol in a "one-pot procedure" in overall yields of 60-80%. Activation of the reaction with an equimolar mixture of imidazole and carbon disulfide at the triester formation step permits selective phosphorylation at room temperature. The compounds synthesized represent new triester phospholipid model compounds in which (in addition to glycerol and another requisite alcohol) a steroid and an element other than oxygen are bond to phosphorus.


A long-term conditional survival analysis for gastric cancer based on 7th and 8th TNM classification in Eastern and Western populations.
To compare the power to predict the 5-year conditional disease-specific survival (CS5) between the 7th and 8th editions of the TNM for gastric cancer (GC) patients. This retrospective study recruited 20,548 patients who underwent GC surgery from the databases of the Surveillance, Epidemiology, End Results and a center in Asia. The CS5 was evaluated with the 7th and 8th TNM classification. A two-step model showed that at the 3-5th postoperative years, the 8th staging remained an independent risk factor, whereas there was no significant difference for 7th -edition staging. Further analysis of the ability to predict CS5 indicated that there were significant differences in the CS5 of 7th -edition stages IIb and IIIa at baseline and at the postoperative 1-4th years (all p < 0.05, Cohen's d > 0.5). However, the CS5 of the fifth year was similar between them (p = 0.307, Cohen's d = 0.35). Meanwhile, the results indicated that the 8th -edition staging could effectively determine the CS5 among stages Ⅰa, Ⅰb, Ⅱa, Ⅱb, Ⅲa, and Ⅲb at baseline and at the postoperative 1-5th years (all p < 0.05). However, neither the 7th - nor the 8th -edition staging could predict the CS5 for stages Ⅲb and Ⅲc from the postoperative third to fifth years (all p > 0.05). For patients with stages IIB and IIIA GC, the 8th TNM has a higher discriminatory value than the 7th edition for CS5 after the postoperative fourth year. However, a more detailed classification system is still needed to predict conditional survival for GC.


Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits.
To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA). Twenty rabbits were divided randomly into four groups (n = 5 in each): a control group, model group, acupotomy group, and sodium hyaluronate injection group. The model, acupotomy, and sodium hyaluronate groups underwent anterior cruciate ligament transection plus partial medial meniscectomy. Sodium hyaluronate injection and acupotomy were administered to the respective groups from weeks 5 to 8, and samples of the tibial plateau and medial condyle of the femur were collected in week 9. Vascular endothelial growth factor (VEGF) expression was assessed in cartilage and subchondral bone by immunohistochemical staining. Articular cartilage degeneration was less pronounced in the acupotomy compared with the model and sodium hyaluronate groups. VEGF expression levels in cartilage and subchondral bone were increased in the model group compared with the control group (P < 0.01), and acupotomy had a more pronounced therapeutic effect than sodium hyaluronate injection (P < 0.01). Acupotomy and sodium hyaluronate injection may both reduce degeneration in the cartilage and subchondral bone in KOA based on the results from a rabbit model, but acupotomy improved the histopathology and reduced the VEGF content more effectively than sodium hyaluronate injection, probably by reducing venous stasis and intraosseous pressure. Acupotomy may improve KOA by lowering VEGF.


Support systems for cyclists in automated traffic: A review and future outlook.
Interaction with vulnerable road users in complex urban traffic environments poses a significant challenge for automated vehicles. Solutions to facilitate safe and acceptable interactions in future automated traffic include equipping automated vehicles and vulnerable road users, such as cyclists, with awareness or notification systems, as well as connecting road users to a network of motorised vehicles and infrastructure. This paper provides a synthesis of the current literature on communication technologies, systems, and devices available to cyclists, including technologies present in the environment and on motorised interaction partners such as vehicles, and discusses the outlook for technology-driven solutions in future automated traffic. The objective is to identify, classify, and count the technologies, systems, and devices that have the potential to aid cyclists in traffic with automated vehicles. Additionally, this study aims to extrapolate the potential benefits of these systems and stimulate discourse on the implications of connected vulnerable road users. We analysed and coded 92 support systems using a taxonomy of 13 variables based on the physical, communicational, and functional attributes of the systems. The discussion frames these systems into four categories: cyclist wearables, on-bike devices, vehicle systems, and infrastructural systems, and highlights the implications of the visual, auditory, motion-based, and wireless modes of communication of the devices. The most common system was cyclist wearables (39%), closely followed by on-bike devices (38%) and vehicle systems (33%). Most systems communicated visually (77%). We suggest that interfaces on motorised vehicles accommodate cyclists with visibility all around the car and incorporate two-way communication. The type of system and the effect of communication modality on performance and safety needs further research, preferably in complex and representative test scenarios with automated vehicles. Finally, our study highlights the ethical implications of connected road users and suggests that the future outlook of transport systems may benefit from a more inclusive and less car-centred approach, shifting the burden of safety away from vulnerable road users and promoting more cyclist-friendly solutions.


Association of Triglyceride-Glucose Index and Liver Function Parameters Among Healthy Obese Civil Servants: A Center-Based Study.
To investigate the correlation between Triglyceride-glucose (TyG) index and liver function parameters in healthy obese civil servants in Shijiazhuang, China. This was an outpatient-based cross-sectional study in which 6452 participants were recruited. A total of 784 participants were analyzed according to inclusion and exclusion criteria. A TyG index was calculated based on fasting glucose and triglycerides. All patients were divided into a high TyG index group and a low TyG index group, using the median TyG index as a cut-off. Finally, patients were further divided into two subgroups: males and females. While AST/ALT and direct bilirubin levels were lower in the high TyG index group compared to the low TyG index group, ALT, AST, total protein, and albumin levels were greater. Particularly in male participants, TyG index was inversely connected with AST/ALT and direct bilirubin levels and favorably correlated with ALT, AST, total protein, and albumin levels. These connections persisted in the multilinear regression study even after adjusting for confounding variables. This study describes the correlation between TyG index and liver function parameters in obese populations without co-morbid diseases, providing a new idea for early interventional treatment in this group.


Hyaluronic acid-grafted polyamidoamine dendrimers enable long circulation and active tumor targeting simultaneously.
Herein, we developed dualfunctional hyaluronic acid (HA)-grafted polyamidoamine (PAMAM) dendrimers for simultaneous systemic long circulation and active tumor targeting and delivery of topotecan hydrochloride (TPT). The possibility of these modified dendrimers as nanocarriers for promoting tissue distribution and antitumor efficiency, as well as a drug release profile, cytotoxicity and cellular uptake, was investigated. The fine targeting efficiency of HA-PAMAM/TPT was confirmed by the CD44 receptor-mediated high cellular uptake efficiency and low cytotoxicity in HCT-116 cells, and the in vivo higher tumor distribution percentage than in other tissues in mice bearing an S-180 tumor. Pharmacokinetic studies showed that the t1/2 and MRT of TPT were significantly extended after intravenous administration of HA-PAMAM/TPT in normal rats. Moreover, TPT-loaded nanovehicles demonstrated higher antitumor activity compared with free drug and PAMAM/TPT. Overall, HA-PAMAM may be an alternative vector for the effective targeted delivery of and tumor therapy with antitumor drugs.


Quercetin inhibits the cytotoxicity and oxidative stress in liver of rats fed aflatoxin-contaminated diet.
This study was conducted to evaluate the protective role of quercetin (Q) against the cytotoxicity, DNA damage and oxidative stress in rats fed aflatoxin (AFs)-contaminated diet. Female Sprague-Dawley rats were divided into six groups and treated for 21 days as follows: the control group; the group fed AFs-contaminated diet (1.4 mg/kg diet); the groups treated orally with Q at low or high dose (50 and 100 mg/kg b.w.) and the groups AFs-contaminated diet plus low or high dose of Q. At the end of experiment, blood and liver samples were collected for biochemical, histological, histochemical and genetic analyses. The results indicated that animal fed AFs-contaminated diet showed significant increase in serum biochemical parameters, oxidative stress markers and DNA fragmentation accompanied with significant decrease in total proteins, GPX, SOD, DNA and RNA content and fatty acid synthase (Fas) and TNFα gene expression in the liver tissue. Q at the two tested doses succeeded to normalize the biochemical parameters, improved the content of nucleic acids in hepatic tissues, the gene expression, the histopathological and histochemical picture of the liver. It could be concluded that Q has a potential antioxidant activity, a protective action and regulated the alteration of genes expression induced by AFs.


Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition.
Progression to renal parenchymal damage and end-stage renal disease, which seems to be largely independent of the initial insult, is the final common pathway for chronic, proteinuric nephropathies in animals and humans. The key event is enhanced glomerular capillary pressure; this impairs glomerular permeability to proteins and permits excessive amounts of proteins to reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute to renal interstitial injury by activating intracellular events, including upregulation of the genes encoding vasoactive and inflammatory mediators. Both interstitial inflammation and progression of disease can be controlled by such drugs as angiotensin-converting enzyme inhibitors, which strengthen the glomerular permeability barrier to proteins and thereby limit proteinuria and filtered protein-dependent inflammatory signals. Clinical data strongly suggest that remission can now be achieved in some patients with chronic renal disease. Because of the current lag time between starting treatment and remission, however, a substantial proportion of patients still progress to end-stage renal disease before renal function begins to stabilize. A multimodal approach that centers on reducing or removing all risk factors associated with the progression of renal disease may decrease the time to remission of the disease for most patients with proteinuric nephropathies.


Stemness targeting of colorectal cell lines mediated by BAMLET and 5-Flourouracil.
Stemness is the potential for self-renewal and repopulation causing the relapse, progression, and drug resistance of colorectal cancer. We investigated the effects of bovine alpha-lactalbumin made lethal to tumor cells and 5-Flourouracil consisting of bovine α-lactalbumin protein and oleic acid, on colorectal cancer cells on stemness. The quantitative real-time polymerase chain reaction assessed the expression levels of stemness-related genes (c-myc, Lgr5, OCT4). Expression of stemness-related surface markers (CD44 and CD24) was also measured by the flow cytometry technique following the treatments. Our results indicated decreased expression levels of C-Myc, Lgr5, oct4 as the stemness-related genes (P < 0.0001), and reduced population of CD44+ as the stemness-related cell surface marker upon treatment with BAMLET and 5-Flourouracil. BAMLET inhibited the stemness more effectively than 5-Flourouracil (P < 0.0001). Based on the result, inhibition of the Stemness related-genes (C-Myc, Lgr5, Oct4) and the surface markers (CD 24+ and CD44+) is a promising therapeutic approach using BAMLET.


Cytotoxicity, apoptosis induction, and mitotic arrest by a novel podophyllotoxin glucoside, 4DPG, in tumor cells.
To define the in vitro cytotoxic activities of 4-demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), a new podophyllotoxin glucoside. Antiproliferation activity was measured in several tumor cell lines by using the microculture tetrazolium MTT assays. Cell cycle distribution was analyzed using flow cytometry and mitosis index assays. Furthermore, transmission electron microscopy, TUNEL, DNA agarose electrophoresis, and activated caspase-3 were used to analyze the induction of apoptotic cell death. Moreover, intracellular changes in the cytoskeleton were detected using immunocytochemistry. 4DPG effectively inhibited the proliferation of cancer cells (HeLa, CNE, SH-SY5Y, and K562 cell lines). For the K562 cell line, the antiproliferation effect of 4DPG was much more potent than that of etoposide (IC50 value: 7.79 x 10(-9) mol/L for 4DPG vs 2.23 x 10(-5) mol/L for etoposide). Further, 4DPG blocked the cell cycle in the mitotic phase. The induction of apoptosis and elevated levels of activated caspase-3 were confirmed in cells treated with 4DPG. The microtubule skeleton of HeLa cells was disrupted immediately after treatment with 4DPG. The cytotoxicity of 4DPG is due to its inhibition of the microtubule assembly of cancer cells at a low concentration, thus inducing apoptosis. These properties qualify 4DPG to be a potential antitumor drug.


Preclinical evaluation of [11 C]L-235 as a radioligand for Positron Emission Tomography cathepsin K imaging in bone.
The cathepsin K (CatK) enzyme is abundantly expressed in osteoclasts, and CatK inhibitors have been developed for the treatment of osteoporosis. In our effort to support discovery and clinical evaluations of a CatK inhibitor, we sought to discover a radioligand to determine target engagement of the enzyme by therapeutic candidates using positron emission tomography (PET). L-235, a potent and selective CatK inhibitor, was labeled with carbon-11. PET imaging studies recording baseline distribution of [11 C]L-235, and chase and blocking studies using the selective CatK inhibitor MK-0674 were performed in juvenile and adult nonhuman primates (NHP) and ovariectomized rabbits. Retention of the PET tracer in regions expected to be osteoclast-rich compared with osteoclast-poor regions was examined. Increased retention of the radioligand was observed in osteoclast-rich regions of juvenile rabbits and NHP but not in the adult monkey or adult ovariectomized rabbit. Target engagement of CatK was observed in blocking studies with MK-0674, and the radioligand retention was shown to be sensitive to the level of MK-0674 exposure. [11 C]L-235 can assess target engagement of CatK in bone only in juvenile animals. [11 C]L-235 may be a useful tool for guiding the discovery of CatK inhibitors.


Efficient biosorption of chromium(VI) ion by dry Araucaria leaves.
In this paper, batch removal of hexavalent chromium from aqueous solutions by Araucaria heterophylla leaves was investigated. The batch experiments were conducted to study the adsorption of metal species and effect of different pH, contact time, metal concentration, biosorbent concentration, and adsorption capacity. Freundlich and Langmuir's isotherm model were used to describe the adsorption behavior, and the experimental results fitted Freundlich model well. The adsorption efficiency observed for all chromium concentrations, i.e., 1, 3, 5, and 10 mg/L was 100% and the equilibrium was achieved in 30 min for 1 and 3 mg/L, whereas for 5 and 10 mg/L, it was less than 60 min. FTIR spectra was taken to identify functional groups involved in the biosorption. Thus, Araucaria leaves can be considered as one of the cheap and efficient biosorbent for toxic hexavalent chromium removal from natural or wastewaters.


Antigenic regions defined by monoclonal antibodies on tumor-associated antigens of bovine leukemia virus-induced lymphosarcoma cells.
Tumor-associated antigens (TAAs) expressed on enzootic bovine leukosis tumors were divided previously into three types by use of 13 monoclonal antibodies (MAbs): common TAA, partially common TAA and individually distinct TAA. Since MAb-defined epitopes on the common TAA were conserved on both soluble TAA prepared from bovine B-lymphoma cells and untreated viable same cells, all the MAbs that bound to the soluble TAA also bound to untreated viable cells. By contrast, MAb-defined epitopes on the partially common and individually distinct TAAs varied according to the test systems used. Two of seven MAbs were found to bind to both the soluble TAA and viable cells and one MAb bound to the soluble TAA but not to the viable cells.


Effect of food matrix on rapid detection of Vibrio parahaemolyticus in aquatic products based on toxR gene.
Vibrio parahaemolyticus has become an important public threat to human health. Rapid and robust pathogen diagnostics are necessary for monitoring its outbreak and spreading. Herein, we report an assay for the detection of V. parahaemolyticus based on recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD), namely RAA-LFD. The RAA-LFD took 20 min at 36~38 ℃, and showed excellent specificity. It detected as low as 6.4 fg/µL of V. parahaemolyticus in genomic DNA, or 7.4 CFU/g spiked food samples with 4 h of enrichment. The limit of detection in shrimp (Litopenaeus Vannamei), fish (Carassius auratus), clam (Ruditapes philippinarum) evidenced that sensitivity was considerably affected by the food matrix. The presence of food matrix reduced the sensitivity of spiked food samples by 10 ~ 100 times. In the filed samples detection, RAA-LFD method showed good coincidence with GB4789.7-2013 method and PCR method at rates of 90.6% and 94.1%, respectively. RAA-LFD has high accuracy and sensitivity for the detection of V. parahaemolyticus, which can serve as a model tool to meet the growing need for point-of-care diagnosis of V. parahaemolyticus.


Associations of components of PTEN/AKT/mTOR pathway with cancer stem cell markers and prognostic value of these biomarkers in hepatocellular carcinoma.
We aimed to investigate the associations between components of the phosphatase and tensin homolog deleted on chromosome 10/protein kinase B/mammalian target of rapamycin (PTEN/AKT/mTOR) pathway and liver cancer stem cell (LCSC) markers, including CD133, CD90, CD44, and epithelial cell adhesion molecule (EpCAM), and to further evaluate the predictive values of these biomarkers for recurrence and survival in hepatocellular carcinoma (HCC). Protein expressions and mRNA levels of PTEN and LCSC markers were determined in 110 HCC tissues and 98 adjacent non-tumor tissues. Protein expressions of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were detected to evaluate the activation of the PTEN/AKT/mTOR pathway by using immunohistochemistry. Prognostic significance was analyzed by univariate and multivariate analysis. Loss of PTEN expression was negatively correlated with positive expression of CD133, CD90, and EpCAM (P < 0.05). Positive expression of p-AKT and p-mTOR were positively associated with positive expression for CD133, CD90, and EpCAM (P < 0.05). By univariate and multivariate analysis, a higher level of α-fetoprotein, loss of PTEN expression, and CD133-positive, p-AKT-positive, p-mTOR-positive, and EpCAM-positive signals were predictors for HCC recurrence, whereas advanced TNM stage, loss of PTEN expression, and positive expression of p-AKT, p-mTOR, and CD133 were predictors for survival. Patients with PTEN- /CD133+ or PTEN- /EpCAM+ HCC had shorter recurrence-free survival and overall survival times. The PTEN/AKT/mTOR pathway might play a crucial role in driving recurrence and influencing prognosis in HCC. There could be a potential repressive relationship between components of the PTEN/AKT/mTOR pathway and LCSCs. The combination of PTEN with CD133 or EpCAM expression may serve as a screening tool to monitor recurrence and predict prognosis.


Three species of polyoma virus tumor antigens share common peptides probably near the amino termini of the proteins.
Detergent extracts of polyoma virus-infected mouse cells contain three major proteins of approximately 100,000--108,000 (100K), 55,000 (55K) and 21,500 (22K) daltons, which react with sera obtained from rats carrying tumors induced by the virus. A comparison of the 35S-methionine-, 3H-leucine- and 3H-proline-labeled tryptic peptides of each of these proteins by cation-exchange chromatography followed by descending paper chromatography has shown that: at least five peptides are shared by all three T-reactive proteins; at least three peptides are shared by the 55K and 22K proteins, but not by the 100K protein; at least three peptides are found only in the 22K protein; at least six peptides are found only in the 55K protein; and at least sixteen peptides are found only in the 100K protein. The results are consistent with the hypothesis that the polypeptide chains of the 100K, 55K and 22K dalton tumor antigens of polyoma virus share a common virus-coded amino terminal region. The data also suggest that there is a portion of the polypeptide chains (probably immediately adjacent to the common amino terminal region of the molecules) that is shared by the 55K and 22K proteins, but not by the 100K protein (perhaps because this portion of the genetic information is spliced out of the messenger RNA coding for the 100K protein). The facts that all the peptides common to the 100K and 55K proteins are also found in the 22K protein and are thus assigned to the common amino terminal region of the molecules, and that there are several peptides unique to the 100K protein, as well as several peptides unique to the 55K protein, suggest that the presumed carboxy terminal portion of the polypeptide chain of the 100K protein is considerably, if not entirely, different from that of the 55K protein.


Status of Caribbean coral reefs in seven countries in 1986.
There are few long-term datasets available to make reliable statements about trends in cover and structure in many coral reefs around the world. We present 27year old summary data of the cover of corals and other biota on Caribbean and Western Atlantic coral reefs in 7 countries collected in late 1985 and early 1986. These data were collected to support research on sponge populations and show relatively low coral cover on many of these reefs with particularly low cover of Acropora spp. We present these summaries to encourage other researchers to compare with current conditions or repeat the surveys to show long-term trends; the raw data will be supplied on request.


Inherent biophysical stability of foot-and-mouth disease SAT1, SAT2 and SAT3 viruses.
Foot-and-mouth disease (FMD) virus (FMDV) isolates show variation in their ability to withstand an increase in temperature. The FMDV is surprisingly thermolabile, even though this virus is probably subjected to a strong extracellular selective pressure by heat in hot climate regions where FMD is prevalent. The three SAT serotypes, with their particularly low biophysical stability also only yield vaccines of low protective capacity, even with multiple booster vaccinations. The aim of the study was to determine the inherent biophysical stability of field SAT isolates. To characterise the biophysical stability of 20 SAT viruses from Southern Africa, the thermofluor assay was used to monitor capsid dissociation by the release of the RNA genome under a range of temperature, pH and ionic conditions. The SAT2 and SAT3 viruses had a similar range of thermostability of 48-54 °C. However, the SAT1 viruses had a wider range of thermostability with an 8 °C difference but with many viruses being unstable at 43-46 °C. The thermostable A-serotype A24 control virus had the highest thermostability of 55 °C with some SAT2 and SAT3 viruses of similar thermostability. There was a 10 °C difference between the most unstable SAT virus (SAT1/TAN/2/99) and the highly stable A24 control virus. SAT1 viruses were generally more stable compared to SAT2 and SAT3 viruses at the pH range of 6.7-9.1. The effect of ionic buffers on capsid stability showed that SAT1 and SAT2 viruses had an increased stability of 2-9 °C and 2-6 °C, respectively, with the addition of 1 M NaCl. This is in contrast to the SAT3 viruses, which did not show improved stabilisation after addition of 1 M or 0.5 M NaCl buffers. Some buffers showed differing results dependent on the virus tested, highlighting the need to test SAT viruses with different solutions to establish the most stabilising option for storage of each virus. This study confirms for the first time that more stable SAT field viruses are present in the southern Africa region. This could facilitate the selection of the most stable circulating field strains, for adaptation to cultured BHK-21 cells or manipulation by reverse genetics and targeted mutation to produce improved vaccine master seed viruses.


Insights into the impact of quaternary ammonium disinfectant on sewage sludge anaerobic digestion: Dose-response, performance variation, and potential mechanisms.
Wide commercial applications of antimicrobial quaternary ammonium compounds (QACs) inevitably lead to the release into wastewater and enrichment in sewage sludge. This study evaluated the impacts of levels and structures of QACs on sewage sludge properties, microbial community, and methane production during anaerobic digestion. Methane production was stimulated or not affected at low QACs concentrations, but significantly inhibited at high QACs concentrations. Compared with benzyl and alkyltrimethyl QACs, dialkyl QACs showed least toxicity on digestion performance. Meanwhile, microbial community analysis indicated that shifts in bacterial communities mainly depended on QACs doses, but the archaeal communities were affected by both QACs doses and types. The dominant methanogenic pathway shifted from acetotrophic/methylotrophic methanogens to mixotrophic methanogens by low levels of benzyl and alkyltrimethyl QACs but not dialkyl QACs, and further to hydrogenotrophic methanogens at high QACs concentration. Mechanism exploration revealed that the presence of QACs promoted sludge solubilization by the integrated effects of cell lysis, electric neutralization, and hydrophobicity improvement, but inhibited methanogenesis due to the accumulation of volatile fatty acids and susceptibility of methanogens to QACs. These findings provided a reference for potential impacts of different QACs on sludge biological treatment, which had implications for the use and selection of QACs disinfectants.


What are dually diagnosed patients' problems represented to be in mental health? A WPR analysis of the multistability purpose of digital health records.
No previous studies have investigated how political measures, opinions and views of people with dual diagnoses, organisational requirements and professional values are purposefully communicated, mediated and/or integrated in digital records in mental health care. It remains unclear how health records function as both clinical vehicles for documentation, audit and quality assurance in patient care as well as political vehicles of power to articulate and reproduce idealised relations among actors and their roles in mental health. Informed by Bacchi's 'What's the problem represented to be' (WPR) approach, we consider how problems of dually diagnosed persons with co-occurring mental health conditions and drug use (DDPs) are represented and how the tools required to fix the patients' problems are communicated and legitimised in 10 digital health records consisting of 3830 pages of data. In the discussion, we distinguish their multiple purposes by discussing how their structure is shaped by broader discourses in health care. Then, we consider how the structure of records delineates professionals' autonomy, discretionary action and service provision in ways that limit possibilities for including mental health patients' experiences and exclude service users' voices from care planning.


Do Intrathecal Opioids Improve Surgical Outcomes After Coronary Artery Bypass Grafting? A Systematic Review and Analysis.
Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have been used preoperatively as a pain management adjuvant for open cardiac and thoracic procedures. This study aims to analyze the impact of administering intrathecal opioids before cardiac and thoracic surgeries on postoperative pain and mechanical ventilation. Systematic review and meta-analysis. University, School of Medicine, and several university-affiliated hospitals. Five outcomes were studied, including the primary outcome of time to extubation, secondary outcomes of analgesia requirements at 24 and 48 hours, resting pain scores at 1 and 24 hours post-extubation, ICU length of stay in hours, and hospital length of stay in days. A search of multiple databases provided 28 studies reporting 4,000 total patients. Outcomes were measured using continuous mean difference with a 95% confidence interval, and the studies were examined for heterogeneity and sensitivity analysis. The primary outcome analysis suggested that time to extubation was 42 minutes shorter in the intrathecal opioid group (ranging from 82 to 1 minute, P = 0.04). There was also a decrease in postoperative analgesia requirements at both 24 hours (mean difference (MD) = -8.95 mg morphine equivalent doses (MED) [-9.4, -8.5], P < 0.001) and 48 hours (MD = -17.7 mg MED [-23.1, -12.4], P < 0.001) with I2 of 94% and 85% respectively, an improvement of pain scores at both 1 hour (MD = -2.24 [-3.16, -1.32], P < 0.001) and 24-hours (MD = -1.64 [-2.48, -0.80], P =< 0.001) I2 of 94% and 85%, no change in both ICU length of stay (MD = -0.27 hours [-0.55, 0.01], P = 0.06) I2 = 77% and hospital length of stay (MD = -0.30 days [-0.66, 0.06], P = 0.11) I2 = 32%. The major limitation of this meta-analysis was the inconsistent dosages of intrathecal opioids utilized. Some used the same dose for each patient, while other studies used weight-based doses. The differences in the outcomes observed may then be a result of the different amounts of opioids administered rather than the technique itself. Another limitation was the inconsistent timing of reports for pain scores and postoperative analgesic requirements. Further studies were analyzed at the 2 time periods for both secondary outcomes, making it difficult to attribute the 2 effects solely to the intervention. We conclude that preoperative injection of intrathecal opioids is significantly associated with decreased time to extubation, decreased postoperative analgesia requirement, and improved pain scores. In controlled conditions with adequate staff education, this method of analgesia may make it possible to extubate the patients after the surgery in the operating room and fast-track their discharge from the hospital.


Description and comparative genomic analysis of a mcr-1-carrying Escherichia coli ST683/CC155 recovered from touristic coastal water in Northeastern Brazil.
Polymyxin resistance is an emerging health issue aggravated by mcr dissemination among Enterobacterales recovered from various sources. Commensal Escherichia coli plays a key role in the spread of antimicrobial resistance in community settings and is likely to spread silently. It may transfer resistance genes to pathogenic bacteria in the gastrointestinal tract and the environment, and may cause difficult-to-treat infections, especially in immunocompromised patients. Unraveling actors disseminating resistance to last-resort antimicrobials might support the future development of control measures. Here we report the occurrence of a commensal ST683/CC155 colistin-resistant mcr-1.1-harboring E. coli (JP24) obtained from touristic coastal water. JP24's genome was sequenced and comparatively analyzed with other genomes from ST683/CC155 isolated worldwide and with mcr-carrying isolates recovered from various sources in Brazil. Besides mcr-1, JP24 carried blaCTX-M-8, tet(A), tet(34), dfrA12, sul2, sul3, aph(3')-Ia, aph(3')-IIa, aadA1, aadA2, cmlA1, Inu(G), mef(B) and mdf(a). mcr-1 and blaCTX-M-8 were transferable by IncX4 and IncI1/Iγ plasmids, respectively. Tree-based phylogeny of the ST683/CC155 isolates core genome revealed two larger clades. E. coli JP24 was grouped into a subclade together with an isolate from Thailand (ERR4221036), both carrying mcr-1. The core genome-based tree of the isolates carrying mcr-1 from Brazil revealed proximity with E. coli ECEST9 recovered from a mangrove also located in Northeastern Brazil. Accessory genome-based tree clustered most environmental isolates apart from the clinical ones and remained JP24 closer to ECEST9. High sequence conservation was observed between mcr-1-harboring plasmids detected in different species and reservoirs in Brazil and other countries. In addition to recreational coastal waters being potential sources for community exposure to antimicrobial-resistant bacteria, our findings reinforce a more prominent role of horizontal gene transfer, other than clonal expansion, in mcr dissemination in the community.


Can lactate-evoked cardiovascular responses be used to identify muscle ergoreceptors?
The increase in blood pressure and heart rate which accompanies muscular exercise is in part a reflex mediated by afferent nerve fibres in the group III and IV (small myelinated and unmyelinated) range. It has been reported that perfusion of lactate ions into hind limb muscles is an effective stimulus for these reflex responses. To investigate this hypothesis further, and to test adequacy of the controls used, a solution containing 15 mM lactic acid was perfused through a hind limb of urethane-anaesthetised rats, the leg's circulation being isolated from the rest of the body. During lactate perfusion, increases were seen in arterial blood pressure and heart rate. Denervation of the entire leg abolished the responses. To locate the receptors involved in the reflex, selective denervations of skin or muscle were performed. Clear responses were never seen when the leg was skinned or denervated by section of cutaneous nerves. On the other hand, responses to lactate perfusion were still seen following section of all nerves supplying the muscles of the leg, leaving the cutaneous innervation largely intact. It is concluded that perfusion of a hindlimb with lactate solutions is not an adequate technique to identify ergoreceptors in muscle.


Oral midazolam with an antacid may increase the speed of onset of sedation in children prior to general anaesthesia.
The aim of the study was to see whether sodium citrate solution would speed the gastric absorption of oral midazolam. Forty presurgical ASA I and II patients (aged 2-6 years) were randomly assigned to one of two groups. Group I received midazolam 0.5 mg x kg(-1) mixed with sodium citrate while group II (control) received midazolam 0.5 mg x kg(-1) mixed with Hawaiian fruit punch. There was no statistical difference between the ages, weights, preoperative sedation and anxiety scores in the two groups. After premedication, the onset of sedation (mean +/- SD) measured by the first change in sedation score was found to be significantly faster (P < 0.05) in group I (17.8 +/- 7.11) compared with group II (21.9 +/- 5.34). There was no statistical difference in anxiety at any time intervals, separation or induction scoring for both groups. Gastric volumes and the pH of gastric aspirates between the two groups were not statistically significant. The time to onset of sedation can potentially be shortened, by using a preparation of intravenous midazolam and antacid, given orally.


Introducing a Measurement Feedback System for Youth Mental Health: Predictors and Impact of Implementation in a Community Agency.
Measurement feedback systems (MFSs) that routinely collect and report client progress to mental health therapists have demonstrated beneficial impact on outcomes in numerous studies, with evidence that there is a dose-response relationship related to the implementation of the MFS. The current study examined the impact of MFS implementation (Implementation Index) on youth symptom outcomes separately by caregiver and youth self-report. Additionally, we tested the extent to which Implementation Index rates varied by individual therapists and clients, and whether therapist and client characteristics predicted MFS implementation. Methods: Administrative data (client charts, youth- and caregiver-reported Youth Outcome Questionnaires) for 229 youth (52.83% Latinx, 42.79% girls, M age = 10.33) treated during a 1-year period at a community mental health organization in Central Texas were analyzed using multi-level modeling. Caregiver-reported symptoms decreased faster for those with a higher MFS Implementation Index. Between-group differences among therapists accounted for a significant proportion of variance in the Implementation Index for caregiver report, whereas client differences accounted for most of the variance in the Implementation Index for youth self-report. Therapist trainee status predicted a significant increase in the Implementation Index for caregiver-report data. Youth symptom improvement as reported by caregivers varied with the extent of MFS implementation fidelity, and MFS implementation fidelity was higher for clients treated by trainees relative to staff therapists for caregiver report of symptoms.


The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis.
Dihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mm did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mm inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mm inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mm increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG.


Hydroxylated and methoxylated polybrominated diphenyl ethers and polybrominated dibenzo-p-dioxins in red alga and cyanobacteria living in the Baltic Sea.
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are present in the ecosystem of the Baltic Sea. OH-PBDEs are known to be both natural products from marine environments and metabolites of the anthropogenic polybrominated diphenyl ethers (PBDEs), whereas, MeO-PBDEs appear to be solely natural in origin. Polybrominated dibenzo-p-dioxins (PBDDs) are by-products formed in connection with the combustion of brominated flame retardants (BFRs), but are also indicated as natural products in a red alga (Ceramium tenuicorne) and blue mussels living in the Baltic Sea. The aims of the present investigation were to quantify the OH-PBDEs and MeO-PBDEs present in C. tenuicorne; to verify the identities of PBDDs detected previously in this species of red alga and to investigate whether cyanobacteria living in this same region of the Baltic Sea contain OH-PBDEs, MeO-PBDEs and/or PBDDs. The red alga was confirmed to contain tribromodibenzo-p-dioxins (triBDDs), by accurate mass determination and additional PBDD congeners were also detected in this sample. This is the first time that PBDDs have been identified in a red alga. The SigmaOH-PBDEs and SigmaMeO-PBDEs concentrations, present in C. tenuicorne were 150 and 4.6 ng g(-1) dry weight, respectively. In the cyanobacteria 6 OH-PBDEs, 6 MeO-PBDEs and 4 PBDDs were detected by mass spectrometry (electron capture negative ionization (ECNI)). The PBDDs and OH-PBDEs and MeO-PBDEs detected in the red alga and cyanobacteria are most likely of natural origin.