The standard of integrity may be useful when assessing arguments over qualitative review methods: The case of the Joanna Briggs Institute's rebuttal of a fundamental critique.

One challenge for those reading methodological debates in low consensus fields is determining the outcome when participants do not share standards. When parties to a debate do not agree on the standards to be used in assessing their arguments (i.e., quality), it may be useful to ask first if parties' contributions meet their own expectations (i.e., integrity). Most protocols for review of qualitative research specify some form of quality assessment. These protocols normally require some test of internal coherence. Coherence is also relevant when describing the match between a rebuttal and the argument it answers. In 2019, Nursing Inquiry published a critique and rebuttal of the methods used by the Joanna Briggs Institute. In this essay, we attempted to use the Joanna Briggs Institute's own quality assessment standards to assess their rebuttal of this fundamental critique. We found it possible to use the Joanna Briggs Institute's own quality assessment standards to assess this rebuttal, and we found that JBI's rebuttal did not meet their own standards.

Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.

In cytotoxic T cells (CTL), Akt, also known as protein kinase B, is activated by the T cell antigen receptor (TCR) and the cytokine interleukin 2 (IL-2). Akt can control cell metabolism in many cell types but whether this role is important for CTL function has not been determined. Here we have shown that Akt does not mediate IL-2- or TCR-induced cell metabolic responses; rather, this role is assumed by other Akt-related kinases. There is, however, a nonredundant role for sustained and strong activation of Akt in CTL to coordinate the TCR- and IL-2-induced transcriptional programs that control expression of key cytolytic effector molecules, adhesion molecules, and cytokine and chemokine receptors that distinguish effector versus memory and naive T cells. Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate.

Involvement of the PD-1/PD-L1 Co-Inhibitory Pathway in the Pathogenesis of the Inflammatory Stage of Early-Onset Preeclampsia.

The programmed cell death protein 1 (PD-1) receptor has been reported to downregulate T cell activation effectively via binding to its ligands PD-L1 or PD-L2 in a negative co-stimulatory manner. Little is known about the involvement of PD-1 mediated immunoregulation in pregnancy and in pregnancy-related disorders. In this work, we investigated the possible role of the PD-1 co-stimulatory pathway in the pathogenesis of the clinical phase of early-onset preeclampsia characterized by a systemic maternal inflammatory response. We performed a cross-sectional study for comparative analysis of phenotypic and functional characteristics of peripheral blood mononuclear cells in women with early-onset preeclampsia and third-trimester healthy pregnant controls. According to our findings, enhanced expression of either PD-1 or its ligand PD-L1, or both, on the cell surface of effector cells (T cells, natural killer (NK) cells, natural killer T (NKT)-like cells) and Tregs could be observed, but PD-1 expression did not correlate with effector cells exhaustion. These results suggest the failure of the axis to downregulate Th1 responses, contributing thereby to the exaggerated immunoactivation observed in early-onset preeclampsia.

L-arginine metabolism in early-onset and late-onset pre-eclamptic pregnancies.

OBJECTIVE: The present case-control study was undertaken to investigate l-arginine metabolism in pregnant women with early-onset and late-onset pre-eclampsia. Attempts were made to differentiate these two distinct diseases entities by using measured and derived parameters of l-arginine metabolism. STUDY DESIGN: Thirty-six patients with early-onset, 17 patients with late-onset pre-eclampsia and 15 healthy pregnant women at term were studied. Patients were categorized according to the weeks of gestation (< 34 vs. ≥ 34) at the appearance of clinical symptoms (hypertension + proteinuria). Venous samples were taken at gestational age of 29.8 ± 2.5, 36.1 ± 2.2 and 39.2 ± 1.2 weeks, respectively. L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), monomethylarginine (MMA) and l-ornithine were measured by LC-MS/MS method. L-arginine/ADMA, l-ornithine/l-arginine, ADMA/SDMA ratios and the arginine methylation index (arg-MI) were calculated. RESULTS: Plasma levels of ADMA and MMA were significantly higher (p < 0.002) in pre-eclamptic patients than in healthy women. No significant differences could be detected between patients with early-onset and late-onset pre-eclampsia in either parameter studied. L-ornithine correlated positively with ADMA (r = 0.526, p < 0.001) and MMA (r = 0.533, p < 0.001) in the whole study population, and inversely with l-arginine (r = - 0.277, p < 0.044) in the pre-eclamptic group. When compared with maternal plasma in venous cord blood l-arginine was markedly reduced (p < 0.05) and there was a significant elevation in ADMA, SDMA, MMA and l-ornithine (p < 0.001, for each) without discernible differences between the study groups. CONCLUSIONS: Parameters of l-arginine metabolism do not discriminate the early-onset from late-onset pre-eclampsia. Our study provided indirect evidences for the redirection of l-arginine-NOS to the l-arginine-arginase pathway.

Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes.

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKalpha1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca(2+) with Ca(2+) ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca(2+) stimulation of AMPK required the activity of Ca(2+)-calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca(2+) signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it.

The two faces of preeclampsia / A praeeclampsia két arca

During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence and also the extreme extent regarding the volume expansion are likely accompanied with serious conditions. Undoubtedly, preeclampsia, defined as the appearance of hypertension and proteinuria during the second half of pregnancy, is not a homogenous disease. The early onset which begins prior to the 34th week, is characteristically a hypovolemia-associated form and depicts the placental origination, in which endothelial damage leads to hypertension and organ damage due to vasoconstriction and microthrombosis. Fetal blood supply progressively worsens due to placental insufficiency. The outcome of this condition often leads to fetal death, eclampsia, or placental abruption. Management is confined to a diligent prolongation of pregnancy to accomplish improved neonatal pulmonary function. The late onset form, associated with high cardiac output, is a maternal disease, in which obesity is a risk factor since it predisposes individuals to enhanced water retention, hypertension, and a weakened endothelial dysfunction. Initially, low extremity edema often times progresses to a generalized form and frequently results in hypertension. In several cases proteinuria appears. This condition entirely meets the preedampsia criteria. Fetal weight is normal or frequently over the average. It is very likely, the increasing parenchymal stasis will lead to ascites, eclampsia, or placental abruption. During the management of this hypervolemia-associated preedampsia, the administration of diuretic furosemide treatment seemingly offers promise.

Nonlinear fiber-bundle-cells-based phenomenological modeling of human tissue samples.

Certain assemblies of fibers, called fiber bundles, play a crucial role in the statistical macroscale properties of fibrous structures like natural or artificial materials. Based on the concept of using idealized statistical fiber bundle cells (FBCs) as model elements, the software named FiberSpace was developed by us earlier for the phenomenological modeling of the tensile test process of real fibrous structures. The model fibers of these FBCs had been considered linear elastic, which was suitable for modeling certain textiles and composites. However, the biological tissues are multilevel structures with fiber-like building elements on every structural level where the fiber elements on the dominant level are statistical bundles of elementary fibers. Hence, their modeling required us to introduce model fibers of nonlinear mechanical behavior and derive the proper mathematical formulas for the calculation of the expected tensile force processes of the FBCs. Accordingly, we developed a new version of FiberSpace. The proposed nonlinear FBCs-based modeling method is essentially phenomenological that decomposes the measured and averaged stress-strain curve into the weighted sum of the responses of different idealized nonlinear FBCs. However, this decomposition can give certain information about the fibrous structure and some details of its damage and failure sub-processes. A special application of nonlinear E-bundles, where the measured stress-strain curve is expanded into a product-function series, may give another type of description for the failure process and can be applied to single measurements of structured failure process containing significant peaks and drops as well. The fitted phenomenological FBC models provide a decomposition of the measured force-strain curve, which enables to construct informative damage and failure maps. The applicability of the phenomenological modeling method and the fitting procedure is demonstrated with the tensile test data of some human and animal tissues, such as facial nerves and tendons.

Characteristics of Homebirth in Hungary: A Retrospective Cohort Study.

Homebirth is legal and has been regulated by law in Hungary since 2012. Despite the obvious advantages of homebirth, it has not yet been broadly accepted, due to various opinions related to safety and risks associated with giving birth outside of a hospital. Our study aimed at exploring both real maternal and feto-neonatal characteristics associated with Hungarian homebirths. A total of 2997 cases were considered in support of our retrospective cohort study. In the examined period, there was a significant, continual rise in the number of homebirths by a rate of 0.22% on average per year. Aggregated maternal complications (primary uterine inertia, prolonged second stage labour, and third stage haemorrhage) were prevalent among homebirth cases (1.29% vs. 0.72%, p < 0.05) and were associated with an average of 11.77% rate of transfer to a health care institution. On the other hand, the rate of operative (vaginal or caesarean) delivery was 26.31% among institutionalized births. A slightly better Apgar score and relatively high rate (20%) of caesarean deliveries were correlated with institutionalized births (p < 0.05). However, the overall intervention rate was lower among homebirths (0.11% vs. 42.57%) than institutional birth cases (p < 0.001). Overall, homebirth is a reliable option for childbirth for healthy and low-risk mothers with uncomplicated pregnancies, which is reflected in the increasing number of deliveries at home in Hungary. Furthermore, utilizing the experiences of countries where homebirth is a long-established method may further improve the outcome of homebirths in Hungary.

Preeclampsia subtypes: Clinical aspects regarding pathogenesis, signs, and management with special attention to diuretic administration.

During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence coupled with the extreme extent regarding the volume expansion, are likely accompanied with pathological conditions. Undoubtedly, preeclampsia, defined as the appearance of hypertension and organ deficiency, such as proteinuria during the second half of pregnancy, is not a homogenous disease. Clinically speaking, two main types of preeclampsia can be distinguished, in which a marked difference between them is vascular condition, and consequently, the blood volume. The "classic" preeclampsia, as a two-phase disease, described in the first, latent phase, in which, placenta development is diminished. Agents from this malperfused placenta generate a maternal disease, the second phase, in which endothelial damage leads to hypertension and organ damage due to vasoconstriction and thrombotic microangiopathy. In this hypovolemia-associated condition, decreasing platelet count, signs of hemolysis, renal and liver involvement are characteristic findings; proteinuria is marked and increasing. In the terminal phase, visible edema develops due to increasing capillary transparency, augmenting end-organ damages. "Classic" preeclampsia is a severe and quickly progressing condition with placental insufficiency and consequent fetal growth restriction and oligohydramnios. The outcome of this condition often leads to fetal hypoxia, eclampsia or placental abruption. The management is limited to a diligent prolongation of pregnancy to accomplish improved neonatal pulmonary function, careful diminishing high blood pressure, and delivery induction in due time. The other subtype, associated with relaxed vasculature and high cardiac output, is a maternal disease, in which obesity is an important risk factor since predisposes to enhanced water retention, hypertension, and a weakened endothelial dysfunction. Initially, enhanced water retention leads to lowered extremity edema, which oftentimes progresses to a generalized form and hypertension. In several cases, proteinuria appears most likely due to tissue edema. This condition already fully meets preeclampsia criteria. Laboratory alterations, including proteinuria, are modest and platelet count remains within the normal range. Fetal weight is also normal or frequently over average due to enhanced placental blood supply. It is very likely, further water retention leads to venous congestion, a parenchyma stasis, responsible for ascites, eclampsia, or placental abruption. During the management of this hypervolemia-associated preeclampsia, the administration of diuretic furosemide treatment seemingly offers promise.

LKB1 is essential for the proliferation of T-cell progenitors and mature peripheral T cells.

The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co-ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differentiation to ensure that they can meet the energy requirements for development. The present study explores the role of LKB1 in this process and shows that loss of LKB1 prevents thymocyte differentiation and the production of peripheral T lymphocytes. We find that LKB1 is required for several key metabolic processes in T-cell progenitors. For example, LKB1 controls expression of CD98, a key subunit of the L-system aa transporter and is also required for the pre-TCR to induce and sustain the regulated phosphorylation of the ribosomal S6 subunit, a key regulator of protein synthesis. In the absence of LKB1 TCR-beta-selected thymocytes failed to proliferate and did not survive. LBK1 was also required for survival and proliferation of peripheral T cells. These data thus reveal a conserved and essential role for LKB1 in the proliferative responses of both thymocytes and mature T cells.

Comparison of Changes in the Plumage and Body Condition, Egg Production, and Mortality of Different Non-Beak-Trimmed Pure Line Laying Hens during the Egg-Laying Period.

The experiment was carried out with altogether 1740 non-beak-trimmed laying hens, which originated from Bábolna TETRA Ltd., representing two different types (Rhode Island Red (RIR) and Rhode Island White (RIW)) and four different lines (Lines 1-2: RIR, Lines 3-4: RIW). The plumage and body condition of randomly selected 120 hens (30 hens/line) was examined at 20, 46, and 62 weeks of age. The egg production and the mortality of the sampled hens were recorded daily. Based on the results, it was established that the lines differ clearly in most of the examined traits. It was also pointed out that injurious pecking of the hens resulted not only in damages in the plumage but also in the body condition. The results obviously demonstrated that the highest egg production and the lowest mortality rate were reached by those hens, which had the best plumage and body condition. Because the occurrence of injurious pecking seems to depend on the genetic background, selection of the hens (lines, families, individuals) for calm temperament will be very important in the future in order to maintain the high production level in non-beak-trimmed layer flocks.

Investigation of mucosal-associated invariant T (MAIT) cells expressing immune checkpoint receptors (TIGIT and CD226) in early-onset preeclampsia.

OBJECTIVE: During our work, we examined the possible contribution of MAIT cells in the pathogenesis of the clinical phase of early-onset preeclampsia and how this could be influenced by TIGIT and CD226 immune checkpoint molecules. STUDY DESIGN: 37 pregnant women diagnosed with early-onset preeclampsia and 36 healthy, age-matched control women were involved in this study. Peripheral blood mononuclear cells were isolated by density gradient and frozen. After thawing, cells were stained with monoclonal antibodies to characterize MAIT, MAIT-like, and non-MAIT cells. Flow cytometric analyses were used to measure TIGIT, CD226, intracellular perforin, and granzyme B expression. RESULTS: MAIT (CD3+ CD8+ Vα7.2+ CD161++), MAIT-like (CD3+ CD8+ Vα7.2+ CD161+) and non-MAIT (CD3+ CD8+ Vα7.2+ CD161-) cell population were identified based on their CD161 receptor positivity. MAIT cells markedly differed in proportion, TIGIT expression, granzyme B, and perforin content compared to MAIT-like and non-MAIT cells. A significant difference was determined in TIGIT expression by non-MAIT cells and in CD8/CD226 positive relationship between the preeclamptic and healthy condition. CONCLUSIONS: Considering that we did not detect a notable difference between early-onset preeclampsia and healthy pregnancy, we suppose that peripheral MAIT cells expressing TIGIT and CD226 immune checkpoint molecules have a marginal role in the pathogenesis of early-onset preeclampsia.

Optimization of Municipal Waste Collection Routing: Impact of Industry 4.0 Technologies on Environmental Awareness and Sustainability.

The accelerated movement of people towards cities led to the fact that the world's urban population is now growing by 60-million persons per year. The increased number of cities' population has a significant impact on the produced volume of household waste, which must be collected and recycled in time. The collection of household waste, especially in downtown areas, has a wide range of challenges; the collection system must be reliable, flexible, cost efficient, and green. Within the frame of this paper, the authors describe the application possibilities of Industry 4.0 technologies in waste collection solutions and the optimization potential in their processes. After a systematic literature review, this paper introduces the waste collection process of downtowns as a cyber-physical system. A mathematical model of this waste collection process is described, which incorporates routing, assignment, and scheduling problems. The objectives of the model are the followings: (1) optimal assignment of waste sources to garbage trucks; (2) scheduling of the waste collection through routing of each garbage truck to minimize the total operation cost, increase reliability while comprehensive environmental indicators that have great impact on public health are to be taken into consideration. Next, a binary bat algorithm is described, whose performance is validated with different benchmark functions. The scenario analysis validates the model and then evaluates its performance to increase the cost-efficiency and warrant environmental awareness of waste collection process.

Investigation of Shear-Induced Deformation of Reinforcing Textiles by Optical Measurement Devices.

When fiber-reinforced plastic (FRP) components are designed, it is very important to ensure that textiles are formed into complex 3D geometries without folds, and that the reinforcing structure is oriented appropriately. Most research in this context is focused on finite element (FE) forming simulations and the required characterization of textile reinforcements. However, the early stage of the design of FRPs, where kinematic draping simulations are used, is barely considered. In particular, the need for a critical shear angle for the execution and evaluation of kinematic draping simulations is often neglected. This paper presents an extended picture frame test stand with an optical device recording shear-induced deformations with the help of a laser line emitter. Associated hardware and software for detecting and quantifying the fold formation during a picture frame test were developed. With the additional recorded information, a material-specific critical shear angle can be determined, material behaviors can be compared, and FE-based simulation methods can be evaluated. This innovative test stand and the associated software tools will help engineers to decide on suitable materials and improve transparency in the early stages of the design process.

Searching for evidence or approval? A commentary on database search in systematic reviews and alternative information retrieval methodologies.

Despite recognition that database search alone is inadequate even within the health sciences, it appears that reviewers in fields that have adopted systematic review are choosing to rely primarily, or only, on database search for information retrieval. This commentary reminds readers of factors that call into question the appropriateness of default reliance on database searches particularly as systematic review is adapted for use in new and lower consensus fields. It then discusses alternative methods for information retrieval that require development, formalisation, and evaluation. Our goals are to encourage reviewers to reflect critically and transparently on their choice of information retrieval methods and to encourage investment in research on alternatives.

The possible role of CD8+/Vα7.2+/CD161++ T (MAIT) and CD8+/Vα7.2+/CD161lo T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia.

PROBLEM: The objective of this study was to compare the expressions of different immune-checkpoint molecules by MAIT and MAIT-like cells in healthy pregnancy and in early-onset pre-eclampsia. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMC) were stained with monoclonal antibodies to characterize MAIT and MAIT-like cells. Flow cytometric analyses were used to measure PD-1, TIM-3, activation markers, and intracellular perforin expression. RESULTS: We identified CD3+/CD8+/Vα7.2+/CD161++ MAIT cells and a minor cell population characterized by CD3+/CD8+/Vα7.2+/CD161lo surface markers. In measuring the expression of PD-1 receptor, we found a significantly lower expression by MAIT cells in women with early-onset pre-eclampsia. CD69 expression by MAIT cells was significantly elevated in early-onset pre-eclamptic patients. Intracellular perforin content by MAIT and PD-1+ MAIT cells was significantly increased in pre-eclamptic patients compared with healthy individuals. CONCLUSION: Altered frequency and reduced PD-1 expression combined together with the elevated perforin content of MAIT cells insinuate their potential roles in the pathogenesis of early-onset pre-eclampsia.

Inducible phosphorylation of cortactin is not necessary for cortactin-mediated actin polymerisation.

Cortactin is an SH3 domain-containing protein that contributes to the formation of dynamic cortical actin-associated structures, such as lamellipodia and membrane ruffles. It was originally identified as a substrate for the protein kinase Src; however, the role of tyrosine phosphorylation in the translocation of cortactin to the cell periphery and in the subsequent actin polymerisation is still unclear. Recently, two serine/threonine kinases, Pak1 and Erk, have been implicated in the regulation of cortactin. Therefore, we systematically investigated whether phosphorylation on either tyrosine or serine/threonine residues is necessary for cortactin function. In COS7 cells over-expressing Vav2 or treated with EGF, we could not detect tyrosine phosphorylation, although cortactin was translocated to cell periphery and induced membrane ruffle formation. In addition, the selective MEK inhibitor, PD98059, did not influence in vivo the ability of cortactin to bind to and induce membrane ruffles upon Vav2 over-expression or short-term EGF treatment. Finally, using a constitutively active Pak1 mutant, Pak1 T423E, we showed that Pak1 is not capable of phosphorylating cortactin either in vitro or in COS7 cells. These results suggest that cortactin-mediated actin polymerisation at cell periphery requires only Rac activation but neither tyrosine nor serine/threonine phosphorylation.

Relationship between adolescent amenorrhea and climacteric osteoporosis.

OBJECTIVES: The relationship between climacteric osteoporosis and disturbances in menstrual cycle during adolescence was examined. METHODS: Seven hundred and seventy-one questionnaires were shared out among women visiting the outpatient department for climacteric complaints for the first time between 2001 and 2004. Questions revealed the age, age at menarche and menopause, the regularity or irregularity of menstrual cycle during adolescence and adult ages. The bone mineral density was examined using the Dual Energy X-ray Absorptiometry (DEXA) method on the lumbar spine. RESULTS: Six hundred and thirty-five of the 771 questionnaires were suitable for analysis. Osteoporosis was observed in 30.1% of the cases. Age, age at the menarche or at the menopause did not alter in the subgroups with or without osteoporosis. The incidence and severity of osteoporosis were significantly higher in patients reporting secondary amenorrhea during adolescent ages (42.1%; average BMD of the lumbar spine 71.6+/-3.9), as compared to the patients with normal cycle (30.4%; average BMD of the lumbar spine 84.8+/-7.8). No correlation between the occurrence of osteoporosis and the frequency of menstrual cycle during adulthood was observed. CONCLUSIONS: Secondary amenorrhea during the years of adolescence might play a role in the development of more severe osteoporosis in menopause.

Preliminary study of the effects of furosemide on blood pressure during late-onset pre-eclampsia in patients with high cardiac output.

OBJECTIVE: To examine the effect of furosemide on hypertension and edema in patients with pre-eclampsia experiencing high cardiac output. METHODS: The present cohort study enrolled patients with pre-eclampsia who were admitted to the pregnancy pathology unit of the Department of Obstetrics and Gynecology, University of Pécs, Hungary, between January 1 and December 31, 2015. Eligible patients had singleton pregnancies with no fetal anomalies, high blood volume, visible edema, and a hematocrit concentration below 37 L/L. Blood pressure was measured and impedance cardiography was used to determine cardiac output for all patients before they received a 40-mg dose of furosemide; after 60 minutes blood pressure and cardiac output were measured again. RESULTS: The study enrolled 14 patients. Lower cardiac output (P=0.002), systolic blood pressure (P=0.002), and diastolic blood pressure (P=0.002) were recorded after furosemide administration, with patient heart rates remaining stable. CONCLUSION: The heart-rate stability suggests that the change of cardiac output was due to a decrease in blood volume. These data suggest that diuretics could be useful in the management of late-onset pre-eclampsia, indicating that an increase in water retention could play a role in the development of late-onset pre-eclampsia.