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iScience. 2022 Apr 30;25(5):104328. doi: 10.1016/j.isci.2022.104328. eCollection 2022 May 20.

ABSTRACT

This paper develops a multi-sector and multi-factor structural gravity model that allows an analytical and quantitative decomposition of the emission and output changes into composition and technique effects. We find that the negative production shock of China’s containment policy propagates globally via supply chains, with the carbon-intensive sectors experiencing the greatest carbon emission shocks. We further reveal that China’s current stimulus package in 2021-2025 is consistent with China’s emission intensity-reduction goals for 2025, but further efforts are required to meet China’s carbon emissions-peaking target in 2030 and Cancun 2°C goal. Short-term changes in carbon emissions resulting from lockdowns and initial fiscal stimuli in “economic rescue” period have minor long-term effects, whereas the transitional direction of future fiscal stimulus exerts more predominant impact on long-term carbon emissions. The efficiency improvement effects are more important than the sectoral structure effects of the fiscal stimulus in achieving greener economic growth.

PMID:35602942 | PMC:PMC9118742 | DOI:10.1016/j.isci.2022.104328

Front Psychol. 2022 May 6;13:810569. doi: 10.3389/fpsyg.2022.810569. eCollection 2022.

ABSTRACT

Despite policy efforts targeted at making universities more inclusive and equitable, academia is still rife with harassment and bullying, and opportunities are far from equal for everyone. The present preregistered survey research (N = 91) aimed to explore whether an intersectional approach can be useful to examine the tangible effects of policy ineffectiveness, even when legislative and ideologic constraints limit the possibility to conduct a full-fledged intersectional analysis. Policy ineffectiveness was operationalized as experiences of harassment, discrimination, institutional resistance to gender equality, and retaliation against reporters of misconduct in universities. Policy ineffectiveness was negatively related to women academics’ inclination to pursue an academic career. This relationship was mediated by lower levels of psychological safety associated with policy ineffectiveness. Importantly, women academics who differ from the majority on multiple dimensions show a stronger and more negative relationship between policy ineffectiveness and psychological safety. The study further shows that self-report measures are useful to uncover intersectional privilege afforded to overrepresented groups in academia. The study discusses the benefits of intersectional approaches for designing and implementing effective policies to tackle harassment and inequality in academia, even when the available methodologies are constrained by legislation and ideology. Overall, self-report measurement can have an important function for signalling areas that warrant further intersectional inquiry to ensure that policies serve everyone.

PMID:35602685 | PMC:PMC9122029 | DOI:10.3389/fpsyg.2022.810569

Front Psychol. 2022 May 4;13:864763. doi: 10.3389/fpsyg.2022.864763. eCollection 2022.

ABSTRACT

INTRODUCTION: It has been proposed that bilinguals’ language use patterns are differentially associated with executive control. To further examine this, the present study relates the social diversity of bilingual language use to performance on a color-shape switching task (CSST) in a group of bilingual university students with diverse linguistic backgrounds. Crucially, this study used language entropy as a measure of bilinguals’ language use patterns. This continuous measure reflects a spectrum of language use in a variety of social contexts, ranging from compartmentalized use to fully integrated use.

METHODS: Language entropy for university and non-university contexts was calculated from questionnaire data on language use. Reaction times (RTs) were measured to calculate global RT and switching and mixing costs on the CSST, representing conflict monitoring, mental set shifting, and goal maintenance, respectively. In addition, this study innovatively recorded a potentially more sensitive measure of set shifting abilities, namely, pupil size during task performance.

RESULTS: Higher university entropy was related to slower global RT. Neither university entropy nor non-university entropy were associated with switching costs as manifested in RTs. However, bilinguals with more compartmentalized language use in non-university contexts showed a larger difference in pupil dilation for switch trials in comparison with non-switch trials. Mixing costs in RTs were reduced for bilinguals with higher diversity of language use in non-university contexts. No such effects were found for university entropy.

DISCUSSION: These results point to the social diversity of bilinguals’ language use as being associated with executive control, but the direction of the effects may depend on social context (university vs. non-university). Importantly, the results also suggest that some of these effects may only be detected by using more sensitive measures, such as pupil dilation. The paper discusses theoretical and practical implications regarding the language entropy measure and the cognitive effects of bilingual experiences more generally, as well as how methodological choices can advance our understanding of these effects.

PMID:35602687 | PMC:PMC9116486 | DOI:10.3389/fpsyg.2022.864763

BMC Med Educ. 2022 May 23;22(1):396. doi: 10.1186/s12909-022-03476-7.

ABSTRACT

BACKGROUND: Limited data regarding the perspectives of other observers (i.e. those who educate, employ or receive care from) of new graduates’ preparedness to practice is available. The present study aimed to explore perceptions of different observers regarding the preparedness to practice and work readiness of newly qualified dental professionals. This broader range of perspectives is crucial to inform the development of educational programs, including continuing professional development, for newly qualified dental professionals, by clarifying the skills, knowledge and behaviours expected by the dental profession and wider public.

RESULTS: Nineteen individual qualitative interviews were undertaken. Interview participants included clinical demonstrators (n = 9; 2 Oral Health Therapists; 5 Dentists; and 2 Prosthetists), dental course convenors (n = 4), representatives of large employers (n = 2), and consumers (n = 4). According to this diverse group of respondents, dental students receive adequate theoretical and evidence-based information in their formal learning and teaching activities, which prepares them for practice as dental professionals. There were no specific clinical areas or procedures where preparedness was highlighted as a major concern. Notwithstanding this, specific graduate skills which would benefit from further training and consolidation were identified, including areas where higher levels of experience would be beneficial. Nonetheless, respondents indicated that new graduates were aware of their limitations and had developed self-discipline and ethics that would allow them to identify conditions/situations where they would not have the experience or expertise to provide care safely.

CONCLUSIONS: From an observer perspective, dental students appeared to have gained adequate theoretical and evidence-based information in their formal learning and teaching activities to prepared them to commence practicing safely as dental professionals. Areas were identified in which new graduates were underprepared and when transitional support may be required.

PMID:35606758 | DOI:10.1186/s12909-022-03476-7

Prog Cardiovasc Dis. 2022 May 19:S0033-0620(22)00046-9. doi: 10.1016/j.pcad.2022.05.003. Online ahead of print.

ABSTRACT

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

PMID:35605696 | DOI:10.1016/j.pcad.2022.05.003

Neurosci Lett. 2022 May 20:136691. doi: 10.1016/j.neulet.2022.136691. Online ahead of print.

ABSTRACT

Anodal transcranial direct current stimulation (tDCS) can enhance the retention of a previously practiced motor skill. However, the effects of tDCS on the performance of the choice reaction time task are not fully understood. We examined the effects of anodal tDCS over the left primary motor cortex (M1) on the retention of a 4-choice visual-motor reaction time task (4-ChRT). Right-handed healthy participants (n=100) were randomly assigned to five groups: three groups received anodal tDCS: before (tDCS_before), during (tDCS_during), or after (tDCS_after) motor practice. In addition, there were two control groups: with (CON_mp) and without (CON) motor practice. We evaluated the speed and precision of the 4-ChRT task before (PRE), during, and 24 h (POST) after the interventions. All groups, including the non-stimulation (CON_mp) and non-practice groups (CON), improved (p<0.05) motor retention (Δ4-ChRT: 35.8 ± 36.0 ms). These findings suggest that the tDCS effects over M1 may differ for serial versus choice RT tasks, perhaps due to the different brain areas involved in each motor task.

PMID:35605902 | DOI:10.1016/j.neulet.2022.136691

Acta Biomater. 2022 May 20:S1742-7061(22)00307-5. doi: 10.1016/j.actbio.2022.05.031. Online ahead of print.

ABSTRACT

Extracellular matrix (ECM) is a dynamic network of proteins, proteoglycans and glycosaminoglycans, providing structure to the tissue and biochemical and biomechanical instructions to the resident cells. In fibrosis, the composition and the organization of the ECM are altered, and these changes influence cellular behaviour. Biochemical (i. e. protein composition) and biomechanical changes in ECM take place simultaneously in vivo. Investigating these changes individually in vitro to examine their (patho)physiological effects has been difficult. In this study, we generated an in vitro model to reflect the altered mechanics of a fibrotic microenvironment through applying fibre crosslinking via ruthenium/sodium persulfate crosslinking on native lung ECM-derived hydrogels. Crosslinking of the hydrogels without changing the biochemical composition of the ECM resulted in increased stiffness and decreased viscoelastic stress relaxation. The altered stress relaxation behaviour was explained using a generalized Maxwell model. Fibre analysis of the hydrogels showed that crosslinked hydrogels had a higher percentage of matrix with a high density and a shorter average fibre length. Fibroblasts seeded on ruthenium-crosslinked lung ECM-derived hydrogels showed myofibroblastic differentiation with a loss of spindle-like morphology together with greater α-smooth muscle actin (α-SMA) expression, increased nuclear area and circularity without any decrease in the viability, compared with the fibroblasts seeded on the native lung-derived ECM hydrogels. In summary, ruthenium crosslinking of native ECM-derived hydrogels provides an exciting opportunity to alter the biomechanical properties of the ECM-derived hydrogels while maintaining the protein composition of the ECM to study the influence of mechanics during fibrotic lung diseases. STATEMENT OF SIGNIFICANCE: Fibrotic lung disease is characterized by changes in composition and excessive deposition of extracellular matrix (ECM). ECM fibre structure also changes due to crosslinking, which results in mechanical changes. Separating the changes in composition and mechanical properties has been difficult to date. In this study, we developed an in vitro model that allows alteration of the mechanical changes alone by applying fibre crosslinking in native lung ECM-derived hydrogels. Characterisations of the crosslinked hydrogels indicated the model mimicked mechanical properties of fibrotic lung tissue and reflected altered fibre organisation. This ECM-based fibrosis model provides a method to preserve the native protein composition while altering the mechanical properties providing an important tool not only for lung but also other organ fibrosis.

PMID:35605955 | DOI:10.1016/j.actbio.2022.05.031

Learn Behav. 2022 May 23. doi: 10.3758/s13420-022-00527-3. Online ahead of print.

ABSTRACT

Experiences during immature phases of development, especially social experiences with individuals of the opposite sex, have implications for adult sexual behavior. Nevertheless, whether and how early experience can affect sexual learning in adulthood is still unclear. We present two experiments exploring how early experience impacts adult sexual Pavlovian conditioning in male Japanese quail. In Experiment 1, 25 male Japanese quail divided into three groups received different stimuli presentations at an early age, namely paired presentations of a conditioned stimulus (CS; a terry cloth model) and an unconditioned stimulus (US; an adult female quail), unpaired presentations of CS and US, and no exposure to stimuli. When they reached sexual maturity, we performed a sexual Pavlovian conditioning procedure with all groups using the same stimuli and tested their conditional response. In Experiment 2, we replicated the first experiment but with younger subjects and additional control variables. In the first experiment, we observed shorter approaching latencies to the CS and longer times near the CS in subjects with paired CS-US presentations compared to unpaired stimuli presentations. This was not replicated in Experiment 2. In both experiments, we found shorter approaching latencies and longer times near the CS in the groups with early exposure to the stimuli (paired or unpaired) compared to the group without this experience. Our findings indicate that the early presentations of stimuli at early stages of life can influence males’ (speed of) sexual Pavlovian conditioning during adulthood.

PMID:35606675 | DOI:10.3758/s13420-022-00527-3

Surg Endosc. 2022 May 23. doi: 10.1007/s00464-022-09326-3. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of the LOLA trial.

METHODS: Within the LOLA arm of the international, multicentre LADIES trial, patients with perforated diverticulitis with purulent peritonitis were randomised between laparoscopic lavage and sigmoidectomy. Outcomes were collected up to 36 months. The primary outcome of the present study was cumulative morbidity and mortality. Secondary outcomes included reoperations (including stoma reversals), stoma rates, and sigmoidectomy rates in the lavage group.

RESULTS: Long-term follow-up was recorded in 77 of the 88 originally included patients, 39 were randomised to sigmoidectomy (51%) and 38 to laparoscopic lavage (49%). After 36 months, overall cumulative morbidity (sigmoidectomy 28/39 (72%) versus lavage 32/38 (84%), p = 0·272) and mortality (sigmoidectomy 7/39 (18%) versus lavage 6/38 (16%), p = 1·000) did not differ. The number of patients who underwent a reoperation was significantly lower for lavage compared to sigmoidectomy (sigmoidectomy 27/39 (69%) versus lavage 17/38 (45%), p = 0·039). After 36 months, patients alive with stoma in situ was lower in the lavage group (proportion calculated from the Kaplan-Meier life table, sigmoidectomy 17% vs lavage 11%, log-rank p = 0·0268). Eventually, 17 of 38 (45%) patients allocated to lavage underwent sigmoidectomy.

CONCLUSION: Long-term outcomes showed that laparoscopic lavage was associated with less patients who underwent reoperations and lower stoma rates in patients alive after 36 months compared to sigmoidectomy. No differences were found in terms of cumulative morbidity or mortality. Patient selection should be improved to reduce risk for short-term complications after which lavage could still be a valuable treatment option.

PMID:35606544 | DOI:10.1007/s00464-022-09326-3

Nat Commun. 2022 May 23;13(1):2857. doi: 10.1038/s41467-022-30358-9.

ABSTRACT

Signal transduction via phosphorylated CheY towards the flagellum and the archaellum involves a conserved mechanism of CheY phosphorylation and subsequent conformational changes within CheY. This mechanism is conserved among bacteria and archaea, despite substantial differences in the composition and architecture of archaellum and flagellum, respectively. Phosphorylated CheY has higher affinity towards the bacterial C-ring and its binding leads to conformational changes in the flagellar motor and subsequent rotational switching of the flagellum. In archaea, the adaptor protein CheF resides at the cytoplasmic face of the archaeal C-ring formed by the proteins ArlCDE and interacts with phosphorylated CheY. While the mechanism of CheY binding to the C-ring is well-studied in bacteria, the role of CheF in archaea remains enigmatic and mechanistic insights are absent. Here, we have determined the atomic structures of CheF alone and in complex with activated CheY by X-ray crystallography. CheF forms an elongated dimer with a twisted architecture. We show that CheY binds to the C-terminal tail domain of CheF leading to slight conformational changes within CheF. Our structural, biochemical and genetic analyses reveal the mechanistic basis for CheY binding to CheF and allow us to propose a model for rotational switching of the archaellum.

PMID:35606361 | DOI:10.1038/s41467-022-30358-9

J Heart Lung Transplant. 2022 Jun;41(6):765-772. doi: 10.1016/j.healun.2022.03.006. Epub 2022 Mar 16.

ABSTRACT

BACKGROUND: Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression.

METHODS: The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson’s correlation coefficient was calculated to correlate serological responses to TTV load.

RESULTS: Humoral responses to COVID-19 vaccination were observed in 41 of 103 (40%) LTR at 28 days after the second vaccination. Sixty-two of 103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation.

CONCLUSIONS: This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response.

PMID:35606065 | DOI:10.1016/j.healun.2022.03.006

Br J Gen Pract. 2022 Mar 15:BJGP.2021.0581. doi: 10.3399/BJGP.2021.0581. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about prescription patterns of expensive non-recommended newer long-acting insulins (glargine 300 U/mL and degludec) for patients with type 2 diabetes mellitus (T2DM).

AIM: To identify practice variation in, and practice- and patient-related characteristics associated with, the prescription of newer long-acting insulins to patients with T2DM in primary care.

DESIGN AND SETTING: A retrospective cohort study in Dutch general practices (Nivel Primary Care Database).

METHOD: A first prescription for intermediate or long-acting insulins in 2018 was identified in patients aged ≥40 years using other T2DM drugs. Per practice, the median percentage and interquartile range (IQR) of patients with newer insulin prescriptions were calculated. Multilevel logistic regression models were constructed to calculate intraclass correlation coefficients (ICCs) and quantify the association of patient and practice characteristics with prescriptions for newer insulins (odds ratios [ORs] and 95% confidence intervals [CIs]).

RESULTS: In total, 7757 patients with prescriptions for intermediate or long-acting insulins from 282 general practices were identified. A median percentage of 21.2% (IQR 12.5-36.4%) of all patients prescribed intermediate or long-acting insulins per practice received a prescription for newer insulins. After multilevel modelling, the ICC decreased from 20% to 19%. Female sex (OR 0.77, 95% CI = 0.69 to 0.87), age ≥86 years compared with 40-55 years (OR 0.22, 95% CI = 0.15 to 0.34), prescriptions for metformin (OR 0.66, 95% CI = 0.53 to 0.82), sulfonylurea (OR 0.58, 95% CI = 0.51 to 0.66), or other newer T2DM drugs (OR 3.10, 95% CI = 2.63 to 3.66), and dispensing practices (OR 1.78, 95% CI = 1.03 to 3.10) were associated with the prescription of newer insulins.

CONCLUSION: The inter-practice variation in the prescription of newer insulins is large and could only be partially explained by patient- and practice-related differences. This indicates substantial opportunities for improvement.

PMID:35606162 | DOI:10.3399/BJGP.2021.0581

Diabetes Metab Res Rev. 2022 May 23:e3549. doi: 10.1002/dmrr.3549. Online ahead of print.

ABSTRACT

AIM: To perform an updated systematic review of randomised controlled trials examining the efficacy of at-home foot temperature monitoring in reducing the risk of a diabetes-related foot ulcer (DFU).

METHODS: Systematic review performed according to PRISMA guidelines. Risk-of-bias was assessed using version 2 of the Cochrane risk-of-bias tool. Meta-analyses were performed using random effects models. Leave-one-out sensitivity analyses and a sub-analysis excluding trials considered at high risk-of-bias assessed the consistency of findings. The certainty of the evidence was assessed with GRADE.

RESULTS: Five randomised controlled trials involving 772 participants meeting the IWGDF risk category 2 or 3 were included. All trials reported instructing participants to measure skin temperature at-home at six or more sites on each foot using a hand-held infra-red thermometer at least daily and reduce ambulatory activity in response to hotspots (temperature differences >2.2°C on two consecutive days between similar locations in both feet). One, one and three trials were considered at low, moderate and high risk-of-bias respectively. Participants allocated to at-home foot temperature monitoring had a reduced risk of developing a DFU (relative risk 0.51, 95% CI 0.31 to 0.84) compared to controls. Sensitivity and sub-analyses suggested that the significance of this finding was consistent. The GRADE assessment suggested a low degree of certainty in the finding.

CONCLUSION: At-home daily foot temperature monitoring and reduction of ambulatory activity in response to hotspots reduces the risk of a DFU in moderate or high risk people with a low level of certainty. This article is protected by copyright. All rights reserved.

PMID:35605998 | DOI:10.1002/dmrr.3549

BMC Prim Care. 2022 May 24;23(1):125. doi: 10.1186/s12875-022-01739-2.

ABSTRACT

BACKGROUND: The aim of this article is to describe the courses of vomiting, diarrhea, fever, and clinical deterioration, in children with uncomplicated gastroenteritis at presentation. This study was performed as a 7-day prospective follow-up study in an out-of-hours primary care service. The course of vomiting, diarrhea, and fever was analyzed by generalized linear mixed modeling. Because young children (≤ 12 months) and children with severe vomiting are at increased risk of dehydration, the potentially more complicated courses of these groups are described separately. The day(s) most frequently associated with deterioration and the symptoms present in children who deteriorated during follow-up were also described.

RESULTS: In total, 359 children presented with uncomplicated acute gastroenteritis to the out-of-hours primary care service. Of these, 31 (8.6%) developed a complicated illness and needed referral or hospitalization. All symptoms decreased within 5 days in most children (> 90%). Vomiting and fever decreased rapidly, but diarrhea decreased at a somewhat slower pace, especially among children aged 6-12 months. Children who deteriorated during follow-up had a higher frequency of vomiting at presentation and higher frequencies of vomiting and fever during follow-up.

CONCLUSIONS: The frequency of vomiting, not its duration, appears to be the more important predictor of deterioration. When advising parents, it is important to explain the typical symptom duration and to focus on alarm symptoms. Clinicians should be vigilant for children with higher vomiting frequencies at presentation and during follow-up because these children are more likely to deteriorate.

PMID:35606695 | DOI:10.1186/s12875-022-01739-2

Eur J Surg Oncol. 2022 May 16:S0748-7983(22)00428-0. doi: 10.1016/j.ejso.2022.05.003. Online ahead of print.

ABSTRACT

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54-0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies.

PMID:35599137 | DOI:10.1016/j.ejso.2022.05.003

J Geriatr Oncol. 2022 May 19:S1879-4068(22)00112-6. doi: 10.1016/j.jgo.2022.05.004. Online ahead of print.

ABSTRACT

INTRODUCTION: Older patients have a higher risk for complications after rectal cancer surgery. Although screening for geriatric impairments may improve risk prediction in this group, it has not been studied previously.

METHODS: We retrospectively investigated patients ≥70 years with elective surgery for non-metastatic rectal cancer between 2014 and 2018 in nine Dutch hospitals. The predictive value of six geriatric parameters in combination with standard preoperative predictors was studied for postoperative complications, delirium, and length of stay (LOS) using logistic regression analyses. The geriatric parameters included the four VMS-questionnaire items pertaining to functional impairment, fall risk, delirium risk, and malnutrition, as well as mobility problems and polypharmacy. Standard predictors included age, sex, body mass index, American Society of Anesthesiologists (ASA)-classification, comorbidities, tumor stage, and neoadjuvant therapy. Changes in model performance were evaluated by comparing Area Under the Curve (AUC) of the regression models with and without geriatric parameters.

RESULTS: We included 575 patients (median age 75 years; 32% female). None of the geriatric parameters improved risk prediction for complications or LOS. The addition of delirium risk to the standard preoperative prediction model improved model performance for predicting postoperative delirium (AUC 0.75 vs 0.65, p = 0.03).

CONCLUSIONS: Geriatric parameters did not improve risk prediction for postoperative complications or LOS in older patients with rectal cancer. Delirium risk screening using the VMS-questionnaire improved risk prediction for delirium. Older patients undergoing rectal cancer surgery are a pre-selected group with few impairments. Geriatric screening may have additional value earlier in the care pathway before treatment decisions are made.

PMID:35599096 | DOI:10.1016/j.jgo.2022.05.004

J Affect Disord. 2022 May 19:S0165-0327(22)00587-0. doi: 10.1016/j.jad.2022.05.073. Online ahead of print.

NO ABSTRACT

PMID:35598750 | DOI:10.1016/j.jad.2022.05.073

Eur J Heart Fail. 2022 May 21. doi: 10.1002/ejhf.2534. Online ahead of print.

ABSTRACT

AIMS: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men.

METHODS AND RESULTS: In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuroinflammatory response in men (all p < 0.0001).

CONCLUSION: In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies. This article is protected by copyright. All rights reserved.

PMID:35596674 | DOI:10.1002/ejhf.2534

Schizophr Bull. 2022 May 21:sbac028. doi: 10.1093/schbul/sbac028. Online ahead of print.

ABSTRACT

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode.

STUDY DESIGN: We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button.

STUDY RESULTS: We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode.

CONCLUSIONS: The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the “voice” imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.

PMID:35596662 | DOI:10.1093/schbul/sbac028

J Cachexia Sarcopenia Muscle. 2022 May 21. doi: 10.1002/jcsm.12969. Online ahead of print.

ABSTRACT

BACKGROUND: Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24-h height-indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFR_Cr ), muscle mass-independent cystatin C (eGFR_Cys ), and the combination of creatinine and cystatin C (eGFR_Cr-Cys ) and predicted probabilities of discordant classification given age, sex, and CER index.

METHODS: We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFR_Cr <60 mL/min per 1.73 m² when eGFR_Cys was <60 mL/min/1.73 m² . Baseline effects of age and sex on CER index were quantified with linear models using generalized least squares. Baseline effects of CER index on eGFR were quantified with quantile regression and logistic regression. Effects of annual changes in CER index on trajectories of eGFR were quantified with linear mixed-effects models. Missing observations in covariates were multiply imputed.

RESULTS: Mean (SD) CER index was 8.0 (1.7) and 6.1 (1.3) mmol/24 h per meter in male and female participants, respectively (P_difference < 0.001). In male participants, baseline CER index increased until 45 years of age followed by a gradual decrease, whereas a gradual decrease across the entire range of age was observed in female participants. For a 70-year-old male participant with low muscle mass (CER index of 2 mmol/24 h per meter), predicted baseline eGFR_Cr and eGFR_Cys disagreed by 24.7 mL/min/1.73 m² (and 30.1 mL/min/1.73 m² when creatinine was not corrected for race). Percentages (95% CI) of discordant classification in male and female participants aged 60 years and older with low muscle mass were 18.5% (14.8-22.1%) and 15.2% (11.4-18.5%), respectively. For a 70-year-old male participant who lost muscle during follow-up, eGFR_Cr and eGFR_Cys disagreed by 1.5, 5.0, 8.5, and 12.0 mL/min/1.73 m² (and 6.7, 10.7, 13.5, and 15.9 mL/min/1.73 m² when creatinine was not corrected for race) at baseline, 5 years, 10 years, and 15 years of follow-up, respectively.

CONCLUSIONS: Low muscle mass may cause considerable overestimation of single measurements of eGFR_Cr . Muscle wasting may cause spurious overestimation of repeatedly measured eGFR_Cr . Implementing muscle mass-independent markers for estimating renal function, like cystatin C as superior alternative to creatinine, is crucial to accurately assess renal function in settings of low muscle mass or muscle wasting. This would also eliminate the negative consequences of current race-based approaches.

PMID:35596604 | DOI:10.1002/jcsm.12969