The comfort perception in the critically ill patient from the Kolcaba theoretical model.

BACKGROUND: The stay in a critical care unit (CCU) has a serious impact on physical condition causing numerous discomfort factors such as pain or difficulty in communicating. All of these are associated with possible sequelae following discharge from the Intensive Care Unit (ICU) named post-ICU syndrome. The Kolcaba Comfort Theory allows, from a holistic approach, to identify care needs from the patient's perspective using instruments such as the General Comfort Questionnaire (GCQ). OBJECTIVES: To determine the comfort level of patients admitted to the CCU using the GCQ of Kolcaba and to identify the discomfort factors. METHODS: Cross-sectional descriptive observational prospective study. POPULATION: 580 patients admitted to adult CCU of two high complexity hospitals from June 2015 to March 2020 with stay ≥24 h were interviewed. Descriptive analysis, Student's t-test and ANOVA and multivariate analysis were performed using SPSS v26 and STATA v16. RESULTS: The mean age was 52,62 (16,21), 357 (61,6%) were male and 434 (74,8%) were believers. The type of admission was planned in 322 (55,5%) and the most prevalent reason for admission was surgical 486 (83,8%). The median pain score (NRS) was 3,00 [0-4] and severity score (APACHE II) was 13,26 (5,89), the median length of stay was 4,00 [2-7] days. The mean comfort level was 3,02 (0,31) showing the highest value Reanimation 3.02 (0.30) and the lowest Trauma and Emergency Unit 2.95 (0.38). Statistically significant differences were found between the units in the comfort level of patients >65 years of age (p = 0.029). The Relief comfort type obtained the lowest mean 2.81 (0.33) and the physical context 2.75 (0.41) in the three units. In the multivariate analysis, statistically significant differences were found between the comfort level and the pain level: no pain (p = 0,000) OR 4,361 CI [2,184-8,707], mild pain (p = 0,000) OR 4,007 CI [2,068-7,763], moderate pain (p = 0,007) OR 2,803 CI [1,328-5,913], and the APACHE II score equal to or greater than 10 (p = 0,000) OR 0,472 CI [0,316-0,705]. CONCLUSIONS: The comfort level showed high scores in all three units. The physical and environmental contexts and the relief comfort type negatively affected the perception of comfort. The variables that explained comfort were pain and severity of illness. The evaluation of comfort from the patient's perspective through the GCQ could be considered an indicator of quality of nursing interventions.

Implementation of Direct-to-Patient Mobile Teledermatology in VA.

BACKGROUND: Innovative technology can enhance patient access to healthcare but must be successfully implemented to be effective. OBJECTIVE: We evaluated Department of Veterans Affairs' (VA's) implementation of My VA Images, a direct-to-patient asynchronous teledermatology mobile application enabling established dermatology patients to receive follow-up care remotely instead of in-person. DESIGN /PARTICIPANTS/APPROACH: Following pilot testing at 3 facilities, the app was introduced to 28 facilities (4 groups of 7) every 3 months using a stepped-wedge cluster-randomized design. Using the Organizational Theory of Implementation Effectiveness, we examined the app's implementation using qualitative and quantitative data consisting of encounter data from VA's corporate data warehouse; app usage from VA's Mobile Health database; bi-monthly reports from facility representatives; phone interviews with clinicians; and documented communications between the operational partner and facility staff. KEY RESULTS: Implementation policies and practices included VA's vision to expand home telehealth and marketing/communication strategies. The COVID-19 pandemic dominated the implementation climate by stressing staffing, introducing competing demands, and influencing stakeholder attitudes to the app, including its fit to their values. These factors were associated with mixed implementation effectiveness, defined as high quality consistent use. Nineteen of 31 exposed facilities prepared to use the app; 10 facilities used it for actual patient care, 7 as originally intended. Residents, nurse practitioners, and physician assistants were more likely than attendings to use the app. Facilities exposed to the app pre-pandemic were more likely to use and sustain the new process. CONCLUSIONS: Considerable heterogeneity existed in implementing mobile teledermatology, despite VA's common mission, integrated healthcare system, and stakeholders' broad interest. Identifying opportunities to target favorable facilities and user groups (such as teaching facilities and physician extenders, respectively) while addressing internal implementation barriers including incomplete integration with the electronic health record as well as inadequate staffing may help optimize the initial impact of direct-to-patient telehealth. The COVID pandemic was a notable extrinsic barrier. CLINICAL TRIALS REGISTRATION: NCT03241589.

Improving EEG-based decoding of the locus of auditory attention through domain adaptation.

Objective.This paper presents a novel domain adaptation (DA) framework to enhance the accuracy of electroencephalography (EEG)-based auditory attention classification, specifically for classifying the direction (left or right) of attended speech. The framework aims to improve the performances for subjects with initially low classification accuracy, overcoming challenges posed by instrumental and human factors. Limited dataset size, variations in EEG data quality due to factors such as noise, electrode misplacement or subjects, and the need for generalization across different trials, conditions and subjects necessitate the use of DA methods. By leveraging DA methods, the framework can learn from one EEG dataset and adapt to another, potentially resulting in more reliable and robust classification models.Approach.This paper focuses on investigating a DA method, based on parallel transport, for addressing the auditory attention classification problem. The EEG data utilized in this study originates from an experiment where subjects were instructed to selectively attend to one of the two spatially separated voices presented simultaneously.Main results.Significant improvement in classification accuracy was observed when poor data from one subject was transported to the domain of good data from different subjects, as compared to the baseline. The mean classification accuracy for subjects with poor data increased from 45.84% to 67.92%. Specifically, the highest achieved classification accuracy from one subject reached 83.33%, a substantial increase from the baseline accuracy of 43.33%.Significance.The findings of our study demonstrate the improved classification performances achieved through the implementation of DA methods. This brings us a step closer to leveraging EEG in neuro-steered hearing devices.

Oral Nicotinamide for Actinic Keratosis Prevention in Kidney Transplant Recipients: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Oral nicotinamide (NAM) has shown promise in preventing actinic keratoses (AKs) in trials based outside of the United States. We assessed the efficacy of oral NAM supplementation in kidney transplant recipients with a history of keratinocyte carcinoma. MATERIAL AND METHODS: Patients enrolled in a 2-week run-in phase, during which NAM 1000 mg was taken twice daily. After a washout period, patients who tolerated the run-in phase were randomized to NAM 500 mg twice daily or placebo. At baseline, 4, 8, and 12 months, dermatologists conducted full-body skin exams to document area-specific AKs. Routine lab work was collected to ensure the stability of renal allograft function. RESULTS: The dosage was reduced from 1000 to 500 mg due to gastrointestinal symptoms in the run-in phase. Patients were randomized to NAM (n = 10) or placebo (n = 11). At 12 months, mean AK count was 30.8 (95% CI -11.7-73.4) for NAM and 26.6 (95% CI 10.8-42.5) for placebo. The difference in percent AK count change at 12 months compared with baseline was 259.8% (95% CI -385.9 to 905.5) for NAM and 72.4% (95% CI -118.6 to 263.5) for placebo. The between-group difference in percent AK change was not significant (P = .38). There was no attrition in the placebo group and 40% attrition in the NAM arm. DISCUSSION: Nicotinamide did not decrease AK development among kidney transplant recipients. Limitations include drug tolerability, small sample size, and single-center trial nature.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Carbapenemase-producing Gram-negative bacteria in hospital wastewater, wastewater treatment plants and surface waters in a metropolitan area in Germany, 2020.

Carbapenemase-producing bacteria (CPB) such as Klebsiella pneumoniae and Escherichia coli are causing hospital outbreaks worldwide. An important transfer route into the aquatic environment is the urban water cycle. We aimed to determine the presence of CPB in hospital wastewater, wastewater treatment plants (WWTPs) and surface waters in a German metropolitan area and to characterise these bacteria by whole-genome comparisons. During two periods in 2020, 366 samples were collected and cultivated on chromogenic screening media. Bacterial colonies were selected for species identification and PCR-based carbapenemase gene screening. Genomes of all detected CPB were sequenced and analysed for resistance gene content, followed by multilocus sequence typing (MLST) and core genome MLST (cgMLST) for K. pneumoniae and E. coli isolates. Carbapenemase genes were detected in 243 isolates, most of which belonged to genera/species Citrobacter spp. (n = 70), Klebsiella spp. (n = 57), Enterobacter spp. (n = 52) and E. coli (n = 42). Genes encoding KPC-2 carbapenemase were detected in 124 of 243 isolates. K. pneumoniae produced mainly KPC-2 and OXA-232 whereas E. coli harboured various enzymes (KPC-2, VIM-1, OXA-48, NDM-5, KPC-2 + OXA-232, GES-5, GES-5 + VIM-1, IMP-8 + OXA-48). Eight and twelve sequence types (STs) were identified for K. pneumoniae and E. coli, respectively, forming different clusters. The detection of numerous CPB species in hospital wastewater, WWTPs and river water is of concern. Genome data highlight a hospital-specific presence of distinct carbapenemase-producing K. pneumoniae and E. coli strains belonging to "global epidemic clones" in wastewater samples representing local epidemiology. The various detected CPB species including E. coli ST635, which is not known to cause human infections, could serve as reservoirs/vectors for the spread of carbapenemase genes in the environment. Therefore, effective pretreatment of hospital wastewater prior to discharge into the municipal wastewater system may be required, although swimming lakes do not appear to be a relevant risk factor for CPB ingestion and infection.

'Nesting networks': Women's experiences of social network support in high-risk pregnancy.

OBJECTIVE: Social support, an individual's social relationships (both online and offline), may provide protection against adverse mental health outcomes, such as anxiety and depression, which are high in women who have been hospitalised with high-risk pregnancy. This study explored the social support available to women at higher risk of preeclampsia during pregnancy by examining personal social networks. DESIGN: Semi-structured interviews were accompanied by social network mapping using the web-based social networking tool GENIE. SETTING: England. PARTICIPANTS: Twenty-one women were recruited, of whom 18 were interviewed both during pregnancy and postnatally between April 2019 and April 2020. Nineteen women completed maps pre-natally, 17 women completed maps pre-natally and post-natally. Women were taking part in the BUMP study, a randomised clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. RESULTS: Women's social networks tightened during pregnancy. The inner network changed most dramatically postnatally with women reporting fewer network members. Interviews revealed networks were primarily 'real-life' rather than online social networks, with members providing emotional, informational, and practical support. Women with a high-risk pregnancy valued the relationships they developed with health professionals during pregnancy, and would like their midwife to have a more central role in their networks by providing informational and, where needed, emotional support. The social network mapping data supported the qualitative accounts of changing networks across high-risk pregnancy. CONCLUSION: Women with a high-risk pregnancy seek to build "nesting networks" to support them through pregnancy into motherhood. Different types of support are sought from trusted sources. Midwives can play a key role. PRACTICE IMPLICATIONS: As well as highlighting other potential needs during pregnancy and the ways in which they can be met, support from midwives has a key role. Through talking to women early in their pregnancy, signposting information and explaining ways to contact health professionals regarding informational or emotional support would fill a gap that currently is met by other aspects of their network.

Role of single-dose intravenous iron therapy for the treatment of anaemia after orthopaedic trauma: protocol for a pilot randomised controlled trial.

INTRODUCTION: Orthopaedic trauma and fracture care commonly cause perioperative anaemia and associated functional iron deficiency due to a systemic inflammatory state. Modern, strict transfusion thresholds leave many patients anaemic; managing this perioperative anaemia is an opportunity to impact outcomes in orthopaedic trauma surgery. The primary outcome of this pilot study is feasibility for a large randomised controlled trial (RCT) to evaluate intravenous iron therapy (IVIT) to improve patient well-being following orthopaedic injury. Measurements will include rate of participant enrolment, screening failure, follow-up, missing data, adverse events and protocol deviation. METHODS AND ANALYSIS: This single-centre, pilot, double-blind RCT investigates the use of IVIT for acute blood loss anaemia in traumatically injured orthopaedic patients. Patients are randomised to receive either a single dose infusion of low-molecular weight iron dextran (1000 mg) or placebo (normal saline) postoperatively during their hospital stay for trauma management. Eligible subjects include adult patients admitted for lower extremity or pelvis operative fracture care with a haemoglobin of 7-11 g/dL within 7 days postoperatively during inpatient care. Exclusion criteria include history of intolerance to intravenous iron supplementation, active haemorrhage requiring ongoing blood product resuscitation, multiple planned procedures, pre-existing haematologic disorders or chronic inflammatory states, iron overload on screening or vulnerable populations. We follow patients for 3 months to measure the effect of iron supplementation on clinical outcomes (resolution of anaemia and functional iron deficiency), patient-reported outcomes (fatigue, physical function, depression and quality of life) and translational measures of immune cell function. ETHICS AND DISSEMINATION: This study has ethics approval (Oregon Health & Science University Institutional Review Board, STUDY00022441). We will disseminate the findings through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05292001; ClinicalTrials.gov.

Topographic Mapping of Isolated Thalamic Infarcts Using Vascular and Novel Probabilistic Functional Thalamic Landmarks.

PURPOSE: We aimed to re-evaluate the relationship between thalamic infarct (TI) localization and clinical symptoms using a vascular (VTM) and a novel functional territorial thalamic map (FTM). METHODS: Magnetic resonance imaging (MRI) and clinical data of 65 patients with isolated TI were evaluated (female n = 23, male n = 42, right n = 23, left n = 42). A VTM depicted the known seven thalamic vascular territories (VT: inferolateral, anterolateral, inferomedial, posterior, central, anteromedian, posterolateral). An FTM was generated from a probabilistic thalamic nuclei atlas to determine six functionally defined territories (FT: anterior: memory/emotions; ventral: motor/somatosensory/language; medial: behavior/emotions/nociception, oculomotor; intralaminar: arousal/pain; lateral: visuospatial/somatosensory/conceptual and analytic thinking; posterior: audiovisual/somatosensory). Four neuroradiologists independently assigned diffusion-weighted imaging (DWI) lesions to the territories mapped by the VTM and FTM. Findings were correlated with clinical features. RESULTS: The most frequent symptom was a hemisensory syndrome (58%), which was not specific for any territory. A co-occurrence of hemisensory syndrome and hemiparesis had positive predictive values (PPV) of 76% and 82% for the involvement of the inferolateral VT and ventral FT, respectively. Thalamic aphasia had a PPV of 63% each for involvement of the anterolateral VT and ventral FT. Neglect was associated with involvement of the inferolateral VT/ventral FT. Interrater reliability for the assignment of DWI lesions to the VTM was fair (κ = 0.36), but good (κ = 0.73) for the FTM. CONCLUSION: The FTM revealed a greater reproducibility for the topographical assignment of TI than the VTM. Sensorimotor hemiparesis and neglect are predictive for a TI in the inferolateral VT/ventral FT. The hemisensory syndrome alone does not allow any topographical assignment.

In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules.

The brain's connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations? We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations. Remarkably, the magnitude and selectivity of connectivity weights followed a specific order across most of the inferred connectivity configurations. We argue that this order stems from the specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning. Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than their magnitudes, represent a connectivity motif supporting canonical V1 computations.

Elucidating mobilization mechanisms of uranium during recharge of river water to contaminated groundwater.

The recharge of stream water below the baseflow water table can mobilize groundwater contaminants, particularly redox-sensitive and sorptive metals such as uranium. However, in-situ tracer experiments that simulate the recharge of stream water to uranium-contaminated groundwater are lacking, thus limiting the understanding of the potential mechanisms that control the mobility of uranium at the field scale. In this study, a field tracer test was conducted by injecting 100 gal (379 l) of oxic river water into a nearby suboxic and uranium-contaminated aquifer. The traced river water was monitored for 18 days in the single injection well and in the twelve surrounding observation wells. Mobilization of uranium from the solid to the aqueous phase was not observed during the tracer test despite its pre-test presence being confirmed on the aquifer sediments from lab-based acid leaching. However, strong evidence of oxidative immobilization of iron and manganese was observed during the tracer test and suggested that immobile uranium was likely in its oxidized state as U(VI) on the aquifer sediments; these observations ruled out oxidation of U(IV) to U(VI) as a potential mobilization mechanism. Therefore, desorption of U(VI) appeared to be the predominant potential mobilization mechanism, yet it was clearly not solely dependent on concentration as evident when considering that uranium-poor river water (<0.015 mg/L) was recharged to uranium-rich groundwater (≈1 mg/L). It was possible that uranium desorption was limited by the relatively higher pH and lower alkalinity of the river water as compared to the groundwater; both factors favor immobilization. However, it was likely that the immobile uranium was associated with a mineral phase, as opposed to a sorbed phase, thus desorption may not have been possible. The results of this field tracer study successfully ruled out two common mobilization mechanisms of uranium: (1) oxidative dissolution and (2) concentration-dependent desorption and ruled in the importance of advection, dispersion, and the mineral phase of uranium.

Trace mineral mixture supplemented to in vitro maturation medium improves subsequent embryo development and embryo quality in cattle.

Trace minerals participate in reproductive processes and are crucial for oocyte maturation. The objective of the present study was to investigate the effect of combined supplementation with copper (Cu), manganese (Mn), selenium (Se) and zinc (Zn) during bovine in vitro maturation (IVM) on subsequent embryo development and quality. The IVM medium was supplemented as follows: a) Control (no mineral supplementation); b) MScz (6 ng/mL Mn + 100 ng/mL Se + 200 ng/mL Cu + 400 ng/mL Zn); c) MScZ (6 ng/mL Mn + 100 ng/mL Se + 200 ng/mL Cu + 1200 ng/mL Zn); d) MSCz (6 ng/mL Mn + 100 ng/mL Se + 600 ng/mL Cu + 400 ng/mL Zn). Supplementation with MScz and MSCz produced more blastocysts compared with the control. Total blastocyst cell number was higher when minerals were added at any combination. Day-8 blastocysts derived from oocytes treated with minerals had lower intracellular reactive oxygen species concentration and lipid content than the control. In conclusion, combined supplementation with Cu, Mn, Se and Zn during bovine oocyte IVM increased in vitro production performance, improving embryo developmental ability and quality.

nor 3'-Demethoxyisoguaiacin from Larrea tridentata Is a Potential Alternative against Multidrug-Resistant Bacteria Associated with Bovine Mastitis.

Bovine mastitis is one of the most common diseases in dairy cows, and it causes significant economic losses in dairy industries worldwide. Gram-positive and Gram-negative bacteria can cause bovine mastitis, and many of them have developed antimicrobial resistance. There is an urgent need for novel therapeutic options to treat the disease. Larrea tridentata-derived compounds represent an important potential alternative treatment. The aim of the present study was to isolate and characterize antibacterial compounds from Larrea tridentata against multidrug-resistant bacteria associated with bovine mastitis. The L. tridentata hydroalcoholic extract (LTHE) exhibited antibacterial activity. The extract was subjected to a bipartition, giving an aqueous fraction (moderate antibacterial activity) and an organic fraction (higher antibacterial activity). Chromatographic separation of the organic fraction enabled us to obtain four active sub-fractions. Chemical analyses through HPLC techniques were conducted for the LTHE, fractions, and sub-fraction Ltc1-F3, from which we isolated two compounds, characterized by 1H and 13C NMR analyses. Compound nor-3 demethoxyisoguaiacin exhibited the best antibacterial activity against the evaluated bacteria (MIC: 0.01-3.12 mg/mL; MBC: 0.02-3.12 mg/mL). The results indicated that nor-3 demethoxyisoguaiacin can be used as an alternative treatment for multidrug-resistant bacteria associated with mastitis.

Three Dimensions of Association Link Migraine Symptoms and Functional Connectivity.

Migraine is a heterogeneous disorder with variable symptoms and responsiveness to therapy. Because of previous analytic shortcomings, variance in migraine symptoms has been inconsistently related to brain function. In the current analysis, we used data from two sites (n = 143, male and female humans), and performed canonical correlation analysis, relating resting-state functional connectivity (RSFC) with a broad range of migraine symptoms, ranging from headache characteristics to sleep abnormalities. This identified three dimensions of covariance between symptoms and RSFC. The first dimension related to headache intensity, headache frequency, pain catastrophizing, affect, sleep disturbances, and somatic abnormalities, and was associated with frontoparietal and dorsal attention network connectivity, both of which are major cognitive networks. Additionally, RSFC scores from this dimension, both the baseline value and the change from baseline to postintervention, were associated with responsiveness to mind-body therapy. The second dimension was related to an inverse association between pain and anxiety, and to default mode network connectivity. The final dimension was related to pain catastrophizing, and salience, sensorimotor, and default mode network connectivity. In addition to performing canonical correlation analysis, we evaluated the current clustering of migraine patients into episodic and chronic subtypes, and found no evidence to support this clustering. However, when using RSFC scores from the three significant dimensions, we identified a novel clustering of migraine patients into four biotypes with unique functional connectivity patterns. These findings provide new insight into individual variability in migraine, and could serve as the foundation for novel therapies that take advantage of migraine heterogeneity.SIGNIFICANCE STATEMENT Using a large multisite dataset of migraine patients, we identified three dimensions of multivariate association between symptoms and functional connectivity. This analysis revealed neural networks that relate to all measured symptoms, but also to specific symptom ensembles, such as patient propensity to catastrophize painful events. Using these three dimensions, we found four biotypes of migraine informed by clinical and neural variation together. Such findings pave the way for precision medicine therapy for migraine.

Biological Activities of Organic Extracts of the Genus Aristolochia: A Review from 2005 to 2021.

Different ethnomedicinal studies have investigated the relationship between various phytochemicals as well as organic extracts and their bioactive aspects. Studies on biological effects are attributed to secondary metabolites such as alkaloids, phenolic compounds, and terpenes. Since there have been no reviews in the literature on the traditional, phytochemical, and ethnomedicinal uses of the genus Aristolochia so far, this article systematically reviews 141 published studies that analyze the associations between secondary metabolites present in organic extracts and their beneficial effects. Most studies found associations between individual secondary metabolites and beneficial effects such as anticancer activity, antibacterial, antioxidant activity, snake anti-venom and anti-inflammatory activity. The aim of this review was to analyze studies carried out in the period 2005-2021 to update the existing knowledge on different species of the genus Aristolochia for ethnomedicinal uses, as well as pharmacological aspects and therapeutic uses.

Robust effects of corticothalamic feedback and behavioral state on movie responses in mouse dLGN.

Neurons in the dorsolateral geniculate nucleus (dLGN) of the thalamus receive a substantial proportion of modulatory inputs from corticothalamic (CT) feedback and brain stem nuclei. Hypothesizing that these modulatory influences might be differentially engaged depending on the visual stimulus and behavioral state, we performed in vivo extracellular recordings from mouse dLGN while optogenetically suppressing CT feedback and monitoring behavioral state by locomotion and pupil dilation. For naturalistic movie clips, we found CT feedback to consistently increase dLGN response gain and promote tonic firing. In contrast, for gratings, CT feedback effects on firing rates were mixed. For both stimulus types, the neural signatures of CT feedback closely resembled those of behavioral state, yet effects of behavioral state on responses to movies persisted even when CT feedback was suppressed. We conclude that CT feedback modulates visual information on its way to cortex in a stimulus-dependent manner, but largely independently of behavioral state.

Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.

Misleading estimates of economic impacts of biological invasions: Including the costs but not the benefits.

The economic costs of non-indigenous species (NIS) are a key factor for the allocation of efforts and resources to eradicate or control baneful invasions. Their assessments are challenging, but most suffer from major flaws. Among the most important are the following: (1) the inclusion of actual damage costs together with various ancillary expenditures which may or may not be indicative of the real economic damage due to NIS; (2) the inclusion of the costs of unnecessary or counterproductive control initiatives; (3) the inclusion of controversial NIS-related costs whose economic impacts are questionable; (4) the assessment of the negative impacts only, ignoring the positive ones that most NIS have on the economy, either directly or through their ecosystem services. Such estimates necessarily arrive at negative and often highly inflated values, do not reflect the net damage and economic losses due to NIS, and can significantly misguide management and resource allocation decisions. We recommend an approach based on holistic costs and benefits that are assessed using likely scenarios and their counter-factual.

The utilization of hyperbaric oxygenation therapy in hypospadias repair: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to evaluate the efficacy and safety of Hyperbaric Oxygen Therapy (HBOT) use in hypospadias repair through systematic review and meta-analysis of comparative studies. METHODS: A systematic literature search was performed in May 2021. Comparative studies assessing the surgical outcome of hypospadias repair between control versus HBOT utilization were identified and evaluated according to Cochrane collaboration recommendations. The assessed outcome includes hypospadias repair failures and graft failure for staged repair using a buccal graft. Relative risk with corresponding 95% confidence intervals (CI) were extrapolated. A random-effect model was used to generate pooled effect estimates. Heterogeneity and inter-study variability were assessed using Chi-square and I-square. Subgroup analysis was performed according to primary repair versus redo-hypospadias with buccal graft. PROSPERO registration (CRD42021251423). RESULTS: Five comparative studies with 576 cases (301 HBOT versus 275 controls) were included. Overall pooled effect estimates showed that the HBOT group has significantly lesser hypospadias repair failure (RR 0.52, 95%CI 0.37, 0.72). Subgroup analysis on the use of HBOT for graft take showed lesser graft failure compared to the control group (RR 0.20, 95% CI 0.05, 0.75), while the use of HBOT for primary and redo single staged hypospadias repair showed lesser complication rate (RR 0.56, 95%CI 0.40, 0.78). Based on ROBINS-I assessment, all included comparative studies are determined to be of serious risk of bias mainly due to presence of confounding. CONCLUSION: The currently available low-quality of evidence suggests that compared to control groups, HBOT as an adjunctive intervention to complicated hypospadias repair was able to reduce surgical outcome failure and graft failure rates.