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1.
Surgeon ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38724298

ABSTRACT

BACKGROUND AND PURPOSE: The rise in hip and knee arthroplasty for osteoarthritis requires addressing healthcare system pollution to support Ireland's climate change goals. This research aimed to quantify waste generated and determine environmental and economic impacts to promote sustainable strategies in joint arthroplasty and shed light on the suboptimal waste management practices. METHODS: The study was conducted at National Orthopaedic Hospital Cappagh (NOHC), measuring waste generated during hip and knee arthroplasty. Clinical, domestic, and recycled waste weights were recorded, including the segregation of Central Sterile Supply Department (CSSD) Blue Wrap waste in ten operations. Kilograms of carbon dioxide emissions (kgCO2e) and disposal costs were calculated. RESULTS: In a sample of 100 joint arthroplasty operations, the study found that revision knees produced 23.58 â€‹kgCO2e per case, revision hips 23.50 â€‹kgCO2e, primary knees 15.82 â€‹kgCO2e, and primary hips 14.64 â€‹kgCO2e. CSSD Blue Wrap contributed on average 13.5% of OT waste. Extrapolating these findings to the estimated number of joint arthroplasties performed in 2022 â€‹at NOHC (1556 hip and knee joint arthroplasties), the emissions were estimated to be 24,576 kgCO2e, with the cost of disposal up to €29,228. Strategies to mitigate this waste have been identified and proposed. CONCLUSION: The research aimed to address the environmental impact of orthopaedic joint arthroplasties, offering strategies to reduce waste generation, carbon emissions, and cost. Utilising our methodology to calculate greenhouse gas emissions will empower sustainability offices to conduct their own waste audits and implementing our strategies for waste management practices can help minimise environmental waste.

2.
Article in English | MEDLINE | ID: mdl-38757543

ABSTRACT

OBJECTIVE: Placenta accreta spectrum (PAS) is a complex disorder of uterine wall disruption with significant morbidity and mortality, particularly at time of delivery. Both physician and physical hospital resource allocation/utilization remains a challenge in PAS cases including intensive care unit (ICU) beds. The primary objective of the present study was to identify preoperative risk factors for ICU admission and create an ICU admission prediction model for patient counseling and resource utilization decision making in an evidence-based manner. METHODS: This was a case-control study of 145 patients at our PAS referral center undergoing cesarean hysterectomy for PAS. Final confirmation by histopathology was required for inclusion. Patient disposition after surgery (ICU vs post-anesthesia care unit) was our primary outcome and pre-/intra-/postoperative variables were obtained via electronic medical records with an emphasis on the predictive capabilities of the preoperative variables. Uni- and multivariate analysis was performed to identify independent predictive factors for ICU admission. RESULTS: In this large cohort of 145 patients who underwent cesarean hysterectomy for PAS, with histopathologic confirmation, 63 (43%) were admitted to the ICU following delivery. These patients were more likely to be delivered at an earlier gestational age (34 vs 35 weeks, P < 0.001), have had >2 episodes of vaginal bleeding and emergent delivery compared to patients admitted to patients with routine recovery care (44% vs 18.3%, P = 0.009). Uni- and multivariate logistic regression showed an area under the curve of 0.73 (95% CI: [0.63, 0.81], P < 0.001) for prediction of ICU admission with these three variables. Patients with all three predictors had 100% ICU admission rate. CONCLUSION: Resource prediction, utilization and allocation remains a challenge in PAS management. By identifying patients with preoperative risk factors for ICU admission, not only can patients be counseled but this resource can be requested preoperatively for staffing and utilization purposes.

3.
Medicina (Kaunas) ; 60(4)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674323

ABSTRACT

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days. Results: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (p < 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks, p < 0.01), and increased composite maternal morbidity (76, 84, and 94%, p = 0.03). Conclusions: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients.


Subject(s)
Cesarean Section , Placenta Accreta , Uterine Hemorrhage , Humans , Female , Placenta Accreta/surgery , Pregnancy , Case-Control Studies , Adult , Cesarean Section/adverse effects , Cesarean Section/statistics & numerical data , Hysterectomy/statistics & numerical data , Retrospective Studies , Pregnancy Outcome/epidemiology
4.
ACS Appl Mater Interfaces ; 16(12): 14633-14644, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38483312

ABSTRACT

Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage. As pharmaceutical utility also demands that this is achieved using biocompatible materials that provide colloidal stability, our aim was to develop a nanoparticle (NP) delivery system loaded with the COX-2 inhibitor celecoxib that can meet these criteria. We devised a reproducible and economical method to synthesize the colloidally stable albumin NPs loaded with celecoxib without the use of any of the following conditions: high temperatures at which albumin denaturation occurs, polymer coatings, oils, Class 1/2 solvents, and chemical protein cross-linkers. The spherical NP suspensions were biocompatible, monodisperse with average diameters of 72 nm (ideal for OA cartilage penetration), and they were stable over 6 months at 4 °C. Moreover, the NPs loaded celecoxib at higher levels than those required for the therapeutic response in arthritic joints. For these reasons, they are the first of their kind. Labeled NPs were internalized by primary human articular chondrocytes cultured from the knee joints of OA patients. The NPs reduced the concentration of inflammatory mediator prostaglandin E2 released by the primaries, an indication of retained bioactivity following NP synthesis. Similar results were observed in lipopolysaccharide-stimulated human THP-1 monocytes. The IA administration of these NPs is expected to avoid side-effects associated with oral administration of celecoxib and to maintain a high local concentration in the knee joint over a sustained period. They are now ready for evaluation by IA administration in animal models of OA.


Subject(s)
Nanoparticles , Osteoarthritis , Animals , Humans , Celecoxib/pharmacology , Celecoxib/therapeutic use , Injections, Intra-Articular , Osteoarthritis/drug therapy , Knee Joint , Albumins
7.
Biol Psychiatry Glob Open Sci ; 4(1): 165-181, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38298784

ABSTRACT

Background: Learning requires the activation of protein kinases with distinct temporal dynamics. In Aplysia, nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown. Methods: We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear extinction experiments. Immunohistochemistry was performed to evaluate pCREB (phosphorylated cAMP response element binding)\protein levels in brain regions that have been implicated in fear acquisition. Results: Rats exposed to the optimal conditioning protocol with irregular ITIs exhibited impaired extinction memory acquisition within the session using a standard footshock intensity, and stronger fear memory retrieval and spontaneous recovery with a weaker footshock intensity, compared with rats that received massed or spaced conditioning protocols with fixed ITIs. Rats exposed to the optimal extinction protocol displayed improved extinction of contextual fear memory and reduced spontaneous recovery compared with rats that received standard extinction protocols. Moreover, the optimal conditioning protocol increased pCREB levels in the dentate gyrus of the dorsal hippocampus, suggesting enhanced induction of long-term potentiation. Conclusions: These findings demonstrate that a computational model-driven behavioral intervention can enhance associative learning in mammals and may provide insight into strategies to improve cognition in humans.

9.
Obstet Gynecol ; 143(2): 219-228, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37944145

ABSTRACT

OBJECTIVE: To estimate the maternal survival and live-birth rates in pregnant women with acute respiratory distress syndrome (ARDS) secondary to critical coronavirus disease 2019 (COVID-19) who are treated with extracorporeal membrane oxygenation (ECMO) by performing a systematic review and meta-analysis. DATA SOURCES: From database inception through August 2023, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Studies reporting maternal survival and live-birth rates in pregnant women with critical COVID-19 undergoing ECMO were included. METHODS OF STUDY SELECTION: Two reviewers separately ascertained studies, obtained data, and evaluated study quality. Summary estimates of maternal survival and live-birth rates were measured, and 95% CIs were calculated. TABULATION, INTEGRATION, AND RESULTS: Nine retrospective case series and 12 retrospective cohort studies were identified with 386 pregnant women with critical COVID-19 who underwent ECMO. Studies evaluated women that were treated from January 2020 to October 2022. Four studies were from the United States; three were from Turkey; two were from France; two were from Israel; and one each was from Columbia, Germany, Italy, Kuwait, Poland, Republic of Srpska, the United Arab Emirates, the United Kingdom, a consortium from Belgium, France, Switzerland, and an international registry. The pooled estimate of the maternal survival rate among pregnant patients who were initiated on ECMO was 75.6% (95% CI, 66.0-84.1%, I2 =72%). The pooled estimate of the live-birth rate among pregnant patients who were initiated on ECMO was 83.7% (95% CI, 76.8-89.6%, 153 neonates, I2 =11%). When the case series and cohort studies were examined separately, the results were similar. CONCLUSION: Among pregnant women with acute respiratory distress syndrome attributable to critical COVID-19 who were managed with ECMO, maternal survival and live-birth rates were high. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023442800.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Female , Humans , Infant, Newborn , Pregnancy , COVID-19/therapy , Respiratory Distress Syndrome/therapy , Retrospective Studies
10.
Pregnancy Hypertens ; 35: 1-5, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38029452

ABSTRACT

BACKGROUND: Preeclampsia with severe features (SPE) is a multisystem syndrome associated with long-term cardiovascular morbidity. Serum concentrations of N-terminal B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin-T (hs-cTnT) are sensitive markers of cardiac stretch and ischemia, respectively. OBJECTIVE: Our aim was to examine NT-proBNP and hs-cTnT in patients with SPE during labor. We hypothesized that patients with severe preeclampsia would have increased serum concentrations of these analytes as compared with normotensive laboring patients. STUDY DESIGN: This was a prospective cohort study of intrapartum patients with SPE and normotensive controls. Patients were recruited at the time of SPE diagnosis or admission to the labor unit, and those with medical conditions that could predispose to baseline cardiac dysfunction were excluded. Serum from venous blood was collected for NT-proBNP and hs-cTnT measurement at three time points: 0-2 h, 4 h, and 12 h after admission. A mixed random effects regression model was used to compare analyte levels at each time point and to compare trends over time. The primary outcome was NT-proBNP concentration at each collection time point in patients with severe preeclampsia as compared to normotensive controls. Power analysis yielded a goal sample of 25 patients with a 12 h and at least 1 other sample in each arm. Two-tailed P values less than 0.05 were considered statistically significant. P value adjustment for multiple comparisons was performed. RESULTS: Of 78 patients analyzed, 36 had severe preeclampsia and 42 were normotensive controls with 25 in each cohort having a 12 h and at least 1 other sample. The NT-proBNP trend was significantly different in the two cohorts (P < 0.001). After adjustment for multiple comparisons, the mean serum concentration of NT-proBNP was elevated in the severe preeclampsia group at 0-2 and 4 h, but not at 12 h. After similar adjustment, detectable serum concentrations of hs-cTnT were more frequent in patients with severe preeclampsia at all three timepoints. CONCLUSION: Intrapartum serum concentrations of NT-proBNP were elevated nearly twofold in patients with SPE when compared with normotensive controls, with the most pronounced differences found during early labor. Detectable but low serum concentrations of hs-cTnT were more common in women with severe preeclampsia as compared with normotensive controls. These findings suggest cardiac dysfunction with SPE may be present at the time of admission and contribute to features of maternal cardiovascular morbidity and mortality.


Subject(s)
Cardiovascular Diseases , Heart Diseases , Peptide Fragments , Pre-Eclampsia , Humans , Female , Natriuretic Peptide, Brain , Prospective Studies , Troponin T , Pre-Eclampsia/diagnosis , Biomarkers , Disease Progression
11.
Circulation ; 149(1): 7-23, 2024 01 02.
Article in English | MEDLINE | ID: mdl-37795617

ABSTRACT

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.


Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Microvascular Angina , Humans , Female , Middle Aged , Male , Coronary Artery Disease/diagnostic imaging , Coronary Angiography , United Kingdom
13.
Eur J Obstet Gynecol Reprod Biol ; 293: 32-35, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38100939

ABSTRACT

BACKGROUND: Placenta Accreta Spectrum (PAS) represents a particularly morbid condition for which blood transfusion is the leading cause. Delivery by cesarean hysterectomy is recommended for the management of PAS. Massive Transfusion Protocols (MTP) in obstetrics vary in definition and implementation. Given the significant blood loss during PAS cesarean hysterectomy, this is particularly important for surgeons and blood banks. Our objective was to identify risk factors for MTP in patients with antenatally suspected PAS. METHODS: We performed a case-control study over a 11-year period from 2012 to 2022 at our center for Placenta Accreta Spectrum. MTP was defined by two methods, >4 units or > 10 units of red blood cells/whole blood transfused over 24 h. Antenatal, operative and post-operative outcomes were obtained from electronic medical records of these cases. RESULTS: During the study time frame, 142 cases were managed by our PAS team and met all criteria. 85 % (120/142) of patients were transfused at least 1 unit of blood, 64 patients (45 %) received 0-3 units of blood, 50 patients (35 %) received 4-9 units of blood and 28 patients (19.7 %) were transfused > 10 units of blood. Pre-delivery vaginal bleeding, preterm labor and delivery < 34 weeks were independently significant in transfused patients. ROC analysis revealed an area under the curve (AUC) of 0.79 (p < 0.0001) in patients transfused > 10 units, showing predictive capability for this subgroup. DISCUSSION: We here report pre-operative risk factors for MTP in patients undergoing cesarean hysterectomy for PAS. This allows for both resource utilization and patient counseling for this morbid maternal condition.


Subject(s)
Placenta Accreta , Infant, Newborn , Humans , Female , Pregnancy , Case-Control Studies , Placenta Accreta/surgery , Blood Transfusion , Hysterectomy/adverse effects , Hysterectomy/methods , Risk Factors , Retrospective Studies , Placenta
14.
Eur Heart J Case Rep ; 7(12): ytad562, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38093823

ABSTRACT

Background: People who are transgender may utilize masculinizing or feminizing gender-affirming hormonal therapy. Testosterone and oestrogen receptors are expressed throughout the cardiovascular system, yet the effects of these therapies on cardiovascular risk and outcomes are largely unknown. We report the case of a young transgender man with no discernible cardiovascular risk factors presenting with an acute coronary syndrome. Case summary: A 31-year-old transgender man utilizing intramuscular testosterone masculinizing gender-affirming hormonal therapy presented with central chest pain radiating to the left arm. He had no past medical history of hypertension, dyslipidaemia, diabetes, or smoking. Electrocardiography demonstrated infero-septal ST depression, and high-sensitivity troponin-I was elevated and increased to 19 686 ng/L. He was diagnosed with a non-ST-segment elevation myocardial infarction. Inpatient coronary angiography confirmed a critical focal lesion in the mid right coronary artery, which was managed with two drug-eluting stents. Medical management (i.e. aspirin, ticagrelor, atorvastatin, ramipril, and bisoprolol) and surveillance of residual plaque disease evident in the long tubular left main stem, proximal left anterior descending, and proximal circumflex vessels was undertaken. The masculinizing gender-affirming hormonal therapy was continued. Discussion: Despite a greater awareness of the potential risk of increased cardiovascular disease in transgender people, the fundamental lack of data regarding cardiovascular outcomes in transgender people may be contributing to healthcare inequalities in this population. We must implement better training, awareness, and research into transgender cardiovascular health to facilitate equitable and evidence-based outcomes.

15.
Ann Surg Open ; 4(4): e351, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38144505

ABSTRACT

Objective: Using health records from the Department of Veterans Affairs (VA), the largest healthcare training platform in the United States, we estimated independent associations between the intensity of attending supervision of surgical residents and 30-day postoperation patient outcomes. Background: Academic leaders do not agree on the level of autonomy from supervision to grant surgery residents to best prepare them to enter independent practice without risking patient outcomes. Methods: Secondary data came from a national, systematic 1:8 sample of n = 862,425 teaching encounters where residents were listed as primary surgeon at 122 VA medical centers from July 1, 2004, through September 30, 2019. Independent associations between whether attendings had scrubbed or not scrubbed on patient 30-day all-cause mortality, complications, and 30-day readmission were estimated using generalized linear-mixed models. Estimates were tested for any residual confounding biases, robustness to different regression models, stability over time, and validated using moderator and secondary factors analyses. Results: After accounting for potential confounding factors, residents supervised by scrubbed attendings in 733,997 nonemergency surgery encounters had fewer deaths within 30 days of the operation by 14.2% [0.3%, 29.9%], fewer case complications by 7.9% [2.0%, 14.0%], and fewer readmissions by 17.5% [11.2%, 24.2%] than had attendings not scrubbed. Over the 15 study years, scrubbed surgery attendings may have averted an estimated 13,700 deaths, 43,600 cases with complications, and 73,800 readmissions. Conclusions: VA policies on attending surgeon supervision have protected patient safety while allowing residents in selected teaching encounters to have limited autonomy from supervision.

16.
Front Sociol ; 8: 1232555, 2023.
Article in English | MEDLINE | ID: mdl-37693799

ABSTRACT

Introduction: Globally, an epidemic of psychological distress, burnout, and workforce attrition signify an acute deterioration in hospital doctors' relationship with their work-intensified by COVID-19. This deterioration is more complicated than individual responses to workplace stress, as it is heavily regulated by social, professional, and organizational structures. Moving past burnout as a discrete "outcome," we draw on theories of emotion management and alienation to analyze the strategies through which hospital doctors continue to provide care in the face of resource-constraints and psychological strain. Methods: We used Mobile Instant Messaging Ethnography (MIME), a novel form of remote ethnography comprising a long-term exchange of digital messages to elicit "live" reflections on work-life experiences and feelings. Results: The results delineate two primary emotion-management strategies-acquiescence and depersonalization-used by the hospital doctors to suppress negative feelings and emotions (e.g., anger, frustration, and guilt) stemming from the disconnect between professional norms of expertise and self-sacrifice, and organizational realities of impotence and self-preservation. Discussion: Illustrating the continued relevant of alienation, extending its application to doctors who disconnect to survive, we show how the socio-cultural ideals of the medical profession (expertise and self-sacrifice) are experienced through the emotion-management and self-estrangement of hospital doctors. Practically, the deterioration of hospital doctors' relationship with work is a threat to health systems and organizations. The paper highlights the importance of understanding the social structures and disconnects that shape this deteriorating relationship and the broad futility of self-care interventions embedded in work contexts of unrealized professional ideals, organizational resource deficits and unhappy doctors, patients, and families.

17.
J Neurosci ; 43(45): 7601-7615, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37699717

ABSTRACT

Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau potentials that, once elicited, can lead to prolonged activity that is independent of stimulus intensity or duration. To better understand this diversity of information processing, we compared the voltage-gated and Ca2+-gated currents of three identified neurons from hermaphroditic Aplysia californica Two of these neurons, B51 and B64, generated plateau potentials and a third neuron, B8, exhibited regular firing and was incapable of generating a plateau potential. With the exception of the Ca2+-gated potassium current (I KCa), all three neuron types expressed a similar array of outward and inward currents, but with distinct voltage-dependent properties for each neuron type. Inhibiting voltage-gated Ca2+ channels with Ni+ prolonged the plateau potential, indicating I KCa is important for plateau potential termination. In contrast, inhibiting persistent Na+ (I NaP) blocked plateau potentials, empirically and in simulations. Surprisingly, the properties and level of expression of I NaP were similar in all three neurons, indicating that the presence of I NaP does not distinguish between regular-firing neurons and neurons capable of generating plateau potentials. Rather, the key distinguishing factor is the relationship between I NaP and outward currents such as the delayed outward current (I D), and I KCa We then demonstrated a technique for predicting complex physiological properties such as plateau duration, plateau amplitude, and action potential duration as a function of parameter values, by fitting a curve in parameter space and projecting the curve beyond the tested values.SIGNIFICANCE STATEMENT Plateau potentials are intrinsic properties of neurons that are important for information processing in a wide variety of nervous systems. We examined three identified neurons in Aplysia californica with different propensities to generate a plateau potential. No single conductance was found to distinguish plateau generating neurons. Instead, plateau generation depended on the ratio between persistent Na+ current (I NaP), which favored plateaus, and outward currents such as I KCa, which facilitated plateau termination. Computational models revealed a relationship between the individual currents that predicted the features of simulated plateau potentials. These results provide a more solid understanding of the conductances that mediate plateau generation.


Subject(s)
Calcium , Neurons , Calcium/metabolism , Neurons/physiology , Action Potentials/physiology
18.
SICOT J ; 9: 25, 2023.
Article in English | MEDLINE | ID: mdl-37560993

ABSTRACT

INTRODUCTION: Developmental dysplasia of the hip (DDH) refers to congenital and/or developmental hip instability that can result in hip joint subluxation or dislocation. When detected neonatally, conservative treatment with hip bracing can restore normal hip anatomy. Missed detection of DDH in the neonatal period or late development of DDH often requires surgical intervention to correct the abnormal anatomy. Furthermore, despite surgical intervention, residual sequelae may persist leading to early osteoarthritis of the hip joint requiring joint replacement surgery. AIM: This study investigates the prevalence of hip dysplasia in patients undergoing total hip arthroplasty (THA) under 50 years of age. METHODS: The hip arthroplasty database at a national referral centre was investigated from January 2014 to December 2020. In patients under 50 years of age, those with an adequate pre-operative anteroposterior pelvic radiograph without previous hip arthroplasty were included, while those with inadequate radiographs were excluded. The following measurements were made on the contralateral non-operated hip: (1) lateral centre-edge angle (LCEA), (2) Tönnis angle, (3) acetabular version, (4) acetabular depth, (5) femoral head lateralisation, (6) femoral head extrusion index, and (7) acetabular depth-to-width ratio. RESULTS: In total, 451 patients were included in this study. Twenty two percent of the patients had hip dysplasia, based on a LCEA of <25° and 42.6% of patients had hip dysplasia, based on a Tönnis angle of > 10°. The mean LCEA and Tönnis angle were 31.47 ± 9.64 and 9.82 ± 6.79°, respectively. CONCLUSION: Hip dysplasia is common in patients undergoing THA under the age of 50 years with over 40% having dysplasia according to the Tönnis angle. Classification of primary and secondary osteoarthritis in the joint registries will benefit our knowledge on the prevalence of DDH in the adult population.

19.
Oxf Open Neurosci ; 2: kvac014, 2023.
Article in English | MEDLINE | ID: mdl-37649778

ABSTRACT

Phosphorylation of the MAPK family member extracellular signal-regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse - the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20 min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45 min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed within 5 h. A second wave of increased pERK was detected 18 h post-treatment for all protocols. This late phase was blocked by inhibitors of protein kinase A, TrkB and TGF-ß. These results suggest that complex interactions among kinase pathways and growth factors contribute to the late increase of pERK. ERK activity returned to basal 24 h after the standard or two-pulse protocols, but remained elevated 24 h for the enhanced protocol. This 24-h elevation was also dependent on PKA and TGF-ß, and partly on TrkB. These results begin to characterize long-lasting ERK activation, plausibly maintained by positive feedback involving growth factors and PKA, that appears essential to maintain LTF and LTM. Because many processes involved in LTF and late LTP are conserved among Aplysia and mammals, these findings highlight the importance of examining the dynamics of kinase cascades involved in vertebrate long-term memory.

20.
Health Policy ; 135: 104863, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37399678

ABSTRACT

Healthcare worker (HCW) mental well-being has become a global public health priority as health systems seek to strengthen their resilience in the face of the COVID-19 pandemic. Analysing data from the Health System Response Monitor, we present six case studies (Denmark, Italy, Kyrgyzstan, Lithuania, Romania, and the United Kingdom) as a comparative review of policy interventions supporting HCW mental health during the pandemic. The results illustrate a wide range of interventions. While Denmark and the United Kingdom built on pre-existing structures to support HCW mental wellbeing during the pandemic, the other countries required new interventions. Across all cases, there was a reliance on self-care resources, online training tools, and remote professional support. Based on our analysis, we develop four policy recommendations for the future of HCW mental health supports. First, HCW mental health should be seen as a core facet of health workforce capacity. Second, effective mental health supports requires an integrated psychosocial approach that acknowledges the importance of harm prevention strategies and organisational resources (psychological first aid) alongside targeted professional interventions. Third, personal, professional and practical obstacles to take-up of mental health supports should be addressed. Fourth, any specific support or intervention targeting HCW's mental health is connected to, and dependent on, wider structural and employment factors (e.g. system resourcing and organisation) that determine the working conditions of HCWs.


Subject(s)
COVID-19 , Humans , Mental Health , Pandemics/prevention & control , Health Personnel/psychology , Psychological Well-Being
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