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1.
Cell Rep Med ; 5(7): 101629, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38959886

ABSTRACT

Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis.


Subject(s)
Adiponectin , Fibroblast Growth Factors , Leptin , Sphingolipids , Weight Loss , Humans , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/blood , Adiponectin/blood , Adiponectin/metabolism , Leptin/blood , Leptin/metabolism , Sphingolipids/metabolism , Sphingolipids/blood , Male , Female , Obesity/metabolism , Obesity/blood , Middle Aged , Adult , Ceramides/metabolism , Ceramides/blood , Growth Differentiation Factor 15/metabolism , Growth Differentiation Factor 15/blood
2.
Int J Public Health ; 69: 1606861, 2024.
Article in English | MEDLINE | ID: mdl-39022447

ABSTRACT

Objectives: To assess the association between socioeconomic status (SES) and self-reported adherence to preventive measures in Switzerland during the COVID-19 pandemic. Methods: 4,299 participants from a digital cohort were followed between September 2020 and November 2021. Baseline equivalised disposable income and education were used as SES proxies. Adherence was assessed over time. We investigated the association between SES and adherence using multivariable mixed logistic regression, stratifying by age (below/above 65 years) and two periods (before/after June 2021, to account for changes in vaccine coverage and epidemiological situation). Results: Adherence was high across all SES strata before June 2021. After, participants with higher equivalised disposable income were less likely to adhere to preventive measures compared to participants in the first (low) quartile [second (Adj.OR, 95% CI) (0.56, 0.37-0.85), third (0.38, 0.23-0.64), fourth (0.60, 0.36-0.98)]. We observed similar results for education. Conclusion: No differences by SES were found during the period with high SARS-CoV-2 incidence rates and stringent measures. Following the broad availability of vaccines, lower incidence, and eased measures, differences by SES started to emerge. Our study highlights the need for contextual interpretation when assessing SES impact on adherence to preventive measures.


Subject(s)
COVID-19 , SARS-CoV-2 , Social Class , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Switzerland/epidemiology , Male , Female , Middle Aged , Adult , Aged , Cohort Studies , Patient Compliance/statistics & numerical data , Pandemics
3.
Inorg Chem ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008564

ABSTRACT

We prepare iron(II) and iron(III) complexes with polydentate ligands that contain quinols, which can act as electron proton transfer mediators. Although the iron(II) complex with N-(2,5-dihydroxybenzyl)-N,N',N'-tris(2-pyridinylmethyl)-1,2-ethanediamine (H2qp1) is inactive as an electrocatalyst, iron complexes with N,N'-bis(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H4qp2) and N-(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H2qp3) were found to be much more active and more selective for water production than a previously reported cobalt-H2qp1 electrocatalyst while operating at low overpotentials. The catalysts with H2qp3 can enter the catalytic cycle as either Fe(II) or Fe(III) species; entering the cycle through Fe(III) lowers the effective overpotential. On the basis of their TOF0 values, the successful iron-quinol complexes are better electrocatalysts for oxygen reduction than previously reported iron-porphyrin compounds, with the Fe(III)-H2qp3 arguably being the best homogeneous electrocatalyst for this reaction. With iron, the quinol-for-phenol substitution shifts the product selectivity from H2O2 to water with little impact on the overpotential, but unlike cobalt, this substitution also greatly improves the activity, as assessed by TOFmax, by hastening the protonation and oxygen binding steps. The addition of a second quinol further enhances the activity and selectivity for water but modestly increases the effective overpotential.

4.
Brain Pathol ; : e13288, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982662

ABSTRACT

Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

5.
Transl Stroke Res ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980519

ABSTRACT

Cerebral cavernous malformation (CCM) is a hemorrhagic cerebrovascular disease where lesions develop in the setting of endothelial mutations of CCM genes, with many cases also harboring somatic PIK3CA gain of function (GOF) mutations. Rapamycin, an mTORC1 inhibitor, inhibited progression of murine CCM lesions driven by Ccm gene loss and Pik3ca GOF, but it remains unknown if rapamycin is beneficial in the absence of induction of Pik3ca GOF. We investigated the effect of rapamycin at three clinically relevant doses on lesion development in the Ccm3-/-PDGFb-icreERPositive murine model of familial CCM disease, without induction of Pik3ca GOF. Lesion burden, attrition, and acute and chronic hemorrhaging were compared between placebo and rapamycin-treated mice. Plasma miRNome was compared to identify potential biomarkers of rapamycin response. Outlier, exceptionally large CCM lesions (> 2 SD above the mean lesion burden) were exclusively observed in the placebo group. Rapamycin, across all dosages, may have prevented the emergence of large outlier lesions. Yet rapamycin also appeared to exacerbate mean lesion burden of surviving mice when outliers were excluded, increased attrition, and did not alter hemorrhage. miR-30c-2-3p, decreased in rapamycin-treated mouse plasma, has gene targets in PI3K/AKT and mTOR signaling. Progression of outlier lesions in a familial CCM model may have been halted by rapamycin treatment, at the potential expense of increased mean lesion burden and increased attrition. If confirmed, this can have implications for potential rapamycin treatment of familial CCM disease, where lesion development may not be driven by PIK3CA GOF. Further studies are necessary to determine specific pathways that mediate potential beneficial and detrimental effects of rapamycin treatment, and whether somatic PIK3CA mutations drive particularly aggressive lesions.

6.
Int J Pediatr Otorhinolaryngol ; 183: 112044, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39029310

ABSTRACT

OBJECTIVES: In the pediatric population, nasal septal perforations (NSP) are rare, and management is not well described. The use of various techniques has been reported in adults, including the use of interposition grafts, however this technique has not been described in the pediatric population. Our hypothesis is that the closure rate using absorbable d-lactide and l-lactide (each 50 %), polymer (PDLLA) plates as interposition grafts with temporalis fascia for NSP repair in the pediatric population will be an effective method compared to previous techniques. METHODS: Chart review was performed on patients who underwent NSP repair before June 2021, results were compared to a prospective evaluation of an interposition plate graft for repair at a tertiary care children's hospital. RESULTS: Fifteen patients via previous techniques and 5 patients via PDLLA and fascia graft were reviewed. Etiology of perforations included 45 % idiopathic, 25 % traumatic, and 15 % iatrogenic. In the previous techniques group, 10 were male, mean (median) age 14.4 years (15.2). Average size of NSP was 12.6 mm ± 6.6 mm (SD). 14/15 (93 %) patients had resolution of symptoms at 10-week follow-up, and 2/15 (13 %) required repeat repair. Five prospective patients were repaired with a PDLLA and fascia interposition graft, 4 were female, mean (median) age 14.6 years (Nassif and Scott, 2021 Feb 1) [14]. Average size of NSP was 11 mm ± 2.2 mm (SD). 100 % had resolution of symptoms at 10-week follow-up, 0 needed repeat surgery. No significant difference was found in size of NSP or in need for repeat procedure (p > 0.05) between the groups. CONCLUSION: Use of absorbable PDLLA interposition grafts with temporalis fascia for NSP repair in the pediatric population is effective at closing and resolving symptoms associated with NSP.

7.
Clin Neurophysiol ; 165: 1-15, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38941959

ABSTRACT

OBJECTIVE: Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application. METHODS: In this study, seven patients with idiopathic Parkinson's disease and one with familial Parkinson's disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations. RESULTS: While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block). CONCLUSION: We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson's disease to rapidly control pathological subthalamic beta oscillations. SIGNIFICANCE: Fully-implanted DBS electrode-guided neurofeedback is feasible and can now be explored over extended timespans.

8.
J Water Health ; 22(6): 1044-1052, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38935455

ABSTRACT

Current methods for testing water for faecal contamination rely on the culture of faecal indicator bacteria (FIB; Escherichia coli and Enterococci) that take 24-48 h, which leads to delays in taking proactive measures and poses a risk to public health. More rapid methods are therefore required. Here, we have tested a rapid, portable assay (Bacterisk) that detects the bacterial biomarker endotoxin in 30 min to quantify the bacterial biomass present, to evaluate 159 coastal water samples and to compare the results with the traditional culture of FIB. There was a significant correlation between the Bacterisk data given in endotoxin risk (ER) units and FIB culture that could accurately distinguish between poor and sufficient or good quality bathing water using the EU bathing directive values. Receiver operating characteristic analysis was used to determine the optimal ER threshold for coastal water samples, and the area under the curve was 0.9176 with a p-value of <0.0001. The optimal threshold was 7,300 ER units with a sensitivity of 95.45% and a specificity of 83.48%. In conclusion, we have shown that the Bacterisk assay provides a rapid and easy-to-use in situ method to assess bathing water quality.


Subject(s)
Endotoxins , Environmental Monitoring , Feces , Seawater , Feces/microbiology , Endotoxins/analysis , Environmental Monitoring/methods , Seawater/microbiology , Risk Assessment , Biomarkers/analysis , Water Microbiology , Bathing Beaches/standards , Escherichia coli/isolation & purification , Water Quality
9.
Brain Stimul ; 17(4): 769-779, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906529

ABSTRACT

BACKGROUND: Enhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, could potentially benefit patients with Parkinson's disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in real-time in the surface EEG signal. OBJECTIVE: We aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and assess the electrophysiological changes related to PTAS. METHODS: We recruited patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients underwent three full-night recordings, including one between-surgeries recording and two during rehabilitation, one with DBS+ (on) and one with DBS- (off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions. RESULTS: Our results show that during NREM sleep, slow waves of the cortex and STN are time-locked. PTAS application resulted in power and coherence changes, which can be detected in STN-LFP. CONCLUSION: Our findings suggest the feasibility of implementing PTAS using solely STN-LFP signal for slow wave detection, thus without a need for an external EEG device alongside the implanted neurostimulator. Moreover, we propose options for more efficient STN-LFP signal preprocessing, including different referencing and filtering to enhance the reliability of cortical slow wave detection in STN-LFP recordings.

10.
Vaccines (Basel) ; 12(6)2024 May 31.
Article in English | MEDLINE | ID: mdl-38932330

ABSTRACT

The effectiveness of COVID-19 vaccines depends on widespread vaccine uptake. Employing a telephone-administered weighted survey with 19,502 participants, we examined the determinants of COVID-19 vaccine acceptance among adults in Texas. We used multiple regression analysis with LASSO-selected variables to identify factors associated with COVID-19 vaccine uptake and intentions to receive the vaccine among the unvaccinated. The prevalence of unvaccinated individuals (22%) was higher among those aged 18-39, males, White respondents, English speakers, uninsured individuals, those facing financial challenges, and individuals expressing no concern about contracting the illness. In a fully adjusted regression model, higher odds of being unvaccinated were observed among males (aOR 1.11), the uninsured (aOR 1.38), smokers (aOR 1.56), and those facing financial struggles (aOR 1.62). Conversely, Asians, Blacks, and Hispanics were less likely to be unvaccinated compared to Whites. Among the unvaccinated, factors associated with stronger intent to receive the vaccine included age (over 65 years), Black and Hispanic ethnicity, and perceived risk of infection. Hispanic individuals, the uninsured, those covered by public insurance, and those facing financial challenges were more likely to encounter barriers to vaccine receipt. These findings underscore the importance of devising tailored strategies, emphasizing nuanced approaches that account for demographic, socioeconomic, and attitudinal factors in vaccine distribution and public health interventions.

11.
Nat Rev Immunol ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862638

ABSTRACT

Malaria, caused by infection with Plasmodium parasites, drives multiple regulatory responses across the immune landscape. These regulatory responses help to protect against inflammatory disease but may in some situations hamper the acquisition of adaptive immune responses that clear parasites. In addition, the regulatory responses that occur during Plasmodium infection may negatively affect malaria vaccine efficacy in the most at-risk populations. Here, we discuss the specific cellular mechanisms of immunoregulatory networks that develop during malaria, with a focus on knowledge gained from human studies and studies that involve the main malaria parasite to affect humans, Plasmodium falciparum. Leveraging this knowledge may lead to the development of new therapeutic approaches to increase protective immunity to malaria during infection or after vaccination.

12.
Oxf J Leg Stud ; 44(2): 376-404, 2024.
Article in English | MEDLINE | ID: mdl-38855119

ABSTRACT

The 18th century is often treated by scholars as a period of juristic consensus. This article argues, in contrast, that the late 18th century saw the emergence of rival 'Patriot' and 'Tory' legal traditions. Through a detailed study of the jurisprudence of Lords Camden and Mansfield-who were both pillars of the law, as well as political and juristic rivals-we show that they differed systematically in their understanding of the common law, and that those differences had a partisan cast: although they were not crude attempts to instrumentalise law to political ends, their political and jurisprudential commitments influenced each other and emerged from the same intellectual roots. We place these differences in the context of the fragmentation of 18th-century Whig politics, and argue that they have important implications for how we understand and make use of the common law tradition in present-day scholarship.

13.
Cell Syst ; 15(6): 544-562.e8, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38861992

ABSTRACT

Most biological processes are regulated by signaling modules that bind to short linear motifs. For protein kinases, substrates may have full or only partial matches to the kinase recognition motif, a property known as "substrate quality." However, it is not clear whether differences in substrate quality represent neutral variation or if they have functional consequences. We examine this question for the kinase CK2, which has many fundamental functions. We show that optimal CK2 sites are phosphorylated at maximal stoichiometries and found in many conditions, whereas minimal substrates are more weakly phosphorylated and have regulatory functions. Optimal CK2 sites tend to be more conserved, and substrate quality is often tuned by selection. For intermediate sites, increases or decreases in substrate quality may be deleterious, as we demonstrate for a CK2 substrate at the kinetochore. The results together suggest a strong role for substrate quality in phosphosite function and evolution. A record of this paper's transparent peer review process is included in the supplemental information.


Subject(s)
Casein Kinase II , Casein Kinase II/metabolism , Phosphorylation , Humans , Substrate Specificity , Kinetochores/metabolism , Evolution, Molecular , Binding Sites
14.
Foods ; 13(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38890961

ABSTRACT

The aim of the present research was to determine if the developed ovo-vegetarian sausage (SO), which was made with 15% chickpea flour, 51% albumin and 34% soy protein concentrate, exhibited improved physicochemical and sensory characteristics compared to vegetarian sausages available on the local market (classic vegan sausage, SC; vegan fine herb sausage, SH; and quinoa sausage, SQ). According to the physicochemical results, the developed sample, SO, presented significant differences (p < 0.05) compared to the others, including higher protein content, lower pH and a higher a* value. Three types of sensory analyses were conducted-flash profile, overall liking and purchase intention (to determine consumers' willingness to purchase the product)-with the first involving 15 consumers and the second and third involving 60 participants each. Descriptors for each sample were determined using the vocabulary provided by consumers in the flash profile analysis. Descriptors for SO included 'elastic', 'smell of cooked corn', 'characteristic flavor', 'pasty', 'soft' and 'pastel color', contributing to its greater overall liking and purchase intention compared to the others. Through the hierarchical multiple factor analysis, a positive correlation was observed between the texture and sensory descriptors of the flash profile. Conversely, a correlation was found between the physicochemical characteristics (pH, aw, color) and overall liking and purchase intention.

15.
Influenza Other Respir Viruses ; 18(6): e13333, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38845394

ABSTRACT

BACKGROUND: There is debate about the causes of the recent birth rate decline in high-income countries worldwide. During the pandemic, concern about the effects on reproductive health has caused vaccine hesitancy. We investigated the association of SARS-CoV-2 vaccination and infection with involuntary childlessness. METHODS: Females in fertility age within a prospective multicenter cohort of healthcare workers (HCW) were followed since August 2020. Data on baseline health, SARS-CoV-2-infection, and vaccination were obtained and regularly updated, in which serum samples were collected repetitively and screened for anti-nucleocapsid and anti-spike antibodies. In October 2023, participants indicated the presence of involuntary childlessness with onset during the pandemic, whereas those indicating an onset before the pandemic were excluded. The association of involuntary childlessness and SARS-CoV-2-vaccination and infection was investigated using univariable and multivariable analysis. Sensitivity analysis was performed to compare those reporting involuntary childlessness with those birthing a child since 2020. RESULTS: Of 798 participants, 26 (3.2%) reported involuntary childlessness starting since the pandemic. Of the involuntary childless women, 73.1% (19/26) were vaccinated compared to 86.0% (664/772) without involuntary childlessness (p = 0.73). SARS-CoV-2 infection was reported by 76.9% (20/26) compared to 72.4% (559/772) of controls (p = 0.64). Neither SARS-CoV-2 vaccination (aOR 0.91 per dose, 95%CI 0.67-1.26) nor infection (aOR per infection 1.05, 95%CI 0.62-1.71) was associated with involuntary childlessness. Sensitivity analysis confirmed these results. CONCLUSIONS: Among female HCW of fertility age, 3.2% indicated involuntary childlessness, which is comparable to pre-pandemic data. No association between involuntary childlessness and SARS-CoV-2 vaccination or infection was found.


Subject(s)
COVID-19 Vaccines , COVID-19 , Health Personnel , SARS-CoV-2 , Vaccination , Humans , Female , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/immunology , Health Personnel/statistics & numerical data , Adult , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Prospective Studies , Vaccination/statistics & numerical data , Cohort Studies , Vaccination Hesitancy/statistics & numerical data , Middle Aged
16.
J Man Manip Ther ; : 1-7, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768018

ABSTRACT

OBJECTIVES: To assess needle placement accuracy in the rectus abdominis (RA) muscle during dry needling (DN) without entering the peritoneum. METHODS: Two physical therapists performed DN on a cadaver, making 10 attempts each to needle the RA without entering the peritoneum. Techniques followed two common DN approaches. Ultrasound verified needle depth and safety. RESULTS: Seventy percent of attempts were recorded as safe needle placement, while 30% were unsafe. Accurate RA needle placement without peritoneal entry occurred in 55% of attempts. DISCUSSION/CONCLUSION: Inadvertent peritoneal needle placement during RA DN poses risks regardless of experience. Ultrasound guidance may enhance safety and precision in clinical practice.

17.
J Allergy Clin Immunol Glob ; 3(3): 100267, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38800615

ABSTRACT

Background: Forkhead box protein N1 (FOXN1) transcription factor plays an essential role in the development of thymic epithelial cells, required for T-cell differentiation, maturation, and function. Biallelic pathogenic variants in FOXN1 cause severe combined immunodeficiency (SCID). More recently, heterozygous variants in FOXN1, identified by restricted gene panels, were also implicated with causing a less severe and variable immunodeficiency. Objective: We undertook longitudinal follow-up and advanced genetic investigations, including whole exome sequencing and whole genome sequencing, of newborns with a heterozygous variant in FOXN1. Methods: Five patients (3 female, 2 male) have been followed since they were first detected with low T-cell receptor excision circles during newborn screening for SCID. Patients underwent immune evaluation as well as genetic testing, including a primary immunodeficiency panel, whole exome sequencing, and whole genome sequencing in some cases. Results: Median follow-up time was 6.5 years. Initial investigations revealed low CD3+ T lymphocytes in all patients. One patient presented with extremely low lymphocyte counts and depressed phytohemagglutinin responses leading to a tentative diagnosis of SCID. Over a period of 2 years, CD3+ T-cell counts rose, although in some patients it remained borderline low. One of 5 children continues to experience recurrent upper respiratory infections and asthma episodes. The remaining are asymptomatic except for eczema in 2 of 5 cases. Lymphocyte proliferation responses to phytohemagglutinin were initially low in 3 patients but normalized by age 10 months. In 3 of 5 cases, T lymphocyte counts remain low/borderline low. Conclusion: In cases of monoallelic FOXN1 variants, using whole exome sequencing and whole genome sequencing to rule out possible other significant pathogenic variants allowed us to proceed with confidence in a conservative manner, even in extreme cases consistent with newborn screen-positive early presentation of SCID.

18.
Front Psychiatry ; 15: 1377205, 2024.
Article in English | MEDLINE | ID: mdl-38818020

ABSTRACT

Messages regarding climate change that are intended to stimulate responsible engagement can impact our mental health in both positive and negative ways, which in turn can increase or limit the potential engagement being sought through those very messages. Increasingly alarmist environmental metaphors are being brought into question due to their possibly detrimental impact on mental health and well-being, and in their place, relational environmental metaphors are proffered to instill hopeful and constructive individual and collective engagement for responsible climate action. This article discusses how both alarmist and relational environmental metaphors interact with eco-emotions. It proposes, in light of concepts arising from Porges' Polyvagal Theory - on the psychophysiology of autonomic states created in contexts of threatening cues and feelings of safety and connection -, that relational environmental metaphors are preferable for stimulating responsible collective engagement and fostering global well-being in the midst of climate change.

19.
Swiss Med Wkly ; 154: 3734, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38689545

ABSTRACT

AIMS OF THE STUDY: We aimed to assess the extent of SARS-CoV-2 humoral immunity elicited by previous infections and/or vaccination among healthcare workers, and to identify reasons why healthcare workers decided against vaccination. METHODS: This nested cross-sectional study included volunteer healthcare workers from 14 healthcare institutions in German-speaking Switzerland. In January 2021, SARS-CoV-2 vaccines were available for healthcare workers. In May and June 2022, participants answered electronic questionnaires regarding baseline characteristics including SARS-CoV-2 vaccination status (with one or more vaccine doses defined as vaccinated) and previous SARS-CoV-2 infections. Unvaccinated participants indicated their reasons for non-vaccination. Participants underwent testing for SARS-CoV-2 anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies. Antibody prevalence was described across age groups. In addition, we performed multivariable logistic regression to identify baseline characteristics independently associated with non-vaccination and described reasons for non-vaccination. RESULTS: Among 22,438 eligible employees, 3,436 (15%) participated; the median age was 43.7 years (range 16-73), 2,794 (81.3%) were female, and 1,407 (47.7%) identified as nurses; 3,414 (99.4%) underwent serology testing, among whom 3,383 (99.0%) had detectable anti-S (3,357, 98.3%) antibodies, anti-N (2,396, 70.1%) antibodies, or both (2,370, 69.4%). A total of 296 (8.6%) healthcare workers were unvaccinated, whereas 3,140 (91.4%) were vaccinated. In multivariable analysis, age (adjusted OR [aOR] 1.02 per year, 95% CI 1.01-1.03), being a physician (aOR 3.22, 95% CI 1.75-5.92) or administrator (aOR 1.88, 95% CI 1.27-2.80), and having higher education (aOR 2.23, 95% CI 1.09-4.57) were positively associated with vaccine uptake, whereas working in non-acute care (aOR 0.58, 95% CI 0.34-0.97), active smoking (aOR 0.68, 95% CI 0.51-0.91), and taking prophylactic home remedies against SARS-CoV-2 (aOR 0.42, 95% CI 0.31-0.56) were negatively associated. Important reasons for non-vaccination were a belief that the vaccine might not have long-lasting immunity (267/291, 92.1%) and a preference for gaining naturally acquired instead of vaccine-induced immunity (241/289, 83.4%). CONCLUSIONS: Almost all healthcare workers in our cohort had specific antibodies against SARS-CoV-2 from natural infection and/or from vaccination. Young healthcare workers and those working in non-acute settings were less likely to be vaccinated, whereas physicians and administrative staff showed higher vaccination uptake. Presumed ineffectiveness of the vaccine is an important reason for non-vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Health Personnel , SARS-CoV-2 , Humans , Switzerland , Cross-Sectional Studies , COVID-19/prevention & control , COVID-19/immunology , Health Personnel/statistics & numerical data , Female , Male , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Adult , Middle Aged , Antibodies, Viral/blood , Vaccination/statistics & numerical data , Young Adult , Adolescent , Immunity, Humoral , Surveys and Questionnaires , Aged
20.
Death Stud ; : 1-9, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698573

ABSTRACT

Although scholars note advantages and disadvantages to using humor and profanity, influential leaders in the Death Positive Movement (DPM) use both message features to motivate end-of-life (EOL) advance care planning (ACP). Through the lens of expectancy violations theory (EVT), this study examined relationships between perceived humor, profanity in messages, trait profanity use in receivers, perceived offensiveness, perceived speaker effectiveness, and perceived message effectiveness. Participants (N = 604) were randomly exposed to a podcast about ACP containing clean humor, profane humor, or no humor. Results indicated that profanity and perceived humor were positively related to offensiveness, and offensiveness was negatively related to perceived speaker and message effectiveness. When perceived as non-offensive, perceived humor was positively related to perceived speaker and message effectiveness. Surprisingly, profane messages offended profane receivers more than they offended less-profane receivers. These results suggest that to be maximally effective, ACP motivators should use humor cautiously and avoid profanity.

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