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1.
BMJ Open ; 14(6): e075110, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830741

ABSTRACT

INTRODUCTION: Screening for atrial fibrillation (AF) in the general population may help identify individuals at risk, enabling further assessment of risk factors and institution of appropriate treatment. Algorithms deployed on wearable technologies such as smartwatches and fitness bands may be trained to screen for such arrhythmias. However, their performance needs to be assessed for safety and accuracy prior to wide-scale implementation. METHODS AND ANALYSIS: This study will assess the ability of the WHOOP strap to detect AF using its WHOOP Arrhythmia Notification Feature (WARN) algorithm in an enriched cohort with a 2:1 distribution of previously diagnosed AF (persistent and paroxysmal) and healthy controls. Recruited participants will collect data for 7 days with the WHOOP wrist-strap and BioTel ePatch (electrocardiography gold-standard). Primary outcome will be participant level sensitivity and specificity of the WARN algorithm in detecting AF in analysable windows compared with the ECG gold-standard. Similar analyses will be performed on an available epoch-level basis as well as comparison of these findings in important subgroups. ETHICS AND DISSEMINATION: The study was approved by the ethics board at the study site. Participants will be enrolled after signing an online informed consent document. Updates will be shared via clinicaltrials.gov. The data obtained from the conclusion of this study will be presented in national and international conferences with publication in clinical research journals. TRIAL REGISTRATION NUMBER: NCT05809362.


Subject(s)
Algorithms , Atrial Fibrillation , Wearable Electronic Devices , Humans , Atrial Fibrillation/diagnosis , Electrocardiography , Male , Female , Observational Studies as Topic , Middle Aged , Adult , Arrhythmias, Cardiac/diagnosis
2.
Biomedicines ; 12(3)2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38540194

ABSTRACT

In Long COVID, dysfunction in the pituitary-adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary-adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.

3.
Schizophr Res ; 267: 113-121, 2024 May.
Article in English | MEDLINE | ID: mdl-38531158

ABSTRACT

A decreased expression of specific interneuron subtypes, containing either the calcium binding protein parvalbumin (PV) or the neurotransmitter somatostatin (SST), are observed in the cortex and hippocampus of both patients with schizophrenia and rodent models used to study the disorder. Moreover, preclinical studies suggest that this loss of inhibitory function is a key pathological mechanism underlying the symptoms of schizophrenia. Interestingly, decreased expression of Lhx6, a key transcriptional regulator specific to the development and migration of PV and SST interneurons, is seen in human postmortem studies and following multiple developmental disruptions used to model schizophrenia preclinically. These results suggest that disruptions in interneuron development in utero may contribute to the pathology of the disorder. To recapitulate decreased Lhx6 expression during development, we used in utero electroporation to introduce an Lhx6 shRNA plasmid and knockdown Lhx6 expression in the brains of rats on gestational day 17. We then examined schizophrenia-like neurophysiological and behavioral alterations in the offspring once they reached adulthood. In utero Lhx6 knockdown resulted in increased ventral tegmental area (VTA) dopamine neuron population activity and a sex-specific increase in locomotor response to a psychotomimetic, consistent with positive symptomology of schizophrenia. However, Lhx6 knockdown had no effect on social interaction or spatial working memory, suggesting behaviors associated with negative and cognitive symptom domains were unaffected. These results suggest that knockdown of Lhx6 during development results in neurophysiological and behavioral alterations consistent with the positive symptom domain of schizophrenia in adult rats.


Subject(s)
Disease Models, Animal , LIM-Homeodomain Proteins , Schizophrenia , Transcription Factors , Animals , Schizophrenia/metabolism , Schizophrenia/physiopathology , Schizophrenia/genetics , Female , Male , LIM-Homeodomain Proteins/genetics , LIM-Homeodomain Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Rats , Pregnancy , Gene Knockdown Techniques , Ventral Tegmental Area/metabolism , Ventral Tegmental Area/physiopathology , Interneurons/metabolism , Interneurons/physiology , Rats, Sprague-Dawley , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/physiology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , RNA, Small Interfering
4.
Clin Rheumatol ; 43(5): 1615-1622, 2024 May.
Article in English | MEDLINE | ID: mdl-38436770

ABSTRACT

OBJECTIVES: (I) To identify and measure the clinical consequences of a delayed diagnosis in patients with primary obstetric antiphospholipid syndrome (POAPS), in terms of time and events associated to antiphospholipid syndrome (APS), and (II) to evaluate the impact of their treatment status on perinatal outcomes, before and after diagnosis. METHODS: This retrospective multicentre study included 99 POAPS women who were separated in two groups of timelines based on their diagnostic status: group 1: women who met the clinical criteria for POAPS; group 2: included the same patients from group 1 since they meet the laboratory criteria for APS. In group 1, we assessed the following variables: obstetric events, thrombotic events and time (years) to diagnosis of APS. We also compared perinatal outcomes between patients in group 1 vs. group 2. Women in group 2 were treated with standard of care for POAPS. Simple and multivariable logistic regression analyses were performed. RESULTS: Regarding the impact of the delay on diagnosis, a total of 87 APS-related events were recorded: 46 miscarriages, 32 foetal losses and 9 premature deliveries before the 34th week due to preeclampsia, and one thrombosis. The estimated rate of preventable events was 20.58 per year/100 patients. The mean diagnostic delay time was 4.27 years. When we compared both groups during pregnancy, we found that patients in group 1 (no treatment) had a higher association with pregnancy losses [OR = 6.71 (95% CI: 3.59-12.55), p < 0.0001]. CONCLUSION: Our findings emphasize the negative impact of POAPS underdiagnosis on patient health and the critical importance of a timely intervention to improve pregnancy outcomes. Key Points •Our study shows the relevance of underdiagnosis on primary obstetric antiphospholipid syndrome (POAPS). •These patients presented a high risk of APS-related events with each passing year. •Shorter diagnostic delay time was observed in the reference centres.


Subject(s)
Abortion, Spontaneous , Antiphospholipid Syndrome , Thrombosis , Pregnancy , Humans , Female , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/therapy , Antiphospholipid Syndrome/complications , Antibodies, Antiphospholipid , Delayed Diagnosis , Pregnancy Outcome , Thrombosis/complications
5.
Biomedicines ; 11(8)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37626797

ABSTRACT

Antiphospholipid antibodies (APLA) are strongly associated with thrombosis seen in patients with antiphospholipid syndrome. In COVID-19, thrombosis has been observed as one of the main comorbidities. In patients hospitalised for COVID-19, we want to check whether APLA positivity is associated with COVID-19-related thrombosis, inflammation, severity of disease, or long COVID-19. We enrolled 92 hospitalised patients with COVID-19 between March and April 2020 who were tested for 18 different APLAs (IgG and IgM) with a single line-immunoassay test. A total of 30 healthy blood donors were used to set the cut-off for each APLA positivity. Of the 92 COVID-19 inpatients, 30 (32.61%; 95% CI [23.41-43.29]) tested positive for APLA, of whom 10 (33.3%; 95% CI [17.94-52.86]) had more than one APLA positivity. Anti-phosphatidylserine IgM positivity was described in 5.4% of inpatients (n = 5) and was associated with the occurrence of COVID-19-related thrombosis (p = 0.046). Anti-cardiolipin IgM positivity was the most prevalent among the inpatients (n = 12, 13.0%) and was associated with a recorded thrombosis in their clinical history (p = 0.044); however, its positivity was not associated with the occurrence of thrombosis during their hospitalisation for COVID-19. Anti-phosphatidylinositol IgM positivity, with a prevalence of 5.4% (n = 5), was associated with higher levels of interleukin (IL)-6 (p = 0.007) and ferritin (p = 0.034). Neither of these APLA positivities was a risk factor for COVID-19 severity or a predictive marker for long COVID-19. In conclusion, almost a third of COVID-19 inpatients tested positive for at least one APLA. Anti-phosphatidylserine positivity in IgM class was associated with thrombosis, and anti-phosphatidylinositol positivity in IgM class was associated with inflammation, as noticed by elevated levels of IL-6. Thus, testing for non-criteria APLA to assess the risk of clinical complications in hospitalised COVID-19 patients might be beneficial. However, they were not related to disease severity or long COVID-19.

6.
Int J Mol Sci ; 24(14)2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37511546

ABSTRACT

Of the 35 million people in the world suffering from Alzheimer's Disease (AD), up to half experience comorbid psychosis. Antipsychotics, used to treat psychosis, are contraindicated in elderly patients because they increase the risk of premature death. Reports indicate that the hippocampus is hyperactive in patients with psychosis and those with AD. Preclinical studies have demonstrated that the ventral hippocampus (vHipp) can regulate dopamine system function, which is thought to underlie symptoms of psychosis. A viral-mediated approach was used to express mutated human genes known to contribute to AD pathology: the Swedish (K670N, M671L), Florida (I716V), and London (V717I) mutations of amyloid precursor protein and two mutations (M146L and L286V) of presenilin 1 specifically in the vHipp, to investigate the selective contribution of AD-like pathology in this region. We observed a significant increase in dopamine neuron population activity and behavioral deficits in this AD-AAV model that mimics observations in rodent models with psychosis-like symptomatologies. Further, systemic administration of MP-III-022 (α5-GABAA receptor selective positive allosteric modulator) was able to reverse aberrant dopamine system function in AD-AAV rats. This study provides evidence for the development of drugs that target α5-GABAA receptors for patients with AD and comorbid psychosis.


Subject(s)
Alzheimer Disease , Psychotic Disorders , Rats , Humans , Animals , Aged , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Receptors, GABA-A/metabolism , Dopamine/metabolism , Psychotic Disorders/drug therapy , Psychotic Disorders/metabolism , Hippocampus/metabolism , Disease Models, Animal
7.
Schizophr Res ; 258: 1-8, 2023 08.
Article in English | MEDLINE | ID: mdl-37364392

ABSTRACT

BACKGROUND: In 1950, Drs. Chevigny and Braverman authored a book about people's attitudes and prejudices toward the blind, noting that out of the thousands of schizophrenia patients they and others had treated, not one was blind. This led some to the intriguing hypothesis that congenital blindness may provide protection against schizophrenia. In this study, we directly examined whether congenital blindness protects against a schizophrenia-related phenotype in the methylazoxymethanol acetate (MAM) rodent model. DESIGN: Enucleation surgeries were performed on pups of MAM- or saline-treated rats on post-natal day 10. Once pups reached adulthood, male and female rats were evaluated for schizophrenia-like phenotypes using behavioral and electrophysiological measures. Consistent with previous work, MAM-treated rats display elevated dopamine neuron population activity, deficits in pre-pulse inhibition of startle, and hypersensitivity to psychomotor stimulants. RESULTS: Blindness did not protect against any of the MAM-induced phenotypes. Surprisingly, blindness in saline-treated rats caused changes in behavior and dopamine neuron activity. To examine the circadian rhythms of enucleated rats, we performed non-invasive measurements of corticosterone, a steroid hormone known to vary across the light/dark period, revealing blind rats display aberrant (non-cycling) corticosterone levels. CONCLUSIONS: Alterations in dopamine neuron activity and associated behaviors observed in blind rats are likely secondary to aberrant circadian regulation. This is the first preclinical study examining whether congenital blindness protects against a schizophrenia-like phenotype. While support of this hypothesis would have led to novel avenues of research and potential novel therapies, the results of current study suggest that blindness does not protect against schizophrenia.


Subject(s)
Rodentia , Schizophrenia , Rats , Male , Female , Animals , Rats, Sprague-Dawley , Schizophrenia/complications , Schizophrenia/chemically induced , Corticosterone , Methylazoxymethanol Acetate , Blindness/prevention & control , Phenotype , Disease Models, Animal
9.
Placenta ; 136: 29-34, 2023 05.
Article in English | MEDLINE | ID: mdl-37028222

ABSTRACT

INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.


Subject(s)
Antiphospholipid Syndrome , Pregnancy Complications , Female , Pregnancy , Humans , Male , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/epidemiology , Placenta , Antibodies, Antiphospholipid , Registries
10.
Int J Mol Sci ; 24(8)2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37108357

ABSTRACT

Antipsychotics increase the risk of death in elderly patients with Alzheimer's disease (AD). Thus, there is an immediate need for novel therapies to treat comorbid psychosis in AD. Psychosis has been attributed to a dysregulation of the dopamine system and is associated with aberrant regulation by the hippocampus. Given that the hippocampus is a key site of pathology in AD, we posit that aberrant regulation of the dopamine system may contribute to comorbid psychosis in AD. A ferrous amyloid buthionine (FAB) rodent model was used to model a sporadic form of AD. FAB rats displayed functional hippocampal alterations, which were accompanied by decreases in spontaneous, low-frequency oscillations and increases in the firing rates of putative pyramidal neurons. Additionally, FAB rats exhibited increases in dopamine neuron population activity and augmented responses to the locomotor-inducing effects of MK-801, as is consistent with rodent models of psychosis-like symptomatology. Further, working memory deficits in the Y-maze, consistent with an AD-like phenotype, were observed in FAB rats. These data suggest that the aberrant hippocampal activity observed in AD may contribute to dopamine-dependent psychosis, and that the FAB model may be useful for the investigation of comorbid psychosis related to AD. Understanding the pathophysiology that leads to comorbid psychosis in AD will ultimately lead to the discovery of novel targets for the treatment of this disease.


Subject(s)
Alzheimer Disease , Rats , Animals , Alzheimer Disease/pathology , Dopamine/pharmacology , Hippocampus , Dopaminergic Neurons/pathology , Amyloid , Amyloidogenic Proteins/pharmacology , Disease Models, Animal , Amyloid beta-Peptides/pharmacology
11.
Biol Psychiatry Glob Open Sci ; 3(1): 78-86, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36712569

ABSTRACT

Background: Aberrant dopamine neuron activity is attributable to hyperactivity in hippocampal subfields driving a pathological increase in dopamine neuron activity, which is positively correlated with psychosis in humans. Evidence indicates that hippocampal hyperactivity is due to loss of intrinsic GABAergic (gamma-aminobutyric acidergic) inhibition. We have previously demonstrated that hippocampal GABAergic neurotransmission can be modulated by targeting α5-GABAA receptors, which are preferentially expressed in hippocampal regions. Positive and negative allosteric modulators of α5-GABAA receptors (α5-PAMs and α5-NAMs) elicit effects on hippocampal-dependent behaviors. We posited that the selective manipulation of hippocampal inhibition, using α5-PAMs or α5-NAMs, would modulate dopamine activity in control rats. Further, α5-PAMs would reverse aberrant dopamine neuron activity in a rodent model with schizophrenia-related pathophysiologies (methylazoxymethanol acetate [MAM] model). Methods: We performed in vivo extracellular recordings of ventral tegmental area dopamine neurons in anesthetized rats to compare the effects of two novel, selective α5-PAMs (GL-II-73, MP-III-022), a nonselective α-PAM (midazolam), and two selective α5-NAMs (L-655,708, TB 21007) in control and MAM-treated male Sprague Dawley rats (n = 5-9). Results: Systemic or intracranial administration of selective α5-GABAA receptor modulators regulated dopamine activity. Specifically, both α5-NAMs increased dopamine neuron activity in control rats, whereas GL-II-73, MP-III-022, and L-655,708 attenuated aberrant dopamine neuron activity in MAM-treated rats, an effect mediated by the ventral hippocampus. Conclusions: This study demonstrated that α5-GABAA receptor modulation can regulate dopamine neuron activity under control or abnormal activity, providing additional evidence that α5-PAMs and α5-NAMs may have therapeutic applications in psychosis and other psychiatric diseases where aberrant hippocampal activity is present.

12.
Schizophr Bull Open ; 3(1): sgac067, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36387971

ABSTRACT

Aberrant dopamine system function is thought to contribute to the positive symptoms of schizophrenia. Clinical imaging studies have demonstrated that the largest dopamine abnormality in patients appears to be an increase in presynaptic dopamine activity. Indeed, studies utilizing [ 18 F]DOPA positive emission tomography reliably report increases in presynaptic dopamine bioavailability in patients and may serve as a biomarker for treatment response. The mechanisms contributing to this increased presynaptic activity in human patients is not yet fully understood, which necessitates the use of preclinical models. Dopamine system function can be directly examined in experimental animals using in vivo electrophysiology. One consistent finding from preclinical studies in rodent models used to study schizophrenia-like neuropathology is a 2-fold increase in the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), termed population activity. We posit that increased striatal dopamine synthesis capacity is attributed to an augmented VTA dopamine neuron population activity. Here, we directly test this hypothesis using [3H]DOPA ex vivo autoradiography, to quantify striatal dopamine synthesis capacity, in the methylazoxymethanol acetate (MAM) model, a validated rodent model displaying neurophysiological and behavioral alterations consistent with schizophrenia-like symptomatologies. Consistent with human imaging studies, dopamine synthesis capacity was significantly increased in dorsal and ventral striatal subregionis, including the caudate putamen and nucleus accumbens, of MAM-treated rats and associated with specific increases in dopamine neuron population activity. Taken together, these data provide a link between mechanistic studies in rodent models and clinical studies of increased presynaptic dopamine function in human subjects.

13.
Vaccines (Basel) ; 10(5)2022 May 20.
Article in English | MEDLINE | ID: mdl-35632569

ABSTRACT

Longitudinal data comparing SARS-CoV-2 serology in individuals following infection and vaccination over 12 months are limited. This study compared the magnitude, decay, and variability in serum IgG, IgA, and neutralizing activity induced by natural infection (n = 218) or mRNA vaccination in SARS-CoV-2 naïve (n = 143) or experienced (n = 122) individuals over time using enzyme-linked immunosorbent assays and an in vitro virus neutralization assay. Serological responses were found to be highly variable after natural infection compared with vaccination but durable through 12 months. Antibody levels in vaccinated, SARS-CoV-2 naïve individuals peaked by 1 month then declined through 9 months, culminating in non-detectable SARS-CoV-2-specific serum IgA. Individuals with both infection and vaccination showed SARS-CoV-2-specific IgG and IgA levels that were more robust and slower to decline than the other groups; neutralizing activity remained highest in this group at 9 months past vaccination. These data reinforce the benefit of vaccination after SARS-CoV-2 recovery.

14.
J Immigr Minor Health ; 24(5): 1375-1378, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35301642

ABSTRACT

The COVID-19 pandemic affected how adults with diabetes perform self-management, and impacts may be greater among vulnerable populations. We assessed the impact of the pandemic on diabetes self-management among adults with type 2 diabetes at a Federally Qualified Health Center. Participants were surveyed by phone in Spanish and English from July to October of 2020. Most respondents (74%) were Latino and preferred to speak Spanish, with mean age of 54 years and mean HbA1c of 9.2%. Fifty-three percent reported less physical activity during the pandemic. While 43% had more difficulty obtaining healthy food, 38% reported eating more healthfully. Sixty-one percent had increased difficulty accessing medical care. Many felt more socially isolated (49%) and stressed (51%). Changes in diabetes self-management were both positive and negative for majority Latino patients in this low-resource community, which may require tailored approaches to mitigate negative impacts of the pandemic on physical and mental health.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Self-Management , Adult , Humans , Middle Aged , COVID-19/epidemiology , COVID-19/pathology , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/therapy , Hispanic or Latino/psychology , Pandemics , Self-Management/psychology
15.
Lupus ; 31(3): 354-362, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35157809

ABSTRACT

OBJECTIVES: (1) To assess the clinical utility of the adjusted global antiphospholipid syndrome score (aGAPSS) to predict new obstetric events during follow-up in primary obstetric antiphospholipid syndrome (POAPS) patients under standard-of-care treatment (SC) based on the use of low-dose aspirin (LDA) + heparin and (2) to study the risk of a first thrombotic event and to evaluate whether stratification according to this score could help to identify POAPS patients who would benefit from long-term thromboprophylaxis. METHODS: This is a retrospective, multicentre study. 169 women with POAPS were evaluated for the presence of a new obstetric event and/or a first thrombotic event during follow-up [time period: 2008-2020, median: 7 years (6-12 years)]. The outcomes of 107 pregnancies from these POAPS patients with SC were studied to evaluate relapses. Simple and multivariable logistic regression analyses were performed. RESULTS: Regarding obstetric morbidity, only triple positivity for antiphospholipid antibodies (aPLs) [OR = 8.462 (95% CI: 2.732-26.210); p < 0.0001] was found to be a strong risk factor independently associated with treatment failure. On the other hand, triple positivity for aPLs [OR=10.44 (95% CI: 2.161-50.469), p = 0.004] and an aGAPSS ≥7 [OR = 1.621 (95% CI: 1.198-2.193), p = 0.002] were independent risk factors associated with a first thrombotic event. LDA was marginally associated with a decrease in the risk of thrombosis only in patients with aGAPSS ≥ 7 (p = 0.048). CONCLUSION: aGAPSS appears to be useful in predicting the occurrence of a first thrombotic event in POAPS patients, and these stratification of patients could be helpful in selecting patients who would benefit from thromboprophylaxis with LDA.


Subject(s)
Antiphospholipid Syndrome , Lupus Erythematosus, Systemic , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/drug therapy , Aspirin/therapeutic use , Female , Humans , Lupus Erythematosus, Systemic/complications , Pregnancy , Retrospective Studies , Thrombosis/complications , Thrombosis/prevention & control
16.
Pediatrics ; 149(2)2022 02 01.
Article in English | MEDLINE | ID: mdl-34981122

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been detected in human milk up to 6 weeks post-coronavirus disease 2019 (COVID-19) vaccination. We evaluated SARS-CoV-2-specific antibodies, neutralization activity, effect of pasteurization, and persistence through 6 months after vaccination. METHODS: This prospective longitudinal study enrolled 30 pregnant or lactating women. SARS-CoV-2 antibodies and neutralization capacity were analyzed using an enzyme-linked immunosorbent assay compared at prevaccination and 1, 3, and 6 months postvaccination, and through Holder pasteurization. RESULTS: Human milk SARS-CoV-2-specific IgG levels peaked at 1 month postvaccination and persisted above prevaccination levels for at least 6 months (P = .005). SARS-CoV-2-specific IgA was detected at 1 and 3 months (both P < .001) but waned by 6 months compared with baseline (P = .07). Milk SARS-CoV-2-specific IgG and IgA correlated with serum IgG at the same time point (R2 = 0.37, P < .001 and R2 = 0.19, P < .001). Neutralization activity was seen in 83.3%, 70.4%, and 25.0% of milk samples at 1, 3, and 6 months postvaccination. Neutralization most strongly correlated with SARS-CoV-2-specific IgG (R2 = 0.57, P < .001). Pre- and postpasteurization samples showed similar IgG (0.84 vs 1.07, P = .36) and neutralizing activity (57.7% vs 58.7% inhibition, P = .27), but lower IgM and IgA levels postpasteurization (0.09 vs 0.06, P = .004 and 0.21 vs 0.18, P = .043). CONCLUSIONS: The data suggest that human milk SARS-CoV-2-specific antibodies may be available to milk-fed infants for up to 6 months. In addition, donor milk from vaccinated mothers retain IgG and neutralizing activity.


Subject(s)
Antibodies, Viral/analysis , COVID-19 Vaccines , Milk, Human/chemistry , SARS-CoV-2/immunology , Adult , Breast Feeding , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Infant , Infant, Newborn , Lactation , Longitudinal Studies , Pasteurization , Prospective Studies
17.
Influenza Other Respir Viruses ; 16(2): 255-264, 2022 03.
Article in English | MEDLINE | ID: mdl-34668322

ABSTRACT

BACKGROUND: Age and obesity status are associated with severe outcomes among hospitalized individuals with COVID-19. It remains unclear whether age and obesity are risk factors for milder COVID-19 illness. METHODS: We prospectively enrolled SARS-CoV-2-exposed individuals. Participants recorded symptoms for 28 days and were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and serology. Type, number, and duration of symptoms and SARS-CoV-2 laboratory parameters were compared by age and obesity status. RESULTS: Of 552 individuals enrolled from June 2020 to January 2021, 470 (85.1%) tested positive for SARS-CoV-2 including 261 (55.5%) adults ≥18 years, 61 (13.0%) adolescents 12-17 years, and 148 (31.5%) children <12 years. Children had fewer symptoms (median 2 vs. 3, p < 0.001) lasting fewer days (median 5 vs. 7, p < 0.001) compared with adolescents/adults. Body mass index of 300 (63.8%) individuals classified with overweight or obesity (OWOB). Individuals with OWOB suffered more symptoms compared with individuals without OWOB (median 3 vs. 2, p = 0.037), including more cough and shortness of breath (p = 0.023 and 0.026, respectively). Adolescents with OWOB were more likely to be symptomatic (66.7% vs. 34.2%, p = 0.008) and have longer respiratory symptoms (median 7 vs. 4 days, p = 0.049) compared with adolescents without OWOB. Lower RT-PCR Ct values were found in children and symptomatic individuals compared with adolescent and adults and asymptomatic individuals, respectively (p = 0.001 and 0.022). CONCLUSIONS: Adolescents and adults with OWOB experience more respiratory symptoms from COVID-19 despite similar viral loads. These findings underscore the importance of vaccinating individuals with OWOB.


Subject(s)
COVID-19 , Adolescent , Adult , Child , Humans , Obesity , SARS-CoV-2 , Serologic Tests , Viral Load
18.
J Neurophysiol ; 126(4): 1361-1374, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34525322

ABSTRACT

Reaching movements performed from a crouched body posture require a shift of body weight from both arms to one arm. This situation has remained unexamined despite the analogous load requirements during step initiation and the many studies of reaching from a seated or standing posture. To determine whether the body weight shift involves anticipatory or exclusively reactive control, we obtained force plate records, hand kinematics, and arm muscle activity from 11 healthy right-handed participants. They performed reaching movements with their left and right arm in two speed contexts, "comfortable" and "as fast as possible," and two postural contexts, a less stable knees-together posture and a more stable knees-apart posture. Weight-shifts involved anticipatory postural actions (APAs) by the reaching and stance arms that were opposing in the vertical axis and aligned in the side-to-side axis similar to APAs by the legs for step initiation. Weight-shift APAs were correlated in time and magnitude, present in both speed contexts, more vigorous with the knees placed together, and similar when reaching with the dominant and nondominant arm. The initial weight-shift was preceded by bursts of muscle activity in the shoulder and elbow extensors (posterior deltoid and triceps lateral) of the reach arm and shoulder flexor (pectoralis major) of the stance arm, which indicates their causal role; leg muscles may have indirectly contributed but were not recorded. The strong functional similarity of weight-shift APAs during crouched reaching to human stepping and cat reaching suggests that they are a core feature of posture-movement coordination.NEW & NOTEWORTHY This work demonstrates that reaching from a crouched posture is preceded by bimanual anticipatory postural adjustments (APAs) that shift the body weight to the stance limb. Weight-shift APAs are more robust in an unstable body posture (knees together) and involve the shoulder and elbow extensors of the reach arm and shoulder flexor of the stance arm. This pattern mirrors the forelimb coordination of cats reaching and humans initiating a step.


Subject(s)
Anticipation, Psychological/physiology , Motor Activity/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology , Posture/physiology , Psychomotor Performance/physiology , Adult , Biomechanical Phenomena , Electromyography , Humans , Young Adult
20.
J Fish Biol ; 99(3): 818-830, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33900630

ABSTRACT

The Cephaloscyllium ventriosum shark is present in the artisanal fisheries of elasmobranchs on the western coast of Baja California Sur, Mexico. The main characteristics of the sexual maturation of this species based on individuals captured from off north-west Mexico in 2013-2016 are described. The size at maturity of this species was determined for the first time (total length 82 cm for females and 76 cm for males). Most females had one egg case per one uterus, and two per one uterus was an isolated event of low incidence. From the histological analysis of females, it was possible to show sperm storage in the oviducal gland. Fully developed sperm in immature organisms were identified in the testes. The main indicator of the maturity stage of males and their mating activity is the clasper. The present study provides evidence for a reliable estimation of the sexual maturity of these organisms, demonstrating the need for the combination of macroscopic and microscopic methods.


Subject(s)
Sharks , Animals , Biology , Female , Fisheries , Male , Mexico , Reproduction
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