RESUMO
Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.
Assuntos
Esclerose Lateral Amiotrófica , Caracteres Sexuais , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/metabolismo , Masculino , Feminino , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologiaRESUMO
Endocrine disorders are associated with joint pain and tendon injury in humans, but the effects in the horse are only starting to be understood. Similar patterns of clinical signs and injury appear to affect horses and humans for both orthopedic and endocrine disorders, supporting the use of a one-health approach to tackle these issues. In this Currents in One Health, we will discuss common equine endocrinopathies, current testing recommendations, dietary management, genetic predispositions, and endocrine disorders' effects on performance. Our aim is to use a one-health lens to describe current comparative research so that veterinarians can employ cutting-edge preventative, diagnostic, and therapeutic recommendations. Identified key gaps in knowledge include whether equine metabolic osteoarthritis exists, if steroid joint injections are safe in horses with endocrine disorders, and if the return to performance percentage improves with concurrent treatment of endocrine and musculoskeletal disorders. Key takeaways include that the relationship between endocrine disorders and musculoskeletal disease in the horse goes beyond laminitis to include lameness, muscle atrophy, suspensory ligament degeneration, osteochondritis dissecans, and potentially metabolic osteoarthritis. Approaches learned from human and equine comparative studies can offer insight into injury recognition and management, thus mitigating the impact of endocrine disorders on performance in both species. Readers interested in an in-depth description of current and future research involving pathophysiology, novel interventions, and multiomic approaches to identify individuals with athletic limitations induced by endocrine disorders are invited to read the companion Currents in One Health by Manfredi et al, AJVR, February 2023.
Assuntos
Doenças dos Cavalos , Saúde Única , Osteoartrite , Esportes , Humanos , Cavalos , Animais , Atletas , Osteoartrite/terapia , Osteoartrite/veterinária , Doenças dos Cavalos/diagnósticoRESUMO
Endocrinopathies affect multiple species in ever-increasing percentages of their populations, creating an opportunity to apply one-health approaches to determining creative preventative measures and therapies in athletes. Obesity and alterations in insulin and glucose dynamics are medical concerns that play a role in whole-body health and homeostasis in both horses and humans. The role and impact of endocrine disorders on the musculoskeletal, cardiovascular, and reproductive systems are of particular interest to the athlete. Elucidation of both physiologic and pathophysiologic mechanisms involved in disease processes, starting in utero, is important for development of prevention and treatment strategies for the health and well-being of all species. This review focuses on the unrecognized effects of endocrine disorders associated with the origins of metabolic disease; inflammation at the intersection of endocrine disease and related diseases in the musculoskeletal, cardiovascular, and reproductive systems; novel interventions; and diagnostics that are informed via multiomic and one-health approaches. Readers interested in further details on specific equine performance conditions associated with endocrine disease are invited to read the companion Currents in One Health by Manfredi et al, JAVMA, February 2023.
Assuntos
Doenças do Sistema Endócrino , Saúde Única , Humanos , Cavalos , Animais , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/terapia , Doenças do Sistema Endócrino/veterinária , Atletas , Insulina , PulmãoRESUMO
In this article we review complications to the peripheral nervous system that occur as a consequence of viral infections, with a special focus on complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We discuss neuromuscular complications in three broad categories; the direct consequences of viral infection, autoimmune neuromuscular disorders provoked by viral infections, and chronic neurodegenerative conditions which have been associated with viral infections. We also include discussion of neuromuscular disorders that are treated by immunomodulatory therapies, and how this affects patient susceptibility in the current context of the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is associated with direct consequences to the peripheral nervous system via presumed direct viral injury (dysgeusia/anosmia, myalgias/rhabdomyolysis, and potentially mononeuritis multiplex) and autoimmunity (Guillain Barré syndrome and variants). It has important implications for people receiving immunomodulatory therapies who may be at greater risk of severe outcomes from COVID-19. Thus far, chronic post-COVID syndromes (a.k.a: long COVID) also include possible involvement of the neuromuscular system. Whether we may observe neuromuscular degenerative conditions in the longer term will be an important question to monitor in future studies.
RESUMO
Nerve injury affecting the upper limb is a leading cause of lifelong disability. Damage to the nerves in the arm often causes weakness and somatosensory dysfunction ranging from numbness to pain. Previous studies show that combining brief bursts of electrical vagus nerve stimulation (VNS) with motor or tactile rehabilitation can restore forelimb function after median and ulnar nerve injury, which causes hyposensitivity of the ventral forelimb. Here, we sought to determine whether this approach would be similarly effective in a model of radial nerve injury that produces allodynia in the ventral forelimb. To test this, rats underwent complete transection of the radial nerve proximal to the elbow followed by tubular repair. In the first experiment, beginning ten weeks after injury, rats received six weeks of tactile rehabilitation, consisting of mechanical stimulation of either the dorsal or ventral region of the forepaw in the injured limb, with or without concurrent VNS. In a second experiment, a separate cohort of rats underwent six weeks of forelimb motor rehabilitative training with or without paired VNS. Contrary to findings in previous models of hyposensitivity, VNS therapy fails to improve recovery of either somatosensory or motor function in the forelimb after radial nerve injury. These findings describe initial evidence that pain may limit the efficacy of VNS therapy and thus highlight a characteristic that should be considered in future studies that seek to develop this intervention.
Assuntos
Neuralgia , Estimulação do Nervo Vago , Animais , Membro Anterior/fisiologia , Humanos , Neuralgia/terapia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Extremidade Superior , Nervo VagoRESUMO
As the coronavirus pandemic continues to evolve, so does the understanding of different presentations of disease. In this case report, we describe a patient whose presentation of COVID-19 was with acute icteric hepatitis without respiratory symptoms. This is the first case in the literature to our knowledge to report jaundice as the initial presentation of disease and adds to just a handful of cases in the literature of acute hepatitis as the sole presentation of COVID-19. Additionally, despite severe hepatitis, the patient had a benign course of COVID-19 and did not require aggressive medical care; this strays from conventional paradigms that associate severity of COVID-19 with a degree of aminotransferase elevation. The purpose of this report is to make physicians aware of acute icteric hepatitis as a presentation of COVID-19 infection and to facilitate discussion and further research in the area of COVID-19-induced hepatitis.
RESUMO
Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.
Assuntos
Infecções por Herpesviridae/virologia , Herpesvirus Equídeo 1/imunologia , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/virologia , Leucócitos Mononucleares/virologia , Transcriptoma/genética , Animais , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Perfilação da Expressão Gênica/métodos , Infecções por Herpesviridae/imunologia , Cavalos , Interleucina-6/genética , Interleucina-6/imunologia , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Doenças Respiratórias/genética , Doenças Respiratórias/imunologia , Doenças Respiratórias/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/virologia , Transcriptoma/imunologia , Regulação para Cima/genética , Regulação para Cima/imunologiaRESUMO
INTRODUCTION: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency. METHODS: A retrospective chart review was conducted using electronic medical records of patients seen at Children's Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males - both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation. RESULTS: Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2-5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2-5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001). CONCLUSIONS: These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the -pediatric population.
Assuntos
Hidrocortisona/sangue , Puberdade/fisiologia , Fatores Sexuais , Adolescente , Insuficiência Adrenal/sangue , Hormônio Adrenocorticotrópico/administração & dosagem , Índice de Massa Corporal , Criança , Pré-Escolar , Ritmo Circadiano , Feminino , Humanos , Masculino , Valores de Referência , Estudos RetrospectivosRESUMO
CASE DESCRIPTION: A 6-year-old castrated male Bactrian camel was evaluated because of a 14hour history of oliguria and stranguria that progressed to anuria. CLINICAL FINDINGS: Perineal urethral pulsations and intermittent tail flagging with no accompanying urination were observed. Ultrasonography of the urethra revealed multiple hyperechoic foci with shadowing artifact indicative of calculi present in the penile urethra distal to the sigmoid flexure. Rectal palpation revealed a pulsating hard urethra and intact distended urinary bladder. Further clinical examination was not possible because of challenges associated with handling the camel. TREATMENT AND OUTCOME: Urethral catheterization through a perineal urethral incision failed to achieve urinary bladder decompression. Tube cystostomy was performed to prevent bladder rupture. Urethrocystography performed 3 days after surgery revealed a urethral rupture at the level of the prepuce. Five weeks after surgery, the camel could urinate a steady stream via the urethrotomy site. Seven weeks after surgery, the cystostomy tube was removed, and the urethrotomy site was modified to provide a permanent urethral opening via perineal urethrostomy. During 6 years of subsequent periodic follow-up by telephone, the owner reported that the camel continued to do well and urinate through the revised opening. CLINICAL RELEVANCE: To the authors' knowledge, this is the first detailed description of a tube cystostomy in an adult camel with obstructive urolithiasis that includes information on the patient's long-term outcome. This technique was a viable option in the surgical management of obstructive urolithiasis in this camel and may be useful for other large camelids as well.
Assuntos
Camelus , Obstrução Uretral/veterinária , Urolitíase/veterinária , Animais , Cistostomia/métodos , Cistostomia/veterinária , Masculino , Uretra , Obstrução Uretral/cirurgia , Urolitíase/cirurgiaRESUMO
OBJECTIVE: To determine whether anesthesiologists need to rely on polysomnography (PSG) when predicting need for airway intervention during induction in patients with sleep-disordered breathing (SDB). METHODS: Prospective case-control observational study at a tertiary care pediatric hospital. Children between the ages of 2-17 undergoing tonsillectomy were divided into three groups: those presenting with OSA observed by history and/or physical examination alone (SDB; nâ¯=â¯33), those with OSA determined by preoperative PSG (OSA; nâ¯=â¯32), and a control group (nâ¯=â¯35) undergoing tonsillectomy for recurrent tonsillitis. An anesthesiologist ranked each case on the level of intervention required to maintain ventilation. RESULTS: Age, height and BMI were associated with greater induction difficulty (r'sâ¯>â¯.225, p'sâ¯<â¯.025). Compared to controls, induction difficulty was significantly greater for the SDB group (mean differenceâ¯=â¯-0.751, 95% confidence interval [CI]â¯=â¯-1.241, -0.261, pâ¯=â¯.003), but not for the OSA group (pâ¯=â¯.061). No significant difference in induction difficulty was observed between SDB and OSA groups. In a subgroup analysis of the OSA group, an apnea-hypopnea index (AHI)â¯>â¯10 correlated with increased level of intervention during induction (râ¯=â¯.228, pâ¯=â¯.022). Race was also associated with AHI >10 (odds ratioâ¯=â¯3.859, 95% CIâ¯=â¯1.485, 10.03, pâ¯=â¯.006). CONCLUSION: Children with OSA undergoing tonsillectomy require more airway intervention during induction than children with recurrent tonsillitis. Age and BMI were correlated with greater induction difficulty, suggesting that PSG data should be considered in light of these clinical characteristics to ensure an optimal postoperative course for children undergoing tonsillectomy.
Assuntos
Anestesia Geral , Apneia Obstrutiva do Sono/complicações , Tonsilectomia , Fatores Etários , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Polissonografia , Período Pós-Operatório , Estudos Prospectivos , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Tonsilite/cirurgiaRESUMO
BACKGROUND: Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). OBJECTIVES: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. ANIMALS: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). METHODS: Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. RESULTS: Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management.
Assuntos
Doenças do Pé/veterinária , Doenças dos Cavalos/metabolismo , Insulina/metabolismo , Síndrome Metabólica/veterinária , Obesidade/veterinária , Animais , Glicemia/análise , Feminino , Doenças do Pé/metabolismo , Teste de Tolerância a Glucose/veterinária , Casco e Garras , Cavalos , Insulina/sangue , Masculino , Síndrome Metabólica/metabolismo , Metabolômica , Obesidade/metabolismoRESUMO
A 13-month-old Holstein bull was presented for right-sided exophthalmos. Ophthalmologic examination noted that the animal was visual in both eyes, but that the right pupil was persistently dilated and very sluggish to constrict when stimulated with a bright light and that normal ocular motility was absent. Fundic examination of the right eye was normal as was a complete ophthalmologic examination of the left eye. Radiographs at presentation did not reveal the presence of sinusitis or other skull abnormalities. Initial treatment comprised intravenous antibiotics and anti-inflammatories for orbital inflammation over a 14-day period. There was no perceptible change in the appearance or neuro-ophthalmologic examination of the right eye during hospitalization. The animal was discharged to the owner's care, but 3 weeks later was found recumbent with unilateral strabismus of the left eye and a fixed right pupil. Due to the inability to rise and rapid deterioration, humane euthanasia was performed, and a full postmortem examination, preceded by a MRI, was performed that identified abscesses extending bilaterally through the round foramina obliterating the cavernous sinus region, as well as abscessation of the right mandible, right trigeminal neuritis, right-sided sinusitis, and right-sided otitis media. Cavernous sinus syndrome should be considered in cattle with a combination of exophthalmos and neuro-ophthalmologic abnormalities involving cranial nerves III, IV, V, and VI, whose branches are located within the cavernous sinus.
Assuntos
Abscesso Encefálico/veterinária , Doenças dos Bovinos/patologia , Seio Cavernoso/patologia , Animais , Abscesso Encefálico/patologia , Bovinos , Masculino , SíndromeRESUMO
Antarctic and Southern Ocean (ASO) marine ecosystems have been changing for at least the last 30 years, including in response to increasing ocean temperatures and changes in the extent and seasonality of sea ice; the magnitude and direction of these changes differ between regions around Antarctica that could see populations of the same species changing differently in different regions. This article reviews current and expected changes in ASO physical habitats in response to climate change. It then reviews how these changes may impact the autecology of marine biota of this polar region: microbes, zooplankton, salps, Antarctic krill, fish, cephalopods, marine mammals, seabirds, and benthos. The general prognosis for ASO marine habitats is for an overall warming and freshening, strengthening of westerly winds, with a potential pole-ward movement of those winds and the frontal systems, and an increase in ocean eddy activity. Many habitat parameters will have regionally specific changes, particularly relating to sea ice characteristics and seasonal dynamics. Lower trophic levels are expected to move south as the ocean conditions in which they are currently found move pole-ward. For Antarctic krill and finfish, the latitudinal breadth of their range will depend on their tolerance of warming oceans and changes to productivity. Ocean acidification is a concern not only for calcifying organisms but also for crustaceans such as Antarctic krill; it is also likely to be the most important change in benthic habitats over the coming century. For marine mammals and birds, the expected changes primarily relate to their flexibility in moving to alternative locations for food and the energetic cost of longer or more complex foraging trips for those that are bound to breeding colonies. Few species are sufficiently well studied to make comprehensive species-specific vulnerability assessments possible. Priorities for future work are discussed.
Assuntos
Organismos Aquáticos , Mudança Climática , Camada de Gelo , Regiões Antárticas , Biota , Ecossistema , Oceanos e Mares , Movimentos da Água , VentoRESUMO
The expression and perception of expressed emotion (EE) in schizophrenic patients and their relatives are likely to differ. The presented exploratory study compares the two views. EE in relatives of 25 chronic schizophrenic patients was assessed using an extended version of the Five-Minute Speech Sample (FMSS). Patients rated their relatives with the Perceived Criticism Scale (PCS), the Family Emotional Involvement and Criticism Scale (FEICS), and a German questionnaire on family atmosphere (FEF). Forty-eight percent of relatives were rated high in EE, due to criticism in all cases but one. Patients' assessments of the whole family on the FEICS and FEF criticism subscales were related to their relatives' EE status. Correlations between the self-rating instruments were moderate to good. As the patients' and the relatives' views corresponded with regard to the criticism domain, the application of a self-rating instrument may be a simple and useful tool for clinical and research purposes.
Assuntos
Cuidadores/psicologia , Emoções Manifestas , Transtornos Psicóticos/diagnóstico , Reforço Psicológico , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mães/psicologia , Comunicação não Verbal , Determinação da Personalidade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Transtornos Psicóticos/psicologia , Percepção Social , Estatística como AssuntoRESUMO
Relatives of first-episode and chronic schizophrenic and depressed patients were examined with respect to their expressed emotion (EE) status. The two aims of the study were to (1) investigate whether relatives of first-episode patients differed from family members of chronic patients, and (2) whether EE indices of relatives of schizophrenic patients were comparable to those of depressed subjects. Twenty patients of each diagnostic group (DSM-III-R and DSM-IV) were included, i.e. a total of 80 patients. The EE status of key relatives was assessed with the Five-Minute Speech Sample on the basis of critical comments and emotional overinvolvement. Additionally, the new criterion 'covert criticism' was applied to detect indirect expressions of critique. Relatives of first-episode and chronic patients of both diagnostic groups did not differ significantly regarding their EE status; in first-episode patients, 52.5% of relatives were classified high EE; in chronic patients, 45%. Moreover, EE indices of relatives of schizophrenic and depressed patients were comparable. Analysis revealed 52.5 and 45% high-EE relatives in the depression and the schizophrenia subsamples, respectively. Thus, the overall incidence of high-EE relatives was comparable to numbers reported in the literature. In our study EE status of relatives was not disease-specific, and it was independent of chronicity of illness.