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1.
Int J Eat Disord ; 56(9): 1717-1729, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37243388

RESUMEN

OBJECTIVE: Within the eleventh edition of the International Classification of Diseases (ICD-11), diagnostic criteria for feeding and eating disorders were revised and new diagnoses including avoidant/restrictive food intake disorder (ARFID) are classifiable; however, nothing is known about how these changes affect the prevalence of feeding and eating disorders. This study compared the distribution and clinical characteristics of restrictive feeding and eating disorders between ICD-10 and ICD-11. METHOD: The Eating Disorder Examination (EDE), its child version, and the EDE ARFID module were administered to N = 82 patients (0-17 years) seeking treatment for restrictive feeding and eating disorders and their parents. Clinical characteristics were derived from medical records, questionnaires, and objective anthropometrics. RESULTS: The number of residual restrictive eating disorders (rrED) significantly decreased from ICD-10 to ICD-11 due to a crossover to full-threshold disorders, especially anorexia nervosa (AN) or ARFID. Patients reclassified to ICD-11 ARFID were younger, had an earlier age of illness onset, more restrictive eating behaviors, and tended to have more somatic comorbidities compared to those reclassified to ICD-11 AN. Patients with rrED according to both ICD-10 and ICD-11 were younger, had an earlier age of illness onset, less shape concern, and more somatic comorbidities than patients who were reclassified from ICD-10 rrED to ICD-11 AN or ARFID. DISCUSSION: This study highlights the inclusive approach of ICD-11 criteria, paving the way for more targeted treatment, and ARFID's high clinical relevance. Future studies considering nonrestrictive feeding and eating disorders across the life span may allow further analyses on diagnostic crossover. PUBLIC SIGNIFICANCE: Changes in diagnostic criteria for restrictive eating disorders within the newly published ICD-11 led to an increase in full-threshold disorders, while the number of rrED was significantly lowered compared to ICD-10 criteria. The results thus highlight the diagnostic utility of ICD-11 criteria and may help providing adequate treatment to children and adolescents with rrED.


Asunto(s)
Anorexia Nerviosa , Trastorno de la Ingesta Alimentaria Evitativa/Restrictiva , Trastornos de Alimentación y de la Ingestión de Alimentos , Niño , Adolescente , Humanos , Clasificación Internacional de Enfermedades , Estudios Retrospectivos , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Anorexia Nerviosa/terapia , Comorbilidad , Ingestión de Alimentos
2.
Artículo en Inglés | MEDLINE | ID: mdl-37668699

RESUMEN

Maternal capacity to mentalize (= reflective functioning, RF), secure attachment and emotionally available parenting has an impact on the child's development. The transmission of mothers' past attachment experiences gained with both her caregivers in her own childhood and the impact on current mother-child interaction is part of the 'transmission gap.' This study explores the transgenerational transmission mechanisms and the potential moderating effect of RF in a clinical sample of 113 mother-child dyads suffering from mental health problems. In a cross-sectional study, the associations between maternal attachment experiences, RF (coded based on Adult Attachment Interviews) and current mother-child interaction (Emotional Availability Scales) were examined with univariate correlation, moderator analyses, and structural equation models. We found relationships between attachment experiences and mother-child interaction, but RF had no moderating effect. Past loving experiences and perceived neglection, particularly with the own father in childhood, were predictors for the present mother-child interaction. There seems to be an intergenerational transmission of attachment experiences to the ongoing generation. Particularly past adverse childhood experiences with the own father seem to explain currently disruptive interactions with the child.Trial registration: DRKS00017008 and DRKS00016353.

3.
Int J Eat Disord ; 55(12): 1708-1720, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36054036

RESUMEN

OBJECTIVE: This study presents a psychometric evaluation of the avoidant/restrictive food intake disorder (ARFID) module 2.0 for the Eating Disorder Examination (EDE), its child (ChEDE), and parent version. Within a pediatric sample seeking treatment for restrictive feeding or eating disorders and non-treatment-seeking controls, the module's interrater reliability, parent-child agreement, and its convergent, divergent, and discriminant validity were examined. METHOD: The child, adult, and/or parent version of the German ARFID module was administered to N = 176 children and adolescents (0-17 years) and their parents, as were the (Ch)EDE, well-established measures on food-avoidance behaviors, food variety, and body esteem, and objective anthropometric measures. RESULTS: Across all versions of the ARFID module, substantial to almost perfect interrater reliability was shown. Parent-child agreement for ARFID diagnosis was substantial. Based on medium-to-large associations between interview-assessed avoidant/restrictive food intake and questionnaire-assessed food-avoidance behaviors, food variety, and objective weight status, the module showed high convergent validity, especially for the child and parent version. Low associations of avoidant/restrictive food intake with weight and shape concern demonstrated divergent validity. Individuals with ARFID differed significantly from those with anorexia nervosa and individually matched controls in a range of clinical characteristics, indicating discriminant validity. DISCUSSION: This comprehensive validation supports the EDE ARFID module to be a valuable measure for the assessment and diagnosis of ARFID in 0-17-year-olds based on self- and parent-report. Validation of the ARFID module against other interview-based measures on ARFID and its evaluation in an adult sample are pending. PUBLIC SIGNIFICANCE: Based on good reliability and validity of the avoidant/restrictive food intake disorder (ARFID) module for the Eating Disorder Examination (EDE) in its child, adult, and parent version, the present study paves the way for the clinical and research use of the interview-based EDE ARFID module for assessing ARFID across childhood and adolescence.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Padres , Adulto , Humanos , Niño , Adolescente , Reproducibilidad de los Resultados , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico
4.
BMC Psychiatry ; 21(1): 118, 2021 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-33639894

RESUMEN

BACKGROUND: The first years of life are a significant period for child development, when children are particularly sensitive and prone to crises. This early phase lays the foundation for healthy growth. Clinical assessment of psychological symptoms in early infancy and adequate treatment are both important in improving the diagnostic outcome and preventing later long-term developmental consequences. The most common psychological problems in the first 3 years of life are regulatory disorders. The aim of this trial is to investigate the efficacy of Parent-Infant Psychotherapy (PIP) for infants and young children (aged 0-36 months, diagnosed with at least one regulatory disorder) and their mothers, compared to care as usual (CAU). METHODS: In this open multicentre randomised controlled trial, 160 mother-infant dyads are randomised to receive PIP or CAU for 6 weeks of intervention in clinical or outpatient (including home treatment) settings. The primary outcome is the maternal sensitivity (sensitivity scale of the Emotional Availability Scales (EAS)) after 6 weeks. Secondary outcomes include assessment of interaction, mental health problems, attachment, development, psychological factors, treatment adherence, health care system utilisation, and costs, after 6 weeks and 12 months. DISCUSSION: This study will evaluate whether a manualised focus-based short-term psychodynamic psychotherapeutic intervention in mother-child dyads improves the care situation for families of children diagnosed with regulatory disorders, and helps prevent long-term psychopathologies. Assessment of the intervention in different settings will support the development of more tailored interventions for affected infants and their mothers. TRIAL REGISTRATION: German Clinical Trial Register, ID: DRKS00017008 . Registered 03/20/2019.


Asunto(s)
Relaciones Madre-Hijo , Pacientes Ambulatorios , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Madres , Estudios Multicéntricos como Asunto , Relaciones Padres-Hijo , Psicoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
5.
Artículo en Alemán | MEDLINE | ID: mdl-33146761

RESUMEN

After the birth of a child, parents may experience episodes of stress and psychological strain. Some infants show psychological or somatic stress in the form of early regulatory disorders. While the close connection between parental psychological stress, early regulatory disorders, and the development of the parent-child relationship is well documented, current data on effective treatment options are lacking. Previous care services mostly operate on a preventive basis; evidence-based psychotherapeutic services with a special focus on the parent-child relationship are rare.SKKIPPI is a multicenter research project (Berlin, Flensburg, Hamburg, Leipzig) and consists of several study parts with a mixed methods approach: an epidemiological cohort study, two randomized controlled intervention studies (RCTs), and a qualitative study. A population-based cohort study records the occurrence and determinants of psychosocial stress and mental health disorders, as well as the use of health and social services by parents and their children within the first two years of life, using online questionnaires and telephone interviews. The aim of the two RCTs is to evaluate the efficacy of a focused, dyadic parent-infant psychotherapy (Eltern-Säugling-Kleinkind-Psychotherapie, ESKP) compared to routine treatment in inpatient and outpatient settings. The focus of these RCTs is on the improvement of maternal sensitivity and on mother-child attachment, as well as child development and the reduction of mother-child psychopathological symptoms. The qualitative study intends to reconstruct the perspectives of parents on the assistance system and to explore reasons for underuse. The results are expected to help develop preventive as well as therapeutic strategies in the German health system.


Asunto(s)
Salud Mental , Relaciones Madre-Hijo , Berlin , Niño , Estudios de Cohortes , Femenino , Alemania , Humanos , Lactante , Padres , Periodo Posparto , Psicoterapia
6.
Pflugers Arch ; 470(6): 867-881, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29430615

RESUMEN

Considering that obesity is one of the leading risks for death worldwide, it should be noted that a brain-related mechanism is involved in AngII-induced and AT1-receptor-dependent weight loss. It is moreover established that activation of the Ang(1-7)/ACE2/Mas axis reduces weight, but it remains unclear whether this Ang(1-7) effect is also mediated via a brain-related mechanism. Additionally to Sprague Dawley (SD) rats, we used TGR(ASrAOGEN) selectively lacking brain angiotensinogen, the precursor to AngII, as we speculated that effects are more pronounced in a model with low brain RAS activity. Rats were fed with high-calorie cafeteria diet. We investigated weight regulation, food behavior, and energy balance in response to chronic icv.-infusions of AngII (200 ng•h-1), or Ang(1-7) (200/600 ng•h-1) or artificial cerebrospinal fluid. High- but not low-dose Ang(1-7) slightly decreased weight gain and energy intake in SD rats. AngII showed an anti-obese efficacy in SD rats by decreasing energy intake and increasing energy expenditure and also improved glucose control. TGR(ASrAOGEN) were protected from developing obesity. However, Ang(1-7) did not reveal any effects in TGR(ASrAOGEN) and those of AngII were minor compared to SD rats. Our results emphasize that brain AngII is a key contributor for regulating energy homeostasis and weight in obesity by serving as a negative brain-related feedback signal to alleviate weight gain. Brain-related anti-obese potency of Ang(1-7) is lower than AngII but must be further investigated by using other transgenic models as TGR(ASrAOGEN) proved to be less valuable for answering this question.


Asunto(s)
Angiotensina I/uso terapéutico , Fármacos Antiobesidad/uso terapéutico , Obesidad/prevención & control , Fragmentos de Péptidos/uso terapéutico , Angiotensina I/administración & dosificación , Animales , Fármacos Antiobesidad/administración & dosificación , Dieta Alta en Grasa/efectos adversos , Infusiones Intraventriculares , Masculino , Obesidad/tratamiento farmacológico , Obesidad/etiología , Fragmentos de Péptidos/administración & dosificación , Ratas , Ratas Sprague-Dawley
7.
Pflugers Arch ; 470(11): 1673-1689, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29978352

RESUMEN

Obesity is a global health problem and treatment options are still insufficient. When chronically treated with the angiotensin II receptor blocker telmisartan (TEL), rodents do not develop diet-induced obesity (DIO). However, the underlying mechanism for this is still unclear. Here we investigated whether TEL prevents leptin resistance by enhancing leptin uptake across the blood-brain barrier (BBB). To address this question, we fed C57BL/6 mice a high-fat diet (HFD) and treated them daily with TEL by oral gavage. In addition to broadly characterizing the metabolism of leptin, we determined leptin uptake into the brain by measuring BBB transport of radioactively labeled leptin after long-term and short-term TEL treatment. Additionally, we assessed BBB integrity in response to angiotensin II in vitro and in vivo. We found that HFD markedly increased body weight, energy intake, and leptin concentration but that this effect was abolished under TEL treatment. Furthermore, glucose control and, most importantly, leptin uptake across the BBB were impaired in mice on HFD, but, again, both were preserved under TEL treatment. BBB integrity was not impaired due to angiotensin II or blocking of angiotensin II receptors. However, TEL did not exhibit an acute effect on leptin uptake across the BBB. Our results confirm that TEL prevents DIO and show that TEL preserves leptin transport and thereby prevents leptin resistance. We conclude that the preservation of leptin sensitivity is, however, more a consequence than the cause of TEL preventing body weight gain.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Fármacos Antiobesidad/uso terapéutico , Barrera Hematoencefálica/metabolismo , Leptina/metabolismo , Obesidad/tratamiento farmacológico , Telmisartán/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Fármacos Antiobesidad/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Peso Corporal , Línea Celular , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/metabolismo , Telmisartán/farmacología
8.
PLoS Pathog ; 12(12): e1006091, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28006011

RESUMEN

Different biomolecules have been identified in bacterial pathogens that sense changes in temperature and trigger expression of virulence programs upon host entry. However, the dynamics and quantitative outcome of this response in individual cells of a population, and how this influences pathogenicity are unknown. Here, we address these questions using a thermosensing virulence regulator of an intestinal pathogen (RovA of Yersinia pseudotuberculosis) as a model. We reveal that this regulator is part of a novel thermoresponsive bistable switch, which leads to high- and low-invasive subpopulations within a narrow temperature range. The temperature range in which bistability is observed is defined by the degradation and synthesis rate of the regulator, and is further adjustable via a nutrient-responsive regulator. The thermoresponsive switch is also characterized by a hysteretic behavior in which activation and deactivation occurred on vastly different time scales. Mathematical modeling accurately mirrored the experimental behavior and predicted that the thermoresponsiveness of this sophisticated bistable switch is mainly determined by the thermo-triggered increase of RovA proteolysis. We further observed RovA ON and OFF subpopulations of Y. pseudotuberculosis in the Peyer's patches and caecum of infected mice, and that changes in the RovA ON/OFF cell ratio reduce tissue colonization and overall virulence. This points to a bet-hedging strategy in which the thermoresponsive bistable switch plays a key role in adapting the bacteria to the fluctuating conditions encountered as they pass through the host's intestinal epithelium and suggests novel strategies for the development of antimicrobial therapies.


Asunto(s)
Proteínas Bacterianas/metabolismo , Factores de Transcripción/metabolismo , Factores de Virulencia/metabolismo , Infecciones por Yersinia pseudotuberculosis/parasitología , Yersinia pseudotuberculosis/patogenicidad , Animales , Western Blotting , Modelos Animales de Enfermedad , Ensayo de Cambio de Movilidad Electroforética , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos BALB C , Temperatura , Imagen de Lapso de Tiempo , Virulencia
9.
Pharmacol Res ; 125(Pt A): 72-90, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28687340

RESUMEN

Cardiovascular diseases (CVD) are among the main causes of death globally and in this context hypertension represents one of the key risk factors for developing a CVD. It is well established that the peripheral renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). All components of the classic RAS can also be found in the brain but, in contrast to the peripheral RAS, how the endogenous RAS is involved in modulating cardiovascular effects in the brain is not fully understood yet. It is a complex system that may work differently in diverse areas of the brain and is linked to the peripheral system by the circumventricular organs (CVO), which do not have a blood brain barrier (BBB). In this review, we focus on the brain angiotensin peptides, their interactions with each other, and the consequences in the central nervous system (CNS) concerning cardiovascular control. Additionally, we present potential drug targets in the brain RAS for the treatment of hypertension.


Asunto(s)
Angiotensinas/metabolismo , Encéfalo/fisiopatología , Enfermedades Cardiovasculares/patología , Sistema Renina-Angiotensina/fisiología , Animales , Presión Sanguínea/fisiología , Encéfalo/metabolismo , Enfermedades Cardiovasculares/metabolismo , Humanos
10.
J Virol ; 87(8): 4475-85, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23388710

RESUMEN

The nuclear egress complex (NEC) is required for efficient translocation of newly synthesized herpesvirus nucleocapsids from the nucleus to the cytosol. It consists of the type II membrane protein pUL34 which interacts with pUL31 at the inner nuclear membrane (INM). To map regions within pUL34 required for nuclear membrane targeting and pUL31 interaction, we constructed deletion/substitution mutations. Previously, we showed that 50 C-terminal amino acids (aa) of pseudorabies virus (PrV) pUL34, including the transmembrane domain, could be functionally replaced by cellular lamina-associated polypeptide 2ß (Lap2ß) sequences. In contrast, replacement of the C-terminal 100 aa abrogated complementation but not pUL31 interaction. To further delineate essential sequences within this region, C-terminal pUL34 truncations of 60, 70, 80, 85, and 90 aa fused to Lap2ß sequences were generated. While truncations up to 85 aa were functional, deletion of the C-terminal 90 aa abrogated function, which indicates that the important region is located between aa 171 and 176. Amino acids 173 to 175 represent RQR, a motif suggested to mediate INM targeting. Mutagenesis to RQG revealed that the mutant protein exhibited pronounced Golgi localization, but a fraction still reached the INM. Deletion mutations in the N-terminal domain of pUL34 demonstrated that absence of the first 4 aa was tolerated, while removal of 9 or more residues resulted in a nonfunctional protein. In addition, mutation of three conserved cysteines did not abrogate pUL34 function, whereas alteration of a conserved glutamine/tyrosine sequence yielded a nonfunctional protein.


Asunto(s)
Transporte Activo de Núcleo Celular , Herpesvirus Suido 1/fisiología , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación Viral , Animales , Línea Celular , Análisis Mutacional de ADN , Herpesvirus Suido 1/genética , Interacciones Huésped-Patógeno , Nucleocápside/metabolismo
11.
RNA Biol ; 11(5): 580-93, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24786463

RESUMEN

In this study we investigated the influence of the global response regulator PhoP on the complex regulatory cascade controlling expression of early stage virulence genes of Yersinia pseudotuberculosis via the virulence regulator RovA. Our analysis revealed the following novel features: (1) PhoP activates expression of the CsrC RNA in Y. pseudotuberculosis, leading to activation of RovA synthesis through the CsrABC-RovM cascade, (2) activation of csrC transcription is direct and PhoP is shown to bind to two separate PhoP box-like sites, (3) PhoP-mediated activation results in transcription from two different promoters closely downstream of the PhoP binding sites, leading to two distinct CsrC RNAs, and (4) the stability of the CsrC RNAs differs significantly between the Y. pseudotuberculosis strains YPIII and IP32953 due to a 20 nucleotides insertion in CsrC(IP32953), which renders the transcript more susceptible to degradation. In summary, our study showed that PhoP-mediated influence on the regulatory cascade controlling the Csr system and RovA in Y. pseudotuberculosis varies within the species, suggesting that the Csr system is a focal point to readjust and adapt the genus to different hosts and reservoirs.


Asunto(s)
Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , ARN Bacteriano/genética , ARN Pequeño no Traducido/genética , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/metabolismo , Proteínas Bacterianas/genética , Modelos Biológicos , Unión Proteica , Estabilidad del ARN , ARN Bacteriano/metabolismo , ARN Pequeño no Traducido/metabolismo , Secuencias Reguladoras de Ácido Ribonucleico , Factores de Transcripción/genética , Sitio de Iniciación de la Transcripción , Activación Transcripcional , Virulencia/genética , Yersinia pseudotuberculosis/patogenicidad , Infecciones por Yersinia pseudotuberculosis/microbiología
12.
Trials ; 25(1): 229, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570873

RESUMEN

BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).


Asunto(s)
Artritis Gotosa , Gota , Humanos , Artritis Gotosa/tratamiento farmacológico , Colchicina/efectos adversos , Gota/diagnóstico , Gota/tratamiento farmacológico , Dolor , Prednisolona/efectos adversos , Atención Primaria de Salud , Estudios Prospectivos , Resultado del Tratamiento , Masculino , Femenino
13.
Child Maltreat ; 29(1): 142-154, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-36426806

RESUMEN

Different forms of maltreatment are thought to incur a cumulative and non-specific toll on mental health. However, few large-scale studies draw on psychiatric diagnoses manifesting in early childhood and adolescence to identify sequelae of differential maltreatment exposures, and emotional maltreatment, in particular. Fine-grained multi-source dimensional maltreatment assessments and validated age-appropriate clinical interviews were conducted in a sample of N = 778 3 to 16-year-olds. We aimed to (a) substantiate known patterns of clinical outcomes following maltreatment and (b) analyse relative effects of emotional maltreatment, abuse (physical and sexual), and neglect (physical, supervisory, and moral-legal/educational) using structural equation modeling. Besides confirming known relationships between maltreatment exposures and psychiatric disorders, emotional maltreatment exerted particularly strong effects on internalizing disorders in older youth and externalizing disorders in younger children, accounting for variance over and above abuse and neglect exposures. Our data highlight the toxicity of pathogenic relational experiences from early childhood onwards, urging researchers and practitioners alike to prioritize future work on emotional maltreatment.


Asunto(s)
Maltrato a los Niños , Trastornos Mentales , Humanos , Adolescente , Preescolar , Niño , Anciano , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Salud Mental , Maltrato a los Niños/psicología , Emociones , Análisis de Clases Latentes
14.
J Virol ; 86(4): 2079-88, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22156520

RESUMEN

Herpesvirus proteins pUL34 and pUL31 form a complex at the inner nuclear membrane (INM) which is necessary for efficient nuclear egress. Pseudorabies virus (PrV) pUL34 is a type II membrane protein of 262 amino acids (aa). The transmembrane region (TM) is predicted to be located between aa 245 and 261, leaving only one amino acid in the C terminus that probably extends into the perinuclear space. It is targeted to the nuclear envelope in the absence of other viral proteins, pointing to intrinsic localization motifs, and shows structural similarity to cellular INM proteins like lamina-associated polypeptide (Lap) 2ß and Emerin. To investigate which domains of pUL34 are relevant for localization and function, we constructed chimeric proteins by replacing parts of pUL34 with regions of cellular INM proteins. First the 18 C-terminal amino acids encompassing the TM were exchanged with TM regions and C-terminal domains of Lap2ß and Emerin or with the first TM region of the polytopic lamin B receptor (LBR), including the nine following amino acids. All resulting chimeric proteins complemented the replication defect of PrV-ΔUL34, demonstrating that the substitution of the TM and the extension of the C-terminal domain does not interfere with the function of pUL34. Complementation was reduced but not abolished when the C-terminal 50 aa were replaced by corresponding Lap2ß sequences (pUL34-LapCT50). However, replacing the C-terminal 100 aa (pUL34-LapCT100) resulted in a nonfunctional protein despite continuing pUL31 binding, pointing to an important functional role of this region. The replacement of the N-terminal 100 aa (pUL34-LapNT100) had no effect on nuclear envelope localization but abrogated pUL31 binding and function.


Asunto(s)
Herpesvirus Suido 1/metabolismo , Membrana Nuclear/virología , Seudorrabia/virología , Proteínas Virales/química , Proteínas Virales/metabolismo , Secuencias de Aminoácidos , Animales , Línea Celular , Herpesvirus Suido 1/química , Herpesvirus Suido 1/genética , Transporte de Proteínas , Conejos , Proteínas Virales/genética
15.
J Pediatr Endocrinol Metab ; 26(5-6): 569-74, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23412866

RESUMEN

The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism.


Asunto(s)
Ciclo del Ácido Cítrico/efectos de los fármacos , Ácido Cítrico/uso terapéutico , Acidemia Propiónica/tratamiento farmacológico , Acidemia Propiónica/metabolismo , Enfermedad Aguda , Anticoagulantes/uso terapéutico , Niño , Enfermedad Crítica , Metabolismo Energético/efectos de los fármacos , Femenino , Humanos , Resultado del Tratamiento
16.
J Eat Disord ; 11(1): 190, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37885020

RESUMEN

BACKGROUND: Although avoidant/restrictive food intake disorder (ARFID) presents the replacement and extension of feeding disorders of infancy and childhood, previous research into ARFID concentrated mainly on older patients. While birth-related characteristics play an etiologic role in feeding disorders, virtually nothing is known so far in ARFID. Therefore, the first aim of the study was to identify differences in birth-related characteristics in younger vs. older children with ARFID. Second, differences in physical and mental comorbidities, and third, diagnostic features between age groups were analysed. METHODS: Among N = 51 in- and outpatient treatment-seeking patients, n = 23 patients aged 0-5 years (30% girls) and n = 28 patients aged 6-17 years (57% girls), with an interview-based diagnosis of ARFID were included. Data on the pre- and perinatal period and mental and physical comorbidities were derived from patients' medical records, while diagnostic criteria, main ARFID presentation, and sociodemographic variables were collected through diagnostic interview. RESULTS: Significantly, younger patients with ARFID were born more often preterm and had more pre- and perinatal complications and a higher incidence of postnatal invasive procedures. Patients with ARFID aged 0-5 years presented significantly more physical comorbidities and conditions, especially congenital anomalies, while mental comorbidities, especially mood disorders, were significantly more common in patients with ARFID aged 6-17 years. No age differences were found for the distribution of diagnostic criteria and main ARFID presentation. CONCLUSION: This is the first study which aimed to identify age-specific characteristics in patients with ARFID with potential relevance for diagnosis and treatment. Especially birth-related complications, including invasive procedures postnatally, may be associated with developing ARFID, highlighting the importance of a closer view on these potential risk factors of the disorder. Future research with longitudinal design and larger samples may allow more detailed information on further age-specific associations, symptom trajectories, and age-specific risk factors for ARFID.


Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder characterized by a highly limited amount and/or variety of food intake accompanied by weight loss or reduced growth, nutritional deficiencies, the dependency on enteral nutrition or oral nutritional supplements, or psychosocial impairment. Although the knowledge about ARFID is currently expanding, there is still a lack of information whether the disorder presents differentially among younger and older youths. The present study examined n = 23 children aged 0­5 years in comparison to n = 28 patients aged 6­17 years in birth-related, medical, and diagnostic features. ARFID was assessed by clinical interview and questionnaire data, and medical records were used to derive clinical information. While younger patients with ARFID were more likely to be born preterm, had complications after birth and more co-occurring physical diseases, older patients with ARFID showed more mental illnesses. These findings underline the relevance of further investigations on age-dependent characteristics of ARFID to adapt diagnostic assessment and treatment of the disorder. No significant age differences were found for diagnostic criteria and presentations of ARFID, indicating that these features are applicable for patients of all child ages.

17.
Trials ; 24(1): 643, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798801

RESUMEN

BACKGROUND: Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen. METHODS: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients' global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed. DISCUSSION: This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680.


Asunto(s)
Artritis Gotosa , Gota , Adulto , Humanos , Colchicina/efectos adversos , Prednisolona/efectos adversos , Estudios Prospectivos , Artritis Gotosa/diagnóstico , Artritis Gotosa/tratamiento farmacológico , Gota/diagnóstico , Gota/tratamiento farmacológico , Dolor , Resultado del Tratamiento , Atención Primaria de Salud , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
18.
Children (Basel) ; 10(11)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-38002860

RESUMEN

Mental health problems in early childhood are common, but there is a lack of psychiatric research on this age group. DC:0-5 is a multiaxial classification system for mental disorders in early childhood, providing a framework for standardizing clinical practice and research. However, research on the validity of DC:0-5 is scarce. The Developmental Psychiatry Diagnostic Challenges Study (DePsy) is a multi-site, prospective clinical study including six German early childhood mental health (ECMH) clinics. The main objective of the study is to contribute to the validation of Axis I and Axis II of DC:0-5. A second aim of the study is to describe the population of the participating clinics regarding diagnoses, family context, and treatment outcomes. Additionally, the impact of environmental risk factors, including parental Adverse Childhood Experiences (ACEs) and media use, on child psychopathology and caregiver-child relationships will be examined. Over two years, patients aged 0.0-5.9 years old will be enrolled in the study. Assessments include ICD-10 and DC:0-5 diagnoses, developmental tests, video-based observations of caregiver-child interactions, and questionnaires on child psychopathology, media use, parental stress, and treatment satisfaction. Study results will promote the standardization of assessment and treatment in ECMH clinics aiming to improve the development of patients and their families.

19.
Children (Basel) ; 10(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38136087

RESUMEN

The COVID-19 pandemic and the ongoing lockdowns might have had a strong impact on mental health of mothers and their infants/toddlers. For example, families had to deal with health issues and social isolation, which might have affected mental health and parent-child interactions. The aim of this study is to evaluate differences in (1) infantile regulatory disorders, (2) maternal mental health, (3) the impact of maternal mental health on infantile regulatory disorders, and (4) alterations in the mother-child interaction for participants recruited before versus after the onset of the first German lockdown. For this reason, mother-child dyads have been divided into two groups and were compared by analyzing clinical interviews on psychopathology of mother and child (M.I.N.I. & DC:05) and mother-child-interactions (Emotional Availability Scales). Results showed that (1) differences in infantile sleeping disorders emerged (phi = 0.243; p = 0.016) compared to the pre-lockdown group, while (2) the occurrence of maternal panic and anxiety increased in the post-lockdown group (phi = 0.229; p = 0.022). Moreover, there was (3) an association for maternal panic and child's sleep disorder, and (4) specific associations with maternal non-hostility in the mother-child-interaction. In conclusion, the present study highlights the differences of maternal mental health occurrences and infants' regulatory problems, as well as the possible effects of the COVID-19 pandemic for infants. In the pre-lockdown group, maternal non-hostility might have acted as a promotive factor against regulatory disorders, while this mechanism was mitigated in the post-lockdown group.

20.
Pediatr Obes ; 17(1): e12842, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34553841

RESUMEN

BACKGROUND: While previous research indicates that low maternal sensitivity in mother-child interactions puts children at risk of overweight and obesity, maternal intrusiveness has rarely been investigated in association with children's weight. We investigated whether maternal sensitivity and intrusiveness in early childhood predict children's increased body mass index standard deviation scores (BMI-SDS) at school age. BMI-SDS are standardized for age and gender with respect to a reference standard. METHODS: At baseline (t1), we assessed maternal sensitivity and (non-)intrusiveness of 116 mothers with their children (48.3% female) aged 5-47 months (M = 24.00, SD = 11.36) using the emotional availability scales. We obtained anthropometric data for mothers at t1 by measuring height and weight in the laboratory and for children at birth assessed by medical staff. Six years later (t2) we obtained anthropometric data for children in the laboratory or based on parental report. Linear regression analyses were run with child BMI-SDS at t2 as outcome and sensitivity and (non-)intrusiveness as predictors, adjusting for confounders and exploring child age and gender as moderators. RESULTS: Maternal sensitivity only negatively predicted children's BMI-SDS in girls, while maternal intrusiveness predicted higher child BMI-SDS at school age regardless of child gender. The effect of maternal non-intrusiveness remained significant when controlling for confounders. CONCLUSION: Maternal intrusiveness in early childhood seems to represent a risk factor for increased BMI-SDS in children, while lower maternal sensitivity tends to be a risk factor for increased BMI-SDS in girls. This may have implications for prevention or intervention programmes.


Asunto(s)
Obesidad Infantil , Índice de Masa Corporal , Peso Corporal , Preescolar , Femenino , Humanos , Recién Nacido , Masculino , Madres , Sobrepeso , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Instituciones Académicas
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