[Indicative prevention programs for mental health promotion in preschool and primary school age: Willingness of pediatricians and families to participate in an innovative care chain]. / Indikative Präventionsprogramme zur Förderung der seelischen Gesundheit im Vor- und Grundschulalter: Teilnahmebereitschaft von Kinderärzt*innen und Familien an einer innovativen Versorgungskette.

BACKGROUND: Mental health problems usually have their onset in childhood. Undiagnosed, they may progress into mental disorders. Despite their effectiveness, existing preventive programs have been rarely used. We aimed to examine to what extent the establishment of a care chain can identify children at high risk at an early stage and assign them to preventive interventions. In addition, prevention program participation was assessed. METHODS: In a prospective implementation study, the Strengths and Difficulties Questionnaire was administered as a screening instrument to families during regular pediatric health examinations (U9-U11, child age 5-10 years). Families received feedback directly from the pediatrician, and in the case of borderline abnormal emotional or behavioral problems, a recommendation for an indicative prevention program. Program indication was additionally determined in an entry examination prior to program participation. RESULTS: In the area of Dresden (Germany), n = 46 (38.7%) pediatricians participated in the project. In n = 28 pediatric practices, n = 3231 (86.4%) families participated in the screening and n = 864 (26.7%) children received a prevention recommendation. Of the families, n = 118/864 (13.7%) self-registered for the prevention programs, n = 215/624 (35.5%) showed interest after being contacted by the study teamn. Through other pathways, n = 139 families requested participation. Clinical evaluation interviews to assess prevention indication were conducted in n = 337 children (n = 461; via all entry pathways). Finally, n = 237 (n = 337) children participated in an indicated prevention program. CONCLUSION: Expanding screening to mental health problems during regular health checkups is feasible, useful, and widely accepted. In order to implement a care chain, a supply structure should be established to enable referral to and uptake of preventive interventions.

Social Interactions in Everyday Life of Socially Anxious Adolescents: Effects on Mental State, Anxiety, and Depression.

Unfavorable interpersonal behavior in social anxiety disorder (SAD) contributes to the maintenance of the disorder and may also be related to the development of secondary depression. Since there is limited research on daily life behavior in SAD, this study aimed to describe social interaction behavior and analyze the effect of positive interactions on depression, anxiety, and mental state. Data were obtained from the Behavior and Mind Health study (11/2015-12/2016), an epidemiological cohort study of adolescents and young adults (n = 1,180, aged 14-21 years) from Dresden, Germany. Interpersonal behavior, current mental state, anxiety, and depression were assessed eight times per day over four days using smartphone-based ecological momentary assessments. The analyzed subsample consisted of n = 723 participants, comparing 12-month SAD (n = 60) and healthy controls (HC; n = 663). The interaction behavior of participants with SAD did not differ substantially from that of HC in terms of frequency of social interactions, type of interaction partner, and time spent communicating, although they reported fewer real-life interaction partners (SAD: M = 2.49, SD = 4.78; HC: M = 3.18, SD = 6.43; F(17,044) = 23.92, p < 0.001). When comparing mental state, anxiety, and depression after interactions with familiar people to no interaction, no differences were found between SAD and HC. However, interactions with unfamiliar people negatively affected depressive symptoms in individuals with SAD (b = 0.53; SE = 0.25; 95%CI: 0.04-1.03; p = 0.036). In adolescents with SAD, social situations with unfamiliar people seem to be processed in a dysfunctional way, contributing to increased depressive mood in everyday life. This is particularly interesting given the high rate of secondary depression in SAD.

Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders.

Bipolar disorder (BD) and major depressive disorder (MDD) are severe psychiatric illnesses that share among their environmental risk factors the exposure to adverse childhood experiences (ACE). Exposure to ACE has been associated with long-term changes in brain structure and the immune response. In the lasts decades, brain abnormalities including alterations of white matter (WM) microstructure and higher levels of peripheral immune/inflammatory markers have been reported in BD and MDD and an association between inflammation and WM microstructure has been shown. However, differences in these measures have been reported by comparing the two diagnostic groups. The aim of the present study was to investigate the interplay between ACE, inflammation, and WM in BD and MDD. We hypothesize that inflammation will mediate the association between ACE and WM and that this will be different in the two groups. A sample of 200 patients (100 BD, 100 MDD) underwent 3T MRI scan and ACE assessment through Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling for the assessment of immune/inflammatory markers. We observed that ACE associated with higher peripheral levels of IL-2, IL-17, bFGF, IFN-γ, TNF-α, CCL3, CCL4, CCL5, and PDGF-BB only in the BD group. Further, higher levels of CCL3 and IL-2 associated with lower FA in BD. ACE were found to differently affect WM microstructure in the two diagnostic groups and to be negatively associated with FA and AD in BD patients. Mediation analyses showed a significant indirect effect of ACE on WM microstructure mediated by IL-2. Our findings suggest that inflammation may mediate the detrimental effect of early experiences on brain structure and different mechanisms underlying brain alterations in BD and MDD.

Congenital primary aphakia.

PURPOSE: To describe the natural history, management, and visual outcome in children with congenital primary aphakia (CPA). METHODS: This is a multicenter retrospective consecutive case series from five academic centers in England and North America. RESULTS: A total of 27 eyes of 14 patients were included (male:female, 1.7:1). Thirteen patients had bilateral CPA, and 1 patient had unilateral CPA. Mean age at diagnosis was 18 months (median, 21; range, 0.5-144). Of 11 patients who underwent genetic testing, 9 had FOXE3 pathogenic variants. In all patients, visual acuity at presentation was not better than fixing and following light. Typical findings included silvery appearance of the cornea with vascularization (96%), glaucoma (81%), iridocorneal adhesions (74%), optic nerve coloboma (55%), abnormal vitreous (33%), retinal detachment (30%), and aniridia with hypoplasia of ciliary body (19%). Surgical interventions in select patients included penetrating keratoplasty (PKP), glaucoma drainage device implantation, and cyclophotocoagulation (CPC). CONCLUSIONS: Eyes with corneal ectasia and a silvery appearance of the cornea with vascularization should alert the physician to the possibility of CPA. Glaucoma causes globe enlargement and may increase the risk of corneal perforation, but glaucoma is often refractory to medical treatment, and the threshold for surgical treatment should be low. PKP outcomes are very poor.

Keratoconus in a child with partial trisomy 13.

Background: Clinical studies suggest the importance of genetic components in the etiology of keratoconus. However, the contributing genes and variants remain elusive. We present a case of bilateral keratoconus in a child with partial trisomy 13, with a trisomic region spanning loci that have been associated with keratoconus.Materials and Methods: This is a single, retrospective case report of a child with a molecular diagnosis of partial trisomy 13, who was diagnosed with bilateral keratoconus for which at the age of 11 years, she underwent successive epithelium-off corneal cross-linking (CXL) procedures in both eyes, followed by temporary central tarsorrhaphy under general anesthesia.Results: Patient's molecular diagnosis was 70 Megabase trisomic region 13q14.11q34. Pre CXL pachymetry was 426 µm and 496 µm, maximum K values were 52.28 D and 55.45 D in right and left eyes, respectively; at last follow up (12 months post-op) these were 494 µm and 509 µm for pachymetry and maximum K values 50.50 D and 52.43 D in the right and left eyes, respectively. No signs of progression were detected.Conclusion: To the best of our knowledge, this is the first case report to document bilateral keratoconus in a child with partial trisomy 13, in whom successful epithelium-off CXL was achieved with general anesthesia. We emphasize the importance of screening, early diagnosis, and therapy of this treatable but rare cause of decreased vision in partial trisomy 13 patients.

Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.

A 5-year-old girl presented with treatment-refractory dry eye and recurrent episodes of eye pain. She had been previously diagnosed with syndromic congenital sodium diarrhea (SCSD) caused by a pathogenic variant in SPINT2. Her local pediatric ophthalmologist had made the diagnosis of severe dry eye with corneal erosions, based on which, we arranged an eye exam under anesthesia (EUA) and punctal plug placement. Anterior segment optical coherence tomography (OCT) and corneal photographs were taken during the procedure. There are reports describing similar ophthalmic findings in this syndrome. However, to the best of our knowledge, this is the first case report to document OCT imaging and corneal photographs in a patient with SCSD, which we feel expands the ophthalmic phenotype of this rare genetic disorder.

Ocular findings of albinism in DYRK1A-related intellectual disability syndrome.

BACKGROUND: Pathogenic variants in DYRK1A are associated with DYRK1A-related intellectual disability syndrome (DIDS). Common features of this diagnosis include microcephaly, intellectual disability, speech impairment, and distinct facial features. Reported ocular features include deep-set eyes, myopia, and strabismus. We present a case of DYRK1A-related intellectual disability syndrome with ocular findings of albinism and explore the possible pathogenesis of this previously unreported manifestation. MATERIALS AND METHODS: This is a single, retrospective case report of a child with DIDS who underwent an ophthalmic exam including detailed visual electrophysiology. Results: A 21-month-old female with microcephaly, failure to thrive, language delay, cleft palate, and cardiac defects had an ophthalmic exam showing myopia, strabismus, a hypopigmented fundus and crossed asymmetry on visual evoked potential (VEP), consistent with ocular findings of albinism. Whole exome sequencing identified a pathogenic DYRK1A variant; no albinism gene variants were reported. Her constellation of features is consistent with a diagnosis of DYRK1A-related intellectual disability syndrome; however, ocular features of albinism have not previously been reported in this condition. CONCLUSIONS: This is, to the best of our knowledge, the first report of ocular findings of albinism in a case of DYRK1A-related intellectual disability syndrome. We propose that ocular albinism is a novel ocular phenotype of DYRK1A-related disease. Ophthalmic exams in patients with this diagnosis should include thorough evaluation for ocular albinism, including VEPs.

Methamphetamine Users Show No Behavioral Deficits in Response Selection After Protracted Abstinence.

Introduction: Chronic recreational methamphetamine use causes dopaminergic neurotoxicity, which has been linked to impairments in executive functioning. Within this functional domain, response selection and the resolution of associated conflicts have repeatedly been demonstrated to be strongly modulated by dopamine. Yet, it has never been investigated whether chronic methamphetamine use leads to general impairments in response selection (i.e., irrespective of consumption-associated behavior) after substance use is discontinued. Materials and Methods: We tested n = 24 abstinent methamphetamine users (on average 2.7 years of abstinence) and n = 24 individually matched controls in a cross-sectional design with a flanker task. Results: Compared to healthy controls, former methamphetamine consumers had significantly slower reaction times, but did not show differences in the size of the flanker or Gratton effect, or post-error slowing. Complementary Bayesian analyses further substantiated this lack of effects despite prior consumption for an average of 7.2 years. Discussion: The ability to select a correct response from a subset of conflicting alternatives, as well as the selective attention required for this seem to be largely preserved in case of prolonged abstinence. Likewise, the ability to take previous contextual information into account during response selection and to process errors seem to be largely preserved as well. Complementing previously published finding of worse inhibition/interference control in abstinent consumers, our results suggest that not all executive domains are (equally) impaired by methamphetamine, possibly because different cognitive processes require different levels of dopamine activity.

Polyester-based particles to overcome the obstacles of mucus and biofilms in the lung for tobramycin application under static and dynamic fluidic conditions.

Pulmonary infections with Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) are difficult to treat and related with high mortality in some diseases like cystic fibrosis due to the recurrent formation of biofilms. The biofilm formation hinders efficient treatment with inhaled antibiotics due to a low penetration of the antibiotics through the polyanionic biofilm matrix and increased antimicrobial resistance of the biofilm-embedded bacteria. In this study, tobramycin (Tb) was encapsulated in particles based on poly(d,l,-lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-co-poly(d,l,-lactide-co-glycolide) diblock (PEG-PLGA) to overcome the biofilm barrier with particle sizes of 225-231 nm (nanoparticles) and 896-902 nm (microparticles), spherical shape and negative zeta potentials. The effectiveness against biofilms of P. aeruginosa and B. cepacia was strongly enhanced by the encapsulation under fluidic experimental condition as well as under static conditions in artificial mucus. The biofilm-embedded bacteria were killed by less than 0.77 mg/l encapsulated Tb, whereas 1,000 mg/l of free Tb or the bulk mixtures of Tb and the particles were ineffective against the biofilms. Moreover, encapsulated Tb was even effective against biofilms of the intrinsically aminoglycoside-resistant B. cepacia, indicating a supportive effect of PEG and PLGA on Tb. No cytotoxicity was detected in vitro in human lung epithelial cells with any formulation.

A blue fluorescent labeling technique utilizing micro- and nanoparticles for tracking in LIVE/DEAD® stained pathogenic biofilms of Staphylococcus aureus and Burkholderia cepacia.

Strategies that target and treat biofilms are widely applied to bacterial cultures using popular live/dead staining techniques with mostly red or green fluorescent markers (eg, with SYTO(®) 9, propidium iodide, fluorescein). Therefore, visualizing drugs or micro- and nanoparticulate delivery systems to analyze their distribution and effects in biofilms requires a third fluorescent dye that does not interfere with the properties of the live/dead markers. The present study establishes and evaluates a model for tracking polymeric particles in fluorescently stained biological material. To this end, poly(D,L-lactide-co-glycolide) (PLGA)-based micro- and nanoparticles were used as well-established model systems, which, because of their favorable safety profiles, are expected to play important future roles with regard to drug delivery via inhalation. PLGA was covalently and stably labeled with 7-amino-4-methyl-3-coumarinylacetic acid (AMCA), after which blue fluorescent poly(ethylene glycol)-block-PLGA (PEG-PLGA) particles were prepared using a mixture of fluorescent AMCA-PLGA and PEG-PLGA. Because chitosan is known to reduce negative surface charge, blue fluorescent PEG-PLGA-particles with chitosan were also prepared. These micro- and nanoparticles were physicochemically characterized and could be clearly distinguished from live/dead stained bacteria in biofilms using confocal laser scanning microscopy.

Cyclic AMP increases cytoplasmic free calcium in renin-secreting cells from rat kidney.

The renin-secreting juxtaglomerular cells (JGC) in the media of the afferent arteriole at the vessel pole are the major source of circulating renin. The control of renin secretion is complex with increases in cAMP being the major stimulus and increases in intracellular free Ca2+ concentration ([Ca2+]i) being inhibitory. We measured [Ca2+]i in the afferent arteriole from mostly JGC. Manoeuvres that increase cAMP (e.g. isoproterenol) or dibutyryl-cAMP elicited an increase in [Ca2+]i which was approximately 40% of that induced by angiotensin II (3 nmol/l). The Ca2+ response occurred in 50-90% of the cases, and increasing the stimulus increased responder frequency but not response size. The response was (almost) abolished by removal of extracellular Ca2+, prevented by inhibitors of store-operated Ca2+ channels (Gd3+ and 2-aminoethoxydiphenyl-borate), but was unaffected by isradipine or protein kinase A inhibitors. It was not produced by an activator of EPACs (exchange protein activated by cAMP) and was not accompanied by changes in membrane potential. The data suggest that in rat JGC, cAMP, perhaps directly, activates store-operated Ca2+ channels to increase [Ca2+]i. One could speculate that this increase in [Ca2+]i serves to finely adjust the stimulating effect cAMP-increasing signals on the renin-angiotensin system.

Effect of adenosine on membrane potential and Ca2+ in juxtaglomerular cells. Comparison with angiotensin II.

BACKGROUND: Renin is mainly secreted from the juxtaglomerular cells (JGC) in the kidney situated in the afferent arteriole close to the vessel pole. Angiotensin II (ANG II) and adenosine inhibit renin secretion and synergistically constrict the afferent arteriole. ANG II depolarises JGC and increases the cytoplasmic free Ca2+ concentration [Ca2+]i. The responses of JGC to adenosine are less known. METHODS: Effects of adenosine on membrane potential and [Ca2+]i were studied in afferent arterioles from NaCl-depleted rats and mice. RESULT: Stimulation of A1 adenosine receptors (A1AR) by adenosine (10 microM) or cyclohexyladenosine (1 microM) increased the spiking frequency of JGC, slightly depolarised the cells and, in < or =50% of the cases, increased [Ca2+]i. These effects were much smaller than those of ANG II (3 nM). Simultaneous application of cyclohexyladenosine and ANG II gave only additive effects on [Ca2+]i; in addition, responses to ANG II in JGC from A1AR knockout mice were similar to those from control mice. CONCLUSION: The small changes in membrane potential and [Ca2+]i in response to A1AR stimulation as compared to those of ANG II may suggest that these 2 tissue hormones use different signal transduction mechanisms to affect JGC function, including the inhibition of renin release.