Agreement and disagreement in pediatric functional neurological symptom disorders: Comparing patient reported outcome measures (PROMs) and clinician assessments.

Youth with functional neurological symptom disorder (FNSD) often perceive themselves as having limited capabilities, which may not align with clinical evaluations. This study assessed the disparities between clinician evaluations and patient-reported outcome measures (PROMs) regarding pain, motor function, and learning difficulties in youth with FNSD. Sixty-two youths with FNSD participated in this study, all of whom reported experiencing pain, motor problems, and/or learning difficulties. Clinicians also assessed these domains, resulting in a two-by-two categorization matrix: (1) agreement: child and clinician report "problems"; (2) agreement: child and clinician report "no problems"; (3) disagreement: child reports "problems" while the clinician does not; and (4) disagreement: clinician reports "problems" while the child does not. Agreement/disagreement differences were analyzed. No significant differences in prevalence were observed between the evaluators regarding pain (clinician-85%, child-88%), motor (clinician-98%, child-95%), or learning problems (clinician-69%, child-61%). More than 80% of the children and clinicians report pain and motor disorders. Instances in which children and clinicians reported learning problems (40.3%) exceeded cases in which both reported no problems (9.6%) or only the child reported problems (20.9%). Overall, the agreement between pain and motor function assessments was high (>90%), whereas that concerning learning difficulties was moderate (49.9%). Disagreement in pain/motor assessments was minimal (<5%), whereas for learning difficulties, disagreement rates were high (>20%). In conclusion, a significant concordance exists between PROMs and clinician assessments of pain and motor problems. However, the higher frequency of disagreements regarding learning difficulties emphasizes the importance of incorporating patient and clinician evaluations in pediatric FNSD treatment.

Repercussions of the COVID-19 pandemic on child and adolescent mental health: A matter of concern-A joint statement from EAP and ECPCP.

COVID-19 pandemic and the consequent rigid social distancing measures implemented, including school closures, have heavily impacted children's and adolescents' psychosocial wellbeing, and their mental health problems significantly increased. However, child and adolescent mental health were already a serious problem before the Pandemic all over the world. COVID-19 is not just a pandemic, it is a syndemic and mentally or socially disadvantaged children and adolescents are the most affected. Non-Communicable Diseases (NCDs) and previous mental health issues are an additional worsening condition. Even though many countries have responded with decisive efforts to scale-up mental health services, a more integrated and community-based approach to mental health is required. EAP and ECPCP makes recommendations to all the stakeholders to take action to promote, protect and care for the mental health of a generation.

Effect of maternal body mass index on cord blood erthropoietin concentrations.

OBJECTIVE: To examine the hypothesis that maternal body mass index (BMI) (an index of maternal adiposity) correlates with cord blood concentrations of erythropoietin (EPO). STUDY DESIGN: Cross-sectional cohort study of consecutively born singleton term healthy infants born to mothers with various BMIs. Excluded were infants with major factors known to be associated with a potential increase in fetal erythropoiesis. Prepregnancy maternal BMI was calculated from maternal recollection. RESULT: There was a significant correlation between EPO concentrations and maternal BMI (R = 0.427, P = 0.007). This correlation remained significant in multiple stepwise regression analysis using the EPO concentration as the dependent variable, and maternal age, parity, gestational age and Apgar scores (1 or 5 min) as potential confounders. CONCLUSION: Cord blood concentrations of EPO correlate with maternal BMI. We speculate that increasing maternal BMI may represent a relative hypoxic burden on the fetus.

Chromatin remodeling--a novel strategy to control excessive alcohol drinking.

Harmful excessive use of alcohol has a severe impact on society and it remains one of the major causes of morbidity and mortality in the population. However, mechanisms that underlie excessive alcohol consumption are still poorly understood, and thus available medications for alcohol use disorders are limited. Here, we report that changing the level of chromatin condensation by affecting DNA methylation or histone acetylation limits excessive alcohol drinking and seeking behaviors in rodents. Specifically, we show that decreasing DNA methylation by inhibiting the activity of DNA methyltransferase (DNMT) with systemic administration of the FDA-approved drug, 5-azacitidine (5-AzaC) prevents excessive alcohol use in mice. Similarly, we find that increasing histone acetylation via systemic treatment with several histone deacetylase (HDAC) inhibitors reduces mice binge-like alcohol drinking. We further report that systemic administration of the FDA-approved HDAC inhibitor, SAHA, inhibits the motivation of rats to seek alcohol. Importantly, the actions of both DNMT and HDAC inhibitors are specific for alcohol, as no changes in saccharin or sucrose intake were observed. In line with these behavioral findings, we demonstrate that excessive alcohol drinking increases DNMT1 levels and reduces histone H4 acetylation in the nucleus accumbens (NAc) of rodents. Together, our findings illustrate that DNA methylation and histone acetylation control the level of excessive alcohol drinking and seeking behaviors in preclinical rodent models. Our study therefore highlights the possibility that DNMT and HDAC inhibitors can be used to treat harmful alcohol abuse.

Positive autoregulation of GDNF levels in the ventral tegmental area mediates long-lasting inhibition of excessive alcohol consumption.

Glial cell line-derived neurotrophic factor (GDNF) is an essential growth factor for the survival and maintenance of the midbrain dopaminergic (DA-ergic) neurons. Activation of the GDNF pathway in the ventral tegmental area (VTA), where the GDNF receptors are expressed, produces a long-lasting suppression of excessive alcohol consumption in rats. Previous studies conducted in the DA-ergic-like cells, SHSY5Y, revealed that GDNF positively regulates its own expression, leading to a long-lasting activation of the GDNF signaling pathway. Here we determined whether GDNF activates a positive autoregulatory feedback loop in vivo within the VTA, and if so, whether this mechanism underlies the long-lasting suppressive effects of the growth factor on excessive alcohol consumption. We found that a single infusion of recombinant GDNF (rGDNF; 10 µg) into the VTA induces a long-lasting local increase in GDNF mRNA and protein levels, which depends upon de novo transcription and translation of the polypeptide. Importantly, we report that the GDNF-mediated positive autoregulatory feedback loop accounts for the long-lasting inhibitory actions of GDNF in the VTA on excessive alcohol consumption. Specifically, the long-lasting suppressive effects of a single rGDNF infusion into the VTA on excessive alcohol consumption were prevented when protein synthesis was inhibited, as well as when the upregulation of GDNF expression was prevented using short hairpin RNA to focally knock down GDNF mRNA in the VTA. Our results could have implications for the development of long-lasting treatments for disorders in which GDNF has a beneficial role, including drug addiction, chronic stress and Parkinson's disease.

Comparison of functional outcomes of reverse shoulder arthroplasty versus hemiarthroplasty in the primary treatment of acute proximal humerus fracture.

BACKGROUND: Treatment of complex proximal humeral fractures remains controversial. In cases where adequate open reduction and internal fixation cannot be achieved, hemiarthroplasty has been the traditional treatment; however, clinical results have been mixed. Reverse shoulder arthroplasty (RSA) has been suggested as an alternative, and this study aimed to compare the functional results of RSA versus hemiarthroplasty in patients with acute proximal humeral fracture. METHODS: Ten patients with acute proximal humerus fractures unsuitable for internal fixation (mean age 77) who underwent RSA for acute proximal humerus fracture unsuitable for internal fixation against the outcomes of 10 patients (mean age 75) who had previously undergone hemiarthroplasty for the same indication. Functional scores and radiographic outcomes were assessed at 22-44 months follow up. RESULTS: At follow up the mean American Shoulder and Elbow Scorev score was 65 (range 40-88) in the RSA group and 67 (26-100) in the hemiarthroplasty group. Mean Oxford Shoulder scores were 29 (15-56) and 22 (12-34), respectively. Mean forward elevation was 115 degrees (range 45-140 degrees) and active external rotation was 49 degrees (5-105 degrees) in the RSA group, versus 108 degrees (50-180 degrees) and 48 degrees (10-90 degrees) in the hemiarthroplasty group. No statistically significant differences in outcome scores or range of motion were seen. CONCLUSION: In these early results, the anticipated functional gains of RSA over hemiarthroplasty were not realized, suggesting the use of RSA for treatment of proximal humeral fractures should remain guarded. Larger prospective trials are necessary to identify the optimal management of patients in this situation.

The future of primary paediatric care in Europe: reflections and Report of the EPA/UNEPSA Committee.

BACKGROUND: Changes in the scope of the field of paediatrics and the variability in primary paediatric care (PPC) and practice throughout Europe motivated the European Paediatric Association and Union of National European Paediatric Societies and Associations (EPA/UNEPSA) to establish a working group to discuss definitions of paediatric coverage in terms of age limits, find common denominators in the provision of PPC and examine the challenges and goals of 21st century paediatrics relevant to the continent. These issues were presented at the 2008 Europaediatrics in Istanbul, where a consensus declaration was drawn up and accepted by the EPA/UNEPSA Executive Committee. AIM: To present an outline of the essential elements of the 2008 EPA/UNEPSA Executive Committee consensus declaration. CONCLUSION: The definition of basic characteristics and the establishment of requirements for optimal PPC and practice are important steps in overcoming the differences among European countries and pave the way for an acceptable formulation of standardized high-quality paediatric medical care in Europe.

Periodontal changes in liver cirrhosis and post-transplantation patients. I: clinical findings.

BACKGROUND: Cyclosporin A (CsA) is widely used to prevent liver transplantation failure. CsA-induced gingival overgrowth is a common side effect. However, the effect of cirrhotic liver disease, liver transplantation, and immunosuppressive therapy on the periodontium is yet unclear. The aim of the present cross-sectional study was to examine the effect of liver cirrhosis, transplantation, and immunosuppressive therapy on the periodontium. METHODS: The experimental group (LC) consisted of 13 liver cirrhosis patients. A second experimental group (PT) included 24 patients, post-liver transplantation, receiving immunosuppressive therapy. Seventeen healthy subjects formed a control group. The Ramfjord index teeth were recorded for plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and gingival overgrowth (GO). RESULTS: Mean PI and mean GI for the LC, PT, and C groups were not statistically different (P >0.05). Mean PD for the LC (3.32+/-0.24 mm) and PT group (3.41+/-0.13 mm) was significantly higher (P = 0.0001, ANOVA) compared to the C group (2.45+/-0.16 mm). Likewise, CAL for the LC (4.89+/-0.47 mm) and PT group (4.68+/-0.47 mm) was significantly higher (P = 0.001, ANOVA) than the C group (2.78+/-0.23 mm). Patients in the PT group exhibited the greatest mean GO scores (0.88+/-0.09) compared to the LC group (0.37+/-0.07) and the C group (0.09+/-0.02). All 3 groups were significantly different from each other (P = 0.0001) despite great variability within the groups. GO in the CsA-treated patients (1.1+/-0.09) was significantly higher (P = 0.0001) than in those treated with tacrolimus (0.57+/-0.1). CONCLUSIONS: Liver cirrhosis patients demonstrated greater pocketing and attachment loss compared to healthy matched controls. These same differences were observed in patients post-transplantation. Gingival overgrowth occurred as a result of the immunosuppressive therapy with CsA, while to a lesser degree with tacrolimus. Replacement of CsA by tacrolimus in patients manifesting gingival overgrowth might be recommended whenever possible to overcome this problem.

Transcriptional and posttranscriptional regulation of the glycolate oxidase gene in tobacco seedlings.

The roles of light and of the putative plastid signal in glycolate oxidase (GLO) gene expression were investigated in tobacco (Nicotiana tabacum cv. Samsun NN) seedlings during their shift from skotomorphogenic to photomorphogenic development. GLO transcript and enzyme activities were detected in etiolated seedlings. Their respective levels increased three- and six-fold during 96 h of exposure to light. The GLO transcript was almost undetectable in seedlings in which chloroplast development was impaired by photooxidation with the herbicide norflurazon. In transgenic tobacco seedlings, photooxidation inhibited the light-dependent increase in GUS activity when it was placed under the regulation of the GLO promoter P(GLO). However, even under these photooxidative conditions, a continuous increase in GUS activity was observed as compared to etiolated seedlings. When GUS expression was driven by the CaMV 35S promoter (P35S), no apparent difference was observed between etiolated, deetiolated and photooxidized seedlings. These observations indicate that the effects of the putative plastid development signal and light on GUS expression can be separated. Translational yield analysis indicated that the translation of the GUS transcript in P(GLO)::GUS seedlings was enhanced 30-fold over that of the GUS transcript in P35S::GUS seedlings. The overall picture emerging from these results is that in etiolated seedlings GLO transcript, though present at a substantial level, is translated at a low rate. Increased GLO transcription is enhanced, however, in response to signals originating from the developing plastids. GLO gene expression is further enhanced at the translational level by a yet undefined light-dependent mechanism.

Engineering zucchini yellow mosaic potyvirus as a non-pathogenic vector for expression of heterologous proteins in cucurbits.

Plant virus vectors provide an attractive biotechnological tool for the transient expression of foreign genes in whole plants. As yet there has been no use of recombinant viruses for the improvement of commercial crops. This is mainly because the viruses used to create vectors usually cause significant yield loss and can be transmitted in the field. A novel attenuated zucchini yellow mosaic potyvirus (AG) was used for the development of an environmentally safe non-pathogenic virus vector. The suitability of AG as an expression vector in plants was tested by analysis of two infectious viral constructs, each containing a distinct gene insertion site. Introduction of a foreign viral coat protein gene into AG genome between the P1 and HC-Pro genes, resulted in no expression in planta. In contrast, the same gene was stably expressed when inserted between NIb and CP genes, suggesting that this site is more suitable for a gene vector. Virus-mediated expression of reporter genes was observed in squash and cucumber leaves, stems, roots and edible fruit. Furthermore, AG stably expressed human interferon-alpha 2, an important human anti-viral drug, without affecting plant development and yield. Interferon biological activity was measured in cucumber and squash fruit. Together, these data corroborate a biotechnological utility of AG as a non-pathogenic vector for the expression of a foreign gene, as a benefit trait, in cucurbits and their edible fruit.

All in good time: the Arabidopsis circadian clock.

Biological time-keeping mechanisms have fascinated researchers since the movement of leaves with a daily rhythm was first described >270 years ago. The circadian clock confers a approximately 24-hour rhythm on a range of processes including leaf movements and the expression of some genes. Molecular mechanisms and components underlying clock function have been described in recent years for several animal and prokaryotic organisms, and those of plants are beginning to be characterized. The emerging model of the Arabidopsis clock has mechanistic parallels with the clocks of other model organisms, which consist of positive and negative feedback loops, but the molecular components appear to be unique to plants.

Cyclosporine A-induced gingival hyperplasia pemphigus vulgaris: literature review and report of a case.

Gingival hyperplasia appears in 8% to 85% of patients treated with cyclosporine. Most studies show an association between oral hygiene status and the prevalence and severity of this gingival overgrowth. Thus, besides attempting to substitute this drug with another whenever possible, treatment usually involves maintenance of strict oral hygiene coupled with scaling and root planing and removal of iatrogenic factors. Sometimes a second treatment phase involving periodontal surgery is necessary. Cyclosporine-induced gingival overgrowth has been mainly described in post-organ transplant patients. The present case describes, for the first time, a severe form of cyclosporine-induced gingival overgrowth arising in a 15 year-old male with pemphigus vulgaris. Periodontal treatment included oral hygiene and scaling and root planing under local anesthesia. There was a significant reduction in gingival enlargement, as well as a reduction in plaque levels and inflammation. Cessation of drug administration, combined with continuous periodontal treatment, brought further improvement. This successful conservative treatment of cyclosporine-induced gingival overgrowth in a pemphigus vulgaris patient suggests that early diagnosis and comprehensive treatment of these lesions may yield good response and reduce the need for periodontal surgery.

Thermal changes in endosseous root-form implants as a result of CO2 laser application: an in vitro and in vivo study.

Carbon dioxide (CO2) laser surgery is advantageous in current clinical situations. The controlled and precise destruction of target tissue has made it a recommended procedure in intraoral surgery. Implant surgery demands minimal thermal changes in bone surrounding the implant. In this experimental study, different types of implants were placed in vitro in the mandible of a pig and in vivo in the mandibles of two dogs. In continuous mode, 4 and 6 watts, and in repeated pulse, 5 and 8 watts, for 2, 4, and 5 seconds, the CO2 laser contacted several places around and on the implants. Temperature changes were measured at the implant-bone junction. The results showed that the CO2 laser produced minimal temperature changes in the continuous mode power setting at less than 4 watts and in the repeated pulse, 0.05 second-interval power setting at less than 8 watts.

Promoter activity of the 5' flanking region of a tobacco glycolate oxidase gene in transgenic tobacco plants.

A clone harboring the 5' flanking region of a tobacco glycolate oxidase (GLO) gene was isolated from a lambda EMBL3-tobacco genomic DNA library. Primer extension analysis indicated two major transcripts with 76 and 81 bp 5' UTRs. An RT-PCR assay mapped the major mRNA transcription initiation site to thymine at position 81 upstream of the translation initiation codon. A putative TATA box spanning positions -56 to -50 upstream of the transcription initiation site was found. Promoter activity of the 5' flanking region (-3.0 kb to +82 bp) was demonstrated in tobacco plants transformed with a GLO-beta-glucuronidase (GUS) chimeric gene. Furthermore, in these transgenic plants, GUS expression patterns mimicked the expression patterns of the endogenous GLO.

Permanent neurologic deficit after inferior alveolar nerve block: a case report.

Permanent neurologic damage after an inferior dental nerve block is reported. Clinical manifestations included hemisensory syndrome, facial nerve palsy, hearing impairment, and ataxia. Possible mechanisms and preventive measures are discussed.

Ligand-induced association of the type I interferon receptor components.

Two transmembrane polypeptides, IFNAR and IFN-alpha/Beta R, were previously identified as essential components of the type I interferon (IFN) receptor, but their interrelationship and role in ligand binding were not clear. To study these issues, we stably expressed and characterized the two polypeptides in host murine cells. In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon reduction only a 51-kDa protein is detected. In host murine cells human IFN-alpha/beta R was expressed as a 51-kDa protein. Host cells expressing IFN-alpha/beta R bound IFN-alpha 2 with a high affinity (Kd of 3.6 nM), whereas cells expressing IFNAR exhibited no ligand binding. Upon coexpression of IFNAR and the 51-kDa IFN-alpha/beta R, the affinity for IFN-alpha 2 was increased 10-fold, approaching that of the native receptor. We show by cross-linking that both the cloned (51-kDa) and native (102-kDa) IFN-alpha/beta R bind IFN-alpha 2 to form an intermediate product, while IFNAR associates with this product to form a ternary complex. Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN receptor, cooperating in ligand binding. Ligand-induced association of IFNAR and IFN-alpha/beta R probably triggers transmembrane signaling.